FN Thomson Reuters Web of Science™ VR 1.0 PT J AU GOTO, T MAROTA, JJA CROSBY, G AF GOTO, T MAROTA, JJA CROSBY, G TI VOLATILE ANESTHETICS ANTAGONIZE NITROUS-OXIDE AND MORPHINE ANALGESIA IN THE RAT SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT ANESTHESIA,BOSTON,MA 02115. NR 4 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1994 VL 81 IS 3A SU S BP A915 EP A915 PG 1 WC Anesthesiology SC Anesthesiology GA PJ091 UT WOS:A1994PJ09100914 ER PT J AU GOUDSOUZIAN, N CHAKRAVORTI, S DENMAN, W DEBROS, F PATEL, S AF GOUDSOUZIAN, N CHAKRAVORTI, S DENMAN, W DEBROS, F PATEL, S TI LACK OF ACCUMULATION OF THE CIS-CIS ISOMER OF MIVACURIUM IN PATIENTS WITH LOW PLASMA CHOLINESTERASE ACTIVITY SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ANESTHESIOL,BOSTON,MA 02114. CHILDRENS HOSP PITTSBURGH,PITTSBURGH,PA 15213. BURROUGHS WELLCOME CO,RES TRIANGLE PK,NC 27709. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1994 VL 81 IS 3A SU S BP A1060 EP A1060 PG 1 WC Anesthesiology SC Anesthesiology GA PJ091 UT WOS:A1994PJ09101059 ER PT J AU ICHINOSE, F ADRIE, C HURFORD, WE ZAPOL, WM AF ICHINOSE, F ADRIE, C HURFORD, WE ZAPOL, WM TI PROLONGED DURATION OF ACTION OF INHALED NITRIC-OXIDE BY THE CGMP PHOSPHODIESTERASE INHIBITOR ZAPRINAST IN AWAKE LAMBS SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ANAESTHESIA,BOSTON,MA 02114. RI Hurford, William/G-6386-2013 OI Hurford, William/0000-0003-1201-0313 NR 2 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1994 VL 81 IS 3A SU S BP A640 EP A640 PG 1 WC Anesthesiology SC Anesthesiology GA PJ091 UT WOS:A1994PJ09100639 ER PT J AU KEARSE, LA LOPEZBRESNAHAN, M MCPECK, K ZASLAVSKY, A AF KEARSE, LA LOPEZBRESNAHAN, M MCPECK, K ZASLAVSKY, A TI AWAKE BASE-LINE ABNORMALITIES AND ASYMMETRIES AFTER INDUCTION OF ANESTHESIA IN THE EEGS OF PATIENTS UNDERGOING CAROTID ENDARTERECTOMY ARE NOT RELATED TO PATIENTS AGE OR EEG ISCHEMIC CHANGES AT CAROTID-ARTERY CROSS CLAMP SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ANESTHESIA,BOSTON,MA 02114. NR 2 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1994 VL 81 IS 3A SU S BP A210 EP A210 PG 1 WC Anesthesiology SC Anesthesiology GA PJ091 UT WOS:A1994PJ09100210 ER PT J AU KURREK, MM CASTILLO, L BLOCH, KD TANNENBAUM, SR HURFORD, WE ZAPOL, WM AF KURREK, MM CASTILLO, L BLOCH, KD TANNENBAUM, SR HURFORD, WE ZAPOL, WM TI INHALED NITRIC-OXIDE DOES NOT ALTER ENDOTOXIN-INDUCED NITRIC-OXIDE SYNTHASE ACTIVITY DURING PERFUSION OF THE ISOLATED RAT LUNG SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT PEDIAT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,BOSTON,MA 02114. BETH ISRAEL HOSP,DEPT ANESTHESIA,BOSTON,MA 02215. MIT,DEPT NUTR & FOOD SCI,CAMBRIDGE,MA 02139. RI Hurford, William/G-6386-2013 OI Hurford, William/0000-0003-1201-0313 NR 5 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1994 VL 81 IS 3A SU S BP A639 EP A639 PG 1 WC Anesthesiology SC Anesthesiology GA PJ091 UT WOS:A1994PJ09100638 ER PT J AU LONDON, MJ SHROYER, AL GROVER, FL SETHI, GK MARSHALL, G MORITZ, T TOBLER, HG MCCARTHY, MJ HENDERSON, W HAMMERMEISTER, KE AF LONDON, MJ SHROYER, AL GROVER, FL SETHI, GK MARSHALL, G MORITZ, T TOBLER, HG MCCARTHY, MJ HENDERSON, W HAMMERMEISTER, KE TI EVALUATING ANESTHESIA HEALTH-CARE-DELIVERY FOR CARDIAC-SURGERY - THE ROLE OF PROCESS AND STRUCTURE VARIABLES SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 UNIV COLORADO,HLTH SCI CTR,DENVER VAMC,DEPT ANESTHESIOL,DENVER,CO 80220. UNIV COLORADO,HLTH SCI CTR,DENVER VAMC,DEPT CARDIOL,DENVER,CO 80220. UNIV COLORADO,HLTH SCI CTR,DENVER VAMC,DEPT CARDIAC SURG,DENVER,CO 80220. RI Shroyer, Annie Laurie/B-8836-2016 OI Shroyer, Annie Laurie/0000-0001-6461-0623 NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1994 VL 81 IS 3A SU S BP A1255 EP A1255 PG 1 WC Anesthesiology SC Anesthesiology GA PJ091 UT WOS:A1994PJ09101254 ER PT J AU MAROTA, JJA GOTO, T WILSON, S ROOT, C CROSBY, G AF MAROTA, JJA GOTO, T WILSON, S ROOT, C CROSBY, G TI NITROUS-OXIDE PRODUCES NALTREXONE REVERSIBLE ATTENUATION OF NOXIOUS STIMULATION-INDUCED PROENKEPHALIN GENE-EXPRESSION SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT ANESTHESIA,BOSTON,MA 02115. NR 2 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1994 VL 81 IS 3A SU S BP A871 EP A871 PG 1 WC Anesthesiology SC Anesthesiology GA PJ091 UT WOS:A1994PJ09100870 ER PT J AU MAROTA, JJA ROOT, C ABE, K CROSBY, G AF MAROTA, JJA ROOT, C ABE, K CROSBY, G TI PROTEIN-SYNTHESIS INHIBITORS ANTAGONIZE NITROUS-OXIDE ANALGESIA SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1994 VL 81 IS 3A SU S BP A839 EP A839 PG 1 WC Anesthesiology SC Anesthesiology GA PJ091 UT WOS:A1994PJ09100838 ER PT J AU RAINES, DE RANKIN, SE MILLER, KW AF RAINES, DE RANKIN, SE MILLER, KW TI ISOFLURANES ACTIONS ON THE NICOTINIC ACETYLCHOLINE-RECEPTOR ARE DEPENDENT UPON THE COMPOSITION OF THE LIPID BILAYER SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. NR 4 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1994 VL 81 IS 3A SU S BP A884 EP A884 PG 1 WC Anesthesiology SC Anesthesiology GA PJ091 UT WOS:A1994PJ09100883 ER PT J AU RYAN, BA DAMBRA, MN LARUE, RM LYNCH, KE MAIONE, TE AF RYAN, BA DAMBRA, MN LARUE, RM LYNCH, KE MAIONE, TE TI EFFECT OF HEPARIN-PROTAMINE VS HEPARIN-PLATELET FACTOR-IV COMPLEXES ON WHOLE-BLOOD PLATELET-AGGREGATION SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. NR 2 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1994 VL 81 IS 3A SU S BP A634 EP A634 PG 1 WC Anesthesiology SC Anesthesiology GA PJ091 UT WOS:A1994PJ09100633 ER PT J AU SHEPHERD, KE FAULKNER, CS LEITER, JC AF SHEPHERD, KE FAULKNER, CS LEITER, JC TI ALKALINE SUCRALFATE ASPIRATION - SUBACUTE AND CHRONIC HISTOLOGIC EFFECTS IN RATS SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 DARTMOUTH COLL,HITCHCOCK MED CTR,DARTMOUTH MED SCH,DEPT PHYSIOL,HANOVER,NH 03756. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ANESTHESIA,BOSTON,MA 02114. DARTMOUTH COLL,HITCHCOCK MED CTR,DARTMOUTH MED SCH,DEPT PATHOL,HANOVER,NH 03756. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1994 VL 81 IS 3A SU S BP A314 EP A314 PG 1 WC Anesthesiology SC Anesthesiology GA PJ091 UT WOS:A1994PJ09100314 ER PT J AU SIMPSON, JI EIDE, TR KOSKI, G SCHIFF, GA CLAGNAZ, JF HOSSAIN, I TVERSKOY, A AF SIMPSON, JI EIDE, TR KOSKI, G SCHIFF, GA CLAGNAZ, JF HOSSAIN, I TVERSKOY, A TI INTRATHECAL MAGNESIUM PROTECTS AGAINST THE SPINAL-CORD ISCHEMIA SEEN WITH THORACIC AORTIC CROSS-CLAMPING SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 LONG ISL JEWISH MED CTR,DEPT ANESTHESIOL,NEW HYDE PK,NY 11042. MASSACHUSETTS GEN HOSP,HENRY K BEECHER MEM LABS,BOSTON,MA 02114. NR 3 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1994 VL 81 IS 3A SU S BP A686 EP A686 DI 10.1097/00000542-199409001-00685 PG 1 WC Anesthesiology SC Anesthesiology GA PJ091 UT WOS:A1994PJ09100685 ER PT J AU SMALL, S CULLEN, DJ BATES, D COOPER, JB LEAPE, L AF SMALL, S CULLEN, DJ BATES, D COOPER, JB LEAPE, L TI THE INCIDENT REPORTING SYSTEM LACKS VALIDITY AS THE BASIS FOR A QUALITY ASSURANCE PROGRAM SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH PUBL HLTH,BOSTON,MA 02114. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH PUBL HLTH,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1994 VL 81 IS 3A SU S BP A1226 EP A1226 PG 1 WC Anesthesiology SC Anesthesiology GA PJ091 UT WOS:A1994PJ09101225 ER PT J AU STOVER, EP SIEGEL, LC PARKS, R LEVIN, J BODY, SC SPIESS, BD DAMBRA, MN MADDI, R AF STOVER, EP SIEGEL, LC PARKS, R LEVIN, J BODY, SC SPIESS, BD DAMBRA, MN MADDI, R TI VARIABILITY IN TRANSFUSION PRACTICE FOR CORONARY-ARTERY BYPASS-SURGERY PERSISTS DESPITE NATIONAL CONSENSUS GUIDELINES - A 23-INSTITUTION STUDY SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 STANFORD UNIV,MED CTR,SCH MED,DEPT PHYSIOL REPROD,STANFORD,CA 94305. UNIV CALIF SAN FRANCISCO,DEPT LAB MED,SAN FRANCISCO,CA 94121. UNIV WASHINGTON,SEATTLE,WA 98195. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. MCSPI,SAN FRANCISCO,CA 94134. NR 1 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1994 VL 81 IS 3A SU S BP A1224 EP A1224 PG 1 WC Anesthesiology SC Anesthesiology GA PJ091 UT WOS:A1994PJ09101223 ER PT J AU YANG, HS MARTYN, JAJ GOUDSOUZIAN, N AF YANG, HS MARTYN, JAJ GOUDSOUZIAN, N TI THE INFLUENCE OF AGE ON THE DOSE-RESPONSE TO MIVACURIUM IN THE RAT SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ANESTHESIA,BOSTON,MA 02114. NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1994 VL 81 IS 3A SU S BP A1365 EP A1365 PG 1 WC Anesthesiology SC Anesthesiology GA PJ091 UT WOS:A1994PJ09101364 ER PT J AU GASSER, T WSZOLEK, ZK TROFATTER, J OZELIUS, L UITTI, RJ LEE, CS GUSELLA, J PFEIFFER, RF CALNE, DB BREAKEFIELD, XO AF GASSER, T WSZOLEK, ZK TROFATTER, J OZELIUS, L UITTI, RJ LEE, CS GUSELLA, J PFEIFFER, RF CALNE, DB BREAKEFIELD, XO TI GENETIC-LINKAGE STUDIES IN AUTOSOMAL-DOMINANT PARKINSONISM - EVALUATION OF 7 CANDIDATE GENES SO ANNALS OF NEUROLOGY LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; LEWY BODY DISEASE; REPEAT POLYMORPHISM; ALZHEIMERS-DISEASE; SUBSTANTIA-NIGRA; CYP2D LOCUS; ASSOCIATION; MUTATIONS; NEURONS; BDNF AB Linkage studies were performed in three families (A, B, and C) with autosomal dominantly inherited parkinsonism affecting multiple members in three generations. Affected individuals exhibited the cardinal signs and symptoms of Parkinson's disease, with a mean age of onset of 51, 62, and 61 years in Families A, B, and C, respectively. Parkinsonian symptoms responded to L-dopa treatment, and an [F-18]6-fluoro-L-dopa positron emission tomography scan in 1 affected member of Family B showed decreased striatal uptake typical of Parkinson's disease. Ancestors of all three families were traced to a small region in northern Germany and southern Denmark, suggesting the possibility of a common mutation. Linkage studies were performed with polymorphic markers associated with the following candidate genes: the genes for glutathione peroxidase (GPX1, 3q11), tyrosine hydroxylase (TH, 11p15.5), brain-derived neurotrophic factor (BDNF, 11p14), catalase (CAT, 11p13), amyloid precursor protein (APP, 21q21), copper-zinc superoxide dismutase (SOD1, 21q21), and debrisoquin 4-hydroxylase (CYP2D6, 22q13.1). Summed lod scores for all families excluded linkage to the genes GPX1, TH, APP, SOD1, and CYP2D6, as well as to the chromosomal region containing the genes CAT and BDNF. If families were analyzed individually, exclusion was possible for two (Family A), six (Family B), and five (Family C) of the seven candidate genes. There was strong evidence against linkage for the remaining loci in all families analyzed individually, except for TH, which was uninformative in Families A and B, and CYP2D6, which gave slightly positive pairwise lod scores in Family A. Our results indicate that the candidate genes investigated are not involved in the etiology of parkinsonism in these families. C1 MASSACHUSETTS GEN HOSP,MOLEC NEUROGENET UNIT,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA. HARVARD UNIV,SCH MED,NEUROSCI PROGRAM,BOSTON,MA 02115. UNIV NEBRASKA,MED CTR,DEPT INTERNAL MED,NEUROL SECT,OMAHA,NE. UNIV BRITISH COLUMBIA,CTR NEURODEGENERAT DISORDERS,VANCOUVER,BC,CANADA. RP GASSER, T (reprint author), UNIV MUNICH,KLINIKUM GROSSHADERN,DEPT NEUROL,MARCHIONINISTR 15,D-81377 MUNICH,GERMANY. FU NINDS NIH HHS [NS28384] NR 43 TC 82 Z9 82 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 SEP PY 1994 VL 36 IS 3 BP 387 EP 396 DI 10.1002/ana.410360310 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA PF966 UT WOS:A1994PF96600009 PM 7915897 ER PT J AU ZEITELS, SM VAUGHAN, CW AF ZEITELS, SM VAUGHAN, CW TI EXTERNAL COUNTERPRESSURE AND INTERNAL DISTENSION FOR OPTIMAL LARYNGOSCOPIC EXPOSURE OF THE ANTERIOR GLOTTAL COMMISSURE SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE LARYNGOSCOPE; LARYNGOSCOPY; MICROLARYNGOSCOPY; MICROSURGERY; PHONOSURGERY; VOCAL CORDS; VOCAL FOLDS AB External laryngeal counterpressure and internal laryngeal distention produce forces that are helpful for enhancing laryngoscopic exposure of the anterior glottis. These principles were formally described in the early 20th century, but are seldom used today. Hand pressure has been the typical source for external counterpressure. Since this maneuver is unstable if provided by an assistant and wasteful if provided by the surgeon, it is often neglected. Current phonomicrosurgical techniques require wider glottal exposure; therefore, a reexamination of the value of external counterpressure and internal distention is worthwhile. During the last 2 years, 125 microlaryngoscopic procedures were performed for a variety of benign, premalignant, and malignant lesions. All patients were placed in the Boyce-Jackson position and sustained with a modified Killian gallows, with resulting elevated-vector suspension. internal distention was achieved by placing the largest-lumen glottiscope possible between the endotracheal tube and the infrapetiole region. Exposure was also improved by using silk adhesive tape to apply external counterpressure to the lower laryngeal framework. The use of both external counterpressure and internal distention as an adjunct to microlaryngoscopy was most helpful for the surgical management of lesions located near the anterior commissure. Seemingly, the two resultant forces are in opposition to each other, but in fact they are complementary, both to each other and to the orthodox laryngoscopic principle of elevated-vector suspension. C1 HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02115. BOSTON UNIV,SCH MED,BOSTON,MA 02118. VET AFFAIRS MED CTR,OTOLARYNGOL SECT,BOSTON,MA. RP ZEITELS, SM (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,243 CHARLES ST,BOSTON,MA 02114, USA. NR 39 TC 51 Z9 52 U1 0 U2 1 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD SEP PY 1994 VL 103 IS 9 BP 669 EP 675 PG 7 WC Otorhinolaryngology SC Otorhinolaryngology GA PF982 UT WOS:A1994PF98200002 PM 8085725 ER PT J AU SARANTOS, P ABOUHAMZE, Z COPELAND, EM SOUBA, WW AF SARANTOS, P ABOUHAMZE, Z COPELAND, EM SOUBA, WW TI DECREASE OF GLUTAMINASE EXPRESSION BY INTERFERON-GAMMA IN HUMAN INTESTINAL EPITHELIAL-CELLS SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 46th Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 18-21, 1993 CL LOS ANGELES, CA SP SOC SURG ONCOL DE INTERFERON-GAMMA; GLUTAMINASE EXPRESSION; HUMAN INTESTINAL EPITHELIAL CELLS ID TUMOR-NECROSIS-FACTOR; CANCER CACHEXIA; MONOLAYERS; CACO-2; MODEL; SERUM AB Background: Glutaminase, the principal enzyme of glutamine hydrolysis, breaks down glutamine to supply energy and intermediates for cell growth and is present in high concentrations in replicating tissues such as intestinal epithelium and malignant tumors. In the host with cancer, glutaminase activity in the gut mucosa diminishes as the tumor grows, but the regulation of this response is unknown. Because cytokines may regulate the altered glutamine metabolism that is characteristic of the host with cancer, we studied the effects of cytokines on gut mucosal glutaminase expression in vitro using the human enterocytic Caco-2 cell line. Methods: Differentiated confluent cells were incubated with interleukin (IL)-1, IL-6, tumor necrosis factor, or interferon-gamma (IFN-gamma). After a 12-h incubation, glutaminase-specific activity and kinetic parameters (maximal enzyme activity [V(max)] and enzyme affinity [K(m)]) were determined. Glutaminase protein concentration was determined by Western blot analysis using a rabbit antirat polyclonal antibody. Total cellular RNA was extracted for Northern hybridization and radiolabeled with a glutaminase cDNA probe. Results: Of the cytokines studied, only IFN-gamma altered glutaminase activity. Kinetic studies indicated a decrease in activity secondary to a 25% decrease in V(max) with no change in K(m) consistent with a reduction in the number of glutaminase molecules rather than a change in enzyme affinity. Glutaminase protein was decreased 50% in IFN-gamma-treated cells when compared with controls. This decrease was dose-independent and was associated with a concomitant 75% decrease in glutaminase messenger RNA levels. These reductions in message and protein translated into a 60-80% decrease in functional glutaminase-specific activity. Conclusions. This IFN-gamma-mediated decrease in glutaminase activity may be one mechanism by which gut glutamine metabolism is diminished as the tumor grows and becomes the principal organ of glutamine use. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,DIV SURG ONCOL,BOSTON,MA 02114. UNIV FLORIDA,COLL MED,DEPT SURG,GAINESVILLE,FL 32611. FU NCI NIH HHS [CA 45327, T32-CA09605-03] NR 26 TC 9 Z9 9 U1 0 U2 2 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 SEP PY 1994 VL 1 IS 5 BP 428 EP 435 DI 10.1007/BF02303817 PG 8 WC Oncology; Surgery SC Oncology; Surgery GA PC576 UT WOS:A1994PC57600013 PM 7850545 ER PT J AU GRILLO, HC AF GRILLO, HC TI SLIDE TRACHEOPLASTY FOR LONG-SEGMENT CONGENITAL TRACHEAL STENOSIS SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 30th Annual Meeting of the Society-of-Thoracic-Surgeons CY JAN 31-FEB 02, 1994 CL NEW ORLEANS, LA SP SOC THORAC SURGEONS ID PERICARDIAL PATCH; CHILDREN; MANAGEMENT; INFANTS AB Resection and reconstruction of long congenital tracheal stenosis often is impossible or results in excessive anastomotic tension. Anterior tracheoplasty using a patch of pericardium or cartilage may result in granulation tissue needing repeated bronchoscopies, tracheostomy, and stents and may produce recurrent stenosis. Tracheoplasty may be performed by dividing the stenosis at midpoint, incising the proximal and distal. narrowed segments vertically on opposite anterior and posterior surfaces and sliding these together. The stenotic segment is shortened by half, the circumference doubled, and the lumenal cross-section quadrupled. Approach is cervical or with partial sternotomy. Cardiopulmonary bypass is not necessary. Four patients (ages: 3 months, 31/2 years, 19 years, and 19 years) were so treated for stenosis of 36% to 83% of tracheal length. Blood supply was not impaired. Healing was excellent and complications were minimal. C1 HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. RP GRILLO, HC (reprint author), MASSACHUSETTS GEN HOSP,GEN THORAC SURG UNIT,BOSTON,MA 02114, USA. NR 16 TC 101 Z9 108 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD SEP PY 1994 VL 58 IS 3 BP 613 EP 620 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA PJ395 UT WOS:A1994PJ39500001 PM 7944680 ER PT J AU GRILLO, HC AF GRILLO, HC TI SLIDE TRACHEOPLASTY FOR LONG-SEGMENT CONGENITAL TRACHEAL STENOSIS - RESPONSE SO ANNALS OF THORACIC SURGERY LA English DT Note C1 HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. RP GRILLO, HC (reprint author), MASSACHUSETTS GEN HOSP,GEN THORAC SURG UNIT,BOSTON,MA 02114, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD SEP PY 1994 VL 58 IS 3 BP 621 EP 621 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA PJ395 UT WOS:A1994PJ39500003 ER PT J AU AKINS, CW HILGENBERG, AD BUCKLEY, MJ VLAHAKES, GJ TORCHIANA, DF DAGGETT, WM AUSTEN, WG AF AKINS, CW HILGENBERG, AD BUCKLEY, MJ VLAHAKES, GJ TORCHIANA, DF DAGGETT, WM AUSTEN, WG TI MITRAL-VALVE RECONSTRUCTION VERSUS REPLACEMENT FOR DEGENERATIVE OR ISCHEMIC MITRAL REGURGITATION SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 30th Annual Meeting of the Society-of-Thoracic-Surgeons CY JAN 31-FEB 02, 1994 CL NEW ORLEANS, LA SP SOC THORAC SURGEONS ID CARPENTIER TECHNIQUES; REPAIR; INSUFFICIENCY; DISEASE; INCOMPETENCE; MORBIDITY AB Between January 1985 and June 1992, 263 consecutive patients had mitral valve reconstruction (133 patients) or replacement (130 patients) for degenerative or ischemic mitral regurgitation. The two groups were similar in sex, age, prior infarctions or cardiac operations, hypertension, angina, and functional class. Both groups were similar in mean ejection fraction, pulmonary artery pressure, cardiac index, and incidence of coronary artery disease. More reconstruction than replacement patients had ischemic etiology (22 [16%] versus 12 [9%]; p = not significant), and fewer reconstruction patients had ruptured anterior leaflet chordae (9 [7%] versus 39 [30%]; p < 0.01). More reconstruction than replacement patients had concomitant cardiac procedures (67 [50%] versus 59 [45%]; p = not significant). Hospital death occurred in 4 reconstruction patients (3%) and 15 (12%) replacement patients (p < 0.01). Median postoperative stay was shorter in reconstruction patients (10 versus 12 days; p = 0.02). Late valve-related death occurred in 3 reconstruction patients (2%) and 8 (6%) replacement patients (p = 0.08). Six-year actuarial freedom from thromboembolism was 92% for the reconstruction group and 85% for the replacement group (p = 0.12). Freedom from all valve-related morbidity and mortality was 85% for the reconstruction patients and 73% for the replacement patients (p = 0.03). Significant multivariate predictors of hospital death were age, mitral valve replacement, functional class, congestive heart failure, no posterior chordal rupture, and nonelective operation. Mitral valve reconstruction, when technically feasible, is the procedure of choice for degenerative or ischemic mitral regurgitation because of significantly lower hospital mortality and late valve-related events. C1 MASSACHUSETTS GEN HOSP,CARDIAC SURG UNIT,BOSTON,MA 02114. NR 27 TC 138 Z9 149 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD SEP PY 1994 VL 58 IS 3 BP 668 EP 676 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA PJ395 UT WOS:A1994PJ39500010 PM 7944687 ER PT J AU THEODOSIADIS, PG MOULTON, RS WALSH, AW GRAGOUDAS, ES DAMICO, DJ AF THEODOSIADIS, PG MOULTON, RS WALSH, AW GRAGOUDAS, ES DAMICO, DJ TI EXPERIMENTAL TRANSIENT EXUDATIVE RETINAL-DETACHMENT IN THE RAT SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID HYPERTENSIVE CHOROIDOPATHY; PIGMENT EPITHELIOPATHY; MALIGNANT HYPERTENSION; FUNDUS LESIONS; SECONDARY; INJURY; DAMAGE AB Objective: To establish a new model of exudative retinal detachment in the rat. Methods: Photothrombosis was produced in a single retinal vein using direct treatment with a dye laser operating in the yellow wavelength (577 nm). Control eyes received identical laser applications, but treatment was placed alongside the vessel and photothrombosis was not produced. Eyes were examined at intervals during the subsequent week with ophthalmoscopy, photography, fluerescein angiography, and light microscopy. Results: In 13 (41%) of 32 eyes with photothrombosis, bullous retinal detachments developed 1 day after laser treatment, and continued occlusion of the vein was confirmed with fluorescein angiography. Detachments persisted for 2 to 4 days and spontaneously resolved; resolution coincided with restored venous patency at 5 to 7 days. None of the 20 control eyes developed bullous detachments (P<.005). Conclusions: Laser photothrombosis in the rat offers a simple and accessible model of transient exudative retinal detachment without the need for exogenous chromophores. C1 MASSACHUSETTS EYE & EAR INFIRM,RETINA SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT OPHTHALMOL,BOSTON,MA. MASSACHUSETTS EYE & EAR INFIRM,LASER RES LAB,BOSTON,MA 02114. NR 20 TC 4 Z9 4 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 SEP PY 1994 VL 112 IS 9 BP 1236 EP 1242 PG 7 WC Ophthalmology SC Ophthalmology GA PG194 UT WOS:A1994PG19400018 PM 8085967 ER PT J AU COLE, BF GELBER, RD ANDERSON, KM AF COLE, BF GELBER, RD ANDERSON, KM TI PARAMETRIC APPROACHES TO QUALITY-ADJUSTED SURVIVAL ANALYSIS SO BIOMETRICS LA English DT Article DE ACCELERATED FAILURE TIME REGRESSION; COMPETING RISKS; MAXIMUM LIKELIHOOD ESTIMATION; MEAN SURVIVAL; MULTIVARIATE SURVIVAL; QUALITY OF LIFE; SURVIVAL ANALYSIS; UTILITY FUNCTIONS ID OPERABLE BREAST-CANCER; FAILURE TIME DATA; OF-LIFE; REGRESSION-ANALYSIS; ADJUVANT THERAPY; CLINICAL-TRIALS; ENDPOINT; MODELS AB We present a parametric methodology for performing quality-of-life-adjusted survival analysis using multivariate censored survival data. It represents a generalization of the nonparametric Q-TWIST method (Quality-adjusted Time without Symptoms and Toxicity). The event times correspond to transitions between states of health that differ in terms of quality of life. Each transition is governed by a competing risks model where the health states are the competing risks. Overall survival is the sum of the amount of time spent in each health state. The first step of the proposed methodology consists of defining a quality function that assigns a ''score'' to a life having given health state transitions. It is a composite measure of both quantity and quality of life. In general, the quality function assigns a small value to a short life with poor quality and a high value to a long life with good quality. In the second step, parametric survival models are fit to the data. This is done by repeatedly modeling the conditional cause-specific hazard functions given the previous transitions. Covariates are incorporated by accelerated failure time regression, and the model parameters are estimated by maximum likelihood. Lastly, the modeling results are used to estimate the expectation of quality functions. Standard errors and confidence intervals are computed using the bootstrap and delta methods. The results are useful for simultaneously evaluating treatments in terms of quantity and quality of life. To demonstrate the proposed methods, we perform an analysis of data from the international Breast Cancer Study Group Trial V, which compared short-duration chemotherapy versus long-duration chemotherapy in the treatment of node-positive breast cancer. The events studied are: (1) the end of treatment toxicity, (2) disease recurrence, and (3) overall survival. C1 HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,BOSTON,MA 02115. DANA FARBER CANC INST,DIV BIOSTAT,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DANA FARBER CANC INST,DEPT BIOSTAT,DIV BIOSTAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. CENTOCOR INC,MALVERN,PA 19355. RI Cole, Bernard/I-3775-2012 FU NCI NIH HHS [CA-06516] NR 24 TC 24 Z9 24 U1 0 U2 1 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 SEP PY 1994 VL 50 IS 3 BP 621 EP 631 DI 10.2307/2532777 PG 11 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA PL748 UT WOS:A1994PL74800003 PM 7981389 ER PT J AU GRAY, RJ AF GRAY, RJ TI SPLINE-BASED TESTS IN SURVIVAL ANALYSIS SO BIOMETRICS LA English DT Article DE PENALIZED LIKELIHOOD; PROPORTIONAL HAZARDS; SPLINE-BASED TESTS; SURVIVAL ANALYSIS; TIME-VARYING COEFFICIENTS ID PROPORTIONAL HAZARDS MODEL; NEGATIVE BREAST-CANCER; NONPARAMETRIC REGRESSION; FLOW-CYTOMETRY AB This paper examines a method for testing hypotheses on covariate effects in a proportional hazards model, and also on how effects change over time in regression analysis of survival data. The technique used is very general and can be applied to testing many other aspects of parametric and semiparametric models. The basic idea is to formulate a flexible parametric alternative using fixed knot splines, together with a penalty function that penalizes noisy alternatives more than smooth ones, to focus the power of the tests toward smooth alternatives. The test statistics are the analogs of ordinary likelihood-based statistics, only computed from a penalized likelihood formed by subtracting the penalty function from the ordinary log-likelihood. Large-sample approximations to the distributions are found when the number of knots is held fixed as the sample size increases. Numerical results suggest these approximations may be adequate with moderate sized samples. C1 HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. RP GRAY, RJ (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT BIOSTAT,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA-39929, CA-51962] NR 29 TC 101 Z9 103 U1 1 U2 8 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 SEP PY 1994 VL 50 IS 3 BP 640 EP 652 DI 10.2307/2532779 PG 13 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA PL748 UT WOS:A1994PL74800005 PM 7981391 ER PT J AU LIPSITZ, SR DEAR, KBG ZHAO, LP AF LIPSITZ, SR DEAR, KBG ZHAO, LP TI JACKKNIFE ESTIMATORS OF VARIANCE FOR PARAMETER ESTIMATES FROM ESTIMATING EQUATIONS WITH APPLICATIONS TO CLUSTERED SURVIVAL-DATA SO BIOMETRICS LA English DT Note DE CLUSTERED SURVIVAL DATA; QUASI-LIKELIHOOD; SCORE VECTOR ID MODELS AB An estimate of a parameter vector beta is often obtained by setting a ''score'' vector equal to zero and solving for ($) over cap beta. Estimating equations of this type include maximum likelihood, quasi-likelihood (McCullagh, 1983, Annals of Statistics 11, 59-67), and generalized estimating equations (Liang and Zeger, 1986, Biometrika 73, 13-22). White (1982, Econometrica 50, 1-26) proposed a variance estimator for ($) over cap beta that is robust to model misspecification. We show that a ''one-step'' jackknife estimator of variance is asymptotically equivalent to the variance estimator proposed by White. The one-step variance estimator may be preferred when the appropriate computer packages are not available to compute White's estimator directly. This jackknife estimator is very useful in our example with clustered survival data. C1 DANA FARBER CANC INST,BOSTON,MA 02115. UNIV NEWCASTLE,DEPT STAT,NEWCASTLE,NSW 2308,AUSTRALIA. FRED HUTCHINSON CANC RES CTR,PROGRAM EPIDEMIOL,SEATTLE,WA 98104. LIMBURGS UNIV CTR,DIEPENBEEK,BELGIUM. RP LIPSITZ, SR (reprint author), HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA 55576]; NIAID NIH HHS [AI 24643]; NIGMS NIH HHS [GM 29745] NR 6 TC 53 Z9 53 U1 0 U2 3 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 808 17TH ST NW SUITE 200, WASHINGTON, DC 20006-3910 SN 0006-341X J9 BIOMETRICS JI Biometrics PD SEP PY 1994 VL 50 IS 3 BP 842 EP 846 DI 10.2307/2532797 PG 5 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA PL748 UT WOS:A1994PL74800023 PM 7981404 ER PT J AU LIPSITZ, SR FITZMAURICE, G AF LIPSITZ, SR FITZMAURICE, G TI AN EXTENSION OF YULE-Q TO MULTIVARIATE BINARY DATA SO BIOMETRICS LA English DT Note DE EM ALGORITHM; LOG-LINEAR MODEL; PAIRWISE ASSOCIATION AB In this note we describe a summary measure of pairwise association for multivariate binary data based on the conditional odds ratio. The proposed measure is an extension of Yule's Q to more than two binary random variables. Unlike marginal measures of association, this measure is not constrained by the marginal probabilities of success. For example, when each binary variable has a different probability of success, the upper limit of the pairwise marginal correlation coefficient is constrained to be less than 1. If one prefers a measure of association that is unconstrained, then With only two binary variables, Bishop, Fienberg, and Holland (1975, Discrete Multivariate Analysis: Theory and Practice, Cambridge, Massachusetts: MIT Press) suggest the use of the odds ratio or, equivalently, Yule's Q. Yule's Q transforms the odds ratio between the two binary variables from [0, infinity) to [-1, 1]. We propose an extension of Yule's Q to more than two binary random variables. This measure of pairwise association is based on the conditional odds ratio from a log-linear model. C1 DANA FARBER CANC INST,DIV BIOSTAT & EPIDEMIOL,BOSTON,MA 02115. RP LIPSITZ, SR (reprint author), HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,677 HUNTINGTON AVE,BOSTON,MA 02115, USA. FU NIEHS NIH HHS [ES07142]; NIGMS NIH HHS [GM29745]; NIMH NIH HHS [MH17119] NR 11 TC 4 Z9 4 U1 0 U2 1 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 SEP PY 1994 VL 50 IS 3 BP 847 EP 852 DI 10.2307/2532798 PG 6 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA PL748 UT WOS:A1994PL74800024 PM 7981405 ER PT J AU GRAY, RJ AF GRAY, RJ TI A KERNEL-METHOD FOR INCORPORATING INFORMATION ON DISEASE PROGRESSION IN THE ANALYSIS OF SURVIVAL SO BIOMETRIKA LA English DT Article DE AUXILIARY END-POINTS; CENSORED DATA; SEMI-MARKOV MODEL ID KAPLAN-MEIER STATISTICS; TIME DATA; INFERENCE; SAMPLE AB This paper considers incorporating information on disease progression in the analysis of survival. A three-state model is assumed, with the distribution of each transition estimated separately. The distribution of survival following progression can depend on the time of progression. Kernel methods are used to give consistent estimators under general forms of dependence. The estimators for the individual transitions are then combined into an overall estimator of the survival distribution. A test statistic for equality of survival between treatment groups is proposed based on the tests of Pepe and Fleming (1989, 1991). In simulations the kernel method successfully incorporated dependence on the time of progression in some reasonable settings, but under extreme forms of dependence the tests had substantial bias. If survival beyond progression can be predicted fairly accurately, then gains in power over standard methods that ignore progression can be substantial, but the gains are smaller when survival beyond progression is more variable. The methodology is illustrated with an application to a breast cancer clinical trial. RP GRAY, RJ (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT BIOSTAT,44 BINNEY ST,BOSTON,MA 02115, USA. NR 20 TC 34 Z9 36 U1 0 U2 3 PU BIOMETRIKA TRUST PI LONDON PA UNIV COLLEGE LONDON GOWER ST-BIOMETRIKA OFFICE, LONDON, ENGLAND WC1E 6BT SN 0006-3444 J9 BIOMETRIKA JI Biometrika PD SEP PY 1994 VL 81 IS 3 BP 527 EP 539 PG 13 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA PP367 UT WOS:A1994PP36700007 ER PT J AU HARRIS, NL JAFFE, ES STEIN, H BANKS, PM CHAN, JKC CLEARY, ML DELSOL, G DEWOLFPEETERS, C FALINI, B GATTER, KC GROGAN, TM ISAACSON, PG KNOWLES, DM MASON, DY MULLERHERMELINK, HK PILERI, SA PIRIS, MA RALFKIAER, E WARNKE, RA AF HARRIS, NL JAFFE, ES STEIN, H BANKS, PM CHAN, JKC CLEARY, ML DELSOL, G DEWOLFPEETERS, C FALINI, B GATTER, KC GROGAN, TM ISAACSON, PG KNOWLES, DM MASON, DY MULLERHERMELINK, HK PILERI, SA PIRIS, MA RALFKIAER, E WARNKE, RA TI A REVISED EUROPEAN-AMERICAN CLASSIFICATION OF LYMPHOID NEOPLASMS - A PROPOSAL FROM THE INTERNATIONAL LYMPHOMA STUDY-GROUP SO BLOOD LA English DT Review ID LARGE-CELL LYMPHOMA; REED-STERNBERG CELLS; NON-HODGKINS-LYMPHOMA; ACUTE LYMPHOBLASTIC-LEUKEMIA; EPSTEIN-BARR-VIRUS; CHRONIC LYMPHOCYTIC-LEUKEMIA; POLYMERASE CHAIN-REACTION; RECEPTOR GENE REARRANGEMENTS; LARGE GRANULAR LYMPHOCYTES; T(14-18) CHROMOSOMAL TRANSLOCATION C1 NCI, DEPT PATHOL, BETHESDA, MD 20892 USA. FREE UNIV BERLIN, KLINIKUM BENJAMIN FRANKLIN, DEPT PATHOL, W-1000 BERLIN, GERMANY. UNIV TEXAS, HLTH SCI CTR, DEPT PATHOL, SAN ANTONIO, TX 78284 USA. QUEEN ELIZABETH HOSP, DEPT PATHOL, HONG KONG, HONG KONG. STANFORD UNIV, SCH MED, DEPT PATHOL, STANFORD, CA 94305 USA. UNIV TOULOUSE 3, FAC MED PURPAN, DEPT PATHOL, F-31062 TOULOUSE, FRANCE. UNIV LOUVAIN, DEPT PATHOL, LOUVAIN, BELGIUM. UNIV ARIZONA, SCH MED, DEPT PATHOL, TUCSON, AZ USA. UCL, SCH MED, DEPT PATHOL, LONDON W1N 8AA, ENGLAND. 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. UNIV OXFORD, JOHN RADCLIFFE HOSP, DEPT CELLULAR SCI, OXFORD OX3 9DU, ENGLAND. UNIV PERUGIA, INST HEMATOL, I-06100 PERUGIA, ITALY. RP HARRIS, NL (reprint author), HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, DEPT PATHOL, WARREN 2, BOSTON, MA 02114 USA. OI Piris, Miguel A/0000-0001-5839-3634 NR 296 TC 5064 Z9 5214 U1 14 U2 90 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 1994 VL 84 IS 5 BP 1361 EP 1392 PG 32 WC Hematology SC Hematology GA PE387 UT WOS:A1994PE38700002 PM 8068936 ER PT J AU ENGEL, P GRIBBEN, JG FREEMAN, GJ ZHOU, LJ NOZAWA, Y ABE, M NADLER, LM WAKASA, H TEDDER, TF AF ENGEL, P GRIBBEN, JG FREEMAN, GJ ZHOU, LJ NOZAWA, Y ABE, M NADLER, LM WAKASA, H TEDDER, TF TI THE B7-2 (B70) COSTIMULATORY MOLECULE EXPRESSED BY MONOCYTES AND ACTIVATED B-LYMPHOCYTES IS THE CD86 DIFFERENTIATION ANTIGEN SO BLOOD LA English DT Note ID T-CELL ACTIVATION; CTLA-4 COUNTER-RECEPTOR; MONOCLONAL-ANTIBODY; CD28; LIGAND; INTERLEUKIN-2; PROLIFERATION; INDUCTION; PROVIDES; B7/BB-1 C1 DUKE UNIV,MED CTR,DEPT IMMUNOL,DURHAM,NC 27710. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. FUKUSHIMA MED COLL,DEPT PATHOL,FUKUSHIMA,JAPAN. RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X FU NCI NIH HHS [CA-34183, CA-54464]; NIAID NIH HHS [AI-26872] NR 30 TC 77 Z9 78 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 SEP 1 PY 1994 VL 84 IS 5 BP 1402 EP 1407 PG 6 WC Hematology SC Hematology GA PE387 UT WOS:A1994PE38700005 PM 7520767 ER PT J AU KUTER, DJ ROSENBERG, RD AF KUTER, DJ ROSENBERG, RD TI APPEARANCE OF A MEGAKARYOCYTE GROWTH-PROMOTING ACTIVITY, MEGAPOIETIN, DURING ACUTE THROMBOCYTOPENIA IN THE RABBIT SO BLOOD LA English DT Article ID THROMBOPOIETIC ACTIVITY; PLATELET PRODUCTION; STIMULATORY FACTOR; INTERLEUKIN-6; PLASMA; RAT; PURIFICATION; ENDOMITOSIS; INVIVO; CELLS C1 MASSACHUSETTS GEN HOSP,HEMATOL UNIT,BOSTON,MA 02114. BETH ISRAEL HOSP,DEPT MED,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA. RP KUTER, DJ (reprint author), MIT,WHITAKER COLL HLTH SCI & TECHNOL,DEPT BIOL,77 MASSACHUSETTS AVE,CAMBRIDGE,MA 02139, USA. FU NHLBI NIH HHS [HL39753] NR 39 TC 70 Z9 70 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 SEP 1 PY 1994 VL 84 IS 5 BP 1464 EP 1472 PG 9 WC Hematology SC Hematology GA PE387 UT WOS:A1994PE38700014 PM 8068941 ER PT J AU LAZARUS, HM GRAY, R CIOBANU, N WINTER, J WEINER, RS AF LAZARUS, HM GRAY, R CIOBANU, N WINTER, J WEINER, RS TI PHASE-I TRIAL OF HIGH-DOSE MELPHALAN, HIGH-DOSE ETOPOSIDE AND AUTOLOGOUS BONE-MARROW RE-INFUSION IN SOLID TUMORS - AN EASTERN-COOPERATIVE-ONCOLOGY-GROUP (ECOG) STUDY SO BONE MARROW TRANSPLANTATION LA English DT Article ID METASTATIC BREAST-CANCER; COLORECTAL-CARCINOMA; TRANSPLANTATION; CHEMOTHERAPY; SUPPORT; CYCLOPHOSPHAMIDE; THERAPY; VP-16-213; INTENSIFICATION; MALIGNANCIES AB The purpose of this work was to determine the maximum tolerated (phase II) dose of melphalan and etoposide that can be given in conjunction with autologous BM re-infusion in patients who have refractory or relapsed solid tumors. Twenty-six patients with refractory or relapsed breast cancer (n = 15), small cell lung cancer (n = 1), ovarian cancer (n = 3), colorectal cancer (n = 3) or malignant melanoma (n = 4) were enrolled and treated in this phase I study. Patients ranged in age from 31 to 60 years (median 44.5 years). Melphalan 180 mg/m(2) (60 mg/m(2)/day for 3 consecutive days iv over 30 min) and etoposide 1200-3600 mg/m(2) (400-1200 mg/m(2)/day for 3 consecutive days iv over 4 h) were given followed by autologous BM infusion 60-72 h after completion of chemotherapy. Ten patients received GM-CSF or G-CSF therapy after marrow re-infusion. Regimen-related toxicities included fever, pancytopenia, mucositis, nausea, vomiting, diarrhea, esophagitis, hepatic dysfunction and infection. Neutrophils recovered to > 500 x 10(6)/l and platelets recovered to > 20 x 10(9)/l (without transfusions) a median of 17 days and 20.5 days after marrow infusion, respectively. Dose-limiting toxicity occurred at an etoposide dose of 3600 mg/m(2) since 4 of 6 patients treated at this dose level experienced grade 4 NCI Common Toxicity Criteria (mucositis (n = 3) and infection (n = 1)). Complete responses were noted in 7 patients (breast cancer (n = 5), colorectal cancer (n = 1) and melanoma (n = 1)); partial responses were observed in 5 patients. Melphalan 180 mg/m(2) and etoposide 3000 mg/m(2) is a potent high-dose chemotherapy regimen with significant antineoplastic activity, particularly for breast cancer, and has acceptable toxicity when administered in conjunction with autologous BM re-infusion. C1 UNIV FLORIDA, J HILLIS MILLER CANC CTR, GAINESVILLE, FL USA. NORTHWESTERN UNIV, EVANSTON, IL 60208 USA. CASE WESTERN RESERVE UNIV, IRELAND CANC CTR, EASTERN COOPERAT ONCOL GRP, CLEVELAND, OH 44106 USA. DANA FARBER CANC CTR, BOSTON, MA USA. ALBERT EINSTEIN CANC CTR, NEW YORK, NY USA. RP LAZARUS, HM (reprint author), CASE WESTERN RESERVE UNIV, IRELAND CANC CTR, DEPT MED, 2074 ABINGTON RD, CLEVELAND, OH 44106 USA. FU NCI NIH HHS [CA 21115, CA 14548, P30CA43703] NR 43 TC 14 Z9 14 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD SEP PY 1994 VL 14 IS 3 BP 443 EP 448 PG 6 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA PH586 UT WOS:A1994PH58600020 PM 7994270 ER PT J AU GOFF, BA HERMANTO, U RUMBAUGH, J BLAKE, J BAMBERG, M HASAN, T AF GOFF, BA HERMANTO, U RUMBAUGH, J BLAKE, J BAMBERG, M HASAN, T TI PHOTOIMMUNOTHERAPY AND BIODISTRIBUTION WITH AN OC125-CHLORIN IMMUNOCONJUGATE IN AN IN-VIVO MURINE OVARIAN-CANCER MODEL SO BRITISH JOURNAL OF CANCER LA English DT Article ID ANTIBODY-TARGETED PHOTOLYSIS; OC-125 MONOCLONAL-ANTIBODY; PHOTODYNAMIC THERAPY; INTRAPERITONEAL INJECTION; CARCINOMA CELLS; TUMOR; MICE; PHOTOSENSITIZERS; HEMATOPORPHYRIN; RADIOIMMUNOTHERAPY AB Photodynamic therapy (PDT) is an experimental approach to the treatment of neoplasms in which photosensitisers (PSs) accumulated in malignant tissues are photoactivated with appropriate wavelengths of light. The target specificity of PSs may be improved by linking them with carrier macromolecules such as monoclonal antibodies (MAbs). OC125 is a murine MAb that recognises the antigen CA 125, which is expressed on 80% of non-mucinous ovarian tumours. A chlorin derivative conjugated to OC125 was shown to be selectively phototoxic to ovarian cancer and other CA 125-positive cells in vitro and ex vivo. We now report in vivo studies using an ascitic Balb/c nude mouse ovarian cancer model. Ascites was induced by intraperitoneal injection of cells from the human ovarian cancer cell line NIH:OVCAR3. Six weeks after injection, when the animals had developed ascites, biodistribution studies were carried out by injecting the immunoconjugate (IC) or free PS intraperitoneally and sacrificing the animals at 3, 6, 12, 24, 48, 72 and 168 h later. The PS was quantitated by extraction and fluorescence spectroscopy. For both the IC and free PS, peak tumour concentrations were reached at 24 h; however, the absolute concentrations for the IC were always higher (2- to 3-fold) than the free PS. Tumour to non-tumour ratios at 24 h for the IC were 6.8 for blood, 6.5 for liver, 7.2 for kidney, 5.7 for skin and 3.5 for intestine. Evaluation of Viable tumour cells in ascites following in vivo PDT with a single light exposure demonstrated a dose-dependent relationship with fluence and IC concentration. However, there was significant treatment-related toxicity at all fluences. With multiple low-dose treatments, the percentage of viable tumour cells was also significantly reduced and there were no treatment-related deaths. These data suggest that, while photoimmunotherapy remains promising as a new treatment modality for ovarian cancers, careful quantitative dosimetry of both IC and light may need to be combined with multiple treatments (as with radiation therapy and chemotherapy) to control malignant disease yet maintain acceptable toxicity in vivo. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT DERMATOL,WELLMAN LABS PHOTOMED,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT DERMATOL,VINCENT GYNECOL SERV,BOSTON,MA 02114. FU NIAMS NIH HHS [1RO1 AR40352-01A1] NR 46 TC 62 Z9 64 U1 1 U2 5 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD SEP PY 1994 VL 70 IS 3 BP 474 EP 480 DI 10.1038/bjc.1994.330 PG 7 WC Oncology SC Oncology GA PD313 UT WOS:A1994PD31300018 PM 8080733 ER PT J AU NAVON, SE RUBIN, PAD AF NAVON, SE RUBIN, PAD TI ECTOPIC CONJUNCTIVALISATION IN STEVENS-JOHNSON SYNDROME SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Note C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BOSTON,MA 02114. NR 7 TC 2 Z9 2 U1 0 U2 0 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 SEP PY 1994 VL 78 IS 9 BP 727 EP 728 DI 10.1136/bjo.78.9.727 PG 2 WC Ophthalmology SC Ophthalmology GA PD634 UT WOS:A1994PD63400016 PM 7947557 ER PT J AU LEES, S PROSTAK, KS INGLE, VK KJOLLER, K AF LEES, S PROSTAK, KS INGLE, VK KJOLLER, K TI THE LOCI OF MINERAL IN TURKEY LEG TENDON AS SEEN BY ATOMIC-FORCE MICROSCOPE AND ELECTRON-MICROSCOPY SO CALCIFIED TISSUE INTERNATIONAL LA English DT Article DE COLLAGEN; CRYSTAL HABIT; ULTRASTRUCTURE; TURKEY LEG TENDON ID BONE; COLLAGEN; CRYSTALS; DIFFRACTION AB Transmission electron micrographs of fully mineralized turkey leg tendon in cross-section show the ultrastructure to be more complex than has been previously described. The mineral is divided into two regions. Needlelike-appearing crystallites fill the extrafibrillar volume whereas only platelike crystallites are found within the fibrils. When the specimen is tilted through a large angle, some of the needlelike-appearing crystallites are replaced by platelets, suggesting that the needlelike crystallites are platelets viewed on edge. If so, these platelets have their broad face roughly parallel to the fibril surface and thereby the fibril axis, where the intrafibrillar platelets are steeply inclined to the fibril axis. The projection of the intrafibrillar platelets is perpendicular to the fibril axis. The extrafibrillar volume is at least 60% of the total, the fibrils occupying 40%. More of the mineral appears to be extrafibrillar than within the fibrils. Micrographs of the mineralized tendon in thickness show both needlelike-appearing and platelet crystallites. Stereoscopic views show that the needlelike-appearing crystallites do not have a preferred orientation. From the two-dimensional Fourier transform of a selected area of the cross-sectional image, the platelike crystallites have an average dimension of 58 nm. The needlelike-appearing crystallites have an average thickness of 7 nm. The maximum length is at least 90 nm. Atomic force microscopy (AFM) of unstained, unmineralized turkey leg tendon shows collagen fibrils very much like shadow replicas of collagen in electron micrographs. AFM images of the mineralized tendon show only an occasional fibril. Mineral crystallites are not visible. Because the collagen is within the fibrils, the extrafibrillar mineral must be embedded in noncollagenous organic matter. When the tissue is demineralized, the collagen fibrils are exposed. The structure as revealed by the two modalities is a composite material in which each component is itself a composite. Determination of the properties of the mineralized tendon from the properties of its elements is more difficult than considering the tendon to be just mineral-filled collagen. C1 FORSYTH DENT CTR,DEPT ELECTRON MICROSCOPY,BOSTON,MA 02115. NORTHEASTERN UNIV,DEPT ELECT & COMP ENGN,BOSTON,MA 02115. DIGITAL INSTRUMENTS CO,SANTA BARBARA,CA 93103. RP LEES, S (reprint author), FORSYTH DENT CTR,DEPT BIOENGN,140 FENWAY,BOSTON,MA 02115, USA. FU NIA NIH HHS [R01 AG02325] NR 23 TC 86 Z9 86 U1 0 U2 5 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0171-967X J9 CALCIFIED TISSUE INT JI Calcif. Tissue Int. PD SEP PY 1994 VL 55 IS 3 BP 180 EP 189 DI 10.1007/BF00425873 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PC725 UT WOS:A1994PC72500006 PM 7987731 ER PT J AU TEICHER, BA HOLDEN, SA CHEN, YN ARA, G KORBUT, TT NORTHEY, D AF TEICHER, BA HOLDEN, SA CHEN, YN ARA, G KORBUT, TT NORTHEY, D TI CAI - EFFECTS ON CYTOTOXIC THERAPIES IN-VITRO AND IN-VIVO SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE L651582; CAI; COMBINATION THERAPY; ANTITUMOR ALKYLATING AGENTS ID LEWIS LUNG-CARCINOMA; MELPHALAN ANTITUMOR-ACTIVITY; MALIGNANT-TUMOR CELLS; 4 PLATINUM COMPLEXES; MOUSE MAMMARY-TUMOR; EXTRACELLULAR-MATRIX; INVASIVE ACTIVITY; FLUOSOL-DA; INVIVO; METASTASIS AB CAI (NSC 609974; L651582), a new agent that has demonstrated antimetastatic activity in vitro and in vivo, was not very cytotoxic toward EMT-6 mouse mammary carcinoma cells in culture or toward FSaIIC fibrosarcoma cells in vivo. Coexposure of EMT-6 cells to CAI and antitumor alkylating agents under various environmental conditions did not markedly increase the cytotoxicity of cisplatin (CDDP), melphalan, or carmustine (BCNU). However, the combination of CAI and 4-hydroperoxycyclophosphamide (4-HC) produced much greater than additive killing of EMT-6 cells. CAI also increased the sensitivity of hypoxic EMT-6 cells to X-rays. CAI increased the cytotoxicity of cyclophosphamide toward FSaIIC tumor cells when animals were treated with single doses of both drugs. The effect of CAI on tumor cell killing by cyclophosphamide was greatest at high doses of the antitumor alkylating agent. CAI administration appeared to result in increased serum levels of prostaglandin E(2) and leukotriene B-4 in animals bearing the Lewis lung tumor. Administration of CAI on days 4-18 did not alter the growth of the Lewis lung carcinoma but did result in an increase in the tumor-growth delay produced by treatment with CDDP, cyclophosphamide, melphalan, BCNU, and fractionated radiation. Although CAI did not reduce the number of lung metastases present in Lewis lung carcinoma-bearing mice on day 20, it did appear to reduce the number of large (vascularized) metastases present on that day. C1 JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. RP TEICHER, BA (reprint author), DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. NR 48 TC 9 Z9 9 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD SEP PY 1994 VL 34 IS 6 BP 515 EP 521 DI 10.1007/BF00685664 PG 7 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA PL404 UT WOS:A1994PL40400012 PM 7923563 ER PT J AU SMITH, CM KELSEY, KT WIENCKE, JK LEYDEN, K LEVIN, S CHRISTIANI, DC AF SMITH, CM KELSEY, KT WIENCKE, JK LEYDEN, K LEVIN, S CHRISTIANI, DC TI INHERITED GLUTATHIONE-S-TRANSFERASE DEFICIENCY IS A RISK FACTOR FOR PULMONARY ASBESTOSIS SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID LUNG-CANCER; ALVEOLAR MACROPHAGES; EXPOSED SUBJECTS; IRREGULAR OPACITIES; LIPID-PEROXIDATION; CIGARETTE-SMOKING; HUMAN-LEUKOCYTES; PROTECTIVE ROLE; SUSCEPTIBILITY; WORKERS AB Pulmonary diseases attributable to asbestos exposure constitute a significant public health burden, yet few studies have investigated potential genetic determinants of susceptibility to asbestos-related diseases. The glutathione-S-transferases are a family of conjugating enzymes that both catalyze the detoxification of a variety of potentially cytotoxic electrophilic agents and act in the generation of sulfadipeptide leukotriene inflammatory mediators. The gene encoding glutahione-S-transferase class mu (GSTM-1) is polymorphic; approximately 50% of Caucasian individuals have a homozygous deletion of this gene and do not produce functional enzyme. Glutathione-S-transferease mu (GST-mu) deficiency has been previously reported to be associated with smoking-induced lung cancer. We conducted a cross-sectional study to examine the prevalence of the homozygous deletion for the GSTM-1 gene in members of the carpentry trade occupationally exposed to asbestos. Members of the United Brotherhood of Carpenters and Joiners of American attending their 1991 National Union conference were invited to participate. Each participant was offered a chest X-ray and was asked to complete a comprehensive questionnaire and have their blood drawn. All radiographs were assessed for the presence of pneumoconiosis in a blinded fashion by a National Institute for Occupational Safety and Health-certified International Labor Office ''B'' reader. Individual GSTM-1 status was determined using polymerase chain reaction methods. Six hundred fifty-eight workers were studied. Of these, 80 (12.2%) had X-ray abnormalities associated with asbestos exposure. Individuals genetically deficient in GST-mu were significantly more likely to have radiographic evidence of nonmalignant asbestos-related disease than those who were not deficient (chi2 = 5.0; P < 0.03). Logistic regression analysis showed that susceptibility was most strongly associated with individuals with radiographic evidence of parenchymal disease (odds ratio, 2.1; P < 0.05). Further, no significant association between GSTM-1 deletion and X-ray abnormalities was noted in current smokers, while ex-smokers and never-smokers with the deleted genotype were significantly more likely to have radiographic evidence of asbestos-induced parenchymal fibrosis (chi2 = 6.5; P < 0.01). Inherited GST-mu deficiency appears to contribute to individual susceptibility to asbestos-induced pulmonary disease. This may be due to a reduced ability of GST-mu deficient cells in the lung to detoxify reactive electrophiles associated with asbestos exposure. Alternatively, an altered inflammatory response to asbestos fibers resident in the lung may be present in GST-mu-deficient individuals that results in more pronounced pulmonary fibrogenesis. C1 HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,665 HUNTINTON AVE,BOSTON,MA 02115. UNIV CALIF SAN FRANCISCO,SCH MED,DEPT EPIDEMIOL & BIOSTAT,SAN FRANCISCO,CA 94143. HARVARD UNIV,SCH PUBL HLTH,OCCUPAT HLTH PROGRAM,BOSTON,MA 02115. MT SINAI MED CTR,DEPT COMMUNITY MED,NEW YORK,NY 10029. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,PULM & CRIT CARE UNIT,BOSTON,MA 02114. RI Kelsey, Karl/I-1252-2014 FU NCI NIH HHS [CA-09078]; NIEHS NIH HHS [ES-00002]; NIOSH CDC HHS [K01-OH-00110] NR 63 TC 62 Z9 65 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 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD SEP PY 1994 VL 3 IS 6 BP 471 EP 477 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA PF475 UT WOS:A1994PF47500004 PM 8000297 ER PT J AU YUAN, F SALEHI, HA BOUCHER, Y VASTHARE, US TUMA, RF JAIN, RK AF YUAN, F SALEHI, HA BOUCHER, Y VASTHARE, US TUMA, RF JAIN, RK TI VASCULAR-PERMEABILITY AND MICROCIRCULATION OF GLIOMAS AND MAMMARY CARCINOMAS TRANSPLANTED IN RAT AND MOUSE CRANIAL WINDOWS SO CANCER RESEARCH LA English DT Note ID BLOOD-BRAIN-BARRIER; HUMAN ADENOCARCINOMA LS174T; MICROVASCULAR PERMEABILITY; CAPILLARY-PERMEABILITY; ENDOTHELIAL-CELLS; SCID MICE; TUMORS; FLOW AB Many brain tumors are highly resistant to chemotherapy, presumably due to the presence of a tight blood-tumor barrier. For a better understanding of the regulation of this barrier by the brain environment, a new intravital microscopy model was established by transplanting tumor tissue into cranial windows in both rats and mice. The model was characterized by RBC velocities, vessel diameters, and vascular permeabilities of various tumors: R3230AC (a rat mammary adenocarcinoma), MCaIV (a mouse mammary adenocarcinoma), and U87 and HGL21 (human malignant astrocytomas). Our results showed that tumor blood flow in cranial windows was one to three orders of magnitude lower than the blood flow in pial vessels and similar to that in dorsal skin-fold chambers observed in previous studies. The mean vessel diameter ranged from 6.8 +/- 1.3 mu m for HGL21 to 30.4 +/- 8.5 mu m for MCaIV. At least one order of magnitude difference in vascular permeability to albumin was observed between tumor lines: 0.11 +/- 0.05x10(-7) cm/s for HGL21 versus 3.8 +/- 1.2x10(-7) cm/s for U87. The low vascular permeability of HGL21, which was also confirmed by both sodium fluorescein and Lissamine green injections, suggests that not all tumors are leaky to tracer molecules and that the blood-tumor barrier of this tumor still possesses some characteristics of blood-brain barrier as observed in other intracranial tumors. The model presented here will allow us to manipulate the vascular permeability in brain tumors and thus may provide new information on the regulation of the blood-tumor barrier and new strategies for improving drug delivery in brain tumors. C1 TEMPLE UNIV,HLTH SCI CTR,SCH MED,DEPT PHYSIOL,PHILADELPHIA,PA 19140. TEMPLE UNIV,HLTH SCI CTR,SCH MED,DEPT NEUROSURG,PHILADELPHIA,PA 19140. RP YUAN, F (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02114, USA. RI Yuan, Fan/A-1287-2011 FU NCI NIH HHS [R35-CA-56591] NR 23 TC 295 Z9 301 U1 0 U2 24 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 SEP 1 PY 1994 VL 54 IS 17 BP 4564 EP 4568 PG 5 WC Oncology SC Oncology GA PD695 UT WOS:A1994PD69500003 PM 8062241 ER PT J AU RUBIO, MP CORREA, KM UEKI, K MOHRENWEISER, HW GUSELLA, JF VONDEIMLING, A LOUIS, DN AF RUBIO, MP CORREA, KM UEKI, K MOHRENWEISER, HW GUSELLA, JF VONDEIMLING, A LOUIS, DN TI THE PUTATIVE GLIOMA TUMOR-SUPPRESSOR GENE ON CHROMOSOME 19Q MAPS BETWEEN APOC2 AND HRC SO CANCER RESEARCH LA English DT Article ID MARKERS; LOCUS; OLIGODENDROGLIOMAS; HETEROZYGOSITY; ASTROCYTOMAS; POLYMORPHISM; PCR AB The frequent allelic loss of chromosome 19q in human gliomas suggests that 19q harbors a tumor suppressor gene that is integral to glioma tumorigenesis. Our initial deletion mapping of this gene localized the common region of deletion to the distal long arm, 19q3.2-13.4. To bracket the putative tumor suppressor gene further, we have studied this region in 55 gliomas, using loss of heterozygosity studies for 11 well mapped, highly informative microsatellite polymorphisms that cover this area: D19S178; BCL3; APOC2; ERCC1; DM; D19S112; HRC; D19S246; KLK; D19S180; and D19S254 (from centromeric to telomeric). Twenty astrocytic, oligodendroglial, and mixed gliomas had deletions affecting this region. Of nine partial deletions, two cases maintained heterozygosity at APOC2 while showing allelic loss at the more telomeric markers, ERCC1 and DM, while five cases maintained heterozygosity at HRC but lost the more centromeric markers, D19S112 and DM. Nine cases lost the entire D19S178 to D19S254 region. Three astrocytic gliomas, including one with an interstitial deletion, had terminal deletions of 19q13.4. The minimum area of overlap shared by the interstitial deletions is between APOC2 and HRC, including ERCC1, DM, and D19S112. These findings suggest that the glioma tumor suppressor gene maps to an approximately 8-cM/5-megabase region on 19q13.2-13.3 between the proximal marker APOC2 and the distal marker HRC. Among the DNA repair/DNA metabolism genes on chromosome 19q, ERCC1, LIG1, and perhaps ERCC2 are within the common area of deletion; XRCC1 is centromeric and is therefore excluded as a candidate. C1 MASSACHUSETTS GEN HOSP,MOLEC NEUROONCOL LAB,NEUROSURG SERV,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,DEPT PATHOL NEUROPATHOL,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,MOLEC NEUROGENET UNIT,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,DEPT GENET,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02129. LAWRENCE LIVERMORE NATL LAB,CTR HUMAN GENOME,LIVERMORE,CA 94550. UNIV HOSP BONN,INST NEUROPATHOL,D-53105 BONN,GERMANY. RI Rubio, Mari-Paz/K-4364-2014; von Deimling, Andreas/F-7774-2013 OI Rubio, Mari-Paz/0000-0003-3963-5903; von Deimling, Andreas/0000-0002-5863-540X FU NCI NIH HHS [CA 57683] NR 26 TC 80 Z9 81 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 SEP 1 PY 1994 VL 54 IS 17 BP 4760 EP 4763 PG 4 WC Oncology SC Oncology GA PD695 UT WOS:A1994PD69500041 PM 8062276 ER PT J AU DHAUNSI, GS SINGH, I ORAK, JK SINGH, AK AF DHAUNSI, GS SINGH, I ORAK, JK SINGH, AK TI ANTIOXIDANT ENZYMES IN CIPROFIBRATE-INDUCED OXIDATIVE STRESS SO CARCINOGENESIS LA English DT Article ID RAT-LIVER PEROXISOMES; PROLIFERATOR-INDUCED HEPATOCARCINOGENESIS; SUPEROXIDE-DISMUTASE; ENDOPLASMIC-RETICULUM; BETA-OXIDATION; GLUTATHIONE-PEROXIDASE; HYPOLIPIDEMIC DRUGS; FATTY-ACIDS; PROTEIN; CLOFIBRATE AB To understand the mechanism of peroxisome proliferator-induced oxidative stress in non-mutagenic carcinogenesis, the effect of ciprofibrate, a peroxisome proliferator, on the activities and protein amounts of various antioxidant enzymes in different subcellular compartments was examined. Ciprofibrate treatment for short-term (3 weeks) as well as long-term (12 weeks) duration increased the total cellular catalase activity, whereas superoxide dismutase (SOD) and glutathione peroxidase (GPX) activities were decreased significantly. Withdrawal of ciprofibrate from the diet did not normalize these activities. The observed decreases in total cellular SOD and GPX activities following ciprofibrate treatment were due to significant decreases in cytosolic CuZn SOD and GPX, whereas mitochondrial levels of Mn SOD and GPX were relatively unchanged. The peroxisomal CuZn SOD acid GPX activities were increased significantly after both short- and long-term treatment, whereas catalase activity was reduced. Western blot analysis of cytoplasm for GPX and CuZn SOD showed a significant decrease in GPX and CuZn SOD proteins. Mitochondrial GPX protein was found to be slightly decreased, whereas Mn SOD protein levels did not show any significant change. The excessive production of H2O2 by oxidases and O-2(-) by the cytochrome P450 enzyme system, along with the observed loss of antioxidant protection by loss of activities of catalase in peroxisomes and GPX and CuZn SOD in cytoplasm, may be the critical factors in peroxisomal proliferator-induced oxidative stress and initiation and promotion of carcinogenesis by this class of non-mutagenic agents. Both enzyme activities, as well as protein amounts of GPX and CuZn SOD, were higher in peroxisomes but lower in cytoplasm in ciprofibrate-treated liver as compared to control liver. The Mn SOD protein was decreased in peroxisomes, whereas mitochondrial Mn SOD was relatively unaffected in ciprofibrate-treated liver as compared to control. These observations suggest that the regulation of expression of peroxisomal CuZn SOD and Mn SOD is different from their counterparts in other cellular compartments. C1 MED UNIV S CAROLINA,DEPT PEDIAT,CHARLESTON,SC 29425. RALPH H JOHNSON VET AFFAIRS MED CTR,DEPT PATHOL & LAB MED,CHARLESTON,SC 29403. FU NINDS NIH HHS [NS-22576] NR 60 TC 34 Z9 36 U1 0 U2 0 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 SEP PY 1994 VL 15 IS 9 BP 1923 EP 1930 DI 10.1093/carcin/15.9.1923 PG 8 WC Oncology SC Oncology GA PJ846 UT WOS:A1994PJ84600024 PM 7923586 ER PT J AU DUAN, XC ACKERLY, M VIVIER, E ANDERSON, P AF DUAN, XC ACKERLY, M VIVIER, E ANDERSON, P TI EVIDENCE FOR INVOLVEMENT OF BETA-GLUCAN-BINDING CELL-SURFACE LECTINS IN HUMAN NATURAL-KILLER-CELL FUNCTION SO CELLULAR IMMUNOLOGY LA English DT Article ID INTEGRAL MEMBRANE-PROTEINS; HUMAN NK CELLS; CRYPTOCOCCUS-NEOFORMANS; MONOCLONAL-ANTIBODY; SEQUENCE HOMOLOGY; MOUSE NKR-P1; FC RECEPTOR; LYMPHOCYTES; COMPLEMENT; FAMILY AB We have studied the effects of yeast cell wall derivatives (zymosan and particulate beta-glucan), on the cytolytic effector function of human natural killer cells. Both zymosan and particulate beta-glucan were found to inhibit the NK-cell-mediated killing of K562, Molt-4, U937, and HL60 tumor cells. Zymosan also inhibited the IL-2-dependent proliferation of NK cells, suggesting that some component of the yeast cell wall delivers a down-modulatory signal affecting multiple NK cell functions. NK cell surface molecules capable of binding both zymosan and Sepharose-immobilized pustulan (linear 1,6-beta-D-glucan, a carbohydrate component of zymosan and particulate beta-glucan) were identified in detergent lysates prepared from surface iodinated NK cells. Our results suggest that NK cells express tell surface beta-glucan-binding lectins that may contribute to NK-cell-mediated natural cytotoxicity. (C) 1994 Academic Press, Inc. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT RHEUMATOL & IMMUNOL,BOSTON,MA 02115. RP DUAN, XC (reprint author), HARVARD UNIV,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA53595] NR 36 TC 28 Z9 28 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD SEP PY 1994 VL 157 IS 2 BP 393 EP 402 DI 10.1006/cimm.1994.1236 PG 10 WC Cell Biology; Immunology SC Cell Biology; Immunology GA PE520 UT WOS:A1994PE52000009 PM 8069924 ER PT J AU VATNER, DE SATE, N KIUCHI, K SHANNON, RP VATNER, SF AF VATNER, DE SATE, N KIUCHI, K SHANNON, RP VATNER, SF TI DECREASE IN MYOCARDIAL RYANODINE RECEPTORS AND ALTERED EXCITATION-CONTRACTION COUPLING EARLY IN THE DEVELOPMENT OF HEART-FAILURE SO CIRCULATION LA English DT Article DE RECEPTORS; CALCIUM CHANNELS; PACING; HEART FAILURE ID CARDIAC SARCOPLASMIC-RETICULUM; CALCIUM-RELEASE CHANNEL; MECHANICAL RESTITUTION; VENTRICULAR MYOCARDIUM; DILATED CARDIOMYOPATHY; ANTAGONIST RECEPTORS; DOGS; BINDING; EXPRESSION; STIMULATION AB Background Rapid ventricular pacing for 1 day reduced myocardial contractile function without inducing heart failure in conscious, chronically instrumented dogs. After 4 to 7 weeks of pacing, myocardial contractility was depressed further and overt signs of congestive heart failure, eg, ascites, dyspnea, and edema, were evident. Methods and Results The mechanical restitution response, a physiological index of calcium release, was depressed at 1 day of rapid ventricular pacing. Postextrasystolic potentiation was also depressed by a similar amount, 14+/-3%, at 1 day after pacing. The response to isoproterenol 0.2 mu g/kg per minute was depressed by a significantly greater amount (P<.05), 52+/-7%, at 1 day after pacing. H-3-ryanodine receptor binding fell from 1013+/-25 to 808+/-42 fmol/mg after 1 day of pacing and remained depressed at similar levels (782+/-61 fmol/mg) at 4 to 7 weeks when heart failure was manifest. Ryanodine receptor affinity was unchanged from control values. Neither dihydropyridine binding nor affinity for H-3-PN200-110 was changed from control levels. Within 5 days after recovery from 1 day of pacing, physiological responses to isoproterenol, postextrasystolic potentiation, and mechanical restitution recovered, as did H-3-ryanodine binding density. Conclusions These findings suggest that the changes in excitation-contraction coupling and potentially the sarcoplasmic reticulum calcium release channel occur early in the development of heart failure and therefore may be important in the pathogenesis of the contractile abnormalities in this disease state. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT MED,BOSTON,MA 02115. BETH ISRAEL HOSP,DEPT MED,BOSTON,MA 02215. MASSACHUSETTS GEN HOSP,CHILDRENS SERV,BOSTON,MA 02114. RP VATNER, DE (reprint author), NEW ENGLAND REG PRIMATE RES CTR,1 PINE HILL DR,POB 9102,SOUTHBOROUGH,MA 01772, USA. FU NHLBI NIH HHS [HL-45332, HL-37404, HL-38070] NR 36 TC 88 Z9 92 U1 1 U2 5 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP PY 1994 VL 90 IS 3 BP 1423 EP 1430 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PG602 UT WOS:A1994PG60200035 PM 7522133 ER PT J AU CHEN, CG GUERRERO, JL DEPRADA, JAV PADIAL, LR SCHWAMMENTHAL, E CHEN, MH JIANG, L SVIZZERO, T SIMON, H THOMAS, JD LEVINE, RA WEYMAN, AE AF CHEN, CG GUERRERO, JL DEPRADA, JAV PADIAL, LR SCHWAMMENTHAL, E CHEN, MH JIANG, L SVIZZERO, T SIMON, H THOMAS, JD LEVINE, RA WEYMAN, AE TI INTRACARDIAC ULTRASOUND MEASUREMENT OF VOLUMES AND EJECTION FRACTION IN NORMAL, INFARCTED, AND ANEURYSMAL LEFT-VENTRICLES USING A 10-MHZ ULTRASOUND CATHETER SO CIRCULATION LA English DT Article DE ULTRASONICS; VENTRICLES; ECHOCARDIOGRAPHY ID TWO-DIMENSIONAL ECHOCARDIOGRAPHY; CROSS-SECTIONAL ECHOCARDIOGRAPHY; CANINE LEFT-VENTRICLE; 2-DIMENSIONAL ECHOCARDIOGRAPHY; QUANTIFYING VOLUME; MATHEMATIC MODELS; REAL-TIME; ACCURACY; OBLIQUE AB Background Our objective was to examine the accuracy of intracardiac ultrasound (ICUS) measurement of left ventricular (LV) volumes and ejection fraction (EF) using a 10-MHz ultrasound catheter. ICUS can image the LV in cross sections at all levels along the long axis with a transducer mounted on the tip of a catheter. Sequential serial LV cross-sectional images can be obtained during cardiac catheterization and used to calculate LV volumes by Simpson's rule. This technique may be an alternative to contrast LV angiography. Methods and Results A beating-heart in vivo model was created to measure LV volume directly and continuously with an intracavity high-compliance latex balloon connected to a calibrated extracardiac reservoir in eight dogs in 35 experimental stages. A 10F ICUS catheter with a 10-MHz single-element transducer was introduced retrogradely via the aortic valve to the apex. Series of sequential LV cross-sectional images were recorded from the apex to the base during a calibrated pullback of the catheter. At each 5-mm interval, the LV cross section was traced at end diastole and end systole. LV volume was calculated by Simpson's rule by integrating all segmental areas multiplied by segmental height. The effect on accuracy of selecting 5-, 10-, or 15-mm heights or a single section at the midventricular level for measurement was assessed. The influence of distorted ventricular shape on the accuracy of ICUS measurements of LV volume was evaluated. This method was applied in 19 experimental stages in 10 intact dogs and pigs catheterized via the femoral artery. In the in vivo canine model, LV end-diastolic volume, end-systolic volume, and EF determined by ICUS using 5-, 10-, or 15-mm segments were not different from the actual measurements. But correlation and agreement between ICUS end-diastolic volume and direct measurements for 5- and 10-mm segments were significantly better than for 15-mm segments or a single section. Similar excellent correlations and agreement were observed for actual and ICUS-derived end-systolic volumes using 5-, 10-, or 15-mm segments. The ICUS-derived EF correlated very well with actual EF with a small measurement error of 3.91+/-2.59% for 5-mm or 4.13+/-2.79% for 10-mm segments but a significantly greater measurement error for 15-mm segments (5.35+/-3.76%) or single sections (14.8+/-12.2%). The presence of LV infarction or aneurysm did not significantly influence the accuracy of ICUS calculations for segmental heights less than or equal to 10 mm. Application in intact animals demonstrated a good correlation between stroke volume measured by ICUS and by thermodilution or flowmeter. ICUS-derived LV volumes correlated well with biplane angiographic volumes, with a tendency toward underestimation. There was no significant difference between ICUS-determined LV EF and EF determined by angiography. Conclusions Intracardiac echocardiography accurately measures LV volumes and global systolic function in both regularly shaped and distorted left ventricles. This technique directly and continuously visualizes circumferential LV endocardium and wall thickness without contrast agents or geometric assumptions for calculation of LV volume. Thus, it should be particularly useful in patients at high risk for contrast-related complications or distorted LV shapes in which geometric assumptions may not be valid. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,NONINVAS CARDIAC LABS,CARDIAC UNIT,BOSTON,MA. CLEVELAND CLIN FDN,DEPT CARDIOL,CLEVELAND,OH 44195. RP CHEN, CG (reprint author), UNIV CONNECTICUT,SCH MED,HARTFORD HOSP,DIV CARDIOL,80 SEYMOUR ST,HARTFORD,CT 06115, USA. RI Guerrero, Jorge/I-3666-2015 OI Guerrero, Jorge/0000-0003-4315-7318 FU NHLBI NIH HHS [HL-38176] NR 32 TC 25 Z9 25 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP PY 1994 VL 90 IS 3 BP 1481 EP 1491 PG 11 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PG602 UT WOS:A1994PG60200040 PM 8087955 ER PT J AU IMAMURA, T MCDERMOTT, PJ KENT, RL NAGATSU, M COOPER, G CARABELLO, BA AF IMAMURA, T MCDERMOTT, PJ KENT, RL NAGATSU, M COOPER, G CARABELLO, BA TI ACUTE CHANGES IN MYOSIN HEAVY-CHAIN SYNTHESIS RATE IN PRESSURE VERSUS VOLUME OVERLOAD SO CIRCULATION RESEARCH LA English DT Article DE HYPERTROPHY; MYOSIN SYNTHESIS RATE; PRESSURE OVERLOAD; VOLUME OVERLOAD ID LEFT-VENTRICULAR FUNCTION; AORTIC-VALVE REPLACEMENT; CHRONIC MITRAL REGURGITATION; PROTEIN-SYNTHESIS; CONTRACTILE FUNCTION; CARDIAC-HYPERTROPHY; ULTRAMICRO METHOD; PERFORMANCE; STENOSIS; HEART AB The left ventricular hypertrophy that develops with the volume overload of mitral regurgitation is relatively less than that which develops with the pressure overload of aortic stenosis even when both lesions are severe, The hypertrophy that develops must be the sum of changes in the rate of myocardial protein synthesis and degradation. In the present canine study, we explored early changes in the synthesis rate of myosin heavy chain in response to severe acute pressure overload versus that of the severe acute volume overload of mitral regurgitation. We tested the hypothesis that in acute overload, the rate of protein synthesis would increase less in the volume-overload model than in the pressure-overload model, a potential partial mechanism for the discrepancy in the eventual total amount of hypertrophy that develops in these two lesions. Acute pressure overload was produced by inflating a balloon in the descending aorta, and acute volume overload was produced by using our closed-chest mitral chordal rupture technique. In both models, the hemodynamic lesion that was created was severe. In eight dogs with pressure overload, the average gradient across the balloon wa 119.8 +/- 6.1 mm Hg. In six dogs with volume overload, the average regurgitant fraction was 0.67 +/- 0.06. Six other dogs served as controls. The average rate of myosin heavy chain synthesis in control dogs was 2.7 +/- 0.2% per day, virtually identical to the rate we found in the severe volume-overload model. In contrast, the rate was increased in the pressure-overload model by 30% to 3.5 +/- 0.3% per day (P<.05). We conclude that the rate of myocardial protein synthesis increases measurably after 6 hours of severe pressure overload but does not after 6 hours of severe volume overload. If these early qualitative differences persisted, they would help explain the relative lack of hypertrophy in the volume overload of mitral regurgitation. C1 MED UNIV S CAROLINA,DEPT MED,DIV CARDIOL,CHARLESTON,SC 29425. MED UNIV S CAROLINA,GAZES CARDIAC RES INST,CHARLESTON,SC 29425. RALPH H JOHNSON DEPT VET AFFAIRS MED CTR,CHARLESTON,SC. FU NHLBI NIH HHS [NHLBI R01 HL-38185] NR 39 TC 56 Z9 59 U1 1 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7330 J9 CIRC RES JI Circ.Res. PD SEP PY 1994 VL 75 IS 3 BP 418 EP 425 PG 8 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA PC935 UT WOS:A1994PC93500003 PM 8062416 ER PT J AU BLOCH, DB RABKINA, D QUERTERMOUS, T BLOCH, KD AF BLOCH, DB RABKINA, D QUERTERMOUS, T BLOCH, KD TI THE IMMUNOREACTIVE REGION IN A NOVEL AUTOANTIGEN CONTAINS A NUCLEAR-LOCALIZATION SEQUENCE SO CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY LA English DT Article ID DNA-BINDING; TOPOISOMERASE-I; CELL BIOLOGY; PROTEINS; ANTIGEN; IMMUNOGLOBULIN; PURIFICATION; ANTIBODIES; CLONING; EPITOPE AB Antibodies in the serum of patients with autoimmune diseases have been used to identify human autoantigens. Because autoantibodies often recognize active sites within corresponding protein antigens, autoantibodies have facilitated the functional characterization of these polypeptides. In the present study, serum from a patient with Sjogren's syndrome was used to identify a novel autoantigen which was designated Ge-1. Using the patient's serum, a 4.8-kb cDNA encoding Ge-1 was identified. Fragments of the cDNA were ligated into prokaryotic expression vectors, expressed in Escherichia coli, and used to produce recombinant Ge-1 fusion proteins. Fusion proteins containing different portions of Ge-1 were used to identify a 58 amino acid immunoreactive region within the protein. This immunoreactive region contained the protein's putative nuclear localization sequence (NLS). To demonstrate that the immunoreactive region was capable of functioning as a NLS, a eukaryotic expression plasmid was constructed to encode the immunoreactive region fused to the cytoplasmic protein, chicken muscle pyruvate kinase. After transfection of this plasmid into COS-1 cells, the fusion protein was detected in the nucleus. The presence of the NLS motif within the immunoreactive region of Ge-1 and other nuclear autoantigens suggests that the NLS may be a target of human autoantibodies. (C) 1994 Academic Press, Inc. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,CARDIAC UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,GEN MED SERV,BOSTON,MA. RP BLOCH, DB (reprint author), MASSACHUSETTS GEN HOSP,ARTHRIT UNIT,BOSTON,MA, USA. FU NHLBI NIH HHS [HL45895]; NIAMS NIH HHS [AR01866] NR 34 TC 9 Z9 10 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0090-1229 J9 CLIN IMMUNOL IMMUNOP JI Clin. Immunol. Immunopathol. PD SEP PY 1994 VL 72 IS 3 BP 380 EP 389 DI 10.1006/clin.1994.1156 PG 10 WC Immunology; Pathology SC Immunology; Pathology GA PC728 UT WOS:A1994PC72800013 PM 7520377 ER PT J AU SABOLIC, I BROWN, D AF SABOLIC, I BROWN, D TI WATER TRANSPORT IN RENAL TUBULES IS MEDIATED BY AQUAPORINS SO CLINICAL INVESTIGATOR LA English DT Article; Proceedings Paper CT 25th Congress of the Gesellschaft-fur-Nephrologie/27th Annual Meeting of the Deutsche-Arbeitsgemeinschaft-fur-Klinische-Nephrologie CY 1994 CL ZURICH, SWITZERLAND SP GESELL NEPHROL, DEUT ARBEITSGEMEINSCH KLIN NEPHROL DE KIDNEY TUBULES; VASOPRESSIN; WATER CHANNELS; WATER TRANSPORT ID RAT-KIDNEY; CHANNEL AB Water reabsorption in mammalian renal tubules is mediated by channel-forming membrane glycoproteins termed aquaporins (AQP). So far three different kinds of AQP have been described in renal tubules. AQP CHIP is localized to the luminal and contraluminal membranes of the proximal tubule and descending thin limb cells, i.e., in tubule segments that exhibit a constitutive high permeability to water that is insensitive to vasopressin. AQP-CD is present in subapical vesicles and the luminal membrane of collecting duct principal cells. Its intracellular distribution depends on vasopressin or hydration status of the animal and, thus, may represent the vasopressin-sensitive water channel. The basolateral integral protein (BLIP) may represent the vasopressin-insensitive water channel in basolateral membrane of collecting duct principal cells. The exact localization of a recently cloned homologue, WCH3, which may be either related to BLIP or represent yet another kind of AQP, is not known. Heterogeneity of aquaporins in the renal tubule may provide a molecular basis for the treatment of certain diseases with disturbances in water homeostasis. C1 MASSACHUSETTS GEN HOSP,RENAL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RP SABOLIC, I (reprint author), UNIV ZAGREB,INST MED RES & OCCUPAT HLTH,KSAVERSKA CESTA 2,POB 291,ZAGREB 41001,CROATIA. NR 11 TC 2 Z9 4 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0941-0198 J9 CLIN INVESTIGATOR JI Clin. Investig. PD SEP PY 1994 VL 72 IS 9 BP 698 EP 700 DI 10.1007/BF00212993 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA PL475 UT WOS:A1994PL47500013 PM 7531521 ER PT J AU JENDERS, RA MORGAN, M BARNETT, GO AF JENDERS, RA MORGAN, M BARNETT, GO TI USE OF OPEN STANDARDS TO IMPLEMENT HEALTH MAINTENANCE GUIDELINES IN A CLINICAL WORKSTATION SO COMPUTERS IN BIOLOGY AND MEDICINE LA English DT Article DE WORKSTATION; ARDEN SYNTAX; KNOWLEDGE REPRESENTATION; GUIDELINES; RELATIONAL DATABASE; EXPERT SYSTEM ID MEDICAL INFORMATION-SYSTEM AB We are developing a clinical workstation which integrates access to health maintenance guidelines with access to a computer-based medical record. In order to enhance the portability of such a system, we emphasize the use of open standards which can be used in diverse clinical environments. We discuss the use of relational database and expert system technology to provide both patient-specific and patient-independent access to clinical guidelines. We use the Arden Syntax as the format for a textual library which facilitates the storage of structured medical knowledge. RP JENDERS, RA (reprint author), MASSACHUSETTS GEN HOSP,COMP SCI LAB,BOSTON,MA 02114, USA. FU AHRQ HHS [HS06575]; NLM NIH HHS [1-T15-LM07092, 1-LM-1-3538] NR 13 TC 4 Z9 4 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0010-4825 J9 COMPUT BIOL MED JI Comput. Biol. Med. PD SEP PY 1994 VL 24 IS 5 BP 385 EP 390 DI 10.1016/0010-4825(94)90006-X PG 6 WC Biology; Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Computer Science; Engineering; Mathematical & Computational Biology GA QE550 UT WOS:A1994QE55000006 PM 7705070 ER PT J AU CULLEN, DJ CHERNOW, B AF CULLEN, DJ CHERNOW, B TI PREDICTING OUTCOME IN CRITICALLY ILL PATIENTS SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE PATIENT OUTCOME ASSESSMENT; SEVERITY OF ILLNESS INDEX; PROGNOSTICATION; CRITICAL ILLNESS; INTENSIVE CARE UNIT ID INTENSIVE-CARE UNITS; MULTICENTER; COST C1 JOHNS HOPKINS UNIV,SINAI HOSP,SCH MED,BALTIMORE,MD. RP CULLEN, DJ (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA, USA. NR 19 TC 27 Z9 28 U1 1 U2 1 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 SEP PY 1994 VL 22 IS 9 BP 1345 EP 1348 PG 4 WC Critical Care Medicine SC General & Internal Medicine GA PF017 UT WOS:A1994PF01700001 PM 8062554 ER PT J AU CULLEN, DJ NEMESKAL, AR ZASLAVSKY, AM AF CULLEN, DJ NEMESKAL, AR ZASLAVSKY, AM TI INTERMEDIATE TISS - A NEW THERAPEUTIC INTERVENTION SCORING SYSTEM FOR NON-ICU PATIENTS SO CRITICAL CARE MEDICINE LA English DT Article DE INTENSIVE CARE; INTERMEDIATE CARE; SEVERITY OF ILLNESS; OUTCOMES ANALYSIS; MONITORING SYSTEMS; PATIENT OUTCOME ASSESSMENT; DIABETES MELLITUS; CRITICAL ILLNESS; MONITORING, PHYSIOLOGICAL; PROGNOSTICATION ID INTENSIVE-CARE AB Objective: To modify the Therapeutic Intervention Scoring System (TISS) for intermediate and floor care nursing units. Design: Prospective study. Setting: University teaching hospital. Patients: In-patients on medical and surgical nursing units. Interventions: None. Measurements and Main Results: Intermediate TISS retains 49 Original TISS items, adds 26 Intermediate TISS items, deletes 18 Original TISS items, and reweights 10 Original TISS items. Intermediate TISS score sums up the monitoring and therapeutic modalities used within the previous 24 hrs, each of which is assigned a weighted score from 1 to 4 points. A total of 3,073 patient days for 1,013 patients were simultaneously scored for Original TISS and Intermediate TISS over a 4-month period. A random sample of 435 patients was examined to identify those patients for whom Intermediate TISS added information over and above that obtained from Original TISS. Original TISS and Intermediate TISS correlated well, regression equation: Intermediate TISS = 4.4 + 1.4 x Original TISS (r(2) = .83). We identified two groups of outliers, together constituting 96 of 435 patients: a) patients whose sum of new TISS items was unusually high relative to the sum of old TISS items included those patients with diabetes mellitus, those patients receiving serial electrocardiograms to rule out myocardial infarction and patients requiring cardiac or pulmonary therapy; b) those patients whose sum of new TISS items was low relative to the sum of old TISS items were largely surgical patients outside the intensive care unit (ICU), in whom Original TISS still worked well because it had been designed for surgical ICU patients. Conclusions: Intermediate TISS is useful to score medical patients receiving intermediate or floor care in non-ICU nursing units within the hospital. RP CULLEN, DJ (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ANESTHESIA,BOSTON,MA 02114, USA. NR 11 TC 41 Z9 45 U1 0 U2 0 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 SEP PY 1994 VL 22 IS 9 BP 1406 EP 1411 DI 10.1097/00003246-199409000-00009 PG 6 WC Critical Care Medicine SC General & Internal Medicine GA PF017 UT WOS:A1994PF01700009 PM 8062562 ER PT J AU VENEGAS, JG FREDBERG, JJ AF VENEGAS, JG FREDBERG, JJ TI UNDERSTANDING THE PRESSURE COST OF VENTILATION - WHY DOES HIGH-FREQUENCY VENTILATION WORK SO CRITICAL CARE MEDICINE LA English DT Article DE HIGH-FREQUENCY VENTILATION; BAROTRAUMA; MECHANICAL VENTILATION; PULMONARY GAS EXCHANGE; POSITIVE END-EXPIRATORY PRESSURE; TIDAL VOLUME; PULMONARY DISEASES; RESPIRATORY INSUFFICIENCY ID MEAN AIRWAY PRESSURE; PULMONARY INTERSTITIAL EMPHYSEMA; GAS-TRANSPORT; ALVEOLAR PRESSURE; PERIODIC-FLOW; OSCILLATORY VENTILATION; JET VENTILATION; LUNG-INFLATION; DOGS; RABBITS AB Objectives: To understand when the use of high-frequency ventilation would be advantageous, we formulated the problem of achieving adequate alveolar ventilation at minimal pressure cost by dividing it into two simpler problems: a) the pressure cost per unit of convective oscillatory now; and b) the convective flow cost necessary to achieve a unit of alveolar ventilation. Methods: Simple solutions for each of these cost functions were formulated using established models of gas exchange and lung mechanics, including the effects of lung inflation tidal volume and respiratory frequency in alveolar ventilation, nonlinear lung tissue compliance, and alveolar recruitment and derecruitment. Solutions to these models were combined to assess the total pressure cost of high-frequency ventilation as a function of the ventilatory settings and the pathophysiologic variables of the patient. Main Results: The model predicted that for variables applicable to an infant with respiratory distress syndrome, the selection of positive end-expiratory pressure (PEEP) becomes critical because the penalties in pressure cost are amplified for both high and low values of PEEP. The selection of frequency is not as critical for frequencies >10 Hz, although it is more important than in the normal neonatal lung. Conclusions: This analysis illustrates the importance of using high-frequency ventilation in infant respiratory distress syndrome and of optimizing the amount of PEEP. It also points out the danger of barotrauma in the derecruited lung. When the lungs are in a derecruited state, the combinations of frequency, PEEP, and tidal volume that yield adequate ventilation with safe distention of recruited alveoli are severely Limited. C1 HARVARD UNIV,SCH MED,BOSTON,MA. HARVARD UNIV,SCH PUBL HLTH,DEPT ENVIRONM HLTH,BOSTON,MA 02115. RP VENEGAS, JG (reprint author), MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA BIOENGN,CLN-2,BOSTON,MA 02114, USA. FU NHLBI NIH HHS [HL38267] NR 31 TC 43 Z9 43 U1 1 U2 1 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 SEP PY 1994 VL 22 IS 9 SU S BP S49 EP S57 PG 9 WC Critical Care Medicine SC General & Internal Medicine GA PF715 UT WOS:A1994PF71500004 PM 8070270 ER PT J AU ELZAATARI, FAK ENGSTRAND, L HACHEM, CY GRAHAM, DY NASER, SA AF ELZAATARI, FAK ENGSTRAND, L HACHEM, CY GRAHAM, DY NASER, SA TI IDENTIFICATION AND CHARACTERIZATION OF MYCOBACTERIUM-PARATUBERCULOSIS RECOMBINANT PROTEINS EXPRESSED IN ESCHERICHIA-COLI SO CURRENT MICROBIOLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; CROHNS-DISEASE; IMMUNOLOGICAL ANALYSIS; SEQUENCE DETERMINATION; 65-KILODALTON PROTEIN; PARA-TUBERCULOSIS; CONTROL TISSUES; JOHNES DISEASE; BOVIS BCG; FIBRONECTIN AB Mycobacterium paratuberculosis is the causative agent of Johne's disease, a chronic enteritis in ruminants, and it has also been isolated and identified from patients with Crohn's disease, an inflammatory bowel disease. The control of Johne's disease has been hampered by the lack of a reliable diagnostic test because of the large degree of antigenic cross-reactivity between mycobacterial and non-mycobacterial species. To help identify specific antigen(s) or epitope(s), an M. paratuberculosis expression library was screened with antibodies and DNA probes. In total, 54 clones were randomly picked, purified, and characterized by DNA probes and monoclonal antibodies with known specificity to individual mycobacterial antigens. Four clones carrying the heat shock protein 65K-, two representing the secreted protein 32K-, three representing the 21K-, and 20 clones representing the specific insertion element of M. paratuberculosis (IS900)-encoding genes and their gene products were identified and characterized. Well-defined recombinant antigens and/or epitopes representing M. paratuberculosis may facilitate the development of specific diagnostic tests and the investigation of their role in these chronic diseases. C1 BAYLOR COLL MED,DIV MOLEC VIROL,HOUSTON,TX 77030. RP ELZAATARI, FAK (reprint author), VET AFFAIRS MED CTR 111D,DEPT MED,INFLAMMATORY BOWEL DIS LAB,2002 HOLCOMBE BLVD,HOUSTON,TX 77030, USA. NR 36 TC 31 Z9 31 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0343-8651 J9 CURR MICROBIOL JI Curr. Microbiol. PD SEP PY 1994 VL 29 IS 3 BP 177 EP 184 DI 10.1007/BF01570760 PG 8 WC Microbiology SC Microbiology GA NX667 UT WOS:A1994NX66700009 PM 7765093 ER PT J AU FERNANDEZDELCASTILLO, C WARSHAW, AL AF FERNANDEZDELCASTILLO, C WARSHAW, AL TI PANCREATIC-CARCINOMA SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Article AB Epidemiologic studies have provided strong evidence linking chronic pancreatitis with pancreatic carcinoma. For patients with alcoholic and idiopathic chronic pancreatitis, the standardized incidence rate was 16.5; for those with tropical pancreatitis it was 100. The molecular events leading to the development of this cancer continue to be the subject of intense research, with mutations of the K-ras oncogene playing a major role. Although early diagnosis of pancreatic cancer continues to be elusive, better tools for the differential diagnosis of pancreatic and biliary strictures are becoming available. Surgery continues to offer the only possibility of cure; however, most patients still have local recurrence after resection. More aggressive treatment protocols combining preoperative chemoradiation and intraoperative radiation with surgery are being used. RP FERNANDEZDELCASTILLO, C (reprint author), MASSACHUSETTS GEN HOSP,ACC-464,15 PARKMAN ST,BOSTON,MA 02114, USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0267-1379 J9 CURR OPIN GASTROEN JI Curr. Opin. Gastroenterol. PD SEP PY 1994 VL 10 IS 5 BP 507 EP 512 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PD682 UT WOS:A1994PD68200006 ER PT J AU SOLNICAKREZEL, L DRIEVER, W AF SOLNICAKREZEL, L DRIEVER, W TI MICROTUBULE ARRAYS OF THE ZEBRAFISH YOLK CELL - ORGANIZATION AND FUNCTION DURING EPIBOLY SO DEVELOPMENT LA English DT Article DE TELEOST; YOLK SYNCYTIAL LAYER; MORPHOGENETIC MOVEMENTS; NOCODAZOLE; TAXOL ID ASPERGILLUS-NIDULANS; DROSOPHILA EMBRYO; SYNCYTIAL LAYER; XENOPUS-LAEVIS; FUNDULUS; MOVEMENTS; GASTRULATION; MIGRATION; TUBULIN; TAXOL AB In zebrafish (Danio rerio), meroblastic cleavages generate an embryo in which blastomeres cover the animal pole of a large yolk cell. At the 500-1000 cell stage, the marginal blastomeres fuse with the yolk cell forming the yolk syncytial layer. During epiboly the blastoderm and the yolk syncytial layer spread toward the vegetal pole. We have studied developmental changes in organization and function during epiboly of two distinct microtubule arrays located in the cortical cytoplasm of the yolk cell. In the anuclear yolk cytoplasmic layer, an array of microtubules extends along the animal-vegetal axis to the vegetal pole. In the early blastula the yolk cytoplasmic layer microtubules appear to originate from the marginal blastomeres. Once formed, the yolk syncytial layer exhibits its own network of intercrossing mitotic or interphase microtubules. The microtubules of the yolk cytoplasmic layer emanate from the microtubule network of the syncytial layer. At the onset of epiboly, the external yolk syncytial layer narrows, the syncytial nuclei become tightly packed and the network of intercrossing microtubules surrounding them becomes denser. Soon after, there is a vegetal expansion of the blastoderm and of the yolk syncytial layer with its network of intercrossing microtubules. Concomitantly, the yolk cytoplasmic layer diminishes and its set of animal-vegetal microtubules becomes shorter. We investigated the involvement of microtubules epiboly using the microtubule depolymerizing agent nocodazole and a stabilizing agent taxol. In embryos treated with nocodazole, microtubules were absent and epibolic movements of the yolk syncytial nuclei were blocked. In contrast, the vegetal expansion of the enveloping layer and deep cells was only partially inhibited. The process of endocytosis, proposed to play a major role in epiboly of the yolk syncytial layer (Betchaku, T. and Trinkaus, J. P. (1986) Ain. Zool. 26, 193-199), was still observed in nocodazole-treated embryos. Treatment of embryos with taxol led to a delay in all epibolic movements. We propose that the yolk cell microtubules contribute either directly or indirectly to all epibolic movements. However, the epibolic movements of the yolk syncytial layer nuclei and of the blastoderm are not coupled, and only movements of the yolk syncytial nuclei are absolutely dependent on microtubules. We hypothesize that the microtubule network of the syncytial layer and the animal-vegetal set of the yolk cytoplasmic layer contribute differently to various aspects of epiboly. Models that address the mechanisms by which the two microtubule arrays might function during epiboly are discussed. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02129. RP SOLNICAKREZEL, L (reprint author), MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,13TH ST,BLDG 149,BOSTON,MA 02129, USA. FU NICHD NIH HHS [HD29761] NR 43 TC 153 Z9 157 U1 1 U2 9 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 SEP PY 1994 VL 120 IS 9 BP 2443 EP 2455 PG 13 WC Developmental Biology SC Developmental Biology GA PF176 UT WOS:A1994PF17600008 PM 7956824 ER PT J AU LYONS, TJ LI, W WELLSKNECHT, MC JOKL, R AF LYONS, TJ LI, W WELLSKNECHT, MC JOKL, R TI TOXICITY OF MILDLY MODIFIED LOW-DENSITY LIPOPROTEINS TO CULTURED RETINAL CAPILLARY ENDOTHELIAL-CELLS AND PERICYTES SO DIABETES LA English DT Article ID DEPENDENT DIABETES-MELLITUS; MONOCYTE-DERIVED MACROPHAGES; CHOLESTERYL ESTER SYNTHESIS; MAILLARD REACTION-PRODUCTS; GLYCEMIC CONTROL; SKIN COLLAGEN; CYTO-TOXICITY; RISK-FACTORS; RETINOPATHY; INSULIN AB To investigate the role of modified low-density lipoproteins (LDL) in the pathogenesis of diabetic retinopathy, we studied the cytotoxicity of normal and mildly modified human LDL to bovine retinal capillary endothelial cells and pericytes in vitro. Pooled LDL was incubated (in phosphate-buffered saline-EDTA, 3 days, 37 degrees C) under 1) nitrogen with additional chelating agents and 2) air, to prepare normal and minimally oxidized LDL, respectively. Similar conditions, but with the addition of 50 mM D-glucose, were used to prepare glycated and glycoxidized LDL. None of the LDL preparations was recognized by the macrophage scavenger receptor, confirming Limited modification. Retinal capillary endothelial cells and pericytes were grown to confluence and then exposed for 2 or 3 days to serum-free medium (1% albumin) supplemented with normal or modified LDL (100 mg/l) or to serum-free medium alone. Cytotoxicity was assessed by cell counting (live and total cells) and by cell protein determination. Compared with normal LDL, modified LDL were cytotoxic to both cell types at both time points, causing highly significant decreases in live and total cell counts (P < 0.001) (analysis of variance). Reductions in cell protein also were significant for pericytes at day 3 (P = 0.016) and of borderline significance for endothelial cells at day 2 (P = 0.05) and day 3 (P = 0.063). Cytotoxicity increased as follows: normal < glycated less than or equal to minimally oxidized < glycoxidized LDL. We conclude that, in diabetes, mild modification of LDL resulting from separate or combined processes of glycation and oxidation may contribute to chronic retinal capillary injury and thus to the development of diabetic retinopathy. C1 RALPH H JOHNSON DEPT VET AFFAIRS MED CTR,CHARLESTON,SC. UNIV S CAROLINA,DEPT CHEM & BIOCHEM,COLUMBIA,SC 29208. RP LYONS, TJ (reprint author), MED UNIV S CAROLINA,DIV ENDOCRINOL DIABET & METAB,171 ASHLEY AVE,CHARLESTON,SC 29425, USA. FU NIDDK NIH HHS [DK-19971] NR 47 TC 81 Z9 82 U1 0 U2 6 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD SEP PY 1994 VL 43 IS 9 BP 1090 EP 1095 DI 10.2337/diabetes.43.9.1090 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PC974 UT WOS:A1994PC97400002 PM 8070608 ER PT J AU XIA, P INOGUCHI, T KERN, TS ENGERMAN, RL OATES, PJ KING, GL AF XIA, P INOGUCHI, T KERN, TS ENGERMAN, RL OATES, PJ KING, GL TI CHARACTERIZATION OF THE MECHANISM FOR THE CHRONIC ACTIVATION OF DIACYLGLYCEROL-PROTEIN KINASE-C PATHWAY IN DIABETES AND HYPERGALACTOSEMIA SO DIABETES LA English DT Article ID PANCREATIC-ISLETS; GLYCEMIC CONTROL; DENOVO SYNTHESIS; GLUCOSE; RATS; RETINOPATHY; AORTA; CELLS; PATHOGENESIS; GALACTOSEMIA AB Similar vascular pathological conditions are observed in diabetic animals and those with diet-induced hypergalactosemia. Both diabetes and hypergalactosemia are believed to cause vascular dysfunction via a common biochemical mechanism. In this study, we have found that both diabetes and hypergalactosemia in the short term (2-4 months) can increase total diacylglycerol (DAG) levels by 52 +/- 9 and 74 +/- 13% in the retina and aorta, respectively, of diabetic dogs, and by 94 +/- 9 and 78 +/- 11% in the retina and aorta, respectively, in dogs with hypergalactosemia as compared with normal control animals (P < 0.01). The elevation of DAG levels was maintained for 5 years in the aortas of diabetic and hypergalactosemic dogs. To characterize the mechanism of the DAG increases, we have determined that total DAG levels were significantly increased in cultured macro- and microvascular cells exposed to elevated glucose (22 mM) and galactose (16.5 mM) levels. These increased levels were not prevented by sorbinil, an aldose reductase inhibitor. One of the sources of the increased DAG levels was probably derived from de novo synthesis from both hexoses as determined by radiolabeling studies. Intracellularly, the DAG elevation activated protein kinase C (PKC) activity with increases of 58 +/- 12% (P < 0.05) and 66 +/- 8% (P < 0.01) in the membrane fraction of cultured aortic smooth muscle cells exposed to elevated glucose and galactose levels, respectively. These findings have clearly demonstrated a possible common biochemical mechanism by which hyperglycemia and hypergalactosemia can chronically activate the DAG-PKC pathway in the vasculature and could be a possible explanation for the development of diabetic vascular complications. C1 HARVARD UNIV, SCH MED, JOSLIN DIABET CTR, DIV RES, BOSTON, MA 02215 USA. UNIV WISCONSIN, DEPT OPHTHALMOL & VISUAL SCI, MADISON, WI USA. PFIZER INC, DEPT METAB DIS, GROTON, CT 06340 USA. RI Xia, Pu/G-3090-2010 OI Xia, Pu/0000-0003-4705-8878 FU NEI NIH HHS [EY-00300, EY-05110]; NIDDK NIH HHS [DK-36836] NR 34 TC 311 Z9 327 U1 0 U2 7 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD SEP PY 1994 VL 43 IS 9 BP 1122 EP 1129 DI 10.2337/diabetes.43.9.1122 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PC974 UT WOS:A1994PC97400007 PM 8070612 ER PT J AU SARNOW, MR VEVES, A GIURINI, JM ROSENBLUM, BI CHRZAN, JS HABERSHAW, GM AF SARNOW, MR VEVES, A GIURINI, JM ROSENBLUM, BI CHRZAN, JS HABERSHAW, GM TI IN-SHOE FOOT PRESSURE MEASUREMENTS IN DIABETIC-PATIENTS WITH AT-RISK FEET AND IN HEALTHY-SUBJECTS SO DIABETES CARE LA English DT Article ID NEUROPATHY; ULCERATION; HOSIERY AB OBJECTIVE- To measure in-shoe foot pressures in diabetic patients and healthy subjects and compare them with the foot pressures when they walked without their shoes. RESEARCH DESIGN AND METHODS- Forty-four diabetic patients at risk of foot ulceration and 65 healthy subjects were matched for age, sex, race, and weight. Neuropathy was evaluated clinically, and the F-Scan program was used to measure the foot pressures. Foot pressures were measured with the sensors placed in the shoes (S measurements), between the foot and the sock with shoes (H measurements) or with their socks alone (B measurements). RESULTS- In the control group, significant differences were found between S (4.77 +/- 1.87 kg/cm(2)) and H measurements (5.12 +/- 1.87 kg/cm(2), P < 0.001),between S and B (7.23 +/- 2.95 kg/cm(2), P < 0.0001), and between H and B (P < 0.0001). In the diabetic group, no difference was found between S and H measurements (5.28 +/- 2.22 vs. 5.27 +/- 2.39 kg/cm(2), NS). In contrast, the B pressure was significantly higher when compared with both (8.77 +/- 4.67 kg/cm(2), P < 0.02). When compared with the control group, the S and H pressures did not differ significantly, but the B pressure in the diabetic group was significantly higher (P < 0.02). The peak S pressure was above the normal limit in 24 (27%) diabetic and 21 (16%) control feet (P < 0.05), the H pressure in 17 (19%) diabetic feet and 22 (17%) control feet (NS), and the B pressure in 24 (27%) diabetic and 21 (16%) control feet (P < 0.05). CONCLUSIONS- In-shoe foot pressure measurements are significantly lower than the ones measured when walking with the socks only in both diabetic patients and healthy subjects. The shoes of diabetic patients provided a higher pressure reduction than did those of the control group, but the number of feet with abnormally high pressures did not change. The F-Scan system may be particularly helpful in designing footwear suitable for diabetic patients with at-risk feel. C1 DEACONESS JOSLIN FOOT CTR,BOSTON,MA 02215. NR 16 TC 34 Z9 38 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 SEP PY 1994 VL 17 IS 9 BP 1002 EP 1006 DI 10.2337/diacare.17.9.1002 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PD088 UT WOS:A1994PD08800008 PM 7988297 ER PT J AU CHERUBIN, CE STRATTON, CW AF CHERUBIN, CE STRATTON, CW TI ASSESSMENT OF THE BACTERICIDAL ACTIVITY OF SPARFLOXACIN, OFLOXACIN, LEVOFLOXACIN, AND OTHER FLUOROQUINOLONES COMPARED WITH SELECTED AGENTS OF PROVEN EFFICACY AGAINST LISTERIA-MONOCYTOGENES SO DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE LA English DT Article ID INVITRO ACTIVITY; QUINOLONE; SULFAMETHOXAZOLE; TRIMETHOPRIM; MENINGITIS AB The search for alternative therapeutic agents for listeriosis includes the quinolone group. Accordingly, the bactericidal activity of ciprofloxacin, levofloxacin, lomefloxacin, ofloxacin, sparfloxacin, and temofloxacin, in comparison with that of ampicillin and sulfamethoxazole-trimethoprim, was evaluated against Listeria monocytogenes at 24 and 48 h of incubation using time-kill kinetic methodology. The inhibitory concentrations for each agent fell into a narrow range comparable with ampicillin. For example, the minimum inhibitory concentration (MIC) ranges, MIC(90) (24 h), and MIC(90) (48 h) of the most active quinolone, sparfloxacin, were 0.25-2, 2, and 2 mu g/ml, respectively, with 4 mu g/ml achieving greater than or equal to 99.9% killing of the inoculum at 24 h with no regrowth by 48 h. At 2-4 times the MIC, bactericidal activity for all quinolones tested was noted at 24 h, unlike the action of ampicillin, which only becomes bactericidal at 48 h. These concentrations are within the achievable range of serum concentrations for a number of these agents. Because selected new fluoroquinolones at two to four times the MIC show bactericidal activity at 24 h, these agents may prove useful as therapeutic alternatives for the treatment of listeriosis. C1 W LOS ANGELES VET AFFAIRS MED CTR,INFECT DIS SECT,WILKES BARRE,PA. VANDERBILT UNIV,SCH MED,NASHVILLE,TN 37212. NR 21 TC 8 Z9 8 U1 0 U2 2 PU ELSEVIER SCIENCE 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 SEP PY 1994 VL 20 IS 1 BP 21 EP 25 DI 10.1016/0732-8893(94)90014-0 PG 5 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA PT229 UT WOS:A1994PT22900004 PM 7867294 ER PT J AU BEIJERSBERGEN, RL HIJMANS, EM ZHU, L BERNARDS, R AF BEIJERSBERGEN, RL HIJMANS, EM ZHU, L BERNARDS, R TI INTERACTION OF C-MYC WITH THE PRB-RELATED PROTEIN P107 RESULTS IN INHIBITION OF C-MYC-MEDIATED TRANSACTIVATION SO EMBO JOURNAL LA English DT Article DE C-MYC; P107; PRB; TRANSACTIVATION ID RETINOBLASTOMA GENE-PRODUCT; ADENOVIRUS E1A PROTEINS; CELL-CYCLE; ACTIVATES TRANSCRIPTION; EXPRESSION; E2F; TRANSFORMATION; BINDING; DOMAIN; PHASE AB The product of the c-myc proto-oncogene, c-Myc, is a sequence-specific DNA binding protein with an N-terminal transactivation domain and a C-terminal DNA binding domain. Several lines of evidence indicate that c-Myc activity is essential for normal cell cycle progression. Since the abundance of c-Myc during the cell cycle is constant, c-Myc's activity may be regulated at a post-translational level. We have shown previously that the N-terminus of c-Myc can form a specific complex with the product of the retinoblastoma gene, pRb, in vitro. These data suggested a model in which pRb, or pRb-related proteins, regulate c-Myc activity through direct binding. We show here that the pRb-related protein p107, but not pRb itself, forms a specific complex with the N-terminal transactivation domain of c-Myc in vivo. Binding of p107 to c-Myc causes a significant inhibition of c-Myc transactivation. Expression of c-Myc releases cells from a p107-induced growth arrest, but not from pRb-induced growth arrest. Our data suggest that p107 can control c-Myc activity through direct binding to the transactivation domain and that c-Myc is a target for p107-mediated growth suppression. C1 MASSACHUSETTS GEN HOSP,CTR CANC,DIV MOLEC ONCOL,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02129. RP BEIJERSBERGEN, RL (reprint author), NETHERLANDS CANC INST,MOLEC CARCINOGENESIS LAB,PLESMANLAAN 121,1066 CX AMSTERDAM,NETHERLANDS. OI Bernards, Rene/0000-0001-8677-3423 NR 36 TC 126 Z9 126 U1 0 U2 0 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 SEP 1 PY 1994 VL 13 IS 17 BP 4080 EP 4086 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA PF606 UT WOS:A1994PF60600018 PM 8076603 ER PT J AU IKEDA, H YOSHIMOTO, T YANDELL, DW AF IKEDA, H YOSHIMOTO, T YANDELL, DW TI HORMONE PRODUCTION AND C-MYC PROTEIN LABELING IN PLURIHORMONAL PITUITARY-ADENOMAS SO ENDOCRINE PATHOLOGY LA English DT Article ID GENE-PRODUCT; EXPRESSION; BINDING; TUMORS AB The biological activity of plurihormonal pituitary adenomas was compared with that of tumors producing only one hormone by evaluating the percentage of c-myc protein-labeled cells and ultrastructural characteristics. Twenty-five pituitary adenomas producing 3 or more hormones and 14 adenomas producing only 1 hormone were studied. Tissue sections were stained immunohistochemically using antibodies for pituitary hormones and c-myc protein. and they were examined by electronmicroscopy. DNA extracted from ethanol-fixed, paraffin-embedded tissue was analyzed for p53 mutations by polymerase chain reaction and single-strand conformation polymorphism analysis. The percentage of c-myc protein-labeled cells in adenomas producing 4 or 5 pituitary hormones was significantly higher (p < 0.01) than in those producing 3 or 1 hormones. There were no p53 mutations in plurihormonal adenomas. Pituitary adenomas producing 4 or 5 pituitary hormones demonstrate biological aggressiveness; therefore, multihormone production reflects aggressive capacity rather than degree of differentiation. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHAMOL,BOSTON,MA. RP IKEDA, H (reprint author), TOHOKU UNIV,SCH MED,INST BRAIN DIS,DIV NEUROSURG,AOBA KU,SEIRYO MACHI 1-1,SENDAI,MIYAGI 980,JAPAN. NR 13 TC 6 Z9 6 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 SN 1046-3976 J9 ENDOCR PATHOL JI Endocr. Pathol. PD SEP PY 1994 VL 5 IS 3 BP 162 EP 168 DI 10.1007/BF02921472 PG 7 WC Endocrinology & Metabolism; Pathology SC Endocrinology & Metabolism; Pathology GA PJ573 UT WOS:A1994PJ57300004 ER PT J AU OKANO, K WU, SX HUANG, XP PIROLA, CJ JUPPNER, H ABOUSAMRA, AB SEGRE, GV IWASAKI, K FAGIN, JA CLEMENS, TL AF OKANO, K WU, SX HUANG, XP PIROLA, CJ JUPPNER, H ABOUSAMRA, AB SEGRE, GV IWASAKI, K FAGIN, JA CLEMENS, TL TI PARATHYROID-HORMONE (PTH)/PTH-RELATED PROTEIN (PTHRP) RECEPTOR AND ITS MESSENGER-RIBONUCLEIC-ACID IN RAT AORTIC VASCULAR SMOOTH-MUSCLE CELLS AND UMR OSTEOBLAST-LIKE CELLS - CELL-SPECIFIC REGULATION BY ANGIOTENSIN-II AND PTHRP SO ENDOCRINOLOGY LA English DT Article ID ROS 17/2.8 CELLS; HUMORAL HYPERCALCEMIA; BINDING PROTEINS; BONE-RESORPTION; COMMON RECEPTOR; FREE CALCIUM; KINASE-C; PEPTIDE; EXPRESSION; GENE AB PTH-related protein (PTHrP) is produced in vascular smooth muscle, where it is believed to act as a local vasorelaxant by activating either the classical PTH or a unique PTHrP receptor. We used a newly cloned complementary DNA encoding the rat PTH/PTHrP receptor to study the expression of its messenger RNA (mRNA) in primary aortic vascular smooth muscle cells (VSMC) and in UMR-106 osteoblast-like cells under basal conditions and in response to treatment with agonists. Both cell types expressed a 2.4-kilobase PTH/PTHrP receptor mRNA transcript and exhibited hormone-induced desensitization of PTHrP-(1-34)NH2-stimulated cAMP. In VSMC, angiotensin-II, which induces PTHrP expression, also rapidly (30 min) desensitized the cAMP response and down-regulated (75-90%) receptor mRNA within 1 h. Treatment of cells with phorbol 12-myristate 13-acetate (0.1 mu M) mimicked these effects, whereas neither PTHrP-(1-34)NH2, forskolin, nor (Bu)(2)cAMP altered receptor mRNA expression. By contrast, in UMR-106 cells, PTHrP-(1-34)NH2 induced time- and dose-dependent decreases in receptor mRNA that were preceded by pronounced desensitization (cAMP and ligand binding) of cell surface receptors. These effects were mimicked by (Bu)(2)cAMP and forskolin, but not by phorbol 12-myristate 13-acetate, suggesting that both receptor mRNA down-regulation and receptor desensitization in UMR cells were mediated through a protein kinase-A pathway. We suggest that VSMC and UMR cells express a common receptor, which is subject to cell-specific regulation. Such diversity in the PTH/PTHrP receptor regulatory mechanisms provides a means for restricting the length and duration of the cellular response to hormone in a cell/tissue-specific manner. C1 CEDARS SINAI MED CTR, CEDARS SINAI RES INST, DEPT MED, DIV ENDOCRINOL, LOS ANGELES, CA 90048 USA. CEDARS SINAI MED CTR, CEDARS SINAI RES INST, DIV CARDIOL, LOS ANGELES, CA 90048 USA. MASSACHUSETTS GEN HOSP, ENDOCRINE UNIT, BOSTON, MA 02114 USA. NAGASAKI UNIV, SCH MED, DEPT ORTHOPED SURG, NAGASAKI 852, JAPAN. OI Pirola, Carlos/0000-0001-8234-4058; Abou-Samra, Abdul/0000-0001-8735-1142 FU NCI NIH HHS [CA-50906]; NHLBI NIH HHS [HL-47811]; NIDDK NIH HHS [DK-42792] NR 35 TC 74 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 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD SEP PY 1994 VL 135 IS 3 BP 1093 EP 1099 DI 10.1210/en.135.3.1093 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PD460 UT WOS:A1994PD46000039 PM 8070351 ER PT J AU GARDELLA, TJ JUPPNER, H WILSON, AK KEUTMANN, HT ABOUSAMRA, AB SEGRE, GV BRINGHURST, FR POTTS, JT NUSSBAUM, SR KRONENBERG, HM AF GARDELLA, TJ JUPPNER, H WILSON, AK KEUTMANN, HT ABOUSAMRA, AB SEGRE, GV BRINGHURST, FR POTTS, JT NUSSBAUM, SR KRONENBERG, HM TI DETERMINANTS OF [ARG(2)]PTH-(1-34) BINDING AND SIGNALING IN THE TRANSMEMBRANE REGION OF THE PARATHYROID-HORMONE RECEPTOR SO ENDOCRINOLOGY LA English DT Article ID EXPRESSION CLONING; NEUROKININ-1 RECEPTOR; EXTRACELLULAR DOMAIN; MOLECULAR-CLONING; SUBSTANCE-P; SPECIFICITY; ANTAGONIST; PEPTIDE; GROWTH; CELLS AB Previously, we reported that [Arg(2)]PTH-(1-34) bound to the rat osteosarcoma cell line, ROS 17/2.8, with 2-fold higher apparent affinity than it did to the opossum kidney cell line, OK, yet the analog was only a weak partial agonist for cAMP stimulation with ROS 17/2.8 cells, whereas it was a full cAMP agonist with OK cells. These results suggested that the rat and opossum PTH receptors differ in a region recognized by the hormone's amino-terminus. In this report we show that the cloned PTH receptors derived from ROS 17/2.8 and OK cells, expressed in COS-7 cells, also displayed altered responses to [Arg(2)] PTH-(1-34). Thus, [Arg(2)]PTH-(1-34) bound to the cloned rat PTH receptor with 7-fold higher affinity than it did to the cloned opossum PTH receptor, and in cAMP stimulation assays, it was a much weaker agonist with the rat receptor than it was with the opossum receptor. Studies with rat/opossum PTH receptor chimeras suggested that the membrane-spanning region of the receptor contributed to the different binding and signaling responses to [Arg(2)]PTH-(1-34). Point mutation analysis identified three sites in or near the extracellular ends of transmembrane domains V and VI, which specifically affected [Arg(2)] PTH-(1-34) binding and signaling. C1 HARVARD UNIV, SCH MED, BOSTON, MA 02114 USA. RP GARDELLA, TJ (reprint author), MASSACHUSETTS GEN HOSP, ENDOCRINE UNIT, BOSTON, MA 02114 USA. OI Abou-Samra, Abdul/0000-0001-8735-1142 NR 34 TC 77 Z9 77 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD SEP PY 1994 VL 135 IS 3 BP 1186 EP 1194 DI 10.1210/en.135.3.1186 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PD460 UT WOS:A1994PD46000051 PM 8070362 ER PT J AU BILLER, BMK AF BILLER, BMK TI PATHOGENESIS OF PITUITARY CUSHINGS-SYNDROME - PITUITARY VERSUS HYPOTHALAMIC SO ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA LA English DT Article ID CORTICOTROPIN-RELEASING FACTOR; X-CHROMOSOME INACTIVATION; ECTOPIC PRODUCTION; ADRENOCORTICOTROPIN SECRETION; CANDIDATE ONCOGENE; INDUCED REMISSION; SODIUM VALPROATE; TRANSGENIC MICE; CLONAL ORIGIN; DISEASE AB There has been a long-standing controversy as to whether Cushing's disease is caused by hypothalamic dysregulation or by a primary pituitary defect. There have been data supporting both concepts. Recent molecular biology techniques have confirmed, however, that coricotroph adenomas are monoclonal, supporting a genetic defect at the level of the pituitary as the cause of the disorder in most cases. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. RP BILLER, BMK (reprint author), MASSACHUSETTS GEN HOSP,NEUROENDOCRINE UNIT,FRUIT ST JACKSON 10,BOSTON,MA 02114, USA. FU NCRR NIH HHS [M01-RR1066] NR 66 TC 19 Z9 19 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-8529 J9 ENDOCRIN METAB CLIN JI Endocrinol. Metabol. Clin. North Amer. PD SEP PY 1994 VL 23 IS 3 BP 547 EP 554 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PH546 UT WOS:A1994PH54600007 PM 7805653 ER PT J AU HANDFORTH, A TREIMAN, DM AF HANDFORTH, A TREIMAN, DM TI EFFICACY AND TOLERANCE OF LONG-TERM, HIGH-DOSE GABAPENTIN - ADDITIONAL OBSERVATIONS SO EPILEPSIA LA English DT Article DE EPILEPSY; PARTIAL-ONSET SEIZURES; GABAPENTIN; ANTIEPILEPTIC DRUGS; PSYCHOSTIMULATION; ADVERSE EVENTS; TOLERANCE ID SEIZURES AB Gabapentin (GBP) has shown antiepileptic efficacy and good tolerance in clinical trials. Much remains to be learned about its clinical use. As a participating center in the US Gabapentin Study Group, we report observations that have practical implications for patient management. Twenty-three patients with intractable partial-onset seizures initiated open-label treatment after a blinded placebo-controlled add-on dose efficacy study. In the titration phase, GBP and concurrent antiepileptic drugs (AEDs) were adjusted to achieve optimal efficacy on maximally tolerated GBP doses. Nine patients had no significant improvement in seizure control and discontinued GBP. The remaining 14 patients were observed while treated long-term with stable-dose GBP and concurrent AEDs. Improvement was maintained as long as patients were followed: less than or equal to 4 years. The protocol-allowed upper dose limit, 2,400 mg/day, was well tolerated by 16 of 23 patients, indicating that higher doses may be tolerated. GBP discontinuation did net cause rebound increases in seizure frequency. The most common adverse events (AEs) (in 14 of 23) were similar to those induced by concurrent AEDs and responded to reduction of concurrent AEDs. Many patients reported positive psychostimulatory effects. These observations extend previous findings indicating that GBP is an effective and well-tolerated drug for treatment of partial-onset seizures. C1 W LOS ANGELES VET AFFAIRS MED CTR,RES SERV,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,SCH MED,DEPT NEUROL,LOS ANGELES,CA 90024. RP HANDFORTH, A (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,NEUROL SERV,11301 WILSHIRE BLVD,LOS ANGELES,CA 90073, USA. NR 13 TC 46 Z9 46 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD SEP-OCT PY 1994 VL 35 IS 5 BP 1032 EP 1037 DI 10.1111/j.1528-1157.1994.tb02551.x PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA PP612 UT WOS:A1994PP61200019 PM 7925148 ER PT J AU HANDFORTH, A TREIMAN, DM AF HANDFORTH, A TREIMAN, DM TI A NEW, NONPHARMACOLOGICAL MODEL OF CONVULSIVE STATUS EPILEPTICUS INDUCED BY ELECTRICAL-STIMULATION - BEHAVIORAL/ELECTROENCEPHALOGRAPHIC OBSERVATIONS AND RESPONSE TO PHENYTOIN AND PHENOBARBITAL SO EPILEPSY RESEARCH LA English DT Article DE STATUS EPILEPTICUS; EXPERIMENTAL SEIZURES; PHENYTOIN; PHENOBARBITAL; TREATMENT ID RODENT MODEL; KAINIC ACID; PILOCARPINE; SEIZURES; RATS; PATHOLOGY; LITHIUM AB Much remains to be learned about mechanisms underlying entry into, and temporal progression of, status epilepticus (SE). This report describes a non-pharmacologic model of generalized convulsive SE in rat. Pulsed trains of suprathreshold electric current were administered bilaterally to either of four rostral forebrain sites: orbital cortex, medial precentral cortex, deep prepiriform cortex, or rostral caudate-putamen (n=8 per site). This induction method resulted in 30/32 animals attaining limb-clonic convulsive SE within a mean of 30-35 min for each forebrain site, with no differences between sites. Subsequent SE proceeded without further interventions, permitting observation of the natural course of progression. A stereotyped behavioral/electrographic sequence occurred, characterized by devolution. Behaviorally, animals progressed from predominantly limb clonus to head clonus, then to subtle twitching, and finally to electrical SE before cessation of spikes. The corresponding electrographic progression was from fast and slow spiking to periodic epileptiform discharges (PEDs). In 20 animals surviving to 48 h, pathologic damage affected mainly limbic sites; damage was related to total convulsive time rather than to clonic activity. High-dose phenobarbital but not phenytoin suppressed SE when given during orbital cortex-induced limb-clonic SE. These findings are compatible with human observations and indicate that this model will enable investigations of generalized SE mechanisms and evaluation of new therapeutic agents for refractory SE. C1 W LOS ANGELES VET AFFAIRS MED CTR,RES SERV,LOS ANGELES,CA. UNIV CALIF LOS ANGELES,DEPT NEUROL,LOS ANGELES,CA 90024. RP HANDFORTH, A (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,WADSWORTH DIV,NEUROL SERV,WILSHIRE & SAWTELLE BLVDS,LOS ANGELES,CA 90073, USA. NR 33 TC 11 Z9 11 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-1211 J9 EPILEPSY RES JI Epilepsy Res. PD SEP PY 1994 VL 19 IS 1 BP 15 EP 25 DI 10.1016/0920-1211(94)90084-1 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA PE965 UT WOS:A1994PE96500002 PM 7813410 ER PT J AU PANTAZIS, P MENDOZA, JT DEJESUS, A RUBIN, E KUFE, D GIOVANELLA, BC AF PANTAZIS, P MENDOZA, JT DEJESUS, A RUBIN, E KUFE, D GIOVANELLA, BC TI PARTIAL CHARACTERIZATION OF HUMAN LEUKEMIA U-937 CELL SUBLINES RESISTANT TO 9-NITROCAMPTOTHECIN SO EUROPEAN JOURNAL OF HAEMATOLOGY LA English DT Article DE CAMPTOTHECIN; DRUG RESISTANCE; DIFFERENTIATION; TOPOISOMERASE; TUMORIGENICITY ID DNA TOPOISOMERASE-I; NUDE-MICE; HL-60 CELLS; S-PHASE; CAMPTOTHECIN; DIFFERENTIATION; INVITRO; GROWTH; INHIBITORS; XENOGRAFTS AB (H)uman leukemia U-937 cell sublines exhibiting various levels of resistance to 9-nitrocamptothecin (9NC) were developed after exposure to progressively increased 9NC concentrations. Increases in 9NC resistance of the cells were accompanied by decreases in proliferation rate; appearance of morphological and functional features that correlate with granulocytic maturation; decreased synthesis of topoisomerase I; increased synthesis of topoisomerase II; and inability or decreased ability to induce tumors when xenografted in nude mice. 9NC-resistant cells, transferred and propagated in 9NC-free media for 6 months, continue to exhibit resistance and other features similar to cells propagated in continual presence of 9NC. Finally, 9NC-resistant U-937 cells respond to physiological and non-physiological agents of cell differentiation, indicating that alternative treatments can be successfully used to inhibit growth of 9NC-resistant U-937 cells and tumors. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. RP PANTAZIS, P (reprint author), ST JOSEPH HOSP,STEHLIN FDN CANC RES,1918 CHENEVERT ST,HOUSTON,TX 77003, USA. NR 38 TC 17 Z9 17 U1 1 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0902-4441 J9 EUR J HAEMATOL JI Eur. J. Haematol. PD SEP PY 1994 VL 53 IS 3 BP 135 EP 144 PG 10 WC Hematology SC Hematology GA PM853 UT WOS:A1994PM85300002 PM 7925856 ER PT J AU BUTINI, L DEFOUGEROLLES, AR VACCAREZZA, M GRAZIOSI, C COHEN, DI MONTRONI, M SPRINGER, TA PANTALEO, G FAUCI, AS AF BUTINI, L DEFOUGEROLLES, AR VACCAREZZA, M GRAZIOSI, C COHEN, DI MONTRONI, M SPRINGER, TA PANTALEO, G FAUCI, AS TI INTERCELLULAR-ADHESION MOLECULES (ICAM)-1 ICAM-2 AND ICAM-3 FUNCTION AS COUNTER-RECEPTORS FOR LYMPHOCYTE FUNCTION-ASSOCIATED MOLECULE-1 IN HUMAN IMMUNODEFICIENCY VIRUS-MEDIATED SYNCYTIA FORMATION SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE ADHESION MOLECULES; SYNCYTIA; HUMAN IMMUNODEFICIENCY VIRUS ID FUNCTION-ASSOCIATED ANTIGEN-1; ENVELOPE GLYCOPROTEIN; HIV-INFECTION; AIDS RETROVIRUS; MEMBRANE-FUSION; IMMUNE-SYSTEM; HTLV-III/LAV; T4 MOLECULE; SOLUBLE CD4; LFA-1 AB It has been previously demonstrated that lymphocyte function-associated molecule 1 (LFA-1) plays a major role in human immunodeficiency virus (HIV)-mediated syncytia formation. In the present study we investigated the involvement of intercellular adhesion molecule-1 (ICAM-1), ICAM-2 and ICAM-3 in the process. The ability of monoclonal antibodies (mAb) directed against ICAM-1, ICAM-2 and ICAM-3 to block syncytia was analyzed either in phytohemagglutinin (PHA)-activated lymphocytes infected in vitro with primary or laboratory strains of HIV or by coculturing a T cell line stably expressing HIV envelope with PHA-activated lymphocytes. Complete inhibition of syncytia formation was observed only by the simultaneous addition to the cell cultures of all (i.e. anti-ICAM-1, anti-ICAM-2 and anti-ICAM-3) mAb. These results indicate that the interaction between LFA-1 and ICAM is a critical step in HIV-mediated syncytia formation, and that ICAM-1, ICAM-2 and ICAM-3 are the receptor molecules for the LFA-1-dependent syncytia formation. C1 NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. UNIV ANCONA,INST INTERNAL MED,DEPT CLIN IMMUNOL,ANCONA,ITALY. HARVARD UNIV,SCH MED,DEPT PATHOL,COMM IMMUNOL,BOSTON,MA 02115. CTR BLOOD RES,BOSTON,MA. RI Pantaleo, Giuseppe/K-6163-2016; OI VACCAREZZA, Mauro/0000-0003-3060-318X NR 41 TC 42 Z9 43 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 SEP PY 1994 VL 24 IS 9 BP 2191 EP 2195 DI 10.1002/eji.1830240939 PG 5 WC Immunology SC Immunology GA PJ300 UT WOS:A1994PJ30000038 PM 7916296 ER PT J AU CANNISTRA, SA OTTENSMEIER, C TIDY, J DEFRANZO, B AF CANNISTRA, SA OTTENSMEIER, C TIDY, J DEFRANZO, B TI VASCULAR CELL-ADHESION MOLECULE-1 EXPRESSED BY PERITONEAL MESOTHELIUM PARTLY MEDIATES THE BINDING OF ACTIVATED HUMAN T-LYMPHOCYTES SO EXPERIMENTAL HEMATOLOGY LA English DT Article DE PERITONEUM; MESOTHELIUM; ADHESION; VCAM-1 ID HUMAN ENDOTHELIAL-CELLS; LEUKOCYTE ADHESION; INTEGRIN VLA-4; VCAM-1; RECEPTOR; ADHERENCE; ANTIBODY; PROTEIN; ICAM-1; LFA-1 AB Adhesion molecules such as selectins and integrins are known to mediate leukocyte attachment and transmigration through activated vascular endothelium. However, the molecules that mediate subsequent leukocyte entry into nonvascular spaces such as the abdominal cavity during states of peritoneal inflammation have not been identified. Because the peritoneal mesothelial lining represents the final barrier to leukocyte migration into the abdomen, it is likely that adhesion molecules expressed by mesothelial cells are involved in this process. We have developed an in vitro binding assay using confluent layers of normal human mesothelial cells to determine which adhesion molecules might be involved in T lymphocyte-mesothelial recognition. Normal peripheral blood T lymphocytes exhibit low-level specific binding to mesothelium (mean 13% specific binding, n=4), which is enhanced by phorbol myristate acetate (PMA) treatment (mean 38% specific binding, n=4). This binding is significantly inhibited in the combined presence of antibodies reactive with CD29 and CD18, suggesting a role for beta 1 and beta 2 integrins, respectively, in this interaction. Interestingly, cultured human mesothelial cells were shown to express vascular cell adhesion molecule-1 (VCAM-1), suggesting that this molecule might function as a counter-receptor for alpha 4 beta 1 expressed by T lymphocytes. Mesothelial cells were also noted to express ICAM-1, CD29, and CD44, but not CD18 or selectins. VCAM-1 expression was not a constitutive property of freshly obtained mesothelial cells but was inducible upon culture in the presence of either interleukin-l (IL-1), tumor necrosis factor (TNF), or PMA. Neutralizing antibodies reactive with either alpha 4, VCAM-1, or CD29 were all equally capable of inhibiting the binding of activated leukocytes to mesothelial cells (in the presence of anti-CD18 antibody). Mesothelial VCAM-1 was found to have a molecular mass of 110 kD and an mRNA transcript of approximate to 3.2 kb, consistent with the predominant VCAM-1 species found in activated endothelium. These data suggest that functional VCAM-1 is expressed on activated mesothelial cells and may play a role in the distal arm of leukocyte trafficking to the abdominal cavity. RP CANNISTRA, SA (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV MED ONCOL,44 BINNEY ST,BOSTON,MA 02115, USA. RI Ottensmeier, Christian/E-8131-2012 OI Ottensmeier, Christian/0000-0003-3619-1657 FU NCI NIH HHS [CA 60670] NR 30 TC 44 Z9 45 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD SEP PY 1994 VL 22 IS 10 BP 996 EP 1002 PG 7 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA PG272 UT WOS:A1994PG27200009 PM 7522188 ER PT J AU KIRIKAE, T SCHADE, FU KIRIKAE, F QURESHI, N TAKAYAMA, K RIETSCHEL, ET AF KIRIKAE, T SCHADE, FU KIRIKAE, F QURESHI, N TAKAYAMA, K RIETSCHEL, ET TI DIPHOSPHORYL LIPID-A DERIVED FROM THE LIPOPOLYSACCHARIDE (LPS) OF RHODOBACTER-SPHAEROIDES ATCC-17023 IS A POTENT COMPETITIVE LPS INHIBITOR IN MURINE MACROPHAGE-LIKE J774.1 CELLS SO FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY LA English DT Article DE LIPOPOLYSACCHARIDE; LIPOPOLYSACCHARIDE RECEPTOR; RHODOBACTER SPHAEROIDES LIPID A; MACROPHAGE-LIKE CELL LINE ID TUMOR-NECROSIS-FACTOR; RHODOPSEUDOMONAS-SPHAEROIDES; NONTOXIC LIPOPOLYSACCHARIDE; HUMAN-MONOCYTES; FATTY-ACIDS; BINDING; ATCC-17023; ENDOTOXIN; ACTIVATION; INDUCTION AB Pentaacyl diphosphoryl lipid A derived from the nontoxic lipopolysaccharide (LPS) of Rhodobacter sphaeroides ATCC 17023 (RsDPLA) did not induce tumour necrosis factor-alpha nor interleukin-6 release in the murine macrophage-like cell line J774.1. However, it effectively inhibited the induction of these two cytokines by LPS of Salmonella minnesota Re mutant R595 (ReLPS) in a concentration-dependent manner. Maximal inhibition and half-maximal inhibition occurred when the ReLPS to RsDPLA mass ratio was 1:30 and 1:1, respectively. A binding study was performed in the presence of serum to determine whether RsDPLA is competing with ReLPS for LPS binding sites on J774.1 cells. This assay allows the determination of LPS binding to J774.1 cells via a mechanism involving CD14, a receptor for complexes of LPS with LPS binding protein (LBP), and its possible inhibition. The results show that RsDPLA strongly inhibits the binding of(125) I-labelled ReLPS to J774.1 cells. Maximal and one-half maximal inhibition of binding occurred when the ReLPS to RsDPLA mass ratios were 1:2.5 and 1:0.5, respectively. It was found that the inhibition of binding by RsDPLA was much stronger than that by unlabelled ReLPS. These results suggest that RsDPLA is competing with ReLPS for CD14-dependent recognition of LPS on J774.1 cells. C1 FORSCHUNGSINST BORSTEL,INST EXPTL BIOL & MED,D-23845 BORSTEL,GERMANY. WILLIAM S MIDDLETON MEM VET ADM MED CTR,MYCOBACTERIOL RES LAB,MADISON,WI. UNIV WISCONSIN,COLL AGR & LIFE SCI,DEPT BACTERIOL,MADISON,WI 53706. FU NIGMS NIH HHS [GM-36054] NR 24 TC 27 Z9 28 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0928-8244 J9 FEMS IMMUNOL MED MIC JI FEMS Immunol. Med. Microbiol. PD SEP PY 1994 VL 9 IS 3 BP 237 EP 243 DI 10.1111/j.1574-695X.1994.tb00499.x PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA PH574 UT WOS:A1994PH57400010 PM 7812271 ER PT J AU LOVE, TW QUERTERMOUS, T RUNGE, MS MICHELSON, KD MATSUEDA, GR HABER, E AF LOVE, TW QUERTERMOUS, T RUNGE, MS MICHELSON, KD MATSUEDA, GR HABER, E TI ATTACHMENT OF AN ANTIFIBRIN ANTIBODY TO THE AMINO-TERMINUS OF TISSUE-TYPE PLASMINOGEN-ACTIVATOR IMPAIRS STIMULATION BY FIBRIN SO FIBRINOLYSIS LA English DT Article ID THROMBOLYTIC THERAPY; SINGLE-CHAIN; UROKINASE; KINETICS; POTENCY; INVITRO; INVIVO AB On evidence that the potency and specificity of tissue-type plasminogen activator (t-PA) can be improved by chemical conjugation to an antifibrin antibody (59D8), we constructed a recombinant molecule, 59D8-t-PA(AB), containing a truncated 59D8 antibody attached through peptide linkage to the amino terminus of full-length t-PA. Initial analysis of recombinant 59D8-t-PA(AB) in the absence of fibrin revealed enzymatic characteristics indistinguishable from those of t-PA: for the S-2288 substrate, the respective K-m values of t-PA and 59D8-t-PA(AB) were 0.48+/-0.02mM and 0.52+/-0.02mM; for plasminogen, the values were 82.35+/-5.35 mu M and 81.25+/-2.03 mu M Recombinant 59D8-t-PA(AB) was up to 10-fold more potent than t-PA in an assay measuring the lysis of fibrin monomer. However, in contrast with the chemical conjugate, recombinant 59D8-t-PA(AB) was 2 to 3-fold less potent than t-PA in lysing clots in a plasma milieu. To determine whether this difference in plasma clot lysis was due to impaired fibrin stimulation of the t-PA portion of the recombinant molecule, we devised an assay that quantitates fibrin stimulation of t-PA's catalytic activity. Fibrin stimulation was indeed reduced by 15-fold for recombinant 59D8-t-PA(AB). This observation suggests that attaching a targeting antibody to the amino terminus of t-PA diminishes the ability of fibrin to stimulate the enzyme. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,GEN MED SERV,CARDIAC UNIT,BOSTON,MA 02114. UNIV TEXAS,MED BRANCH,DIV CARDIOL,GALVESTON,TX 77555. BRISTOL MYERS SQUIBB PHARMACEUT RES INST,PRINCETON,NJ 08543. PRINCETON UNIV,PRINCETON,NJ 08544. NR 31 TC 4 Z9 4 U1 0 U2 3 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH, MIDLOTHIAN, SCOTLAND EH1 3AF SN 0268-9499 J9 FIBRINOLYSIS JI Fibrinolysis PD SEP PY 1994 VL 8 IS 5 BP 326 EP 332 DI 10.1016/0268-9499(94)90022-1 PG 7 WC Hematology SC Hematology GA PH568 UT WOS:A1994PH56800009 ER PT J AU MARTIN, P FRIEDMAN, LS AF MARTIN, P FRIEDMAN, LS TI VIRAL-HEPATITIS - PREFACE SO GASTROENTEROLOGY CLINICS OF NORTH AMERICA LA English DT Editorial Material C1 MASSACHUSETTS GEN HOSP, GASTROINTESTINAL UNIT, BOSTON, MA 02114 USA. RP MARTIN, P (reprint author), UNIV CALIF LOS ANGELES, SCH MED, 77-123D CHS, 10833 LE CONTE AVE, LOS ANGELES, CA 90027 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8553 J9 GASTROENTEROL CLIN N JI Gastroenterol. Clin. North Am. PD SEP PY 1994 VL 23 IS 3 BP R11 EP R12 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PE592 UT WOS:A1994PE59200001 ER PT J AU BOVIATSIS, EJ SCHARF, JM CHASE, M HARRINGTON, K KOWALL, NW BREAKEFIELD, XO CHIOCCA, EA AF BOVIATSIS, EJ SCHARF, JM CHASE, M HARRINGTON, K KOWALL, NW BREAKEFIELD, XO CHIOCCA, EA TI ANTITUMOR-ACTIVITY AND REPORTER GENE-TRANSFER INTO RAT-BRAIN NEOPLASMS INOCULATED WITH HERPES-SIMPLEX VIRUS VECTORS DEFECTIVE IN THYMIDINE KINASE OR RIBONUCLEOTIDE REDUCTASE SO GENE THERAPY LA English DT Article ID BETA-GALACTOSIDASE; GLIOMA-CELLS; NERVOUS-SYSTEM; NEURONS; THERAPY; TUMORS; MUTANTS; EXPRESSION; GROWTH; TYPE-1 AB Herpes simplex virus (HSV) mutants or recombinant vectors might be useful oncolytic agents. Three general types of HSV vectors can be potentially used for this purpose: (1) mutants in viral transcription factors, such as ICP0 and ICP4; (2) mutants in enzymes involved in nucleic acid metabolism, such as thymidine kinase (TK) and ribonucleotide reductase (RR); and (3) mutants in neurovirulence factors, such as gamma(34.5). We tested the destructive ability of each type against rat 9L gliosarcoma cells in culture. We found that the HSV vectors defective in TK or RR were more efficient at tumor cell lysis in culture than the other types of HSV vectors. This increased efficiency provided the rationale for evaluating the TK and RR mutants in vivo following their stereotactic inoculation into 9L gliosarcomas implanted in rat brains. We employed the X-gal enzymatic histochemical assay to show that HSV-mediated lacZ gene expression was present in cells within the tumor mass in a relatively selective fashion. Immunoreactive HSV capsid and core antigens were present both in cells within the tumor, as well as in cells such as neurons and astrocytes, directly adjacent to the tumor mass. Long-term survival studies revealed that rats treated with either the TK or RR mutant lived significantly longer than control rats (p = 0.014, Kruskal-Wallis one-way analysis of variance). These results indicate that HSV vectors, defective in enzymes needed in nucleic acid metabolism, can preferentially mediate lacZ gene expression in cells within the tumor. Furthermore, these vectors can enter into endogenous neural cells (accounting for the defection of viral capsid and core antigens), but probably mediate very low levels of lacZ gene expression, presumably due to shut-off of the lacZ gene promoter. The tumoricidal activity of these vectors results in significant prolongation in the survival of rats injects with each mutant. A model of HSV vector infection and propagation within the tumor and adjacent brain is discussed. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,MOLEC NEUROGENET UNIT,BOSTON,MA 02129. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG NEUROSURG SERV,BOSTON,MA 02129. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,NEUROSCI PROGRAM,BOSTON,MA 02129. BEDFORD VA MED CTR,DEPT NEUROL,BEDFORD,MA. BEDFORD VA MED CTR,DEPT PATHOL,BEDFORD,MA. RI Kowall, Neil/G-6364-2012 OI Kowall, Neil/0000-0002-6624-0213 FU NINDS NIH HHS [NS 24279-08] NR 50 TC 104 Z9 105 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0969-7128 J9 GENE THER JI Gene Ther. PD SEP PY 1994 VL 1 IS 5 BP 323 EP 331 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA PT949 UT WOS:A1994PT94900007 PM 7584098 ER PT J AU MASHAL, RD FEJZO, MLS FRIEDMAN, AJ MITCHNER, N NOWAK, RA REIN, MS MORTON, CC SKLAR, J AF MASHAL, RD FEJZO, MLS FRIEDMAN, AJ MITCHNER, N NOWAK, RA REIN, MS MORTON, CC SKLAR, J TI ANALYSIS OF ANDROGEN RECEPTOR DNA REVEALS THE INDEPENDENT CLONAL ORIGINS OF UTERINE LEIOMYOMATA AND THE SECONDARY NATURE OF CYTOGENETIC ABERRATIONS IN THE DEVELOPMENT OF LEIOMYOMATA SO GENES CHROMOSOMES & CANCER LA English DT Article ID X-CHROMOSOME INACTIVATION; HUMAN-TUMORS; POLYMORPHISMS; REMISSION; LEUKEMIA AB Uterine leiomyomata are thought to be monoclonal neoplasms. Accordingly, investigations of clonality with G6PD isoforms used as a marker for X chromosome inactivation have suggested independent origins for multiple tumors within individual uteri. However, results from a recent study assessing methylation differences between DNA of active and inactive X chromosomes have been interpreted to suggest that multiple tumors may arise from a common precursor. We have examined the clonality of 36 leiomyomata from 16 patients by analyzing X chromosome inactivation as indicated by the methylation status of the X-linked androgen receptor gene. As shown by this assay, all informative leiomyomata were monoclonal in origin. In patients with multiple leiomyomata, a random distribution of inactivation between the X homologs was noted, consistent with an independent origin of each tumor. Cytogenetic analysis was also performed on short-term cell cultures of 27 of the 36 tumors. In each of two tumors that had both cells with a clonal karyotypic abnormality and karyotypically normal cells, DNA prepared from short-term cultures showed a monoclonal pattern of X inactivation identical to that of the leiomyoma from which they were derived. These data suggest that karyotypically normal cells present in short-term cultures of uterine leiomyomata are part of the tumor clone, and that clonal expansion of tumor cells precedes the development of cytogenetic aberrations. (C) 1994 Wiley-Liss, Inc. C1 BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT OBSTET GYNECOL & REPROD BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA. FU NCI NIH HHS [CA 01556]; NICHD NIH HHS [HD 30496, HD 30498] NR 19 TC 106 Z9 112 U1 1 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD SEP PY 1994 VL 11 IS 1 BP 1 EP 6 DI 10.1002/gcc.2870110102 PG 6 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA PD822 UT WOS:A1994PD82200001 PM 7529041 ER PT J AU EPSTEIN, JA GLASER, T CAI, JX JEPEAL, L WALTON, DS MAAS, RL AF EPSTEIN, JA GLASER, T CAI, JX JEPEAL, L WALTON, DS MAAS, RL TI 2 INDEPENDENT AND INTERACTIVE DNA-BINDING SUBDOMAINS OF THE PAX6 PAIRED DOMAIN ARE REGULATED BY ALTERNATIVE SPLICING SO GENES & DEVELOPMENT LA English DT Article DE PAX GENES; TRANSCRIPTION FACTOR; ALTERNATIVE MESSENGER-RNA SPLICING; DNA BINDING; OCULAR DEVELOPMENT; ANIRIDIA ID HOMEOBOX-CONTAINING GENE; TRANSCRIPTION FACTOR; ESCHERICHIA-COLI; LFB1 HNF1; EXPRESSION; SEQUENCE; HOMEODOMAIN; MUTATIONS; PROTEIN; SITE AB Vertebrate Pax proteins share a conserved 128-amino-acid DNA-binding motif, the paired domain. The PAX6 gene, which is mutated in the murine Small eye and human aniridia developmental defects, also encodes a second protein with a 14-amino-acid insertion in the paired domain. This protein, which arises by alternative mRNA splicing, exhibits unique DNA-binding properties. Unlike other paired domains, which bind DNA predominantly by their amino termini, the extended Pax6 paired domain interacts with DNA exclusively through its carboxyl terminus. This property can be simulated by deletion of 30 amino-terminal residues from the Pax6 or Pax2 paired domains. Thus, the insertion acts as a molecular toggle to unmask the DNA-binding potential of the carboxyl terminus. The functional nonequivalence of the two Pax6 proteins is underscored by a T --> C mutation at position -3 of the alternative splice acceptor site that changes the ratio of the two isoforms and causes a distinct human ocular syndrome. C1 HARVARD UNIV,SCH MED,DEPT MED,DIV GENET,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,HOWARD HUGHES MED INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,DIV CARDIOL,BOSTON,MA 02115. FU NEI NIH HHS [EY10123] NR 59 TC 280 Z9 287 U1 0 U2 5 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 SEP 1 PY 1994 VL 8 IS 17 BP 2022 EP 2034 DI 10.1101/gad.8.17.2022 PG 13 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA PF914 UT WOS:A1994PF91400003 PM 7958875 ER PT J AU ROBERTSON, NG KHETARPAL, U GUTIERREZESPELETA, GA BIEBER, FR MORTON, CC AF ROBERTSON, NG KHETARPAL, U GUTIERREZESPELETA, GA BIEBER, FR MORTON, CC TI ISOLATION OF NOVEL AND KNOWS GENES FROM A HUMAN FETAL COCHLEAR CDNA LIBRARY USING SUBTRACTIVE HYBRIDIZATION AND DIFFERENTIAL SCREENING SO GENOMICS LA English DT Article ID TOOTH DISEASE TYPE-1A; INSITU HYBRIDIZATION; COLLAGEN GENES; MESSENGER-RNAS; NERVOUS-SYSTEM; EXPRESSION; MOUSE; DUPLICATION; SPARC; DNA AB We used a combination of subtractive hybridization and differential screening strategies to identify genes that may function normally in hearing and, when mutated, result in deafness. A human fetal cochlear (membranous labyrinth) cDNA library was subtracted against total human fetal brain RNAs by an avidin-biotin-based procedure to enrich for cochlear transcripts. Subtracted cochlear clones were differentially screened with P-32-labeled total cochlear and total brain cDNA probes. Sequence analysis of clones that hybridized more intensely with cochlear than with brain cDNA probes revealed some previously characterized genes, including mitochondrial sequences, collagen type I alpha-2 (COL1A2), collagen type II alpha-1 (COL2A1), collagen type III alpha-1 (COL3A1), spermidine/ spermine N-1-acetyltransferase (SAT), osteonectin (SPARC), and peripheral myelin protein 22 (PMP22). Also identified were clones that are potential novel cochlear genes. Northern blots of cochlear and brain RNAs probed with COL1A2, COL2A1, COL3A1, SAT, SPARC, PMP22, and a novel sequence, designated Coch-5B2, confirm results of the subtractive procedure by showing preferential cochlear expression. A number of these genes serve structural or regulatory functions in extracellular matrix or neural conduction; defects in some of these genes are associated with disorders involving hearing loss. Partial sequence analysis of Coch-5B2 reveals a von Willebrand factor type Alike domain in this cDNA. To assess the cochlear specificity of Coch-5B2, a Northern blot panel of 14 human fetal tissue RNAs was probed with Coch-5B2, showing differential expression of this novel gene in the cochlea. (C) 1994 Academic Press, Inc. C1 BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. UNIV COSTA RICA,ESCUELA BIOL,SAN JOSE,COSTA RICA. FU NHLBI NIH HHS [T32 HL07627]; NIDCD NIH HHS [DC00871] NR 68 TC 143 Z9 152 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD SEP 1 PY 1994 VL 23 IS 1 BP 42 EP 50 DI 10.1006/geno.1994.1457 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA PG072 UT WOS:A1994PG07200006 PM 7829101 ER PT J AU RUTAN, JS ALONSO, A AF RUTAN, JS ALONSO, A TI SOME GUIDELINES FOR GROUP THERAPISTS - REPLY SO GROUP LA English DT Letter C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114. RP RUTAN, JS (reprint author), HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HUMAN SCI PRESS INC PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 SN 0362-4021 J9 GROUP JI Group PD FAL PY 1994 VL 18 IS 3 BP 187 EP 188 DI 10.1007/BF01456590 PG 2 WC Psychology, Clinical SC Psychology GA PU109 UT WOS:A1994PU10900008 ER PT J AU GOFF, BA KATO, D SCHMIDT, RA EK, M FERRY, JA MUNTZ, HG CAIN, JM TAMIMI, HK FIGGE, DC GREER, BE AF GOFF, BA KATO, D SCHMIDT, RA EK, M FERRY, JA MUNTZ, HG CAIN, JM TAMIMI, HK FIGGE, DC GREER, BE TI UTERINE PAPILLARY SEROUS CARCINOMA - PATTERNS OF METASTATIC SPREAD SO GYNECOLOGIC ONCOLOGY LA English DT Article ID WHOLE ABDOMINOPELVIC IRRADIATION; I ENDOMETRIAL CANCER; PROGNOSTIC-SIGNIFICANCE; ADENOCARCINOMA; VARIABLES; INVASION AB Uterine papillary serous carcinoma (UPSC) is a distinct histologic type of endometrial cancer which is associated with a high relapse rate and poor prognosis. Between 1983 and 1993, 50 patients with UPSC of the endometrium were surgically staged. Thirty-three patients had pure UPSC and 17 had UPSC admixed with other histologies. Extrauterine disease was found in 36 women (72%). Lymph node metastases were present in 36% of women without myometrial invasion, 50% with inner one-half invasion, and 40% with outer one-half invasion. Similarly, the presence of intraperitoneal disease or positive washings did not correlate with increasing myometrial invasion. Grade and histology (mixed vs pure) were also not predictive of extrauterine disease. Patients with lymphatic/vascular space invasion (LVSI) were more likely to have extrauterine disease (85%); however, even without LVSI the incidence of extrauterine disease was 58% (P = 0.05). Unlike endometrioid adenocarcinomas, grade and depth of myometrial invasion were not significant predictors for extrauterine disease. This study reinforces the need for complete surgical staging in all patients with UPSC regardless of depth of invasion. (C) 1994 Academic Press, Inc. C1 UNIV WASHINGTON,DEPT PATHOL,SEATTLE,WA 98195. MASSACHUSETTS GEN HOSP,VINCENT MEM GYNECOL ONCOL SERV,BOSTON,MA 02114. RP GOFF, BA (reprint author), UNIV WASHINGTON,DEPT OBSTET & GYNECOL,SEATTLE,WA 98195, USA. NR 25 TC 240 Z9 248 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD SEP PY 1994 VL 54 IS 3 BP 264 EP 268 DI 10.1006/gyno.1994.1208 PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA PK892 UT WOS:A1994PK89200002 PM 8088602 ER PT J AU PULS, LE HAMOUS, J MORROW, MS SCHNEYER, A MACLAUGHLIN, DT CASTRACANE, VD AF PULS, LE HAMOUS, J MORROW, MS SCHNEYER, A MACLAUGHLIN, DT CASTRACANE, VD TI RECURRENT OVARIAN SEX CORD TUMOR WITH ANNULAR TUBULES - TUMOR-MARKER AND CHEMOTHERAPY EXPERIENCE SO GYNECOLOGIC ONCOLOGY LA English DT Note ID PEUTZ-JEGHERS SYNDROME; MULLERIAN INHIBITING SUBSTANCE; FALLOPIAN-TUBE; ALPHA-SUBUNIT; NEOPLASMS; SERUM AB Recurrent sex cord tumor with annular tubules is an unusual ovarian cancer. The authors report a patient with recurrent disease that was ultimately followed with multiple tumor markers. During this period the patient was treated only with chemotherapy. Her regimen consisted of a combination of etoposide, bleomycin, and cisplatin. The tumor markers that were followed were CA-125, CEA, inhibin, and Mullerian-inhibiting substance (MIS). There was no elevation of the CA-125 or CEA, but inhibin and MIS proved to be effective markers. Serum inhibin and MIS correlated perfectly with her documented disease status and was brought into the normal range when the patient was disease-free. This disease-free status was proven by surgical reexploration. This report is the first documented complete response in this rare malignancy treated by chemotherapy alone with distant metastatic spread. It also gives strong linkage of inhibin and MIS as good markers in this particularly rare malignancy. (C) 1994 Academic Press, Inc. C1 TEXAS TECH UNIV,HLTH SCI CTR,DEPT OBSTET & GYNECOL,AMARILLO,TX 79106. MASSACHUSETTS GEN HOSP,NATL CTR INFERTIL RES,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,PEDIAT SURG RES LABS,BOSTON,MA 02114. RP PULS, LE (reprint author), TEXAS TECH UNIV,HLTH SCI CTR,DIV GYNECOL ONCOL,1400 WALLACE BLVD,AMARILLO,TX 79106, USA. FU FDA HHS [FDA 000669]; NICHD NIH HHS [R01HD25941, U54HD29164] NR 23 TC 19 Z9 23 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD SEP PY 1994 VL 54 IS 3 BP 396 EP 401 DI 10.1006/gyno.1994.1232 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA PK892 UT WOS:A1994PK89200026 PM 7522202 ER PT J AU COFFEY, BJ MIGUEL, EC SAVAGE, CR RAUCH, SL AF COFFEY, BJ MIGUEL, EC SAVAGE, CR RAUCH, SL TI TOURETTES DISORDER AND RELATED PROBLEMS - A REVIEW AND UPDATE SO HARVARD REVIEW OF PSYCHIATRY LA English DT Review ID OBSESSIVE-COMPULSIVE DISORDER; NEUROPSYCHOLOGICAL PERFORMANCE; BASAL GANGLIA; NARCOTIC-ANTAGONISTS; SEROTONIN HYPOTHESIS; TIC DISORDER; GILLES; CHILDREN; PIMOZIDE; SYMPTOMS AB Tourette's disorder is a complex, multifaceted condition of neurological origin with psychiatric symptomatology characterized by multiple motor and vocal tics. It begins during childhood and has a waxing and waning course. Coexisting obsessive-compulsive symptoms, attentional problems, and other behavioral features are common. Pathophysiology involves dysfunction in basal ganglia and related corticothalamic circuits. Many patients who present in clinical settings have mild to moderate symptoms and require only education, monitoring, and long-term follow-up. Those with more-severe symptoms require treatment, typically including both pharmacotherapy and nonmedication approaches. In addition to traditional neuroleptic treatment, a variety of agents such as clonidine, serotonin-reuptake inhibitors, and tricyclic antidepressants can be used. Further investigation is needed in a variety of areas, including longitudinal follow-up studies of children, adolescents, and adults with Tourette's disorder; systematic investigation of psychiatric comorbidity and the heterogeneity of the disorder; clarification of the phenomenological similarities and differences between Tourette's disorder and obsessive-compulsive disorder; and neuroimaging and neuropsychological studies of Tourette's disorder and related problems. C1 MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA. RP COFFEY, BJ (reprint author), MCLEAN HOSP,115 MILL ST,BELMONT,MA 02178, USA. RI Miguel, Euripedes/B-2871-2008 NR 102 TC 13 Z9 14 U1 10 U2 11 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 SEP-OCT PY 1994 VL 2 IS 3 BP 121 EP 132 DI 10.3109/10673229409017128 PG 12 WC Psychiatry SC Psychiatry GA PH847 UT WOS:A1994PH84700001 PM 9384893 ER PT J AU OTTO, MW POLLACK, MH AF OTTO, MW POLLACK, MH TI TREATMENT STRATEGIES FOR PANIC DISORDER - A DEBATE SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article ID OBSESSIVE-COMPULSIVE DISORDER; BEHAVIORAL TREATMENT; LONDON TORONTO; FOLLOW-UP; ALPRAZOLAM; THERAPY; AGORAPHOBIA; EXPOSURE; DISCONTINUATION; MAINTENANCE RP OTTO, MW (reprint author), MASSACHUSETTS GEN HOSP,BEHAV THERAPY UNIT,15 PARKMAN ST,WAC 815,BOSTON,MA 02114, USA. NR 23 TC 7 Z9 7 U1 1 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD SEP-OCT PY 1994 VL 2 IS 3 BP 166 EP 170 DI 10.3109/10673229409017133 PG 5 WC Psychiatry SC Psychiatry GA PH847 UT WOS:A1994PH84700006 PM 9384898 ER PT J AU SCHOUTEN, R AF SCHOUTEN, R TI DISTORTING POSTTRAUMATIC-STRESS-DISORDER FOR COURT SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article RP SCHOUTEN, R (reprint author), MASSACHUSETTS GEN HOSP,LAW & PSYCHIAT SERV,FRUIT ST,BOSTON,MA 02114, USA. NR 3 TC 2 Z9 2 U1 0 U2 2 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 SEP-OCT PY 1994 VL 2 IS 3 BP 171 EP 173 DI 10.3109/10673229409017134 PG 3 WC Psychiatry SC Psychiatry GA PH847 UT WOS:A1994PH84700007 PM 9384899 ER PT J AU HALL, JA IRISH, JT ROTER, DL EHRLICH, CM MILLER, LH AF HALL, JA IRISH, JT ROTER, DL EHRLICH, CM MILLER, LH TI GENDER IN MEDICAL ENCOUNTERS - AN ANALYSIS OF PHYSICIAN AND PATIENT COMMUNICATION IN A PRIMARY-CARE SETTING SO HEALTH PSYCHOLOGY LA English DT Article DE PHYSICIAN GENDER; PATIENT GENDER; VERBAL COMMUNICATION; NONVERBAL COMMUNICATION ID INTERNAL MEDICINE; DECISION-MAKING; SEX-DIFFERENCES; META-ANALYSIS; SATISFACTION; BEHAVIOR; METAANALYSIS; INFORMATION; CLINICIANS; QUALITY AB The relation of physician and patient gender to verbal and nonverbal communication was examined in 100 routine medical visits. Female physicians conducted longer visits, made more positive statements, made more partnership statements, asked more questions, made more back-channel responses, and smiled and nodded more. Patients made more partnership statements and gave more medical information to female physicians. The combinations of female physician-female patient and female physician-male patient received special attention in planned contrasts. These combinations showed distinctive patterns of physician and patient behavior, especially in nonverbal communication. We discuss the relation of the results to gender differences in nonclinical settings, role strains in medical visits, and current trends in medical education. C1 JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT HLTH POLICY & MANAGEMENT,BALTIMORE,MD 21218. MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. MT SINAI SCH MED,NEW YORK,NY. RP HALL, JA (reprint author), NORTHEASTERN UNIV,DEPT PSYCHOL,125 NI,BOSTON,MA 02115, USA. RI Roter, Debra/N-8830-2014 FU NCRR NIH HHS [RR07143] NR 52 TC 232 Z9 235 U1 2 U2 14 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0278-6133 J9 HEALTH PSYCHOL JI Health Psychol. PD SEP PY 1994 VL 13 IS 5 BP 384 EP 392 DI 10.1037/0278-6133.13.5.384 PG 9 WC Psychology, Clinical; Psychology SC Psychology GA PJ788 UT WOS:A1994PJ78800003 PM 7805632 ER PT J AU KHETARPAL, U ROBERTSON, NG YOO, TJ MORTON, CC AF KHETARPAL, U ROBERTSON, NG YOO, TJ MORTON, CC TI EXPRESSION AND LOCALIZATION OF COL2A1 MESSENGER-RNA AND TYPE-II COLLAGEN IN HUMAN FETAL COCHLEA SO HEARING RESEARCH LA English DT Article DE HUMAN FETAL COCHLEA; COLLAGEN TYPE II, ALPHA 1; HYBRIDIZATION, IN SITU; IMMUNOHISTOCHEMISTRY ID INSITU HYBRIDIZATION; MESSENGER-RNAS; GENE COL2A1; TRANSIENT EXPRESSION; TECTORIAL MEMBRANE; 3' END; PROCOLLAGEN; CARTILAGE; CLONES; CDNA AB The expression and localization of COL2A1 mRNA and protein was examined in human fetal cochlea to study the role of this gene in hearing and to begin to understand the pathogenesis of mutations in COL2A1 in hearing disorders. Northern blot analysis revealed COL2A1 expression in fetal membranous cochlea to be markedly greater than that in fetal skin, kidney, cartilage, eye and brain. In situ hybridization revealed COL2A1 expression in marrow cells, osteoblasts, fibroblasts and some osteocytes, in addition to chondrocytes in otic capsule. In the membranous cochlea, connective tissue elements (spiral ligament, spiral limbus and modiolar connective tissue), neuronal cells, secretory cells (stria vascularis) and organ of Corti cells (sensory hair cells) were found to express COL2A1. Immunohistochemistry was performed to assess distribution of type TI collagen and correlation with COL2A1 mRNA in these morphologically and functionally diverse cell populations. In otic capsule, only cartilage was found to stain positively, and in membranous cochlea, only connective tissue structures including spiral ligament, spiral limbus, tectorial and basilar membranes, modiolar and spiral lamina cartilage contained type II collagen. Nonconnective tissue cells, marrow cells and osteoblasts did not contain immunohistochemically identifiable protein. Absence of type II collagen in a subset of cochlear cells may reflect potentially either inability to detect low levels of protein in these cells or posttranscriptional regulation. C1 BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. UNIV TENNESSEE,DEPT MED,DIV ALLERGY & IMMUNOL,MEMPHIS,TN 38163. FU NHLBI NIH HHS [T32 HL07627]; NIDCD NIH HHS [DC00871] NR 50 TC 24 Z9 24 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD SEP PY 1994 VL 79 IS 1-2 BP 59 EP 73 DI 10.1016/0378-5955(94)90127-9 PG 15 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA PG269 UT WOS:A1994PG26900006 PM 7806485 ER PT J AU MORGAN, YV RYUGO, DK BROWN, MC AF MORGAN, YV RYUGO, DK BROWN, MC TI CENTRAL TRAJECTORIES OF TYPE-II (THIN) FIBERS OF THE AUDITORY-NERVE IN CATS SO HEARING RESEARCH LA English DT Article DE TYPE II NEURONS; PRIMARY AFFERENTS; HORSERADISH PEROXIDASE; CAT ID CENTRAL PROJECTIONS; COCHLEAR NUCLEUS; SPIRAL GANGLION; HORSERADISH-PEROXIDASE; AFFERENT-FIBERS; ADULT CATS; INNERVATION; CELLS; NEURONS; MOUSE AB This paper describes the central projections of thin fibers of the auditory nerve in cats. Both thin (type II) and thick (type I) fibers are labeled by extracellular injections of horseradish peroxidase (HRP) into the auditory nerve. Type I and almost all type II fibers bifurcate upon reaching the auditory nerve root of the cochlear nucleus. For a given bundle of auditory nerve fibers labeled by a discrete injection of HRP, bifurcations of type II and type I fibers are restricted to a narrow region of the nerve root. After the bifurcation, the pathways of type II branches within the anteroventral cochlear nucleus (AVCN) and posteroventral cochlear nucleus (PVCN) are similar to those of type I branches. This similarity in bifurcation and course of type I and type II fibers was observed in the ventral as well as dorsal parts of the ventral cochlear nucleus. The complete axonal course of most type II fibers could not be reconstructed, however, due to fading of the reaction product. Type II fibers produce very few collaterals in the cochlear nucleus (CN), but possess many 'en passant' swellings along their main processes and collaterals. Compared with type II fibers previously studied in mice (Berglund and Brown, 1989; 1994; Brown and Ledwith, 1990), cat type II fibers are similar in their general projections within the main body of the nucleus and in the frequency of 'en passant' swellings per length of fiber, but cat fibers have a higher percentage of 'complex' or pedunculated 'en passant' swellings. C1 MASSACHUSETTS EYE & EAR INFIRM,EATON PEABODY LAB,BOSTON,MA 02114. JOHNS HOPKINS UNIV HOSP,CTR HEARING SCI,BALTIMORE,MD 21205. HARVARD UNIV,SCH MED,DEPT CELLULAR & MOLEC PHYSIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02115. HARVARD UNIV,MIT,DIV HLTH SCI & TECHNOL,CAMBRIDGE,MA 02139. FU NIDCD NIH HHS [DC 00119, DC 00232, DC 01089] NR 23 TC 10 Z9 10 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD SEP PY 1994 VL 79 IS 1-2 BP 74 EP 82 DI 10.1016/0378-5955(94)90128-7 PG 9 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA PG269 UT WOS:A1994PG26900007 PM 7806486 ER PT J AU FREEMAN, DM COTANCHE, DA EHSANI, F WEISS, TF AF FREEMAN, DM COTANCHE, DA EHSANI, F WEISS, TF TI THE OSMOTIC RESPONSE OF THE ISOLATED TECTORIAL MEMBRANE OF THE CHICK TO ISOSMOTIC SOLUTIONS - EFFECT OF NA+, K+, AND CA2+ CONCENTRATION SO HEARING RESEARCH LA English DT Article DE TECTORIAL MEMBRANE; LYMPH COMPOSITION; CHICK ID MECHANICAL-PROPERTIES; CHONDROITIN SULFATE; CORNEAL STROMA; GUINEA-PIG; INNER-EAR; BINDING; CALCIUM; INVITRO; GLYCOSAMINOGLYCANS; ORGANIZATION AB Changes in the size, shape, and structure of the isolated tectorial membrane of the chick were measured in response to isosmotic changes in the ionic composition of the perfusion solution. Substitution of artificial perilymph (AP) for artificial endolymph (AE) caused a small (similar to 15%), slow (time constants tau similar to 12 min) shrinkage of the thickness of the tectorial membrane that was largely reversed on return to AE. Substitution of AP for AE alters not only the predominate cation (from K+ to Na+) but also the Ca2+ concentration(from < 7 mu mol/l to 2 mmol/l). Additional experiments were performed to separate effects of each of these changes. When a high-Na+, low-Ca2+ solution was substituted for a high-K+, low-Ca2+ solution (AE), the tectorial membrane swelled significantly, often to more than twice its original thickness (the largest swelling was 337%), with a slow time course (tau similar to 23 min). Addition of Ca2+ to either high-K+ or high-Na+ solutions caused rapid shrinkage of the tectorial membrane (tau similar to 2-3 min). Addition of the Ca2+ chelator EGTA caused rapid swelling (tau similar to 4 min). Large osmotic responses were only partially reversible and caused long-lasting changes. For example, long-duration solution changes that produced large, rapid osmotic responses early in an experiment tended to produce smaller and slower responses later in the experiment. In contrast, the small osmotic responses to short-duration solution changes were repeatable for tens of hours. Changes in ionic composition of the bath affected not only the thickness of the tectorial membrane but also its other dimensions. Responses were not generally isotropic; both the size and shape of the tectorial membrane generally changed. Consistent changes in microstructure accompanied the osmotic changes. C1 MIT,ELECTR RES LAB,CAMBRIDGE,MA 02139. MASSACHUSETTS EYE & EAR INFIRM,EATON PEABODY LAB AUDITORY PHYSIOL,BOSTON,MA 02114. BOSTON UNIV,SCH MED,DEPT ANAT & NEUROBIOL,BOSTON,MA 02118. RP FREEMAN, DM (reprint author), MIT,DEPT ELECT ENGN & COMP SCI,CAMBRIDGE,MA 02139, USA. NR 52 TC 22 Z9 22 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD SEP PY 1994 VL 79 IS 1-2 BP 197 EP 215 DI 10.1016/0378-5955(94)90141-4 PG 19 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA PG269 UT WOS:A1994PG26900020 PM 7806483 ER PT J AU KOZIEL, MJ LIANG, TJ AF KOZIEL, MJ LIANG, TJ TI VACCINATION AGAINST HEPATITIS-C VIRUS-INFECTION - MILES TO GO BEFORE WE SLEEP SO HEPATOLOGY LA English DT Note ID GLYCOPROTEIN; ANTIBODIES; HCV C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP KOZIEL, MJ (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 10 TC 7 Z9 7 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD SEP PY 1994 VL 20 IS 3 BP 758 EP 760 DI 10.1016/0270-9139(94)90114-7 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PE828 UT WOS:A1994PE82800028 PM 8076932 ER PT J AU MUSE, KE OBERLEY, TD SEMPF, JM OBERLEY, LW AF MUSE, KE OBERLEY, TD SEMPF, JM OBERLEY, LW TI IMMUNOLOCALIZATION OF ANTIOXIDANT ENZYMES IN ADULT HAMSTER-KIDNEY SO HISTOCHEMICAL JOURNAL LA English DT Article ID GLUTATHIONE-S-TRANSFERASE; CUZN-SUPEROXIDE-DISMUTASE; HUMAN CELL-LINES; COPPER-ZINC; IMMUNOHISTOCHEMICAL LOCALIZATION; RAT HEPATOCYTES; SYRIAN-HAMSTER; XANTHINE-OXIDASE; FREE-RADICALS; HUMAN-TISSUES AB Immunoperoxidase and immunogold techniques were used to localize the following antioxidant enzyme systems in the adult hamster kidney at the light and ultrastructural levels: superoxide dismutases, catalases, peroxidases and glutathione S-transferases. Each cell type in the kidney showed specific patterns of labelling of these enzymes. For example, proximal and distal tubular and transitional epithelial cells showed significant staining for all of these enzymes, while glomerular cells and cells of the thin loop of Henle did not show significant staining at the light microscope level. In addition, high levels of glutathione peroxidase were found in smooth muscle cells of renal arteries. At the ultrastructural level, each enzyme was found in a specific subcellular location. Manganese superoxide dismutase was found in mitochondria, catalase was localized in peroxisomes, while copper, zinc superoxide dismutase and glutathione S-transferase (liver and placental forms) were found in both the nucleus and cytoplasm. Glutathione peroxidase was found to have a broad intracellular distribution, with localization in mitochondria, peroxisomes, nucleus, and cytoplasm. Microvilli of tubular cells were labelled by antibodies to catalase, copper, zinc superoxide dismutase, glutathione peroxidase, and glutathione S-transferases. Cell types that were negative by light microscopy immunoperoxidase studies showed definite labelling with immunogold post-embedding ultrastructural techniques (glomerular cells and cells of the loop of Henle), demonstrating the greater sensitivity of the latter technique. These observations demonstrate that there are large variations in the levels of antioxidant enzymes in different cell types, and that even within a distinct cell type, the levels of these enzymes vary in different subcellular locations. Our results demonstrate for the first time the overall antioxidant enzyme status of individual kidney cell types, thereby explaining why different cell types have differing susceptibilities to oxidant stress. Possible physiological and pathological consequences of these findings are discussed. C1 WILLIAM S MIDDLETON MEM VET ADM MED CTR,PATHOL & LAB MED SERV,ELECTRON MICROSCOPY SECT,MADISON,WI 53705. UNIV WISCONSIN,SCH MED,DEPT PATHOL,MADISON,WI 53706. UNIV IOWA,COLL MED,RADIAT RES LAB,IOWA CITY,IA 52242. FU NCI NIH HHS [CA 41267] NR 55 TC 73 Z9 74 U1 0 U2 1 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 SEP PY 1994 VL 26 IS 9 BP 734 EP 753 DI 10.1007/BF00158205 PG 20 WC Cell Biology SC Cell Biology GA PH500 UT WOS:A1994PH50000005 PM 7843985 ER PT J AU WILSON, L SPIES, T VANDENELSEN, PJ AF WILSON, L SPIES, T VANDENELSEN, PJ TI CELLULAR IMMUNE RECOGNITION OF HLA-A-ASTERISK-0201 FOLLOWING GENE-TRANSFER INTO A HUMAN EMBRYONAL CARCINOMA CELL-LINE SO HUMAN IMMUNOLOGY LA English DT Article; Proceedings Paper CT 8th European Histocompatibility Conference CY MAR 07-09, 1994 CL STRASBOURG, FRANCE SP EUROPEAN FDN IMMUNOGENET ID MAJOR HISTOCOMPATIBILITY COMPLEX; PUTATIVE PEPTIDE TRANSPORTER; CLASS-I MOLECULES; EXPRESSION; ANTIGEN; SEQUENCES; REGION AB Previously, we have established that transcription and cell surface expression of MHC class I and beta(2)m genes in undifferentiated Tera-2 stem cells, a teratocarcinoma-derived cell line, was extremely low. In this study, we have transfected an HLA-A*0201-encoding cDNA driven by the CMV-promoter into Tera-2 cells. Prior to IFN gamma treatment, membrane expression of HLA-A*0201 by these Tera-2 transfectants was nearly lacking. Consequently, the HLA-A*0201 Tera-2 transfectants were not recognized by the allo-HLA-A*0201-specific CTL clone 3E7. Following IFN gamma treatment, which resulted in upregulation of HLA-A*0201, Tera-2 cells were lysed by CTL clone 3E7. In contrast, loading of HLA-A*0201 with the influenza-A-matrix peptide 58-66 resulted in partial lysis of Tera-2 cells by the influenza-A-matrix protein-specific CTL clone Q66-9, and nearly complete lysis was observed following IFN gamma treatment. These results suggest that the HLA-A*0201 transgenes in Tera-2 cells can be loaded with peptides and used as targets for peptide-specific CTLs. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMORVIROL,BOSTON,MA 02115. RP WILSON, L (reprint author), LEIDEN UNIV HOSP,DEPT IMMUNOHEMATOL & BLOOD BANK,BLDG 1,E3-Q POB 9600,2300 RC LEIDEN,NETHERLANDS. NR 12 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD SEP PY 1994 VL 41 IS 1 BP 74 EP 78 DI 10.1016/0198-8859(94)90088-4 PG 5 WC Immunology SC Immunology GA PK893 UT WOS:A1994PK89300012 PM 7836068 ER PT J AU SEMIGRAN, MJ ARONEY, CN HERRMANN, HC DEC, GW BOUCHER, CA FIFER, MA AF SEMIGRAN, MJ ARONEY, CN HERRMANN, HC DEC, GW BOUCHER, CA FIFER, MA TI EFFECTS OF ATRIAL-NATRIURETIC-PEPTIDE ON LEFT-VENTRICULAR FUNCTION IN HYPERTENSION SO HYPERTENSION LA English DT Article DE ATRIAL NATRIURETIC PEPTIDE; VENTRICULAR FUNCTION; HYPERTENSION, SYSTEMIC ID ORTHOTOPIC CARDIAC TRANSPLANTATION; CONGESTIVE HEART-FAILURE; BLOOD-PRESSURE; ATRIOPEPTIN-II; HEMODYNAMIC-RESPONSES; DIASTOLIC FUNCTION; TIME-COURSE; HYPERTROPHY; RELAXATION; RAT AB Atrial natriuretic peptide (ANP) has natriuretic and vasodilator actions that lower arterial pressure and may be beneficial to hypertensive patients. To assess the effects of ANP on left ventricular function in patients with hypertension, we compared it with the pure vasodilator nitroprusside. Simultaneous left ventricular micromanometer pressure and radionuclide volume were obtained at baseline, during nitroprusside infusion, during a second baseline period, and during ANP infusion in 10 patients with hypertension. Mean arterial pressure fell during ANP and nitroprusside. Heart rate and plasma norepinephrine levels increased by similar amounts during the two agents, whereas cardiac index and stroke volume index were unchanged during both. Peak positive left ventricular dP/dt fell similarly during ANP and nitroprusside, but left ventricular dP/dt at a developed pressure of 40 mm Hg, a less load-dependent index of contractility, was unchanged during both. The relation between end-systolic pressure and volume during ANP infusion was not shifted leftward or rightward from that during nitroprusside infusion, indicating no inotropic effect. Both ANP and nitroprusside shortened the time constant of isovolumic relaxation calculated by the logarithmic method but did not change the time constant calculated by the derivative method. Peak filling rate was unchanged from baseline during both agents. ANP did not shift the end-diastolic pressure-volume point away from the relation constructed from baseline and nitroprusside points. We conclude that ANP has no direct effect on myocardial contractile or diastolic function in patients with hypertension. C1 MASSACHUSETTS GEN HOSP,DEPT MED,CARDIAC UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RI Aroney, Constantine/A-7672-2013 OI Aroney, Constantine/0000-0002-0908-7179 NR 50 TC 5 Z9 6 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0194-911X J9 HYPERTENSION JI Hypertension PD SEP PY 1994 VL 24 IS 3 BP 271 EP 279 PG 9 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PG268 UT WOS:A1994PG26800007 PM 8082932 ER PT J AU KREUTZ, R HUBNER, N JACOB, H GANTEN, D LINDPAINTNER, K AF KREUTZ, R HUBNER, N JACOB, H GANTEN, D LINDPAINTNER, K TI EVIDENCE THAT THE HYPERTENSION-ASSOCIATED LOCUS ON RAT CHROMOSOME-10, BP-SP1, NOT IDENTICAL WITH THE ANGIOTENSIN-CONVERTING ENZYME (ACE) GENE LOCUS SO HYPERTENSION LA English DT Meeting Abstract C1 BRIGHAM & WOMENS HOSP,DIV CARDIOVASC,BOSTON,MA 02115. CHILDRENS HOSP,DEPT CARDIOL,BOSTON,MA 02115. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA. MAX DELBRUCK CTR MOLEC MED,BERLIN,GERMANY. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0194-911X J9 HYPERTENSION JI Hypertension PD SEP PY 1994 VL 24 IS 3 BP 373 EP 373 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PG268 UT WOS:A1994PG26800027 ER PT J AU RUSTGI, AK AF RUSTGI, AK TI MODELING OF THE GLASS MICROELECTRODE TIP SO IEE PROCEEDINGS-SCIENCE MEASUREMENT AND TECHNOLOGY LA English DT Article DE MICROELECTRODE; EQUIVALENT ELECTRICAL CIRCUIT; FREQUENCY DOMAIN METHODS; BODE PLOTS AB In the paper a glass microelectrode tip is analysed in terms of an equivalent electrical circuit. It is shown that this electrical circuit, postulated in the literature as an RC circuit, can be verified using the frequency domain methods. Electrodes are placed in feedback with an operational amplifier and subjected to sinusoidal analysis; Bode plots of impedance are generated and used to verify the existence of the parallel RC network at the electrode tip. RP RUSTGI, AK (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,GASTROINTESTINAL UNIT,JACKSON 7,32 FRUIT ST,BOSTON,MA 02114, USA. NR 13 TC 0 Z9 1 U1 0 U2 0 PU IEE-INST ELEC ENG PI HERTFORD PA MICHAEL FARADAY HOUSE SIX HILLS WAY STEVENAGE, HERTFORD, ENGLAND SG1 2AY SN 1350-2344 J9 IEE P-SCI MEAS TECH JI IEE Proc.-Sci. Meas. Technol. PD SEP PY 1994 VL 141 IS 5 BP 391 EP 394 DI 10.1049/ip-smt:19941074 PG 4 WC Engineering, Electrical & Electronic SC Engineering GA PG505 UT WOS:A1994PG50500010 ER PT J AU KLEIN, BS JONES, JM AF KLEIN, BS JONES, JM TI PURIFICATION AND CHARACTERIZATION OF THE MAJOR ANTIGEN WI-1 FROM BLASTOMYCES-DERMATITIDIS YEASTS AND IMMUNOLOGICAL COMPARISON WITH A-ANTIGEN SO INFECTION AND IMMUNITY LA English DT Article ID HISTOPLASMA-CAPSULATUM; POLYACRYLAMIDE GELS; PROTEINS; ELECTROPHORESIS; DIAGNOSIS; ACID AB The lack of well-defined antigens from Blastomyces dermatitidis has hampered the ability to reliably diagnose human infection and study the immunobiology of blastomycosis. We recently discovered a novel surface protein on B. dermatitidis yeasts, designated WI-1, and demonstrated it to be a key antigenic target of humoral and cellular responses during infection. In the present article, we purified acid characterized WI-1 and cbmpared it immunologically with the only Blastomyces antigen commercially available, A antigen. WI-1 was purified by high-performance liquid chromatography over a DEAE cellulose column. It eluted from the column at a point on the salt gradient corresponding to 460 to 490 mM NaCI, reflecting its acidic pi of congruent to 5.2. Purified WI-1 had a molecular mass of 120 kDa and contained a large amount of cysteine (85 residues) and aromatic amino acids but undetectable carbohydrate. In contrast, A antigen had a molecular mass of 135 kDa and contained 37% carbohydrate. Immunological comparison of the two antigens showed that, when radiolabeled, WI-1 was more reactive with anti-Blastomyces antisera than A antigen but did not cross-react with anti-Histoplasma antisera. Proteinase digestion of WI-1 eliminated its recognition by anti-WI-1 and anti-Blastomyces antisera. Proteinase treatment of A antigen had no effect on its recognition by anti-Blastomyces or anti-Histoplasma antisera, but periodate treatment abolished recognition by anti-Histoplasma antisera, indicating that the cross-reactive determinant(s) of A antigen is displayed on the accompanying carbohydrate. In further studies, anti-WI-1 antiserum reacted with A antigen and, conversely, anti-A antiserum and monoclonal antibodies (MAbs) reacted with WI-1, indicating a shared determinant on the two antigens. A recombinant 25-amino-acid repeat, recently cloned from WI-1 and found to be the major target of antibody recognition of WI-1, reacted strongly with anti-A antiserum and MAbs. In MAb competition tests, MAbs specific for the 25-residue repeat abolished binding of anti-A antiserum to A antigen. In antigen inhibition tests, the recombinant repeat abolished binding of anti-a antiserum to A antigen. These results demonstrate that the repeat is the major site of antibody recognition of both WI-1 and A antigen and that the recombinant, nonglycosylated peptide could replace either native antigen in formatting better diagnostic tests for blastomycosis. Moreover, they suggest that producing fungal protein antigens as nonglycosylated peptides in a procaryotic expression system may circumvent problems of antigen cross-reactivity that are due to posttranslational modification. C1 UNIV WISCONSIN HOSP & CLIN,SCH MED,DEPT INTERNAL MED,MADISON,WI 53705. UNIV WISCONSIN HOSP & CLIN,SCH MED,DEPT MED MICROBIOL & IMMUNOL,MADISON,WI 53705. WILLIAM S MIDDLETON MEM VET ADM MED CTR,RES SERV,MADISON,WI 53705. RP KLEIN, BS (reprint author), UNIV WISCONSIN HOSP & CLIN,SCH MED,DEPT PEDIAT,INFECT DIS SECT,K4-434,600 HIGHLAND AVE,MADISON,WI 53792, USA. FU PHS HHS [A131479, A100905] NR 32 TC 37 Z9 38 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD SEP PY 1994 VL 62 IS 9 BP 3890 EP 3900 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA PC836 UT WOS:A1994PC83600039 PM 7520423 ER PT J AU PIER, GB DESJARDIN, D GROUT, M GARNER, C BENNETT, SE PEKOE, G FULLER, SA THORNTON, MO HARKONEN, WS MILLER, HC AF PIER, GB DESJARDIN, D GROUT, M GARNER, C BENNETT, SE PEKOE, G FULLER, SA THORNTON, MO HARKONEN, WS MILLER, HC TI HUMAN IMMUNE-RESPONSE TO PSEUDOMONAS-AERUGINOSA MUCOID EXOPOLYSACCHARIDE (ALGINATE) VACCINE SO INFECTION AND IMMUNITY LA English DT Article ID CYSTIC-FIBROSIS PATIENTS; INFECTION; POLYSACCHARIDE; ANTIBODY; IMMUNOGENICITY; PATHOGENESIS; ANTIGENS; STRAINS; CELLS; LUNGS AB Chronic lung infection with mucoid Pseudomonas aeruginosa is the major pathologic feature of cystic fibrosis. Previous studies suggested that a failure to produce opsonic antibody to the mucoid exopolysaccharide (MEP; also called alginate) capsule is associated with the maintenance of chronic bacterial infection. Provision of MEP-specific opsonic antibodies has therapeutic potential. To evaluate the ability of MEP to elicit opsonic antibodies, humans were immunized with two lots of MEP vaccine that differed principally in molecular size. Lot 2 had a larger average MEP polymer size. Both vaccines were well tolerated, but lot 1 was poorly immunogenic, inducing long-lived opsonic antibodies in only 2 of 28 vaccinates given doses of 10 to 150 mu g. In contrast, at the optimal dose of 100 mu g, lot 2 elicited long-lived opsonic antibodies in 80 to 30% of the vaccinates. The antibodies elicited by both lots enhanced deposition of C3 onto mucoid P. aeruginosa cells and mediated opsonic killing of heterologous mucoid strains expressing distinct MEP antigens. These results indicate that the polymers of MEP with the largest molecular sizes safely elicit opsonic antibodies in a sufficiently large proportion of vaccinates to permit studies of active and passive immunization of cystic fibrosis patients against infection with mucoid P. aeruginosa. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,GEN INTERNAL MED UNIT,BOSTON,MA 02114. UNIVAX BIOL INC,ROCKVILLE,MD 20852. FIRST CINCINNATI PHYSICIANS ASSOCIATES,CINCINNATI,OH 45209. RP PIER, GB (reprint author), HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT MED,CHANNING LAB,180 LONGWOOD AVE,BOSTON,MA 02115, USA. FU NIAID NIH HHS [AI 22806] NR 37 TC 55 Z9 58 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 SEP PY 1994 VL 62 IS 9 BP 3972 EP 3979 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA PC836 UT WOS:A1994PC83600049 PM 8063415 ER PT J AU SCHUMANN, G DASGUPTA, JD AF SCHUMANN, G DASGUPTA, JD TI SPECIFICITY OF SIGNAL-TRANSDUCTION THROUGH CD16, TCR-CD3 AND BCR RECEPTOR CHAINS CONTAINING THE TYROSINE-ASSOCIATED ACTIVATION MOTIF SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE PROTEIN TYROSINE KINASE; RECEPTOR CHAINS; SIGNAL TRANSDUCTION; TYROSINE-ASSOCIATION ACTIVATION MOTIF ID CELL ANTIGEN RECEPTOR; NATURAL-KILLER-CELLS; FC-GAMMA-RIII; T-CELL; ZETA-CHAIN; PHOSPHOLIPASE C-GAMMA-1; KINASE ACTIVATION; EFFECTOR FUNCTION; CYTOPLASMIC TAIL; CD3 CHAINS AB FcR gamma III (CD16) is a member of a family of receptor proteins that bind to Fc regions of IgG molecules. Ligation of CD16 transduces signal and alters tyrosine phosphorylation of proteins in natural killer, B and T cells. However, the identity of protein tyrosine kinases (PTKs) involved in CD16 signaling and the mode of their interaction with the receptor are not completely understood. Here, we show that the transmembrane form of CD16 transfected in a CD3(-) Jurkat cell line associates with p56(lck) and ZAP-70 PTKs. Using chimeric proteins consisting of the extracellular domain of CD16 and the cytoplasmic portions of the zeta chain, we find that these PTKs interact with the 17-residue activation motif present in the zeta chain. Substitution of tyrosine residues in the motif with phenylalanine blocks the interaction of PTKs and abrogates signal transduction. Comparative studies demonstrate that similar to zeta, MB1 protein of the IgM receptor also binds to p56(lck) and ZAP-70 in T cells and induces strong activation responses, whereas CD3 gamma, delta and epsilon chains do not interact with ZAP-70 and transduce weak signals. Together, these results demonstrate that: (i) PTKs bound to CD16 mediate signal transduction, (ii) ZAP-70 plays a crucial role in signaling and (iii) apart from tyrosine residues in the activation motif, other structural constraints also regulate the interaction of PTKs with the receptor molecule. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PATHOL,DIV IMMUNOGENET,BOSTON,MA 02115. NR 49 TC 2 Z9 2 U1 1 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 SEP PY 1994 VL 6 IS 9 BP 1383 EP 1392 DI 10.1093/intimm/6.9.1383 PG 10 WC Immunology SC Immunology GA PK413 UT WOS:A1994PK41300011 PM 7819147 ER PT J AU VITALE, AT PEDROZASERES, M ARRUNATEGUICORREA, V LEE, SJ DIMEO, S FOSTER, CS COLVIN, B AF VITALE, AT PEDROZASERES, M ARRUNATEGUICORREA, V LEE, SJ DIMEO, S FOSTER, CS COLVIN, B TI DIFFERENTIAL EXPRESSION OF ALTERNATIVELY SPLICED FIBRONECTIN IN NORMAL AND WOUNDED RAT CORNEAL STROMA VERSUS EPITHELIUM SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE PCR (POLYMERASE CHAIN REACTION); FIBRONECTIN ISOFORMS; ALTERNATIVE SPLICING; EPITHELIAL SCRAPE WOUNDS; WOUND HEALING ID MESSENGER-RNA; TOPICAL FIBRONECTIN; BASEMENT-MEMBRANE; RABBIT; CELLS; KERATECTOMY; LOCALIZATION; INTEGRIN; DEFECTS; PATTERN AB Purpose. The polymerase chain reaction was used to examine fibronectin (FN) expression during corneal scrape wounding with specific attention to the presence, absence, or gross changes of alternatively spliced FN as differentially expressed in the corneal stroma versus the epithelium in normal and wounded tissue. Methods. Specific FN cDNA sequences were synthesized from rat cornea with total RNA and were amplified using various sets of synthetic oligonucleotide primers. Results. The authors observed the presence and sustained the expression of total FN, EIIIA, EIIIB, and V-region FN mRNA in normal and injured corneal stroma for up to 3 weeks after scrape wounding. In contrast, complementary overlying epithelial samples were virtually devoid of FN message. Conclusions. These data suggest that functionally different, alternatively spliced FN isoforms may be involved both in the maintenance of the normal cornea and in wound healing, and that their synthesis occurs in situ principally by the stroma rather than by the epithelium. C1 MASSACHUSETTS EYE & EAR INFIRM,RHOADS MOLEC IMMUNOL LABS,IMMUNOL SERV,BOSTON,MA 02114. MASSACHUSETTS EYE & EAR INFIRM,HILLES IMMUNOL LABS,BOSTON,MA 02114. MASSACHUSETTS EYE & EAR INFIRM,MOLEC GENET LABS,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,BOSTON,MA. FU NCI NIH HHS [R37CA208822] NR 36 TC 11 Z9 11 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD SEP PY 1994 VL 35 IS 10 BP 3664 EP 3672 PG 9 WC Ophthalmology SC Ophthalmology GA PH607 UT WOS:A1994PH60700015 PM 8088955 ER PT J AU KNISELY, TL HOSOI, J NAZARENO, R GRANSTEIN, RD AF KNISELY, TL HOSOI, J NAZARENO, R GRANSTEIN, RD TI THE PRESENCE OF BIOLOGICALLY SIGNIFICANT CONCENTRATIONS OF GLUCOCORTICOIDS BUT LITTLE OR NO CORTISOL BINDING GLOBULIN WITHIN AQUEOUS-HUMOR - RELEVANCE TO IMMUNE PRIVILEGE IN THE ANTERIOR-CHAMBER OF THE EYE SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE AQUEOUS HUMOR; HYDROCORTISONE; CORTICOSTERONE; CORTISOL BINDING GLOBULIN; IMMUNE PRIVILEGE ID TRANSFORMING GROWTH-FACTOR; MELANOCYTE-STIMULATING HORMONE; TUMOR NECROSIS FACTOR; FACTOR-BETA; STEROID-HORMONES; GENE-EXPRESSION; HUMAN-MONOCYTES; IMMUNOSUPPRESSIVE FACTOR; NEUTROPHIL MIGRATION; CEREBROSPINAL-FLUID AB Purpose. Immunosuppressive factors in aqueous humor (AH) contribute to the immune-privileged status of the anterior chamber of the eye. One such factor is transforming growth factor-beta (TGF-beta); other relevant inhibitors have not been fully identified. The authors examined AH to search for other putative inhibitors and to determine their effect on TGF-beta inhibitory activity. Methods. Radioimmunoassays (RIA) were used to detect the presence of hydrocortisone, corticosterone, cortisol binding globulin (CBG), and alpha-melanocyte stimulating hormone (alpha-MSH) in AH. The ability of these factors to inhibit murine thymocyte proliferation stimulated by phytohemagglutinin-interleukin 1 (PHA/IL-1) and proliferation of a TGF-beta-sensitive cell line (CCL64) in vitro was examined. The ability of hydrocortisone to inhibit a one-way mixed lymphocyte reaction (MLR) and the ability of epidermal cells to present soluble tumor-associated antigens (TAA) for elicitation of immunity in mice in the concentration range present in AH was also examined. Results. Hydrocortisone was detected in mouse, rat, and human AH (10.8 +/- 1.1 ng/ml, 9.3 +/- 2.1 ng/ml, and 18.0 +/- 1.0 ng/ml, respectively; mean +/- SEM), as was corticosterone (2.7 +/- 0.9 ng/ml, 2.2 +/- 0.3 ng/ml, and 0.7 +/- 0.1 ng/ml, respectively). Whereas normal plasma contains a binding protein for corticosteroids (i.e., CBC), the concentration in mouse, rat, and human AH was less than the level detectable by an RIA. Hydrocortisone inhibited PHA/IL-1-stimulated murine thymocyte proliferation and CCL64 cell proliferation in the concentration range present in AH. When hydrocortisone was combined with TGF-beta(2) (125 pg/ml), the degree of inhibition observed was greater than with either alone. Corticosterone inhibited thymocyte costimulation only slightly at concentrations present in AH but was inhibitory for CCL64 cells. alpha-MSH was also detected in AH. The concentration present had only slight inhibitory effects for CCL64 cell proliferation and did not enhance TGF-beta(2)-mediated (62 pg/ml to 250 pg/ml) inhibition of CCL64 or thymocyte proliferation. Hydrocortisone inhibited the one-way MLR in the concentration range present in AH and, at 10 ng/ml, inhibited the ability of epidermal cells to present TAA for elicitation of delayed-type hypersensitivity in tumor-immune mice. Conclusions. These results show that AH contains biologically relevant concentrations of glucocorticoids and that CBG is relatively absent so that glucocorticoids present are largely free, and they suggest that regional sites take advantage of the activities of multiple factors to maintain an immune-privileged status. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP EAST,CUTANEOUS BIOL RES CTR,DEPT DERMATOL,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA. FU NEI NIH HHS [EY07782] NR 92 TC 44 Z9 45 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD SEP PY 1994 VL 35 IS 10 BP 3711 EP 3723 PG 13 WC Ophthalmology SC Ophthalmology GA PH607 UT WOS:A1994PH60700020 PM 8088958 ER PT J AU BABA, Y LERCH, MM STARK, DD TANIMOTO, A KREFT, BP ZHAO, LH SALUJA, AK TAKAHASHI, M AF BABA, Y LERCH, MM STARK, DD TANIMOTO, A KREFT, BP ZHAO, LH SALUJA, AK TAKAHASHI, M TI TIME AFTER EXCISION AND TEMPERATURE ALTER EX-VIVO TISSUE RELAXATION-TIME MEASUREMENTS SO JMRI-JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE BIOPSIES, TECHNOLOGY; LIVER, MR; PANCREAS, MR; RELAXOMETRY; TISSUE CHARACTERIZATION ID NUCLEAR MAGNETIC-RESONANCE; SPIN-LATTICE RELAXATION; MANGANESE; DEPENDENCE AB Previously unreported effects of tissue storage were recently observed in the authors' experimental magnetic resonance (MR) studies. To evaluate the effect of elapsed time after excision and storage temperature on tissue relaxation time measurements, tissue samples from the liver, pancreas, kidney, testis, spleen, and brain were obtained in rats. T1 and T2 were first measured within 5 minutes of excision, and between subsequent measurements, tubes were kept in a water bath at 40-degrees-C, at room temperature (28-degrees-C), or in an ice bath (4-degrees-C). Cellular and organellar integrity was assessed with electron microscopy and correlated with the MR findings. At 40-degrees-C (20-MHz spectrometer), the T1 of liver decreased from 280 msec +/- 8 to 212 msec +/- 10 during the first 60 minutes; the T1 of pancreas decreased from 276 msec +/- 3 to 208 msec +/- 2. Other tissues showed less than a 5% decrease in T1. T2 changes were smaller than T1 changes in all tissues. Electron microscopy of pancreatic acinar cells showed postmortem changes in mitochondria evolving over the first 60 minutes after death. Manganese loading experiments implicated mitochondrial manganese stores in the observed enhanced postmortem decrease in T1. This study calls into question reported relaxation time data for liver and pancreas. MR studies of excised tissues must account for time and temperature to prevent systematic experimental errors. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. BETH ISRAEL HOSP,DEPT SURG,BOSTON,MA 02215. RP BABA, Y (reprint author), KUMAMOTO UNIV,SCH MED,DEPT RADIOL,HONJO 1-1-1,KUMAMOTO 860,JAPAN. RI Lerch, Markus M./E-2206-2016 OI Lerch, Markus M./0000-0002-9643-8263 FU NCI NIH HHS [R01 CA50353-01] NR 23 TC 9 Z9 9 U1 0 U2 1 PU SOC MAGNETIC RESONANCE IMAGING PI EASTON PA 1991 NORTHAMPTON ST, EASTON, PA 18042-3189 SN 1053-1807 J9 JMRI-J MAGN RESON IM JI JMRI-J. Magn. Reson. Imaging PD SEP-OCT PY 1994 VL 4 IS 5 BP 647 EP 651 DI 10.1002/jmri.1880040504 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PH089 UT WOS:A1994PH08900002 PM 7981509 ER PT J AU GABUZDA, DH LI, HD LAWRENCE, K VASIR, BS CRAWFORD, K LANGHOFF, E AF GABUZDA, DH LI, HD LAWRENCE, K VASIR, BS CRAWFORD, K LANGHOFF, E TI ESSENTIAL ROLE OF VIF IN ESTABLISHING PRODUCTIVE HIV-1 INFECTION IN PERIPHERAL-BLOOD T-LYMPHOCYTES AND MONOCYTE/MACROPHAGES SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE HIV-1; VIF; T LYMPHOCYTES; MACROPHAGES ID IMMUNODEFICIENCY-VIRUS TYPE-1; COMPLETE NUCLEOTIDE-SEQUENCE; CELL-LINE; SOR GENE; DNA-SYNTHESIS; REPLICATION; IDENTIFICATION; DETERMINANTS; MACROPHAGE; MUTANTS AB The role of vif during the establishment of human immunodeficiency virus type 1 (HIV-1) infection of peripheral blood T lymphocytes and monocyte/macrophages was investigated using vif mutants of three HIV-1 proviral DNAs. Vif was found to be essential for the establishment of productive HIV-1 infection in peripheral blood T lymphocytes after cell-free infection with HXB2 and DFCI-HD, a vpr-positive, vpu-positive, nef-positive derivative of HXB2. A chimeric HIV-1 provirus in which the T-cell line-tropic env sequences in DFCI-HD were replaced with the macrophagetropic env of the ADA strain was constructed for studies on the role of vif during the establishment of HIV-1 infection in primary monocyte/macrophages. These studies showed that vif is also essential for the initiation of productive HIV-1 infection in primary monocyte/macrophage cultures after cell-free virus transmission. The DFCI-HD-ADA virus was shown to replicate in the CD4(+) T-cell line Molt 4 clone 8 but not in other T-cell or monocytic cell lines, as previously shown for another macrophagetropic strain YU-2 (1), suggesting that this cell line may be useful for future studies on at least some macrophagetropic strains of HIV-1. The finding that vif is essential for the establishment of productive HIV-1 infection in primary T lymphocytes and monocyte/macrophages suggests that vif may be required for HIV-1 transmission and disease pathogenesis during natural infections and thus may be a good target for prophylactic or therapeutic intervention. C1 HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. CTR BLOOD RES,BOSTON,MA 02115. RP GABUZDA, DH (reprint author), DANA FARBER CANC INST,DIV HUMAN RETROVIROL,JF824,44 BINNEY ST,BOSTON,MA 02115, USA. FU NIAID NIH HHS [AI01017, AI33837, AI28734] NR 33 TC 69 Z9 69 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD SEP PY 1994 VL 7 IS 9 BP 908 EP 915 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA PC635 UT WOS:A1994PC63500004 PM 7519673 ER PT J AU OGAWA, M AF OGAWA, M TI HEMATOPOIESIS SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article; Proceedings Paper CT New Trends in Immunopharmacology 1993 Conference CY JUL 17, 1993 CL TOKYO, JAPAN DE HEMATOPOIETIC STEM CELLS; HEMATOPOIETIC PROGENITORS; DIFFERENTIATION OF STEM CELLS; CYTOKINES; INTERLEUKIN; GROWTH FACTORS ID COLONY-STIMULATING FACTOR; MURINE LYMPHOHEMATOPOIETIC PROGENITORS; PRIMITIVE STEM-CELLS; PAIRED PROGENITORS; GROWTH-FACTORS; FACTOR-I; INTERLEUKIN-3-DEPENDENT PROLIFERATION; HUMAN MEGAKARYOCYTOPOIESIS; DISPARATE DIFFERENTIATION; RECOMBINANT HUMAN AB Cellular turnover of the hematopoietic system is supported by a small population of cells termed hematopoietic stem cells. Stem cells are capable of self-renewal and differentiation into individual lymphomyeloid lineages. Available evidence indicates that the decision of a stem cell to self-renew or differentiate and the decision of a multipotential progenitor to select a lineage pathway during differentiation (commitment) are intrinsic to the progenitors and are stochastic in nature. In contrast, proliferative kinetics of the progenitors, namely survival and expansion of the progenitors, appear to be controlled by a number of interacting cytokines. Whereas proliferation and maturation of committed progenitors are controlled by late-acting factors such as erythropoietin, macrophage colony-stimulating factor, granulocyte colony-stimulating factor, and interleukin-5, progenitors at earlier stages of development are controlled by a group of several overlapping cytokines. Interleukin-3, granulocyte/macrophage colony-stimulating factor, and interleukin-4 regulate proliferation of multipotential progenitors only after they are triggered to exit from dormancy state. Triggering of cycling of dormant primitive progenitors and proliferation of lymphohemopoietic primitive progenitors appear to require interactions of early acting cytokines including interleukin-6 granulocyte colony-stimulating factor, interleukin-11, interleukin-12 leukemia inhibitory factor and steel factor. C1 MED UNIV S CAROLINA,DEPT MED,CHARLESTON,SC 29425. RP OGAWA, M (reprint author), RALPH H JOHNSON DEPT VET AFFAIRS MED CTR,109 BEE ST,CHARLESTON,SC 29401, USA. FU NIDDK NIH HHS [DK32294] NR 65 TC 35 Z9 35 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD SEP PY 1994 VL 94 IS 3 SU S BP 645 EP 650 DI 10.1016/0091-6749(94)90142-2 PN 2 PG 6 WC Allergy; Immunology SC Allergy; Immunology GA PH235 UT WOS:A1994PH23500011 PM 8083474 ER PT J AU SCHMALZRIED, TP JASTY, M ROSENBERG, A HARRIS, WH AF SCHMALZRIED, TP JASTY, M ROSENBERG, A HARRIS, WH TI POLYETHYLENE WEAR DEBRIS AND TISSUE-REACTIONS IN KNEE AS COMPARED TO HIP-REPLACEMENT PROSTHESES SO JOURNAL OF APPLIED BIOMATERIALS LA English DT Article ID TIBIAL COMPONENTS; IDENTIFICATION; FAILURE AB Differences in bearing surface conformity and wear mechanisms suggest that the polyethylene (PE) wear debris generated by total knee replacement (TKR) prostheses should be different than that in total hip replacement prostheses (THR). To address this issue, PE near debris and the cellular response in periprosthetic tissues from 19 failed TKRs was compared to that from 24 failed THRs using polarized light microscopy and a semiquantitative grading system. The foreign-body inflammatory reaction in the THR cases was characterized by plump macrophages with a diffuse cytoplasmic birefringence when examined under polarized light, indicating the presence of multiple submicron particles of PE. The majority of the PE particles were <1 mu m in size and only a small fraction of the total were >10 mu m. The foreign-body inflammatory reaction in the TKR eases was characterized by giant cells with fewer macrophages. In the TKR specimens, the size range of PE particles was broader than in the hips. PE particles between 2 and 20 pm were frequent in TKR specimens; particles. <1 mu m in length were less common than in the THR specimens. Diffuse cytoplasmic birefringence was not a characteristic of the TKR cases. These histologic differences were so consistently distinct that the source of the specimen (i.e., from a THR or TKR) could be blindly determined by light microscopy. The size distribution of the PE wear particles in these cases indicate that THRs generate a higher number of submicron PE particles and relatively few large particles while TKRs generate a broader range of particles that includes fewer submicron particles. The observed differences in the cellular responses is likely a direct result of the differences in the spectrum of PE wear particles. These differences mag in part account far differences in periprosthetic bone resorption and loosening in TKRs as compared to THRs. (C) 1994 John Wiley & Sons, Inc. C1 MASSACHUSETTS GEN HOSP,DEPT ORTHOPAED SURG,ORTHOPAED BIOMECH LAB,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT ORTHOPAED SURG,HIP & IMPLANT UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 28 TC 92 Z9 94 U1 0 U2 2 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1045-4861 J9 J APPL BIOMATER JI J. Appl. Biomater. PD FAL PY 1994 VL 5 IS 3 BP 185 EP 190 DI 10.1002/jab.770050302 PG 6 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA PC764 UT WOS:A1994PC76400001 PM 10147443 ER PT J AU JANSSENS, SP THOMPSON, BT SPENCE, CR HALES, CA AF JANSSENS, SP THOMPSON, BT SPENCE, CR HALES, CA TI FUNCTIONAL AND STRUCTURAL-CHANGES WITH HYPOXIA IN PULMONARY CIRCULATION OF SPONTANEOUSLY HYPERTENSIVE RATS SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE PULMONARY HYPERTENSION; PULMONARY RESISTANCE; VASCULAR REMODELING ID VASCULAR SMOOTH-MUSCLE; RESISTANCE VESSELS; MEDIAL HYPERTROPHY; REACTIVITY; GROWTH; CONTRACTILITY; IMPAIRMENT; CELLS AB Chronic hypoxic pulmonary hypertension involves both vasoconstriction and vascular remodeling. Spontaneously hypertensive rats (SHR) have an increased systemic vascular resistance and a greater responsiveness to constricting stimuli. We hypothesized that, in contrast to age-matched normotensive Wistar-Kyoto rats (WKY), SHR also display spontaneous pulmonary hypertension in normoxia and increased vascular response to acute and chronic hypoxia. Baseline mean pulmonary arterial pressure (PAP) and total pulmonary resistance (TPR) were higher in SHR than in WKY. With acute hypoxia (10% O-2 for 15 min), PAP increased to the same extent in SHR and WKY and cardiac output (CO) was unchanged in WKY but increased in SHR. Thus, the rise in PAP in the SHR might be accounted for by the rise in CO, as TPR did not rise, but not that in the WKY, as TPR increased. After 12 days in hypoxia (10% O-2), mean arterial pressure was unchanged in WKY but decreased significantly in SHR without a change in CO. PAP increased by 59% in SHR and 54% in WKY when the rats were taken from the hypoxic chamber for 1 h. Acute hypoxic challenge caused a further increase in PAP only in WKY. Medial wall thickness of alveolar duct and terminal bronchial vessels was similar in WKY and SHR after chronic hypoxia. We conclude that SHR exhibit mild baseline pulmonary hypertension in normoxia and that chronic hypoxia does not produce a disproportionate increase in SHR pulmonary vascular remodeling and pulmonary hypertension. C1 MASSACHUSETTS GEN HOSP,DEPT MED,PULM CRIT CARE UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. FU FIC NIH HHS [IF05TW04379-1] NR 32 TC 24 Z9 24 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 SEP PY 1994 VL 77 IS 3 BP 1101 EP 1107 PG 7 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA PG916 UT WOS:A1994PG91600009 PM 7836110 ER PT J AU LARSON, DE HESSLINK, RL HROVAT, MI FISHMAN, RS SYSTROM, DM AF LARSON, DE HESSLINK, RL HROVAT, MI FISHMAN, RS SYSTROM, DM TI DIETARY-EFFECTS ON EXERCISING MUSCLE METABOLISM AND PERFORMANCE BY P-31-MRS SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE GLYCOLYSIS; PHOSPHATE SPECTROSCOPY; PHOSPHOCREATINE; VENTILATION; SKELETAL MUSCLE ID MAGNETIC-RESONANCE SPECTROSCOPY; BLOOD LACTATE ACCUMULATION; HIGH-FAT DIET; PROLONGED EXERCISE; INCREMENTAL EXERCISE; ANAEROBIC THRESHOLD; GLYCOGEN DEPLETION; SKELETAL-MUSCLE; FATIGUE; INHIBITION AB To determine how diet modulates short-term exercise capacity, skeletal muscle pH and bioenergetic state were examined by P-31-magnetic resonance spectroscopy in nine healthy volunteers. Subjects performed incremental quadriceps exercise to exhaustion after 5 days of high-carbohydrate (HCHO) or high-fat (HFAT) diet randomly assigned in crossover fashion and separated by a 2.5-day period of ad libitum mixed diet. Simultaneous measurements were made of pulmonary gas exchange, minute ventilation, and quadriceps muscle pH and phosphorylation potential. At rest and peak exercise, respiratory exchange ratio and minute ventilation were higher after HCHO than after HFAT (P < 0.05), reflecting greater CHO utilization. Peak O-2 consumption VO2) was not increased after HCHO (P > 0.05), but exercise duration was (339 +/- 34 s for HCHO vs. 308 +/- 25 s for HFAT; P < 0.05). HCHO was associated with a blunted early fall of phosphocreatine (PCr)/P-i vs. VO2 (-4.1 +/- 0.7 x 10(-2) min/ml for HCHO vs. -5.6 +/- 1.2 X 10(-2) min/ml for HFAT; P < 0.05). On both study days, the slope of PCr/P-i vs. VO2, before and after the PCr threshold, was correlated with exercise time. The results suggest that a diet rich in CHO improves exercise efficiency through beneficial effects on intracellular phosphorylation potential. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,MASSACHUSETTS INST TECHNOL,BOSTON,MA 02114. NIDDKD,CLIN DIABET & NUTR SECT,PHOENIX,AZ 85016. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,MASSACHUSETTS INST TECHNOL,BOSTON,MA 02114. USN,HLTH RES CTR,SAN DIEGO,CA 92128. FU NHLBI NIH HHS [HL-07354-14, K08-HL-02593-01A2] NR 39 TC 20 Z9 20 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 SEP PY 1994 VL 77 IS 3 BP 1108 EP 1115 PG 8 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA PG916 UT WOS:A1994PG91600010 PM 7836111 ER PT J AU BUTTERTON, JR CALDERWOOD, SB AF BUTTERTON, JR CALDERWOOD, SB TI IDENTIFICATION, CLONING, AND SEQUENCING OF A GENE REQUIRED FOR FERRIC VIBRIOBACTIN UTILIZATION BY VIBRIO-CHOLERAE SO JOURNAL OF BACTERIOLOGY LA English DT Article ID MEDIATED IRON TRANSPORT; OUTER-MEMBRANE PROTEINS; ESCHERICHIA-COLI; NUCLEOTIDE-SEQUENCE; TRANSCRIPTIONAL REGULATION; NEISSERIA-MENINGITIDIS; SUICIDE VECTOR; VIRULENCE; ENTEROBACTIN; SIDEROPHORE AB Chromosomal DNA downstream of the Vibrio cholerae ferric vibriobactin receptor gene, viuA, was cloned and sequenced, revealing an 813-bp open reading frame encoding a deduced protein of 271 amino acids. In vitro transcription-translation of this DNA confirmed expression of a protein of the expected size. A deletion mutation of this gene, viuB, was created in the classical V. cholerae strain O395 by in vivo marker exchange. By cross-feeding studies, this mutant was unable to utilize exogenous ferric vibriobactin but synthesized the siderophore normally; synthesis of siderophore by the mutant was also confirmed by the Arnow assay. Complementation of the mutant with a plasmid encoding only viuB restored ferric vibriobactin utilization to normal. Unexpectedly, hydropathicity analysis of ViuB did not reveal a signal sequence or transmembrane domain, suggesting that ViuB is not a periplasmic or membrane protein but may be a cytoplasmic protein involved in ferric vibriobactin uptake and processing, perhaps analogous to the Escherichia coli protein Fes. ViuB was not, however, homologous to Fes or to other proteins in the database. Complementation studies revealed that the cloned V. cholerae viuB gene could complement an E. coli fes mutant but that the cloned E. coli fes gene could not complement a V. cholerae viuB mutant; Northern (RNA) blot analysis of RNA from wild-type V. cholerae grown in high- and low-iron media revealed a monocistronic viuB message that was negatively regulated by iron at the transcriptional level. The promoter of viuB was located by primer extension and contained a nucleotide sequence highly homologous to the E. coli Fur binding consensus sequence, suggesting that expression of viuB is under the control of the V. cholerae fur gene. C1 MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOLEC GENET,BOSTON,MA 02115. FU NIAID NIH HHS [AI27329, AI34968] NR 39 TC 58 Z9 59 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD SEP PY 1994 VL 176 IS 18 BP 5631 EP 5638 PG 8 WC Microbiology SC Microbiology GA PF222 UT WOS:A1994PF22200006 PM 8083157 ER PT J AU JUPITER, JB SEILER, JG ZIENOWICZ, R AF JUPITER, JB SEILER, JG ZIENOWICZ, R TI SYMPATHETIC MAINTAINED PAIN (CAUSALGIA) ASSOCIATED WITH A DEMONSTRABLE PERIPHERAL-NERVE LESION - OPERATIVE TREATMENT SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID DYSTROPHY SYNDROME; PHYSIOLOGY; MECHANISMS; BLOCKADE; CRITERIA; SURGERY; NEUROMA; RAT AB Nine patients who had sympathetic maintained pain (causalgia) and a total of ten identifiable lesions involving peripheral nerves were managed with a continuous sympathetic block; repair, reconstruction, or lysis of the involved nerve, or a combination of these procedures; and rotation of a muscle Bap over the nerve in an attempt to enhance the blood supply in the area and to reduce scarring in the region surrounding the nerve. The lesions were located in the median nerve at the wrist in five of the patients; in both the ulnar nerve at the elbow and the median nerve at the wrist in one; and in the ulnar nerve at the elbow the radial digital nerve of the index finger, and the posterior tibial nerve near the ankle in one patient each. The average duration of symptoms before treatment was seventeen weeks. All nine patients had clinical findings that were considered diagnostic of sympathetic maintained pain or causalgia. Electrophysiological evidence of dysfunction of one peripheral nerve or more was found in the eight patients who had an electromyogram and a nerve-conduction study In all nine patients, the causalgic pain diminished within the first seventy-two hours after the operation, and none of the patients had had any recurrence of symptoms at an average of forty-eight months. Although all of the patients had some residual limitation of function, all had improvement after this treatment, and the improvement was maintained. RP JUPITER, JB (reprint author), MASSACHUSETTS GEN HOSP,WAC-529,15 PARKMAN ST,BOSTON,MA 02114, USA. NR 46 TC 22 Z9 22 U1 0 U2 1 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 SEP PY 1994 VL 76A IS 9 BP 1376 EP 1384 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA PH555 UT WOS:A1994PH55500013 PM 8077268 ER PT J AU GELBERMAN, RH EATON, R URBANIAK, JR AF GELBERMAN, RH EATON, R URBANIAK, JR TI UNTITLED - REPLY SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Letter C1 COLUMBIA UNIV,ST LUKES ROOSEVELT HOSP CTR,CTR HAND SURG,NEW YORK,NY 10019. DUKE UNIV,MED CTR,DURHAM,NC 27710. RP GELBERMAN, RH (reprint author), MASSACHUSETTS GEN HOSP,WACC-527,BOSTON,MA 02114, USA. NR 4 TC 0 Z9 0 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 SEP PY 1994 VL 76A IS 9 BP 1434 EP 1434 PG 1 WC Orthopedics; Surgery SC Orthopedics; Surgery GA PH555 UT WOS:A1994PH55500024 ER PT J AU JASTY, M AF JASTY, M TI SURFACE DAMAGE TO FEMORAL-HEAD PROSTHESES - REPLY SO JOURNAL OF BONE AND JOINT SURGERY-BRITISH VOLUME LA English DT Letter RP JASTY, M (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BRITISH EDITORIAL SOC BONE JOINT SURGERY PI LONDON PA 22 BUCKINGHAM STREET, LONDON, ENGLAND WC2N 6ET SN 0301-620X J9 J BONE JOINT SURG BR JI J. Bone Joint Surg.-Br. Vol. PD SEP PY 1994 VL 76B IS 5 BP 852 EP 852 PG 1 WC Orthopedics; Surgery SC Orthopedics; Surgery GA PH526 UT WOS:A1994PH52600045 ER PT J AU LEES, S HANSON, D PAGE, E MOOK, HA AF LEES, S HANSON, D PAGE, E MOOK, HA TI COMPARISON OF DOSAGE-DEPENDENT EFFECTS OF BETA-AMINOPROPIONITRILE, SODIUM-FLUORIDE, AND HYDROCORTISONE ON SELECTED PHYSICAL-PROPERTIES OF CORTICAL BONE SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID SONIC PLESIO-VELOCITY; NEUTRON-DIFFRACTION; SEX-DIFFERENCES; RABBIT FEMURS; COMPACT-BONE; COLLAGEN; OSTEOPOROSIS AB BAPN, sodium fluoride, and hydrocortisone are reported to induce altered mineralization states. Three separate sets of experiments, one set for each agent, were performed using male New Zealand white rabbits. In each experiment the rabbits were segregated into groups, each fed a specified weight-determined dose for 13 weeks and then sacrificed. Compact bone from the left femur and tibia were tested for density, composition, sonic velocity, longitudinal elastic modulus, equatorial diffraction spacing of mineralized collagen, diaphyseal cross-sectional area, and relative load stress. P-Aminopropionitrile (BAPN) induced monotonic degradation of all properties at all dose levels, corresponding to the decreasing density with dosage level. The elastic moduli show a decrease; the equatorial diffraction spacing of the collagen increases. The cross-sectioned diaphysis resembled woven bone. The variability in properties increased with dosage. The total cross-sectional area for a given weight increased, implying that the decreased elastic properties were compensated for by a larger area to support the weight. There was a slight increase in average density and other properties for fluoride-treated rabbits, peaking at 20 mg/kg BW/day. For higher dosages the properties are degraded and the values were much lower at high fluoride dosages than for BAPN. There was no peak for the equatorial diffraction spacing, which increased with dosage. It is inferred that the fluorosed apatite is denser than normal apatitic mineral and therefore has a smaller specific volume. A greater weight fraction of fluorosed mineral has a smaller volume fraction than the equivalent normal apatitic mineral. The bone sections look more normal, except for the porosis. The total cross-sectional area decreases when the bone density increases and then increases as the density falls, again implying that the area required to support body weight depends on the magnitude of the elastic moduli. There was a smalt change in some of the properties of the bones of the hydrocortisone-treated rabbits, but the effects on others were undetectable within the uncertainty of the procedures. There was no change in the cross-sectional areas of the diaphyses. C1 FORSYTH DENT CTR,DEPT BIOENGN,BOSTON,MA 02115. OAK RIDGE NATL LAB,OAK RIDGE,TN. FU NIA NIH HHS [AG02325]; NIEHS NIH HHS [ES05064] NR 23 TC 28 Z9 31 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 1994 VL 9 IS 9 BP 1377 EP 1389 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PD706 UT WOS:A1994PD70600008 PM 7817821 ER PT J AU IDA, R LEE, A HUANG, J BRANDI, ML YAMAGUCHI, DT AF IDA, R LEE, A HUANG, J BRANDI, ML YAMAGUCHI, DT TI PROSTAGLANDIN-STIMULATED 2ND MESSENGER SIGNALING IN BONE-DERIVED ENDOTHELIAL-CELLS IS DEPENDENT ON CONFLUENCY IN CULTURE SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID ARACHIDONIC-ACID METABOLISM; CYTOSOLIC FREE CALCIUM; OSTEOBLAST-LIKE CELLS; PARATHYROID-HORMONE; BOVINE BONE; CYCLIC-AMP; RELEASE; CAMP; MOBILIZATION; TRANSDUCTION AB New bone formation is associated with an increase in blood flow by the invasion of capillaries. Endothelial cells that line the capillaries can produce paracrine factors that affect bone growth and development, and in turn, could be affected by products produced by bone cells, in particular the osteoblasts. Since osteoblasts produce prostaglandins E(2) and F-2 alpha (PGE(2), PGF(2 alpha)), it was investigated if these PGs were agonists to bone-derived endothelial cells (BBE) by assessing changes in cAMP and free cytosolic calcium concentration ([Ca2+]i) second messenger generation. We found that confluent cultures of BBE cells, a clonal endothelial cell line derived from bovine sternal bone, responded to 1 mu M PGE(2) by an increase in cAMP. PGF(2 alpha) at the same concentration was less potent in stimulating an increase in cAMP production in confluent BBE cells. Subconfluent cells with a morphology similar to that of fibroblastic cells were not as sensitive to PGE(2)-stimulated cAMP generation. PGF(2 alpha) failed to elicit any cAMP production in subconfluent cultures. PGE(2) and PGF(2 alpha) both stimulated an increase in [Ca2+]i concentration in a dose-dependent manner. The potency of PGE(2) was similar to that of PGF(2 alpha) in stimulating an increase in [Ca2+]i. The Ca2+ response was mostly independent of extracellular Ca+, was unchanged even with prior indomethacin treatment, was unaffected by caffeine pretreatment, but was abolished subsequent to thapsigargin pretreatment. The PG-induced increase in [Ca2+]i was also dependent on the confluency oi the cells. In a subconfluent state, the responses to PGE(2) or PGF(2 alpha) were either negligible, or only small increases in [Ca2+]i were noted with high concentrations of these two PGs. Consistent, dose-dependent increases in [Ca2+]i were stimulated by these PGs only when the cells were confluent and had a cobblestoned appearance. Since it was previously demonstrated that BBE cells respond to parathyroid hormone (PTH) by the production of cAMP, we tested if bovine PTH(1-34) amide [bPTH(1-34) also increased [Ca2+]i in these cells. No change in [Ca2+]i was found in response to bPTH (1-34), although bPTH (1-34) stimulated a nine to tenfold increase in cAMP. We conclude that BBE cells respond to PGE(2) and PGF(2 alpha) but not to bPTH(1-34) by an increase in [Ca2+]i probably secondary to stimulation of phospholipase C and that the cAMP and [Ca2+]i second messenger responses in BBE cells are dependent on the state of confluency of the cells. (C) 1994 Wiley-Liss, Inc. C1 W LOS ANGELES VET AFFAIRS MED CTR,DENT SERV,LOS ANGELES,CA 90073. UNIV FLORENCE,ENDOCRINE UNIT,FLORENCE,ITALY. UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA 90073. W LOS ANGELES VET AFFAIRS MED CTR,CTR GERIATR RES EDUC & CLIN 11G,LOS ANGELES,CA 90073. NR 42 TC 9 Z9 9 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 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD SEP PY 1994 VL 160 IS 3 BP 585 EP 595 DI 10.1002/jcp.1041600322 PG 11 WC Cell Biology; Physiology SC Cell Biology; Physiology GA PF218 UT WOS:A1994PF21800021 PM 8077296 ER PT J AU DEMONACO, HJ SHAH, AS AF DEMONACO, HJ SHAH, AS TI ECONOMIC-CONSIDERATIONS IN THE USE OF NEUROMUSCULAR BLOCKING-DRUGS SO JOURNAL OF CLINICAL ANESTHESIA LA English DT Article DE COST CONTROL; COST-BENEFIT ANALYSIS; NONDEPOLARIZING NEUROMUSCULAR BLOCKING DRUGS PANCURONIUM, PIPECURONIUM, VECURONIUM AB The acceptance of new and increasingly expensive technologies is a major component of the rising costs of health care. While the practice of anesthesia has been relatively immune from the effects of cost containment, it is inevitable that practitioners will have to justify costly practices. Available pharmacoeconomic methods can be applied to the use of all anesthetic drugs, particularly neuromuscular blocking drugs. Cost-effectiveness analysis allows the practicing anesthesiologist to prioritize the use of neuromuscular blocking drugs to maximize their benefit while reducing unnecessary costs. RP DEMONACO, HJ (reprint author), MASSACHUSETTS GEN HOSP,DEPT PHARM,32 FRUIT ST,BOSTON,MA 02114, USA. NR 0 TC 14 Z9 15 U1 0 U2 0 PU BUTTERWORTH-HEINEMANN PI WOBURN PA 225 WILDWOOD AVE #UNITB PO BOX 4500, WOBURN, MA 01801-2084 SN 0952-8180 J9 J CLIN ANESTH JI J. Clin. Anesth. PD SEP-OCT PY 1994 VL 6 IS 5 BP 383 EP 387 DI 10.1016/S0952-8180(05)80008-X PG 5 WC Anesthesiology SC Anesthesiology GA PH951 UT WOS:A1994PH95100007 PM 7986510 ER PT J AU ADAMS, JM TAYLOR, AE SCHOENFELD, DA CROWLEY, WF HALL, JE AF ADAMS, JM TAYLOR, AE SCHOENFELD, DA CROWLEY, WF HALL, JE TI THE MIDCYCLE GONADOTROPIN SURGE IN NORMAL WOMEN OCCURS IN THE FACE OF AN UNCHANGING GONADOTROPIN-RELEASING-HORMONE PULSE FREQUENCY SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HUMAN MENSTRUAL-CYCLE; FREE ALPHA-SUBUNIT; FOLLICLE-STIMULATING-HORMONE; LUTEINIZING-HORMONE; GNRH SECRETION; RHESUS-MONKEY; NEUROENDOCRINE REGULATION; PROGESTERONE; ESTRADIOL; ESTROGEN AB The midcycle gonadotropin surge is a critical event in normal reproductive cycles and requires functional integration of the hypothalamus, pituitary, and ovary. To determine whether a change in GnRH frequency occurs coincident with the onset or termination of the surge in normal women, 20 studies were performed at a sampling interval of every 5 min for up to 36 h. The frequency of pulsatile GnRH secretion was assessed by the use of two surrogate markers of its secretion, LH and free alpha-subunit (FAS). The timing of the studies was prospectively determined by serial ultrasound and previous cycle history, whereas measurements of LH, FSH, estradiol, and progesterone in daily blood samples were used retrospectively to locate the frequent sampling study in relation to the day of ovulation in each individual. The frequent sampling studies were divided into late follicular phase (LFP; days -4 to -2) and early, mid-, and late portions of the midcycle surge (days -1 to 1) in relation to the 95% confidence limits of the LH peak derived from daily samples in 69 normal ovulatory women. The patterns of LH and FAS secretion were pulsatile at all times during the midcycle surge. The amplitude of LH pulsations increased from the LFP and early surge to the midportion of the midcycle surge (5.9 +/- and 15.1 +/- 5 vs. 39.0 +/- 3 IU/L; P < 0.0001) and decreased from the mid- to the late portion of the surge (13.4 +/- 5 IU/L; P < 0.0001). Likewise, the amplitude of FAS pulses increased from the LFP and early surge to the midportion of the surge (82.4 +/- 59 and 153.1 +/- 50 vs. 421.4 +/- 35 ng/L; P < 0.0001) and decreased from the mid- to the late portion of the surge (190.8 +/- 49 ng/L; P < 0.0002). Although there was excellent concordance of pulsatile secretion of LH and FAS, significantly more pulses of FAS were detected than of LH (P < 0.0001). There was no change in frequency (expressed as interpulse interval) between the LFP and the early and midportions of the surge for LH (70.0 +/- 8, 67.5 +/- 7, and 65 +/- 5 min, respectively) or FAS (55.1 +/- 7, 54.6 +/- 6, and 60.0 +/- 4 min). However, there was an increase in LH interpulse interval (decrease in pulse frequency) in the late portion of the surge (87.0 +/- 6 min) compared to the early and midportions of the surge (P < 0.02 and P < 0.0005, respectively). FAS pulse frequency also decreased significantly from the early to the late (71.5 +/- 6 min) portion of the surge (P < 0.05). These studies indicate that LH, FAS, and, by inference, GnRH continue to be secreted in a pulsatile manner throughout the duration of the midcycle surge in normal women. Despite the marked increase in pulse amplitude of both LH and FAS that accompanies the onset the midcycle gonadotropin surge, there is no increase in GnRH pulse frequency, as assessed by two independent markers of its secretion. However, a decrease in GnRH pulse frequency may contribute to the termination of the surge. C1 MASSACHUSETTS GEN HOSP, DEPT MED, REPROD ENDOCRINE SCI CTR, BOSTON, MA 02114 USA. RP MASSACHUSETTS GEN HOSP, NATL CTR INFERTIL RES, DEPT MED, 32 FRUIT ST, BOSTON, MA 02114 USA. FU NCRR NIH HHS [MO1-RR-01066]; NICHD NIH HHS [P30 HD028138, T32 HD007396, R01 HD-15080, U54-HD-29164] NR 43 TC 60 Z9 60 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 1994 VL 79 IS 3 BP 858 EP 864 DI 10.1210/jc.79.3.858 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PF386 UT WOS:A1994PF38600031 PM 7521353 ER PT J AU EMANUEL, EJ AF EMANUEL, EJ TI COMMENTARY ON DISCUSSIONS ABOUT LIFE-SUSTAINING TREATMENTS SO JOURNAL OF CLINICAL ETHICS LA English DT Editorial Material ID ADVANCE DIRECTIVES; HEALTH-CARE; RESUSCITATION; DECISIONS; PATIENT C1 HARVARD UNIV,SCH MED,DEPT SOCIAL MED,BOSTON,MA 02115. RP EMANUEL, EJ (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC EPIDEMIOL & CONTROL,BOSTON,MA 02115, USA. NR 17 TC 1 Z9 1 U1 1 U2 1 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 FAL PY 1994 VL 5 IS 3 BP 250 EP 256 PG 7 WC Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Biomedical Social Sciences GA PN860 UT WOS:A1994PN86000014 PM 7841478 ER PT J AU RABENECK, L AF RABENECK, L TI AIDS ENTEROPATHY - WHATS IN A NAME SO JOURNAL OF CLINICAL GASTROENTEROLOGY LA English DT Article DE HIV; ACQUIRED IMMUNODEFICIENCY SYNDROME; SMALL INTESTINE ID HUMAN IMMUNODEFICIENCY VIRUS; CHRONIC DIARRHEA; HIV ENTEROPATHY; INFECTIONS AB The term acquired immunodeficiency syndrome (AIDS) enteropathy was first used in 1984 to refer to changes in intestinal structure and function in human immunodeficiency virus (HIV)-infected patients. Since then, confusion has arisen regarding the meaning of the term. To identify the sources of this confusion we performed a methodologic critique of published clinical research on the topic. We carried out a literature search to identify clinical studies that included at least 20 subjects. Among the six cross-sectional studies we identified, no consensus exists regarding the term itself, to whom it applies, the elements on which it is based, and the criteria for its definition. Further, methodologic problems pertaining to the selection of cases and controls limited the conclusions that could be drawn from these studies. Alterations of mucosal structure and function occur in some HIV-infected patients. However, the nature of these alterations and their relationships to symptoms (diarrhea), immune function, and enteric pathogens remain unclear. Further research is needed to develop a taxonomy for AIDS enteropathy. In carrying out this research, attention to methodologic issues will be important. C1 BAYLOR COLL MED,DEPT MED,HOUSTON,TX 77030. RP RABENECK, L (reprint author), VET AFFAIRS MED CTR 111D,2002 HOLCOMBE BLVD,HOUSTON,TX 77030, USA. NR 21 TC 9 Z9 9 U1 0 U2 1 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 SEP PY 1994 VL 19 IS 2 BP 154 EP 157 DI 10.1097/00004836-199409000-00017 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PD968 UT WOS:A1994PD96800016 PM 7963365 ER PT J AU HALES, CA AF HALES, CA TI SQUAT LIKE A TOAD CLOSE AT THE EAR OF EVE SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID HYPOXIC PULMONARY-HYPERTENSION C1 HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138. RP HALES, CA (reprint author), MASSACHUSETTS GEN HOSP,DEPT PULM & CRIT CARE MED,BOSTON,MA 02114, USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 1994 VL 94 IS 3 BP 919 EP 920 DI 10.1172/JCI117456 PG 2 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA PF354 UT WOS:A1994PF35400002 PM 8083375 ER PT J AU BERSON, EL AF BERSON, EL TI VISUAL FUNCTION TESTING - CLINICAL CORRELATIONS (REPRINTED FROM DUANES-FOUNDATIONS-OF-CLINICAL-OPHTHALMOLOGY, VOL 2, PG 1-10, 1991) SO JOURNAL OF CLINICAL NEUROPHYSIOLOGY LA English DT Reprint DE VISUAL FUNCTION TEST; RETINA; ELECTRORETINOGRAPHY; VISUAL-EVOKED CORTICAL POTENTIAL; ELECTROOCULOGRAM; DARK ADAPTATION TESTING; RETINITIS PIGMENTOSA ID DOMINANT RETINITIS-PIGMENTOSA; JUVENILE MACULAR DEGENERATION; GYRATE ATROPHY; CONE ELECTRORETINOGRAMS; RHODOPSIN GENE; OCULAR FINDINGS; POINT MUTATION; FOVEAL; DEFECT AB Visual function tests provide criteria to determine the extent and type of retinal malfunction in patients with retinal disease. This chapter provides an overview of some selected measures of retinal function that are useful as aids in diagnosis of retinal diseases, particularly those that involve the cone and rod photoreceptors. RP BERSON, EL (reprint author), HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BERMAN GUND LAB STUDY RETINAL DEGENERAT,BOSTON,MA 02114, USA. FU NEI NIH HHS [EY00169] NR 39 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0736-0258 J9 J CLIN NEUROPHYSIOL JI J. Clin. Neurophysiol. PD SEP PY 1994 VL 11 IS 5 BP 472 EP 481 DI 10.1097/00004691-199409000-00002 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA PN467 UT WOS:A1994PN46700002 PM 7844238 ER PT J AU CANNISTRA, SA AF CANNISTRA, SA TI PACLITAXEL IN OVARIAN-CANCER - HOW CAN WE MAKE IT BETTER SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material RP CANNISTRA, SA (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. NR 5 TC 7 Z9 7 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP PY 1994 VL 12 IS 9 BP 1743 EP 1744 PG 2 WC Oncology SC Oncology GA PG300 UT WOS:A1994PG30000001 PM 7916037 ER PT J AU ADKINS, DR SALZMAN, D BOLDT, D KUHN, J IRVIN, R ROODMAN, GD LYONS, R SMITH, L FREYTES, CO LEMAISTRE, CF AF ADKINS, DR SALZMAN, D BOLDT, D KUHN, J IRVIN, R ROODMAN, GD LYONS, R SMITH, L FREYTES, CO LEMAISTRE, CF TI PHASE-I TRIAL OF DACARBAZINE WITH CYCLOPHOSPHAMIDE, CARMUSTINE, ETOPOSIDE, AND AUTOLOGOUS STEM-CELL TRANSPLANTATION IN PATIENTS WITH LYMPHOMA AND MULTIPLE-MYELOMA SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID BONE-MARROW TRANSPLANTATION; RELAPSED HODGKINS-DISEASE; METASTATIC MALIGNANT-MELANOMA; HIGH-DOSE CYCLOPHOSPHAMIDE; 5-(3,3-DIMETHYL-1-TRIAZENO)IMIDAZOLE-4-CARBOXAMIDE NSC-45388; COMBINATION CHEMOTHERAPY; REFRACTORY MALIGNANCIES; MAMMALIAN-CELLS; ALKYLTRANSFERASE; CANCER AB Purpose: We investigated the feasibility of escalating doses of dacarbazine (DTIC) in combination with high-dose cyclophosphamide, carmustine, and etoposide (CBV) given with autologous stem-cell transplantation in 33 patients with relapsed or refractory lymphoma or multiple myeloma. Patients and Methods: Eligible patients were treated in this phase I study with cyclophosphamide (7.2 g/m(2)), carmustine (BCNU) (600 mg/m(2)), etoposide (2.4 g/m(2)), and escalating doses of DTIC (3,000 to 6,591 mg/m(2)) administered either as a 2- (in 23 patients) or a 6- (in 10 patients) hour infusion to determine the maximum-tolerated dose (MTD) of DTIC and the toxicity profile of this combination. Results: The MTD of DTIC infused over 2 hours and given with the CBV regimen was 3,900 mg/m(2), with the dose-limiting toxicity being hypotension. Seven patients experienced transient acute hypocalcemia in association with the DTIC infusion. Prolonging the DTIC infusion to 6 hours or administration of supplemental calcium did not allow further dose escalation of DTIC to occur. Other non-hematologic toxicities observed with this regimen have been reported with CBV alone. Of 25 patients assessable for tumor response at first evaluation posttransplant, 13 (52%) were in complete remission (CR), four (16%) were in partial remission (PR), five (20%) had stable disease (SD), and three (12%) had progressive disease (PROG). Of 31 patients assessable for relapse-free survival, 22 are alive with 13 in CR, one in PR, two with SD, and six with FROG at a median follow-up duration of 313 days (range, 35 to 749+). Treatment-related mortality occurred in six patients (18%). Conclusion: The feasibility of combining DTIC in high doses with the CBV regimen has been demonstrated. Dose-limiting hypotension is transient and reversible when DTIC is administered at 3,900 mg/m(2) with CBV. Future trials to evaluate the effect of the addition of DTIC to the CBV regimen on response rate and relapse-free survival are encouraged. (C) 1994 by American Society of Clinical Oncology. C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX. NR 43 TC 8 Z9 8 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP PY 1994 VL 12 IS 9 BP 1890 EP 1901 PG 12 WC Oncology SC Oncology GA PG300 UT WOS:A1994PG30000022 PM 7916039 ER PT J AU SADOWITZ, PD DUBOWY, R SOUID, A POLLOCK, BH WEINSTEIN, H PARMLEY, RT BOWMAN, WP LAND, V VATS, T PRATT, C BUCHANAN, GR AF SADOWITZ, PD DUBOWY, R SOUID, A POLLOCK, BH WEINSTEIN, H PARMLEY, RT BOWMAN, WP LAND, V VATS, T PRATT, C BUCHANAN, GR TI PHASE-I TRIAL OF CONTINUOUS-INFUSION CARBOPLATIN AND ETOPOSIDE IN CHILDREN WITH REFRACTORY ACUTE-LEUKEMIA - A PEDIATRIC-ONCOLOGY-GROUP STUDY SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; ACUTE LYMPHOCYTIC-LEUKEMIA; CANCER-STUDY-GROUP; COMBINATION CHEMOTHERAPY; CHILDHOOD; RELAPSE; CIS-DICHLORODIAMMINEPLATINUM(II); TOXICITY AB Purpose: The purpose of this phase I study was to determine the toxicities and response to continuous infusion carboplatin in combination with a fixed dose of etoposide (VP-16) in children with refractory acute leukemia. Patients and Methods: From January 1989 to February 1992, 20 patients received 28 courses of treatment. Each course of treatment consisted of a 1-hour intravenous (IV) infusion of VP-16 100 mg/m(2)/d for 5 days, followed by a 23-hour IV infusion of carboplatin each day. The initial, total 5-day dose of carboplatin (1,000 mg/m(2)) was escalated by 250- to 375-mg increments to a final, total dose of 1,875 mg/m(2) over 5 days. Results: Significant marrow suppression was observed in all patients, with prolonged marrow aplasia at the 1,875-mg/m(2) dose level. Grade III diarrhea occurred in three patients; 10 patients experienced life-threatening infection and three had severe thrombocytopenic bleeding. Major marrow responses (two complete remissions and two partial remissions) occurred in four patients (20%). Conclusion: In view of the apparent antileukemic efficacy extramedullary toxicity, carboplatin deserves further study in a phase II trial. (C) 1994 by American Society of Clinical Oncology. C1 SUNY HLTH SCI CTR, DEPT PEDIAT, SYRACUSE, NY 13210 USA. SUNY HLTH SCI CTR, DEPT EMERGENCY MED, SYRACUSE, NY USA. PEDIAT ONCOL GRP, STAT OFF, GAINESVILLE, FL USA. UNIV FLORIDA, DEPT PEDIAT, GAINESVILLE, FL USA. CHILDRENS HOSP, DANA FARBER CANC INST, BOSTON, MA 02115 USA. UNIV TEXAS, HLTH SCI CTR, SAN ANTONIO, TX USA. COOK FT WORTH CHILDRENS MED CTR, FT WORTH, TX USA. UNIV TEXAS, SW MED CTR, DALLAS, TX USA. WASHINGTON UNIV, MED CTR, ST LOUIS CHILDRENS HOSP, ST LOUIS, MO USA. UNIV KANSAS, MED CTR, KANSAS CITY, MO USA. ST JUDE CHILDRENS RES HOSP, MEMPHIS, TN USA. FU NCI NIH HHS [CA-20549, CA-30969, CA-29691] NR 20 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP PY 1994 VL 12 IS 9 BP 1969 EP 1973 PG 5 WC Oncology SC Oncology GA PG300 UT WOS:A1994PG30000032 PM 8083718 ER PT J AU ETTINGER, GJ GORDON, GG GOODSON, JM SOCRANSKY, SS WILLIAMS, R AF ETTINGER, GJ GORDON, GG GOODSON, JM SOCRANSKY, SS WILLIAMS, R TI DEVELOPMENT OF AUTOMATED REGISTRATION ALGORITHMS FOR SUBTRACTION RADIOGRAPHY SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE DENTAL RADIOGRAPHY; DIGITAL SUBTRACTION; IMAGE ANALYSIS ID PERIODONTAL BONE-LESIONS; GEOMETRY AB An algorithm is described which provides necessary information for automated registration and computation of alveolar height for subtraction radiographic analysis. This procedure involves identification of the cemento-enamel junctions from radiographic images by incrementally comparing a characteristic image signature along computed tooth boundaries. The identification of these anatomically invariant structures provides information necessary to warp images and create automatic superimposition, correcting for geometric misalignment. The present report describes and demonstrates the feasibility of utilizing automated CEJ, edge finding and image warping algorithms to align automatically sequential radiographs and permit their subtraction. C1 FORSYTH DENT CTR,DEPT PHARMACOL,BOSTON,MA 02115. TASC,READING,MA. HARVARD UNIV,SCH DENT MED,BOSTON,MA 02115. FU NIDCR NIH HHS [DE04881] NR 13 TC 14 Z9 14 U1 1 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0303-6979 J9 J CLIN PERIODONTOL JI J. Clin. Periodontol. PD SEP PY 1994 VL 21 IS 8 BP 540 EP 543 DI 10.1111/j.1600-051X.1994.tb01170.x PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA PF220 UT WOS:A1994PF22000005 PM 7989617 ER PT J AU NIERENBERG, AA AF NIERENBERG, AA TI THE TREATMENT OF SEVERE DEPRESSION - IS THERE AN EFFICACY GAP BETWEEN SSRI AND TCA ANTIDEPRESSANT GENERATIONS SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Symposium on Factors to Consider in Selecting an Antidepressant CY JAN 28, 1994 CL DALLAS, TX ID MAJOR DEPRESSION; DISORDER; FLUOXETINE AB Background: Depression is classified along a spectrum of severity that may have implications for treatment. Since the newer generation of serotonin selective reuptake inhibitors (SSRIs) has, for the most part, displaced the older tricyclic antidepressants (TCAs) as first-line treatment, the efficacy of the SSRIs compared with the TCAs for severe depressions has been questioned. Method: I reviewed all available English-language literature in the MEDLINE data base that compared the SSRIs with the TCAs, especially those studies on severe depression. Results: Most of the studies that explored the efficacy of the SSRIs, as compared with the TCAs, for severe depression found that these two classes of antidepressants were equivalent. Nevertheless, only a few studies actually studied severely depressed inpatients. Conclusion: The data suggest that the SSRIs are just as effective as the TCAs for severe depressions. C1 HARVARD UNIV,SCH MED,CONSOLIDATED DEPT PSYCHIAT,BOSTON,MA 02115. RP NIERENBERG, AA (reprint author), MASSACHUSETTS GEN HOSP,CLIN PSYCHOPHARMACOL UNIT,DEPRESS RES PROGRAM,WACC 815,15 PARKMAN ST,BOSTON,MA 02114, USA. NR 24 TC 32 Z9 32 U1 0 U2 1 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 SEP PY 1994 VL 55 SU A BP 55 EP 59 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA PQ449 UT WOS:A1994PQ44900010 PM 7961543 ER PT J AU ROOSE, SP NIERENBERG, AA PRESKORN, SH FEIGHNER, JP DREVETS, WC AF ROOSE, SP NIERENBERG, AA PRESKORN, SH FEIGHNER, JP DREVETS, WC TI THE TREATMENT OF SEVERE DEPRESSION - IS THERE AN EFFICACY GAP BETWEEN SSRI AND TCA ANTIDEPRESSANT GENERATIONS - DISCUSSION SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Discussion C1 PSYCHIAT RES INST,WICHITA,KS 67214. UNIV KANSAS,SCH MED,DEPT PSYCHIAT,WICHITA,KS. MASSACHUSETTS GEN HOSP,CLIN PSYCHOPHARMACOL UNIT,DEPRESS RES PROGRAM,BOSTON,MA 02114. FEIGHNER RES INST,POWAY,CA 92064. FEIGHNER RES INST,SAN DIEGO,CA. UNIV CALIF SAN DIEGO,SCH MED,DEPT PSYCHIAT,LA JOLLA,CA 92093. WASHINGTON UNIV,SCH MED,DEPT PSYCHIAT,ST LOUIS,MO 63110. WASHINGTON UNIV,SCH MED,DEPT RADIOL,ST LOUIS,MO 63110. RP ROOSE, SP (reprint author), COLUMBIA UNIV COLL PHYS & SURG,NEW YORK STATE PSYCHIAT INST,DEPT PSYCHIAT,722 W 168TH ST,NEW YORK,NY 10032, USA. RI Preskorn, Sheldon/L-9839-2016 NR 4 TC 0 Z9 0 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 SEP PY 1994 VL 55 SU A BP 60 EP 61 PG 2 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA PQ449 UT WOS:A1994PQ44900011 ER PT J AU CORZO, D YUNIS, JJ YUNIS, EJ HOWARD, A LIEBERMAN, JA AF CORZO, D YUNIS, JJ YUNIS, EJ HOWARD, A LIEBERMAN, JA TI HS70-2 9.0-KB VARIANT IS IN LINKAGE DISEQUILIBRIUM WITH THE HLA-B AND DRB1-ASTERISK ALLELES ASSOCIATED WITH CLOZAPINE-INDUCED AGRANULOCYTOSIS SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Symposium-Clozapine 1994 CY FEB 25-26, 1994 CL GARDEN CITY, NY ID HEAT-SHOCK PROTEINS; COLONY-STIMULATING FACTOR; LINKED HSP70 GENES; STRESS PROTEINS; MOLECULAR CHAPERONES; ESCHERICHIA-COLI; CELL; INDUCTION; CHLORPROMAZINE; ACTIVATION AB In order to extend the analysis of the association between class I and class II HLA markers and HSP-70 alleles, we studied the genetic polymorphism of HSP70-2 genes by restriction fragment length polymorphism analysis in a panel of HLA-homozygous cell lines carrying the HLA-B alleles known to be associated with clozapine-induced agranulocytosis. We have found a linkage disequilibrium between the 9.0 kb variant of HSP70-2 with the class I antigens HLA-B7, B38, and B44 and with the class II antigens HLA-DR2 and DR4. We discuss the importance of analyzing the variants of HSP70-2 in patients with agranulocytosis to confirm that the 9.0 kb allele is a genetic marker for the disease. If that is the case, HSP-70 variants could explain the different associations of HLA alleles in individuals of Jewish and non-Jewish ancestry because the HLA alleles are in linkage disequilibrium with the 9.0 kb band. We postulate that HSP-70 molecules could also play a significant role in determining the molecular mechanisms that induce agranulocytosis by clozapine. C1 HILLSIDE HOSP,LONG ISL JEWISH MED CTR,GLEN OAKS,NY. ALBERT EINSTEIN COLL MED,GLENOAKS,NY. RP CORZO, D (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV IMMUNOGENET,44 BINNEY ST,BOSTON,MA 02115, USA. FU NIMH NIH HHS [MH-00537, MH-41960, MH-47029] NR 45 TC 16 Z9 17 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 SEP PY 1994 VL 55 IS 9 SU B BP 149 EP 152 PG 4 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA PQ450 UT WOS:A1994PQ45000035 PM 7961560 ER PT J AU SOKOLSKI, KN CUMMINGS, JL ABRAMS, BI DEMET, EM KATZ, LS COSTA, JF AF SOKOLSKI, KN CUMMINGS, JL ABRAMS, BI DEMET, EM KATZ, LS COSTA, JF TI EFFECTS OF SUBSTANCE-ABUSE ON HALLUCINATION RATES AND TREATMENT RESPONSES IN CHRONIC PSYCHIATRIC-PATIENTS SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 144th Annual Meeting of the American-Psychiatric-Association CY MAY 07-12, 1991 CL NEW ORLEANS, LA SP AMER PSYCHIAT ASSOC ID AUDITORY HALLUCINATIONS; TEMPORAL-LOBE; VISUAL HALLUCINATIONS; CLINICAL COURSE; SCHIZOPHRENIA; ABNORMALITIES; DIAGNOSIS; PSYCHOSIS; PERFUSION; DISORDER AB Background: Few data systematically document the effects of illicit drug exposure on psychotic illness. We examined the effect of substance abuse on rates and treatment responses of hallucinations in a chronic psychiatric population. Method: 113 cooperative patients consecutively admitted to a state psychiatric hospital were administered the Structured Clinical Diagnostic Interview for DSM-III-R, a Hallucination Interview, and an inventory of past and current substances of abuse. Demographic information was obtained on 104 of 108 patients who declined interview. Medication dosage was analyzed for one third of the interviewed sample; hospital records, nursing reports, contacts with relatives, and urine drug screens were used to confirm information from patient interviews. Hallucination rates and response were compared by diagnositic groups (chi-square). Results: Noninterviewed patients had more frequent hospitalizations, more patients diagnosed with psychosis not otherwise specified or schizoaffective disorder, and fewer females with comorbid substance abuse than the study population. Among interviewed subjects, those with substance abuse and psychiatric illness had first admissions at an earlier age than patients with no substance abuse (p = .005). Schizophrenics experienced higher rates of visual (p = .04) and olfactory (p = .05) hallucinations when using illicit drugs. Substance abuse was associated with decreased treatment responsiveness of auditory (p < .03) and tactile (p < .004) hallucinations in schizophrenic or manic patients. Compared with nonparanoid patients, there was a trend for paranoid schizophrenics with substance abuse to experience more frequent visual (p = .09) and tactile (p = .06) and more refractory auditory (p = .08) hallucinations. No differences in medication dosages were found between patients with treatment-responsive and treatment-refractory hallucinations. Conclusion: Abused substances may interact selectively with primary psychiatric illness to increase rates and treatment resistance of specific hallucination modalities; etiologies are discussed. C1 METROPOLITAN STATE HOSP,NORWALK,CA. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA. UNIV CALIF IRVINE,DEPT PSYCHIAT & HUMAN BEHAV,IRVINE,CA 92717. UNIV CALIF LOS ANGELES,DEPT NEUROL,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,DEPT PSYCHIAT,LOS ANGELES,CA 90024. RP SOKOLSKI, KN (reprint author), LONG BEACH VA MED CTR,DEPT PSYCHIAT 116A,5901 E 7TH ST,LONG BEACH,CA 90822, USA. NR 41 TC 20 Z9 20 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 SEP PY 1994 VL 55 IS 9 BP 380 EP 387 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA PQ172 UT WOS:A1994PQ17200002 PM 7929017 ER PT J AU REIMER, P SAINI, S HAHN, PF BRADY, TJ COHEN, MS AF REIMER, P SAINI, S HAHN, PF BRADY, TJ COHEN, MS TI CLINICAL-APPLICATION OF ABDOMINAL ECHOPLANAR IMAGING (EPI) - OPTIMIZATION USING A RETROFITTED EPI SYSTEM SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE ABDOMEN; MAGNETIC RESONANCE IMAGING, TECHNIQUES; MAGNETIC RESONANCE IMAGING ID GRASE GRADIENT-ECHO; MAGNETIC-RESONANCE; MR; LIVER; BODY AB Objective: Echoplanar MRI (EPI) with data acquisition times as short as 36 ms has been advocated for imaging body areas where gross physiologic motion degrades images. In this study we investigated the effect of various operator-defined parameters on image quality in EPI of the abdomen using a commercially available scanner. Materials and Methods: Specifically, we assessed the effect of breathholding, slice thickness, k-space coverage (raw data size), and high resolution EPI in volunteers. The effect of these parameters on signal-to-noise ratio (SNR) and image quality of liver, spleen, kidney, and pancreas was evaluated to propose guidelines for clinical EPI of the abdomen. The requirements for contiguous imaging were analyzed in a phantom experiment. Results: Our study suggests that optimum clinical EPI requires a minimum slice thickness of 7 mm. Breathhold single shot techniques are preferred to avoid spatial misregistrations and to optimize the signal yield for segmented techniques. Maximum k-space coverage at a given TE should be implemented. High resolution techniques (128 x 512) suffer from low SNR and are clinically not useful for routine EPI. Contiguous imaging requires a scan time of >6 s to eliminate effects of cross-talk. Conclusion: The results suggest that clinical EPI requires careful attention to the choice of imaging parameters. The practical recommendations may help other investigators to optimize their clinical EPI studies. C1 MASSACHUSETTS GEN HOSP E,CTR MGH NMR,DEPT RADIOL,BOSTON,MA. MASSACHUSETTS GEN HOSP,DEPT RADIOL,DIV ABDOMINAL & INTERVENT RADIOL,BOSTON,MA 02114. RP REIMER, P (reprint author), UNIV MUNSTER,INST CLIN RADIOL,ALBERT SCHWEITZER STR 33,D-48129 MUNSTER,GERMANY. RI Cohen, Mark/C-6610-2011 OI Cohen, Mark/0000-0001-6731-4053 NR 23 TC 18 Z9 19 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD SEP-OCT PY 1994 VL 18 IS 5 BP 673 EP 679 DI 10.1097/00004728-199409000-00001 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PG292 UT WOS:A1994PG29200001 PM 8089312 ER PT J AU TAYLOR, CR ANDERSON, RR AF TAYLOR, CR ANDERSON, RR TI INEFFECTIVE TREATMENT OF REFRACTORY MELASMA AND POSTINFLAMMATORY HYPERPIGMENTATION BY Q-SWITCHED RUBY-LASER SO JOURNAL OF DERMATOLOGIC SURGERY AND ONCOLOGY LA English DT Article ID GUINEA-PIG SKIN; TATTOOS AB BACKGROUND. Melasma and postinflammatory pigmentation are cosmetic problems with limited options for treatment. OBJECTIVE. To determine whether selective photothermolysis of pigmented cells by Q-switched ruby laser treatment would produce clinical benefit in these disorders. METHODS. Eight subjects with melasma or postinflammatory hyperpigmentation refractory to traditional treatments were treated with Q-switched ruby laser pulses (694 nm, 40 nanoseconds) at fluences of 15-7.5 J/cm2, and followed. Histology was obtained before and after treatment. RESULTS. Regardless of fluence, no permanent improvement and, in some cases, darkening was seen in each type of lesion. Except for small depression at high fluences in black patients, there were no textural changes after healing. Immediately after treatment, there was epidermal and dermal injury, with extracellular melanin. Several months later, epidermal pigmentation had returned to baseline and dermal macrophages were apparently focally increased. CONCLUSIONS. The Q-switched ruby laser by itself does not provide an effective treatment for refractory melasma or postinflammatory hyperpigmentation. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,WELLMAN LABS PHOTOMED,BOSTON,MA 02114. FU NIAMS NIH HHS [1R3 AR-38992] NR 24 TC 106 Z9 110 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0148-0812 J9 J DERMATOL SURG ONC PD SEP PY 1994 VL 20 IS 9 BP 592 EP 597 PG 6 WC Oncology; Dermatology; Surgery SC Oncology; Dermatology; Surgery GA PH779 UT WOS:A1994PH77900007 PM 8089359 ER PT J AU BARTLETT, M CUSHION, MT FISHMAN, JA KANESHIRO, ES LEE, CH LEIBOWITZ, MJ LU, JJ LUNDGREN, B PETERS, SE SMITH, JW SMULIAN, AG STABEN, C STRINGER, JR STRINGER, SL WAKEFIELD, AE WALZER, PD WEINBERG, GA AF BARTLETT, M CUSHION, MT FISHMAN, JA KANESHIRO, ES LEE, CH LEIBOWITZ, MJ LU, JJ LUNDGREN, B PETERS, SE SMITH, JW SMULIAN, AG STABEN, C STRINGER, JR STRINGER, SL WAKEFIELD, AE WALZER, PD WEINBERG, GA TI REVISED NOMENCLATURE FOR PNEUMOCYSTIS-CARINII SO JOURNAL OF EUKARYOTIC MICROBIOLOGY LA English DT Article; Proceedings Paper CT 3rd International Workshops on Opportunistic Protists CY JUN 24-29, 1994 CL CLEVELAND STATE UNIV, CLEVELAND, OH SP SOC OF PROTOZOOLOGIST HO CLEVELAND STATE UNIV ID RIBOSOMAL-RNA GENES; SEQUENCE; RAT; DIVERSITY C1 UNIV CINCINNATI,COLL MED,DEPT MOLEC GENET BIOCHEM & MICROBIOL,CINCINNATI,OH 45267. INDIANA UNIV,SCH MED,DEPT PATHOL & LAB MED,INDIANAPOLIS,IN 46202. VET AFFAIRS MED CTR,CINCINNATI,OH 45267. UNIV CINCINNATI,COLL MED,DEPT INTERNAL MED,CINCINNATI,OH 45267. HARVARD UNIV,MASSACHUSETTS GEN HOSP EAST,SCH MED,DEPT MED,CHARLESTON,MA. UNIV CINCINNATI,DEPT BIOL,CINCINNATI,OH 45267. UNIV MED & DENT NEW JERSEY,ROBERT WOOD JOHNSON MED SCH,DEPT MOLEC GENET & MICROBIOL,PISCATAWAY,NJ 08854. UNIV COPENHAGEN,HVIDOVRE HOSP,DEPT CLIN MICROBIOL,DK-2650 HVIDOVRE,DENMARK. UNIV LONDON,UNIV LONDON QUEEN MARY & WESTFIELD COLL,SCH BIOL SCI,LONDON E1 4NS,ENGLAND. UNIV KENTUCKY,TH MORGAN SCH BIOL SCI,MOLEC & CELL BIOL GRP,LEXINGTON,KY 40506. UNIV CINCINNATI,COLL MED,DEPT MOLEC GENET BIOCHEM & MICROBIOL,CINCINNATI,OH 45267. JOHN RADCLIFFE HOSP,INST MOLEC MED,DEPT PAEDIAT,OXFORD OX3 9DU,ENGLAND. INDIANA UNIV,SCH MED,DEPT PEDIAT,INDIANAPOLIS,IN 46202. RI Staben, Charles/C-1562-2013 NR 16 TC 46 Z9 46 U1 0 U2 1 PU SOC PROTOZOOLOGISTS PI LAWRENCE PA 810 E 10TH ST, LAWRENCE, KS 66044 SN 1066-5234 J9 J EUKARYOT MICROBIOL JI J. Eukaryot. Microbiol. PD SEP-OCT PY 1994 VL 41 IS 5 BP S121 EP S122 PG 2 WC Microbiology SC Microbiology GA PP283 UT WOS:A1994PP28300107 ER PT J AU ROSOWSKY, A BADER, H WRIGHT, JE MORAN, RG AF ROSOWSKY, A BADER, H WRIGHT, JE MORAN, RG TI 5-DEAZA-7-DESMETHYLENE ANALOGS OF 5,10-METHYLENE-5,6,7,8-TETRAHYDROFOLIC ACID AND RELATED-COMPOUNDS - SYNTHESIS AND IN-VITRO BIOLOGICAL-ACTIVITY .49. SO JOURNAL OF HETEROCYCLIC CHEMISTRY LA English DT Article ID OPEN-CHAIN ANALOGS; DENOVO PURINE SYNTHESIS; 5,10-DIDEAZA-5,6,7,8-TETRAHYDROFOLIC ACID; DIHYDROFOLATE-REDUCTASE; METHOTREXATE ANALOGS; ANTITUMOR-ACTIVITY; 5,6,7,8-TETRAHYDROFOLIC ACID; THYMIDYLATE SYNTHASE; STRUCTURAL FEATURES; AGENTS AB 1-[4-(tert-Butyloxycarbonyl)phenyl]-3-pyrrolidinone and 1-[3-(tert-butyloxycarbonyl)phenyl]-4-piperidinone were condensed with ethyl cyanoacetate or malononitrile to form ylidene derivatives, which were then subjected sequentially to (i) catalytic or chemical reduction, (ii) condensation with guanidine, and (iii) gentle trifluoroacetic acid treatment to obtain 3-(2,4-diamino-6(5H)-oxopyrimidin-5-yl)-1-(4-carboxyphenyl)pyrrolidine (27), 4-(2,4-diamino-6(5H)-oxopyrimidin-5-yl)-1-(carboxyphenyl)piperidine (35), and 3-(2,4,6-triaminopyrimidin-5-yl)-1-(carboxyphenyl)pyrrolidine (40). Condensation of 27, 35, and 40 with diethyl or di-tert-butyl L-glutamate followed by removal of the ester groups yielded N-[4-[3-(2,4-diamino-6(5H)-oxopyrimidin-5-yl)pyrrolidino]benzoyl]-L-glutamic acid (13), N-[4-[4-(2,4-diamino-6-(5H)-oxopyrimidin-5-yl)piperidino]benzoyl]-L-glutamic acid (14), and N-[4-[3-(2,4,6-triaminopyrimidin-5-yl)pyrrolidino]benzoyl]-L-glutamic acid (15). Compounds 13 and 14 may be viewed as 5-deaza-7-desmethylene analogues of 5,10-methylene-5,6,7,8-tetrahydrofolic and 5,10-ethylene-5,6,7,8-tetrahydrofolic acid, respectively. Compounds 13 and 15 were good substrates for mouse liver folylpolyglutamate synthetase, with K(m) values of 20 and 18 muM and a relative first-order rate constant V(max)/K(m) of 2.2 (aminopterin = 1.0). In contrast, 14 was a very poor substrate, with a K(m) of 490 muM and a relative V(max)/K(m) of 0.052. As expected from its structure, 15 was a dihydrofolate reductase inhibitor. However its potency was unexceptional (IC50 = 1.2 muM). Compounds 13 and 14 were inactive at concentrations of up to 100 muM, and likewise showed no activity against thymidylate synthase or glycinamide ribotide formyltransferase, two other key enzymes of folate-mediated one-carbon metabolism. Compound 15 was moderately active as an inhibitor of the growth of cultured tumor cells (SCC25 human squamous cell carcinoma), with an IC50 of 0.37 muM (72 hour exposure). By comparison the IC50 of aminopterin was 0.0069 muM. Thus, even though 15 is a good folylpolyglutamate synthetase substrate, the deep-seated skeletal changes embodied in this structure are unfavorable for DHFR binding and may also be unfavorable for transport into cells. C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. UNIV SO CALIF,NORRIS COMPREHENS CANC CTR,LOS ANGELES,CA 90033. RP ROSOWSKY, A (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115, USA. NR 44 TC 8 Z9 8 U1 0 U2 0 PU HETERO CORPORATION PI TAMPA PA BOX 20285, TAMPA, FL 33622-0285 SN 0022-152X J9 J HETEROCYCLIC CHEM JI J. Heterocycl. Chem. PD SEP-OCT PY 1994 VL 31 IS 5 BP 1241 EP 1250 PG 10 WC Chemistry, Organic SC Chemistry GA PL219 UT WOS:A1994PL21900022 ER PT J AU LENSCHOW, DJ SPERLING, AI COOKE, MP FREEMAN, G RHEE, L DECKER, DC GRAY, G NADLER, LM GOODNOW, CC BLUESTONE, JA AF LENSCHOW, DJ SPERLING, AI COOKE, MP FREEMAN, G RHEE, L DECKER, DC GRAY, G NADLER, LM GOODNOW, CC BLUESTONE, JA TI DIFFERENTIAL UP-REGULATION OF THE B7-1 AND B7-2 COSTIMULATORY MOLECULES AFTER IG RECEPTOR ENGAGEMENT BY ANTIGEN SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELL ACTIVATION; CTLA-4 COUNTER-RECEPTOR; INTERLEUKIN-2 GENE; IL-2 PRODUCTION; CLONAL ANERGY; B-CELLS; CD28; PROLIFERATION; EXPRESSION; SIGNAL AB Ag-pulsed B cells are potent APCs, in part, because of the ability of the Ig receptor to mediate rapid and specific Ag uptake. However, it is also known that full T cell activation requires signals delivered by costimulatory molecules, which naive B cells seem to lack. This study examines the effect Ig receptor engagement has on the expression and function of a new CD28 counter-receptor, B7-2. Unlike B7-1 (B7), B7-2 was rapidly induced on the cell surface of B cells after engagement of the Ig receptor by either anti-Ig mAbs or hen egg lysozyme (HEL) on normal and HEL-specific B cell receptor transgenic B cells, respectively. Furthermore, B7-2 expression was up-regulated on tolerant B cells isolated from HEL/anti-HEL double transgenic mice after Ag stimulation, although at lower levels than on nontolerant transgenic B cells. No significant cell surface levels of B7-1(B7) were observed under these conditions. Finally, the B7-2 molecules induced by Ig cross-linking costimulated T cell proliferation in a CD28-dependent manner, independent of B7-1(B7) expression. Thus, the effectiveness of Ag-specific B cells as APCs depends on both their enhanced Ag uptake, mediated by the B cell receptor, and immediate up-regulation of a potent costimulatory molecule, B7-2. C1 UNIV CHICAGO,BEN MAY INST,COMM IMMUNOL,CHICAGO,IL 60637. STANFORD UNIV,HOWARD HUGHES MED INST,STANFORD,CA 94305. STANFORD UNIV,BECKMAN CTR,DEPT MICROBIOL & IMMUNOL,STANFORD,CA 94305. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. REPLIGEN CORP,CAMBRIDGE,MA 02139. FU NCI NIH HHS [CA 40216]; NIAID NIH HHS [P01 AI29531]; NIDDK NIH HHS [P60 DK20595] NR 35 TC 245 Z9 249 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 SEP 1 PY 1994 VL 153 IS 5 BP 1990 EP 1997 PG 8 WC Immunology SC Immunology GA PD075 UT WOS:A1994PD07500009 PM 7519638 ER PT J AU KNOL, EF TACKEY, F TEDDER, TF KLUNK, DA BICKEL, CA STERBINSKY, SA BOCHNER, BS AF KNOL, EF TACKEY, F TEDDER, TF KLUNK, DA BICKEL, CA STERBINSKY, SA BOCHNER, BS TI COMPARISON OF HUMAN EOSINOPHIL AND NEUTROPHIL ADHESION TO ENDOTHELIAL-CELLS UNDER NONSTATIC CONDITIONS - ROLE OF L-SELECTIN SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-BLOOD EOSINOPHILS; LEUKOCYTE ADHESION; ANTIGEN CHALLENGE; MOLECULE-1; ADHERENCE; INVITRO; MIGRATION; INFLAMMATION; STIMULATION; MONOLAYERS AB To simulate adhesion that occurs under conditions of flow, we investigated the attachment of eosinophils to endothelium under rotational conditions. Tissue-culture plates containing monolayers of HUVEC were placed on a horizontal rotator (80 revolutions per minute (rpm)), and equal numbers of purified human eosinophils or neutrophils were added to separate wells at 4 degrees C. Binding of eosinophils and neutrophils to unstimulated endothelial cells was 15 +/- 3 and 31 +/- 11 cells/four high power fields (HPF), respectively. After preincubation of HUVEC with IL-1 beta (1 ng/ml, 4 h, 37 degrees C), adhesion increased to 56 +/- 4 and 290 +/- 26 cells/four HPF, respectively (p < 0.0002 for both, n = 8-14). Eosinophils with reduced levels of L-selectin (blood eosinophils activated in vitro or eosinophils obtained from bronchoalveolar ravage (BAL) performed after segmental lung allergen challenge of allergic subjects) demonstrated reduced binding under rotating conditions. Several L-selectin Abs inhibited adhesion of eosinophils and neutrophils (e.g., LAM1-3: 43 +/- 14% vs 63 +/- 3% inhibition; LAM1-6: 73 +/- 5% vs 36 +/- 6% inhibition, respectively, n greater than or equal to 6). Interestingly, one additional L-selectin Ab, LAM1-11, inhibited eosinophil but not neutrophil adhesion (51 +/- 2% vs 1 +/- 7% inhibition, respectively, n greater than or equal to 5). We conclude that eosinophils like neutrophils, use L-selectin to bind to activated endothelial cells under conditions of flow, although mAb LAM1-11 can selectively inhibit eosinophil attachment to stimulated endothelial cells in vitro, suggesting different functional epitopes on L-selectin among eosinophils and neutrophils. C1 JOHNS HOPKINS ASTHMA & ALLERGY CTR,CLIN IMMUNOL UNIT OFF 3,BALTIMORE,MD 21224. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. FU NHLBI NIH HHS [HL49545]; NIAID NIH HHS [AI26872, AI27429] NR 31 TC 66 Z9 67 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 SEP 1 PY 1994 VL 153 IS 5 BP 2161 EP 2167 PG 7 WC Immunology SC Immunology GA PD075 UT WOS:A1994PD07500029 PM 7519643 ER PT J AU KUPPERMANN, N NELSON, DS SALADINO, RA THOMPSON, CM SATTLER, F NOVITSKY, TJ FLEISHER, GR SIBER, GR AF KUPPERMANN, N NELSON, DS SALADINO, RA THOMPSON, CM SATTLER, F NOVITSKY, TJ FLEISHER, GR SIBER, GR TI COMPARISON OF A RECOMBINANT ENDOTOXIN-NEUTRALIZING PROTEIN WITH A HUMAN MONOCLONAL-ANTIBODY TO ENDOTOXIN FOR THE TREATMENT OF ESCHERICHIA-COLI SEPSIS IN RATS SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID TUMOR-NECROSIS-FACTOR; LIMULUS ANTILIPOPOLYSACCHARIDE FACTOR; CONTROLLED CLINICAL-TRIAL; GRAM-NEGATIVE BACTEREMIA; SEPTIC SHOCK; LIPOPOLYSACCHARIDE FACTOR; HORSESHOE-CRAB; IGM ANTIBODY; HA-1A; MICE AB A recombinant endotoxin-neutralizing protein (ENP) from Limulus polyphemus and a monoclonal IgM anti-lipid A antibody (HA-1A) were compared in a rat model of Escherichia coli sepsis. One hour after intraperitoneal challenge with 10(6) cfu of E. coli O18ac K1, animals were sensitized to endotoxin with lead acetate and treated with ENP, HA-1A, or saline, followed by ceftriaxone and gentamicin. Before treatment, 95% of rats had high-grade bacteremia and high serum endotoxin concentrations, which were similar in all treatment groups (P > .60). One hour after treatment, there was no bacterial growth in any blood sample, and endotoxin concentrations were significantly lower in the ENP group than in the HA-1A and saline groups (P < .01). At 24 h after challenge, survival in the ENP group was significantly higher than in the HA-1A saline group (P < .001). ENP improved survival in a rat model of E. coli sepsis with high mortality despite effective antibiotic therapy. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,INFECT DIS LAB,BOSTON,MA 02115. CHILDRENS HOSP,DEPT MED,DIV EMERGENCY MED,BOSTON,MA 02115. ASSOCIATES CAPE COD INC,WOODS HOLE,MA. FU NIAID NIH HHS [AI-18125] NR 33 TC 18 Z9 19 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 SEP PY 1994 VL 170 IS 3 BP 630 EP 635 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA PE265 UT WOS:A1994PE26500019 PM 8077721 ER PT J AU GADENNE, AS STRUCKE, R DUNN, D WAGNER, M BLEICHER, P BIGBY, M AF GADENNE, AS STRUCKE, R DUNN, D WAGNER, M BLEICHER, P BIGBY, M TI T-CELL LINES DERIVED FROM LESIONAL SKIN OF LICHEN-PLANUS PATIENTS CONTAIN A DISTINCTIVE POPULATION OF T-CELL RECEPTOR GAMMA-DELTA-BEARING CELLS SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE T LYMPHOCYTES; AUTOIMMUNITY; GAMMA-DELTA CELLS ID LYMPHOCYTES-T; LANGERHANS CELLS; EXPRESSION; INTERLEUKIN-2; SUBSETS AB Lichen planus is characterized by a dense infiltrate of T lymphocytes at the dermoepidermal junction. To determine the phenotypic and functional characteristics of the infiltrating lymphocytes, T-cell lines from normal and lesional skin from the same patients with lichen planus were established by culture with interleukin 2 followed by stimulation every 14 d with phytohemagglutinin and irradiated allogeneic feeder cells. Resultant T-cell lines were immunophenotyped by staining with monoclonal antibodies and their reactivity tested by determining their cytolytic activity to selected targets. T-cell lines from 13 lesional and nine normal biopsy specimens were studied. T-cell lines from normal skin were 61% CD4(+) and 32% CD8(+), whereas lines from lesional skin had significantly fewer CD4(+) cells (13%) and more CD8(+) cells (62%). T-cell lines from lesional skin contained a distinctive population of gamma delta T cells that was rarely present in lines derived from normal skin. We were able to culture gamma delta T cells out of the lesional skin of 12 of 13 patients. In these 12 patients, lesional T-cell lines were 17% gamma delta(+) (range 2% to 47%). Only one T-cell line from normal skin contained significant numbers of gamma delta T cells. The gamma delta population from lesional skin was commonly V(delta)1J(delta)1(+). These results suggest that CD8(+) and TCR gamma delta(+) T lymphocytes may be involved in the development or the maintenance of lichen planus. C1 HARVARD UNIV,SCH MED,DEPT DERMATOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CUTANEOUS BIOL RES CTR,BOSTON,MA. MASSACHUSETTS GEN HOSP,BOSTON,MA. NR 27 TC 22 Z9 22 U1 1 U2 1 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 1994 VL 103 IS 3 BP 347 EP 351 DI 10.1111/1523-1747.ep12394904 PG 5 WC Dermatology SC Dermatology GA PG082 UT WOS:A1994PG08200014 PM 8077699 ER PT J AU VANLEEUWEN, RL DEKKER, SK VERMEER, BJ BYERS, HR AF VANLEEUWEN, RL DEKKER, SK VERMEER, BJ BYERS, HR TI ATTACHMENT AND SPREADING OF MELANOMA-CELLS ON VITRONECTIN IS REGULATED BY ALPHA(V)BETA(3) AND ALPHA(V)BETA(5) INTEGRIN EXPRESSION AND ENHANCED AFTER PHORBOL ESTER TREATMENT SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 LEIDEN UNIV,DEPT DERMATOL,LEIDEN,NETHERLANDS. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 1994 VL 103 IS 3 BP 403 EP 403 PG 1 WC Dermatology SC Dermatology GA PG082 UT WOS:A1994PG08200060 ER PT J AU MCGRATH, JA PULKKINEN, L CHRISTIANO, AM BURGESON, RE LEIGH, IM EADY, RAJ UITTO, J AF MCGRATH, JA PULKKINEN, L CHRISTIANO, AM BURGESON, RE LEIGH, IM EADY, RAJ UITTO, J TI MUTATIONS IN THE LAMB3 GENE IN THE GENERALIZED ATROPHIC BENIGN FORM OF JUNCTIONAL EPIDERMOLYSIS-BULLOSA SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 THOMAS JEFFERSON UNIV,DEPT DERMATOL,PHILADELPHIA,PA 19107. THOMAS JEFFERSON UNIV,DEPT BIOCHEM & MOLEC BIOL,PHILADELPHIA,PA 19107. ST THOMAS HOSP,ST JOHNS INST DERMATOL,LONDON,ENGLAND. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CUTANEOUS BIOL RES CTR,BOSTON,MA. ROYAL LONDON HOSP,DEPT DERMATOL,LONDON E1 1BB,ENGLAND. RI McGrath, John/D-6824-2012 OI McGrath, John/0000-0002-3708-9964 NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 1994 VL 103 IS 3 BP 434 EP 434 PG 1 WC Dermatology SC Dermatology GA PG082 UT WOS:A1994PG08200250 ER PT J AU OBRIEN, WA AF OBRIEN, WA TI HIV-1 ENTRY AND REVERSE TRANSCRIPTION IN MACROPHAGES SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE CD4; GP120; ENVELOPE; NEUTRALIZATION; NUCLEOTIDES ID HUMAN-IMMUNODEFICIENCY-VIRUS; RECOMBINANT SOLUBLE CD4; AIDS-RELATED COMPLEX; ENVELOPE V3 LOOP; T-CELLS; MONONUCLEAR PHAGOCYTES; GLYCOPROTEIN GP120; HUMAN MONOCYTES; TYPE-1 VIRIONS; HTLV-III/LAV AB Although CD4 is required for efficient virus entry, it is not sufficient for entry of all primary HIV-1 strains. There may be additional virus-cell interactions, possibly involving the V3 region of the extracellular envelope protein, gp120, that occur following conformational changes induced by CD4 binding. This second interaction would precede fusion events and entry of the virus core. Primary HIV-1 strains appear to have a higher virion envelope density and retain gp120 better than HIV-1 strains adapted to growth in T cell lines in culture. These properties may confer a growth advantage in vivo to primary strains on the basis of less well exposed CD4 binding and neutralization domains. HIV-1 entry into both activated and quiescent T cells, as well as macrophages, is efficient for most primary strains, but there are different patterns of reverse transcription. Productive infection of activated T cells is associated with cell proliferation and accumulation of full-length reverse transcripts within 4 to 6 h. In resting, nondividing T cells, reverse transcription is aborted prior to full-length viral DNA formation. A third pattern of reverse transcription is seen in nondividing cultured macrophages with slow kinetics and accumulation of full-length viral DNA between 36 and 48 h. This rate can be increased by adding exogenous nucleotides, but still not to the rate seen in activated T cells. Future antiretroviral therapies may involve interference with cell-specific functions involved in reverse transcription. C1 UNIV CALIF LOS ANGELES,LOS ANGELES,CA. RP OBRIEN, WA (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,DEPT MED,WILSHIRE & SAWTELLE BLVD,691-111F,LOS ANGELES,CA 90073, USA. FU NIAID NIH HHS [AI 29894] NR 51 TC 20 Z9 20 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD SEP PY 1994 VL 56 IS 3 BP 273 EP 277 PG 5 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA PF341 UT WOS:A1994PF34100010 PM 8083599 ER PT J AU CACCIOLA, JS RUTHERFORD, MJ ALTERMAN, AI SNIDER, EC AF CACCIOLA, JS RUTHERFORD, MJ ALTERMAN, AI SNIDER, EC TI AN EXAMINATION OF THE DIAGNOSTIC-CRITERIA FOR ANTISOCIAL PERSONALITY-DISORDER IN SUBSTANCE-ABUSERS SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article ID INTERVIEW SCHEDULE; BEHAVIOR; VALIDITY; ALCOHOL AB In this article, we compare problem severity and adult antisocial behavior among three groups of cocaine- or alcohol-dependent patients: those with antisocial personality disorder (APD), those who met adult but not childhood APD criteria (A-APD), and those who met neither (non-APD) in order to determine the clinical utility of the A-APD category. Subjects were 269 male veterans admitted for substance abuse treatment. The Addiction Severity Index was used to determine problem severity and the NIMH Diagnostic Interview Schedule was used to obtain positive DSM-III APD criteria and APD diagnoses. More APD subjects reported arrests, illegal behavior, and chronic lying than A-APD and non-APD subjects. On several variables (recent family/social problems, trouble controlling violent behavior, and time incarcerated), A-APD subjects were intermediate in severity. Overall, the non-APD subjects had the least severe problem status. When the APD and A-APD groups were equated on number of positive adult APD criteria, the only differences that consistently remained were difficulty controlling violent behavior and commission of criminal acts, which were endorsed more frequently in the APD group. It appears that the unique contribution of the early onset criteria for the APD diagnosis is that it identifies individuals more likely to engage in criminal and violent behavior. The more general irresponsibility and disregard for the rights of others characteristic of APD is equally evident in both antisocial groups. This work indicates that the APD versus non-APD distinction may not be fine grained enough for clinical or research purposes. C1 PHILADELPHIA VET AFFAIRS MED CTR,PHILADELPHIA,PA. RP CACCIOLA, JS (reprint author), UNIV PENN,CTR STUDIES ADDICT,3900 CHESTNUT ST,PHILADELPHIA,PA 19104, USA. NR 24 TC 32 Z9 32 U1 1 U2 2 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 SEP PY 1994 VL 182 IS 9 BP 517 EP 523 DI 10.1097/00005053-199409000-00007 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA PH205 UT WOS:A1994PH20500007 PM 8083681 ER PT J AU JOHNS, DR SADUN, AA AF JOHNS, DR SADUN, AA TI CUBAN EPIDEMIC OPTIC NEUROPATHY - MITOCHONDRIAL-DNA ANALYSIS SO JOURNAL OF NEURO-OPHTHALMOLOGY LA English DT Article DE OPTIC NEUROPATHY; MITOCHONDRIAL DNA; LEBERS HEREDITARY OPTIC NEUROPATHY; TOXIC-NUTRITIONAL AMBLYOPIA ID CLINICAL MANIFESTATIONS; 11778 MUTATION; HEREDITARY; NEURORETINOPATHY; PEDIGREES; RECOVERY AB Objective: To search for mitochondrial DNA (mtDNA) mutations previously associated with Leber's hereditary optic neuropathy (LHON) in patients with an optic neuropathy that appeared in epidemic form in Cuba. Methods: Twelve Cuban patients underwent a comprehensive neuro-ophthalmologic examination and were found to have a characteristic optic neuropathy, Cuban epidemic optic neuropathy (CEON). At the same time, one patient was diagnosed with typical LHON that occurred during the epidemic. Blood samples were taken from these patients as well as from 3 controls with normal neuro-ophthalologic examinations. These samples were blindly analyzed for 9 LHON-associated mtDNA mutations by molecular genetic methods. Results: CEON bore clinical and epidemiological similarity to LHON, however, family histories, systemic symptoms (especially weight loss and polyuria), and symptoms of peripheral neuropathy permitted a clinical distinction. None of the 12 patients with CEON or 3 controls had any of the LHON-associated mtDNA mutations. Only the patient with clinical LHON, who did not meet the case definition for CEON, harbored the 11778 mtDNA mutation. Conclusions: Known mtDNA mutations are not found frequently in CEON patients but they may contribute to some cases of Cuban optic neuropathy. CEON may represent an acquired variety of mitochondrial dysfunction induced by nutritional deficiencies, toxins, or both. Alternatively, CEON patients may also harbor as yet undiscovered mtDNA mutations that contribute to their genetic susceptibility. C1 HARVARD UNIV,BETH ISRAEL HOSP,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BOSTON,MA 02115. UNIV SO CALIF,SCH MED,DOHENY EYE INST,DEPT OPHTHALMOL,LOS ANGELES,CA 90033. UNIV SO CALIF,SCH MED,DOHENY EYE INST,DEPT NEUROSURG,LOS ANGELES,CA 90033. RP JOHNS, DR (reprint author), HARVARD UNIV,BETH ISRAEL HOSP,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BOSTON,MA 02115, USA. FU NINDS NIH HHS [NS 01359] NR 21 TC 17 Z9 17 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1070-8022 J9 J NEURO-OPHTHALMOL JI J. Neuro-Ophthal. PD SEP PY 1994 VL 14 IS 3 BP 130 EP 134 PG 5 WC Clinical Neurology; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA PX285 UT WOS:A1994PX28500002 PM 7804415 ER PT J AU JOHNS, DR NEUFELD, MJ HEDGES, TR AF JOHNS, DR NEUFELD, MJ HEDGES, TR TI MITOCHONDRIAL-DNA MUTATIONS IN CUBAN OPTIC AND PERIPHERAL NEUROPATHY SO JOURNAL OF NEURO-OPHTHALMOLOGY LA English DT Article DE OPTIC NEUROPATHY; MITOCHONDRIAL DNA; LEBERS HEREDITARY OPTIC NEUROPATHY; TOXIC-NUTRITIONAL AMBLYOPIA ID COMPLETE NUCLEOTIDE-SEQUENCE; CYTOCHROME-C-OXIDASE; GENE ORGANIZATION; CLINICAL MANIFESTATIONS; HEREDITARY; GENOME; VERTEBRATES; PEDIGREES; CODE AB Objective: To investigate the potential role of mito-chondrial DNA (mtDNA) mutations in the recent outbreak in Cuba of optic neuropathy and peripheral neuropathy (COPN). Design and Methods: Historical features were reviewed and neuro-ophthalmologic examinations were performed on a sample of COPN patients (n = 9) and Cuban patients with other forms of optic neuropathy (n = 2). Molecular genetic methods were then used to test for the presence of 9 mtDNA mutations that were previously associated with Leber's hereditary optic neuropathy (LHON). Results: Two (22%) of 9 COPN patients harbored an LHON-associated mtDNA mutation at nucleotide position 9438 and a novel mutation at nucleotide position 9738 in the cytochrome c oxidase subunit III gene. None of the Cuban patients harbored any of the 8 other LHON-associated mtDNA mutations. Detailed sequence analysis revealed that the Cuban patients could be divided into 7 distinct mtDNA haplotypes and that the 2 COPN patients with mtDNA mutations in the cytochrome c oxidase subunit III gene were not members of the same maternal lineage. Conclusions: The pathogenesis of epidemic COPN is likely complex and multifactorial. Our preliminary results in a small sample of Cuban patients suggest that mtDNA mutations may play a role in some cases. mtDNA mutations may render an individual genetically susceptible to a variety of factors that impair oxidative phosphorylation, including nutritional deficiency, tobacco, alcohol, and other toxins. C1 HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DEPT OPHTHALMOL,BOSTON,MA 02115. MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. TUFTS UNIV,SCH MED,DEPT OPHTHALMOL,BOSTON,MA 02111. TUFTS UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02111. NEW ENGLAND EYE CTR,BOSTON,MA. RP JOHNS, DR (reprint author), HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DEPT NEUROL,BLDG B1-242,220 LONGWOOD AVE,BOSTON,MA 02115, USA. FU NINDS NIH HHS [NS 01359] NR 26 TC 26 Z9 27 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1070-8022 J9 J NEURO-OPHTHALMOL JI J. Neuro-Ophthal. PD SEP PY 1994 VL 14 IS 3 BP 135 EP 140 PG 6 WC Clinical Neurology; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA PX285 UT WOS:A1994PX28500003 PM 7804416 ER PT J AU HYMAN, BT TERRY, RD AF HYMAN, BT TERRY, RD TI APOLIPOPROTEIN-E, A-BETA, AND ALZHEIMER-DISEASE - AN EDITORIAL COMMENT SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Editorial Material ID SENILE PLAQUES; PROTEIN; SEVERITY; TANGLES; ALLELE; GENE C1 UNIV CALIF SAN DIEGO,DEPT NEUROSCI,LA JOLLA,CA 92093. RP HYMAN, BT (reprint author), MASSACHUSETTS GEN HOSP,NEUROL SERV,32 FRUIT ST,BOSTON,MA 02114, USA. NR 23 TC 13 Z9 13 U1 2 U2 2 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD SEP PY 1994 VL 53 IS 5 BP 427 EP 428 DI 10.1097/00005072-199409000-00001 PG 2 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA PF349 UT WOS:A1994PF34900001 PM 8083685 ER PT J AU SIMONIAN, NA HYMAN, BT AF SIMONIAN, NA HYMAN, BT TI FUNCTIONAL ALTERATIONS IN ALZHEIMERS-DISEASE - SELECTIVE LOSS OF MITOCHONDRIAL-ENCODED CYTOCHROME-OXIDASE MESSENGER-RNA IN THE HIPPOCAMPAL-FORMATION SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE ALZHEIMERS DISEASE; CYTOCHROME OXIDASE; IN SITU HYBRIDIZATION; MITOCHONDRIA; OXIDATIVE PHOSPHORYLATION ID PERFORANT PATHWAY ZONE; EXPRESSION; SUBUNITS; NUCLEAR; SYSTEM AB The activity of cytochrome oxidase (CO), the terminal enzyme of the electron transport chain, has been reported to be decreased in the brains of individuals with Alzheimer's disease (AD). In experimental models, CO activity decreases following functional deafferentation of neural circuits. CO is a holoenzyme composed of 13 nuclear- and mitochondrial-encoded subunits and experimental data indicate that the change in CO activity following deafferentation is controlled primarily by regulation of mitochondrial CO gene expression. It has been proposed that the hippocampal formation is deafferented in AD. We therefore hypothesized that an alteration in mitochondrial CO gene expression might underlie the reduction in CO activity in AD. Using in situ hybridization, we found a selective reduction in mRNA levels for a mitochondrial-encoded subunit, CO II, with preservation of mRNA for a nuclear-encoded subunit, CO IV, in the hippocampal formation of individuals with AD, The reduction in CO II mRNA levels was seen both in regions with neurofibrillary tangles, senile plaques, and neuronal loss and regions relatively spared from these neuropathological changes. These data suggest that the reduction in CO activity in brain regions from individuals with AD may be a result of an alteration in mitochondrial CO gene expression that extends beyond neurons directly affected by structural pathology. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. FU NIA NIH HHS [P01AG11337, NIA AG08487]; NINDS NIH HHS [NS07009-18] NR 25 TC 92 Z9 94 U1 0 U2 2 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD SEP PY 1994 VL 53 IS 5 BP 508 EP 512 DI 10.1097/00005072-199409000-00010 PG 5 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA PF349 UT WOS:A1994PF34900010 PM 8083692 ER PT J AU GOLDEN, JA HYMAN, BT AF GOLDEN, JA HYMAN, BT TI DEVELOPMENT OF THE SUPERIOR TEMPORAL NEOCORTEX IS ANOMALOUS IN TRISOMY-21 SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE CELL COUNTING; NEOCORTICAL DEVELOPMENT; TRISOMY 21 ID DOWNS-SYNDROME; STEREOLOGICAL METHODS; GOLGI; NEURONS; CORTEX; BRAIN; FETUS AB Trisomy 21 (Down syndrome) is the most common inherited form of mental retardation in the United States, however, the basis of impaired cognition is unknown. We have used recently developed stereological cell counting techniques to quantitatively examine the pattern of neuronal migration and maturation in one neocortical area during gestation in normal development and in trisomy 21. Normal development of the cerebral cortex occurs in two general sequences: Beginning at approximately 7-8 weeks gestation, migration of cells destined to become neurons results in the accumulation of cells in the cortical mantle. This process is largely complete by 20-21 weeks. Over the next 7-10 weeks an ''inside-out'' differentiation into lamina of different neuronal densities occurs. Our data suggest that the second phase of cortical development, the emergence of lamination, is both delayed and disorganized in trisomy 21. The observed pattern of cortical maturation may reflect an abnormality in axonal and dendritic arborization that subsequently subserve the connectional and functional units underlying normal cognition. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,CHARLES S KUBIC LAB NEUROPATHOL,BOSTON,MA. MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114. RP GOLDEN, JA (reprint author), BRIGHAM & WOMENS HOSP,DEPT PATHOL,75 FRANCIS ST,BOSTON,MA 02115, USA. FU NIA NIH HHS [AG08487] NR 22 TC 108 Z9 108 U1 4 U2 8 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD SEP PY 1994 VL 53 IS 5 BP 513 EP 520 DI 10.1097/00005072-199409000-00011 PG 8 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA PF349 UT WOS:A1994PF34900011 PM 8083693 ER PT J AU MEGA, MS CUMMINGS, JL AF MEGA, MS CUMMINGS, JL TI FRONTAL-SUBCORTICAL CIRCUITS AND NEUROPSYCHIATRIC DISORDERS SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID OBSESSIVE-COMPULSIVE DISORDER; BASAL GANGLIA; RHESUS-MONKEY; PARKINSONS-DISEASE; SUBSTANTIA-NIGRA; SQUIRREL-MONKEY; CAUDATE-NUCLEUS; NIGROSTRIATAL PROJECTIONS; EFFERENT PROJECTIONS; MEDIODORSAL NUCLEUS AB Five parallel anatomic circuits link regions of the frontal cortex to the striatum, globus pallidus/substantia nigra, and thalamus. The circuits originate in the supplmentary motor area, frontal eye fields, dorsolateral prefrontal region, lateral orbitofrontal area, and anterior cingulate cortex. Open loop structures that provide input to or receive output from specific circuits share functions, cytoarchitectural features, and phylogenetic histories with the relevant circuits. The circuits mediate motor and oculomotor function as well as executive functions, socially responsive behavior, and motivation. Neuropsychiatric disorders of frontal-subcortical circuits include impaired executive function, disinhibition, and apathy; indicative mood disorders include depression, mania, and lability. Transmitters, modulators, receptor subtypes, and second messengers within the circuits provide a chemoarchitecture that can inform pharmacotherapy. C1 UNIV CALIF LOS ANGELES, SCH MED, DEPT NEUROL & PSYCHIAT, LOS ANGELES, CA USA. UNIV CALIF LOS ANGELES, SCH MED, DEPT BIOBEHAV SCI, LOS ANGELES, CA USA. W LOS ANGELES VET AFFAIRS MED CTR, BEHAV NEUROSCI SECT, LOS ANGELES, CA USA. FU NIA NIH HHS [AG11012-3] NR 65 TC 463 Z9 469 U1 4 U2 17 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD FAL PY 1994 VL 6 IS 4 BP 358 EP 370 PG 13 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA PN731 UT WOS:A1994PN73100004 PM 7841807 ER PT J AU VISWANATHAN, N WEAVER, DR REPPERT, SM DAVIS, FC AF VISWANATHAN, N WEAVER, DR REPPERT, SM DAVIS, FC TI ENTRAINMENT OF THE FETAL HAMSTER CIRCADIAN PACEMAKER BY PRENATAL INJECTIONS OF THE DOPAMINE AGONIST SKF-38393 SO JOURNAL OF NEUROSCIENCE LA English DT Article DE SUPRACHIASMATIC NUCLEUS; CIRCADIAN; DOPAMINE; SKF 38393; D1 RECEPTOR; HAMSTER; DEVELOPMENT; HYPOTHALAMUS ID C-FOS EXPRESSION; SUPRACHIASMATIC NUCLEUS; MATERNAL COORDINATION; GENE-EXPRESSION; RHYTHMS; RAT; LESIONS; SYSTEM; CLOCK AB Prenatal treatment with the D-1-dopamine receptor agonist SKF 38393 or cocaine induces expression of the immediate-early gene c-fos in the fetal rat suprachiasmatic nucleus (SCN) (Weaver et al., 1992). Because the induction of c-fos gene expression in the SCN has been implicated in the entrainment of circadian rhythms by light in mature animals, the present study investigated whether prenatal dopaminergic activation entrains the fetal circadian pacemaker. Injections of SKF 38393 (8 mg/kg) were given to pregnant, SCN-lesioned hamsters during the last 5 d of gestation and the phases of the offspring's wheel-running activity rhythms were measured on postnatal day 20. Pregnant hamsters were each given two injections/day 12 hr apart, but only one of the injections each day contained SKF 38393. One group of hamsters received the drug at 0800 hr while another group received the drug at 2000 hr. The offspring from these treatment groups showed average phases that differed by 11.3 hr, demonstrating that prenatal SKF 38393 set the phase of the offspring's circadian rhythms. These results suggest that the fetal circadian pacemaker can be entrained by dopaminergic activation. In situ hybridization using cRNA probes demonstrated that a single injection of SKF 38393 on the last day of gestation induced c-fos gene expression in the fetal hamster SCN and that mRNA for the D-1-dopamine receptor was present in the SCN at that time. It is possible that maternal entrainment of the fetal circadian pacemaker, which normally occurs during development, is mediated by dopaminergic activation within the fetal hypothalamus. C1 NORTHEASTERN UNIV,DEPT BIOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEV CHRONOBIOL LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. FU NICHD NIH HHS [HD18686, HD14427] NR 36 TC 74 Z9 74 U1 1 U2 5 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD SEP PY 1994 VL 14 IS 9 BP 5393 EP 5398 PG 6 WC Neurosciences SC Neurosciences & Neurology GA PJ126 UT WOS:A1994PJ12600020 PM 7916044 ER PT J AU STRITTMATTER, SM IGARASHI, M FISHMAN, MC AF STRITTMATTER, SM IGARASHI, M FISHMAN, MC TI GAP-43 AMINO-TERMINAL PEPTIDES MODULATE GROWTH CONE MORPHOLOGY AND NEURITE OUTGROWTH SO JOURNAL OF NEUROSCIENCE LA English DT Article DE GROWTH-ASSOCIATED PROTEIN-43; NEUROMODULIN; GTP-BINDING PROTEIN; NEURITE OUTGROWTH; GROWTH CONE COLLAPSE; PERTUSSIS TOXIN; MASTOPARAN; DORSAL ROOT GANGLION; NEUROBLASTOMA CELLS ID CALMODULIN-BINDING-PROTEIN; NEURONAL CELLS; PC12 CELLS; RAT-BRAIN; KINASE-C; RECEPTOR; ACTIVATION; G0; PHOSPHORYLATION; IDENTIFICATION AB The neuronal growth-associated protein GAP-43 is expressed maximally during development and regeneration, and is enriched at the cytosolic surface of the growth cone membrane. GAP-43 can activate the GTP-binding protein G(o), which is also a major component of the growth cone membrane. These findings have led to the hypothesis that GAP-43 might modulate neurite outgrowth by altering G-protein activity. Here we define the sequence requirements for GAP-43 amino terminal peptide stimulation of G(o), and test these peptides as potential modulators of neurite outgrowth. The first 10 amino acids of GAP-43, Met-Leu-Cys-Cys-Met-Arg-ArgThr-Lys-Gln, stimulate G(o). Substitutions at particular residues reveal that cys3, cys4, arg6, and lys9 are critical, but arg7 is not. Both the GAP-43(1-10) peptide and the G-protein-activating peptide mastoparan induce growth cone collapse and inhibit neurite extension from embryonic chick dorsal root ganglion and retinal neurons. This is likely to be mediated by G-proteins: pertussis toxin blocks the inhibition, and mutant peptides that do not activate G(o) do not alter outgrowth. In contrast to the case with embryonic chick dorsal root ganglion cells, neurite outgrowth from N1E-115 neuroblastoma cells is stimulated by GAP-43(1-10). This is probably also a G-protein-mediated event because it is blocked by pertussis toxin, because the sequence requirements match those for G(o) stimulation, and because mastoparan stimulates outgrowth from these cells. The longer GAP-43(1-25) peptide does not alter neurite outgrowth unless the cells are permeabilized, suggesting an intracellular site of action. These data identify a novel set of compounds that modulate neurite outgrowth, and also support the notion that GAP-43 can alter neurite extension by modulating pertussis toxin-sensitive G-protein activity in the growth cone. C1 MASSACHUSETTS GEN HOSP E,DEV BIOL LAB,BOSTON,MA 02129. HARVARD UNIV,MASSACHUSETTS GEN HOSP EAST,SCH MED,DEPT NEUROL,BOSTON,MA 02129. HARVARD UNIV,MASSACHUSETTS GEN HOSP EAST,SCH MED,DEPT MED,BOSTON,MA 02129. OI Strittmatter, Stephen/0000-0001-8188-3092 FU NINDS NIH HHS [K08NS01467, R01NS33020] NR 39 TC 74 Z9 75 U1 1 U2 1 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD SEP PY 1994 VL 14 IS 9 BP 5503 EP 5513 PG 11 WC Neurosciences SC Neurosciences & Neurology GA PJ126 UT WOS:A1994PJ12600029 PM 8083750 ER PT J AU KONRADI, C COLE, RL HECKERS, S HYMAN, SE AF KONRADI, C COLE, RL HECKERS, S HYMAN, SE TI AMPHETAMINE REGULATES GENE-EXPRESSION IN RAT STRIATUM VIA TRANSCRIPTION FACTOR CREB SO JOURNAL OF NEUROSCIENCE LA English DT Article DE PSYCHOSTIMULANT; DOPAMINE; ANTISENSE OLIGONUCLEOTIDES; PHOSPHORYLATION; CREB; C-FOS; STRIATUM ID C-FOS; NUCLEUS-ACCUMBENS; CYCLIC-AMP; DIFFERENTIAL EXPRESSION; MOLECULAR MECHANISMS; ADENYLATE-CYCLASE; SOMATOSTATIN GENE; RESPONSE-ELEMENT; BINDING PROTEIN; DOPAMINE AB Amphetamine is a psychostimulant drug of abuse that can produce long-lived changes in behavior including sensitization and dependence. The neural substrates of these drug effects remain unknown, but based on their prolonged time course, we hypothesize that they involve drug-induced alterations in gene expression. It has recently been demonstrated that amphetamine regulates the expression of several genes, including c-fos, via dopamine D1 receptors in rat striatum. Here we report that amphetamine induces phosphorylation of transcription factor cAMP response element binding protein (CREB) in rat striatum in vivo and that dopamine D1 receptor stimulation induces phosphorylation of CREB within specific complexes bound to cAMP regulatory elements. In addition, we show by antisense injection that CREB is necessary for c-fos induction by amphetamine in vivo. Since CREB has been implicated in the activation of a number of immediate-early genes as well as several neuropeptide genes, CREB phosphorylation may be an important early nuclear event mediating long-term consequences of amphetamine administration. C1 MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,NEUROSCI PROGRAM,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP KONRADI, C (reprint author), MASSACHUSETTS GEN HOSP E,MOLEC & DEV NEUROSCI LAB,CNY2,BLDG 149,13TH ST,BOSTON,MA 02129, USA. RI Heckers, Stephan/F-3051-2010 OI Heckers, Stephan/0000-0003-3601-9910 FU NIDA NIH HHS [DA07134, DA07282]; NIMH NIH HHS [MH44160] NR 47 TC 299 Z9 303 U1 0 U2 3 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD SEP PY 1994 VL 14 IS 9 BP 5623 EP 5634 PG 12 WC Neurosciences SC Neurosciences & Neurology GA PJ126 UT WOS:A1994PJ12600039 PM 8083758 ER PT J AU DYER, CA PHILIBOTTE, TM WOLF, MK BILLINGSGAGLIARDI, S AF DYER, CA PHILIBOTTE, TM WOLF, MK BILLINGSGAGLIARDI, S TI MYELIN BASIC-PROTEIN MEDIATES EXTRACELLULAR SIGNALS THAT REGULATE MICROTUBULE STABILITY IN OLIGODENDROCYTE MEMBRANE SHEETS SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Note DE PHOSPHORYLATION; MYELIN/OLIGODENDROCYTE SPECIFIC PROTEIN; GALACTOCEREBROSIDE; CYTOSKELETON ID MONOCLONAL-ANTIBODIES; RAT-BRAIN; MOUSE; GALACTOCEREBROSIDE; ORGANIZATION; GENE; CULTURE; PHOSPHORYLATION; LOCALIZATION; CYTOSKELETON AB Treatment of cultured oligodendrocytes with a monoclonal antibody to galactocerebroside (GalC) triggers a cascade of events including the redistribution of membrane surface GalC over internal domains of MBP and loss of microtubular structures within the sheets (Dyer and Benjamins: J Neurosci 8:4307-4318, 1988; Dyer and Benjamins: J Neurosci Res 24:212-221, 1989). In this report, wild type and myelin basic protein (MBP)-deficient shiverer oligodendrocytes were used to study the possible relationships between these events, and specifically to determine if MBP mediates signals which destabilize microtubular assemblies in cultured oligodendrocytes. We now show that MBP and GalC, which are both initially Triton X-100 soluble, become Triton X-100 insoluble following anti-GalC binding and anti-GalC:GalC complex redistribution, suggesting that the surface anti-GalC: GalC complexes become associated with cytoplasmic MBP. Mediation of the signaling event by MBP is further demonstrated by 1) a decreased phosphorylation of MBP in wild type oligodendrocytes after antibody binding, and 2) the absence of responses, such as GalC redistribution and microtubule loss, in MBP-deficient shiverer oligodendrocytes treated with anti-GalC. Continuous activation of the GalC/MBP pathway for 7 days in wild type oligodendrocytes results in enlarged cell bodies and production of numerous microprocesses, a morphology that is similar to MBP-deficient shiverer oligodendrocytes. A second signaling pathway which produces an opposite effect, i.e., the stabilization and apparent up-regulation of microtubular structures in cultured oligodendrocyte membrane sheets, remains functional in shiverer oligodendrocytes. Thus, MBP appears to be important for mediating extracellular signals that cause a loss of microtubular structures in oligodendrocyte brane sheets and abnormal morphology. (C) 1994 Wiley-Liss, Inc. C1 UNIV MASSACHUSETTS,SCH MED,DEPT CELL BIOL,WORCESTER,MA 01655. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114. RP DYER, CA (reprint author), EUNICE KENNEDY SHRIVER CTR MENTAL RETARDAT INC,DEPT BIOMED SCI,200 TRAPELO RD,WALTHAM,MA 02254, USA. FU PHS HHS [MA 02254] NR 38 TC 56 Z9 56 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD SEP 1 PY 1994 VL 39 IS 1 BP 97 EP 107 DI 10.1002/jnr.490390112 PG 11 WC Neurosciences SC Neurosciences & Neurology GA PF027 UT WOS:A1994PF02700011 PM 7528819 ER PT J AU BLACK, PM CARROLL, R GLOWACKA, D RILEY, K DASHNER, K AF BLACK, PM CARROLL, R GLOWACKA, D RILEY, K DASHNER, K TI PLATELET-DERIVED GROWTH-FACTOR EXPRESSION AND STIMULATION IN HUMAN MENINGIOMAS SO JOURNAL OF NEUROSURGERY LA English DT Article DE MENINGIOMA; PLATELET-DERIVED GROWTH FACTOR; CELL CULTURE; GROWTH FACTOR; CENTRAL NERVOUS SYSTEM TUMOR ID PDGF-RECEPTOR GENES; BINDING-ACTIVITY; PROGESTERONE; COEXPRESSION; CELLS; SIS AB The platelet-derived growth factor (PDGF) family consists of subunits A and B and receptors alpha and beta. This paper evaluates the potential role of the homodimer PDGF-BB as a growth factor in meningiomas. It analyzes the expression of messenger RNA in members of the PDGF family in these tumors, measures the growth response of meningiomas to exogenous PDGF-BB in culture, and examines the induction of the c-fos proto-oncogene by PDGF-BB. Northern blot analysis was carried out on tissue from 20 meningiomas to measure the expression of PDGF-A, PDGF-B, PDGF-alpha receptor (PDGF-alpha-R) and PDGF-beta receptor (PDGF-beta-R). All tumors expressed PDGF-A and PDGF-B subunits. Nineteen of the 20 tumors expressed PDGF-beta-R and none expressed PDGF-alpha-R as measured by this technique. Because the beta receptor is selectively sensitive to stimulation by the PDGF-B subunit, these data suggest that meningiomas might be susceptible to stimulation by PDGF-BB. To test this hypothesis, the effect of exogenous PDGF-BB on meningioma growth was evaluated by incubating cells from 10 human meningiomas. Tritiated thymidine incorporation was used to evaluate stimulation of growth over a 48-hour period using PDGF-BB concentrations of 1, 3, or 6 ng/Ml. Linear regression analysis and multiple-factor analysis of variance were used to measure PDGF-BB effects. Three of the 10 tumor specimens responded significantly to PDGF-BB, with a three- to sixfold increase in thymidine incorporation over 72 hours of exposure, and there was a significant overall growth-stimulating effect of PDGF-BB in the 10 tumor specimens tested. In the last set of experiments, the functionality of the PDGF-beta-R was determined by examining the induction of the proto-oncogene c-fos by PDGF-BB in meningioma cell cultures. A significant increase in c-fos protein was observed 3 hours after PDGF-BB addition. These findings demonstrate that PDGF-A, PDGF-B, and PDGF-beta-R are expressed in meningiomas and suggest that the beta receptor is functional: when it is activated, c-fos levels are increased, and an increase in meningioma cell division is observed after the addition of PDGF-BB. These studies support the hypothesis that PDGF acts as a growth factor in meningiomas. C1 HARVARD UNIV,CHILDRENS HOSP,SCH MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. RP BLACK, PM (reprint author), HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,BRAIN TUMOR CTR,75 FRANCIS ST,BOSTON,MA 02115, USA. NR 23 TC 61 Z9 62 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD SEP PY 1994 VL 81 IS 3 BP 388 EP 393 DI 10.3171/jns.1994.81.3.0388 PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA PC762 UT WOS:A1994PC76200007 PM 8057146 ER PT J AU TATTER, SB COSGROVE, GR AF TATTER, SB COSGROVE, GR TI HEMORRHAGE INTO A LUMBAR SYNOVIAL CYST CAUSING AN ACUTE CAUDA-EQUINA SYNDROME - CASE-REPORT SO JOURNAL OF NEUROSURGERY LA English DT Note DE SYNOVIAL CYST; JUXTAFACET CYST; ZYGAPOPHYSEAL JOINT; SPINAL CANAL; CAUDA EQUINA SYNDROME; LUMBAR SPINE; EPIDURAL SPACE ID GANGLION CYST; SPINAL FACET; DIAGNOSIS; CT; MR; JOINT AB Juxtafacet cysts of the lumbar spine have been reported with increasing frequency but their pathogenesis remains obscure. These cysts most frequently present with back pain, followed by chronic progressive radiculopathy or gradual onset of symptoms of spinal canal compromise. The authors report an unusual case of hemorrhage into a right L3-4 synovial cyst causing an acute cauda equina syndrome and describe its successful surgical treatment. The clinical, radiographic, and pathological features are discussed. C1 MASSACHUSETTS GEN HOSP,NEUROSURG SERV,BOSTON,MA 02114. NR 28 TC 64 Z9 65 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD SEP PY 1994 VL 81 IS 3 BP 449 EP 452 DI 10.3171/jns.1994.81.3.0449 PG 4 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA PC762 UT WOS:A1994PC76200015 PM 8057153 ER PT J AU STONE, CK CHRISTIAN, BT NICKLES, RJ PERLMAN, SB AF STONE, CK CHRISTIAN, BT NICKLES, RJ PERLMAN, SB TI TECHNETIUM 94M-LABELED METHOXYISOBUTYL ISONITRILE - DOSIMETRY AND RESTING CARDIAC IMAGING WITH POSITRON EMISSION TOMOGRAPHY SO JOURNAL OF NUCLEAR CARDIOLOGY LA English DT Article DE POSITRON EMISSION TOMOGRAPHY; NITROGEN 13-LABELED AMMONIA; TECHNETIUM 94M-LABELED SESTAMIBI; MYOCARDIAL INFARCTION ID HEXAKIS 2-METHOXYISOBUTYL ISONITRILE; MYOCARDIAL BLOOD-FLOW; N-13 AMMONIA; PERFUSION; QUANTIFICATION; TL-201; PET; INFARCTION; DEPENDENCE; THALLIUM AB Background. Development of a positron-emitting form of technetium has allowed the imaging of technetium radiopharmaceuticals with positron emission tomography (PET). We used Tc-94m to compare the distribution of the myocardial perfusion agent sestamibi at rest with the conventional PET perfusion tracer N-13-labeled ammonia (N-13-ammonia). Methods and Results. Dosimetry calculations were performed with the known whole-body distribution of Tc-99m-labeled sestamibi. Dynamic PET imaging of N-13-ammonia and Tc-94m-labeled sestamibi (Tc-94m-sestamibi) for 32 minutes was performed in eight patients with previous myocardial infarction. Initial myocardial and extramyocardial distribution of Tc-94m-sestamibi was compared with that of N-13-ammonia by qualitative and quantitative analysis. Quantitative comparison of the two tracers was performed with region-of-interest analysis and circumferential profiles. Qualitatively, the cardiac distribution of the tracers was similar in normal and infarcted myocardium. A decrease in the definition of the epicardial and endocardial borders of the heart was seen with Tc-94m-sestamibi, presumably because of the lower dose of radionuclide injected. Quantitatively, there was no difference in infarct size, defined prospectively as tracer activity less than 20% of maximum activity for the section, between the two tracers. Circumferential profile analysis with 12-degree radial sections similarly demonstrated no difference in regional cardiac distribution of the tracers. Conclusions. These results revealed no significant difference in myocardial uptake compared with N-13-ammonia suggesting that the myocardial uptake of sestamibi correlates with that of myocardial perfusion. C1 UNIV WISCONSIN,SCH MED,DEPT RADIOL,NUCL MED SECT,MADISON,WI 53792. UNIV WISCONSIN,SCH MED,DEPT MED PHYS,MADISON,WI 53792. UNIV WISCONSIN,WILLIAM S MIDDLETON MEM VET ADM HOSP,CTR POSITRON EMISS TOMOG,MADISON,WI 53792. RP STONE, CK (reprint author), UNIV WISCONSIN,SCH MED,CTR CLIN SCI,DEPT MED,CARDIOL SECT,600 HIGHLAND AVE,MADISON,WI 53792, USA. FU NHLBI NIH HHS [R29 HL47003] NR 30 TC 20 Z9 21 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 1071-3581 J9 J NUCL CARDIOL JI J. Nucl. Cardiol. PD SEP-OCT PY 1994 VL 1 IS 5 BP 425 EP 433 DI 10.1007/BF02961596 PN 1 PG 9 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA PU851 UT WOS:A1994PU85100002 PM 9420726 ER PT J AU KHAW, BA NARULA, J AF KHAW, BA NARULA, J TI ANTIBODY IMAGING IN THE EVALUATION OF CARDIOVASCULAR-DISEASES SO JOURNAL OF NUCLEAR CARDIOLOGY LA English DT Review DE ANTIMYOSIN ANTIBODY; IMMUNOSCINTIGRAPHY; ACUTE MYOCARDIAL INFARCTION; MYOCARDITIS; HEART TRANSPLANT REJECTION; DEEP VEIN THROMBOSIS; PULMONARY EMBOLI; ATHEROSCLEROSIS; NEGATIVE CHARGE MODIFICATION OF ANTIBODY ID ACUTE MYOCARDIAL-INFARCTION; MONOCLONAL ANTIMYOSIN ANTIBODY; MYOSIN-SPECIFIC ANTIBODY; SINGLE-CHAIN FV; IN-111 ANTIMYOSIN; IMMUNOSCINTIGRAPHIC DETECTION; HEART-TRANSPLANTATION; ANTIPLATELET ANTIBODY; CLINICAL IMPLICATIONS; ALLOGRAFT-REJECTION AB Antimyosin antibody was originally developed for in vivo detection of acute myocardial infarction. However, its utility has expanded to include diagnosis of various cardiovascular diseases in which myocyte necrosis constitutes an obligatory component of the disease. Thus antimyosin has also been used clinically for noninvasive diagnosis of acute myocarditis, heart transplant rejection, drug-induced cardiotoxicity, and other cardiomyopathies. This first-generation monoclonal antibody, antimyosin, has opened the way for the second-generation monoclonal antibodies such as antifibrin and antiplatelet for in vivo diagnostic use in the detection of deep venous thrombosis and pulmonary embolism and antiatherosclerotic lesion-specific antibody for diagnosis of metabolically active lesions. Whether the third generation of antibodies will include ultrasmall antigen-binding units or negative charge-modified antibodies must await future studies. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA. RP KHAW, BA (reprint author), NORTHEASTERN UNIV,BOUVE COLL PHARM & HLTH SCI,CTR DRUG TARGETING & ANAL,BOSTON,MA 02115, USA. NR 98 TC 8 Z9 8 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 1071-3581 J9 J NUCL CARDIOL JI J. Nucl. Cardiol. PD SEP-OCT PY 1994 VL 1 IS 5 BP 457 EP 476 DI 10.1007/BF02961600 PN 1 PG 20 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA PU851 UT WOS:A1994PU85100006 PM 9420730 ER PT J AU WYMAN, ET AF WYMAN, ET TI WORKERS COMPENSATION - REPLIES SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article RP WYMAN, ET (reprint author), MASSACHUSETTS GEN HOSP,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 1076-2752 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD SEP PY 1994 VL 36 IS 9 BP 978 EP 978 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PK202 UT WOS:A1994PK20200003 ER PT J AU GEBHARDT, MC KUSUZAKI, K MANKIN, HJ SPRINGFIELD, DS AF GEBHARDT, MC KUSUZAKI, K MANKIN, HJ SPRINGFIELD, DS TI AN ASSAY TO MEASURE ADRIAMYCIN BINDING IN OSTEOSARCOMA CELLS SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article ID SUBRENAL CAPSULE ASSAY; PRIMARY OSTEOGENIC-SARCOMA; COLONY-FORMING ASSAY; TUMOR STEM-CELLS; FLOW-CYTOMETRY; CYTOFLUORESCENCE LOCALIZATION; MULTIDRUG-RESISTANT; LEUKEMIA-CELLS; CANCER-CELLS; CHEMOTHERAPY AB Adjuvant chemotherapy is currently employed in the treatment of patients with osteosarcoma, but the drug regimens, although effective in improving disease-free survival, are unsuccessful in 20-40% of patients and very toxic. It would be useful to know whether tumor cells are sensitive to a given drug prior to its use. To this end, we developed a method of assessing Adriamycin (doxorubicin) binding to tumor nuclei as a possible means of detecting sensitivity to the drug. Adriamycin-sensitive murine osteosarcoma cells were used to develop the assay. The in vitro conditions (drug concentration, duration of incubation, and temperature) were optimized with use of the murine osteosarcoma cells in culture. After the cells had been incubated with Adriamycin, cell viability was determined and Adriamycin fluorescence intensity was measured with a cytofluorometer. The optimal parameters for Adriamycin binding were found to be a 30-minute incubation in a 10 mu g/ml concentration of Adriamycin at 37 degrees C; the frequency of cells that emitted Adriamycin fluorescence from the nucleus compared with the total number of living cells reached 100% under these conditions. In a murine leukemia cell line with known sensitivity to Adriamycin, the cells emitted red fluorescence from the nucleus and cytoplasm, whereas in a resistant line the cells emitted Adriamycin fluorescence from only the cytoplasm. We demonstrated that it is possible to differentiate nuclear from cytoplasmic concentration of Adriamycin in a tumor cell with use of a fluorescent microscope and that resistant cell lines can be distinguished from sensitive cell lines by this method. Since Adriamycin acts by intercalating to DNA, its absence in the nucleus probably indicates a resistant cell. This is a rapid technique that may allow prediction of drug sensitivity at the time of diagnosis or relapse. C1 KYOTO PREFECTURAL UNIV MED,DEPT ORTHOPAED SURG,KYOTO 602,JAPAN. RP GEBHARDT, MC (reprint author), MASSACHUSETTS GEN HOSP,ORTHOPAED ONCOL UNIT,GRAY 6,BOSTON,MA 02114, USA. NR 45 TC 11 Z9 11 U1 0 U2 0 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 SN 0736-0266 J9 J ORTHOPAED RES JI J. Orthop. Res. PD SEP PY 1994 VL 12 IS 5 BP 621 EP 627 DI 10.1002/jor.1100120504 PG 7 WC Orthopedics SC Orthopedics GA PM466 UT WOS:A1994PM46600003 PM 7931778 ER PT J AU JASTY, M OCONNOR, DO HENSHAW, RM HARRIGAN, TP HARRIS, WH AF JASTY, M OCONNOR, DO HENSHAW, RM HARRIGAN, TP HARRIS, WH TI FIT OF THE UNCEMENTED FEMORAL COMPONENT AND THE USE OF CEMENT INFLUENCE THE STRAIN TRANSFER TO THE FEMORAL CORTEX SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article ID TOTAL HIP-REPLACEMENT; 10-YEAR FOLLOW-UP; PROSTHESES AB To determine whether the strain patterns produced in the femoral cortex after uncemented femoral arthroplasty are influenced by the fit of the component and whether these patterns are different from those of cemented components, cortical surface strains of cadaveric femurs subjected to loads simulating single-limb stance were measured before and after the insertion of uncemented, collared, straight-stemmed femoral components. The effects of press fit, loose fit, and precise fit of the components were evaluated and were contrasted to the strain patterns occurring after insertion of cemented femoral components. Strains varied markedly, depending on the fit of the stem of the uncemented femoral component within the isthmus. Nearly normal patterns of femoral strain were produced when the femoral stem was fit precisely at the isthmus, and the proximal femoral strains were similar to those of the intact state. In contrast, press fit and loose fit at the isthmus altered the strain patterns. The proximal medial axial strains were significantly reduced with press fit, to a mean of 39% of normal (p < 0.05), and increased with loose fit, to a mean of 141% of normal (p < 0.05). The prostheses fixed with cement showed a mean reduction in proximal medial axial strains to 33% of normal, which was comparable with press fit uncemented components even though the collar was well seated. Thus, our findings indicated that, in the immediate postoperative period, femoral strain patterns can be influenced by the fit of an uncemented component within the isthmus and by the use of cement. C1 MASSACHUSETTS GEN HOSP,HIP & IMPLANT SURG UNIT,BOSTON,MA. HARVARD UNIV,SCH MED,BOSTON,MA. RP JASTY, M (reprint author), MASSACHUSETTS GEN HOSP,ORTHOPAED BIOMECH LAB,JACKSON 1126,BOSTON,MA 02114, USA. FU NIAMS NIH HHS [R01AR35828-01A1] NR 16 TC 32 Z9 33 U1 0 U2 1 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 SN 0736-0266 J9 J ORTHOPAED RES JI J. Orthop. Res. PD SEP PY 1994 VL 12 IS 5 BP 648 EP 656 DI 10.1002/jor.1100120507 PG 9 WC Orthopedics SC Orthopedics GA PM466 UT WOS:A1994PM46600006 PM 7931781 ER PT J AU SCHAFFER, JL RIZEN, M LITALIEN, GJ BENBRAHIM, A MEGERMAN, J GERSTENFELD, LC GRAY, ML AF SCHAFFER, JL RIZEN, M LITALIEN, GJ BENBRAHIM, A MEGERMAN, J GERSTENFELD, LC GRAY, ML TI DEVICE FOR THE APPLICATION OF A DYNAMIC BIAXIALLY UNIFORM AND ISOTROPIC STRAIN TO A FLEXIBLE CELL-CULTURE MEMBRANE SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article ID BIOSYNTHETIC RESPONSE; CHICKEN OSTEOBLASTS; ENDOTHELIAL-CELLS; TISSUE-CULTURE; SHEAR-STRESS; EXPRESSION; INVITRO; DEFORMATION; FORCES; BONE AB A large number of studies have demonstrated that mechanical perturbation modulates cellular metabolism; however, the systematic characterization of the molecular and cellular transduction mechanisms underlying mechanically induced metabolic modulation has been impeded, in part, by the limitations of the mechanical device. The objective of this investigation was to develop an in vitro experimental system that would provide independent control of the spatial and temporal biaxial strain distribution imposed on a flexible transparent tissue culture membrane that permits attachment, proliferation, and maintenance of the phenotypic expression of cultured embryonic osteoblasts. Such a device would permit a systematic investigation of the cellular response to specific, independently controlled parameters of mechanical deformation. Using a prototype device designed to impose a dynamic sinusoidal spatially isotropic biaxial strain profile, we confirmed experimentally that the strain was biaxially uniform and isotropic (radial = circumferential strain over the entire culture membrane) to within 14% (SD/mean) for the range of the peak strains tested (2.3-9.4%). Additionally, the uniformity was maintained at 1 Hz for at least 5 days of continuous operation. This experimental Verification of the theoretically predicted isotropic strain profile suggests that the design principle is sound. Embryonic osteoblasts cultured on the flexible substrate proliferated and exhibited a temporal pattern of phenotypic expression (extracellular matrix accumulation and mineralization) comparable with that observed on polystyrene of tissue culture grade. C1 MASSACHUSETTS GEN HOSP,DEPT BIOMED ENGN,BOSTON,MA. CHILDRENS HOSP,STUDY SKELETAL DISORDERS LAB,BOSTON,MA. BRIGHAM & WOMENS HOSP,DEPT ORTHOPED SURG,BOSTON,MA. HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,DIV VASC SURG,BOSTON,MA. HARVARD MIT,DIV HLTH SCI & TECHNOL,BOSTON,MA. MIT,DEPT ELECT ENGN & COMP SCI,CAMBRIDGE,MA 02139. OI /0000-0002-0477-1211 FU NHLBI NIH HHS [HL34780]; NIAMS NIH HHS [T32AR07112]; NICHD NIH HHS [HD22400] NR 36 TC 104 Z9 115 U1 0 U2 9 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 SN 0736-0266 J9 J ORTHOPAED RES JI J. Orthop. Res. PD SEP PY 1994 VL 12 IS 5 BP 709 EP 719 DI 10.1002/jor.1100120514 PG 11 WC Orthopedics SC Orthopedics GA PM466 UT WOS:A1994PM46600013 PM 7931788 ER PT J AU IMREY, PB CHILTON, NW PIHLSTROM, BL PROSKIN, HM KINGMAN, A LISTGARTEN, MA ZIMMERMAN, SO CIANCIO, SG COHEN, ME DAGOSTINO, RB FINE, D FISCHMAN, SL FLEISS, JL GUNSOLLEY, JC KENT, RL KILLOY, WJ LASTER, LL MARKS, RG VARMA, AO AF IMREY, PB CHILTON, NW PIHLSTROM, BL PROSKIN, HM KINGMAN, A LISTGARTEN, MA ZIMMERMAN, SO CIANCIO, SG COHEN, ME DAGOSTINO, RB FINE, D FISCHMAN, SL FLEISS, JL GUNSOLLEY, JC KENT, RL KILLOY, WJ LASTER, LL MARKS, RG VARMA, AO TI PROPOSED GUIDELINES FOR AMERICAN-DENTAL-ASSOCIATION ACCEPTANCE OF PRODUCTS FOR PROFESSIONAL, NONSURGICAL TREATMENT OF ADULT PERIODONTITIS SO JOURNAL OF PERIODONTAL RESEARCH LA English DT Article DE ADULT PERIODONTITIS; AMERICAN DENTAL ASSOCIATION; EFFICACY; CLINICAL TRIALS ID CLINICAL-TRIALS; DESIGN; ISSUES AB Guidelines are suggested for determining efficacy of products to supplement scaling and root planing in professional, non-surgical treatment of adult periodontitis. They result from an extended process including a conference on clinical trials in gingivitis and periodontitis, a subsequent workshop, and commentary from industrial, academic, professional and governmental members of the periodontal research community on two drafts. Recommendations are made in the broad areas of basic study design, subject and periodontal site selection, clinical management, choice of outcome variables, statistical summarization and analysis, and criteria for acceptance. Prominent dissenting views, with justifications for positions taken here, are also provided. Groundwork is laid for possible future guidelines addressing products for primary prevention or over-the-counter uses, or for determining superiority or equivalence of competing products. However, issues are identified which require further exploration before responsible and widely acceptable recommendations can be made in these areas. The guidelines suggested here are meant to form the basis of an evolving document rather than a static standard. It is suggested that they be reviewed frequently in the light of improvement in the technology available for periodontal research, and the emergence of products representing new approaches to periodontal therapy. C1 UNIV ILLINOIS,DEPT COMMUNITY HLTH,URBANA,IL 61801. UNIV ILLINOIS,DEPT STAT,URBANA,IL 61801. UNIV ILLINOIS,CTR RES ORAL MOLEC BIOL,URBANA,IL 61801. COLUMBIA UNIV,SCH DENT & ORAL SURG,NEW YORK,NY. COLUMBIA UNIV,DIV BIOSTAT,NEW YORK,NY. UNIV MINNESOTA,MINNESOTA CLIN DENT RES CTR,MINNEAPOLIS,MN 55455. EASTMAN DENT CTR,DIV BIOSTAT,ROCHESTER,NY. NIDR,EPIDEMIOL & ORAL DIS PREVENT PROGRAM,BETHESDA,MD 20892. UNIV PENN,DEPT PERIODONT,PHILADELPHIA,PA 19104. UNIV PENN,EPIDEMIOL SECT,PHILADELPHIA,PA 19104. UNIV TEXAS,MD ANDERSON CANC CTR,DEPT BIOMATH,HOUSTON,TX 77030. SUNY BUFFALO,DEPT PERIODONTOL,BUFFALO,NY. SUNY BUFFALO,DEPT ORAL MED,BUFFALO,NY. USN,DENT RES INST,GREAT LAKES,IL. BOSTON UNIV,DEPT MATH,BOSTON,MA 02215. VIRGINIA COMMONWEALTH UNIV,DEPT PERIODONT,RICHMOND,VA. FORSYTH DENT CTR,BOSTON,MA 02115. UNIV MISSOURI,DEPT PERIODONT,KANSAS CITY,MO 64110. UNIV FLORIDA,DEPT STAT,DIV BIOSTAT,GAINESVILLE,FL 32611. SUNY STONY BROOK,DEPT PREVENT MED,STONY BROOK,NY 11794. RP IMREY, PB (reprint author), UNIV ILLINOIS,DEPT MED INFORMAT SCI,URBANA,IL 61801, USA. OI Imrey, Peter/0000-0002-0533-4603 NR 18 TC 19 Z9 19 U1 0 U2 5 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0022-3484 J9 J PERIODONTAL RES JI J. Periodont. Res. PD SEP PY 1994 VL 29 IS 5 BP 348 EP 360 PG 13 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA PM489 UT WOS:A1994PM48900008 PM 7880252 ER PT J AU PAPAPANOU, PN SANDROS, J LINDBERG, K DUNCAN, MJ NIEDERMAN, R NANNMARK, U AF PAPAPANOU, PN SANDROS, J LINDBERG, K DUNCAN, MJ NIEDERMAN, R NANNMARK, U TI PORPHYROMONAS-GINGIVALIS MAY MULTIPLY AND ADVANCE WITHIN STRATIFIED HUMAN JUNCTIONAL EPITHELIUM IN-VITRO SO JOURNAL OF PERIODONTAL RESEARCH LA English DT Note DE P-GINGIVALIS; INVASION; ORAL EPITHELIUM; PERIODONTITIS; ELECTRON MICROSCOPY ID CELLS C1 GOTHENBURG UNIV,DEPT ANAT & CELL BIOL,S-41390 GOTHENBURG,SWEDEN. BIOSURFACE TECHNOL,CAMBRIDGE,MA. FORSYTH DENT CTR,BOSTON,MA 02115. RP PAPAPANOU, PN (reprint author), GOTHENBURG UNIV,DEPT PERIODONTOL,MEDICINAREGATAN 12,S-41390 GOTHENBURG,SWEDEN. FU NIDCR NIH HHS [DE 04881, DE 08415] NR 7 TC 53 Z9 54 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0022-3484 J9 J PERIODONTAL RES JI J. Periodont. Res. PD SEP PY 1994 VL 29 IS 5 BP 374 EP 375 DI 10.1111/j.1600-0765.1994.tb01237.x PG 2 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA PM489 UT WOS:A1994PM48900012 PM 7799218 ER PT J AU JOSHIPURA, KJ KENT, RL DEPAOLA, PF AF JOSHIPURA, KJ KENT, RL DEPAOLA, PF TI GINGIVAL RECESSION - INTRAORAL DISTRIBUTION AND ASSOCIATED FACTORS SO JOURNAL OF PERIODONTOLOGY LA English DT Article DE DENTAL CALCULUS ADVERSE EFFECTS; GINGIVAL RECESSION, TOOTH ABRASION, ORAL HYGIENE, TOOTHBRUSHING ADVERSE EFFECTS; RISK FACTORS ID ROOT SURFACE CARIES; PREVALENCE AB THIS STUDY ASSESSES THE ROLE OF POOR ORAL HYGIENE and forceful toothbrushing as risk factors for recession. As part of a cross-sectional root surface caries study, 298 subjects, 42 to 67 years of age, with at least one exposed root surface, were examined. Since 66% of the root surface exposure and practically all the abrasion was on buccal surfaces, the analyses focused only on the buccal surface. Analysis of variance on subject means for buccal recession showed both calculus and presence of buccal root surfaces with abrasion to be significantly associated with recession after adjusting for age and gender. Root surface abrasion was considered a surrogate variable for forceful brushing. An additional analysis utilized means for each tooth, aggregating across subjects. For each of the 32 tooth types mean buccal recession, percent of exposed root surfaces with abrasion (%ra), and mean debris and calculus scores were calculated. Partial correlation coefficients across tooth types between recession and calculus, adjusting for abrasion, and for recession and abrasion adjusting for calculus, were 0.55. Interpretation of the %ra as a crude measure of forceful brushing is supported by its strong negative correlation across tooth types, with mean debris (r = -0.8) and mean calculus (r = -0.7). Separate analyses on premolars and on molars suggested that recession on premolars may be primarily due to brushing force and on the molars may be primarily due to debris and calculus. The findings suggest that recession is positively associated with percent abrasion (reflecting forceful brushing) and with poor oral hygiene. C1 FORSYTH DENT CTR,DEPT BIOSTAT,BOSTON,MA 02115. HARVARD UNIV,SCH DENT MED,DEPT DENT CARE ADM,BOSTON,MA 02115. FU NIDCR NIH HHS [DE07009] NR 17 TC 39 Z9 41 U1 0 U2 1 PU AMER ACAD PERIODONTOLOGY PI CHICAGO PA 737 NORTH MICHIGAN AVENUE, SUITE 800, CHICAGO, IL 60611-2690 SN 0022-3492 J9 J PERIODONTOL JI J. Periodont. PD SEP PY 1994 VL 65 IS 9 BP 864 EP 871 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA PG784 UT WOS:A1994PG78400010 PM 7990024 ER PT J AU KAPUR, KK DEUPREE, R DENT, RJ HASSE, AL AF KAPUR, KK DEUPREE, R DENT, RJ HASSE, AL TI A RANDOMIZED CLINICAL-TRIAL OF 2 BASIC REMOVABLE PARTIAL DENTURE DESIGNS .1. COMPARISONS OF 5-YEAR SUCCESS RATES AND PERIODONTAL HEALTH SO JOURNAL OF PROSTHETIC DENTISTRY LA English DT Article ID COOPERATIVE-DENTAL-IMPLANT; BLADE-VENT IMPLANTS; ABUTMENT TEETH; PLACEMENT; MOBILITY; MOVEMENT AB A randomized clinical trial was undertaken to compare the effectiveness of two partial denture designs, one with I-bar (bar) and the other with circumferential retainers (circumferential), in 134 patients with Kennedy class I and class II edentulous conditions. A total of 30 partial dentures were considered failures, five because of abutment failures and 25 because of the lack of removable partial denture use for eating. The 5-year success rate of 71.3% for the circumferential design did not differ significantly from the 76.6% for the bar design (p > 0.05). There were no discernible changes in the nine periodontal health components of abutment teeth with either of the two designs after 60 months. The results indicate that the two designs do not differ significantly in terms of success rates, maintenance care, and effects on abutment teeth. A well-constructed removable partial denture of either design, supported by favorable abutments and accompanied by a regular recall program offers a satisfactory treatment modality. C1 UNIV CALIF LOS ANGELES,SCH DENT,LOS ANGELES,CA 90024. RP KAPUR, KK (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,11301 WILSHIRE BLVD,LOS ANGELES,CA 90073, USA. NR 34 TC 37 Z9 40 U1 2 U2 14 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0022-3913 J9 J PROSTHET DENT JI J. Prosthet. Dent. PD SEP PY 1994 VL 72 IS 3 BP 268 EP 282 DI 10.1016/0022-3913(94)90340-9 PG 15 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA PD992 UT WOS:A1994PD99200009 PM 7965900 ER PT J AU KREIMAN, J GERRATT, BR BERKE, GS AF KREIMAN, J GERRATT, BR BERKE, GS TI THE MULTIDIMENSIONAL NATURE OF PATHOLOGICAL VOCAL QUALITY SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID ROUGHNESS SEVERITY RATINGS; SPECTRAL NOISE-LEVELS; ABNORMAL VOICE QUALITIES; RELIABILITY; BREATHINESS; PERCEPTION; HOARSENESS; DYSPHONIA AB Although the terms ''breathy'' and ''rough'' are frequently applied to pathological voices, widely accepted definitions are not available and the relationship between these qualities is not understood. To investigate these matters, expert listeners judged the dissimilarity of pathological voices with respect to breathiness and roughness. A second group of listeners rated the voices on unidimensional scales for the same qualities. Multidimensional scaling analyses suggested that breathiness and roughness are related, multidimensional constructs. Unidimensional ratings of both breathiness and roughness were necessary to describe patterns of similarity with respect to either quality. Listeners differed in the relative importance given to different aspects of voice quality, particularly when judging roughness. The presence of roughness in a voice did not appear to influence raters' judgments of breathiness; however, judgments of roughness were heavily influenced by the degree of breathiness, the particular nature of the influence varying from listener to listener. Differences in how listeners focus their attention on the different aspects of multidimensional perceptual qualities apparently are a significant source of interrater unreliability (noise) in voice quality ratings. C1 W LOS ANGELES VET AFFAIRS MED CTR,AUDIOL & SPEECH PATHOL 126,LOS ANGELES,CA 90073. RP KREIMAN, J (reprint author), UNIV CALIF LOS ANGELES,SCH MED,DIV HEAD & NECK SURG,CHS 62-132,LOS ANGELES,CA 90024, USA. FU NIDCD NIH HHS [NIDCD DC 01797] NR 46 TC 77 Z9 79 U1 0 U2 0 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD SEP PY 1994 VL 96 IS 3 BP 1291 EP 1302 DI 10.1121/1.410277 PG 12 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA PG307 UT WOS:A1994PG30700005 PM 7962996 ER PT J AU HOU, ZZ PAVLOVIC, CV AF HOU, ZZ PAVLOVIC, CV TI EFFECTS OF TEMPORAL SMEARING ON TEMPORAL RESOLUTION, FREQUENCY-SELECTIVITY, AND SPEECH-INTELLIGIBILITY SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID HEARING-IMPAIRED LISTENERS; COCHLEAR IMPLANTS; NOISE; RECEPTION; LEVEL; SENTENCES; THRESHOLD; WINDOW; SHAPE; AGE AB Envelopes of speech were smeared in 23 parallel frequency channels. The smeared speech was presented to normal-hearing listeners, and the effects of different smearing magnitudes on speech intelligibility were measured by obtaining speech recognition scores. It was demonstrated theoretically and experimentally that the system consisting of the computer smearing and the auditory system had reduced temporal resolution but nearly normal frequency resolution. Speech intelligibility of the processed vowel-consonant nonsense syllables was tested for low- and high-pass filter conditions. The overall speech recognition scores as well as the recognition scores of the consonants grouped according to articulatory features were analyzed. The results indicated that smearing with a narrow temporal window did not degrade speech. The larger equivalent rectangular durations (ERDs) of the resultant temporal window (RTW) of the combined system (temporal smearing plus auditory system) produced a small but significant reduction in speech intelligibility for the low-pass filter condition. Scores for the RTWs>l6 ms were significantly different from the score for the 7.7-ms RTW for the high-pass filter condition; but this effect was small and did not differ across articulatory features. C1 UNIV IOWA,DEPT SPEECH PATHOL & AUDIOL,IOWA CITY,IA 52242. UNIV PROVENCE,AIX EN PROVENCE,FRANCE. RP HOU, ZZ (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT AUDIOL,BOSTON,MA 02114, USA. NR 33 TC 6 Z9 7 U1 0 U2 0 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD SEP PY 1994 VL 96 IS 3 BP 1325 EP 1340 DI 10.1121/1.410279 PG 16 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA PG307 UT WOS:A1994PG30700008 PM 7962999 ER PT J AU MATTHIES, ML SVIRSKY, MA LANE, HL PERKELL, JS AF MATTHIES, ML SVIRSKY, MA LANE, HL PERKELL, JS TI A PRELIMINARY-STUDY OF THE EFFECTS OF COCHLEAR IMPLANTS ON THE PRODUCTION OF SIBILANTS SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID POSTLINGUALLY DEAFENED ADULTS; SPEECH PRODUCTION; USERS; RECOGNITION AB The potential influence of auditory information in the production of /s/ and /integral/ was explored for postlingually deafened adults with four-channel Ineraid cochlear implants. Analyses of the spectra of the sibilant sounds were compared for speech obtained prior to implant activation; after early implant use and after 6 months of use. In addition, the output of the Ineraid device (measured at each of the four electrodes) was analyzed with pre- and postactivation speech samples to explore whether the speech production changes were potentially audible to the cochlear-implant user. Results indicated that subjects who showed abnormally low or incorrect contrast between /s/ and /integral/ preactivation, and who received significant auditory benefit from their implants were able to increase the distinctiveness of their productions of the two speech sounds. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OTOLARYNGOL,BOSTON,MA 02114. NORTHEASTERN UNIV,BOSTON,MA 02115. RP MATTHIES, ML (reprint author), MIT,ELECTR RES LAB,ROOM 36-511,50 VASSAR ST,CAMBRIDGE,MA 02139, USA. RI Svirsky, Mario/A-4160-2008 OI Svirsky, Mario/0000-0002-9238-0682 FU NIDCD NIH HHS [DC01291, NIDCD DC00361] NR 22 TC 26 Z9 26 U1 0 U2 1 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD SEP PY 1994 VL 96 IS 3 BP 1367 EP 1373 DI 10.1121/1.410281 PG 7 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA PG307 UT WOS:A1994PG30700011 PM 7963001 ER PT J AU SAGIE, A SCHWAMMENTHAL, E NEWELL, JB HARRELL, L JOZIATIS, TB WEYMAN, AE LEVINE, RA PALACIOS, IF AF SAGIE, A SCHWAMMENTHAL, E NEWELL, JB HARRELL, L JOZIATIS, TB WEYMAN, AE LEVINE, RA PALACIOS, IF TI SIGNIFICANT TRICUSPID REGURGITATION IS A MARKER FOR ADVERSE OUTCOME IN PATIENTS UNDERGOING PERCUTANEOUS BALLOON MITRAL VALVULOPLASTY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID VALVE REPLACEMENT; ANNULOPLASTY; QUANTIFICATION; VALVOTOMY; STENOSIS; DISEASE AB Objectives. This study examined the association between the presence of tricuspid regurgitation and immediate and late adverse outcomes in patients undergoing balloon mitral valvuloplasty. Background. Significant tricuspid regurgitation has an adverse impact on morbidity and mortality in patients undergoing mitral valve surgery for mitral stenosis. Methods. We studied 318 consecutive patients (mean [+/-SI] age 54 +/- 15 years) who underwent balloon mitral valvuloplasty and had color Doppler echocardiographic studies before the procedure. Patients were classified into three groups: 221 with no or mild (69%), 60 with moderate (19%) and 37 with severe (12%) tricuspid regurgitation. Clinical follow-up ranged from 6 to 62 months. Results. Before mitral valvuloplasty, increasing degrees of tricuspid regurgitation were associated with a smaller initial mitral valve area (p < 0.05), higher echocardiographic score (p < 0.05), lower cardiac output (p < 0.01) and higher pulmonary vascular resistance (p < 0.01). Although the initial success rate did not differ significantly between groups, patients with a higher degree of tricuspid regurgitation had less optimal results, as reflected by a smaller absolute increase in mitral valve area (1.02 vs. 0.9 vs. 0.7 cm(2), p < 0.01). The estimated 4-year event-free survival rate (freedom from death, mitral valve surgery, repeat valvuloplasty and heart failure) was lower for the group with severe tricuspid regurgitation (68% vs. 58% vs. 35%, p < 0.0001). At 4 years, 94% of patients with mild tricuspid regurgitation were alive compared with 90% and 69%, respectively, of patients with moderate or severe tricuspid regurgitation (p < 0.0001). Cox proportional analysis identified tricuspid regurgitation as an independent predictor of late outcome (p < 0.001). Conclusions. Patients with mitral stenosis and severe tricuspid regurgitation undergoing mitral valvuloplasty have advanced mitral valve and pulmonary vascular disease, suboptimal immediate results and poor late outcome. C1 MASSACHUSETTS GEN HOSP,CARDIAC CATHETERIZAT LAB,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MED,CARDIAC ULTRASOUND LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 31 TC 63 Z9 68 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD SEP PY 1994 VL 24 IS 3 BP 696 EP 702 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PH377 UT WOS:A1994PH37700017 PM 8077541 ER PT J AU BASSI, D KOLLIAS, N FERNANDEZDELCASTILLO, C FOITZIK, T WARSHAW, AL RATTNER, DW AF BASSI, D KOLLIAS, N FERNANDEZDELCASTILLO, C FOITZIK, T WARSHAW, AL RATTNER, DW TI IMPAIRMENT OF PANCREATIC MICROCIRCULATION CORRELATES WITH THE SEVERITY OF ACUTE EXPERIMENTAL PANCREATITIS SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID ORGAN-REFLECTANCE SPECTROPHOTOMETRY; HEMOPERFUSION; HEMODYNAMICS; SHOCK; LIVER; RATS AB BACKGROUND: Altered microcirculatory perfusion may be an important factor in the pathogenesis of necrotizing pancreatitis. Diffuse reflectance spectroscopy (DRS) can measure dynamic alterations in the microcirculation over a larger area than intravital microscopy. STUDY DESIGN: We used DRS to characterize changes in the microcirculation during the evolution of pancreatitis of varying severity. Male Sprague Dawley rats (330 to 400 g) were randomly allocated to four groups: control (n=18), mild pancreatitis (n=18), moderate pancreatitis (n=18), or severe pancreatitis (n=34). Within each group, rats were studied 0.5, 3.0, or 6.0 hours after induction of pancreatitis to determine total hemoglobin content (IHb) and hemoglobin oxygenation (ISO2). RESULTS: Total hemoglobin content in the pancreas remained constant in all groups. Hemoglobin oxygenation increased significantly in rats in the control group and in rats with mild pancreatitis for the duration of the experiment, but not in rats with moderate or severe pancreatitis. Rats with severe pancreatitis had a significant decrease in ISO2 six hours after the induction of pancreatitis compared with baseline values (49.18 +/- 1.55 versus 52.01 +/- 0.19, p<0.01) as well as rats in the control group that were studied after six hours (49.18 +/- 1.55 versus 55.92 +/- 1.07, p<0.02). Furthermore, there was marked variability in IHb and ISO2 at different locations within the same pancreas in rats with severe pancreatitis, which was not observed in the control group or in the rats with mild or moderate pancreatitis. CONCLUSIONS: Impaired microcirculatory perfusion characterizes severe, but not mild, pancreatitis. The predominant early change is stasis rather than vasoconstriction. As the changes become more severe, necrosis occurs in a heterogeneous distribution. C1 MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT DERMATOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 22 TC 92 Z9 94 U1 0 U2 0 PU AMER COLL SURGEONS PI CHICAGO PA 54 EAST ERIE ST, CHICAGO, IL 60611 SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 1994 VL 179 IS 3 BP 257 EP 263 PG 7 WC Surgery SC Surgery GA PF153 UT WOS:A1994PF15300001 PM 8069418 ER PT J AU MAHONEY, J DRINKA, TJK ABLER, R GUNTERHUNT, G MATTHEWS, C GRAVENSTEIN, S CARNES, M AF MAHONEY, J DRINKA, TJK ABLER, R GUNTERHUNT, G MATTHEWS, C GRAVENSTEIN, S CARNES, M TI SCREENING FOR DEPRESSION - SINGLE QUESTION VERSUS GDS SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Note ID POPULATION C1 UNIV WISCONSIN,DEPT MED GERIATR,MADISON,WI. ROCKY MT REHABIL INST,AURORA,CO. UNIV WISCONSIN,SCH SOCIAL WORK,MADISON,WI 53706. UNIV WISCONSIN,DEPT MED NEUROL,MADISON,WI. RP MAHONEY, J (reprint author), WILLIAM S MIDDLETON MEM VET ADM MED CTR,GRECC,2500 OVERLOOK TERRACE,MADISON,WI 53705, USA. RI Gravenstein, Stefan/G-1681-2011 NR 17 TC 139 Z9 139 U1 0 U2 4 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 SEP PY 1994 VL 42 IS 9 BP 1006 EP 1008 PG 3 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA PE832 UT WOS:A1994PE83200019 PM 8064088 ER PT J AU HOLTZMAN, EJ KOLAKOWSKI, LF STOW, JL BROWN, D AUSIELLO, DA AF HOLTZMAN, EJ KOLAKOWSKI, LF STOW, JL BROWN, D AUSIELLO, DA TI FUNCTIONAL-CHARACTERIZATION OF CNDI MUTATIONS IN THE VASOPRESSIN V2 RECEPTOR USING EPITOPE-TAGGED RECEPTORS SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,RENAL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 273 EP 273 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77100113 ER PT J AU HOZAWA, S KOLAKOWSKI, LF AUSIELLO, DA HOLTZMAN, EJ AF HOZAWA, S KOLAKOWSKI, LF AUSIELLO, DA HOLTZMAN, EJ TI ISOLATION AND CHARACTERIZATION OF THE 5'-FLANKING REGIONS FROM 2 HUMAN COLLECTING DUCT-SPECIFIC GENES INVOLVED IN WATER HOMEOSTASIS - AVPR2 AND AQP2 SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,RENAL UNIT,BOSTON,MA 02114. 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 273 EP 273 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77100114 ER PT J AU JUNG, FF TANG, SS SABOLIC, I VERBAVATZ, JM DIAMANT, D BROWN, D INGELFINGER, JR AF JUNG, FF TANG, SS SABOLIC, I VERBAVATZ, JM DIAMANT, D BROWN, D INGELFINGER, JR TI ANGIOTENSIN-II (ANG-II) UP-REGULATES CHIP-28 EXPRESSION IN IMMORTALIZED, TRANSFORMED RAT PROXIMAL TUBULE CELLS (IRPTC) SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 2 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 274 EP 274 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77100117 ER PT J AU KATSURA, T VERBAVATZ, JM FARIHAS, J MA, T VERKMAN, AS AUSIELLO, DA BROWN, D AF KATSURA, T VERBAVATZ, JM FARIHAS, J MA, T VERKMAN, AS AUSIELLO, DA BROWN, D TI LOCALIZATION AND EXPRESSION OF FUNCTIONAL AQUAPORIN-2 (AQP2) AND CHIP28 IN STABLY TRANSFECTED LLC-PK1 CELLS SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,RENAL UNIT,BOSTON,MA 02114. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 274 EP 274 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77100118 ER PT J AU PRAT, AG JACKSON, GR AUSIELLO, DA AF PRAT, AG JACKSON, GR AUSIELLO, DA TI ROLE OF THE ACTIN CYTOSKELETON ON THE CYSTIC-FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR (CFTR) CHANNEL FUNCTION SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,RENAL UNIT,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. NR 1 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 297 EP 297 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77100206 ER PT J AU PLOTKIN, M TANG, SS INGELFINGER, J GULLANS, SR AF PLOTKIN, M TANG, SS INGELFINGER, J GULLANS, SR TI GLYT2 GLYCINE TRANSPORTER EXPRESSION AND REGULATION IN RAT-KIDNEY AND BRAIN SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 BRIGHAM & WOMENS HOSP,DIV RENAL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,PEDIAT NEPHROL LAB,BOSTON,MA 02114. NR 0 TC 2 Z9 2 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 318 EP 318 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77100291 ER PT J AU LAFFEL, L WARRAM, J KROLEWSKI, A AF LAFFEL, L WARRAM, J KROLEWSKI, A TI GLYCEMIC CONTROL DOES NOT PREDICT PROGRESSION FROM LOW TO HIGH MICROALBUMINURIA (MA) IN INSULIN-DEPENDENT DIABETES-MELLITUS (IDDM) SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 JOSLIN DIABET CTR,BOSTON,MA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 379 EP 379 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77100532 ER PT J AU WEINRAUCH, L DELIA, J GLEASON, R MANN, D KEOUGH, J KENNEDY, F AF WEINRAUCH, L DELIA, J GLEASON, R MANN, D KEOUGH, J KENNEDY, F TI GENDER DIFFERENCES IN COMPLICATIONS OF DIABETICS WITH PROTEINURIA - AUTONOMIC NERVOUS-SYSTEM TESTS SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 JOSLIN DIABET CTR,BOSTON,MA. MAYO CLIN & MAYO FDN,ROCHESTER,MN 55905. 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 386 EP 386 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77100559 ER PT J AU HAKIM, RM TOLKOFFRUBIN, N HIMMELFARB, J WINGARD, RL PARKER, RA AF HAKIM, RM TOLKOFFRUBIN, N HIMMELFARB, J WINGARD, RL PARKER, RA TI A MULTICENTER COMPARISON OF BIOINCOMPATIBLE (BICM) AND BIOCOMPATIBLE (BCM) MEMBRANES IN THE TREATMENT OF ACUTE-RENAL-FAILURE (ARF) SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 VANDERBILT UNIV,MED CTR,NASHVILLE,TN 37240. MAINE MED CTR,PORTLAND,ME 04102. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 20 Z9 20 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 394 EP 394 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77100592 ER PT J AU PARKER, RA HIMMELFARB, J TOKOFFRUBIN, N WINGARD, RL HAKIM, RM AF PARKER, RA HIMMELFARB, J TOKOFFRUBIN, N WINGARD, RL HAKIM, RM TI SURVIVAL OF DIALYSIS DEPENDENT ACUTE-RENAL-FAILURE (ARF) PATIENTS PREDICTED BY APACHE-II (APII) SCORE SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 VANDERBILT UNIV,MED CTR,NASHVILLE,TN 37240. MAINE MED CTR,PORTLAND,ME 04102. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 4 Z9 4 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 402 EP 402 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77100625 ER PT J AU BROSIUS, FC DESHMUKH, G JACOB, H WILDE, D ALPER, SL AF BROSIUS, FC DESHMUKH, G JACOB, H WILDE, D ALPER, SL TI AE GENE MICROSATELLITE SEQUENCES AND AE2 MESSENGER-RNA EXPRESSION IN SMALL CEREBRAL-ARTERIES OF STROKE-PRONE SPONTANEOUSLY HYPERTENSIVE RATS (SHRSP) SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 UNIV MICHIGAN,SCH MED,ANN ARBOR,MI 48104. VAMC,ANN ARBOR,MI. BETH ISRAEL HOSP,BOSTON,MA 02215. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 535 EP 535 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77101158 ER PT J AU WENZEL, UO FOUQUERAY, B KARAMITSOS, C BHANDARI, B VALENTE, AJ ABBOUD, HE AF WENZEL, UO FOUQUERAY, B KARAMITSOS, C BHANDARI, B VALENTE, AJ ABBOUD, HE TI THROMBIN INDUCES MONOCYTE CHEMOTACTIC PROTEIN-1 (MCP-1) PRODUCTION IN VASCULAR SMOOTH-MUSCLE CELLS (VSMC) DERIVED FROM HUMAN RENAL-ARTERIES SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT PATHOL,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 553 EP 553 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77101230 ER PT J AU WITZGALL, R OLEARY, E KIM, SS BONVENTRE, JV AF WITZGALL, R OLEARY, E KIM, SS BONVENTRE, JV TI IDENTIFICATION OF CONSENSUS BINDING MOTIF FOR THE ZINC FINGERS OF KID-1 SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 641 EP 641 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77101579 ER PT J AU MEJIA, C SILVA, P GUNNING, M AF MEJIA, C SILVA, P GUNNING, M TI KINETIC-STUDIES OF C-TYPE NATRIURETIC PEPTIDE (CNP) SPECIFIC GUANYLATE-CYCLASE (GC) OF SHARK RECTAL GLAND (SRG) SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 JOSLIN CTR,BOSTON,MA. NEW ENGLAND DEACONESS HOSP,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA 02115. 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 664 EP 664 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77101672 ER PT J AU CHOUDHURY, GG ABBOUD, HE AF CHOUDHURY, GG ABBOUD, HE TI VANADATE ACTIVATES PHOSPHATIDYLINOSITOL-3 KINASE (PI3 KINASE) VIA ENHANCED TYROSINE PHOSPHORYLATION OF PLATELET-DERIVED GROWTH-FACTOR RECEPTOR TYPE-BETA (PDGFR-BETA) IN HUMAN MESANGIAL CELLS (HMC) SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 690 EP 690 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77101775 ER PT J AU MARRA, F BONEWALD, LF PARK, IS PARKSNYDER, S WOODRUFF, KA ABBOUD, HE AF MARRA, F BONEWALD, LF PARK, IS PARKSNYDER, S WOODRUFF, KA ABBOUD, HE TI SECRETION OF MULTIPLE FORMS OF LATENT TRANSFORMING GROWTH-FACTOR-BETA BY HUMAN MESANGIAL CELLS SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 UT,HSCSA,DEPT MED,SAN ANTONIO,TX. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 697 EP 697 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77101802 ER PT J AU AMEDTRADUEGE, AM MAJEWSKI, RR VERROUST, PJ HAMMOND, TG AF AMEDTRADUEGE, AM MAJEWSKI, RR VERROUST, PJ HAMMOND, TG TI HETEROTRIMERIC G-PROTEINS MEDIATE STIMULATION OF RENAL CORTICAL ENDOSOMAL FUSION BY SCAVENGER PATHWAY RECEPTORS SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 UNIV WISCONSIN,MADISON,WI 53706. WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI 53705. HOP TENON,INSERM,U64,F-75970 PARIS 20,FRANCE. NR 2 TC 1 Z9 1 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 706 EP 706 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77101839 ER PT J AU KAWASHIMA, A KINANE, TB SHANG, C NISHIMOTO, I ERCOLANI, L AF KAWASHIMA, A KINANE, TB SHANG, C NISHIMOTO, I ERCOLANI, L TI THE ONCOGENE GIP2 REPRESSES ENDOGENOUS C(ALPHA-I2) TRANSCRIPTION BY INHIBITION OF TRANSCRIPTION FACTOR SP1 IN LLC-PK(1) RENAL-CELLS SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,RENAL UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CARDIAC UNIT,BOSTON,MA 02114. NR 1 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 717 EP 717 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77101883 ER PT J AU KINANE, TB FINDER, J KAWASHIMA, A SHANG, C ABBATE, FM BROWN, D HABER, D RAUSCHER, F SUKHATME, V ERCOLANI, L AF KINANE, TB FINDER, J KAWASHIMA, A SHANG, C ABBATE, FM BROWN, D HABER, D RAUSCHER, F SUKHATME, V ERCOLANI, L TI REPRESSION OF THE G-ALPHA-I-2 PROTOONCOGENE IN RENAL-CELLS BY WT1 SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,RENAL UNIT,BOSTON,MA 02114. 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 718 EP 718 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77101887 ER PT J AU KIYOMOTO, H ABBOUD, HE FOUQUERAY, BL CHOUDHURY, GG AF KIYOMOTO, H ABBOUD, HE FOUQUERAY, BL CHOUDHURY, GG TI PHORBOL-MYRISTATE ACETATE (PMA)-INDUCED INHIBITION OF THE CYTOPLASMIC TYROSINE PHOSPHATASE PTP1B ENHANCES TYROSINE PHOSPHORYLATION IN HUMAN MESANGIAL CELLS (HMC) SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 719 EP 719 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77101891 ER PT J AU KREISBERG, J GARONI, J RADNIK, R KREISBERG, S AF KREISBERG, J GARONI, J RADNIK, R KREISBERG, S TI PHORBOL-MYRISTATE ACETATE (PMA) INCREASES FIBRONECTIN (FN) GENE-EXPRESSION THROUGH A CAMP-RESPONSIVE ELEMENT (CRE) IN MESANGIAL CELL-CULTURES SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 UT,HSCSA,DEPT PATHOL,SAN ANTONIO,TX. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 720 EP 720 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77101894 ER PT J AU MANGE, KC STANTON, RC AF MANGE, KC STANTON, RC TI OXIDATIVE STRESS INHIBITS THE RELEASE OF 6-PHOSPHOGLUCONATE DEHYDROGENASE (6PGD) IN PERMEABILIZED CELLS VIA KINASE-DEPENDENT MECHANISMS SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NEW ENGLAND DEACONESS HOSP,BOSTON,MA 02215. JOSLIN DIABET FDN INC,CTR DIABET,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 1 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 723 EP 723 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77101905 ER PT J AU TANG, SS DIAMANT, D JUNG, FF INGELFINGER, JR AF TANG, SS DIAMANT, D JUNG, FF INGELFINGER, JR TI IMMORTALIZED RAT PROXIMAL TUBULAR CELLS (IRPTC) CONTAIN NUCLEAR ANGIOTENSIN-II (ANG-II) BINDING-SITES SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 2 TC 1 Z9 1 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 733 EP 733 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77101945 ER PT J AU BIANCONE, L AHN, H DEMARTINO, C ANDRES, G STAMENKOVIC, I AF BIANCONE, L AHN, H DEMARTINO, C ANDRES, G STAMENKOVIC, I TI INHIBITION OF CD40-DEPENDENT B-CELL ACTIVATION IN MICE WITH MEMBRANOUS GLOMERULONEPHRITIS (MGN) SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02114. IST DERMATOL S GALLICIANO,ROME,ITALY. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 740 EP 740 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77101975 ER PT J AU FOUQUERAY, B GRANDALIANO, G WENZEL, U BHANDARI, B WOODRUFF, K VALENTE, A ABBOUD, HE AF FOUQUERAY, B GRANDALIANO, G WENZEL, U BHANDARI, B WOODRUFF, K VALENTE, A ABBOUD, HE TI CYTOKINES AND THROMBIN REGULATE MCP-1 GENE-EXPRESSION IN BOVINE GLOMERULAR ENDOTHELIAL-CELLS SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. RI Grandaliano, Giuseppe/G-2963-2012 NR 0 TC 5 Z9 5 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 747 EP 747 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77102002 ER PT J AU GENG, L ANDRES, G MCCLUSKEY, RT AF GENG, L ANDRES, G MCCLUSKEY, RT TI INDUCTION OF HEYMANN NEPHRITIS (HN) WITH HUMAN URINARY GP330 SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 779 EP 779 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77102127 ER PT J AU JUNG, F BACHINSKY, D TANG, SS ZHENG, G DIAMANT, D MCCLUSKEY, R BROWN, D INGELFINGER, J AF JUNG, F BACHINSKY, D TANG, SS ZHENG, G DIAMANT, D MCCLUSKEY, R BROWN, D INGELFINGER, J TI IMMORTALIZED RAT PROXIMAL TUBULE CELL-LINES EXPRESSING GP330 SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,PATHOL RES & RENAL LABS,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,PEDIAT NEPHROL LABS,BOSTON,MA 02114. NR 2 TC 1 Z9 1 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 783 EP 783 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77102146 ER PT J AU HAYES, G FORGO, J BRINGHURST, FR BIBER, J SEGRE, G MURER, H AF HAYES, G FORGO, J BRINGHURST, FR BIBER, J SEGRE, G MURER, H TI IN-VITRO EXPRESSION OF THE CLONED PARATHYROID-HORMONE (PTH) RECEPTOR IN DIFFERENTIATED RENAL EPITHELIAL-CELLS SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 UNIV ZURICH,INST PHYSIOL,CH-8006 ZURICH,SWITZERLAND. MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 881 EP 881 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77102536 ER PT J AU KELLY, KJ WILLIAMS, WW COLVIN, RB MEEHAN, SM SPRINGER, TA GUTIERREZRAMOS, JC BONVENTRE, JV AF KELLY, KJ WILLIAMS, WW COLVIN, RB MEEHAN, SM SPRINGER, TA GUTIERREZRAMOS, JC BONVENTRE, JV TI INTERCELLULAR-ADHESION MOLECULE-1 (ICAM-1) KNOCKOUT MICE ARE PROTECTED AGAINST RENAL ISCHEMIA SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 3 Z9 3 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 900 EP 900 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77102612 ER PT J AU RABB, H MENDIOLA, C SABA, SR DIETZ, J SMITH, CW BONVENTRE, JV RAMIREZ, G AF RABB, H MENDIOLA, C SABA, SR DIETZ, J SMITH, CW BONVENTRE, JV RAMIREZ, G TI ANTIBODIES TO P-SELECTIN AND ICAM-1 PROTECT KIDNEYS FROM ISCHEMIC-REPERFUSION INJURY SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 UNIV S FLORIDA,COLL MED,JA HALEY VET ADM HOSP,TAMPA,FL 33612. BAYLOR COLL MED,HOUSTON,TX 77030. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114. NR 0 TC 7 Z9 7 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 907 EP 907 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77102638 ER PT J AU SPECH, RA WITZGALL, R BONVENTRE, JV AF SPECH, RA WITZGALL, R BONVENTRE, JV TI OVEREXPRESSION OF THE CYTOSOLIC PLA(2) (CPLA/(2)) ENHANCES SUSCEPTIBILITY TO OXIDATIVE INJURY IN LLC-PK1 CELLS SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 0 TC 3 Z9 3 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 909 EP 909 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77102649 ER PT J AU ANDERSON, S OYAMA, TT JUNG, FF INGELFINGER, JR AF ANDERSON, S OYAMA, TT JUNG, FF INGELFINGER, JR TI RENIN-ANGIOTENSIN SYSTEM AND THE AGING KIDNEY SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 OREGON HLTH SCI UNIV,PORTLAND,OR 97201. VET ADM MED CTR,PORTLAND,OR 97207. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 2 TC 4 Z9 4 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 937 EP 937 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77102758 ER PT J AU JI, LN KROLEWSKI, AS AF JI, LN KROLEWSKI, AS TI HUMAN SA GENE POLYMORPHISM AND SUSCEPTIBILITY TO DIABETIC NEPHROPATHY (DN) IN IDDM PATIENTS SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,BOSTON,MA 02115. NR 1 TC 2 Z9 2 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 966 EP 966 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77102875 ER PT J AU KASINATH, BS GRELLIER, P TERHUNE, WC MALDONADO, R CHOUDHURY, GG ABBOUD, SL AF KASINATH, BS GRELLIER, P TERHUNE, WC MALDONADO, R CHOUDHURY, GG ABBOUD, SL TI HIGH GLUCOSE MEDIUM REDUCES GLOMERULAR-BASEMENT-MEMBRANE (GBM) HEPARAN-SULFATE PROTEOGLYCAN (HSPG) CORE PROTEIN GENE-EXPRESSION IN GLOMERULAR EPITHELIAL-CELLS (GEC) SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 967 EP 967 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77102877 ER PT J AU KIYOMOTO, H CHOUDHURY, GG FOUQUERAY, BL ABBOUD, HE AF KIYOMOTO, H CHOUDHURY, GG FOUQUERAY, BL ABBOUD, HE TI ACTIVATION OF GLOMERULAR PHOSPHOTYROSINE PHOSPHATASE IN STREPTOZOTOCIN-INDUCED DIABETES (STZD) IN THE RAT SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 967 EP 967 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77102879 ER PT J AU PARK, IS KIYOMOTO, H BARNES, JL WOODRUFF, K ABBOUD, HE AF PARK, IS KIYOMOTO, H BARNES, JL WOODRUFF, K ABBOUD, HE TI GLOMERULAR MONOCYTE INFILTRATION IN EARLY STREPTOZOTOCIN-INDUCED DIABETES (STZD) IS ASSOCIATED WITH INCREASED EXPRESSION OF TRANSFORMING GROWTH-FACTOR-BETA (TGF-BETA) AND CELLULAR FIBRONECTIN (CFN) SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX. NR 0 TC 8 Z9 8 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 971 EP 971 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77102894 ER PT J AU YANG, CW HATTORI, M VLASSARA, H HE, CJ STRIKER, GE STRIKER, LJ AF YANG, CW HATTORI, M VLASSARA, H HE, CJ STRIKER, GE STRIKER, LJ TI OVEREXPRESSION OF TGF-BETA-1 MESSENGER-RNA IS ASSOCIATED WITH UP-REGULATION OF GLOMERULAR TENASCIN AND LAMININ GENE-EXPRESSION IN DIABETIC NOD MICE SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK,RCBS,BETHESDA,MD. JOSLIN DIABET CTR,SII,BOSTON,MA. PICOWER INST MED RES,NEW YORK,NY. 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 975 EP 975 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77102911 ER PT J AU MEEHAN, SM MCCLUSKEY, RT ANDERSON, P SCHLOSSMAN, S COLVIN, RB AF MEEHAN, SM MCCLUSKEY, RT ANDERSON, P SCHLOSSMAN, S COLVIN, RB TI EXPRESSION OF TIA-1, A CYTOTOXIC T-CELL PROTEIN, IN RENAL-ALLOGRAFT REJECTION SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 985 EP 985 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77102949 ER PT J AU MURPHY, B GALLON, L WATSCHINGER, B SAYEGH, MH CARPENTER, CB AF MURPHY, B GALLON, L WATSCHINGER, B SAYEGH, MH CARPENTER, CB TI SELF-RESTRICTED T-CELL RECOGNITION OF ALLO-MHC PEPTIDES OCCURS EARLY IN ACUTE RENAL-ALLOGRAFT REJECTION AND IS INHIBITED BY CONVENTIONAL IMMUNOSUPPRESSION SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 985 EP 985 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77102951 ER PT J AU STEELE, DJR AUCHINCLOSS, H AF STEELE, DJR AUCHINCLOSS, H TI THE ROLE OF CD4+ CELLS AND RECIPIENT VERSUS DONOR MHC CLASS-II ANTIGENS IN ALLOANTIBODY PRODUCTION SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 990 EP 990 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77102970 ER PT J AU CASASNOVAS, JM SPRINGER, TA AF CASASNOVAS, JM SPRINGER, TA TI PATHWAY OF RHINOVIRUS DISRUPTION BY SOLUBLE INTERCELLULAR-ADHESION MOLECULE-1 (ICAM-1) - AN INTERMEDIATE IN WHICH ICAM-1 IS BOUND AND RNA IS RELEASED SO JOURNAL OF VIROLOGY LA English DT Article ID HELA-CELLS; LOW PH; RECEPTOR; POLIOVIRUS; NEUTRALIZATION; BINDING; ENTRY; IMMUNOGLOBULIN; MECHANISM; SURFACE AB We have examined the pathway of rhinovirus interaction with soluble intercellular adhesion molecule 1 (sICAM-1). Binding of sICAM-1 to rhinovirus serotypes 3 and 14 gives particles with sedimentation coefficients from 145 to 120S, depending on the amount of sICAM-1 bound. The formation of 120S particles is faster and more extensive at a neutral pH than at an acidic pH. A large number of receptors (>30) can bind to human rhinovirus 3 without disruption. Disruption by sICAM-1 of rhinovirus that yields 80S particles is strongly temperature dependent and is antagonized by a low pH. Interestingly, sICAM-1 remains bound to the viral capsid after RNA is released, although in smaller amounts than those observed for the native virus. We have found heterogeneity both between and within 80S particle preparations in the VP4 content and number of bound receptors. The ability of the virus to remain bound to its receptor during the uncoating process may facilitate the transport of the viral genome into the cytoplasm in vivo. C1 CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RI Casasnovas, Jose/L-6299-2014 OI Casasnovas, Jose/0000-0002-2873-6410 FU NIAID NIH HHS [AI31921] NR 32 TC 49 Z9 49 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 SEP PY 1994 VL 68 IS 9 BP 5882 EP 5889 PG 8 WC Virology SC Virology GA PB785 UT WOS:A1994PB78500061 PM 7914550 ER PT J AU STERN, Y ALBERT, SM SANO, M RICHARDS, M MILLER, L FOLSTEIN, M ALBERT, M BYLSMA, FW LAFLECHE, G AF STERN, Y ALBERT, SM SANO, M RICHARDS, M MILLER, L FOLSTEIN, M ALBERT, M BYLSMA, FW LAFLECHE, G TI ASSESSING PATIENT DEPENDENCE IN ALZHEIMERS-DISEASE SO JOURNALS OF GERONTOLOGY LA English DT Article ID MULTICENTER; PREDICTION AB Background. While cognitive and functional deficits are the hallmark of Alzheimer's disease (AD), loss of social function (and the dependence this implies) is also critical, especially in early stages of disease. Little attention has been directed to this facet of dementing disease. We describe a scale for assessing dependency in AD and present a baseline profile of dependency in a cohort of AD patients. Methods. In a study of the predictors of the course of AD, 233 patients in early stages of disease (modified MMS greater than or equal to 30) were assessed. Psychometric properties of the dependence scale were established. To validate the scale, dependence scores at baseline were correlated with a series of measures assessing cognition and function. The course of dependency over 18 months of follow-up was also analyzed. Results, The scale shows adequate reliability (test-retest, intraclass correlation). Dependence stage was related to other measures of disease severity. Scalogram analysis shows that the dependence scale is consistent with the course of functional loss established for dementing disease. Prospective data indicate sensitivity of the scale to disease progression. Conclusion, Dependency is a distinct, measurable component of dementing disease and should be considered an important outcome in studies of AD. C1 COLUMBIA UNIV,COLL PHYS & SURG,DEPT NEUROL,NEW YORK,NY 10032. COLUMBIA UNIV,COLL PHYS & SURG,DEPT PSYCHIAT,NEW YORK,NY 10032. JOHNS HOPKINS UNIV,DEPT PSYCHIAT & BEHAV SCI,BALTIMORE,MD 21218. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PSYCHIAT,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROL,BOSTON,MA. RP STERN, Y (reprint author), COLUMBIA UNIV,COLL PHYS & SURG,GERTRUDE H SERGIEVSKY CTR,630 W 168TH ST,NEW YORK,NY 10032, USA. FU NIA NIH HHS [AG-07232, AG-07370, AG-08702] NR 18 TC 89 Z9 89 U1 1 U2 6 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 0022-1422 J9 J GERONTOL JI J. Gerontol. PD SEP PY 1994 VL 49 IS 5 BP M216 EP M222 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA PE106 UT WOS:A1994PE10600017 PM 8056940 ER PT J AU SCHUKNECHT, HF NADOL, JB AF SCHUKNECHT, HF NADOL, JB TI TEMPORAL BONE PATHOLOGY IN A CASE OF COGANS-SYNDROME SO LARYNGOSCOPE LA English DT Article ID SYSTEMIC VASCULITIS; DEAFNESS AB Cogan's syndrome (CS) presents typical and atypical types. Typically, there are episodes of non-syphilitic keratitis and audiovestibular dysfunction. Atypically, there are inflammatory changes in other eye structures and other organ systems, particularly the cardiovascular system. The temporal bone pathology in a case of CS shows changes that are similar to those observed in other autoimmune disorders associated with audiovestibular dysfunction. The following pathologic features characterize autoimmune inner ear disease: 1. acute labyrinthitis resulting in atrophy of inner ear tissues including the sense organs and their supporting structures; 2. endolymphatic hydrops; 3. focal and diffuse proliferation of fibrous tissue and bone; and 4. retrograde neuronal degeneration. These pathologic findings are consistent with an inflammatory (and possibly ischemic) attack on the membranous labyrinth. C1 HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02115. RP SCHUKNECHT, HF (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,243 CHARLES ST,BOSTON,MA 02114, USA. FU NIDCD NIH HHS [R01 DC00079] NR 24 TC 41 Z9 42 U1 0 U2 1 PU LARYNGOSCOPE CO PI ST LOUIS PA 10 S BROADWAY 14TH FLOOR, ST LOUIS, MO 63102-1741 SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD SEP PY 1994 VL 104 IS 9 BP 1135 EP 1142 PG 8 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA PF210 UT WOS:A1994PF21000015 PM 8072362 ER PT J AU KAO, YH SORENSON, JA BAHN, MM WINKLER, SS AF KAO, YH SORENSON, JA BAHN, MM WINKLER, SS TI DUAL-ECHO MRI SEGMENTATION USING VECTOR DECOMPOSITION AND PROBABILITY TECHNIQUES - A 2-TISSUE MODEL SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE SEGMENTATION; VOLUME MEASUREMENT; FRACTIONAL VOLUME; IMAGE PROCESSING ID MAGNETIC-RESONANCE IMAGES; CEREBROSPINAL-FLUID SPACES; TEMPORAL-LOBE; GRAY-MATTER; MULTISPECTRAL ANALYSIS; FIELD INHOMOGENEITIES; HIPPOCAMPAL-FORMATION; VOLUME MEASUREMENTS; BRAIN; NOISE AB We combined a vector decomposition technique with Gaussian probability thresholding in feature space to segment normal brain tissues, tumors, or other abnormalities on dual-echo MR images. The vector decomposition technique assigns to each voxel a fractional volume for each of two tissues. A probability threshold, based on an assumed Gaussian probability density function describing random noise, isolates a region in feature space for fractional volume calculation that minimizes contamination from other tissues. The calculated fractional volumes are unbiased estimates of the true fractional volumes. The contrast-to-noise ratio (CNR) between tissues on the segmented images is the same as the Euclidean norm of CNRs in the original images. The method is capable of segmenting more than two tissues from a set of dual-echo images by sequentially analyzing different pairs of tissues. The model is analyzed mathematically and in experiments with a phantom. Two clinical examples are presented. C1 UNIV WISCONSIN,DEPT PHYS,MADISON,WI 53706. UNIV WISCONSIN,DEPT MED PHYS,MADISON,WI 53706. UNIV WISCONSIN,DEPT RADIOL,MADISON,WI 53706. WILLIAM S MIDDLETON MEM VET ADM MED CTR,SERV RADIOL,MADISON,WI. NR 68 TC 13 Z9 13 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0740-3194 J9 MAGNET RESON MED JI Magn.Reson.Med. PD SEP PY 1994 VL 32 IS 3 BP 342 EP 357 DI 10.1002/mrm.1910320310 PG 16 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PE259 UT WOS:A1994PE25900009 PM 7984067 ER PT J AU EDELMAN, RR GAA, JC WEDEEN, VJ LOH, E HARE, JM PRASAD, P LI, W AF EDELMAN, RR GAA, JC WEDEEN, VJ LOH, E HARE, JM PRASAD, P LI, W TI IN-VIVO MEASUREMENT OF WATER DIFFUSION IN THE HUMAN HEART SO MAGNETIC RESONANCE IN MEDICINE LA English DT Note DE DIFFUSION; CARDIAC; MAGNETIC RESONANCE IMAGING; ECHO PLANAR IMAGING ID CORONARY-ARTERY DISEASE; STROKE; MUSCLE; MOTION; FLOW; MRI AB Existing magnetic resonance methods for diffusion imaging, including echo planar, are ineffective in the beating heart due to motion-induced signal attenuation. To overcome this problem, we used a diffusion-weighted stimulated echo-echo planar magnetic resonance imaging sequence. The two lobes of the diffusion-sensitizing gradient were synchronized to the same point in successive cardiac cycles in order to fix the cardiac position and avoid bulk motion effects. The apparent diffusion coefficients (ADCs) of the interventricular septum in 12 healthy subjects for diffusion gradients along the x-, y-, and z-directions were 1.40 +/- 0.27, 1.48 +/- 0.35, and 1.78 +/- 0.27 x 10(-3) mm(2)/s. The ADCs of the interventricular septum ina second group of 15 healthy subjects for diffusion gradients along the short axis, horizontal and vertical long axes were 0.92 +/- 0.15, 1.50 +/- 0.15, and 1.10 +/- 0.24 x 10(-3) mm(2)/s. Because the ADCs were less than the measured values for skeletal muscle and their standard deviations were low, it seems unlikely that bulk motion effects made the dominant contribution to the measured myocardial ADC for the interventricular septum, although motion and/or susceptibility artifacts frequently degraded measurements in the free wall of the left ventricle. Additional evidence that ADC was not predominantly determined by wall motion was obtained in a third group of patients with various cardiac abnormalities, in whom there was only a weak correlation between ADC and ejection fraction. Although further study is needed to better understand the factors contributing to the myocardial ADC, we hypothesize that the measured diffusional anisotropy in the septum might be explained largely on the basis of myofiber orientation. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. BRIGHAM & WOMENS HOSP,DIV CARDIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA. RP EDELMAN, RR (reprint author), BETH ISRAEL HOSP,MRI,DEPT RADIOL,AN234,330 BROOKLINE AVE,BOSTON,MA 02215, USA. OI Prasad, Pottumarthi/0000-0002-4214-5465 NR 22 TC 69 Z9 69 U1 1 U2 4 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 SEP PY 1994 VL 32 IS 3 BP 423 EP 428 DI 10.1002/mrm.1910320320 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PE259 UT WOS:A1994PE25900019 PM 7984077 ER PT J AU PANCHAMOORTHY, G FUKAZAWA, T STOLZ, L PAYNE, G REEDQUIST, K SHOELSON, S SONGYANG, Z CANTLEY, L WALSH, C BAND, H AF PANCHAMOORTHY, G FUKAZAWA, T STOLZ, L PAYNE, G REEDQUIST, K SHOELSON, S SONGYANG, Z CANTLEY, L WALSH, C BAND, H TI PHYSICAL AND FUNCTIONAL INTERACTIONS BETWEEN SH2 AND SH3 DOMAINS OF THE SRC FAMILY PROTEIN-TYROSINE KINASE P59(FYN) SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID AFFINITY PHOSPHOTYROSYL PEPTIDE; CELL ANTIGEN RECEPTOR; LIGAND-BINDING SITE; SIGNAL-TRANSDUCTION; C-SRC; PHOSPHATIDYLINOSITOL 3-KINASE; HOMOLOGY-2 DOMAIN; T-CELLS; PHOSPHORYLATED PROTEINS; P85-ALPHA SUBUNIT AB The Src family protein tyrosine kinases participate in signalling through cell surface receptors that lack intrinsic tyrosine kinase domains. All nine members of this family possess adjacent Src homology (SI-IZ and SH3) domains, both of which are essential for repression of the enzymatic activity. The repression is mediated by binding between the SH2 domain and a C-terminal phosphotyrosine, and the SH3 domain is required for this interaction. However, the biochemical basis of functional SH2-SH3 interaction is unclear. Here, we demonstrate that when the SH2 and SH3 domains of p59(fyn) (Fyn) were present as adjacent domains in a single protein, binding of phosphotyrosyl peptides and proteins to the SH2 domain was enhanced, whereas binding of a subset of cellular polypeptide ligands to the SH3 domain was decreased. An interdomain communication was further revealed by occupancy with domain-specific peptide ligands: occupancy of the SH3 domain with a proline-rich peptide enhanced phosphotyrosine binding to the linked SH2 domain, and occupancy of the SH2 domain with phosphotyrosyl peptides enhanced binding of certain SH3-specific cellular polypeptides. Second, we demonstrate a direct binding between purified SH2 and SH3 domains of Fyn and Lck Src family kinases. Heterologous binding between SH2 and SH3 domains of closely related members of the Src family, namely, F;vn, Lck, and Src, was also observed. In contrast, Grb2, Crk, Abl, p85 phosphatidylinositol 3-kinase, and GTPase-activating protein SH2 domains showed lower or no binding to Fyn or Lck SH3 domains. SH2-SH3 binding did not require an intact phosphotyrosine binding pocket on the SH2 domain; however, perturbations of the SH2 domain induced by specific high-affinity phosphotyrosyl peptide binding abrogated binding of the SH3 domain. SH3-SH2 binding was observed in the presence of proline-rich peptides or when a point mutation (W119K) was introduced in the putative ligand-binding pouch of the Fyn SH3 domain, although these treatments completely abolished the binding to p85 phosphatidylinositol 3-kinase and other SH3-specific polypeptides. These biochemical SH2-SH3 interactions suggest novel mechanisms of regulating the enzymatic activity of Src kinases and their interactions with other proteins. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT RHEUMATOL & IMMUNOL,LYMPHOCYTE BIOL SECT,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT MED,JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. BETH ISRAEL HOSP,DIV SIGNAL TRANSDUCT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 FU NIAID NIH HHS [R29-AI28508]; NIAMS NIH HHS [AR 36308] NR 83 TC 62 Z9 62 U1 0 U2 5 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 SEP PY 1994 VL 14 IS 9 BP 6372 EP 6385 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA PC750 UT WOS:A1994PC75000078 PM 7520528 ER PT J AU KAWAGUCHI, S BERGELSON, JM FINBERG, RW HEMLER, ME AF KAWAGUCHI, S BERGELSON, JM FINBERG, RW HEMLER, ME TI INTEGRIN ALPHA(2) CYTOPLASMIC DOMAIN DELETION EFFECTS - LOSS OF ADHESIVE ACTIVITY PARALLELS LIGAND-INDEPENDENT RECRUITMENT INTO FOCAL ADHESIONS SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID MEDIATED CELL-ADHESION; BETA-SUBUNIT; MONOCLONAL-ANTIBODIES; FIBRONECTIN RECEPTOR; COLLAGEN RECEPTOR; LAMININ RECEPTOR; BINDING-SITE; VLA-2; EXPRESSION; DISTINCT AB Chinese hamster ovary (CHO) cells transfected with the integrin alpha(2) subunit formed a stable VLA-2 heterodimer that mediated cell adhesion to collagen. Within CHO cells spread on collagen, but not fibronectin, wild-type alpha(2) subunit localized into focal adhesion complexes (FACs). In contrast, alpha(2) with a deleted cytoplasmic domain was recruited into FACs whether CHO cells were spread on collagen or fibronectin. Thus, as previously seen for other integrins, the alpha(2) cytoplasmic domain acts as a negative regulator, preventing indiscriminate integrin recruitment into FACs. Notably, ligand-independent localization of the VLA-2 alpha(2) subunit into FACs was partially prevented if only one or two amino acids were present in the alpha(2) cytoplasmic domain (beyond the conserved GFFKR motif) and was completely prevented by four to seven amino acids. The addition of two alanine residues (added to GFFKR) also partially prevented ligand-independent localization. In a striking inverse correlation, the same mutants showing increased ligand-independent recruitment into FACs exhibited diminished alpha(2)-dependent adhesion to collagen. Thus, control of VLA-2 localization may be closely related to the suppression of cell adhesion to collagen. In contrast to FAC localization and collagen adhesion results, VLA-2-dependent binding and infection by echovirus were unaffected by either alpha 2 cytoplasmic domain deletion or exchange with other cytoplasmic domains. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. RI Finberg, Robert/E-3323-2010 FU NIAID NIH HHS [AI-31628]; NIGMS NIH HHS [GM-46526] NR 53 TC 36 Z9 36 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD SEP PY 1994 VL 5 IS 9 BP 977 EP 988 PG 12 WC Cell Biology SC Cell Biology GA PK648 UT WOS:A1994PK64800005 PM 7841525 ER PT J AU SINGH, IS LUO, ZJ KOZLOWSKI, MT ERLICHMAN, J AF SINGH, IS LUO, ZJ KOZLOWSKI, MT ERLICHMAN, J TI ASSOCIATION OF USF AND C-MYC WITH A HELIX-LOOP-HELIX-CONSENSUS MOTIF IN THE CORE PROMOTER OF THE MURINE TYPE II-BETA REGULATORY SUBUNIT GENE OF CYCLIC ADENOSINE 3',5'-MONOPHOSPHATE-DEPENDENT PROTEIN-KINASE SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID MAJOR LATE PROMOTER; DNA-BINDING; TRANSCRIPTION FACTOR; MOLECULAR-CLONING; RII-BETA; IMMUNOGLOBULIN ENHANCER; CDNA STRUCTURE; CAMP; CELLS; EXPRESSION AB Previous studies showed that the core promoter of the mouse cAMP-dependent protein kinase regulatory subunit type II beta (RII beta) gene was composed of two functional elements. One element was GC rich and bound the Sp1 transcription factor. The second element contained a helix-loop-helix (HLH)-motif. Each element conferred transcriptional activity when inserted upstream of a reporter gene, chloramphenicol acetyltransferase and transfected into mouse NB2a neuroblastoma cells and Chinese hamster ovary (CHO) cells. The core promoter was further characterized by mutational analysis using electrophoretic mobility shift assays and by transfection into CHO and NB2a cells. Electrophoretic mobility shift assays showed that the HLH-consensus motif, CACGTG, present in the RII beta gene bound nuclear factors present in NB2a and CHO cells. Mutations in the HLH-core motif decreased the binding of these factors and reduced the transcriptional activity of constructs containing the chloramphenicol acetyltransferase reporter when transfected into these cells. The results showed that the central nucleotides as well as the adjacent bases were important for the interaction with the nuclear binding factors. UV cross-linking, Southwestern blot analysis, and interference of the mobility shift patterns by specific antisera directed against USF and c-Myc indicated that both of these transcription factors were forming complexes with the HLH-consensus motif. The results suggest that RII beta transcription may be regulated, in part, by USF and c-Myc in NB2a CHO cells. C1 YESHIVA UNIV ALBERT EINSTEIN COLL MED, DEPT MED, BRONX, NY 10461 USA. YESHIVA UNIV ALBERT EINSTEIN COLL MED, DEPT BIOCHEM, BRONX, NY 10461 USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, BOSTON, MA 02129 USA. FU NIDDK NIH HHS [DK-27736]; NINDS NIH HHS [NS-31901] NR 57 TC 12 Z9 12 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD SEP PY 1994 VL 8 IS 9 BP 1163 EP 1174 DI 10.1210/me.8.9.1163 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PH395 UT WOS:A1994PH39500004 PM 7838149 ER PT J AU LEE, JW MOORE, DD HEYMAN, RA AF LEE, JW MOORE, DD HEYMAN, RA TI A CHIMERIC THYROID-HORMONE RECEPTOR CONSTITUTIVELY BOUND TO DNA REQUIRES RETINOID-X RECEPTOR FOR HORMONE-DEPENDENT TRANSCRIPTIONAL ACTIVATION IN YEAST SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID HUMAN ESTROGEN-RECEPTOR; SACCHAROMYCES-CEREVISIAE; V-ERBA; RESPONSE ELEMENTS; AUXILIARY PROTEIN; STEROID-RECEPTORS; ACID RECEPTORS; RXR-ALPHA; BINDING; TRANSACTIVATION AB T-3 receptors (TRs) regulate transcription by binding to specific DNA response elements as heterodimers with the retinoid X receptors (RXRs). To study the consequences of this heterodimerization for transcriptional regulation in the absence of complications associated with its effects an DNA binding affinity, we expressed in the yeast Saccharomyces cerevisiae a chimeric protein consisting of the rat TR beta 1 ligand-binding domain fused to the DNA-binding domain of the bacterial repressor lexA (lexATR). LexATR is a weak, T-3-responsive activator of a beta-galactosidase reporter gene controlled by upstream lexA-binding sites (lexA-beta-gal). In contrast, coexpression of human RXR alpha (hRXR alpha) strongly enhances both the basal and ligand-induced transcriptional activities. Both the N-terminal activation domain of RXR and sequences at the extreme C terminus of lexATR are required for this T-3- and RXR-dependent transcriptional activation. The lexATR chimera was also used to characterize receptor-receptor interactions using the two-hybrid system. Coexpression of B42RXR, a fusion protein of the human RXR alpha ligand-binding domain and the B42 transcriptional activation domain, strongly increases the transcriptional activity of lexATR in the absence of T-3 or 9-cis-retinoic acid. We conclude that RXR is essential for full, T-3-dependent transcriptional activity of the TR in yeast, and that protein-protein interaction of TR and RXR in vivo is ligand-independent. C1 MASSACHUSETTS GEN HOSP, DEPT MOLEC BIOL, BOSTON, MA 02114 USA. RP LEE, JW (reprint author), LIGAND PHARMACEUT INC, DEPT CELL BIOL, 9393 TOWNE CTR DR, SAN DIEGO, CA 92121 USA. FU NIDDK NIH HHS [DK-43382] NR 47 TC 38 Z9 38 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD SEP PY 1994 VL 8 IS 9 BP 1245 EP 1252 DI 10.1210/me.8.9.1245 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PH395 UT WOS:A1994PH39500012 PM 7838157 ER PT J AU FIRESTONE, LL ALIFIMOFF, JK MILLER, KW AF FIRESTONE, LL ALIFIMOFF, JK MILLER, KW TI DOES GENERAL ANESTHETIC-INDUCED DESENSITIZATION OF THE TORPEDO ACETYLCHOLINE-RECEPTOR CORRELATE WITH LIPID DISORDERING SO MOLECULAR PHARMACOLOGY LA English DT Article ID POSTSYNAPTIC MEMBRANES; RICH MEMBRANES; BINDING; PHOSPHOLIPIDS; CHOLESTEROL; CHANNELS; PROTEIN; ETHANOL AB We have tested the hypothesis that general anesthetics stabilize the desensitized state of the nicotinic acetylcholine receptor by disordering its surrounding lipids. Acetylcholine receptor-rich postsynaptic membranes from the electroplaques of Torpedo were used in this study to obtain the highest possible receptor specific activity in native membranes. We examined 18 general anesthetics, including six inhalation agents, eight 1-alcohols, the enantiomers of 2-octanol, and two intravenous general anesthetics (pentobarbital and ethylcarbamate). The degree of desensitization after preincubation with the general anesthetics was determined by brief exposure to [H-3]acetylcholine, making use of the facts that desensitized receptors have much higher affinity than do those in the resting state and that interconversion between the states is slow. All of the general anesthetics desensitized the receptor within minutes, exhibiting steep concentration-response curves with Hill coefficients generally within the range of 2-4. At the highest general anesthetic concentrations, almost all receptors were desensitized. The concentrations that desensitized half of the resting state receptors varied by >3000-fold. The 2-octanol enantiomers were without stereoselectivity. Membrane order was examined in parallel by using spin-labeled fatty acids doped into the native membranes. The spin label 5-doxylpalmitate reported from the most ordered part of the bilayer near the aqueous interface, whereas 12-doxylstearate reported from the less ordered region nearer the center of the bilayer. The spin label deeper in the membranes was 3 times more sensitive to a given anesthetic than was the other probe. At both depths in the membrane general anesthetics decreased lipid order linearly with increasing concentration. The range of disordering potencies (change in order parameter induced by a unit concentration of general anesthetic in the aqueous phase) was 5333 for 5-doxylpalmitate and 7143 for 12-doxylstearate, but the range of disordering compared at equally desensitizing concentrations was reduced by 875- and 1430-fold, respectively. The average degrees of disordering at concentrations that desensitized half of the resting state receptors were 1.5% and 4.4%, respectively. It is unlikely that changes in membrane order parameter per se cause desensitization, because the associated changes in order parameter can be reproduced by changes in cholesterol content or temperature that do not cause desensitization. We conclude that, although there is a strong association between anesthetic-induced membrane disordering and desensitization, more detailed tests of a mechanistic nature will be necessary to elucidate the mechanisms underlying the Meyer-Overton-type behavior we have observed. C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT ANAESTHESIA,BOSTON,MA 02114. FU NIGMS NIH HHS [GM07592, GM35900, GM15904] NR 34 TC 37 Z9 38 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD SEP PY 1994 VL 46 IS 3 BP 508 EP 515 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PJ601 UT WOS:A1994PJ60100015 PM 7935332 ER PT J AU MEYERSWALLEN, VN MACLAUGHLIN, D PALMER, V DONAHOE, PK AF MEYERSWALLEN, VN MACLAUGHLIN, D PALMER, V DONAHOE, PK TI MULLERIAN-INHIBITING SUBSTANCE SECRETION IS DELAYED IN XX-SEX-REVERSED DOG EMBRYOS SO MOLECULAR REPRODUCTION AND DEVELOPMENT LA English DT Article DE TESTIS; OVOTESTIS; TRUE HERMAPHRODITE; MULLERIAN DUCT ID Y-CHROMOSOME; TESTICULAR-DIFFERENTIATION; DETERMINING REGION; SERTOLI CELLS; DUCT SYNDROME; BOVINE; TESTES; FETAL; MOUSE; IMMUNOASSAY AB Sertoli cell secretion of Mullerian-inhibiting substance (MIS) begins shortly after testis differentiation. Mullerian ducts regress following MIS exposure during an embryonic critical period. In dogs with XX sex reversal, Mullerian ducts persist in the presence of testicular tissue. This study was conducted to determine whether MIS is present in ovotestes of XX sex-reversed embryos during the period for Mullerian duct regression in normal males. XX sex-reversed embryos and normal littermates were identified by a combination of karyotype and gonadal histology. The degree of regression in the adjacent Mullerian duct was scored. Immunohistochemical staining was used to detect MIS in the contralateral gonad. Testicular differentiation and MIS secretion were identified in XY embryos at all ages studied (35-46 days). Seminiferous tubules were not observed in gonads of embryos at risk of XX sex reversal between 35-38 days (n = 15), but were observed at 40 and 46 days (n = 3). Although positive staining for MIS was observed in ovotestes, adjacent Mullerian ducts persisted. The degree of seminiferous tubule development was reduced and MIS secretion was delayed in ovotestes, compared to normal testes. Mullerian duct persistence in this model is apparently due to an abnormality in the quantity and timing of MIS secretion during embryonic development. (C) 1994 Wiley-Liss, Inc. C1 CORNELL UNIV,NEW YORK STATE COLL VET MED,DEPT ANAT,ITHACA,NY 14853. MASSACHUSETTS GEN HOSP,DEPT PEDIAT SURG,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PEDIAT,BOSTON,MA 02114. RP MEYERSWALLEN, VN (reprint author), CORNELL UNIV,NEW YORK STATE COLL VET MED,JA BAKER INST ANIM HLTH,HUNGERFORD HILL RD,ITHACA,NY 14853, USA. NR 36 TC 24 Z9 24 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1040-452X J9 MOL REPROD DEV JI Mol. Reprod. Dev. PD SEP PY 1994 VL 39 IS 1 BP 1 EP 7 DI 10.1002/mrd.1080390102 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology; Reproductive Biology SC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology; Reproductive Biology GA PE645 UT WOS:A1994PE64500001 PM 7999353 ER PT J AU ROSS, S RICHARDSON, MD GRAYBILL, JR AF ROSS, S RICHARDSON, MD GRAYBILL, JR TI ASSOCIATION BETWEEN MALASSEZIA-FURFUR COLONIZATION AND SEBORRHEIC DERMATITIS IN AIDS PATIENTS SO MYCOSES LA English DT Article DE MALASSEZIA FURFUR; SEBORRHEIC DERMATITIS; HIV; AIDS ID ACQUIRED IMMUNODEFICIENCY SYNDROME; PITYROSPORUM-ORBICULARE; KETOCONAZOLE; PREVALENCE; DISEASE; SCALP AB A total of 180 HIV-positive patients were assessed for seborrhoeic dermatitis (SD) and colonization with Malassezia species. Diseased skin of patients with seborrhoeic dermatitis were sampled selectively for Malassezia. In patients without SD, uninvolved skin was sampled. The prevalence of SD was 19%. Of the 34 SD patients, 16 were positive for Malassezia. Of the 146 patients without SD, only 27 were culture positive for Malassezia. Analysis of the largest HIV-positive patient population studied thus far yielded only a weak correlation between SD and Malassezia colonization. C1 AUDIE L MURPHY MEM VET ADM MED CTR,INFECT DIS SECT,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. UNIV GLASGOW,DEPT DERMATOL,REG MYCOL REFERENCE LAB,GLASGOW G12 8QQ,LANARK,SCOTLAND. NR 20 TC 3 Z9 4 U1 0 U2 0 PU BLACKWELL WISSENSCHAFTS VERLAG GMBH PI BERLIN PA KURFURSTENDAMM 57, D-10707 BERLIN, GERMANY SN 0933-7407 J9 MYCOSES JI Mycoses PD SEP-OCT PY 1994 VL 37 IS 9-10 BP 367 EP 370 PG 4 WC Dermatology; Mycology SC Dermatology; Mycology GA QN784 UT WOS:A1994QN78400012 PM 7746298 ER PT J AU LORSCH, JR SZOSTAK, JW AF LORSCH, JR SZOSTAK, JW TI IN-VITRO EVOLUTION OF NEW RIBOZYMES WITH POLYNUCLEOTIDE KINASE-ACTIVITY SO NATURE LA English DT Article ID STRANDED-DNA MOLECULES; INVITRO SELECTION; RNA ENZYME; CLEAVAGE; RECOGNITION; TETRAHYMENA; POLYMERASE; CATALYSIS; SEQUENCE; LIGANDS AB We have isolated a large number of polynucleotide kinase ribozymes from a pool of RNA molecules consisting of an ATP-binding domain flanked by regions of random sequence. Different classes of kinases catalyse the transfer of the gamma-thiophosphate of ATP-gamma S to the 5'-hydroxyl or to internal 2'-hydroxyls. An engineered version of one class is able to catalyse the transfer of thiophosphate from ATP-gamma S to the 5'-hydroxyl of an exogenous oligoribonucleotide substrate with multiple turnover, thus acting as a true enzyme. C1 HARVARD UNIV,DEPT BIOCHEM & MOLEC BIOL,CAMBRIDGE,MA 02138. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. RP LORSCH, JR (reprint author), MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114, USA. OI Lorsch, Jon/0000-0002-4521-4999 NR 39 TC 201 Z9 202 U1 4 U2 14 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD SEP 1 PY 1994 VL 371 IS 6492 BP 31 EP 36 DI 10.1038/371031a0 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PE381 UT WOS:A1994PE38100041 PM 7521014 ER PT J AU FISHER, CM AF FISHER, CM TI HUNGER AND THE TEMPORAL-LOBE SO NEUROLOGY LA English DT Review AB A boy experienced two episodes of intracerebral hemorrhage in the region of the right anterior temporal lobe. On both occasions, the bleeding was ushered in by an exclamation of intense hunger. The patient provides further evidence for the temporal lobe localization of the sensation of hunger. We describe a model of the neural system subserving feeding that incorporates the cortical locus of hunger. RP FISHER, CM (reprint author), MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114, USA. NR 17 TC 11 Z9 11 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD SEP PY 1994 VL 44 IS 9 BP 1577 EP 1579 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA PG390 UT WOS:A1994PG39000004 PM 7936276 ER PT J AU KIEBURTZ, K MCDERMOTT, M COMO, P GROWDON, J BRADY, J CARTER, J HUBER, S KANIGAN, B LANDOW, E RUDOLPH, A SAINTCYR, J STERN, Y TENNIS, M THELEN, J SHOULSON, I AF KIEBURTZ, K MCDERMOTT, M COMO, P GROWDON, J BRADY, J CARTER, J HUBER, S KANIGAN, B LANDOW, E RUDOLPH, A SAINTCYR, J STERN, Y TENNIS, M THELEN, J SHOULSON, I TI THE EFFECT OF DEPRENYL AND TOCOPHEROL ON COGNITIVE PERFORMANCE IN EARLY UNTREATED PARKINSONS-DISEASE SO NEUROLOGY LA English DT Note AB We conducted prospective cognitive assessments over 14 +/- 6 (mean +/- SD) months of observation as part of the multicenter trial Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism (DATATOP), which involved 800 patients with early untreated Parkinson's disease. We administered tests that measured memory, visuospatial, and frontal lobe functions. Subjects were randomly assigned to receive placebo, deprenyl (10 mg/d), tocopherol (2,000 IU/d), or both deprenyl and tocopherol. We analyzed treatment effects using annualized rates of cognitive change. We performed exploratory analyses to identify potential clinical and demographic correlates of cognitive performance. There was no significant effect of either deprenyl or tocopherol on cognitive test performance. In early untreated Parkinson's disease, cognitive performance appears to be stable and unrelated to either motor deterioration or treatment with deprenyl or tocopherol. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. UNIV MICHIGAN,ANN ARBOR,MI 48109. OREGON HLTH SCI UNIV,PORTLAND,OR 97201. OHIO STATE UNIV,COLUMBUS,OH 43210. UNIV SASKATCHEWAN,SASKATOON S7N 0W0,SK,CANADA. UNIV VIRGINIA,CHARLOTTESVILLE,VA. TORONTO WESTERN HOSP,TORONTO M5T 2S8,ON,CANADA. COLUMBIA UNIV,NEW YORK,NY. RUSH PRESBYTERIAN ST LUKES MED CTR,CHICAGO,IL 60612. RP KIEBURTZ, K (reprint author), UNIV ROCHESTER,MED CTR,DEPT NEUROL,BOX 673,601 ELMWOOD AVE,ROCHESTER,NY 14642, USA. FU NCRR NIH HHS [RR00645, RR00847]; NINDS NIH HHS [NS24778] NR 10 TC 44 Z9 44 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 SEP PY 1994 VL 44 IS 9 BP 1756 EP 1759 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA PG390 UT WOS:A1994PG39000039 PM 7936311 ER PT J AU BARKER, FG TATTER, SB AF BARKER, FG TATTER, SB TI FLOW-DIRECTED ATRIAL CATHETER PLACEMENT FOR VENTRICULOATRIAL SHUNTS - TECHNICAL NOTE SO NEUROSURGERY LA English DT Note DE CEREBROSPINAL FLUID SHUNT; FLOW-DIRECTED PLACEMENT; HYDROCEPHALUS; VENTRICULOATRIAL SHUNT AB THE PLACEMENT OF the atrial portion of a ventriculoatrial shunt is occasionally rendered difficult by a tendency of the shunt catheter to pass into the contralateral jugular vein or into a subclavian vein instead of into the atrium. We report a simple flow-directed technique that may resolve this problem. C1 MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114. RP BARKER, FG (reprint author), UNIV SAN FRANCISCO,DEPT NEUROSURG,NEUROONCOL SERV,350 PARNASSUS AVE,SUITE 805,SAN FRANCISCO,CA 94117, USA. NR 6 TC 0 Z9 0 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 SEP PY 1994 VL 35 IS 3 BP 534 EP 535 PG 2 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA PE799 UT WOS:A1994PE79900082 PM 7800150 ER PT J AU OLIVIERI, NF NATHAN, DG MACMILLAN, JH WAYNE, AS LIU, PP MCGEE, A MARTIN, M KOREN, G COHEN, AR AF OLIVIERI, NF NATHAN, DG MACMILLAN, JH WAYNE, AS LIU, PP MCGEE, A MARTIN, M KOREN, G COHEN, AR TI SURVIVAL IN MEDICALLY TREATED PATIENTS WITH HOMOZYGOUS BETA-THALASSEMIA SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID BONE-MARROW TRANSPLANTATION; SICKLE-CELL-ANEMIA; SUBCUTANEOUS DEFEROXAMINE; IRON STORES; CHELATION-THERAPY; CARDIAC DISEASE; OVERLOAD; FERRITIN AB Background. The prognosis of patients with homozygous beta-thalassemia (thalassemia major) has been improved by transfusion and iron-chelation therapy. We analyzed outcome and prognostic factors among patients receiving transfusions and chelation therapy who had reached the age at which iron-induced cardiac disease, the most common cause of death, usually occurs. Methods. Using the duration of life without the need for either inotropic or antiarrhythmic drugs as a measure of survival without cardiac disease, we studied 97 patients born before 1976 who were treated with regular transfusions and chelation therapy. We used Cox proportional-hazards analysis to assess the effect of prognostic factors and life-table analysis to estimate freedom from cardiac disease over time. Results. Of the 97 patients, 59 (61 percent) had no cardiac disease; 36 (37 percent) had cardiac disease, and 18 of them had died. Univariate analysis demonstrated that factors affecting cardiac disease-free survival were age at the start of chelation therapy (P<0.001), the natural log of the serum ferritin concentration before chelation therapy began (P=0.01), the mean ferritin concentration (P<0.001), and the proportion of ferritin measurements exceeding 2500 ng per milliliter (P<0.001). With stepwise Cox modeling, only the proportion of ferritin measurements exceeding 2500 ng per milliliter affected cardiac disease-free survival (P<0.001). Patients in whom less than 33 percent of the serum ferritin values exceeded 2500 ng per milliliter had estimated rates of survival without cardiac disease of 100 percent after 10 years of chelation therapy and 91 percent after 15 years. Conclusions. The prognosis for survival without cardiac disease is excellent for patients with thalassemia major who receive regular transfusions and whose serum ferritin concentrations remain below 2500 ng per milliliter with chelation therapy. C1 UNIV TORONTO,TORONTO HOSP,TORONTO,ON,CANADA. HARVARD UNIV,CHILDRENS HOSP,SCH MED,DIV HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. UNIV PENN,CHILDRENS HOSP PHILADELPHIA,SCH MED,DIV HEMATOL,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,DEPT PEDIAT,PHILADELPHIA,PA 19104. RP OLIVIERI, NF (reprint author), UNIV TORONTO,HOSP SICK CHILDREN,DIV HAEMATOL ONCOL,HAEMOGLOBINOPATHY PROGRAM,555 UNIV AVE,TORONTO M5G 1X8,ON,CANADA. FU NCRR NIH HHS [2 M01 RR02172-12, M01 RR00240] NR 25 TC 583 Z9 597 U1 3 U2 10 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 SEP 1 PY 1994 VL 331 IS 9 BP 574 EP 578 DI 10.1056/NEJM199409013310903 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA PD699 UT WOS:A1994PD69900003 PM 8047081 ER PT J AU BRUGGE, WR LEE, MJ AF BRUGGE, WR LEE, MJ TI ADENOCARCINOMA OF THE ESOPHAGUS SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Note RP BRUGGE, WR (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 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 SEP 1 PY 1994 VL 331 IS 9 BP 585 EP 585 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA PD699 UT WOS:A1994PD69900005 PM 8047083 ER PT J AU COPPES, MJ HABER, DA GRUNDY, PE AF COPPES, MJ HABER, DA GRUNDY, PE TI GENETIC EVENTS IN THE DEVELOPMENT OF WILMS-TUMOR SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID WIEDEMANN-BECKWITH SYNDROME; DENYS-DRASH SYNDROME; FACTOR-II GENE; FAMILIAL PREDISPOSITION; MENTAL-RETARDATION; KIDNEY DEVELOPMENT; DISTINCT REGIONS; SUPPRESSOR GENE; POINT MUTATIONS; WT1 GENE C1 TOM BAKER CANC CLIN,DEPT ONCOL,CALGARY,AB,CANADA. HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,CTR CANC,BOSTON,MA. CROSS CANC INST,DEPT PEDIAT,EDMONTON,AB,CANADA. UNIV ALBERTA,FAC MED,EDMONTON,AB,CANADA. RP COPPES, MJ (reprint author), ALBERTA CHILDRENS PROV GEN HOSP,PEDIAT ONCOL PROGRAM,1820 RICHMOND RD SW,CALGARY T2T 5C7,AB,CANADA. NR 58 TC 86 Z9 87 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 SEP 1 PY 1994 VL 331 IS 9 BP 586 EP 590 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA PD699 UT WOS:A1994PD69900006 PM 8047084 ER PT J AU SMITH, SD NAVON, SE AF SMITH, SD NAVON, SE TI COMPUTERIZED TOPOGRAPHY OF A FULL-THICKNESS CORNEAL LACERATION SO OPHTHALMIC SURGERY AND LASERS LA English DT Note ID INJURIES; EYE AB A full-thickness corneal laceration was studied by computerized topography. Measurements taken preoperatively and during healing allowed the effects of the injury, its repair, and subsequent suture removal to be isolated and separately analyzed. C1 MASSACHUSETTS EYE & EAR INFIRM,243 CHARLES ST,BOSTON,MA 02114. NR 7 TC 3 Z9 4 U1 0 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0022-023X J9 OPHTHALMIC SURG LAS JI Ophthalmic Surg. Lasers PD SEP-OCT PY 1994 VL 25 IS 9 BP 630 EP 632 PG 3 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA PN749 UT WOS:A1994PN74900016 PM 7831009 ER PT J AU RIZZO, JF LESSEL, S AF RIZZO, JF LESSEL, S TI CHOROIDAL INFARCTION AFTER OPTIC-NERVE SHEATH FENESTRATION SO OPHTHALMOLOGY LA English DT Article ID POSTERIOR CILIARY ARTERY; PSEUDOTUMOR CEREBRI; VISUAL-LOSS; DECOMPRESSION; NEUROPATHY; OCCLUSION; HYPERTENSION; LESIONS AB Purpose: To describe a visual complication of optic nerve sheath fenestration. Methods: Case review of two patients who underwent seemingly uncomplicated optic nerve sheath fenestration. Findings: Both patients had a surgical complication that resulted in significant depression of their temporal visual field and development of a wedge-shaped region of subretinal pigmentation in the nasal fundus. Conclusions: Both patients had choroidal infarctions as a complication of optic nerve sheath fenestration. Choroidal infarction should be considered in cases of unexpected loss of visual field after this type of surgery, although the funduscopic signs that assist in making the diagnosis may not be evident for several weeks after surgery. 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 15 Z9 15 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD SEP PY 1994 VL 101 IS 9 BP 1622 EP 1626 PG 5 WC Ophthalmology SC Ophthalmology GA PH136 UT WOS:A1994PH13600032 PM 8090466 ER PT J AU DENT, CD DEBOOM, GW HAMLIN, ML AF DENT, CD DEBOOM, GW HAMLIN, ML TI PROLIFERATIVE MYOSITIS OF THE HEAD AND NECK - REPORT OF A CASE AND REVIEW OF THE LITERATURE SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTICS LA English DT Note ID MASSETER MUSCLE AB A case of proliferative myositis arising in the tongue is described. Light and electron micrographs revealed the characteristic infiltrative growth pattern and cellular pleomorphism of this lesion. A review of the literature disclosed 50 reported cases of proliferative myositis, including 10 that originated in the head and neck. The rapid growth rate and unusual gross and histologic appearance of this infiltrative lesion have contributed to its relatively frequent misdiagnosis and inappropriate treatment. Consequently it is hoped that this report will help clarify its benign nature. C1 W LOS ANGELES VA MED CTR,WESTERN DENT EDUC CTR,LOS ANGELES,CA. RP DENT, CD (reprint author), VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,COLL DENT,DEPT ORAL & MAXILLOFACIAL SURG,RICHMOND,VA 23298, USA. NR 13 TC 13 Z9 15 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 1079-2104 J9 ORAL SURG ORAL MED O JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. PD SEP PY 1994 VL 78 IS 3 BP 354 EP 358 DI 10.1016/0030-4220(94)90068-X PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA PG827 UT WOS:A1994PG82700016 PM 7970598 ER PT J AU SWEET, WH AF SWEET, WH TI HISTORY OF SURGERY FOR CRANIOPHARYNGIOMAS SO PEDIATRIC NEUROSURGERY LA English DT Article; Proceedings Paper CT Symposium on Craniopharyngioma: The Answer CY NOV 17-19, 1993 CL NEW YORK, NY DE CRANIOPHARYNGIOMA; SUPRASELLAR CYST; ADAMANTINOMA; EPITHELIOMA; PHOTON RADIATION; LINAC RADIATION; PROTON RADIATION; GLIAL REACTION TO TUMOR; PROTECTIVE EFFECT OF CORTISONE; P-32,Y-90 RADIATION ID RADICAL EXCISION; CHILDREN AB Craniopharyngiomas, although histologically benign, are usually so intimately associated with the hypothalamus that total extirpation of these tumors was generally followed by death from hypotension and gross endocrine deficiencies. include the famous names of Grant, Bailey, Bucy, Feet, Kahn, Olivecrona, Norlen, Sjoqvist, Rougerie and Northfield. Matson and Sweet were the first to achieve major reductions in mortality by giving massive doses of cortisone plus meticulous dissection, which took advantage of the reactive glial envelope which surrounds the great majority of these tumors. RP SWEET, WH (reprint author), MASSACHUSETTS GEN HOSP,NEUROSURG SERV,BOSTON,MA 02114, USA. NR 45 TC 15 Z9 15 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1016-2291 J9 PEDIATR NEUROSURG JI Pediatr. Neurosurg. PD SEP PY 1994 VL 21 SU 1 BP 28 EP 38 DI 10.1159/000120859 PG 11 WC Clinical Neurology; Pediatrics; Surgery SC Neurosciences & Neurology; Pediatrics; Surgery GA PR518 UT WOS:A1994PR51800007 PM 7841076 ER PT J AU TARBELL, NJ BARNES, P SCOTT, RM GOUMNEROVA, L POMEROY, SL BLACK, PM SALLAN, SE BILLETT, A LAVALLY, B HELMUS, A KOOY, HM LOEFFLER, JS AF TARBELL, NJ BARNES, P SCOTT, RM GOUMNEROVA, L POMEROY, SL BLACK, PM SALLAN, SE BILLETT, A LAVALLY, B HELMUS, A KOOY, HM LOEFFLER, JS TI ADVANCES IN RADIATION-THERAPY FOR CRANIOPHARYNGIOMAS SO PEDIATRIC NEUROSURGERY LA English DT Article; Proceedings Paper CT Symposium on Craniopharyngioma: The Answer CY NOV 17-19, 1993 CL NEW YORK, NY DE STEREOTAXIC RADIATION THERAPY; CRANIOPHARYNGIOMA ID CHILDHOOD CRANIOPHARYNGIOMA; FRACTIONATED RADIOTHERAPY; INTRACRANIAL LESIONS; STEREOTAXIC FRAME; BRAIN-TUMORS; RADIOSURGERY; CHILDREN; COMPLICATIONS; RADIOBIOLOGY; IRRADIATION AB The overall survival for patients with craniopharyngioma is excellent. However, conventional treatments that include aggressive surgery and standard irradiation have been associated with significant morbidity. Focal radiation treatment with stereotactic radiosurgery has a role in selected cases, but may also be damaging to sensitive normal tissues such as the optic chiasm. Stereotactic radiotherapy (SRT) is a technique that allows for conventionally fractionated radiation under stereotactic guidance. Thus, highly focal and precise radiotherapy is now coupled with fractionation, enabling the treatment of selected tumors with a potentially improved therapeutic index. Dose optimization with SRT for focally discrete tumors should result in equivalent local control and survival compared to patients treated with conventional irradiation. We anticipate a significant decrease in late effects, especially neuropsychological and neuroendocrine sequelae. C1 BRIGHAM & WOMENS HOSP,CHILDRENS HOSP,DANA FARBER CANC INST,JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT RADIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT RADIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT SURG NEUROSURG,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. FU NINDS NIH HHS [1P20NS3110-01] NR 29 TC 34 Z9 34 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1016-2291 J9 PEDIATR NEUROSURG JI Pediatr. Neurosurg. PD SEP PY 1994 VL 21 SU 1 BP 101 EP 107 DI 10.1159/000120870 PG 7 WC Clinical Neurology; Pediatrics; Surgery SC Neurosciences & Neurology; Pediatrics; Surgery GA PR518 UT WOS:A1994PR51800018 PM 7841067 ER PT J AU SCHLESINGER, DH HAY, DI SCHLUCKEBIER, SK AHERN, JM AF SCHLESINGER, DH HAY, DI SCHLUCKEBIER, SK AHERN, JM TI PRIMARY STRUCTURE OF A NOVEL HUMAN SALIVARY ACIDIC PROLINE-RICH PROTEIN SO PEPTIDE RESEARCH LA English DT Article ID HUMAN-PAROTID SALIVA; APATITIC SURFACES; GENETIC-POLYMORPHISM; CRYSTAL-GROWTH; PHOSPHOPROTEIN; HYDROXYAPATITE; PURIFICATION; ADSORPTION; STATHERIN; ADHESION AB Human salivary acidic proline-rich proteins (PRPs) form a significant fraction of the total salivary protein and fulfill several biologically important roles in the oral cavity. Five commonly occurring PRP polymorphisms, Db, Pa, PIF; Pr2 and Pr1, have been identified, their structures determined, and several uncommon polymorphisms (frequencies < 1:100) have been reported. Most PRPs occur as protein pairs, because of an unusual, limited but well-controlled post-translational cleavage. We now describe an additional uncommon polymorphism Sound in the saliva of one of 127 individuals examined in a recent study, identified by high performance anion-exchange liquid chromatography. By analogy with previous terminology, we designate this protein pair as PRP-5, for the primary 150-residue polypeptide gene product, and PRP-6 for the secondary 106-residue cleavage product. Amino acid analysis of intact PRP-6 and sequence determination of PRP-6 chymotryptic peptides, residues 15-24 and 26-35, show a single difference in PRP-6, compared to the most similar characterized PRF: PRP-4, in that residue 30 is histidine in PRP-6, rather than arginine as in PRP-4 and in all the other sequenced PRPs. This substitution may have implications for the resistance of this polymorphic variant to degradation by trypsin-like enzymes originating from the oral microflora. C1 FORSYTH DENT CTR,BOSTON,MA 02115. RP SCHLESINGER, DH (reprint author), NYU,MED CTR,DEPT MED,550 1ST AVE,NEW YORK,NY 10016, USA. FU NIDCR NIH HHS [DE-3915, DE-6159, DE-7009] NR 44 TC 6 Z9 7 U1 0 U2 0 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 SN 1040-5704 J9 PEPTIDE RES JI Peptide Res. PD SEP-OCT PY 1994 VL 7 IS 5 BP 242 EP 247 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PL961 UT WOS:A1994PL96100002 PM 7849418 ER PT J AU BECK, WS AF BECK, WS TI A TUTORIAL ON RAS SO PERSPECTIVES IN BIOLOGY AND MEDICINE LA English DT Article C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP BECK, WS (reprint author), HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02114, USA. NR 8 TC 0 Z9 0 U1 0 U2 1 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 FAL PY 1994 VL 38 IS 1 BP 85 EP 105 PG 21 WC History & Philosophy Of Science; Medicine, Research & Experimental SC History & Philosophy of Science; Research & Experimental Medicine GA PT203 UT WOS:A1994PT20300008 ER PT J AU CAHALIN, LO AF CAHALIN, LO TI MULTISYSTEM ASSESSMENT SO PHYSICAL THERAPY LA English DT Letter RP CAHALIN, LO (reprint author), MASSACHUSETTS GEN HOSP,BIGELOW 858 FRUIT ST,BOSTON,MA 02114, USA. NR 12 TC 0 Z9 0 U1 0 U2 0 PU AMER PHYS THER ASSN PI ALEXANDRIA PA 1111 N FAIRFAX ST, ALEXANDRIA, VA 22314 SN 0031-9023 J9 PHYS THER JI Phys. Ther. PD SEP PY 1994 VL 74 IS 9 BP 886 EP 887 PG 2 WC Orthopedics; Rehabilitation SC Orthopedics; Rehabilitation GA PE329 UT WOS:A1994PE32900015 PM 8066115 ER PT J AU HU, ZQ HENDERSON, GI MOCK, DM SCHENKER, S AF HU, ZQ HENDERSON, GI MOCK, DM SCHENKER, S TI BIOTIN UPTAKE BY BASOLATERAL MEMBRANE-VESICLES OF HUMAN PLACENTA - NORMAL CHARACTERISTICS AND ROLE OF ETHANOL SO PROCEEDINGS OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Article ID TRANSPORT; RAT; LIVER AB This study assessed the mechanism of uptake of biotin by the fetal-facing (basolateral) membrane of the term human placenta. Using membrane vesicles, we showed that most of the uptake was attributable to transfer of the vitamin Into the vesicle and that the uptake was saturable, Na-dependent, carrier-mediated, and electroneutral. The rate of uptake was less than for biotin uptake by the maternal-facing (apical) membrane of the human placenta. Because ethanol inhibits biotin uptake by the apical membrane, the effect of ethanol on uptake by basolateral vesicles was investigated. With 10-hr exposure at a concentration of 2 and 3 mg/ml, but not 1 mg/ml, ethanol modestly inhibited biotin uptake. The mechanism of inhibition by alcohol is not known. C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV GASTROENTEROL & NUTR,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. UNIV ARKANSAS MED SCI HOSP,DEPT PEDIAT,LITTLE ROCK,AR 72202. ARKANSAS CHILDRENS HOSP,DIV DIGEST ENDOCRINE GENET & NUTR DISORDERS,LITTLE ROCK,AR 72202. UNIV TEXAS,HLTH SCI CTR,DEPT PHARMACOL,DIV GASTROENTEROL & NUTR,SAN ANTONIO,TX 78284. FU NIAAA NIH HHS [NIAAA RO1 AA07514]; NIDDK NIH HHS [NIDDK RO1-36823] NR 18 TC 11 Z9 12 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0037-9727 J9 P SOC EXP BIOL MED JI Proc. Soc. Exp. Biol. Med. PD SEP PY 1994 VL 206 IS 4 BP 404 EP 408 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA PE330 UT WOS:A1994PE33000009 PM 7521055 ER PT J AU VANDERKOLK, BA HERRON, N HOSTETLER, A AF VANDERKOLK, BA HERRON, N HOSTETLER, A TI THE HISTORY OF TRAUMA IN PSYCHIATRY SO PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; DISSOCIATIVE DISORDERS; PSYCHOLOGICAL TRAUMA; SEXUAL ABUSE; SYMPTOMS; SELF; PTSD AB Awareness of the role of psychological trauma in the genesis of a variety of psychiatric problems has waxed and waned throughout the history of psychiatry. Although the traumatic memories that haunt people after experiencing overwhelming terror have always been a central theme in literature, psychiatry has suffered periodically from marked amnesias in which well-established knowledge was forgotten abruptly, and the psychological impact of man's inhumanity to man was ascribed to constitutional or intra-psychic factors alone. C1 MASSACHUSETTS GEN HOSP,TRAUMA CLIN,BOSTON,MA 02114. NR 97 TC 26 Z9 27 U1 1 U2 6 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0193-953X J9 PSYCHIAT CLIN N AM JI Psychiatr. Clin. North Amer. PD SEP PY 1994 VL 17 IS 3 BP 583 EP 600 PG 18 WC Psychiatry SC Psychiatry GA PJ156 UT WOS:A1994PJ15600011 PM 7824384 ER PT J AU FARAONE, SV CHEN, WJ TSUANG, MT AF FARAONE, SV CHEN, WJ TSUANG, MT TI ESTIMATING THE MORBIDITY RISK FOR DISEASES HAVING A VARIABLE AGE AT ONSET SO PSYCHIATRIC GENETICS LA English DT Article DE MORBIDITY RISK; LIFETIME RISK; STATISTICAL METHODS ID SURVIVAL ANALYSIS; MAJOR DEPRESSION; LIFETIME RISK; DISTRIBUTIONS; SCHIZOPHRENIA; RELIABILITY; DISORDERS; DEMENTIA; ILLNESS; RECALL AB The morbidity risk assesses the risk of manifesting illnesses having a variable age at onset. We reviewed the conceptual derivation and critical assumptions of various methods for estimating morbidity risk by classifying them into two approaches. One approach uses an age at onset distribution as a weighting system. A second approach uses methods from survival analysis. Because survival methods estimate the morbidity risk and age at onset distribution simultaneously, they are preferable to weighting methods. Among weighting methods, Stromgren's estimator or Risch's maximum likelihood estimate are the methods of choice; the Kaplan-Meier estimator is the preferred survival analysis approach. C1 HARVARD UNIV,MASSACHUSETTS MENT HLTH CTR,SCH MED,BOSTON,MA 02115. BROCKTON WEST ROXBURY VET AFFAIRS MED CTR,BROCKTON,MA. MASSACHUSETTS GEN HOSP,PEDIAT PSYCHOPHARMACOL CLIN,BOSTON,MA 02114. NATL TAIWAN UNIV,COLL PUBL HLTH,INST PUBL HLTH,TAIPEI,TAIWAN. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [1 R37MH43518-01, 1 RO1MH41879-01, 5 UO1 MH46318-02] NR 38 TC 3 Z9 3 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0955-8829 J9 PSYCHIATR GENET JI Psychiatr. Genet. PD FAL PY 1994 VL 4 IS 3 BP 135 EP 142 DI 10.1097/00041444-199400430-00003 PG 8 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA QA186 UT WOS:A1994QA18600003 PM 7719699 ER PT J AU LEUCHTER, AF COOK, IA MENA, I DUNKIN, JJ CUMMINGS, JL NEWTON, TF MIGNECO, O LUFKIN, RB WALTER, DO LACHENBRUCH, PA AF LEUCHTER, AF COOK, IA MENA, I DUNKIN, JJ CUMMINGS, JL NEWTON, TF MIGNECO, O LUFKIN, RB WALTER, DO LACHENBRUCH, PA TI ASSESSMENT OF CEREBRAL PERFUSION USING QUANTITATIVE EEG CORDANCE SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE ELECTROENCEPHALOGRAPHY; SINGLE PHOTON EMISSION COMPUTED TOMOGRAPHY; DEMENTIA; STROKE; CORDANCE ID ALZHEIMERS-DISEASE; BLOOD-FLOW; SCHIZOPHRENIA; DEMENTIA; SPECT; HIPPOCAMPUS; INFARCTION; CORTICES AB Brain electrical activity is related to cerebral perfusion. The nature of this relationship is unclear, however, and surface-recorded activity has not been a reliable indicator of brain perfusion. We studied 27 subjects, all of whom were examined with single photon emission tomography (SPECT) and quantitative electroencephalography (QEEG), to assess associations between QEEG cordance and relative brain perfusion. Cordance has two indicator states: concordance, which may indicate high perfusion; and discordance, which may indicate low perfusion. We used multiple linear regression to assess the association between cordance and SPECT values, and found that cordance values were strongly associated with tissue perfusion. Concordance in the a band was associated both with mean tissue perfusion and the volume of normally perfused tissue, and it had a stronger association with perfusion than any other QEEG variable. Discordance in the beta(1) band was associated with mean perfusion, and it had a stronger association than did relative but not absolute power. These data suggest that cordance may be useful for the noninvasive assessment of brain perfusion. C1 UNIV CALIF LOS ANGELES,HARBOR MED CTR,DIV NUCL MED,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT PSYCHIAT & BIOBEHAV SCI,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT RADIOL,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT NEUROL,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,DEPT PSYCHIAT,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,SCH PUBL HLTH,DEPT BIOSTAT,LOS ANGELES,CA 90024. RP LEUCHTER, AF (reprint author), UNIV CALIF LOS ANGELES,NEUROPSYCHIAT INST & HOSP,QUANTITAT EEG LAB,760 WESTWOOD PLAZA,LOS ANGELES,CA 90024, USA. OI newton, thomas/0000-0002-3198-5901 FU NIA NIH HHS [P30 AG10123]; NIMH NIH HHS [MH-40705] NR 40 TC 24 Z9 24 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD SEP PY 1994 VL 55 IS 3 BP 141 EP 152 DI 10.1016/0925-4927(94)90022-1 PG 12 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA PR489 UT WOS:A1994PR48900003 PM 7870854 ER PT J AU JACOBSON, AM HAUSER, ST LAVORI, P WILLETT, JB COLE, CF WOLFSDORF, JI DUMONT, RH WERTLIEB, D AF JACOBSON, AM HAUSER, ST LAVORI, P WILLETT, JB COLE, CF WOLFSDORF, JI DUMONT, RH WERTLIEB, D TI FAMILY ENVIRONMENT AND GLYCEMIC CONTROL - A 4-YEAR PROSPECTIVE-STUDY OF CHILDREN AND ADOLESCENTS WITH INSULIN-DEPENDENT DIABETES-MELLITUS SO PSYCHOSOMATIC MEDICINE LA English DT Article DE DIABETES; PSYCHOLOGICAL; GLYCEMIC CONTROL; FAMILY ID METABOLIC CONTROL; GROWTH; COMPLICATIONS; ILLNESS; IDDM AB An onset cohort of children and adolescents with insulin-dependent diabetes mellitus (IDDM) and their parents were studied. Aspects of family environment were evaluated at study inception, and their influence on the initial level of, and change in, glycemic control over 4 years was examined. Family measures of expressiveness, cohesiveness, and conflict were linked to differences in the longitudinal pattern of glycemic control. In particular, the encouragement to act openly and express feelings directly (expressiveness) seemed to ameliorate deterioration of glycemic control over time in both boys and girls. Boys were especially sensitive to variations in family cohesiveness and conflict; those from more cohesive and less conflicted families showed less deterioration in glycemic control. This study demonstrated the important influence of family psychosocial factors present at diabetes onset on glycemic control in children and adolescents over the first 4 years of IDDM. C1 JOSLIN DIABET CTR,DEPT PEDIAT,BOSTON,MA 02215. MASSACHUSETTS MENTAL HLTH CTR,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,PSYCHIAT SERV,BIOSTAT UNIT,BOSTON,MA 02114. HARVARD UNIV,GRAD SCH EDUC,BOSTON,MA 02115. TUFTS UNIV,ELLIOT PEARSON DEPT CHILD STUDY,BOSTON,MA 02111. RP JACOBSON, AM (reprint author), JOSLIN DIABET CTR,DEPT MENTAL HLTH,ONE JOSLIN PL,BOSTON,MA 02215, USA. OI Willett, John/0000-0001-7183-350X FU NIADDK NIH HHS [R01-AM27845]; NIMH NIH HHS [5K-03-MH-70178] NR 28 TC 110 Z9 111 U1 0 U2 7 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD SEP-OCT PY 1994 VL 56 IS 5 BP 401 EP 409 PG 9 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA PK285 UT WOS:A1994PK28500004 PM 7809339 ER PT J AU WOOL, CA BARSKY, AJ AF WOOL, CA BARSKY, AJ TI DO WOMEN SOMATIZE MORE THAN MEN - GENDER DIFFERENCES IN SOMATIZATION SO PSYCHOSOMATICS LA English DT Review ID PSYCHIATRIC-DISORDERS; SEX-DIFFERENCES; PRIMARY CARE; DEPRESSION; PREVALENCE; HYPOCHONDRIASIS; COMMUNITY; SYMPTOMS; SERVICES; FAMILY AB Reviewing the literature of the latter half of the twentieth century, the authors consider the question: do women somatize more than men? The literature review begins with work done in the 1950s in order to look at the phenomenon of somatization as a constellation of symptoms. It encompasses work done in the general community and in the medical arena. The critique of the literature shows why the role of gender in somatizing remains unclear, elucidates inconsistencies, notes the confounding variables, and points out the degree of variable interaction and observer bias. Possible explanations or causes of gender differences are explored. In the present body of literature, women do somatize more than men; however, some of the studies in the literature are flawed. The changing gender difference in medical literature implies that the inquiry at hand concerns the etiology and expression of somatization itself. C1 HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. RP WOOL, CA (reprint author), MASSACHUSETTS GEN HOSP,PSYCHIAT SERV,PRIMARY CARE PSYCHIAT UNIT,ACC 615,FRUIT ST,BOSTON,MA 02114, USA. FU NIMH NIH HHS [MH40487] NR 61 TC 86 Z9 86 U1 5 U2 8 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD SEP-OCT PY 1994 VL 35 IS 5 BP 445 EP 452 PG 8 WC Psychiatry; Psychology SC Psychiatry; Psychology GA PD412 UT WOS:A1994PD41200004 PM 7972659 ER PT J AU EMERSON, J PANKRATZ, L JOOS, S SMITH, S AF EMERSON, J PANKRATZ, L JOOS, S SMITH, S TI PERSONALITY-DISORDERS IN PROBLEMATIC MEDICAL PATIENTS SO PSYCHOSOMATICS LA English DT Article ID DSM-III; DIFFICULT PATIENT; CARE; COMORBIDITY; PHYSICIANS; DIAGNOSIS AB To better understand problematic medical patients, the psychiatric diagnoses of 448 patients referred to a behavioral medicine clinic were examined. Forty-two percent met DSM-III-R personality disorder criteria. Analysis of the comorbidity of Axis I and Axis II diagnoses revealed a statistically significant co-occurrence between somatoform and personality disorders (P < 0.0001). Some of the difficulties in making a personality disorder diagnosis are reviewed, as are reasons why knowledge of personality disorder diagnoses is important to medical providers. C1 PORTLAND VA MED CTR,MED SERV,HLTH SERV RES & DEV PROGRAM,PSYCHIAT SERV,PSYCHOL SERV,PORTLAND,OR. OREGON HLTH SCI UNIV,DEPT PSYCHIAT,PORTLAND,OR 97201. OREGON HLTH SCI UNIV,DEPT MED PSYCHOL,PORTLAND,OR 97201. OREGON HLTH SCI UNIV,DEPT MED,PORTLAND,OR 97201. NR 29 TC 13 Z9 13 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 SEP-OCT PY 1994 VL 35 IS 5 BP 469 EP 473 PG 5 WC Psychiatry; Psychology SC Psychiatry; Psychology GA PD412 UT WOS:A1994PD41200007 PM 7972662 ER PT J AU GREENBERG, DB AF GREENBERG, DB TI LIVER-TRANSPLANTATION AND THE ALCOHOLIC PATIENT - MEDICAL, SURGICAL, AND PSYCHOSOCIAL ISSUES - LUCEY,MR, MERION,RM, BERESFORD,T SO PSYCHOSOMATICS LA English DT Book Review C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. 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 SEP-OCT PY 1994 VL 35 IS 5 BP 501 EP 502 PG 2 WC Psychiatry; Psychology SC Psychiatry; Psychology GA PD412 UT WOS:A1994PD41200013 ER PT J AU CREMENS, MC AF CREMENS, MC TI DIAGNOSIS AND TREATMENT OF DEPRESSION IN LATE-LIFE - RESULTS OF THE NIH CONSENSUS DEVELOPMENT CONFERENCE - SCHNEIDER,LS, REYNOLDS,CF, LEBOVITZ,B, FRIEDHOFF,AJ SO PSYCHOSOMATICS LA English DT Book Review C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP CREMENS, MC (reprint author), MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,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 SEP-OCT PY 1994 VL 35 IS 5 BP 502 EP 504 PG 3 WC Psychiatry; Psychology SC Psychiatry; Psychology GA PD412 UT WOS:A1994PD41200014 ER PT J AU GREENBERG, DB AF GREENBERG, DB TI BEHAVIORAL AND PSYCHOLOGICAL APPROACHES TO BREATHING DISORDERS - TIMMONS,BH, LEY,R SO PSYCHOSOMATICS LA English DT Book Review C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. 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 SEP-OCT PY 1994 VL 35 IS 5 BP 504 EP 505 PG 2 WC Psychiatry; Psychology SC Psychiatry; Psychology GA PD412 UT WOS:A1994PD41200015 ER PT J AU GAZELLE, GS LEE, MJ MUELLER, PR AF GAZELLE, GS LEE, MJ MUELLER, PR TI CHOLANGIOGRAPHIC SEGMENTAL ANATOMY OF THE LIVER SO RADIOGRAPHICS LA English DT Article DE BILE DUCTS, ANATOMY; BILE DUCTS, INTERVENTIONAL PROCEDURE; LIVER ANATOMY; LIVER, INTERVENTIONAL PROCEDURE ID PORTOGRAPHY AB The importance of understanding the Couinaud nomenclature describing hepatic segmental anatomy has been increasingly recognized by practicing radiologists. The normal cholangiographic appearances of the biliary ductal branches, as well as those of their common anatomic variants, are less well known. As percutaneous biliary procedures increase in frequency and complexity, a thorough understanding of this anatomy is of utmost importance. In this article, we present cholangiograms, computed tomographic (CT) scans, and anatomic drawings to illustrate cholangiographic segmental anatomy and its correlation with segmental anatomy as depicted by CT. The significance of the anatomy to percutaneous interventional procedures is discussed. C1 HARVARD UNIV,SCH MED,DEPT RADIOL,BOSTON,MA 02115. RP GAZELLE, GS (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,32 FRUIT ST,BOSTON,MA 02114, USA. NR 8 TC 42 Z9 43 U1 0 U2 2 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD SEP PY 1994 VL 14 IS 5 BP 1005 EP 1013 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PG637 UT WOS:A1994PG63700008 PM 7991810 ER PT J AU LEE, MJ MAYOSMITH, WW HAHN, PF GOLDBERG, MA BOLAND, GW SAINI, S PAPANICOLAOU, N AF LEE, MJ MAYOSMITH, WW HAHN, PF GOLDBERG, MA BOLAND, GW SAINI, S PAPANICOLAOU, N TI STATE-OF-THE-ART MR-IMAGING OF THE ADRENAL-GLAND SO RADIOGRAPHICS LA English DT Article DE ADRENAL GLAND, CYSTS; ADRENAL GLAND, HEMORRHAGE; ADRENAL GLAND, MR; ADRENAL GLAND, NEOPLASMS; MAGNETIC RESONANCE (MR), CHEMICAL SHIFT ID COMPUTED-TOMOGRAPHY; CHEMICAL-SHIFT; MASSES; BENIGN; LESIONS; CT; PHEOCHROMOCYTOMAS AB The authors discuss the appearances of adrenal diseases characterizable with magnetic resonance (MR) imaging (pheochromocytomas, hemorrhage, cysts, adenomas, myelolipomas, and metastases), new imaging techniques, and differentiation of benign from malignant lesions. Most pheochromocytomas appear markedly hyperintense relative to the liver on T2-weighted images. However, this appearance is not specific, since adrenal metastases and adenomas may have similar features. Occasionally, pheochromocytomas may be iso- or hypointense to the liver on T2-weighted images. One of the new techniques for MR imaging of the adrenal gland, fat suppression, reduces cardiac and respiratory motion-induced artifacts, accentuates small differences in tissue contrast, and eliminates chemical shift artifacts. These advantages far outweigh the disadvantages of inhomogeneity of fat suppression and the fewer sections obtained per acquisition. Differentiation of adrenal metastases from adrenal adenomas with MR imaging is problematic with the use of signal intensity ratios (33% overlap) or T2 calculations. The future of discriminating between adrenal metastases and adenomas may rest with chemical shift MR imaging, which uses in-phase and out-of-phase gradient-echo pulse sequences. This approach relies on the fact that adrenal adenomas contain fat whereas metastases do not. The reported accuracy of chemical shift imaging in differentiating adrenal adenomas from metastases is 96%-100%. C1 HARVARD UNIV,SCH MED,DEPT RADIOL,BOSTON,MA 02115. RP LEE, MJ (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,32 FRUIT ST,BOSTON,MA 02114, USA. NR 31 TC 45 Z9 45 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD SEP PY 1994 VL 14 IS 5 BP 1015 EP 1029 PG 15 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PG637 UT WOS:A1994PG63700010 PM 7991811 ER PT J AU LEE, MJ AF LEE, MJ TI STATE-OF-THE-ART MR-IMAGING OF THE ADRENAL-GLAND - RESPONSE SO RADIOGRAPHICS LA English DT Note RP LEE, MJ (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD SEP PY 1994 VL 14 IS 5 BP 1032 EP 1032 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PG637 UT WOS:A1994PG63700012 ER PT J AU GAZELLE, GS MUELLER, PR AF GAZELLE, GS MUELLER, PR TI ABDOMINAL ABSCESS - IMAGING AND INTERVENTION SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID PERCUTANEOUS CATHETER DRAINAGE; SPLENIC ABSCESS; FLUID COLLECTIONS; DIVERTICULAR ABSCESSES; PELVIC ABSCESSES; PERIAPPENDICEAL ABSCESSES; INFLAMMATORY DISEASE; PANCREATIC NECROSIS; COMPUTED-TOMOGRAPHY; CROHN DISEASE AB Techniques for the diagnosis and treatment of intraabdominal abscesses have evolved rapidly over the last decade. Nevertheless, their accurate diagnosis and appropriate treatment remains a challenge to surgeons and radiologists alike. Abscesses are often seen in the postoperative period despite improved surgical techniques and the increasing use of perioperative antibiotics, and they can lead to increased patient morbidity and even mortality. Published reports of mortality range from 30% to 43% in surgically treated patients to 80% to 100% in undrained collections.(2, 3, 8, 21, 29, 30) The ability to examine the abdomen accurately in these ill patients is therefore of critical importance. In addition, radiologically guided, percutaneous abscess drainage has become the preferred treatment for the great majority of abscesses and other fluid collections. In this article, we describe techniques useful for the diagnosis and treatment of abdominal abscesses, with an emphasis on percutaneous drainage. C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP GAZELLE, GS (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,FRUIT ST,BOSTON,MA 02114, USA. NR 77 TC 43 Z9 44 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0033-8389 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD SEP PY 1994 VL 32 IS 5 BP 913 EP 932 PG 20 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PG423 UT WOS:A1994PG42300008 PM 8085004 ER PT J AU BHALLA, M WAIN, JC SHEPARD, JAO MCLOUD, TC AF BHALLA, M WAIN, JC SHEPARD, JAO MCLOUD, TC TI SURGICAL FLAPS IN THE CHEST - ANATOMIC CONSIDERATIONS, APPLICATIONS, AND RADIOLOGIC APPEARANCE SO RADIOLOGY LA English DT Article DE GRAFTS; STERNUM, ABNORMALITIES; THORAX, ABNORMALITIES; THORAX, SURGERY ID CT AB PURPOSE: To determine the frequency of use of surgical flaps-tissue that is transposed from its normal location to promote healing and prevent complications-in noncardiac thoracic surgery and to demonstrate the typical radiologic appearances of such flaps. MATERIALS AND METHODS: The surgical records of 200 patients who underwent thoracotomy br median sternotomy for noncardiac thoracic surgery were reviewed. Postoperative radiologic studies of randomly selected cases were also reviewed. RESULTS: A total of 213 surgical flaps were used in these patients, including 80 pericardial fat pad flaps, (37.6%), 78 greater omental flaps (36.6%), 21 intercostal muscle flaps (9.9%), 16 anterior serratus muscle flaps (7.5%), and 18 greater pectoral muscle, latissimus dorsi muscle, pleural, thymic, or mediastinal fat flaps (8.5%). The flaps produced unusual opacity or attenuation and/or contour of the mediastinum, hilum, or chest wall. CONCLUSION: Knowledge of common thoracic surgical flaps is helpful in interpretation of postoperative radiologic studies. C1 MASSACHUSETTS GEN HOSP,DEPT THORAC SURG,BOSTON,MA 02114. RP BHALLA, M (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,32 FRUIT ST,BOSTON,MA 02114, USA. NR 11 TC 11 Z9 11 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 SEP PY 1994 VL 192 IS 3 BP 825 EP 830 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PD073 UT WOS:A1994PD07300041 PM 8058955 ER PT J AU CATALANO, P WELLER, E AF CATALANO, P WELLER, E TI STATISTICAL VARIABILITY - WHAT DOES IT MEAN IN RISK ASSESSMENT SO REPRODUCTIVE TOXICOLOGY LA English DT Note DE DOSE-RESPONSE; RISK ASSESSMENT; VARIABILITY AB An essential part of toxicologic research involves assessing the risk from exposure to chemicals, drugs, or other potentially harmful substances. Epidemiologic information establishes an association but not a causal relationship between risk factors and adverse health outcomes. Controlled experiments in laboratory animals, however, provide insight into the agent-outcome relationship and aid in establishing low-risk exposure levels for humans. This is especially true in studies of reproduction and development since epidemiologic data are often limited. While controlled experiments reduce certain difficulties inherent in interpreting epidemiologic data, there still remains the problem of careful evaluation of statistical information. This note addresses issues in the interpretation of statistical variability in fitting dose-response models and estimating exposures associated with a low (or at least specified) level of risk. C1 HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,BOSTON,MA 02115. RP CATALANO, P (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV BIOSTAT,44 BINNEY ST,BOSTON,MA 02115, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0890-6238 J9 REPROD TOXICOL JI Reprod. Toxicol. PD SEP-OCT PY 1994 VL 8 IS 5 BP 433 EP 437 DI 10.1016/0890-6238(94)90085-X PG 5 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA PK704 UT WOS:A1994PK70400009 PM 7841664 ER PT J AU SHIOTA, G KAWASAKI, H NAKAMURA, T SCHMIDT, EV AF SHIOTA, G KAWASAKI, H NAKAMURA, T SCHMIDT, EV TI INHIBITORY EFFECT OF HEPATOCYTE GROWTH-FACTOR AGAINST FAO HEPATOCELLULAR-CARCINOMA CELLS MAY BE ASSOCIATED WITH CHANGES OF INTRACELLULAR SIGNALING PATHWAYS MEDIATED BY PROTEIN-KINASE-C SO RESEARCH COMMUNICATIONS IN MOLECULAR PATHOLOGY AND PHARMACOLOGY LA English DT Article ID CULTURE AB Hepatocyte growth factor (HGF) stimulates growth of mature hepatocytes, whereas it inhibits growth of cancer cells including hepatocellular carcinoma (HCC) cells. However, the regulatory mechanisms for this phenomenon remains unclear. An important intermediary in HGF signal transduction in normal hepatocytes, c-myc, was not induced in FaO HCC cells after HGF stimulation, suggesting that intracellular signalling pathways of HGF in FaO HCC cells were different from those in normal hepatocytes. Protein kinase C (PKC) has been reported to be involved in signalling pathways of many growth factors. To study whether PKC is associated with this inhibitory mechanism, we studied the effects of HGF and/or 12-O-tetradecanoyl phorbol-13-acetate (TPA) on the growth of normal hepatocytes and FaO HCC cells. Consequently, HGF or TPA stimulated growth of normal hepatocytes, while equal doses of TPA or HGF inhibited growth of FaO HCC cells, respectively. In addition, TPA reversed the HGF effect in both normal hepatocytes and FaO HCC cells. These data suggest that an inhibitory effect of HGF on FaO HCC cells may be associated with changes of protein kinase C-mediated intracellular signalling pathways. C1 OSAKA UNIV,BIOMED RES CTR,DIV TUMOR BIOCHEM,SUITA,OSAKA 565,JAPAN. MASSACHUSETTS GEN HOSP,CTR CANC,BOSTON,MA 02129. RP SHIOTA, G (reprint author), TOTTORI UNIV,SCH MED,DEPT INTERNAL MED 2,YONAGO,TOTTORI 683,JAPAN. NR 11 TC 21 Z9 22 U1 0 U2 0 PU P J D PUBLICATIONS LTD PI WESTBURY PA PO BOX 966, WESTBURY, NY 11590 SN 1078-0297 J9 RES COMMUN MOL PATH JI Res. Commun. Mol. Pathol. Pharmacol. PD SEP PY 1994 VL 85 IS 3 BP 271 EP 278 PG 8 WC Biochemistry & Molecular Biology; Pathology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pathology; Pharmacology & Pharmacy GA PK025 UT WOS:A1994PK02500003 PM 7827802 ER PT J AU ARRUNATEGUICORREA, V DUTT, J FOSTER, CS AF ARRUNATEGUICORREA, V DUTT, J FOSTER, CS TI THE ROLE OF B-LYMPHOCYTES IN EXPERIMENTAL HERPES-SIMPLEX VIRAL RETINITIS SO SCANDINAVIAN JOURNAL OF IMMUNOLOGY LA English DT Article ID CELL-DEFICIENT MICE; SUPPRESSOR T-CELLS; ANTERIOR-CHAMBER; PASSIVE TRANSFER; CONSTANT-REGION; IMMUNE-RESPONSE; VIRUS; INOCULATION; KERATITIS; SEQUENCE AB The purpose of this study was to examine B cell participation in experimental herpes simplex virus (HSV) retinitis. Passive immunization with anti-herpes antibody protects BALB/c mice from herpes simplex retinitis (HSR). Using anti-Mu antibody treatment, we modified the B cell population of C.B-17 mice, normally resistant to HSR, in order to test the hypothesis that such treatment would render them susceptible to HSR by impairing their early antibody response to anterior chamber (AC) inoculation with HSV. We analysed the effect of anti-Mu treatment on their susceptibility to HSR and then employed Polymerase Chain Reaction (PCR) and ELISA techniques to study the patterns of immunoglobulin gene and protein expression, and the T-cell receptor alpha/beta (TCR alpha beta) gene expression after AC inoculation of HSV. Immunohistopathologic analysis revealed that 100% of the B cell deficient mice (B-) developed contralateral retinitis following AC inoculation, confirming the hypothesis that anti-Mu antibody treatment would convert HSR-resistant mice into HSR-susceptible ones. Transfer of B cells from naive congenic donor mice resulted in 67% of recipient B- mice developing contralateral retinitis. Transfer of anti-HSV antibody conferred nearly complete protection, with only 11% of mice developing retinitis (P < 0.005). PCR and ELISA analysis showed that both untreated and B- C.B-17 mice showed similar dynamic patterns of mRNA IgG isotype expression and of anti-HSV IgG isotypic antibody response following AC inoculation. Thus, we were forced to reject the hypothesis that an impaired early antibody response is primarily responsible for the increased HSR susceptibility seen in B- mice. In contrast, PCR analysis of TCR alpha/beta mRNA expression revealed dramatic differences between susceptible and resistant mice, suggesting that TCR VP selection and usage may be a critical factor influencing HSR-sensitivity in this murine model, and that B cells (and immunoglobulin isotype) may play a role in TCR VP selection and usage after ocular encounter with HSV. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,HILLES IMMUNOL LAB,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,RHOADS MOLEC IMMUNOL LABS,BOSTON,MA. FU NEI NIH HHS [EY-06008] NR 29 TC 8 Z9 8 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0300-9475 J9 SCAND J IMMUNOL JI Scand. J. Immunol. PD SEP PY 1994 VL 40 IS 3 BP 299 EP 307 DI 10.1111/j.1365-3083.1994.tb03466.x PG 9 WC Immunology SC Immunology GA PE544 UT WOS:A1994PE54400004 PM 8091129 ER PT J AU MUELLER, PR DAWSON, SL AF MUELLER, PR DAWSON, SL 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 SEP PY 1994 VL 11 IS 3 BP 180 EP 180 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PG007 UT WOS:A1994PG00700001 ER PT J AU SHEPARD, JAO AF SHEPARD, JAO TI COMPLICATIONS OF PERCUTANEOUS NEEDLE ASPIRATION BIOPSY OF THE CHEST - PREVENTION AND MANAGEMENT SO SEMINARS IN INTERVENTIONAL RADIOLOGY LA English DT Article RP SHEPARD, JAO (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114, USA. NR 0 TC 11 Z9 11 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 SEP PY 1994 VL 11 IS 3 BP 181 EP 186 DI 10.1055/s-2008-1074754 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PG007 UT WOS:A1994PG00700002 ER PT J AU ZERBEY, AL DAWSON, SL MUELLER, PR AF ZERBEY, AL DAWSON, SL MUELLER, PR TI PLEURAL INTERVENTIONS AND COMPLICATIONS SO SEMINARS IN INTERVENTIONAL RADIOLOGY LA English DT Article C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIOL,BOSTON,MA 02114. NR 0 TC 1 Z9 1 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 SEP PY 1994 VL 11 IS 3 BP 187 EP 197 DI 10.1055/s-2008-1074755 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PG007 UT WOS:A1994PG00700003 ER PT J AU MCNICHOLAS, MMJ LEE, MJ DAWSON, SL MUELLER, PR AF MCNICHOLAS, MMJ LEE, MJ DAWSON, SL MUELLER, PR TI COMPLICATIONS OF PERCUTANEOUS BILIARY DRAINAGE AND STRICTURE DILATATION SO SEMINARS IN INTERVENTIONAL RADIOLOGY LA English DT Article C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,FRUIT ST,BOSTON,MA 02114. NR 0 TC 6 Z9 7 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 SEP PY 1994 VL 11 IS 3 BP 242 EP 253 DI 10.1055/s-2008-1074762 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PG007 UT WOS:A1994PG00700010 ER PT J AU BOLAND, GW LEE, MJ DAWSON, SL MUELLER, PR AF BOLAND, GW LEE, MJ DAWSON, SL MUELLER, PR TI PERCUTANEOUS ABSCESS DRAINAGE - COMPLICATIONS SO SEMINARS IN INTERVENTIONAL RADIOLOGY LA English DT Article C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT PATHOL,FRUIT ST,BOSTON,MA 02114. NR 0 TC 4 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 SEP PY 1994 VL 11 IS 3 BP 267 EP 275 DI 10.1055/s-2008-1074764 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PG007 UT WOS:A1994PG00700012 ER PT J AU SUIT, HD SPIRO, I AF SUIT, HD SPIRO, I TI ROLE OF RADIATION IN THE MANAGEMENT OF ADULT PATIENTS WITH SARCOMA OF SOFT-TISSUE SO SEMINARS IN SURGICAL ONCOLOGY LA English DT Article DE SARCOMA; SOFT TISSUES; RADIATION THERAPY; LOCAL CONTROL; PREOPERATIVE AB Radiation in moderate dose levels, viz. 60-65 Gy at 2 Gy/fraction, administered in combination with conservative surgery, yields local control frequencies at least comparable to those achieved by radical resectional surgery alone. The clinical interest in this management strategy is the reduction in the scope of the resection and a consequent gain in cosmetic and functional status. This combined approach is favored for sarcomas so situated that resection with wide margin, greater-than-or-equal-to 2 cm at the most narrow, cannot be realized unless there is a clinically important loss in function. Where radical surgery is planned, there must be great care in assessment of the probability of achieving good margins. The patient is ill served if there is radical surgery and then, because of close margins, postoperative radiation is required. There appears to be clinical gain for the patient with a large sarcoma by administering the radiation preoperatively. Advantages include smaller treatment volume and higher local control rates. The management of the surgical wound in the irradiated patient is discussed. Also, brief consideration is given to current use of brachytherapy, high linear energy transfer (LET) radiation, and combination of radiation and chemotherapy. (C) 1994 Wiley-Liss, Inc. RP SUIT, HD (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02111, USA. NR 0 TC 47 Z9 49 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 8756-0437 J9 SEMIN SURG ONCOL JI Semin. Surg. Oncol. PD SEP-OCT PY 1994 VL 10 IS 5 BP 347 EP 356 DI 10.1002/ssu.2980100507 PG 10 WC Oncology; Surgery SC Oncology; Surgery GA PH270 UT WOS:A1994PH27000006 PM 7997728 ER PT J AU INOUE, Y BODE, BP SOUBA, WW AF INOUE, Y BODE, BP SOUBA, WW TI HEPATIC NA+-INDEPENDENT AMINO-ACID-TRANSPORT IN ENDOTOXEMIC RATS - EVIDENCE FOR SELECTIVE STIMULATION OF ARGININE TRANSPORT SO SHOCK LA English DT Article ID PLASMA-MEMBRANE VESICLES; LIVER; SYSTEM; GLUTAMINE; HEPATOCYTE; CELLS; METABOLISM AB The effects of endotoxin on the activities of the major Na+-independent amino acid transporters in rat liver (Systems n, asc, L, b(o,+) and y(+)) were studied using using hepatic plasma membrane vesicles (HPMVs). Rats were treated with a single dose of Escherichia coli endotoxin (E. coli lipopolysaccharide 0127:B8 (LPS), 7.5, 15, or 30 mg/kg BW) and HPMVs were prepared by Percoll density gradient centrifugation at various timepoints after LPS administration. Vesicle purity and integrity was established by assay of enzyme markers and identical equilibrium uptakes. The activities of the Na+-independent amino acid transport systems y(+) and b(o,+) (arginine), asc (alanine and cysteine), L (leucine), and n (glutamine) were evaluated by measuring the uptake of radiolabeled amino acids using a rapid mixing/filtration technique. Amino acid uptake by HPMVs consisted of saturable and nonsaturable components. Prior treatment with endotoxin did not alter the activities of Systems n, asc, or L but resulted in a time- and dose-dependent stimulation of saturable arginine transport. Arginine transport increased within 2 h of LPS administration and exhibited a return towards basal levels by 24 h. Nonsaturable uptake (diffusion) in HPMVs was unaltered by LPS treatment. Kinetic analysis of arginine transport demonstrated the presence of both a high affinity and a low affinity carrier. Treatment with LPS resulted in a 73% increase in the V-max of the high affinity carrier (System y(+)) and a 25% increase in the V-max of the low affinity transporter (System b(o,+)). The data indicate selective stimulation of Na+-independent arginine transport in the liver during endotoxemia which may serve to support important arginine-dependent pathways during sepsis. C1 MASSACHUSETTS GEN HOSP, DEPT SURG, DIV SURG ONCOL, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA USA. UNIV FLORIDA, COLL MED, DEPT SURG, SURG METAB LAB, GAINESVILLE, FL USA. UNIV FLORIDA, COLL MED, NUTR LAB, GAINESVILLE, FL USA. FU NCI NIH HHS [R01 CA57690] NR 24 TC 17 Z9 17 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1073-2322 EI 1540-0514 J9 SHOCK JI Shock PD SEP PY 1994 VL 2 IS 3 BP 164 EP 170 DI 10.1097/00024382-199409000-00002 PG 7 WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System & Cardiology GA PL651 UT WOS:A1994PL65100002 PM 7743345 ER PT J AU SILVERMAN, PR CAMPBELL, L PATTI, P AF SILVERMAN, PR CAMPBELL, L PATTI, P TI REUNIONS BETWEEN ADOPTEES AND BIRTH PARENTS - THE ADOPTIVE PARENTS VIEW SO SOCIAL WORK LA English DT Article DE ADOPTIVE FAMILIES; BIRTH PARENTS; OPENNESS; REUNIONS; SEARCH PROCESS ID EXPERIENCE AB This article looks at the reactions of adoptive parents to reunions between their adopted children and the children's birth parents. The focus is on how adoptive parents feel the reunion affects the family's integrity. Three types of family responses are identified: (1) closed, (2) divided, and (3) open. Acceptance of the differences between families created by adoption of children and those created by childbirth was a factor in the families' openness. Closed families saw no difference, and reunion suggested to the adults that they had failed as parents. Parents in open families understood the difference in families, saw the children as separate, and felt no threat to their competence as parents. Families' need for boundaries is examined, and the way the concept of family is constructed is discussed. Implications for the practice of adoption are considered. C1 EDISON COMMUNITY COLL,PUNTA GORDA,FL. RP SILVERMAN, PR (reprint author), MASSACHUSETTS GEN HOSP,INST HLTH PROFESS,101 MERRIMAC ST,BOSTON,MA 02114, USA. FU NIMH NIH HHS [MH17058] NR 24 TC 6 Z9 6 U1 0 U2 2 PU NATL ASSOC SOCIAL WORKERS PI WASHINGTON PA 750 FIRST ST, NE, STE 700, WASHINGTON, DC 20002-4241 SN 0037-8046 J9 SOC WORK JI Soc. Work PD SEP PY 1994 VL 39 IS 5 BP 542 EP 549 PG 8 WC Social Work SC Social Work GA PE146 UT WOS:A1994PE14600008 PM 7939866 ER PT J AU BILLETT, AL SALLAN, SE AF BILLETT, AL SALLAN, SE TI ANTIEMETICS IN CHILDREN RECEIVING CANCER-CHEMOTHERAPY SO SUPPORTIVE CARE IN CANCER LA English DT Article; Proceedings Paper CT 6th International Symposium: Supportive Care in Cancer CY MAR 02-05, 1994 CL NEW ORLEANS, LA DE ANTIEMETICS; PEDIATRIC CANCER; NAUSEA AND VOMITING CHEMOTHERAPY SIDE EFFECTS ID CISPLATIN-INDUCED NAUSEA; HIGH-DOSE METOCLOPRAMIDE; ANTI-EMETIC EFFICACY; DOUBLE-BLIND; INDUCED EMESIS; PLUS DEXAMETHASONE; INTRAVENOUS METOCLOPRAMIDE; ONDANSETRON GR-38032F; SEROTONIN ANTAGONIST; PROPHYLAXIS AB Nausea and vomiting are debilitating side effects that often accompany the administration of chemotherapy and may lead to adverse physiological and psychological effects. Chemotherapy agents usually stimulate the chemoreceptor trigger zone, which then sends signals to the vomiting center in the medullary lateral reticular formation. The neurochemistry of vomiting involves serotonin and serotonin S3 receptors. Nausea and vomiting are difficult to treat once they have occurred, and prior poor antiemetic control may lead to future anticipatory nausea and vomiting. Thus, good antiemetic regimens must be prophylactic, scheduled, and individualized. Specific regimens must be adjusted to account for the emetogenic potential of the chemotherapy drug(s) being administered and the individual patient's preferences. The major classes of antiemetics include serotonin S3 receptor antagonists, phenothiazines and metoclopramide. Steroids are ineffective antiemetics alone but good potentiators of other antiemetics. We usually recommend a serotonin S3 receptor antagonist alone for less emetogenic regimens or in conjunction with dexamethasone for more emetogenic regimens. For breakthough vomiting, we usually add lorazepam and/or scopolamine. C1 CHILDRENS HOSP MED CTR,DIV HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. RP BILLETT, AL (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PEDIAT,44 BINNEY ST,BOSTON,MA 02115, USA. NR 38 TC 8 Z9 8 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0941-4355 J9 SUPPORT CARE CANCER JI Support. Care Cancer PD SEP PY 1994 VL 2 IS 5 BP 279 EP 285 DI 10.1007/BF00365578 PG 7 WC Oncology; Health Care Sciences & Services; Rehabilitation SC Oncology; Health Care Sciences & Services; Rehabilitation GA PJ206 UT WOS:A1994PJ20600002 PM 8000723 ER PT J AU FERNANDEZDELCASTILLO, C SCHMIDT, J WARSHAW, AL RATTNER, DW AF FERNANDEZDELCASTILLO, C SCHMIDT, J WARSHAW, AL RATTNER, DW TI INTERSTITIAL PROTEASE ACTIVATION IS THE CENTRAL EVENT IN PROGRESSION TO NECROTIZING PANCREATITIS SO SURGERY LA English DT Article ID DUCT OBSTRUCTION; PLASMA-MEMBRANE; ACINAR-CELLS; RAT; SECRETAGOGUE; STIMULATION; PEPTIDES; ENZYMES; PATHOGENESIS; ENTEROKINASE AB Background. Although intracellular protease activation is thought to be an early event in acute pancreatitis, factors determining progression from edematous to necrotizing pancreatitis are largely unknown. With enterokinase a probe and an immunoassay quantifying free trypsinogen activation peptides (TAP), we sought evidence for the presence of interstitial trypsinogen in edamalous pancreatitis and documented the effects of its ectopic activation. Methods. Edematous pancreatitis in the rat was induced by supramaximal stimulation with cerulein (5 mu g/kg/hr) and coupled with enterokinase infused into the pancreatic duct at 30 mm Hg. Blue dextran infusion at this pressure corroborated interstitial delivery. Rats with no stimulation, maximal physiologic stimulation (0.25 mu g/kg/hr of cerulein), or intraductal saline infusion served as controls. TAP levels measured by enzyme-linked immunosorbent assay, 6-hour survival, and histopathology were used as end points. Results. Intraductal enterokinase infusion alone or in combination with maximal physiologic stimulation generated only slight increases in TAP level and no or minimal pancreatic injury. In contrast, enterokinase superimposed on edematous pancreatitis (supramaximal cerulein stimulation) produced fulminant pancreatitis and rapid death of all animals within 6 hours. Pancreatic histopathology showed severe intrapancreatic hemorrhage, acinar inflammation, and necrosis. TAP levels were significantly higher in plasma (p = 0.02), urine (p = 0.05), and ascites (p < 0.001) when compared with all other groups. Conclusions. In edematous pancreatic pancreatitis a large pool of trypsinogen accumulates in the interstitial space, Activation of these proenzymes leads to catastrophic consequences and may underlie progression from mild to necrotizing pancreatitis. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,BOSTON,MA 02114. NR 28 TC 47 Z9 47 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0039-6060 J9 SURGERY JI Surgery PD SEP PY 1994 VL 116 IS 3 BP 497 EP 504 PG 8 WC Surgery SC Surgery GA PE976 UT WOS:A1994PE97600004 PM 8079180 ER PT J AU SHELLITO, PC AF SHELLITO, PC TI COMBINED LAPAROSCOPIC-ENDOSCOPIC GASTROTOMY - COMMENTARY SO SURGICAL ENDOSCOPY-ULTRASOUND AND INTERVENTIONAL TECHNIQUES LA English DT Note RP SHELLITO, PC (reprint author), MASSACHUSETTS GEN HOSP,DEPT SURG,ACC 336,15 PARKMAN ST,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0930-2794 J9 SURG ENDOSC-ULTRAS JI Surg. Endosc.-Ultrason. Interv. Tech. PD SEP PY 1994 VL 8 IS 9 BP 1144 EP 1144 DI 10.1007/BF00705743 PG 1 WC Surgery SC Surgery GA PF095 UT WOS:A1994PF09500028 ER PT J AU BODIS, S ALEXANDER, E KOOY, H LOEFFLER, JS AF BODIS, S ALEXANDER, E KOOY, H LOEFFLER, JS TI THE PREVENTION OF RADIOSURGERY-INDUCED NAUSEA AND VOMITING BY ONDANSETRON - EVIDENCE OF A DIRECT EFFECT ON THE CENTRAL-NERVOUS-SYSTEM CHEMORECEPTOR TRIGGER ZONE SO SURGICAL NEUROLOGY LA English DT Article DE AREA POSTREMA; ONDANSETRON; RADIATION; STEREOTAXIC RADIOSURGERY; VOMITING ID CISPLATIN-INDUCED EMESIS; DEXAMETHASONE; GR-38032F; SEROTONIN AB Nausea and emesis are significant side effects in patients undergoing stereotactic radiosurgery for brain lesions in the region of the chemoreceptor trigger zone (area postrema of the brain). Even with the current antiemetic treatment (prochlorperazine +/- corticosteroids), those side effects remain significant. The purpose of this study is twofold: [1] to evaluate the efficacy of ondansetron in inhibiting nausea and emesis in stereotactic radiosurgery patients and [2] to demonstrate that ondansetron's locus of action is the central nervous system (CNS) chemoreceptor trigger zone in the area postrema. In a pilot study, 10 patients receiving greater than or equal to 350 cGy in a single fraction of radiosurgery to the region of the area postrema received 32 mg ondansetron iv 1 hour prior to treatment +/- corticosteroids. In a retrospective analysis these results were compared to those of patients with similar features (and matched for radiation dose to the area postrema and the dose of corticosteroids) who received prochlorperazine +/- corticosteriods. Nine of 10 patients in the ondansetron group had no nausea or emesis within 48 hours after treatment; one patient experienced one episode of emesis. In the prochlorperazine group, eight patients had symptoms, three patients needed hospitalization or a physician's care for emesis within 24 hours, and five had nausea with no specific treatment. These preliminary results suggest that ondansetron is a safe and efficient drug to prevent nausea and emesis in this patient group. The precise mechanism of action of ondansetron in these patients is unknown, but is likely due to the drug's serotonin-blocking effect within the CNS. A randomized, prospective study has been started at our institution to confirm these preliminary results. C1 CHILDRENS HOSP,BRIGHAM & WOMENS HOSP,CTR BRAIN TUMOR,BOSTON,MA. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DANA FARBER CANC INST,DEPT NEUROSURG,BOSTON,MA. NR 8 TC 23 Z9 23 U1 0 U2 1 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0090-3019 J9 SURG NEUROL JI Surg. Neurol. PD SEP PY 1994 VL 42 IS 3 BP 249 EP 252 DI 10.1016/0090-3019(94)90272-0 PG 4 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA QB699 UT WOS:A1994QB69900011 PM 7940114 ER PT J AU BONIUK, V NOCKOWITZ, R AF BONIUK, V NOCKOWITZ, R TI PERFORATION OF THE GLOBE DURING RETROBULBAR INJECTION - MEDICOLEGAL ASPECTS OF 4 CASES SO SURVEY OF OPHTHALMOLOGY LA English DT Review DE ANESTHESIA; MEDICOLEGAL CLAIMS; PERFORATION OF GLOBE; RETINAL DETACHMENT; RETROBULBAR INJECTION ID INTRAOCULAR INJECTION; OCULAR PERFORATION; CATARACT-SURGERY; ANESTHESIA; PENETRATION AB Perforation or penetration of the globe is a risk of retrobulbar injection of anesthetic. Visual outcome following this complication depends on the severity of injury to the retina and on the physician's ability to promptly recognize and treat it. Four cases are presented to illustrate factors that contribute to proper management of this complication as well as to a favorable medicolegal position for the physician. C1 MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02114. RP BONIUK, V (reprint author), QUEENS HOSP CTR,DEPT OPHTHALMOL,T BLDG,82-68 164 ST,JAMAICA,NY 11432, USA. NR 14 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0039-6257 J9 SURV OPHTHALMOL JI Surv. Ophthalmol. PD SEP-OCT PY 1994 VL 39 IS 2 BP 141 EP 145 DI 10.1016/0039-6257(94)90159-7 PG 5 WC Ophthalmology SC Ophthalmology GA PH628 UT WOS:A1994PH62800005 PM 7801222 ER PT J AU HERSHMAN, JM AF HERSHMAN, JM TI HIGHLIGHTS OF THIS ISSUE SO THYROID LA English DT Editorial Material RP HERSHMAN, JM (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,BLDG 114,ROOM 200,WILSHIRE & SAWTELLE BLVD,LOS ANGELES,CA 90073, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1050-7256 J9 THYROID JI Thyroid PD FAL PY 1994 VL 4 IS 3 BP 237 EP 237 DI 10.1089/thy.1994.4.237 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PH851 UT WOS:A1994PH85100001 ER PT J AU HERSHMAN, JM AF HERSHMAN, JM TI ASTWOOD,TED INTELLECTUAL LEGACY - SOME PERSONAL VIEWPOINTS SO THYROID LA English DT Article C1 UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA 90073. RP HERSHMAN, JM (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,DEPT MED,BLDG 114,ROOM 200,WILSHIRE & SAWTELLE BLVDS,LOS ANGELES,CA 90073, USA. NR 19 TC 2 Z9 2 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1050-7256 J9 THYROID JI Thyroid PD FAL PY 1994 VL 4 IS 3 BP 313 EP 317 DI 10.1089/thy.1994.4.313 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PH851 UT WOS:A1994PH85100015 PM 7833669 ER PT J AU ROSS, DS AF ROSS, DS TI HYPERTHYROIDISM, THYROID-HORMONE THERAPY, AND BONE SO THYROID LA English DT Article ID TOTALLY THYROIDECTOMIZED PATIENTS; THYROXINE REPLACEMENT THERAPY; MINERAL DENSITY; POSTMENOPAUSAL WOMEN; SUBCLINICAL HYPERTHYROIDISM; CALCITONIN DEFICIENCY; PREMENOPAUSAL WOMEN; PHOTON-ABSORPTIOMETRY; SERUM OSTEOCALCIN; HYPER-THYROIDISM AB Clinically symptomatic osteoporosis and fractures from thyrotoxicosis have been rare since the availability of antithyroid drugs and radioiodine for the treatment of hyperthyroidism. However, the widespread use of bone density measurements and sensitive TSH assays in the past decade has demonstrated that women taking levothyroxine with subclinical hyperthyroidism have reduced bone density. Cortical bone is affected more than trabecular bone, and postmenopausal women are at a greater risk than premenopausal women. However, it is uncertain whether subclinical hyperthyroidism is associated with an increased risk of fracture. Hypothyroidism is associated with an increase in cortical bone width. The initiation of levothyroxine treatment in hypothyroid women results in a reduction in cortical bone width to levels seen in euthyroid controls after 6-12 months. There is no reduction in bone density when women with subclinical hypothyroidism are treated with levothyroxine for a year. A single study showing reduced bone density in patients receiving chronic levothyroxine replacement therapy requires confirmation and raises an important question: Does levothyroxine replacement therapy, which results in higher serum thyroxine concentrations than those seen in euthyroid controls, accurately mimic physiology? C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP ROSS, DS (reprint author), MASSACHUSETTS GEN HOSP,THYROID UNIT ACC730,BOSTON,MA 02114, USA. NR 81 TC 83 Z9 86 U1 2 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1050-7256 J9 THYROID JI Thyroid PD FAL PY 1994 VL 4 IS 3 BP 319 EP 326 DI 10.1089/thy.1994.4.319 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PH851 UT WOS:A1994PH85100016 PM 7833670 ER PT J AU LEWIS, CB AF LEWIS, CB TI FUNCTIONAL ASSESSMENT AND MANAGED CARE READINESS .2. 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. RP LEWIS, CB (reprint author), PHYS THERAPY SERV WASHINGTON DC INC,WASHINGTON,DC, USA. NR 4 TC 0 Z9 0 U1 3 U2 3 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 SEP PY 1994 VL 10 IS 1 BP R5 EP R5 PG 1 WC Gerontology; Rehabilitation SC Geriatrics & Gerontology; Rehabilitation GA QD379 UT WOS:A1994QD37900001 ER PT J AU PEARCE, LB BORODIC, GE FIRST, ER MACCALLUM, RD AF PEARCE, LB BORODIC, GE FIRST, ER MACCALLUM, RD TI MEASUREMENT OF BOTULINUM TOXIN ACTIVITY - EVALUATION OF THE LETHALITY ASSAY SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID ACUTE TOXICITY; DOSE STANDARDIZATION; PROTEOLYTIC CLEAVAGE; LD50; NEUROTOXIN; ANIMALS AB The use of the mouse lethality assay for the estimation of the biologic activity of botulinum toxin was evaluated. The relationship between the number of animals, number of doses, and duration of the assay used to estimate the LD50 and the precision of the assay was investigated. The results of these studies demonstrated that the LD50 for botulinum toxin can be estimated with a high degree of precision (+/-5%). The precision of the assay is not increased by using more than a 5-dose 50-animal assay or extending the duration of the assay beyond 72 hr. Estimates of the LD50 obtained at 48 hr were only slightly less precise but underestimated the LD50 by 15%. Analysis of the commercially available preparations of botulinum toxin with the mouse LD50 assay revealed significant discrepencies between the units of toxin in these preparations. In addition, a 2.67-fold difference in the relative potency of the two preparations of botulinum A toxin was observed using a regional chemodenervation assay that measures paralysis. The mouse LD50 assay could not detect this large difference in the potency of the two approved clinical preparations of botulinum toxin. The results of these studies demonstrate that although the mouse LD50 assay can be used to estimate the number of units of botulinum toxin with a high degree of precision this assay alone is not an adequate method for assessing the preclinical biological potency of botulinum toxin. (C) 1994 Academic Press, Inc. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,BOSTON,MA 02114. RP PEARCE, LB (reprint author), BOSTON UNIV,SCH MED,DEPT PHARMACOL,BOSTON,MA 02118, USA. NR 34 TC 89 Z9 93 U1 3 U2 7 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD SEP PY 1994 VL 128 IS 1 BP 69 EP 77 DI 10.1006/taap.1994.1181 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA PF251 UT WOS:A1994PF25100009 PM 8079356 ER PT J AU LAM, HC KOMINSKI, GF PETZ, LD SOFAER, S AF LAM, HC KOMINSKI, GF PETZ, LD SOFAER, S TI FACTORS AFFECTING THE LABOR EFFICIENCY OF HOSPITAL-BASED BLOOD-BANK LABORATORIES SO TRANSFUSION LA English DT Article AB Background: A variety of financing mechanisms and managerial innovations have been developed in the past decade to control hospital costs. Some evidence suggests that those changes have not produced substantial improvements in labor efficiency among employees in the hospital's technical level, such as in the blood bank laboratories. Study Design and Methods: This study measured labor efficiency in 40 hospital-based blood bank laboratories in Southern California during the year from July 1989 to June 1990 and explored the impact of financial, managerial, and operational factors on labor efficiency. Results: With standardized output measures used in all blood bank laboratories, a wide variation of labor efficiency was found. Multivariate analyses indicate that the labor efficiency of blood bank employees was not influenced by organizational financial incentives, but was affected by the managerial styles of blood bank managers. Conclusion: Interpretation of the findings suggests that labor efficiency is affected by operational designs intended to improve responses to variable workloads and reduce slack time. C1 UNIV CALIF LOS ANGELES,SCH PUBL HLTH,DEPT HLTH SCI,LOS ANGELES,CA 90025. UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA. GEORGE WASHINGTON UNIV,SCH MED,DEPT HLTH SCI,WASHINGTON,DC. RP LAM, HC (reprint author), UNIV CALIF LOS ANGELES,W LOS ANGELES VET ADM MED CTR,2134 PARNELL AVE,LOS ANGELES,CA 90025, USA. NR 7 TC 6 Z9 6 U1 1 U2 3 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 1994 VL 34 IS 9 BP 811 EP 817 DI 10.1046/j.1537-2995.1994.34994378284.x PG 7 WC Hematology SC Hematology GA PJ636 UT WOS:A1994PJ63600014 PM 8091472 ER PT J AU FERRARA, JLM AF FERRARA, JLM TI CELLULAR AND MOLECULAR MECHANISMS OF GRAFT-VERSUS-HOST DISEASE SO TRANSFUSION SCIENCE LA English DT Article RP FERRARA, JLM (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,44 BINNEY ST,ROOM DANA 1640A,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA39542]; NIAID NIH HHS [AI30018] NR 0 TC 3 Z9 3 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0955-3886 J9 TRANSFUS SCI JI Transfus. Sci. PD SEP PY 1994 VL 15 IS 3 BP 197 EP 206 DI 10.1016/0955-3886(94)90132-5 PG 10 WC Hematology SC Hematology GA PE729 UT WOS:A1994PE72900004 PM 10155541 ER PT J AU HOLLANDER, GA BIERER, BE BURAKOFF, SJ AF HOLLANDER, GA BIERER, BE BURAKOFF, SJ TI MOLECULAR AND BIOLOGICAL ACTIONS OF CYCLOSPORINE-A AND FK506 ON T-CELL DEVELOPMENT AND FUNCTION SO TRANSFUSION SCIENCE LA English DT Article AB The microbial products cyclosporin A (CsA) and FK506 are potent immunosuppressive agents in experimental and clinical transplantation. Binding of both drugs to intracellular immunophilins results in the inhibition of calcineurin activity and the prevention of interleukin-2 gene transcription and, thus, in the inhibition of T cell receptor-dependent T cell activation. CsA and FK506 also have a profound effect on the structure and function of the thymus with disruption of positive and negative selection of T cells. These influences on thymic microenvironment and T cell ontogeny disrupt the induction or maintenance of self-tolerance (or both) and are thus of relevance to clinical transplantation immunology. RP HOLLANDER, GA (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115, USA. FU NCI NIH HHS [P01 CA39542-08A1]; PHS HHS [R01 A132514] NR 0 TC 19 Z9 20 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0955-3886 J9 TRANSFUS SCI JI Transfus. Sci. PD SEP PY 1994 VL 15 IS 3 BP 207 EP 220 DI 10.1016/0955-3886(94)90133-3 PG 14 WC Hematology SC Hematology GA PE729 UT WOS:A1994PE72900005 PM 10155542 ER PT J AU STAINIER, DYR FISHMAN, MC AF STAINIER, DYR FISHMAN, MC TI THE ZEBRAFISH AS A MODEL SYSTEM TO STUDY CARDIOVASCULAR DEVELOPMENT SO TRENDS IN CARDIOVASCULAR MEDICINE LA English DT Article ID MYOSIN HEAVY-CHAIN; SKELETAL-MUSCLE; HEART TUBE; CELL FATE; DROSOPHILA; DIFFERENTIATION; EXPRESSION; COMMITMENT; MUTATION; POLARITY AB The zebrafish, Brachydanio rerio, is vapidly becoming a system of choice for vertebrate developmental biologists. It presents unique embryological attributes and is amenable to saturation style mutagenesis, a powerful approach that, in invertebrates, has already led to the identification of a large number of key developmental genes. Since fertilization is external, the zebrafish embryo develops in the dish and is thus accessible for continued observation and manipulation at all stages of development. Furthermore, because the embryo is transparent, the developing heart and vessels can be resolved at the single-cell level. A large number of mutations that affect the development of cardiovascular form and function have recently been isolated front large-scale generic screens for zygotic embryonic lethals. Our further understanding of the development of the cardiovascular system is important not only because of the high incidence, and familial inheritance, of congenital abnormalities, but also because it should lead ro novel, differentiation-based strategies for the analysis and therapy of the diseased state. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. RP STAINIER, DYR (reprint author), MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,BOSTON,MA 02129, USA. NR 37 TC 63 Z9 63 U1 3 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1050-1738 J9 TRENDS CARDIOVAS MED JI Trends Cardiovasc. Med. PD SEP-OCT PY 1994 VL 4 IS 5 BP 207 EP 212 DI 10.1016/1050-1738(94)90036-1 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PK640 UT WOS:A1994PK64000002 PM 21244869 ER PT J AU ACKERMAN, RH AF ACKERMAN, RH TI NEUROIMAGING LOOKS TO THE FUTURE SO WESTERN JOURNAL OF MEDICINE LA English DT Article C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. RP ACKERMAN, RH (reprint author), MASSACHUSETTS GEN HOSP,NEUROL SERV,NEUROVASC LAB,GRAY 2,BOSTON,MA 02114, USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU CALIFORNIA PHYSICIAN MAGAZINE PI SAN FRANCISCO PA C/O DONNA TAYLOR, EDITOR, PO BOX 7690, SAN FRANCISCO, CA 94102-7690 SN 0093-0415 J9 WESTERN J MED JI West. J. Med. PD SEP PY 1994 VL 161 IS 3 BP 315 EP 318 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA PJ261 UT WOS:A1994PJ26100016 PM 7975573 ER PT J AU LIN, EY BRUNICARDI, FC AF LIN, EY BRUNICARDI, FC TI HIV-INFECTION AND SURGEONS SO WORLD JOURNAL OF SURGERY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HEALTH-CARE WORKERS; INTRAVENOUS-DRUG-USERS; OPERATING-ROOM; BLOOD CONTACT; RISK-FACTORS; AIDS; TRANSMISSION; SEROPREVALENCE; EPIDEMIOLOGY AB The human immunodeficiency virus (HIV) causes acquired immunodeficiency syndrome, which remains uniformly fatal in affected individuals. A common route of HIV transmission is via inoculation of contaminated blood, which may occur during surgical procedures. Surgeons may estimate their risk of HIV infection over a 30-year surgical career based on HIV prevalence among surgical patients, percutaneous injury rate per operation, and seroconversion rate. Surgeons can reduce their risk by various means, but the most pragmatic is by reducing the rate of percutaneous injury through optimal surgical technique and proper precautions. C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT SURG,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,DEPT SURG,LOS ANGELES,CA 90073. NR 48 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0364-2313 J9 WORLD J SURG JI World J.Surg. PD SEP-OCT PY 1994 VL 18 IS 5 BP 753 EP 757 PG 5 WC Surgery SC Surgery GA PJ239 UT WOS:A1994PJ23900020 PM 7975695 ER PT J AU MIZUTANI, H ROSWIT, W HEMPERLY, J LAWLEY, T COMPTON, C SWERLICK, R KUPPER, TS AF MIZUTANI, H ROSWIT, W HEMPERLY, J LAWLEY, T COMPTON, C SWERLICK, R KUPPER, TS TI HUMAN DERMAL MICROVASCULAR ENDOTHELIAL-CELLS EXPRESS THE 140-KD ISOFORM OF NEURAL CELL-ADHESION MOLECULE SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID NCAM; DIFFERENTIATION; SEQUENCE; ANTIGEN; BINDING; BRAIN; ACID; CDNA AB It has only recently been appreciated that the level of gene expression of cell surface markers can be different in endothelial cells derived from different anatomical sites, and that these differences can persist in vitro. In this study, we identify an immunoglobulin gene superfamily member, neural cell adhesion molecule (NCAM), that is expressed on the cell surface of human dermal microvascular endothelial cells but not on umbilical vein, pulmonary vein, aorta, or pulmonary artery derived endothelial cells. By western blot analysis, we identified the 140 kD isoform of NCAM on the surface of human dermal microvascular endothelial cells (HDMEC) derived from dermis. Isolates of HDMEC from human foreskin reproducibly expressed high levels of cell surface immunoreactive protein. In contrast, endothelial cells from large vessels never expressed NCAM constitutively and could not be induced to express NCAM by three proinflammatory cytokines. Western blot analysis of membrane preparations of HDMEC indicated that NCAM protein migrated as a single species with a molecular mass of 140 kD. RT-PCR identified NCAM mRNA in HDMEC cells. The potential for expression of NCAM on small vessels in skin can be interpreted in different ways. Members of the immunoglobulin gene family, including ICAM-1, ICAM-2, and VCAM-1, can be expressed on the cell surface of all endothelial cells and serve as adhesion molecules for leukocytes. It is also possible that, by analogy, NCAM serves as a ligand for a receptor on leukocytes, particularly those that also express NCAM (e.g., natural killer cells). Alternatively, it is possible that NCAM expression permits endothelial cell-cell adhesion, enhancing the structural integrity of microvessels or facilitates neural interactions with microvascular endothelium. (C) 1994 Academic Press, Inc. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,BOSTON,MA 02115. MIE UNIV,MIE 514,JAPAN. WASHINGTON UNIV,ST LOUIS,MO. BECTON DICKINSON,RES TRIANGLE PK,NC. EMORY UNIV,ATLANTA,GA 30322. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. FU NIAID NIH HHS [AI25082]; NIAMS NIH HHS [AR40124, AR42124] NR 23 TC 13 Z9 13 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD AUG 30 PY 1994 VL 203 IS 1 BP 686 EP 693 DI 10.1006/bbrc.1994.2237 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA PD473 UT WOS:A1994PD47300098 PM 8074723 ER PT J AU NIXON, AJ RECHT, A NEUBERG, D CONNOLLY, JL SCHNITT, S ABNER, A HARRIS, JR AF NIXON, AJ RECHT, A NEUBERG, D CONNOLLY, JL SCHNITT, S ABNER, A HARRIS, JR TI THE RELATION BETWEEN THE SURGERY-RADIOTHERAPY INTERVAL AND TREATMENT OUTCOME IN PATIENTS TREATED WITH BREAST-CONSERVING SURGERY AND RADIATION-THERAPY WITHOUT SYSTEMIC THERAPY SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 35th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 11-15, 1993 CL NEW ORLEANS, LA SP AMER SOC THERAPEUT RADIOL & ONCOL DE SURGERY-RADIOTHERAPY INTERVAL; TIMING FACTORS; BREAST NEOPLASMS ID CONSERVATIVE SURGERY; CANCER; EXPERIENCE AB Purpose: This analysis was performed to clarify the relationship between the surgery-radiotherapy interval and the risk of recurrence in patients treated with breast-conserving therapy for early stage invasive cancers. Methods and Materials: We retrospectively analyzed data from 653 patients with American Joint Commission on Cancer Stage I or II, pathologically node-negative breast cancer treated by breast-conserving therapy without adjuvant systemic therapy between 1968 and 1985. All patients received a dose of at least 60 Gy to the tumor bed. Two hundred and eighty-three patients started radiotherapy within 4 weeks of surgery, 308 started 5-8 weeks after surgery, and 54 started 9-12 weeks after surgery. Median follow-up in the 531 survivors was 100 months. Results: Pathologic features and treatment characteristics were well balanced between the groups with surgery-radiotherapy intervals of 0-4 weeks and 5-8 weeks. There was no statistically significant difference in the risk of overall recurrence among patients starting radiotherapy 5-8 weeks after surgery compared with those treated within 4 weeks. Analysis of the 5-year crude rates of failure further demonstrated no difference in the distribution of sites of failure in the 5-8 week group compared with the 0-4 week group. A multivariate model controlling for known risk factors, as well as potential treatment-related confounders, also failed to demonstrate an increased risk of recurrence with the longer surgery-radiotherapy interval (risk ratio = 0.89, p = 0.44). Conclusion: This retrospective analysis suggests that a delay of up to 8 weeks in the interval between the last breast surgery and the start of radiotherapy is not associated with an increased risk of recurrence in patients with early stage breast cancer treated with breast irradiation to at least 60 Gy without systemic therapy. C1 HARVARD UNIV,SCH PUBL HLTH,DIV BIOSTAT,BOSTON,MA 02115. DANA FARBER CANC INST,BOSTON,MA. HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DEPT PATHOL,BOSTON,MA. RP NIXON, AJ (reprint author), HARVARD UNIV,SCH MED,JOINT CTR RADIAT THERAPY,DEPT RADIAT ONCOL,50 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA-06516, CA-09001] NR 15 TC 63 Z9 64 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 AUG 30 PY 1994 VL 30 IS 1 BP 17 EP 21 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA PH015 UT WOS:A1994PH01500003 PM 8083111 ER PT J AU WEICHSELBAUM, RR HALLAHAN, D FUKS, Z KUFE, D AF WEICHSELBAUM, RR HALLAHAN, D FUKS, Z KUFE, D TI RADIATION INDUCTION OF IMMEDIATE-EARLY GENES - EFFECTORS OF THE RADIATION-STRESS RESPONSE SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 35th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 11-15, 1993 CL NEW ORLEANS, LA SP AMER SOC THERAPEUT RADIOL & ONCOL DE EARLY RESPONSE GENES; GROWTH FACTORS; RADIATION MEDIATED TRANSCRIPTION; STRESS RESPONSE ID TUMOR-NECROSIS-FACTOR; DNA-BINDING ACTIVITY; C-JUN PROTOONCOGENE; IONIZING-RADIATION; TYROSINE PHOSPHORYLATION; INDUCED ACTIVATION; KAPPA-B; PROTEIN; TRANSCRIPTION; EXPRESSION AB Recent studies have demonstrated that the early response genes c-jun, Egr-1, c-fos, and NFKB are induced following exposure of mammalian cells to ionizing radiation. We propose that the products of these early response genes regulate downstream genes that are important in the adaptation of cells and tissues to radiation-induced stress. Potential downstream targets include cytokine and growth factor genes as well as deoxyribonucleic acid (DNA) repair genes. Early response gene products may also regulate cell cycle progression following cellular x-irradiation. Signal transduction pathways that allow cells to adapt to radiation may provide molecular targets to modify tumor and normal responses to radiotherapy. C1 UNIV CHICAGO,DEPT RADIAT & CELLULAR ONCOL,CHICAGO,IL 60637. MEM SLOAN KETTERING CANC CTR,DEPT RADIAT ONCOL,NEW YORK,NY 10021. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,PHARMACOL LAB,BOSTON,MA 02115. FU NCI NIH HHS [R01 CA-41068, R01 CA-42596] NR 41 TC 152 Z9 152 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 AUG 30 PY 1994 VL 30 IS 1 BP 229 EP 234 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA PH015 UT WOS:A1994PH01500028 PM 8083118 ER PT J AU FERNANDEZ, PA ROTELLO, RJ RANGINI, Z DOUPE, A DREXLER, HCA YUAN, JY AF FERNANDEZ, PA ROTELLO, RJ RANGINI, Z DOUPE, A DREXLER, HCA YUAN, JY TI EXPRESSION OF A SPECIFIC MARKER OF AVIAN PROGRAMMED CELL-DEATH IN BOTH APOPTOSIS AND NECROSIS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE DEVELOPMENT; IMMUNOFLUORESCENCE ID GENE-EXPRESSION; GLYCOL METHACRYLATE; BCL-2; TISSUE; INJURY; ACTIVATION; THYMOCYTES; RESISTANCE; INDUCTION; SURVIVAL AB Apoptosis and necrosis are two types of cell death with different morphologic features. We report here the isolation of a monoclonal antibody, BV2, that specifically recognizes cells undergoing developmental programmed cell death in different tissues of the chicken and zebra-finch embryos. The antigen recognized by BV2 monoclonal antibody is detected in vitro in primary chicken embryonic fibroblasts induced to die by actinomycin D, as well as fibroblasts induced to die by chemical anoxia. The expression of this specific antigen during necrosis appears to require active protein synthesis. These findings provide evidence that cells from different embryonic tissues undergoing programmed cell death during vertebrate development express similar antigens and indicate that apoptosis and necrosis may share similar biochemical features. C1 MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,BOSTON,MA 02129. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. CALTECH,DIV BIOL,PASADENA,CA 91125. FU NIA NIH HHS [AG11017] NR 40 TC 28 Z9 29 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 AUG 30 PY 1994 VL 91 IS 18 BP 8641 EP 8645 DI 10.1073/pnas.91.18.8641 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PE388 UT WOS:A1994PE38800068 PM 8078937 ER PT J AU FURUSAKA, A NISHIYAMA, M OHKAWA, K YAMORI, T TSURUO, T YONEZAWA, K KASUGA, M HAYASHI, SI TANAKA, T AF FURUSAKA, A NISHIYAMA, M OHKAWA, K YAMORI, T TSURUO, T YONEZAWA, K KASUGA, M HAYASHI, SI TANAKA, T TI EXPRESSION OF INSULIN-RECEPTOR SUBSTRATE-1 IN HEPATOCYTES - AN INVESTIGATION USING MONOCLONAL-ANTIBODIES SO CANCER LETTERS LA English DT Article DE INSULIN RECEPTOR SUBSTRATE-1; MONOCLONAL ANTIBODY; HEPATOCYTES (HUMANS) ID PHOSPHATIDYLINOSITOL 3-KINASE; PROTEIN; IRS-1; PHOSPHORYLATION; DEXAMETHASONE; LIVER; GRB2 AB To investigate the expression and subcellular distribution of insulin receptor substrate-1 in hepatocytes, which are major targets of insulin along with muscle and adipose tissue, we obtained monoclonal antibodies by immunizing mice with a fusion protein consisting of the C-terminal portion of the human insulin receptor substrate-1 and glutathione-S-transferase. Two of the monoclonal antibodies (designated as 7B3 and 6G5) were found to be useful for immunohistochemical studies. Using 6G5 we demonstrate a high level of expression of insulin receptor substrate-1 in liver cirrhosis hepatocytes and variable expression in hepatocellular carcinoma cells. These results suggest that insulin receptor substrate-1 may play a role in liver regeneration during cirrhosis and that an insulin signaling cascade may be involved in hepatocarcinogenesis. C1 JIKEI UNIV,SCH MED,DAISAN HOSP,DEPT INTERNAL MED,MINATO KU,TOKYO 105,JAPAN. JIKEI UNIV,SCH MED,DEPT BIOCHEM,MINATO KU,TOKYO 105,JAPAN. JAPANESE FDN CANC RES,CTR CANC CHEMOTHERAPY,TOKYO 170,JAPAN. UNIV TOKYO,TOKYO,JAPAN. MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,E CHARLESTOWN,MA. KOBE UNIV,SCH MED,DEPT INTERNAL MED 2,KOBE 650,JAPAN. RP FURUSAKA, A (reprint author), JIKEI UNIV,SCH MED,DEPT NUTR,MINATO KU,TOKYO 105,JAPAN. NR 17 TC 16 Z9 16 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD AUG 29 PY 1994 VL 84 IS 1 BP 85 EP 92 DI 10.1016/0304-3835(94)90361-1 PG 8 WC Oncology SC Oncology GA PF478 UT WOS:A1994PF47800011 PM 8076365 ER PT J AU FISHER, DE AF FISHER, DE TI APOPTOSIS IN CANCER-THERAPY - CROSSING THE THRESHOLD SO CELL LA English DT Review ID WILD-TYPE P53; PROGRAMMED CELL-DEATH; TUMOR-SUPPRESSOR GENE; ANTICANCER AGENTS; PREVENT APOPTOSIS; CYCLE ARREST; MUTATIONS; BCL-2; AMPLIFICATION; RADIATION C1 HARVARD UNIV,CHILDRENS HOSP,SCH MED,BOSTON,MA 02115. RP FISHER, DE (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT HEMATOL ONCOL,BOSTON,MA 02115, USA. NR 30 TC 1226 Z9 1267 U1 4 U2 41 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD AUG 26 PY 1994 VL 78 IS 4 BP 539 EP 542 DI 10.1016/0092-8674(94)90518-5 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA PD693 UT WOS:A1994PD69300002 PM 8069905 ER PT J AU SLICE, LW WONG, HC STERNINI, C GRADY, EF BUNNETT, NW WALSH, JH AF SLICE, LW WONG, HC STERNINI, C GRADY, EF BUNNETT, NW WALSH, JH TI THE CONSERVED NPX(N)Y MOTIF PRESENT IN THE GASTRIN-RELEASING PEPTIDE RECEPTOR IS NOT A GENERAL SEQUESTRATION SEQUENCE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SWISS 3T3 CELLS; BETA-ADRENERGIC-RECEPTOR; MEDIATED INTERNALIZATION; DOWN-REGULATION; BOMBESIN; RAT; BINDING; IMMUNOREACTIVITY; DESENSITIZATION; PHOSPHORYLATION AB Exposure of the gastrin-releasing peptide (GRP) receptor to agonists causes a rapid desensitization of the receptor-stimulated mobilization of intracellular calcium. Homologous desensitization occurs by uncoupling the G-proteins from the receptor and by ligand induced internalization. The molecular determinants of desensitization of the GRP receptor are not well known. The importance of tyrosine 324 which is located in a highly conserved NPX(2-3)Y motif of the GRP receptor was investigated. Kirsten murine sarcoma virus-transformed rat kidney (KNRK) cells were transfected with expression vectors encoding either the wild type or the mutant (tyrosine 324 to alanine 324) rat GRP receptor. The wild type and mutant GRP receptors were expressed at a high level in the KNRK cells, 2.0 x 10(6) and 0.5 x 10(6) receptors per cell, respectively. The wild type and mutant GRP receptors bound GRP with the same affinity (K-d = 6-7 nM). KNRK cells expressing the wild type or mutant GRP receptor had similar [Ca2+](i) dose response to GRP. KNRK cells expressing the GRP receptor rapidly internalized bound I-125-GRP at 37 degrees C. Internalization was inhibited at 4 degrees C and by 0.45 nl sucrose. The internalization of bound I-125-GRP by the mutant GRP receptor was identical to the wild type receptor. Fluorescent microscopy was used to directly observe the GRP receptor expressed on the surface of the KNRK cells and to visualize its ligand induced internalization. There was no difference in the pattern of internalization between the wild type and mutant GRP receptors expressed in KNRK cells. Therefore, the highly conserved tyrosine 324 does not have a role in GRP binding, receptor-G-protein interaction, or initial events of ligand induced receptor internalization. The NPX(n)Y motif is not a general sequestration sequence for seven transmembrane G-protein linked receptors. C1 UNIV CALIF LOS ANGELES,W LOS ANGELES VET AFFAIRS MED CTR,CTR GASTROENTER BIOL,DEPT PHYSIOL,LOS ANGELES,CA 90073. UNIV CALIF SAN FRANCISCO,DEPT SURG,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,DEPT PHYSIOL,SAN FRANCISCO,CA 94143. RP SLICE, LW (reprint author), UNIV CALIF LOS ANGELES,W LOS ANGELES VET AFFAIRS MED CTR,CTR GASTROENTER BIOL,DEPT MED,LOS ANGELES,CA 90073, USA. FU NIDDK NIH HHS [DK 17294, DK 35740, DK 39957] NR 25 TC 66 Z9 66 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 AUG 26 PY 1994 VL 269 IS 34 BP 21755 EP 21761 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PK973 UT WOS:A1994PK97300057 PM 8063819 ER PT J AU HUDSON, PL PEDERSEN, WA SALTSMAN, WS LISCOVITCH, M MACLAUGHLIN, DT DONAHOE, PK BLUSZTAJN, JK AF HUDSON, PL PEDERSEN, WA SALTSMAN, WS LISCOVITCH, M MACLAUGHLIN, DT DONAHOE, PK BLUSZTAJN, JK TI MODULATION BY SPHINGOLIPIDS OF CALCIUM SIGNALS EVOKED BY EPIDERMAL GROWTH-FACTOR SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-KINASE-C; NECROSIS-FACTOR-ALPHA; FACTOR RECEPTOR PHOSPHORYLATION; CELL-FREE SYSTEM; PHOSPHOLIPASE-C; TYROSINE KINASE; A431 CELLS; CARCINOMA-CELLS; EGF RECEPTOR; TRANSDUCTION PATHWAY AB Receptor activated breakdown of complex sphingolipids has been proposed as a mechanism for generating sphingoid base-containing putative second messenger molecules whose actions may modulate responses to extracellular signals, In human epidermoid carcinoma A431 cells, sphingosine (1-10 mu M) by itself had no effect on intracellular free calcium concentrations ([Ca2+](i)), yet within seconds, markedly enhanced the epidermal growth factor (EGF)-evoked Ca2+ influx (by up to 2.fold), but failed to alter Ca2+ release from the intracellular stores, Ca2+ signals evoked by serum were not affected by sphingosine. The response to sphingosine was dose-dependent and saturable, exhibiting an EC(50) of 2.3 mu M. In contrast, a ceramide, N-acetylsphingosine (10 mu M), sphingosine 1-phosphate (10 mu M) and sphingosylphosphorylcholine (10 mu M) inhibited EGF-evoked elevations in [Ca2+](i) The latter two compounds by themselves transiently increased [Ca2+](i). N-Octanoylsphingosine, N,N-dimethylsphingosine, sphingomyelin, and stearylamine were inactive. The potentiation of calcium signals by sphingosine occurred at all concentrations of EGF tested (0.15-15 nM) and did not alter the EGF receptor protein kinase activity as determined by antiphosphotyrosine immunoblotting. Antiphosphoserine immunoblotting revealed that sphingosine (10 mu M for 3 min) increased the phosphoserine content of two proteins with approximate molecular masses of 40 and 70 kDa, Serine hyperphosphorylation of the 40-kDa protein was also observed in cells treated with EGF alone, whereas the intensity of the 70 kDa band was highest in cells treated with both sphingosine and EGF. The modulation of growth factor receptor-regulated signaling, including changes in [Ca2+](i) may constitute a mechanism by which elevations in cellular levels of specific sphingolipids, which occur transiently upon activation of certain receptors and chronically in sphingolipid storage diseases, exert their physiological and pathophysiological effects. C1 BOSTON UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02118. MASSACHUSETTS GEN HOSP,PEDIAT SURG RES LAB,BOSTON,MA 02114. WEIZMANN INST SCI,DEPT HORMONE RES,IL-76100 REHOVOT,ISRAEL. FU NCI NIH HHS [CA17393]; NIMH NIH HHS [MH46095] NR 84 TC 24 Z9 24 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 AUG 26 PY 1994 VL 269 IS 34 BP 21885 EP 21890 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PK973 UT WOS:A1994PK97300073 PM 8063833 ER PT J AU OCONNELL, M MARTENSON, JA WIEAND, HS KROOK, JE MACDONALD, JS HALLER, DG MAYER, RJ GUNDERSON, LL RICH, TA AF OCONNELL, M MARTENSON, JA WIEAND, HS KROOK, JE MACDONALD, JS HALLER, DG MAYER, RJ GUNDERSON, LL RICH, TA TI IMPROVING ADJUVANT THERAPY FOR RECTAL-CANCER BY COMBINING PROTRACTED-INFUSION FLUOROURACIL WITH RADIATION-THERAPY AFTER CURATIVE SURGERY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID COLORECTAL-CANCER; VENOUS INFUSION; SMALL BOWEL; 5-FLUOROURACIL; CARCINOMA AB Background. The combination of radiation therapy and chemotherapy with fluorouracil plus semustine after surgery has been established as an effective approach to decreasing the risk of tumor relapse and improving survival in patients with rectal cancer who are at high risk for relapse or death. We sought to determine whether the efficacy of chemotherapy could be improved by administering fluorouracil by protracted infusion throughout the duration of radiation therapy and whether the omission of semustine would reduce the toxicity and delayed complications of chemotherapy without decreasing its antitumor efficacy. Methods. Six hundred sixty patients with TNM stage II or III rectal cancer received intermittent bolus injections or protracted venous infusions of fluorouracil during postoperative radiation to the pelvis. They also received systemic chemotherapy with semustine plus fluorouracil or with fluorouracil alone in a higher dose, both before and after the pelvic irradiation. Results. With a median follow-up of 46 months among surviving patients, patients who received a protracted infusion of fluorouracil had a significantly increased time to relapse (P = 0.01) and improved survival (P = 0.005). There was no evidence of a beneficial effect in the patients who received semustine plus fluorouracil. Conclusions. A protracted infusion of fluorouracil during pelvic irradiation improved the effect of combined-treatment postoperative adjuvant therapy in patients with high-risk rectal cancer. Semustine plus fluorouracil was not more effective than a higher dose of systemic fluorouracil given alone. C1 DULUTH CLIN,DULUTH,MN. TEMPLE UNIV,SCH MED,PHILADELPHIA,PA. UNIV PENN,CTR CANC,PHILADELPHIA,PA. DANA FARBER CANC INST,BOSTON,MA. MD ANDERSON CANC CTR,HOUSTON,TX. RP OCONNELL, M (reprint author), MAYO CLIN & MAYO FDN,ROCHESTER,MN 55905, USA. FU NCI NIH HHS [CA-06294, CA-25224, CA-31224] NR 24 TC 798 Z9 811 U1 1 U2 10 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 AUG 25 PY 1994 VL 331 IS 8 BP 502 EP 507 DI 10.1056/NEJM199408253310803 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA PD072 UT WOS:A1994PD07200003 PM 8041415 ER PT J AU ABADJI, V RAINES, DE DALTON, LA MILLER, KW AF ABADJI, V RAINES, DE DALTON, LA MILLER, KW TI LIPID-PROTEIN INTERACTIONS AND PROTEIN DYNAMICS IN VESICLES CONTAINING THE NICOTINIC ACETYLCHOLINE-RECEPTOR - A STUDY WITH ETHANOL SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES LA English DT Article DE ETHANOL; LIPID-PROTEIN INTERACTION; RECONSTITUTION; ACETYLCHOLINE RECEPTOR; EPR ID ELECTRON-SPIN-RESONANCE; GENERAL-ANESTHETICS; PARAMAGNETIC RESONANCE; TORPEDO-CALIFORNICA; MEMBRANES; SATURATION; LABEL; CHANNELS; AFFINITY; ALCOHOL AB Electron paramagnetic resonance (EPR) spectroscopy was used to study the action of ethanol on the protein side chain motions of the nicotinic acetylcholine receptor (nAcChoR) in alkaline extracted membranes from Torpedo nobiliana. EPR spectra of the nAcChoR derivatized with maleimide spin label contain both strongly and weakly immobilized components. The rotational correlation time of the strongly immobilized component decreases by a factor of 2-3-fold with the addition of 1.6 M ethanol, while that of the weakly immobilized component is not significantly altered. EPR spectroscopy was also used to probe the lipid environment immediately surrounding the nAcChoR with stearic acid and phosphatidylcholine spin labeled at the fourteenth acyl carbons (14-SASL and 14-PCSL, respectively), and the steroid spin label androstanol (ASL). EPR spectra of these probes reveal a component corresponding to lipids that are motionally restricted by the receptor (annular lipids) in addition to a more fluid component arising from bulk lipid. Using spectral subtraction, the order of selectivity of these spin labels for the nAcChoR was determined to be ASL greater than or equal to 14-SASL > 14-PCSL. The estimated rotational correlation times of the high affinity 14-SASL and ASL probes ranged from approx. 20 to 35 ns. The correlation times of the lower affinity 14-PCSL were generally shorter than those for 14-SASL and ASL and ranged from about 10 to 25 ns. The addition of up to 0.9 M ethanol altered neither the affinity nor the mobility of the motionally restricted EPR component. This suggests that ethanol's actions on the nAcChoR are not mediated via changes at the lipid/protein interface near the center of the bilayer. C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02114. FU NIAAA NIH HHS [AA-07040]; NIGMS NIH HHS [GM07592] NR 42 TC 27 Z9 28 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2736 J9 BBA-BIOMEMBRANES JI Biochim. Biophys. Acta-Biomembr. PD AUG 24 PY 1994 VL 1194 IS 1 BP 25 EP 34 DI 10.1016/0005-2736(94)90199-6 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA PE492 UT WOS:A1994PE49200004 PM 8075138 ER PT J AU MOSCICKI, RA SANMARTIN, JE QUINTERO, CH RAUCH, SD NADOL, JB BLOCH, KJ AF MOSCICKI, RA SANMARTIN, JE QUINTERO, CH RAUCH, SD NADOL, JB BLOCH, KJ TI SERUM ANTIBODY TO INNER-EAR PROTEINS IN PATIENTS WITH PROGRESSIVE HEARING-LOSS - CORRELATION WITH DISEASE-ACTIVITY AND RESPONSE TO CORTICOSTEROID TREATMENT SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID AUTOANTIBODIES; TESTS AB Objective.-To test whether detection of serum antibody to a 68-kd inner ear protein distinguishes among different causes of sensorineural hearing loss, and identifies patients with active disease and those likely to respond to corticosteroid therapy. Design.-Serum samples were tested by Western blot using bovine inner ear extract as antigen, and results were correlated with patient information obtained by chart review. Setting.-Referral center. Subjects of Study.-Serum samples were obtained from patients with idiopathic, progressive, bilateral sensorineural hearing loss (IPBSNHL) (n=72) otosclerosis (n=11), Cogan's syndrome (n=8), patients with positive tests for antinuclear antibodies (n=10), and normal controls (n=53). Main Outcome Measure.-Detection of serum antibody to a 68-kd inner eat protein. Results.-Serum from 42 of 72 patients with IPBSNHL reacted with a 68-kd protein constituent of inner ear extract. This reactivity was not detected in serum from 11 of 11 patients with otosclerosis, or in eight of eight with Cogan's syndrome. It was found in serum from one of 10 patients with a positive test for antinuclear antibody and in one of 53 normal controls. Antibody to the 68-kd protein was detected in serum from 89% of patients with actively progressing IPBSNHL and none of the 25 patients with inactive disease (P<.001). Patients who were antibody-positive responded to steroid treatment more frequently than did those who were antibody-negative (P<.001). Conclusions.-These results indicate that the presence of circulating antibody to a 68-kd constituent of bovine inner ear extract serves as a marker for IPBSNHL and that its presence correlates with disease activity and responsiveness to corticosteroid treatment. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02115. MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA. MASSACHUSETTS GEN HOSP,ALLERGY UNIT,GEN MED SERV,BOSTON,MA. RP MOSCICKI, RA (reprint author), MASSACHUSETTS GEN HOSP,CLIN IMMUNOL UNIT,32 FRUIT ST,BULLFINCH 422,BOSTON,MA 02114, USA. FU NIDCD NIH HHS [DC00824] NR 18 TC 136 Z9 139 U1 2 U2 2 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 AUG 24 PY 1994 VL 272 IS 8 BP 611 EP 616 DI 10.1001/jama.272.8.611 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA PC398 UT WOS:A1994PC39800031 PM 8057517 ER PT J AU SIVARAJA, M BOTFIELD, MC MUELLER, M JANCSO, A WEISS, MA AF SIVARAJA, M BOTFIELD, MC MUELLER, M JANCSO, A WEISS, MA TI SOLUTION STRUCTURE OF A POU-SPECIFIC HOMEODOMAIN - 3D-NMR STUDIES OF HUMAN B-CELL TRANSCRIPTION FACTOR OCT-2 SO BIOCHEMISTRY LA English DT Article ID NUCLEAR-MAGNETIC-RESONANCE; REPRESSOR-OPERATOR INTERACTIONS; CATABOLITE GENE ACTIVATOR; DNA-BINDING DOMAIN; ANTENNAPEDIA HOMEODOMAIN; PROTEIN-STRUCTURE; NMR-SPECTROSCOPY; IMMUNOGLOBULIN GENES; SECONDARY STRUCTURE; CRYSTAL-STRUCTURE AB The POU DNA-binding motif defines a conserved family of eukaryotic transcription factors involved in regulation of gene expression. This bipartite motif consists of an N-terminal POU-specific domain (POUs), a flexible linker, and a C-terminal POU-specific homeodomain (POUHD) Here we describe the solution structure of a POU-specific homeodomain. An NMR model is obtained from Oct-2, a human B-cell specific transcription factor which participates in the regulation of immunoglobulin genes. A fragment of Oct-2 containing POUHD and an adjoining linker was expressed in Escherichia coli and characterized by three-dimensional nuclear magnetic resonance (3D-NMR) spectroscopy. Complete H-1 and N-15 resonance assignment of the POUHD moiety is presented. The POUHD solution structure, as calculated by distance geometry and simulated annealing (DG/SA), is similar to that of canonical homeodomains. A salient difference between solution and crystal structures is observed in the C-terminal segment of alpha-helix 3 (the HTH recognition helix), which is not well ordered in solution. Because this segment presumably folds upon specific DNA binding, its flexibility in solution may reduce the intrinsic DNA affinity of POUHD in the absence of POUs. C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. FU NIGMS NIH HHS [GM45290] NR 68 TC 33 Z9 34 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD AUG 23 PY 1994 VL 33 IS 33 BP 9845 EP 9855 DI 10.1021/bi00199a005 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PD219 UT WOS:A1994PD21900005 PM 7914745 ER PT J AU WHITE, MF AF WHITE, MF TI HOT PAPERS - CELL BIOLOGY - PHOSPHATIDYLINOSITOL 3'-KINASE IS ACTIVATED BY ASSOCIATION WITH IRS-1 DURING INSULIN STIMULATION BY BACKER,J.M., MYERS,M.G., SHOELSON,S.E., CHIN,D.J., SUN,X.J., MIRALPEIX,M., HU,P., MARGOLIS,B., SKOLNIK,E.Y., SCHLESSINGER,J., WHITE,M.F. SO SCIENTIST LA English DT Article AB Cell biologist Morris F. White comments on circulating insulin in diabetes. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. RP WHITE, MF (reprint author), HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,BOSTON,MA 02115, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU SCIENTIST INC PI PHILADELPHIA PA 3600 MARKET ST SUITE 450, PHILADELPHIA, PA 19104 SN 0890-3670 J9 SCIENTIST JI Scientist PD AUG 22 PY 1994 VL 8 IS 16 BP 16 EP 16 PG 1 WC Information Science & Library Science; Multidisciplinary Sciences SC Information Science & Library Science; Science & Technology - Other Topics GA PC523 UT WOS:A1994PC52300021 ER PT J AU SZOSTAK, JW AF SZOSTAK, JW TI ISOLATION OF NEW RIBOZYMES FROM LARGE POOLS OF RANDOM SEQUENCES SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 2 EP BIOL PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA261 UT WOS:A1994PA26100443 ER PT J AU ROBERTS, RW CROTHERS, DM AF ROBERTS, RW CROTHERS, DM TI KINETIC CONTROL IN THE FORMATION OF INTRAMOLECULAR TRIPLE HELICES SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT MOLEC BIOL,BOSTON,MA 02114. YALE UNIV,DEPT CHEM,NEW HAVEN,CT 06511. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 58 EP BIOL PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA261 UT WOS:A1994PA26100495 ER PT J AU ROBERTS, RW CROTHERS, DM AF ROBERTS, RW CROTHERS, DM TI RULES FOR STABILITY PREDICTION OF DNA TRIPLE HELICES SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. YALE UNIV,DEPT CHEM,NEW HAVEN,CT 06511. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 110 EP ORGN PN 2 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA269 UT WOS:A1994PA26900184 ER PT J AU XIAO, S ROSE, DW SASAOKA, T MAEGAWA, H BURKE, TR ROLLER, PP SHOELSON, SE OLEFSKY, JM AF XIAO, S ROSE, DW SASAOKA, T MAEGAWA, H BURKE, TR ROLLER, PP SHOELSON, SE OLEFSKY, JM TI SYP (SH-PTP2) IS A POSITIVE MEDIATOR OF GROWTH FACTOR-STIMULATED MITOGENIC SIGNAL-TRANSDUCTION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-TYROSINE-PHOSPHATASE; SH2-CONTAINING PHOSPHOTYROSINE PHOSPHATASE; INSULIN-RECEPTOR; KINASE; SH2; PHOSPHORYLATION; CORKSCREW; BINDING; ASSOCIATION; ACTIVATION AB Syp (SH-PTP2) was recently identified as a phosphotyrosine phosphatase containing two SH2 domains within its primary structure. In response to appropriate growth factor stimulation, Syp becomes phosphorylated on tyrosine residues and associates with insulin receptor substrate 1 (IRS-1) and/or the corresponding growth factor receptor via its SH2 domains, leading to increased Syp activity. To assess the importance of Syp in mitogenic signaling, we microinjected mammalian fibroblasts with several reagents designed to interfere with Syp SH2/phosphotyrosine interaction in vivo. Insulin-, insulin-like growth factor-1-, and epidermal growth factor-stimulated DNA synthesis, indicated by bromodeoxyuridine (BrdUrd) incorporation, was dramatically decreased following microinjection of a Syp antibody (Ab) (65-85%) or a Syp GST-SH2 fusion protein (similar to 90%) in comparison with cells microinjected with control IgG or glutathione S-transferase (GST), respectively. In addition, microinjection of an IRS-1-derived phosphonopeptide, which inhibits in vitro binding of Syp-SH2 to IRS-1 with an ED(50) value of similar to 23 mu M, also decreased BrdUrd incorporation in vivo by approximately 50-75%. Microinjection of the Syp Ab, Syp GST-SH2 fusion protein, or the phosphonopeptide had no effect on serum-stimulated BrdUrd incorporation. In conclusion, disruption of Syp function in living cells inhibited cell cycle progression in response to growth factor stimulation, indicating that Syp is a critical positive regulator of mitogenic signal transduction. C1 UNIV CALIF SAN DIEGO,DEPT MED,DIV ENDOCRINOL & METAB,LA JOLLA,CA 92093. VET ADM MED CTR,MED RES SERV,SAN DIEGO,CA 92126. SHIGA UNIV MED SCI,DEPT MED 3,OTSU,SHIGA 52021,JAPAN. NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MED CHEM LAB,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,BOSTON,MA 02115. RI Burke, Terrence/N-2601-2014 FU NIDDK NIH HHS [DK33651] NR 31 TC 253 Z9 253 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 AUG 19 PY 1994 VL 269 IS 33 BP 21244 EP 21248 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PC403 UT WOS:A1994PC40300065 PM 8063747 ER PT J AU PROLLA, TA PANG, QS ALANI, E KOLODNER, RD LISKAY, RM AF PROLLA, TA PANG, QS ALANI, E KOLODNER, RD LISKAY, RM TI MLH1, PMS1, AND MSH2 INTERACTIONS DURING THE INITIATION OF DNA MISMATCH REPAIR IN YEAST SO SCIENCE LA English DT Article ID NONPOLYPOSIS COLORECTAL-CANCER; ESCHERICHIA-COLI; SACCHAROMYCES-CEREVISIAE; GENETIC INSTABILITY; PROTEIN; MUTATIONS; MUTL; ASSOCIATION; HOMOLOG AB The discovery that mutations in DNA mismatch repair genes can cause hereditary nonpolyposis colorectal cancer has stimulated interest in understanding the mechanism of DNA mismatch repair in eukaryotes. In the yeast Saccharomyces cerevisiae, DNA mismatch repair requires the MSH2, MLH1, and PMS1 proteins. Experiments revealed that the yeast MLH1 and PMS1 proteins physically associate, possibly forming a heterodimer, and that MLH1 and PMS1 act in concert to bind a MSH2-heteroduplex complex containing a G-T mismatch. Thus, MSH2, MLH1, and PMS1 are likely to form a ternary complex during the initiation of eukaryotic DNA mismatch repair. C1 OREGON HLTH SCI UNIV,DEPT MOLEC & MED GENET,PORTLAND,OR 97201. YALE UNIV,SCH MED,DEPT MOLEC BIOPHYS & BIOCHEM,NEW HAVEN,CT 06511. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELL & MOLEC BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. FU NHGRI NIH HHS [HG00305/GM50006]; NIGMS NIH HHS [GM 322741, GM 45413] NR 35 TC 268 Z9 271 U1 0 U2 26 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD AUG 19 PY 1994 VL 265 IS 5175 BP 1091 EP 1093 DI 10.1126/science.8066446 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PC539 UT WOS:A1994PC53900035 PM 8066446 ER PT J AU EMANUEL, EJ EMANUEL, LL AF EMANUEL, EJ EMANUEL, LL TI COST SAVINGS AT THE END OF LIFE - REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP EMANUEL, EJ (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115, USA. NR 5 TC 2 Z9 2 U1 1 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 AUG 18 PY 1994 VL 331 IS 7 BP 478 EP 479 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA PB501 UT WOS:A1994PB50100018 ER PT J AU EAGLE, KA CAMBRIA, R COLEY, C ABBOTT, W AF EAGLE, KA CAMBRIA, R COLEY, C ABBOTT, W TI ASSESSMENT OF CARDIAC RISK BEFORE ABDOMINAL AORTIC-SURGERY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID VASCULAR-SURGERY; THALLIUM RP EAGLE, KA (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 4 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 AUG 18 PY 1994 VL 331 IS 7 BP 480 EP 480 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA PB501 UT WOS:A1994PB50100023 PM 8068148 ER PT J AU WARD, JM FOX, JG ANVER, MR HAINES, DC GEORGE, CV COLLINS, MJ GORELICK, PL NAGASHIMA, K GONDA, MA GILDEN, RV TULLY, JG RUSSELL, RJ BENVENISTE, RE PASTER, BJ DEWHIRST, FE DONOVAN, JC ANDERSON, LM RICE, JM AF WARD, JM FOX, JG ANVER, MR HAINES, DC GEORGE, CV COLLINS, MJ GORELICK, PL NAGASHIMA, K GONDA, MA GILDEN, RV TULLY, JG RUSSELL, RJ BENVENISTE, RE PASTER, BJ DEWHIRST, FE DONOVAN, JC ANDERSON, LM RICE, JM TI CHRONIC ACTIVE HEPATITIS AND ASSOCIATED LIVER-TUMORS IN MICE CAUSED BY A PERSISTENT BACTERIAL-INFECTION WITH A NOVEL HELICOBACTER SPECIES SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID CAMPYLOBACTER-JEJUNI; SP-NOV; VIRUS; PYLORI; CARCINOGENESIS; EPITHELIUM; IMMUNOBLOT; MUSTELAE; FERRETS; MUCOSA AB Background: In the autumn of 1992, a novel form of chronic, active hepatitis of unknown etiology was discovered in mice at the National Cancer Institute-Frederick Cancer Research and Development Center (NCI-FCRDC), Frederick, Md. A high incidence of hepatocellular tumors occurred in affected animals. The disease entity was originally identified in A/JCr mice that were untreated controls in a long-term toxicologic study. Purpose: Our original purpose was to determine the origin and etiology of the chronic hepatitis and to quantify its association with hepatocellular tumors in mice of low liver tumor incidence strains. After a helical microorganism was discovered in hepatic parenchyma of diseased mice, we undertook characterization of the organism and investigation of its relationship to the disease process. Methods: Hepatic histopathology of many strains of mice and rats, as well as guinea pigs and Syrian hamsters, in our research and animal production facilities was reviewed. Steiner's modification of the Warthin-Starry stain and transmission electron microscopy were used to identify bacteria in the liver. We transmitted the hepatitis with liver suspensions from affected mice and by inoculation with bacterial cultures. Bacteria were cultivated on blood agar plates maintained under anaerobic or microaerophilic conditions and characterized morphologically, biochemically, and by 16S rRNA sequence. Results: We report here the isolation of a new species of Helicobacter (provisionally designated Helicobacter hepaticus sp. nov.) that selectively and persistently colonizes the hepatic bile canaliculi of mice (and possibly the intrahepatic biliary system and large bower), causing a morphologically distinctive pattern of chronic, active hepatitis and associated with a high incidence of hepatocellular neoplasms in infected animals. Conclusions: The novel Helicobacter is a likely candidate for the etiology of hepatocellular tumors in our mice. The Helicobacter-associated chronic active hepatitis represents a new model to study mechanisms of carcinogenesis by this genus of bacteria. Implications: Adenocarcinoma of the stomach, the second most prevalent of all human malignancies worldwide, is associated with infection at an early age with Helicobacter pylori. Infection leads to several distinctive forms of gastritis, including chronic atrophic gastritis, which is a precursor of adenocarcinoma. H. hepaticus infection in mice constitutes the only other parallel association between a persistent bacterial infection and tumor development known to exist naturally. Study of the H. hepaticus syndrome of chronic active hepatitis and liver tumors in mice may yield insights into the role of H. pylori in human stomach cancer and gastric lymphoma. C1 NCI,OFF LAB ANIM SCI,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,DIV CANC ETIOL,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,FREDERICK,MD 21702. NIAID,MOLEC MICROBIOL LAB,MYCOPLASMA SECT,FREDERICK,MD. NCI,FREDERICK CANC RES & DEV CTR,HARLAN SPRAGUE INC,FREDERICK,MD. FORSYTH DENT CTR,BOSTON,MA 02115. NCI,FREDERICK CANC RES & DEV CTR,DIV CANC ETIOL,VIRAL CARCINOGENESIS LAB,FREDERICK,MD. RP WARD, JM (reprint author), NCI,FREDERICK CANC RES & DEV CTR,OFF LAB ANIM SCI,FAIRVIEW 201,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01CO74102] NR 38 TC 313 Z9 326 U1 0 U2 7 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD AUG 17 PY 1994 VL 86 IS 16 BP 1222 EP 1227 DI 10.1093/jnci/86.16.1222 PG 6 WC Oncology SC Oncology GA PB103 UT WOS:A1994PB10300011 PM 8040890 ER PT J AU BORCHELT, DR LEE, MK SLUNT, HS GUARNIERI, M XU, ZS WONG, PC BROWN, RH PRICE, DL SISODIA, SS CLEVELAND, DW AF BORCHELT, DR LEE, MK SLUNT, HS GUARNIERI, M XU, ZS WONG, PC BROWN, RH PRICE, DL SISODIA, SS CLEVELAND, DW TI SUPEROXIDE-DISMUTASE-1 WITH MUTATIONS LINKED TO FAMILIAL AMYOTROPHIC-LATERAL-SCLEROSIS POSSESSES SIGNIFICANT ACTIVITY SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TRANSGENIC MICE; CELLS; EXPRESSION; SEQUENCE; RADICALS; BLOOD; ALS; SOD AB Familial amyotrophic lateral sclerosis (FALS) has been linked to mutations in the homodimeric enzyme Cu/Zn superoxide dismutase 1 (SOD1). Assay by transient expression in primate cells of six FALS mutant enzymes revealed a continuum of enzymatic activity bounded by the enzyme carrying the mutation Gly-85 --> Arg, which was inactive, and mutant enzyme G37R carrying the Gly-37 --> Arg change, which retained full specific activity but displayed a 2-fold reduction in polypeptide stability. The G37R mutant displayed similar properties in transformed lymphocytes from an individual heterozygous for the G37R and wild-type SOD1 genes; heterodimeric enzymes composed of mutant and wild-type subunits were detected, but there was no measurable diminution in the stability and activity of the wild-type subunits. Thus, for mutants such as G37R, either surprisingly modest losses in activity (involving only the mutant subunit) can yield motor neuron death, or alternatively, mutant SOD1 may acquire properties that injure motor neurons by one or more mechanisms unrelated to the metabolism of oxygen radicals. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT BIOL CHEM,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,NEUROPATHOL LAB,BALTIMORE,MD 21205. MASSACHUSETTS GEN HOSP,DAY NEUROMUSCULAR RES LAB,BOSTON,MA 02129. RP BORCHELT, DR (reprint author), JOHNS HOPKINS UNIV,SCH MED,DEPT PATHOL,BALTIMORE,MD 21205, USA. RI Lee, Michael/D-9491-2013 OI Lee, Michael/0000-0001-5865-9682 FU NIA NIH HHS [AG 05146]; NINDS NIH HHS [NS 20471, NS 27036] NR 28 TC 450 Z9 457 U1 1 U2 15 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 AUG 16 PY 1994 VL 91 IS 17 BP 8292 EP 8296 DI 10.1073/pnas.91.17.8292 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PC242 UT WOS:A1994PC24200096 PM 8058797 ER PT J AU FIFER, MA OGARA, PT MCGOVERN, BA SEMIGRAN, MJ AF FIFER, MA OGARA, PT MCGOVERN, BA SEMIGRAN, MJ TI EFFECTS OF DISOPYRAMIDE ON LEFT-VENTRICULAR DIASTOLIC FUNCTION IN HYPERTROPHIC CARDIOMYOPATHY SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Note ID VERAPAMIL C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP FIFER, MA (reprint author), MASSACHUSETTS GEN HOSP,DEPT MED,CARDIAC UNIT,WACC 478,15 PARKMAN ST,BOSTON,MA 02114, USA. NR 20 TC 6 Z9 6 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD AUG 15 PY 1994 VL 74 IS 4 BP 405 EP 408 DI 10.1016/0002-9149(94)90416-2 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PB381 UT WOS:A1994PB38100022 PM 8059710 ER PT J AU HALUSKA, FG BRUFSKY, AM CANELLOS, GP AF HALUSKA, FG BRUFSKY, AM CANELLOS, GP TI THE CELLULAR BIOLOGY OF THE REED-STERNBERG CELL SO BLOOD LA English DT Review ID EPSTEIN-BARR-VIRUS; POLYMERASE CHAIN-REACTION; RECEPTOR GENE REARRANGEMENTS; LATENT MEMBRANE-PROTEIN; TUMOR-NECROSIS-FACTOR; LYMPHOCYTE PREDOMINANCE TYPE; UNTREATED HODGKINS-DISEASE; HUMAN-MALIGNANT LYMPHOMAS; GROWTH-FACTOR-BETA; INFECTED B-CELLS RP HALUSKA, FG (reprint author), DANA FARBER CANC INST,DIV MED ONCOL,44 BINNEY ST,BOSTON,MA 02115, USA. NR 249 TC 109 Z9 110 U1 1 U2 2 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 AUG 15 PY 1994 VL 84 IS 4 BP 1005 EP 1019 PG 15 WC Hematology SC Hematology GA PC402 UT WOS:A1994PC40200002 PM 8049419 ER PT J AU ANTIN, JH WEINSTEIN, HJ GUINAN, EC MCCARTHY, P BIERER, BE GILLILAND, DG PARSONS, SK BALLEN, KK RIMM, IJ FALZARANO, G BLOEDOW, DC ABATE, L LEBSACK, M BURAKOFF, SJ FERRARA, JLM AF ANTIN, JH WEINSTEIN, HJ GUINAN, EC MCCARTHY, P BIERER, BE GILLILAND, DG PARSONS, SK BALLEN, KK RIMM, IJ FALZARANO, G BLOEDOW, DC ABATE, L LEBSACK, M BURAKOFF, SJ FERRARA, JLM TI RECOMBINANT HUMAN INTERLEUKIN-1 RECEPTOR ANTAGONIST IN THE TREATMENT OF STEROID-RESISTANT GRAFT-VERSUS-HOST DISEASE SO BLOOD LA English DT Article ID TUMOR-NECROSIS-FACTOR; BONE-MARROW TRANSPLANTATION; ANTIBODY; THERAPY; PHASE; PROPHYLAXIS; EXPRESSION; RABBITS; TRIAL; IL-1 C1 CHILDRENS HOSP,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. SYNERGEN INC,BOULDER,CO 80301. RP ANTIN, JH (reprint author), BRIGHAM & WOMENS HOSP,DEPT MED,DIV HEMATOL ONCOL,75 FRANCIS ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA58661, CA 39542] NR 32 TC 107 Z9 108 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 AUG 15 PY 1994 VL 84 IS 4 BP 1342 EP 1348 PG 7 WC Hematology SC Hematology GA PC402 UT WOS:A1994PC40200045 PM 8049450 ER PT J AU KOPANS, DB HALPERN, E HULKA, CA AF KOPANS, DB HALPERN, E HULKA, CA TI STATISTICAL POWER IN BREAST-CANCER SCREENING TRIALS AND MORTALITY REDUCTION AMONG WOMEN 40-49 YEARS OF AGE WITH PARTICULAR EMPHASIS ON THE NATIONAL BREAST SCREENING STUDY OF CANADA SO CANCER LA English DT Editorial Material ID LOW-COST; MAMMOGRAPHY; OPERATE; RATES RP KOPANS, DB (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIOL,BOSTON,MA 02114, USA. NR 34 TC 62 Z9 63 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 0008-543X J9 CANCER JI Cancer PD AUG 15 PY 1994 VL 74 IS 4 BP 1196 EP 1203 DI 10.1002/1097-0142(19940815)74:4<1196::AID-CNCR2820740403>3.0.CO;2-Y PG 8 WC Oncology SC Oncology GA PC032 UT WOS:A1994PC03200002 PM 8055437 ER PT J AU KOPANS, DB HALPERN, E HULKA, CA AF KOPANS, DB HALPERN, E HULKA, CA TI MAMMOGRAPHY SCREENING FOR BREAST-CANCER - REPLY SO CANCER LA English DT Editorial Material ID WOMEN RP KOPANS, DB (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIOL,BOSTON,MA 02114, USA. NR 20 TC 6 Z9 6 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 AUG 15 PY 1994 VL 74 IS 4 BP 1212 EP 1216 DI 10.1002/1097-0142(19940815)74:4<1212::AID-CNCR2820740406>3.0.CO;2-5 PG 5 WC Oncology SC Oncology GA PC032 UT WOS:A1994PC03200005 PM 8055440 ER PT J AU MILLER, DC HOCHBERG, FH HARRIS, NL GRUBER, ML LOUIS, DN COHEN, H AF MILLER, DC HOCHBERG, FH HARRIS, NL GRUBER, ML LOUIS, DN COHEN, H TI PATHOLOGY WITH CLINICAL CORRELATIONS OF PRIMARY CENTRAL-NERVOUS-SYSTEM NON-HODGKINS-LYMPHOMA - THE MASSACHUSETTS-GENERAL-HOSPITAL EXPERIENCE 1958-1989 SO CANCER LA English DT Article DE CENTRAL NERVOUS SYSTEM LYMPHOMA; BRAIN LYMPHOMA; NON-HODGKINS LYMPHOMA; IMMUNOSTAINS ID IMMUNE-DEFICIENCY-SYNDROME; PARAFFIN-EMBEDDED TISSUE; ACQUIRED IMMUNODEFICIENCY SYNDROME; PRIMARY MALIGNANT-LYMPHOMAS; RETICULUM-CELL SARCOMA; PRIMARY BRAIN LYMPHOMA; HIGH-DOSE METHOTREXATE; PRIMARY CNS LYMPHOMA; MONOCLONAL-ANTIBODIES; INCREASING INCIDENCE AB Background. Primary central nervous system non-Hodgkin's lymphoma (NHL-CNS) is an enigmatic disease of uncertain origin. At the Massachusetts General Hospital, 104 patients with NHL-CNS were seen from 1958 through 1989. An impression of changes in the frequency of diagnosis, character of the tumors, and therapy for this disease prompted this study of the pathologic features, clinical data, and natural history of this tumor in these 104 patients. Methods. Histologic slides (neurosurgical specimens and autopsy tissues) were available for 99 patients. The tumors were classified by the Working Formulation classification. Immunostaining data and all clinical data were retrieved from the relevant offices and hospital charts. Results. Primary central nervous system non-Hodgkin's lymphoma tripled in frequency (5.66 cases per year in 1978-89 versus 1.75 cases per year in 1958-77) and now represents 6.6% of all primary brain neoplasms (versus 3.3% before 1978; chi(2) = 17.52, P < 0.01). For the 99 tumors histologically classified, 89% were high grade. Intermediate grade lymphomas, once the second most common subtype, have disappeared since 1983. All tumors had diffuse architecture; 77% (including all 11 patients with acquired immune deficiency syndrome) were large cell subtypes. Two cases were intravascular lymphoma. With one exception, all of the 41 tumors evaluated were B-cell types; 32 of 40 had monotypic surface immunoglobulin. There was 1 T-cell lymphoma. Of 64 tumor recurrences, 29 were at the initially defined site; 12 were in the leptomeninges, 29 were in other sites in the neuraxis, and 8 were in systemic sites. Systemic metastases have not occurred since 1984. Median survival for the 68 patients who survived after diagnostic surgery and for whom follow-up information could be obtained was 19 months; 9 months for those with high grade tumors and 30.5 months for those with intermediate grade tumors. This difference was not significant (P = 0.13). A separate set of seven patients had focal tumorlike lymphoid infiltrates composed of benign-appearing lymphocytes, which were associated with good long term survival. The differential histologic diagnosis of NHL-CNS was occasionally difficult, and the spectrum of this differential was broader than generally stated. Conclusions. Primary central nervous system non-Hodgkin's lymphoma has increased in frequency even in nonimunocompromised patient populations. This increase has been accompanied by the disappearance of intermediate grade histologic types, suggesting a fundamental shift in the biology of the neoplasms. The introduction of chemotherapeutic regimens appears to have altered the natural history such that systemic metastases outside the central nervous system no longer occur, and there are now some long term survivors of this formerly uniformly fatal disease. C1 NYU,MED CTR,RITA & STANLEY KAPLAN COMPREHENS CANC CTR,NEW YORK,NY 10016. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,JAMES HOMER WRIGHT PATHOL LABS,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CHARLES S KUBIK LAB NEUROPATHOL,BOSTON,MA 02114. NYU,CTR MED,DEPT EPIDEMIOL & BIOSTAT,NEW YORK,NY 10016. RP MILLER, DC (reprint author), NYU,MED CTR,DEPT PATHOL,DIV NEUROPATHOL,550 1ST AVE,NEW YORK,NY 10016, USA. NR 94 TC 220 Z9 225 U1 0 U2 3 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 AUG 15 PY 1994 VL 74 IS 4 BP 1383 EP 1397 DI 10.1002/1097-0142(19940815)74:4<1383::AID-CNCR2820740432>3.0.CO;2-1 PG 15 WC Oncology SC Oncology GA PC032 UT WOS:A1994PC03200031 PM 8055462 ER PT J AU WEICHSELBAUM, RR HALLAHAN, DE BECKETT, MA MAUCERI, HJ LEE, H SUKHATME, VP KUFE, DW AF WEICHSELBAUM, RR HALLAHAN, DE BECKETT, MA MAUCERI, HJ LEE, H SUKHATME, VP KUFE, DW TI GENE-THERAPY TARGETED BY RADIATION PREFERENTIALLY RADIOSENSITIZES TUMOR-CELLS SO CANCER RESEARCH LA English DT Note ID NECROSIS-FACTOR; IONIZING-RADIATION; TNF RECEPTOR; TRANSCRIPTION; ACTIVATION; XENOGRAFTS; CACHEXIA; INVITRO; GROWTH; DOMAIN AB Transcriptional regulation of the promoter/enhancer region of the Egr-1 gene is activated by ionizing radiation. We linked DNA sequences from the promotor region of Egr-1 to a complementary DNA sequence which encodes human tumor necrosis factor (TNF) alpha, a radiosensitizing cytokine. The Egr-TNF construct was transfected into a human cell line of hematopoietic origin, HL525, which was used in an experimental animal system. HL525 (clone 2) cells containing the Egr-TNF construct which exhibits radiation induction of TNF-alpha were injected into human xenografts of the radioresistant human squamous cell carcinoma cell line SQ-ZOB. Animals treated with radiation and clone 2 demonstrated an increase in tumor cures compared with animals treated with radiation alone or unirradiated animals given injections of clone 2 alone. No in crease in local or systemic toxicity was observed in the combined treatment group. The combination of gene therapy and radiation therapy enhances tumor cures without increasing normal tissue toxicity and is a new paradigm for cancer treatment. C1 HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DEPT MED,NEPHROL SECT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC PHARMACOL,BOSTON,MA 02115. RP WEICHSELBAUM, RR (reprint author), UNIV CHICAGO,DEPT RADIAT & CELLULAR ONCOL,CHICAGO,IL 60637, USA. FU NCI NIH HHS [CA 41068, CA 42596, CA 58505] NR 29 TC 129 Z9 167 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 15 PY 1994 VL 54 IS 16 BP 4266 EP 4269 PG 4 WC Oncology SC Oncology GA PB502 UT WOS:A1994PB50200004 PM 8044769 ER PT J AU GREENSTEIN, D HIRD, S PLASTERK, RHA ANDACHI, Y KOHARA, Y WANG, B FINNEY, M RUVKUN, G AF GREENSTEIN, D HIRD, S PLASTERK, RHA ANDACHI, Y KOHARA, Y WANG, B FINNEY, M RUVKUN, G TI TARGETED MUTATIONS IN THE CAENORHABDITIS-ELEGANS POU HOMEO BOX GENE CEH-18 CAUSE DEFECTS IN OOCYTE CELL-CYCLE ARREST, GONAD MIGRATION, AND EPIDERMAL DIFFERENTIATION SO GENES & DEVELOPMENT LA English DT Article DE POU DOMAIN; GERM-LINE DEVELOPMENT; MEIOTIC ARREST; OOCYTE; DNA ENDOREDUPLICATION; HOMEO DOMAIN ID MOS PROTO-ONCOGENE; C-ELEGANS; TRANSCRIPTION FACTOR; DNA-BINDING; GERM-LINE; DOMAIN; DROSOPHILA; MATURATION; EXPRESSION; CONTAINS AB We used targeted gene inactivation to analyze the function of a Caenorhabditis elegans POU gene, ceh-18, and to dissect its functional domains in vivo. In ceh-18 mutants, oocytes exhibit an incompletely penetrant failure to arrest in diakinesis of meiotic prophase I and instead undergo multiple rounds of DNA replication without cytokinesis. ceh-18 is expressed in the gonadal sheath cells that signal the oocyte, but not in the oocyte. This suggests that ceh-18 affects, directly or indirectly, a sheath cell signal that causes oocytes to maintain diakinesis arrest. ceh-18 also participates in directing gonad migration and in specifying the differentiated phenotypes of epidermal cells during postembryonic development. Analysis of targeted deletions that disrupt half of the POU domain selectively by deleting either the POUhd or the POUsp alone, indicates that each CEH-18 POU subdomain is sufficient for partial activity in vivo. C1 MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. NETHERLANDS CANC INST,1066 CX AMSTERDAM,NETHERLANDS. NATL INST GENET,DNA RES CTR,MISHIMA,SHIZUOKA 411,JAPAN. NR 61 TC 71 Z9 75 U1 0 U2 3 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0890-9369 J9 GENE DEV JI Genes Dev. PD AUG 15 PY 1994 VL 8 IS 16 BP 1935 EP 1948 DI 10.1101/gad.8.16.1935 PG 14 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA PE731 UT WOS:A1994PE73100007 PM 7958868 ER PT J AU STRASSMAN, AM POTREBIC, S MACIEWICZ, RJ AF STRASSMAN, AM POTREBIC, S MACIEWICZ, RJ TI ANATOMICAL PROPERTIES OF BRAIN-STEM TRIGEMINAL NEURONS THAT RESPOND TO ELECTRICAL-STIMULATION OF DURAL BLOOD-VESSELS SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Review DE TRIGEMINAL NUCLEUS CAUDALIS; MEDULLARY DORSAL HORN; VASCULAR HEADACHE; CORNEA; INTRACELLULAR HORSERADISH PEROXIDASE ID MEDULLARY DORSAL HORN; THORACIC SPINAL-CORD; PRIMARY AFFERENT-FIBERS; STEM SUBNUCLEUS INTERPOLARIS; SPINOTHALAMIC TRACT NEURONS; LATERAL RETICULAR-FORMATION; VISCERAL PRIMARY AFFERENTS; HORSERADISH-PEROXIDASE; NOCICEPTIVE NEURONS; CENTRAL PROJECTIONS AB Single unit recording studies in anesthetized cats have identified a population of neurons in the brainstem trigeminal complex that can be activated by stimulation of major dural blood vessels. Such dura-responsive neurons exhibit response properties that are appropriate for a role in the mediation of vascular head pain in that they typically exhibit nociceptive facial receptive fields whose periorbital distribution is similar to the region of referred pain evoked by dural stimulation in humans. In the present study, intracellular labelling with horseradish peroxidase was used to examine the anatomical characteristics of brainstem trigeminal neurons that respond to dural stimulation. A total of 17 neurons was labelled that responded to electrical stimulation of dural sites overlying the superior sagittal sinus or middle meningeal artery. Fourteen of these neurons also responded to electrical stimulation of the cornea. The neurons in this sample were located in the rostral two-thirds of the trigeminal nucleus caudalis and the caudalmost part of the nucleus interpolaris. Within caudalis, the neurons were located in the deeper part of the nucleus, primarily lamina V, and were concentrated ventrolaterally. The dendritic arborizations of the dura-responsive neurons typically exhibited a dorsolateral-to-ventro medial orientation and did not extend into the superficial laminae of caudalis. Dura-responsive neurons had axonal collaterals and boutons in the nucleus caudalis, nucleus interpolaris, the infratrigeminal region ventral to nucleus interpolaris, the nucleus of the solitary tract, and the medullary reticular formation. The axonal boutons within the trigeminal complex exhibited a ventrolateral distribution which largely overlapped the distribution of the somata. The results are consistent with previous evidence that dura-responsive brainstem trigeminal neurons may have a role in the mediation of dural vascular head pain and also indicate that such neurons may contribute to nociceptive processing within the dorsal horn. (C) 1994 Wiley-Liss, Inc. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02129. FU NINDS NIH HHS [NS24594] NR 117 TC 27 Z9 28 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 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD AUG 15 PY 1994 VL 346 IS 3 BP 349 EP 365 DI 10.1002/cne.903460304 PG 17 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA PB508 UT WOS:A1994PB50800003 PM 7995855 ER PT J AU AGEMATSU, K KOBATA, T SUGITA, K FREEMAN, GJ BECKMANN, MP SCHLOSSMAN, SF MORIMOTO, C AF AGEMATSU, K KOBATA, T SUGITA, K FREEMAN, GJ BECKMANN, MP SCHLOSSMAN, SF MORIMOTO, C TI ROLE OF CD27 IN T-CELL IMMUNE-RESPONSE - ANALYSIS BY RECOMBINANT SOLUBLE CD27 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GROWTH-FACTOR RECEPTOR; TUMOR-NECROSIS-FACTOR; CTLA-4 COUNTER-RECEPTOR; HUMAN LYMPHOCYTES-B; MOLECULAR-CLONING; SURFACE-ANTIGEN; DIFFERENTIATION ANTIGEN; ACTIVATION ANTIGEN; CYCLIC-AMP; BIOLOGICAL CHARACTERIZATION AB CD27 is a disulfide-linked 120-kDa transmembrane glycoprotein expressed on the majority of T cells, B cells, and NK cells; it has homology to a family of molecules that includes the receptors for nerve growth factor and TNF. Previous studies strongly suggest that the CD27 molecule plays a key role in the process of T cell activation. To further determine its role in T cell activation, a recombinant soluble molecule composing only the extracellular domain of CD27 was produced by transfection of Chinese hamster ovary cells. We have defined the binding properties of recombinant soluble CD27 (rsCD27) to CD27 ligand (CD27L) cDNA transfected NIH 3T3 cells and have determined its functional effects on in vitro T cell activation as well as on PWM-driven B cell IgG synthesis. rsCD27 bound specifically to CD27L and the binding was inhibited by one of our anti-CD27 mAbs, anti-1A4, suggesting that the 1A4 epitope of CD27 plays a role in the binding to CD27L. Functionally, rsCD27 inhibited T cell proliferation induced by various stimuli, such as PHA, tetanus toroid, and anti-CD2, as well as PWM-driven B cell IgG synthesis, similar to the effects of adding anti-1A4. Determination of CD27L expression showed that CD27L mRNA is induced rapidly on activated T and B cells. Taken together, these results provide direct evidence that CD27-CD27L interaction plays a critical role in T cell activation as well as in T cell-dependent B cell IgG synthesis, suggesting that the CD27-CD27L interaction may constitute a component of the T cell-T cell or T cell-B cell interaction seen after activation with Ag or mitogen. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. IMMUNEX RES & DEV CORP,SEATTLE,WA 98108. FU NIAAA NIH HHS [AA33713]; NIAID NIH HHS [AI12609, AI29530] NR 70 TC 59 Z9 59 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 AUG 15 PY 1994 VL 153 IS 4 BP 1421 EP 1429 PG 9 WC Immunology SC Immunology GA PB406 UT WOS:A1994PB40600002 PM 8046222 ER PT J AU BROUILLET, E HENSHAW, DR SCHULZ, JB BEAL, MF AF BROUILLET, E HENSHAW, DR SCHULZ, JB BEAL, MF TI AMINOOXYACETIC ACID STRIATAL LESIONS ATTENUATED BY 1,3-BUTANEDIOL AND COENZYME Q(10) SO NEUROSCIENCE LETTERS LA English DT Article DE MITOCHONDRION; UBIQUINONE; EXCITOTOXICITY; HYPOGLYCEMIA ID MITOCHONDRIAL ENCEPHALOMYOPATHY; ENERGY-METABOLISM; THERAPY; RATS; IMPAIRMENT; UBIQUINONE; REDUCTION; MECHANISM; MELAS; BRAIN AB We previously showed that intrastriatal administration of aminooxyacetic acid (AOAA) produces striatal lesions by a secondary excitotoxic mechanism associated with impairment of oxidative phosphorylation. In the present study, we show that and the specific complex I inhibitor rotenone produces a similar neurochemical profile in the striatum, consistent with an effect of AOAA on energy metabolism. Lesions produced by AOAA were dose-dependently blocked by MK-801, with complete protection against GABA and substance P depletions at a dose of 3 mg/kg. AOAA lesions were significantly attenuated by pretreatment with either 1,3-butanediol or coenzyme Q(10), two compounds which are thought to improve energy metabolism. These results provide further evidence that AOAA produces striatal excitotoxic lesions as a consequence of energy depletion and they suggest therapeutic strategies which may be useful in neurodegenerative diseases. C1 MASSACHUSETTS GEN HOSP,NEUROL SERV,NEUROCHEM LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RI Schulz, Jorg/D-9786-2012; Brouillet, Emmanuel/B-4784-2014 OI Schulz, Jorg/0000-0002-8903-0593; Brouillet, Emmanuel/0000-0001-6322-7403 FU NINDS NIH HHS [NS10828, NS31579]; PHS HHS [16367] NR 23 TC 19 Z9 20 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD AUG 15 PY 1994 VL 177 IS 1-2 BP 58 EP 62 DI 10.1016/0304-3940(94)90044-2 PG 5 WC Neurosciences SC Neurosciences & Neurology GA PE810 UT WOS:A1994PE81000015 PM 7824183 ER PT J AU MARSHALL, G GROVER, FL HENDERSON, WG HAMMERMEISTER, KE AF MARSHALL, G GROVER, FL HENDERSON, WG HAMMERMEISTER, KE TI ASSESSMENT OF PREDICTIVE MODELS FOR BINARY OUTCOMES - AN EMPIRICAL-APPROACH USING OPERATIVE DEATH FROM CARDIAC-SURGERY SO STATISTICS IN MEDICINE LA English DT Article ID PROGNOSTIC PREDICTION; REGRESSION-MODELS; RISK ASSESSMENT; ADVANTAGES AB Predictive models in medical research have gained popularity among physicians as an important tool in medical decision making. Eight methodological strategies for creating predictive models are compared in a large, complex data base consisting of preoperative risk and operative outcome data on 12,712 patients undergoing coronary artery bypass grafting and entered into the Department of Veterans Affairs Cardiac Surgery Risk Assessment Program between April 1987 and March 1990. The models under consideration were developed to predict operative death (any death within 30 days following the surgical procedure or later if the result of a perioperative complication). The two strategies with the best predictive power among the eight examined were stepwise logistic regression done and data reduction by cluster analysis combined with clinical judgement followed by a logistic regression model. The additive model based on unadjusted relative risks, the model based on Bayes' Theorem, and the logistic model using all candidate variables were good alternatives. Whether or not we imputed values did not have a significant impact on the predictive power of the models. C1 US DEPT VET AFFAIRS,COOPERAT STUDIES PROGRAM,HINES,IL 60141. RP MARSHALL, G (reprint author), UNIV COLORADO,SCH MED,DEPT VET AFFAIRS MED CTR,1055 CLEMONT ST,DENVER,CO 80220, USA. RI Marshall, Guillermo/F-2302-2011 NR 15 TC 33 Z9 33 U1 0 U2 1 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 AUG 15 PY 1994 VL 13 IS 15 BP 1501 EP 1511 DI 10.1002/sim.4780131502 PG 11 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 PF482 UT WOS:A1994PF48200001 PM 7973229 ER PT J AU TAKAHASHI, LK AF TAKAHASHI, LK TI ORGANIZING ACTION OF CORTICOSTERONE ON THE DEVELOPMENT OF BEHAVIORAL-INHIBITION IN THE PREWEANLING RAT SO DEVELOPMENTAL BRAIN RESEARCH LA English DT Article DE PREWEANLING RAT; BEHAVIORAL INHIBITION; FREEZING; ULTRASONIC VOCALIZATION; CONSPECIFIC THREAT; SOCIAL ISOLATION; ADRENAL STEROID; CORTICOSTERONE; ADRENALECTOMY ID REGULATE POSTNATAL-DEVELOPMENT; DENTATE GYRUS; SEXUAL-DIFFERENTIATION; PREOPTIC AREA; BRAIN; GLUCOCORTICOIDS; ADRENALECTOMY; RESPONSES; RECEPTOR; STEROIDS AB Altricial rat pups develop the ability to freeze and to terminate their emission of ultrasonic vocalizations when exposed to an unfamiliar adult male rat. This developmental competence in expressing behavioral inhibition is impaired when rat pups are adrenalectomized (ADX) on postnatal day 10, a period prior to the emergence of behavioral inhibition. Adrenalectomy, however, fails to induce similar behavioral deficits when performed after behavioral inhibition has developed. Results suggest that adrenal steroids are involved in promoting the development but not the activation of behavioral inhibition. To critically test this hypothesis, four groups of rats were adrenalectomized on day 10 and tested for behavioral inhibition on day 18. Prior to testing, one group of rats received daily s.c. injections of vehicle whereas another group was treated with daily injections of 3.0 mg/kg of corticosterone (B). The other two groups of rats received daily B injections on only days 10-13 or days 14-17. Results indicated that ADX rats treated with B only on days 10-13 as well as throughout exhibited significantly higher levels of freezing than the other two treatment groups. In order to evaluate whether the behavioral inhibitory deficits produced by ADX at 10 days of age are due to a delayed insensitivity to the 3.0 mg/kg dose of B, day 10 pups were ADX and injected on days 14-17 with doses of B as high as 12 mg/kg. When tested for behavioral inhibition on day 18, these high doses of B were found to be ineffective in potentiating freezing above the level of vehicle-treated rats. Together, results suggest that prior to the end of the second postnatal week endogenous adrenal steroids and in particular B, are critically involved in developmental changes necessary for the eventual species typical expression of behavioral inhibition. C1 WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI 53792. RP TAKAHASHI, LK (reprint author), UNIV WISCONSIN,SCH MED,DEPT PSYCHIAT,600 HIGHLAND AVE,MADISON,WI 53792, USA. NR 46 TC 51 Z9 51 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-3806 J9 DEV BRAIN RES JI Dev. Brain Res. PD AUG 12 PY 1994 VL 81 IS 1 BP 121 EP 127 DI 10.1016/0165-3806(94)90074-4 PG 7 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA PB770 UT WOS:A1994PB77000013 ER PT J AU WEISSBACH, L SETTLEMAN, J KALADY, MF SNIJDERS, AJ MURTHY, AE YAN, YX BERNARDS, A AF WEISSBACH, L SETTLEMAN, J KALADY, MF SNIJDERS, AJ MURTHY, AE YAN, YX BERNARDS, A TI IDENTIFICATION OF A HUMAN RASGAP-RELATED PROTEIN CONTAINING CALMODULIN-BINDING MOTIFS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GTPASE-ACTIVATING PROTEIN; SCHIZOSACCHAROMYCES-POMBE; TYROSINE KINASE; GENE; GAP; MYOSIN; ASSOCIATION; RECEPTOR; ENCODES; CANCER AB Conversion of active GTP-bound has to its inactive GDP-bound form is catalyzed by GTPase-activating proteins (GAPs). Two mammalian Ras-specific GAPs, p120GAP and neurofibromin, the product of the NF1 tumor suppressor gene, have been previously described. We report here the identification of a new human cDNA clone, IQGAP1, which predicts a 1657-amino acid protein that displays extensive sequence similarity to the catalytic domain of all previously reported RasGAPs. IQGAP1 is most closely related to the Schizosaccharomyces pombe RasGAP-like protein, Sar1. Sequence similarity to IQGAP1 is seen throughout the entire Sar1 protein. The N-terminal half of IQGAP1, which does not overlap with Sar1, contains six copies of a unique amino acid motif, as well as four so-called IQ motifs. The latter motifs are found in several proteins, including conventional and unconventional myosins, and mediate the interaction with calmodulin and calmodulin-related proteins. Thus, IQGAP1 appears to represent a novel RasGAP-like protein that may link Ras signaling to some calmodulin-mediated process. C1 MASSACHUSETTS GEN HOSP E,CTR CANC,BOSTON,MA 02129. RP WEISSBACH, L (reprint author), MASSACHUSETTS GEN HOSP,ORTHOPAED RES LABS,BOSTON,MA 02114, USA. FU NIAMS NIH HHS [R1AR16265-19]; NINDS NIH HHS [NS 22224, NS 31747] NR 34 TC 161 Z9 167 U1 1 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 12 PY 1994 VL 269 IS 32 BP 20517 EP 20521 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PB317 UT WOS:A1994PB31700049 PM 8051149 ER PT J AU REISIN, IL PRAT, AG ABRAHAM, EH AMARA, JF GREGORY, RJ AUSIELLO, DA CANTIELLO, HF AF REISIN, IL PRAT, AG ABRAHAM, EH AMARA, JF GREGORY, RJ AUSIELLO, DA CANTIELLO, HF TI THE CYSTIC-FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR IS A DUAL ATP AND CHLORIDE CHANNEL SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MULTIDRUG-RESISTANCE; CL CHANNEL; CFTR; CELLS; GENE; EXPRESSION; BINDING; IDENTIFICATION; NUCLEOTIDES; ACTIVATION AB The cystic fibrosis transmembrane conductance regulator (CFTR) belongs to a superfamily of proteins implicated in the transport of ions, proteins, and hydrophobic substances. Recent studies have demonstrated that CFTR is a protein kinase A-sensitive anion channel regulated by ATP. In the present study, patch-clamp techniques were used to assess the role of CFTR in the transport of Cl- and ATP. The stable transfection of mouse mammary carcinoma cells, C127i, with the cDNA for human CFTR resulted in the appearance of a diphenylamine-2-carboxylate-inhibitable Cl- channel, which was activated by cAMP under whole-cell and cell-attached conditions and by protein kinase A plus ATP under excised, inside-out conditions. CFTR expression was also associated with the electrodiffusional movement of ATP as indicated by the cAMP activation of ATP currents measured under whole-cell conditions. In excised, inside-out patches, it was demonstrated that ATP currents were mediated by ATP-conductive channels, which were also activated by protein kinase A and blocked by the Cl- channel blocker diphenylamine-2-carboxylate under excised, inside-out conditions. Single-channel currents observed in the presence of asymmetrical Cl-/ATP concentrations indicated that the same conductive pathway was responsible for both ATP and Cl- movement. Thus, CFTR is a multifunctional protein with more than one anion transport capability and may modify signal transduction pathways for Cl- or other secretory processes by the selective delivery of nucleotides to the extracellular domain. C1 HARVARD UNIV, SCH MED, DEPT MED, BOSTON, MA 02129 USA. GENZYME CORP, FRAMINGHAM, MA 01701 USA. MASSACHUSETTS GEN HOSP, RENAL UNIT, BOSTON, MA 02129 USA. MASSACHUSETTS GEN HOSP, DEPT RADIAT ONCOL, BOSTON, MA 02129 USA. NR 39 TC 278 Z9 280 U1 0 U2 10 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 AUG 12 PY 1994 VL 269 IS 32 BP 20584 EP 20591 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PB317 UT WOS:A1994PB31700059 PM 7519611 ER PT J AU KHARBANDA, S YUAN, ZM RUBIN, E WEICHSELBAUM, R KUFE, D AF KHARBANDA, S YUAN, ZM RUBIN, E WEICHSELBAUM, R KUFE, D TI ACTIVATION OF SRC-LIKE P56/P53(LYN) TYROSINE KINASE BY IONIZING-RADIATION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; LYMPHOCYTE-B PRECURSORS; WEE1 PROTEIN-KINASE; FACTOR-KAPPA-B; MONOCYTIC DIFFERENTIATION; N-ACETYLCYSTEINE; DNA DAMAGE; CELLS; GENE; TRANSCRIPTION AB Mammalian calls respond to ionizing radiation (IR) with cell cycle arrest, activation of DNA repair, and induction of early response genes. The present work has examined the involvement of Src-like protein-tyrosine kinases in the response of irradiated HL-60 myeloid leukemia cells. The results demonstrate little if any effect of IR on p59(fyn), p56(lck), and pp60(c-src) activity. In contrast, HL-60 cells responded to x-ray exposure with activation of p56/p53(lyn). At a dose of 200 centigrays, induction of p56/p53(lyn) activity was detectable at 15 min. Doses as low as 50 centigrays were effective in activating p56/p53(lyn). H2O2 and the scavenger N-acetylcysteine had no detectable effect on p56/p53(lyn) activation, while the protein-tyrosine kinase inhibitors, herbimycin and genistein, blocked induction by IR. The results also demonstrate that incubation of a glutathione S-transferase-Lyn fusion protein with lysates of irradiated HL-60 cells is associated with binding of the cell cycle regulatory protein, p34(cdc2). The interaction of p56/p53(lyn) and p34(cdc2) was confirmed in similar experiments with a glutathione S-transferase-Cdc2 fusion protein. Moreover, coimmuno-precipitation studies demonstrate the selective binding of activated p56/53(lyn) to p34(cdc2), irradiated cells. These findings indicate that IR activates p56/p53(lyn) in HL-60 cells and that this tyrosine kinase may contribute to the regulation of p34(cdc2). C1 UNIV CHICAGO,PRITZKER SCH MED,DEPT RADIAT & CELLULAR ONCOL,CHICAGO,IL 60637. 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 [CA55241] NR 36 TC 94 Z9 94 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 12 PY 1994 VL 269 IS 32 BP 20739 EP 20743 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PB317 UT WOS:A1994PB31700080 PM 8051175 ER PT J AU ROLLER, PP OTAKA, A NOMIZU, M SMYTH, MS BARCHI, JJ BURKE, TR CASE, RD WOLF, G SHOELSON, SE AF ROLLER, PP OTAKA, A NOMIZU, M SMYTH, MS BARCHI, JJ BURKE, TR CASE, RD WOLF, G SHOELSON, SE TI NORLEUCINE AS A REPLACEMENT FOR METHIONINE IN PHOSPHATASE-RESISTANT LINEAR AND CYCLIC-PEPTIDES WHICH BIND TO P85 SH2 DOMAINS SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID AFFINITY PHOSPHOTYROSYL PEPTIDE; SOLID-PHASE SYNTHESIS; PHOSPHATIDYLINOSITOL 3-KINASE; TARGETS; ANALOGS; BOC AB A Met residue in the pTyr+3 position has previously been shown to be an important determinant for high affinity binding of peptides to PI 3-kinase p85 SH2 domains. In the present work, a series of linear and cyclic peptides based on the sequence ''Gly-pTyr-Val-Pro-Met-Leu'' as well as analogues having pTyr replaced by the phosphatase-resistant pTyr mimetics, phosphonomethyl phenylalanine (Pmp) or difluorophosphonomethyl phenylalanine (F(2)Pmp), were synthesized and their binding potency in p85 SH2 domain preparations compared with corresponding peptides in which the Met has been substituted by Nle. Nle is a chemically more stable, isosteric Met homologue in which the sulfur has been replaced by a methylene. Significant binding potency was retained by the Nle-containing peptides, indicating that Met is not absolutely essential for high affinity binding to this SH2 domain. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MED CHEM LAB,BETHESDA,MD 20893. HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02215. RI Barchi Jr., Joseph/N-3784-2014 NR 25 TC 10 Z9 10 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD AUG 11 PY 1994 VL 4 IS 15 BP 1879 EP 1882 DI 10.1016/S0960-894X(01)80389-9 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA PB556 UT WOS:A1994PB55600019 ER PT J AU ABDELILAH, S SOLNICAKREZEL, L STAINIER, DYR DRIEVER, W AF ABDELILAH, S SOLNICAKREZEL, L STAINIER, DYR DRIEVER, W TI IMPLICATIONS FOR DORSOVENTRAL AXIS DETERMINATION FROM THE ZEBRAFISH MUTATION JANUS SO NATURE LA English DT Article ID OCCURRING DIBLASTODERMIC EGGS; XENOPUS-LAEVIS; CELL LINEAGE; FATE MAP; CLEAVAGE; EMBRYOS; EXPRESSION; ORGANIZER; PATTERN; GENES AB THE mechanisms underlying the formation of dorsoventral polarity in the zebrafish Danio rerio are unknown. Here we describe the zebrafish recessive maternal-effect mutation janus(m55). The mutant phenotype is a division of the blastoderm along the first cleavage plane into two detached half-sized blastoderms. Partial-axis bifurcation occurs in a subset of mutants. Analysis of goosecoid expression in the mutant embryos indicates that only one organizer region is present in each embryo. Furthermore, the position of this organizer region is random with respect to the first cleavage plant bisecting the two blastoderms. Finally, cell tracing in wild-type embryos demonstrates that there is no strict correlation of the dorsoventral axis with early cleavage planes in zebrafish. These findings support the notion that the establishment of the dorsoventral axis and the first cleavage planes are determined by separate mechanisms in the zebrafish embryo. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02129. RP ABDELILAH, S (reprint author), MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,13TH ST,BLDG 149,BOSTON,MA 02129, USA. NR 24 TC 42 Z9 45 U1 0 U2 2 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD AUG 11 PY 1994 VL 370 IS 6489 BP 468 EP 471 DI 10.1038/370468a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PB407 UT WOS:A1994PB40700058 PM 8047167 ER PT J AU KWON, H IMBALZANO, AN KHAVARI, PA KINGSTON, RE GREEN, MR AF KWON, H IMBALZANO, AN KHAVARI, PA KINGSTON, RE GREEN, MR TI NUCLEOSOME DISRUPTION AND ENHANCEMENT OF ACTIVATOR BINDING BY A HUMAN SW1/SNF COMPLEX SO NATURE LA English DT Article ID TRANSCRIPTIONAL ACTIVATION; YEAST; GAL4; DNA; SNF2/SWI2; PROTEINS; INVITRO; FAMILY; CHROMATIN; DOMAINS AB CHROMATIN structure can affect the transcriptional activity of eukaryotic structural genes by blocking access of sequence-specific activator proteins (activators) to their promoter-binding sites(1). For example, the DNA-binding domain of the yeast GAL4 protein interacts very poorly with nucleosome cores compared with naked DNA(2) (and see below), and binding of other activators is even more strongly inhibited(2,3). The way in which activators bind to nucleosomal DNA is therefore a critical aspect of transcriptional activation. Genetic studies have suggested that the multi-component SWI/SNF complex of Saccharomyces cerevisiae facilitates transcription by altering the structure of the chromatin(4,5). Here we identify and partially purify a human homologue of the yeast SWI/SNF complex (hSWI/SNF complex). We show that a partially purified hSWI/SNF complex mediates the ATP-dependent disruption of a nucleosome, thereby enabling the activators, GAL4-VP16 and GAL4-AH, to bind within a nucleosome core. We conclude that the hSWI/SNF complex acts directly to reorganize chromatin structure so as to facilitate binding of transcription factors. C1 UNIV MASSACHUSETTS,SCH MED,HOWARD HUGHES MED INST,PROGRAM MOLEC MED,WORCESTER,MA 01605. MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. STANFORD UNIV,CTR MOILEC & GENET MED,HOWARD HUGHES MED INST,STANFORD,CA 94305. NR 24 TC 556 Z9 560 U1 0 U2 7 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD AUG 11 PY 1994 VL 370 IS 6489 BP 477 EP 481 DI 10.1038/370477a0 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PB407 UT WOS:A1994PB40700061 PM 8047169 ER PT J AU IMBALZANO, AN KWON, H GREEN, MR KINGSTON, RE AF IMBALZANO, AN KWON, H GREEN, MR KINGSTON, RE TI FACILITATED BINDING OF TATA-BINDING PROTEIN TO NUCLEOSOMAL DNA SO NATURE LA English DT Article ID RNA POLYMERASE-II; TRANSCRIPTION FACTOR; CHROMATIN STRUCTURE; CRYSTAL-STRUCTURE; MINOR-GROOVE; TFIID BINDS; BOX COMPLEX; MAJOR LATE; YEAST; INVITRO AB BINDING of the TATA-binding protein (TBP) to the TATA box is required for transcription from many eukaryotic promoters in gene expression. Regulation of this binding is therefore likely to be an important determinant of promoter activity. Incorporation of the TATA sequence into nucleosomes dramatically reduces transcription initiation(1-3), presumably because of stereochemical constraints on binding of general transcription factors. Biochemical and genetic studies imply that cellular factors such as yeast SWI/SNF are required for activator function and might alter chromatin structure(4-11). One step that could be regulated during the activation process is TBP binding in chromatin(12,13) We show here that binding of TBP to the TATA sequence is severely inhibited by incorporation of this sequence into a nucleosome. Inhibition can be overcome by ATP-dependent alterations in nucleosomal DNA structure mediated by hSWI/SNF, a putative human homologue of the yeast SWI/SNF complex. Additionally, the orientation of the TATA sequence relative to the surface of the histone core affects the access of TBP. We propose that the dynamic remodelling of chromatin structure to allow TBP binding is a key step in the regulation of eukaryotic gene expression. C1 MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. UNIV MASSACHUSETTS,MED CTR,HOWARD HUGHES MED INST,PROGRAM MOLEC MED,WORCESTER,MA 01605. NR 30 TC 472 Z9 474 U1 2 U2 9 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD AUG 11 PY 1994 VL 370 IS 6489 BP 481 EP 485 DI 10.1038/370481a0 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PB407 UT WOS:A1994PB40700062 PM 8047170 ER PT J AU GOLDEN, JA LOUIS, DN AF GOLDEN, JA LOUIS, DN TI ACUTE BACTERIAL-MENINGITIS SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Note RP GOLDEN, JA (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 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 AUG 11 PY 1994 VL 331 IS 6 BP 364 EP 364 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA PA374 UT WOS:A1994PA37400005 PM 8028617 ER PT J AU VOLBERDING, PA LAGAKOS, SW GRIMES, JM STEIN, DS BALFOUR, HH REICHMAN, RC BARTLETT, JA HIRSCH, MS PHAIR, JP MITSUYASU, RT FISCHL, MA SOEIRO, R AF VOLBERDING, PA LAGAKOS, SW GRIMES, JM STEIN, DS BALFOUR, HH REICHMAN, RC BARTLETT, JA HIRSCH, MS PHAIR, JP MITSUYASU, RT FISCHL, MA SOEIRO, R TI THE DURATION OF ZIDOVUDINE BENEFIT IN PERSONS WITH ASYMPTOMATIC HIV-INFECTION - PROLONGED EVALUATION OF PROTOCOL-019 OF THE AIDS-CLINICAL-TRIALS-GROUP SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; PLACEBO-CONTROLLED TRIAL; CD4+ CELL COUNTS; CUBIC MILLIMETER; DOUBLE-BLIND; EFFICACY; COMPLEX; AZT AB Objective.-To determine the durability of zidovudine-induced delay in clinical progression of asymptomatic human immunodeficiency virus (HIV) disease and to assess the relationship between this effect and the entry CD4(+) cell count. Design and Interventions.-Extended follow-up data from subjects participating in protocol 019 of the AIDS [acquired immunodeficiency syndrome] Clinical Trials Group were examined. Subjects were offered a total daily dose of 500 mg of open-label zidovudine after the unblinding of the original randomized trial in 1989. Original treatment groups included placebo, 500 mg of zidovudine, or 1500 mg of zidovudine daily in divided doses. Three distinct analyses were conducted to assess the duration of zidovudine's effect on progression to AIDS or death: (1) analysis of all follow-up information from all subjects, (2) analysis of all subjects but with follow-up of original placebo-assigned subjects censored at the time open-label zidovudine was initiated, and (3) analysis of the effect of initiating zidovudine in subjects initially assigned to receive placebo. Setting.-University-based and university-affiliate AIDS research clinics participating in AIDS Clinical Trials Group protocol 019. Patients.-A total of 1565 asymptomatic HIV-infected subjects with entry CD4(+) cell counts less than 0.50x10(9)/L (500/mu L). Main Outcome Measure.-Time to progression to AIDS or death. Results.-During follow-up of up to 4.5 years (mean, 2.6 years), 232 subjects progressed to AIDS or died. In each of the three analyses described herein, zidovudine was associated with a significant (P=.008, .004, .007) decrease in the risk of such progression. However, each of these analyses also indicated a decreasing placebo:zidovudine relative risk with duration of use (P=.002, .08, .04), suggesting a nonpermanent effect. The duration of benefit appeared to be related to entry CD4(+) cell count, with greater benefit in those with higher counts at entry. No significant differences in survival were found between those originally randomized to zidovudine or placebo. Conclusions.-Zidovudine at 500 mg/d caused a significant delay in progression to AIDS or death, but its earlier use in asymptomatic disease was not associated with an additional prolongation of survival compared with delayed initiation. The delay in progression diminished overtime especially in subjects with entry CD4(+) cell counts less than 0.30x10(9)/L (300/mu L). Treatment strategies that alter drug regimens before the loss of zidovudine benefit should be explored. C1 UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA. HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. NIAID,BETHESDA,MD. UNIV MINNESOTA,MINNEAPOLIS,MN 55455. UNIV ROCHESTER,SCH MED & DENT,ROCHESTER,NY. DUKE UNIV,MED CTR,DURHAM,NC. HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NORTHWESTERN UNIV,CHICAGO,IL 60611. UNIV CALIF LOS ANGELES,LOS ANGELES,CA. UNIV MIAMI,SCH MED,MIAMI,FL. ALBERT EINSTEIN MONTEFIORE MED CTR,NEW YORK,NY. RP VOLBERDING, PA (reprint author), SAN FRANCISCO GEN HOSP,AIDS PROGRAM,WARD 84,995 POTRERO AVE,SAN FRANCISCO,CA 94110, USA. NR 21 TC 127 Z9 127 U1 0 U2 1 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 AUG 10 PY 1994 VL 272 IS 6 BP 437 EP 442 DI 10.1001/jama.272.6.437 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA PA278 UT WOS:A1994PA27800024 PM 7913730 ER PT J AU WU, G MILLER, KW AF WU, G MILLER, KW TI ETHANOL ENHANCES AGONIST-INDUCED FAST DESENSITIZATION IN NICOTINIC ACETYLCHOLINE-RECEPTORS SO BIOCHEMISTRY LA English DT Article ID FROG NEUROMUSCULAR-JUNCTION; MEMBRANE-VESICLES; TORPEDO; KINETICS; INACTIVATION; ACTIVATION; CHANNELS; ENDPLATE; INHIBITION; MECHANISM AB The reversible decline of the nicotinic acetylcholine receptor's response to acetylcholine during prolonged exposure to acetylcholine is known as desensitization. Here, we studied ethanol's modulation of fast agonist-induced desensitization of the nicotinic acetylcholine receptor in postsynaptic membrane vesicles from Torpedo using a fast kinetic technique: pulsed quenched flow. Preincubation of the vesicles with various concentrations of acetylcholine at 4 degrees C for times ranging from 80 ms to 1.5 s caused fast desensitization, which was revealed as a decreased Rb-86(+) influx when the vesicles were subsequently briefly exposed to a saturating concentration of acetylcholine in (RbCl)-Rb-86. Acetylcholine-induced fast desensitization had a maximum observed rate, k(d)(max), of 6.8 s(-1), a half-effect concentration, K-D, of 157 mu M, and a Hill coefficient of 1.4. Increasing the ethanol concentration up to 1.0 M causes a linear increase in k(d)(max), such that 1.0 M ethanol doubles the rate. Ethanol (1 M) also decreased K-D 10-fold without changing the Hill coefficient. We consider a modified sequential model to interpret our data. Two acetylcholine molecules bind sequentially to the receptor's resting state to form a pre-open (closed) state, which then opens and, at very high acetylcholine concentrations, is inhibited. A priori fast desensitization might occur from any of these acetylcholine-occupied states. If we assume fast desensitization to occur solely from the pre-open state, our data predict an excessively large action of ethanol on the fast desensitization rate constant (> 200-fold increase in the desensitization rate constant at 1 M ethanol). When we assume fast desensitization to occur from all states, ethanol is seen to have two actions. It shifts the equilibrium between the closed and open states toward the open state, accounting for the shift in the concentration response curve for fast desensitization, and it enhances the fast desensitization rate constant, accounting for the observed increase in the desensitization rate. As a consequence of this dual action, ethanol's net effect depends on both the agonist's concentration and its duration of action. Physiological concentrations of ethanol have their most pronounced effects at low agonist concentrations. C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. FU NIAAA NIH HHS [AA-07040] NR 36 TC 18 Z9 18 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD AUG 9 PY 1994 VL 33 IS 31 BP 9085 EP 9091 DI 10.1021/bi00197a009 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PB763 UT WOS:A1994PB76300009 PM 8049210 ER PT J AU KASSNER, PD KAWAGUCHI, S HEMLER, ME AF KASSNER, PD KAWAGUCHI, S HEMLER, ME TI MINIMUM ALPHA-CHAIN CYTOPLASMIC TAIL SEQUENCE NEEDED TO SUPPORT INTEGRIN-MEDIATED ADHESION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL-ADHESION; MONOCLONAL-ANTIBODY; BETA-SUBUNIT; BINDING-SITE; FIBRONECTIN RECEPTOR; GPIIB-IIIA; T-CELLS; TERMINAL DIFFERENTIATION; LIGAND AVIDITY; DOMAIN AB Previously, we found that deletion of the integrin alpha(4) and alpha(2) subunit cytoplasmic domains, just after the conserved GFFKR motif, causes a loss of adhesive activity mediated by VLA-4 or VLA-2, respectively (Kassner, P. D., and Hemler, M. E. (1993) J. Exp. Med. 178, 649-60; Kawaguchi, S., and Hemler, M. E. (1993) J. Biol. Chem. 268, 16279-12685). Here, we show for alpha(4) and alpha(2) chains (expressed in MIP101 and Chinese hamster ovary cells) that adding only 3-4 amino acids after the GFFKR motif restores substantial adhesive activity and that 5-7 amino acids confers maximal adhesive activity (to VCAM-1, CS1 peptide, or collagen, respectively), Point mutations within the most critical 5 alpha(4) residues had no effect on alpha(4) adhesive activity, nor did exchange of the alpha(4) tail with that of alpha(2). Thus, only a short and relatively nonspecific stretch of alpha chain cytoplasmic domain amino acids may be required to achieve maximal integrin adhesive activity. Also, comprehensive divalent cation titration assays revealed (i) that deletion of alpha chain cytoplasmic domains caused a marked decrease in the efficiency of divalent cation utilization during cell adhesion assays and (ii) that cytoplasmic domain deletion effects could be either suppressed or accentuated depending on the type and amount of divalent cation and the cellular environment utilized. Notably, integrin cu chain tail deletions did not appear to alter the intrinsic ability to interact with ligand because deletion effects were minimal in the presence of metabolic energy inhibitors and were absent during cell-free ligand binding assays. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. FU NIGMS NIH HHS [GM46526] NR 68 TC 66 Z9 66 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 AUG 5 PY 1994 VL 269 IS 31 BP 19859 EP 19867 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PA126 UT WOS:A1994PA12600033 PM 8051067 ER PT J AU FANG, KS SABE, H SAITO, H HANAFUSA, H AF FANG, KS SABE, H SAITO, H HANAFUSA, H TI COMPARATIVE-STUDY OF 3 PROTEIN-TYROSINE PHOSPHATASES - CHICKEN PROTEIN-TYROSINE-PHOSPHATASE-LAMBDA DEPHOSPHORYLATES C-SRC TYROSINE-527 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INSULIN-RECEPTOR KINASE; CELL-TRANSFORMATION; ESCHERICHIA-COLI; V-SRC; ACTIVATION; P60C-SRC; DOMAIN; PHOSPHORYLATION; PURIFICATION; PP60(C-SRC) AB To examine the substrate preference of protein tyrosine phosphatases (PTPs), we compared the activity of three transmembrane PTPs on dephosphorylation and regulation of c-Src and v-Src: chicken PTP lambda (ChPTP lambda), chicken PTP alpha (ChPTP alpha), and human leukocyte common antigen-related molecule (HLAR). In vitro, all three PTPs dephosphorylated v-Src, but only ChPTP lambda dephosphorylated c Src. Their activities were also compared in Cos cells coexpressing Src and the phosphatase domains of three PTPs. These domains were fused with peptides for myristylation, so they associated with the cellular membrane. When c-Src was coexpressed with myrPTP lambda, its kinase activity was elevated 3-4-folds. This activation was less obvious when c-Src was coexpressed with myrPTP alpha or myrLAR. Analysis by cyanogen bromide cleavage showed that ChPTP lambda and myrPTP lambda dephosphorylated Tyr-527 of c-Src. Our data demonstrated the different activities of three PTPs on phosphoproteins, suggesting that Src Tyr-527 may require more specific PTP(s) than Src Tyr-416 for dephosphorylation in vivo. C1 ROCKEFELLER UNIV,MOLEC ONCOL LAB,NEW YORK,NY 10021. HARVARD UNIV,DANA FARBER CANC INST,BOSTON,MA 02115. RI Sabe, Hisataka/A-4066-2012 FU NCI NIH HHS [CA44356] NR 45 TC 42 Z9 43 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 AUG 5 PY 1994 VL 269 IS 31 BP 20194 EP 20200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PA126 UT WOS:A1994PA12600079 PM 7519604 ER PT J AU CHANG, CYY SASTRY, KN GILLIES, SD EZEKOWITZ, RAB SHERIFF, S AF CHANG, CYY SASTRY, KN GILLIES, SD EZEKOWITZ, RAB SHERIFF, S TI CRYSTALLIZATION AND PRELIMINARY-X-RAY ANALYSIS OF A TRIMERIC FORM OF HUMAN MANNOSE-BINDING PROTEIN SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Note DE MANNOSE BINDING PROTEIN CRYSTALLIZATION; X-RAY CRYSTALLOGRAPHY ID DOMAIN AB A trimeric form of the carbohydrate recognition domain of human mannose binding protein has been crystallized in two different forms. The first form crystallizes with symmetry consistent with space group P2(1)2(1)2(1) and a = 61 Angstrom; b = 144 Angstrom; c = 107 Angstrom with presumably two trimers in the asymmetric unit. The second form crystallizes with symmetry consistent with space group P321 and a = b = 77 Angstrom; c = 58 Angstrom and one monomer per asymmetric unit. The molecular and crystallographic S-folds must be coincident in this crystal form C1 BRISTOL MYERS SQUIBB PHARMACEUT RES INST,PRINCETON,NJ 08543. HARVARD UNIV,CHILDRENS HOSP,DEPT PEDIAT,DIV HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. ABBOTT BIOTECH,NEEDHAM HTS,MA 02194. FU NCRR NIH HHS [RR-01646] NR 17 TC 7 Z9 7 U1 1 U2 2 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD AUG 5 PY 1994 VL 241 IS 1 BP 125 EP 127 DI 10.1006/jmbi.1994.1479 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PA947 UT WOS:A1994PA94700013 PM 8051701 ER PT J AU DING, HF RIMSKY, S BATSON, SC BUSTIN, M HANSEN, U AF DING, HF RIMSKY, S BATSON, SC BUSTIN, M HANSEN, U TI STIMULATION OF RNA-POLYMERASE-II ELONGATION BY CHROMOSOMAL PROTEIN HMG-14 SO SCIENCE LA English DT Article ID ASSEMBLED CHROMATIN TEMPLATES; MOBILITY GROUP PROTEIN-14; ACCURATE TRANSCRIPTION; NUCLEOSOMES; GENES; DNA; EXPRESSION; SEQUENCE; INVITRO; CELLS AB The high-mobility group protein 14 (HMG-14) is a non-histone chromosomal protein that is preferentially associated with transcriptionally active chromatin. To assess the effect of HMG-14 on transcription by RNA polymerase II, in vivo-assembled chromatin with elevated amounts of HMG-14 was obtained. Here it is shown that HMG-14 enhanced transcription on chromatin templates but not on DNA templates. This protein stimulated the rate of elongation by RNA polymerase II but not the level of initiation of transcription. These findings suggest that the association of HMG-14 with nucleosomes is part of the cellular process involved in the generation of transcriptionally active chromatin. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV MOLEC GENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOLEC GENET,BOSTON,MA 02115. NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. RI Bustin, Michael/G-6155-2015 FU NIGMS NIH HHS [GM-36667] NR 33 TC 74 Z9 75 U1 1 U2 1 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD AUG 5 PY 1994 VL 265 IS 5173 BP 796 EP 799 DI 10.1126/science.8047885 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PA372 UT WOS:A1994PA37200037 PM 8047885 ER PT J AU TOPPMEYER, DL SLAPAK, CA CROOP, J KUFE, DW AF TOPPMEYER, DL SLAPAK, CA CROOP, J KUFE, DW TI ROLE OF P-GLYCOPROTEIN IN DOLASTATIN-10 RESISTANCE SO BIOCHEMICAL PHARMACOLOGY LA English DT Note DE DOLASTATIN 10; MULTIDRUG RESISTANCE; P-GLYCOPROTEIN; CYTOTOXIC PEPTIDES; PEPTIDE TRANSPORT; TUBULIN BINDING DRUG ID CLASS-II REGION; BACTERIAL TRANSPORT PROTEINS; CALCIUM-CHANNEL BLOCKERS; MULTIDRUG RESISTANCE; ANTINEOPLASTIC AGENTS; MEMBRANE GLYCOPROTEIN; CELLS; GENE; SEQUENCE; HOMOLOGY AB Dolastatin 10, a cytotoxic pentapeptide isolated from the mollusk Dolabella auricularia, exhibits potent antitumor activity. The present studies demonstrated that sublines of murine PC4 and human U-937 leukemia cells expressing a multidrug resistance (MDR) phenotype are cross-resistant to this agent. We also demonstrated that such resistance was reversed by verapamil. While these findings suggested the involvement of the P-glycoprotein (P-gp) in dolastatin 10 resistance, we performed similar studies in a CHO cell line transfected with the human mdr1 cDNA. Expression of P-gp in the transfected cells was associated with resistance to dolastatin 10 by a verapamil-sensitive mechanism. The demonstration that photoaffinity labeling of P-gp was decreased in the presence of dolastatin 10 further supports the interaction of this cytotoxic peptide with P-gp. Taken together, these findings suggest that resistance to dolastatin 10 is conferred, at least in part, by P-gp and that this cytotoxic peptide is a novel member of the MDR phenotype C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. RP TOPPMEYER, DL (reprint author), HARVARD UNIV,SCH MED,DIV CANC PHARMACOL,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA01613, 5T32CA09172-19, CA19589] NR 26 TC 25 Z9 26 U1 0 U2 2 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 AUG 3 PY 1994 VL 48 IS 3 BP 609 EP 612 DI 10.1016/0006-2952(94)90292-5 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PC354 UT WOS:A1994PC35400021 PM 7915113 ER PT J AU BARNARD, GF STANIUNAS, RJ PUDER, M STEELE, GD CHEN, LB AF BARNARD, GF STANIUNAS, RJ PUDER, M STEELE, GD CHEN, LB TI HUMAN RIBOSOMAL-PROTEIN L37 HAS MOTIFS PREDICTING SERINE/THREONINE PHOSPHORYLATION AND A ZINC-FINGER DOMAIN SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION LA English DT Note DE RIBOSOMAL PROTEIN; L37; COLON CANCER; SUBTRACTIVE CDNA HYBRIDIZATION; (HUMAN) ID COLORECTAL-CANCER; MESSENGER-RNAS; COLON-CARCINOMA; GENE; EXPRESSION; SEQUENCE AB Ribosomal protein L37 mRNA is overexpressed in colon cancer. The nucleotide sequences of human L37 from several tumor and normal, colon and liver cDNA sources were determined to be identical. L37 mRNA was similar to 375 nucleotides long encoding 97 amino acids with M(r)=11070, pI=12.6, multiple potential serine/threonine phosphorylation sites and a zinc-finger domain. The human sequence is compared to other species. C1 HARVARD UNIV, SCH MED, DANA FARBER CANC INST, DIV CELLULAR & MOLEC BIOL, BOSTON, MA 02115 USA. HARVARD UNIV, NEW ENGLAND DEACONESS HOSP, SCH MED, DEPT SURG, BOSTON, MA 02215 USA. HARVARD UNIV, BRIGHAM & WOMENS HOSP, SCH MED, BOSTON, MA 02115 USA. RP UNIV MASSACHUSETTS, MED CTR, DEPT MED, DIV DIGEST DIS & NUTR, 55 LAKE AVE N, WORCESTER, MA 01655 USA. FU NCI NIH HHS [CA44704, NCI 5F32CA-0900]; NIDDK NIH HHS [DK07533] NR 24 TC 14 Z9 15 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4781 J9 BBA-GENE STRUCT EXPR JI Biochim. Biophys. Acta-Gene Struct. Expression PD AUG 2 PY 1994 VL 1218 IS 3 BP 425 EP 428 DI 10.1016/0167-4781(94)90197-X PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA PB554 UT WOS:A1994PB55400022 PM 7545944 ER PT J AU PHARR, PN OGAWA, M HOFBAUER, A LONGMORE, GD AF PHARR, PN OGAWA, M HOFBAUER, A LONGMORE, GD TI EXPRESSION OF AN ACTIVATED ERYTHROPOIETIN OR A COLONY-STIMULATING FACTOR-1 RECEPTOR BY PLURIPOTENT PROGENITORS ENHANCES COLONY FORMATION BUT DOES NOT INDUCE DIFFERENTIATION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID BLAST CELL COLONIES; HEMATOPOIETIC PROGENITORS; CSF-1 RECEPTOR; LINEAGE COMMITMENT; POINT MUTATION; GROWTH-FACTOR; PROLIFERATION; ONCOGENE; SUPERFAMILY; DOMAIN AB Whether the presence of specific receptors on the surface of developing cells is the cause of consequence of lineage restriction is not known. If activation of specific receptors is the driving event in differentiation, the premature expression of specific receptors would promote differentiation along that pathway. In this study pluripotent progenitors, obtained from blast cell colonies (pooled or individual) of 5-flurouracil-treated mice, were infected with retroviral vectors containing either an activated receptor for erythropoietin (EPO), an erythroid progenitor growth factor, or the receptor for colony-stimulating factor 1 (CSF-1), a macrophage growth factor. These receptors exhibit expression patterns restricted to committed progenitors. The developmental potential of infected pluripotent progenitors was not changed, although they expressed the exogenous genes, suggesting that in these cells activation of lineage-specific receptors does not induce differentiation. Acquisition of a constitutively activated EPO receptor allowed erythroid development in mixed colonies in the absence of EPO, as expected. Infection of progenitors with a virus containing the CSF-1 receptor promoted the development of granulocyte/macrophage (GM) colonies but did not alter the differentiation potential of either colony-forming unit (CFU)-GM or CFU-mix. C1 MED UNIV S CAROLINA,DEPT MED,CHARLESTON,SC 29401. WASHINGTON UNIV,SCH MED,DEPT MED,ST LOUIS,MO 63110. WASHINGTON UNIV,SCH MED,DEPT CELL BIOL,ST LOUIS,MO 63110. RP PHARR, PN (reprint author), RALPH H JOHNSON DEPT VET AFFAIRS MED CTR,CHARLESTON,SC 29401, USA. FU NCI NIH HHS [CA 50244]; NIDDK NIH HHS [DK 32294] NR 31 TC 43 Z9 44 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 AUG 2 PY 1994 VL 91 IS 16 BP 7482 EP 7486 DI 10.1073/pnas.91.16.7482 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PA376 UT WOS:A1994PA37600022 PM 8052607 ER PT J AU LAM, BK PENROSE, JF FREEMAN, GJ AUSTEN, KF AF LAM, BK PENROSE, JF FREEMAN, GJ AUSTEN, KF TI EXPRESSION CLONING OF A CDNA FOR HUMAN LEUKOTRIENE C-4 SYNTHASE, AN INTEGRAL MEMBRANE-PROTEIN CONJUGATING REDUCED GLUTATHIONE TO LEUKOTRIENE A(4) SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE CYSTEINYL LEUKOTRIENES; 5-LIPOXYGENASE ACTIVATING PROTEIN; ENZYME ID HUMAN-LEUKOCYTES; 5-LIPOXYGENASE-ACTIVATING PROTEIN; HUMAN EOSINOPHILS; SEQUENCE ANALYSIS; BINDING-PROTEIN; S-TRANSFERASE; PURIFICATION; CELLS; IDENTIFICATION; BIOSYNTHESIS AB Leukotriene (LT) C-4 synthase, an integral microsomal membrane protein, conjugates LTA(4), an epoxide intermediate, to reduced glutathione (GSH) to form a proinflammatory mediator, LTC(4). A sensitive fluorescence-linked immunoassay for LTC(4) was used to screen a KG-1 cDNA expression library for LTC(4) synthase activity after transfection of COS cells and addition of substrate LTA(4). Stepwise resolution of 240,000 colonies in 96 pools led to the identification of individual clones with maximal LTC(4) synthase activity that contained a 694-bp cDNA insert. This insert was composed of a 54-bp 5' nontranslated region, an ATTAAA polyadenylylation signal, and a poly(A)(+) tail. The open reading frame encodes a 16.5-kDa protein with a pI of 11.05. Hybridization with a cDNA probe demonstrated a mRNA transcript of 0.7 kbp in RNAs from human eosinophils and KG-1 cells, which contain LTC(4) synthase. The nucleotide and deduced amino acid sequences of the LTC(4) synthase cDNA show no significant homology to GSH S-transferases but share 31% overall amino acid identity with 5-lipoxygenase activating protein (FLAP). The identity at the N-terminal two-thirds of these two proteins is 44%, with some regions of near identity. Peptide structural analysis of the deduced LTC(4) synthase predicts the presence of three transmembrane domains nearly superimposable on those of FLAP. Moreover, LTC(4) synthase is inhibitable by a FLAP inhibitor, MK-886. Therefore, LTC(4) synthase is distinct from the known GSH S-transferases by nucleotide and consensus amino acid sequences, and its GSH-conjugating function represents a distinct integral membrane protein belonging to a distinct gene family. C1 BRIGHAM & WOMENS HOSP,DEPT RHEUMATOL & IMMUNOL,BOSTON,MA 02115. CHILDRENS HOSP,DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. RP LAM, BK (reprint author), HARVARD UNIV,SCH MED,DEPT MED,SEELEY G MUDD BLDG,ROOM 610,250 LONGWOOD AVE,BOSTON,MA 02115, USA. FU NHLBI NIH HHS [HL36110]; NIAID NIH HHS [AI22531, AI31599] NR 33 TC 214 Z9 218 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 AUG 2 PY 1994 VL 91 IS 16 BP 7663 EP 7667 DI 10.1073/pnas.91.16.7663 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PA376 UT WOS:A1994PA37600059 PM 8052639 ER PT J AU YUNIS, JJ MOBINI, N YUNIS, EJ ALPER, CA DEULOFEUT, R RODRIGUEZ, A FOSTER, CS MARCUSBAGLEY, D GOOD, RA AHMED, AR AF YUNIS, JJ MOBINI, N YUNIS, EJ ALPER, CA DEULOFEUT, R RODRIGUEZ, A FOSTER, CS MARCUSBAGLEY, D GOOD, RA AHMED, AR TI COMMON MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II MARKERS IN CLINICAL VARIANTS OF CICATRICIAL PEMPHIGOID SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE PCR; HLA ALLELES AND HAPLOTYPES; AUTOIMMUNITY; EYE DISEASES ID SUSCEPTIBILITY; ALLELES AB Cicatricial pemphigoid (CP) is a chronic autoimmune blistering disease affecting multiple mucous membranes derived from stratified squamous epithelium and occasionally the skin. CP has a wide spectrum of disease manifestations, Patients with oral pemphigoid (OF) have a benign self-limited disease in which pathological changes are restricted to the oral mucosa. On the other hand, patients with ocular cicatricial pemphigoid (OCP), a chronic condition marked with relapses and remissions, have ocular involvement and also perhaps involvement of other mucous membranes. All clinical subsets are characterized by the presence of a similar antibasement zone autoantibody. The factors that determine the development of one form of CP or the other are not known. In a previous study, we described the association between OCP and the DQB1*0301 allele (P = 0.006). In this study, we have analyzed 22 Caucasian patients with OP and their family members for major histocompatibility complex DRB generic, DQA1, and DQB1 allele associations by PCR-sequence-specific oligonucleotide probe hybridization. The results were compared to those obtained from 17 Caucasian patients with OCP and to control Caucasian alleles and haplotypes. The DQB1*0301 allele frequency was 38.6% in OP, 52.9% in OCP, and 17.8% in controls. Statistically significant associations were detected between the DQB1*0301 allele and both OP (P 0.0047) and OCP (P < 0.0001). In addition, DRB1*04 showed a statistically significant association (P = 0.005) with OCP when compared to controls. Analysis of major histocompatibility complex class II haplotypes showed significant statistical associations between both OCP and OP and the HLA-DRB1*04, DRB4*0101, DQA1*03, DQB1*0301 haplotype (P < 0.0001 and P = 0.0012, respectively). Our results indicate that DQB1*0301 is a marker of both oral and ocular forms of CP. The analysis of the amino acid sequence of the DQB1 alleles present in both OP and OCP suggested that amino acid residues at position 57 and positions 71-77 may also be markers of CP. C1 CTR BLOOD RES,BOSTON,MA 02115. DANA FARBER CANC INST,DIV IMMUNOGENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. BOSTON UNIV,SCH MED,DEPT DERMATOL,BOSTON,MA 02118. AMER RED CROSS,BLOOD SERV NE REG,DEDHAM,MA 02026. HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,BOSTON,MA 02114. UNIV S FLORIDA,ALL CHILDRENS HOSP,DEPT PEDIAT,ST PETERSBURG,FL 33701. FU NEI NIH HHS [EY 08379]; NHLBI NIH HHS [HL 29583]; NIDCR NIH HHS [DE 09978] NR 15 TC 49 Z9 52 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 2 PY 1994 VL 91 IS 16 BP 7747 EP 7751 DI 10.1073/pnas.91.16.7747 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PA376 UT WOS:A1994PA37600076 PM 8052655 ER PT J AU AUFIERO, B NEUFELD, EJ ORKIN, SH AF AUFIERO, B NEUFELD, EJ ORKIN, SH TI SEQUENCE-SPECIFIC DNA-BINDING OF INDIVIDUAL CUT REPEATS OF THE HUMAN CCAAT DISPLACEMENT/CUT HOMEODOMAIN PROTEIN SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE PCR SITE SELECTION; METHYLATION INTERFERENCE; TRANSCRIPTIONAL REPRESSOR ID SENSORY ORGAN IDENTITY; GAMMA-GLOBIN GENE; POU-DOMAIN; I-POU; DROSOPHILA; EXPRESSION; TRANSCRIPTION; PROMOTER; REGION; TRANSFORMATION AB CCAAT displacement protein (CDP), a nuclear protein of 180-190 kDa, contains a triplicated moth, the cut domain, similar (80-90% conserved) to three repeats of 60-65 amino acids first identified in Drosophila cut, a homeodomain protein involved in cell fate decisions in development. Cut repeats bind DNA and exhibit subtle differences in target-site recognition. DNA sequences specifically bound by cut repeats were isolated by PCR-mediated DNA target-site selection Sequences selected for cut repeat 2 and 3 (CR2 and CR3) binding are A+T-rich and favor an ATA moth with similar, but not identical, flanking base preferences. CR2 and CR3 discriminate among similar target sequences. CR1, which is more divergent from CR2 and CR3, displays the most restricted pattern of DNA sequence recognition. Methylation interference analysis demonstrates different protein-DNA contacts for CR1 and CR3 binding to a target sequence. Thus, CDP/cut is a complex protein whose DNA-binding properties reflect the combinatorial interaction of four domains (three cut repeats and one homeodomain) with target DNA sequences. C1 CHILDRENS HOSP,DIV HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PEDIAT,BOSTON,MA 02115. HOWARD HUGHES MED INST,BOSTON,MA 02115. RI Neufeld, Ellis/F-9331-2011 NR 30 TC 99 Z9 100 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 AUG 2 PY 1994 VL 91 IS 16 BP 7757 EP 7761 DI 10.1073/pnas.91.16.7757 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PA376 UT WOS:A1994PA37600078 PM 7914370 ER PT J AU BURAK, LJ AF BURAK, LJ TI EXAMINATION AND PREDICTION OF ELEMENTARY-SCHOOL TEACHERS INTENTIONS TO TEACH HIV/AIDS EDUCATION SO AIDS EDUCATION AND PREVENTION LA English DT Article ID REASONED ACTION; PLANNED BEHAVIOR; ATTITUDES; AIDS; KNOWLEDGE AB Although studies have looked at school teachers' beliefs and attitudes toward AIDS and students with HIV/AIDS, none have specifically addressed teachers' intentions and attitudes toward teaching HIV/AIDS education. This study examines and predicts elementary school teachers' intentions to teach their students about HIV/AIDS. The postulates of the theories of reasoned action and planned behavior provided the framework for the examination of teachers' beliefs, attitudes, subjective norms, and perceived behavioral control regarding AIDS education. A sample of 198 elementary school teachers employed in the Commonwealth of Massachusetts completed self-administered questionnaires. Multiple regression analysis was used to predict intentions to teach HIV/AIDS, and to identify the determinants of intentions. Attitude, subjective norm, and perceived behavioral control, the variables of the theory of planned behavior, explained 64% of the variance in teachers' intentions; perceived behavioral control contributed the greatest weight to the prediction. Significant variance was additionally explained by three variables external to the theory of planned behavior: in-service training, grade taught, and past HIV/AIDS teaching behavior. RP BURAK, LJ (reprint author), DANA FARBER CANC INST,WORKSITE TOBACCO CONTROL PROJECT,55 POND AVE 103-E,BROOKLINE,MA 02146, USA. NR 39 TC 11 Z9 11 U1 0 U2 1 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 SN 0899-9546 J9 AIDS EDUC PREV JI Aids Educ. Prev. PD AUG PY 1994 VL 6 IS 4 BP 310 EP 321 PG 12 WC Education & Educational Research; Public, Environmental & Occupational Health SC Education & Educational Research; Public, Environmental & Occupational Health GA PC548 UT WOS:A1994PC54800003 PM 7986652 ER PT J AU JOHNSON, VA AF JOHNSON, VA TI COMBINATION THERAPY - MORE EFFECTIVE CONTROL OF HIV TYPE-1 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article; Proceedings Paper CT 2nd Annual Optimal Management of HIV Disease; Clinical Conference - 10th Anniversary Perspectives on Aids: Clinical Investigation of HIV Disease CY JAN, 1994 CL FT LAUDERDALE, FL ID HUMAN-IMMUNODEFICIENCY-VIRUS; RECOMBINANT INTERFERON-ALPHA; RO 31-8959; IN-VITRO; SYNERGISTIC INHIBITION; REVERSE-TRANSCRIPTASE; MULTIDRUG-RESISTANCE; ZIDOVUDINE; INVITRO; REPLICATION AB The rationale for combining anti-HIV-1 agents is to provide more complete viral suppression, to limit the emergence of drug resistance during chronic viral replication, and to provide more effective antiretroviral treatment even when mixtures of drug-resistant and drug-sensitive strains are present. In vitro experiments reveal increased suppression with multiple-drug therapy, but viral breakthrough occurs after prolonged time in culture even during triple-drug therapy. Clinical results available to date indicate that drugs should be given simultaneously for optimal benefit. There appears to be a rationale for early initiation of combination therapy before the onset of increased viral burden and the emergence of syncytium-inducing viral variants. The results of ACTG protocol 155 revealed benefit of zidovudine and zalcitabine over monotherapy with either agent in patients with CD4(+) cell counts greater than or equal to 150 cells/mm(3). However, further clinical studies will be necessary before firm recommendations can be made about the indications for combination antiretroviral therapy in HIV-l-infected individuals at different stages of disease. Ultimately, we need better drugs, in combination, which significantly impact on HIV-1 burden to achieve more complete viral suppression and to reduce selection of drug-resistant viral variants. C1 UNIV ALABAMA,CTR AIDS RES,DEPT MICROBIOL,BIRMINGHAM,AL 35294. BIRMINGHAM VET AFFAIRS MED CTR,BIRMINGHAM,AL 35294. RP JOHNSON, VA (reprint author), UNIV ALABAMA,CTR AIDS RES,DEPT MED,DIV INFECT DIS,229 TINSLEY HARRISON TOWER,1900 UNIV BLVD,BIRMINGHAM,AL 35294, USA. FU NIAID NIH HHS [AI 32794, AI 32775] NR 32 TC 15 Z9 15 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD AUG PY 1994 VL 10 IS 8 BP 907 EP 912 DI 10.1089/aid.1994.10.907 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PE522 UT WOS:A1994PE52200006 PM 7811541 ER PT J AU CRUMP, AL GRUSBY, MJ GLIMCHER, LH CANTOR, H AF CRUMP, AL GRUSBY, MJ GLIMCHER, LH CANTOR, H TI DEVELOPMENT OF T-CELL SUBSETS - EVIDENCE FOR STOCHASTIC COMMITMENT TO THE CD4 AND CD8 LINEAGES SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT RHEUMATOL & IMMUNOL,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD AUG PY 1994 VL 10 SU 1 BP S103 EP S103 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600305 ER PT J AU JOHNSON, RP KALAMS, S BLATTNER, W WALKER, BD AF JOHNSON, RP KALAMS, S BLATTNER, W WALKER, BD TI HIV SEQUENCE VARIATION AS A MECHANISM OF ESCAPE FROM CYTOTOXIC T-LYMPHOCYTES SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,INFECT DIS UNIT,BOSTON,MA 02129. NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD AUG PY 1994 VL 10 SU 1 BP S39 EP S39 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600077 ER PT J AU KASHANCHI, F PIRAS, G RADONOVICH, MF DUVALL, JF FATTAEY, A BRADY, JN AF KASHANCHI, F PIRAS, G RADONOVICH, MF DUVALL, JF FATTAEY, A BRADY, JN TI DIRECT INTERACTION OF THE HIV-1 TRANSACTIVATOR TAT WITH HUMAN TFIID SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,CTR CANC,BOSTON,MA 02129. NCI,MOLEC VIROL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD AUG PY 1994 VL 10 SU 1 BP S95 EP S95 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600276 ER PT J AU OGAWA, M HIRAYAMA, F AF OGAWA, M HIRAYAMA, F TI CYTOKINE REGULATION OF LYMPHOHEMATOPOIETIC PROGENITORS IN CULTURE SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 RALPH H JOHNSON DEPT VET AFFAIRS MED CTR,CHARLESTON,SC 29401. MED UNIV S CAROLINA,DEPT MED,CHARLESTON,SC 29401. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD AUG PY 1994 VL 10 SU 1 BP S110 EP S110 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600330 ER PT J AU POTASH, MJ TOSI, PF MOUNEIMNE, Y HUANG, XB NICOLAU, C VOLSKY, DJ AF POTASH, MJ TOSI, PF MOUNEIMNE, Y HUANG, XB NICOLAU, C VOLSKY, DJ TI A NEW THERAPEUTIC AGENT, RBC-CD4, EFFICIENTLY INHIBITS TRANSMISSION OF PRIMARY ISOLATES OF HIV-1 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 COLUMBIA UNIV,ST LUKES ROOSEVELT HOSP,MOLEC VIROL LAB,NEW YORK,NY. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD AUG PY 1994 VL 10 SU 1 BP S28 EP S28 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600043 ER PT J AU RAO, A MCCAFFREY, PG JAIN, J MINER, Z LAMBERT, J VERDINE, GL KERPPOLA, TK CURRAN, T AF RAO, A MCCAFFREY, PG JAIN, J MINER, Z LAMBERT, J VERDINE, GL KERPPOLA, TK CURRAN, T TI NUCLEAR FACTOR OF ACTIVATED T-CELLS (NF-AT) - INTERACTION WITH CALCINEURIN AND FOS/JUN PROTEINS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR VIROL,BOSTON,MA 02115. HARVARD UNIV,DEPT CHEM,CAMBRIDGE,MA 02138. ROCHE INST MOLEC BIOL,DEPT MOLEC ONCOL & VIROL,NUTLEY,NJ 07110. RI Curran, Tom/C-1164-2008; Curran, Tom/D-7515-2011 OI Curran, Tom/0000-0003-1444-7551; NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD AUG PY 1994 VL 10 SU 1 BP S101 EP S101 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600300 ER PT J AU REINHERZ, EL AF REINHERZ, EL TI CD4-BASED APPROACHES TO HIV-1 RECEPTOR ANTAGONISTS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,IMMUNOBIOL LAB,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD AUG PY 1994 VL 10 SU 1 BP S103 EP S103 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600307 ER PT J AU RUPRECHT, RM FRATAZZI, C SHARMA, PL LAMBERT, RW PENNINCK, D GREENE, MF AF RUPRECHT, RM FRATAZZI, C SHARMA, PL LAMBERT, RW PENNINCK, D GREENE, MF TI CONGENITAL SIV INFECTION IN RHESUS-MONKEYS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 TUFTS UNIV,SCH VET MED,BOSTON,MA 02111. HARVARD UNIV,SCH MED,BOSTON,MA. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. DANA FARBER CANC INST,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD AUG PY 1994 VL 10 SU 1 BP S85 EP S85 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600245 ER PT J AU RUSCONI, S CHOW, YK MERRILL, DP HIRSCH, MS AF RUSCONI, S CHOW, YK MERRILL, DP HIRSCH, MS TI INHIBITION OF HIV-1 REPLICATION BY CONVERGENT COMBINATION THERAPY IN MONOCYTE/MACROPHAGES SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD AUG PY 1994 VL 10 SU 1 BP S25 EP S25 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600031 ER PT J AU THALI, M CHARLES, M MOORE, JP ROBINSON, J HO, DD BURTON, DR SULLIVAN, N CHOE, HR WYATT, R SODROSKI, J AF THALI, M CHARLES, M MOORE, JP ROBINSON, J HO, DD BURTON, DR SULLIVAN, N CHOE, HR WYATT, R SODROSKI, J TI FUNCTIONAL-SIGNIFICANCE OF EXPOSURE OF GP120 NEUTRALIZATION EPITOPES UPON GP120-CD4 BINDING SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 HARVARD UNIV, SCH MED,DANA FARBER CANC INST,DEPT PATHOL, DIV RETROVIROL, BOSTON, MA 02115 USA. AARON DIAMOND AIDS RES CTR, NEW YORK, NY 10016 USA. UNIV CONNECTICUT, DEPT PEDIAT, FARMINGTON, CT 06030 USA. SCRIPPS RES INST, DEPT MOLEC BIOL & IMMUNOL, LA JOLLA, CA 92037 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD AUG PY 1994 VL 10 SU 1 BP S37 EP S37 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600070 ER PT J AU WANG, LM MYERS, MG SUN, XJ AARONSON, SA WHITE, M PIERCE, JH AF WANG, LM MYERS, MG SUN, XJ AARONSON, SA WHITE, M PIERCE, JH TI EXPRESSION OF IRS-1 RESTORES INSULIN-MEDIATED AND IL-4-MEDIATED MITOGENESIS IN HEMATOPOIETIC-CELLS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,DEPT MED,BOSTON,MA 02215. NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD AUG PY 1994 VL 10 SU 1 BP S101 EP S101 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600298 ER PT J AU WEISSMAN, D ZHOU, LJ TEDDER, TF FAUCI, AS AF WEISSMAN, D ZHOU, LJ TEDDER, TF FAUCI, AS TI 2 POPULATIONS OF CELLS WITH A DENDRITIC MORPHOLOGY EXIST IN PERIPHERAL-BLOOD SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. NIAID,LIR,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD AUG PY 1994 VL 10 SU 1 BP S72 EP S72 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600194 ER PT J AU NANJI, AA ZHAO, SP LAMB, RG DANNENBERG, AJ SADRZADEH, SMH WAXMAN, DJ AF NANJI, AA ZHAO, SP LAMB, RG DANNENBERG, AJ SADRZADEH, SMH WAXMAN, DJ TI CHANGES IN CYTOCHROME-P-450, CYTOCHROME-P-450-2E1, CYTOCHROME-P-450-2B1, AND CYTOCHROME-P-450-4A, AND PHOSPHOLIPASE-A AND PHOSPHOLIPASE-C IN THE INTRAGASTRIC FEEDING RAT MODEL FOR ALCOHOLIC LIVER-DISEASE - RELATIONSHIP TO DIETARY FATS AND PATHOLOGICAL LIVER-INJURY SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article ID UDP-GLUCURONOSYLTRANSFERASE; PHENOBARBITAL INDUCTION; ARACHIDONIC-ACID; ETHANOL; GENE; METABOLISM; EXPRESSION; ACTIVATION; QUANTITATION; MECHANISMS AB The influence of dietary fat and alcohol on hepatic microsomal levels of cytochromes P-450 2E1, 2B, and 4A; phospholipases A and C; and UDP-glucuronosyltransferase was studied in the intragastric feeding rat model for alcoholic liver injury. Eight groups of animals were evaluated. Control and ethanol fed rats received either saturated fat or corn oil and were killed after 2 weeks and 1 month of feeding. All animals were pair-fed by continuous infusion of liquid diet through permanently implanted gastric cannulas. Alcoholic liver injury developed only in the corn oil-ethanol fed groups and was manifest by 1 month. Livers were subjected to the following analyses: pathologic evaluation of liver injury; levels of cytochromes P-450 2E1, 2B, and 4A protein and mRNA; aniline hydroxylase activity; and phospholipase A and C and UDP-glucuronosyltransferase activities. Ethanol induced increases in cytochromes P-450 2E1 and 2B protein determined by Western blotting were greatest in the corn oil-ethanolfed group, which developed pathologic changes in the liver. Cytochromes P-450 2E1 and 2B1 mRNA levels were unaffected, suggesting that posttranscriptional mechanisms are responsible for the increase in the corresponding P-450 proteins. In contrast, cytochrome P-450 4A levels were higher in the saturated fat-ethanol groups compared with the corn oil-ethanol groups. Phospholipase A and phospholipase C levels were higher in the corn oil-ethanol groups compared with pair-fed dextrose controls and the saturated fat-ethanol groups. UDP-glucuronosyltransferase levels declined with time in the ethanol-fed groups. These observations are discussed in the context of a model whereby the induction of phospholipases A and C and cytochromes P-450 2E1 and 2B1 in corn oil-ethanol-fed rats provide arachidonic acid substrate and induce lipid peroxidation, respectively. These changes may account for the more severe pathologic changes that develop in corn oil-ethanol-fed animals compared with animals fed saturated fat and ethanol. C1 HARVARD UNIV, SCH MED, DEPT BIOL CHEM & MOLEC PHARMACOL, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DANA FARBER CANC INST, BOSTON, MA 02115 USA. VIRGINIA COMMONWEALTH UNIV, MED COLL VIRGINIA, DEPT PHARMACOL & TOXICOL, RICHMOND, VA 23298 USA. CORNELL UNIV, MED CTR, NEW YORK HOSP, DIV DIGEST DIS, NEW YORK, NY 10021 USA. STRANG CANC PREVENT CTR, NEW YORK, NY USA. RP NEW ENGLAND DEACONESS HOSP, DEPT PATHOL, M323, 185 PILGRIM RD, BOSTON, MA 02215 USA. FU NIDDK NIH HHS [DK33765, DK1992] NR 42 TC 67 Z9 67 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD AUG PY 1994 VL 18 IS 4 BP 902 EP 908 DI 10.1111/j.1530-0277.1994.tb00058.x PG 7 WC Substance Abuse SC Substance Abuse GA PC774 UT WOS:A1994PC77400021 PM 7978103 ER PT J AU ALASSI, MT GENTA, RM KARTTUNEN, TJ GRAHAM, DY AF ALASSI, MT GENTA, RM KARTTUNEN, TJ GRAHAM, DY TI CLARITHROMYCIN AMOXICILLIN THERAPY FOR HELICOBACTER-PYLORI INFECTION SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID METRONIDAZOLE RESISTANCE; DUODENAL-ULCER; CAMPYLOBACTER-PYLORI; TRIPLE THERAPY; ERADICATION; SUSCEPTIBILITY; AMOXICILLIN; COMBINATION; EFFICACY AB Background: More convenient therapies are needed to treat Helicobacter pylori infection successfully. Clarithromycin and amoxycillin are effective against H. pylori both in vivo and in vitro. Recent success with a high dose amoxycillin-metronidazole combination therapy led us to evaluate clarithromycin-amoxycillin dual therapy for H. pylori infection. Methods: We tested the combination of clarithromycin 500 mg t.d.s. with meals plus amoxycillin 750 mg t.d.s. with meals for 10 days for its effect on H. pylori infection in 29 patients with documented H. pylori peptic ulcers. There were 27 men and 2 women, ranging in age from 23 to 77 years. H. pylori and ulcer status were evaluated at entry and at least 4 weeks after ending antimicrobial therapy. For ulcer healing, ranitidine 300 mg was given each evening for 6 weeks. H. pylori status was determined by CLOtest and histology. Results: H. pylori infection was cured in 86% (95% CI = 78-99%). Compliance averaged 93% by pill count. Ten patients (34%) experienced mild side effects: eight reported dysgeusia and two had mild diarrhoea; none discontinued therapy because of side effects. Conclusion: We conclude that dual therapy with clarithromycin and amoxycillin is a safe and effective alternative regimen for the successful treatment of H. pylori infections. C1 VET AFFAIRS MED CTR 111D,DEPT PATHOL,HOUSTON,TX 77030. VET AFFAIRS MED CTR 111D,DIV MOLEC VIROL,HOUSTON,TX 77030. BAYLOR COLL MED,,HOUSTON,TX 77030. RP GRAHAM, DY (reprint author), VET AFFAIRS MED CTR 111D,DEPT MED,2002 HOLCOMBE BLVD,HOUSTON,TX 77030, USA. NR 42 TC 38 Z9 38 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0269-2813 J9 ALIMENT PHARM THERAP JI Aliment. Pharmacol. Ther. PD AUG PY 1994 VL 8 IS 4 BP 453 EP 456 PG 4 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA PB417 UT WOS:A1994PB41700011 PM 7986970 ER PT J AU HUNCHAREK, M AF HUNCHAREK, M TI TYPES OF ASBESTOS FIBERS AND DISEASE-CAUSING POTENTIAL SO AMERICAN FAMILY PHYSICIAN LA English DT Letter RP HUNCHAREK, M (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD FAMILY PHYSICIANS PI KANSAS CITY PA 8880 WARD PARKWAY, KANSAS CITY, MO 64114-2797 SN 0002-838X J9 AM FAM PHYSICIAN JI Am. Fam. Physician PD AUG PY 1994 VL 50 IS 2 BP 306 EP 308 PG 3 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA PA917 UT WOS:A1994PA91700007 PM 8042565 ER PT J AU MENDES, LA DEC, GW PICARD, MH PALACIOS, IF NEWELL, J DAVIDOFF, R AF MENDES, LA DEC, GW PICARD, MH PALACIOS, IF NEWELL, J DAVIDOFF, R TI RIGHT-VENTRICULAR DYSFUNCTION - AN INDEPENDENT PREDICTOR OF ADVERSE OUTCOME IN PATIENTS WITH MYOCARDITIS SO AMERICAN HEART JOURNAL LA English DT Article ID ENDOMYOCARDIAL BIOPSY; DISEASE; CARDIOMYOPATHY; TACHYCARDIA; ARRHYTHMIAS; DIAGNOSIS AB To assess the predictive value of right ventricular systolic function in patients with active myocarditis, the echocardiograms of 23 patients with biopsy-confirmed myocarditis were reviewed. Right ventricular systolic function was evaluated qualitatively and quantitatively by descent of the right ventricular base. Patients were divided into those with normal right ventricular function, in whom right ventricular descent was 1.9 +/- 0.1 cm, and those with abnormal right ventricular function, in whom right ventricular descent was 0.8 +/- 0.1 cm (p < 0.001). There were no differences between the two groups in age, duration of symptoms, baseline hemodynamics, or histologic assessment. Initial left ventricular ejection fraction was significantly lower in patients with depressed right ventricular function (27.5 +/- 4.9%) compared with that in patients with normal right ventricular function (47.5 +/- 6.3%) (p = 0.01). The likelihood of an adverse outcome, defined as death or need for cardiac transplantation, was greater in patients with abnormal right ventricular function (right ventricular descent less than or equal to 1.7 cm) than in patients with normal right ventricular function (right ventricular descent > 1.7 cm) (p < 0.03). Multivariate analysis revealed that right ventricular dysfunction as quantified by right ventricular descent was the most powerful predictor of adverse outcome. C1 BOSTON UNIV MED CTR HOSP,EVANS MEM DEPT CLIN RES,BOSTON,MA 02118. BOSTON UNIV MED CTR HOSP,DEPT MED,DIV CARDIOL,BOSTON,MA 02118. MASSACHUSETTS GEN HOSP,CARDIAC UNIT,BOSTON,MA. RP MENDES, LA (reprint author), BOSTON UNIV MED CTR HOSP,CARDIOL SECT,88 E NEWTON ST,BOSTON,MA 02118, USA. OI Picard, Michael/0000-0002-9264-3243 NR 28 TC 88 Z9 93 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 AUG PY 1994 VL 128 IS 2 BP 301 EP 307 DI 10.1016/0002-8703(94)90483-9 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PA148 UT WOS:A1994PA14800014 PM 8037097 ER PT J AU SUSTER, S WONG, TY AF SUSTER, S WONG, TY TI ON THE DISCRIMINATORY VALUE OF ANTI-HPCA-1 (CD-34) IN THE DIFFERENTIAL-DIAGNOSIS OF BENIGN AND MALIGNANT CUTANEOUS VASCULAR PROLIFERATIONS SO AMERICAN JOURNAL OF DERMATOPATHOLOGY LA English DT Article DE ANTI-HPCA-1 (CD-34); IMMUNOHISTOCHEMISTRY; VASCULAR ENDOTHELIUM; CUTANEOUS VASCULAR NEOPLASMS; ANGIOSARCOMA; EPITHELIOID VASCULAR NEOPLASMS ID VIII-RELATED ANTIGEN; ENDOTHELIAL-CELLS; KAPOSIS-SARCOMA; MONOCLONAL-ANTIBODY; CD34; ANGIOSARCOMA; CARCINOMA; TUMORS; HEMANGIOENDOTHELIOMA; EXPRESSION AB The staining pattern of monoclonal antibody anti-HPCA-1 (CD-34) was studied in 95 cases of benign and malignant cutaneous vascular proliferations and compared with other vascular endothelium-associated antigenic markers in paraffin-embedded tissues. The proliferating vessels in 22 cutaneous capillary hemangiomas, 8 lobular capillary hemangiomas, and 1 case of papillary intravascular endothelial hyperplasia stained strongly positively for anti-HPCA-1, and the intensity of the reaction was paralleled by that of factor VIII-related antigen (FVIII), Ulex europaeus lectin-1 (UEA), and vimentin (VIM). The vessels in 10 cases of granulation tissue, 6 cases of cavernous hemangioma, 6 cases of angiokeratoma, 5 cases of angiolymphoid hyperplasia with eosinophilia (epithelioid hemangioma), and 3 cases of bacillary angiomatosis showed a lack of reactivity with anti-HPCA-1 and staining of variable intensity with the other markers. Twenty cases of Kaposi's sarcoma (seven patch, five plaque, eight nodular stage) showed strong labeling with anti-HPCA-1 in small, well-formed vessels scattered among the spindle-cell proliferation, and four of these cases showed focal positivity of scattered spindle cells. Nine cases of cutaneous angiosarcoma, two cases of low-grade epithelioid angiosarcoma, and one case of spindle-cell hemangioendothelioma were negative for anti-HPCA-1 and showed variable reactivity for FVIII and UEA; all cases stained strongly positively for VIM. The results of this study indicate that although anti-HPCA-1 shows a high sensitivity for the staining of normal vascular endothelium, its specificity may be restricted to mature, well-formed vessels, therefore rendering its discriminatory value very limited for the identification of poorly differentiated vascular endothelial neoplasms. C1 MT SINAI MED CTR,ARKADI M RYWLIN DEPT PATHOL & LAB MED,MIAMI BEACH,FL 33140. UNIV MIAMI,SCH MED,MIAMI,FL 33152. MASSACHUSETTS GEN HOSP,DIV DERMATOPATHOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 32 TC 36 Z9 36 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0193-1091 J9 AM J DERMATOPATH JI Am. J. Dermatopathol. PD AUG PY 1994 VL 16 IS 4 BP 355 EP 363 DI 10.1097/00000372-199408000-00001 PG 9 WC Dermatology SC Dermatology GA PF106 UT WOS:A1994PF10600001 PM 7526723 ER PT J AU DENNING, DW LEE, JY HOSTETLER, JS PAPPAS, P KAUFFMAN, CA DEWSNUP, DH GALGIANI, JN GRAYBILL, JR SUGAR, AM CATANZARO, A GALLIS, H PERFECT, JR DOCKERY, B DISMUKES, WE STEVENS, DA AF DENNING, DW LEE, JY HOSTETLER, JS PAPPAS, P KAUFFMAN, CA DEWSNUP, DH GALGIANI, JN GRAYBILL, JR SUGAR, AM CATANZARO, A GALLIS, H PERFECT, JR DOCKERY, B DISMUKES, WE STEVENS, DA TI NIAID MYCOSES STUDY-GROUP MULTICENTER TRIAL OF ORAL ITRACONAZOLE THERAPY FOR INVASIVE ASPERGILLOSIS SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID PULMONARY ASPERGILLOSIS; DIAGNOSIS; EPIDEMIOLOGY; INVITRO AB BACKGROUND: Invasive aspergillosis is the most common invasive mould infection and a major cause of mortality in immunocompromised patients. Response to amphotericin B, the only antifungal agent licensed in the United States for the treatment of aspergillosis, is suboptimal. METHODS: A multicenter open study with strict entry criteria for invasive aspergillosis evaluated oral itraconazole (600 mg/d for 4 days followed by 400 mg/d) in patients with various underlying conditions. Response was based on clinical and radiologic criteria plus microbiology, histopathology, and autopsy data. Responses were categorized as complete, partial, or stable. Failure was categorized as an itraconazole failure or overall failure. RESULTS: Our study population consisted of 76 evaluable patients. Therapy duration varied from 0.3 to 97 weeks (median 46). At the end of treatment, 30 (39%) patients had a complete or partial response, and 3 (4%) had a stable response, and in 20 patients (26%), the protocol therapy was discontinued early (at 0.6 to 54.3 weeks) because of a worsening clinical course or death due to aspergillosis (itraconazole failure). Twenty-three (30%) patients withdrew for other reasons including possible toxicity (7%) and death due to another cause but without resolution of aspergillosis (20%). Itraconazole failure rates varied widely according to site of disease and underlying disease group: 14% for pulmonary and tracheobronchial disease, 50% for sinus disease, 63% for central nervous system disease, and 44% for other sites; 7% in solid organ transplant, 29% in allogeneic bone marrow transplant patients, and 14% in those with prolonged granulocytopenia (median 19 days), 44% in AIDS patients, and 32% in other host groups. The relapse rates among those who completed therapy and those who discontinued early for possible toxicity were 12% and 40%, respectively; all were still immunosuppressed. CONCLUSION: Oral itraconazole is a useful alternative therapy for invasive aspergillosis with response rates apparently comparable to amphotericin B. Relapse in immunocompromised patients may be a problem. Controlled trials are necessary to fully assess the role of itraconazole in the treatment of invasive aspergillosis. C1 SANTA CLARA VALLEY MED CTR,DEPT MED,DIV INFECT DIS,SAN JOSE,CA 95128. CALIF INST MED RES,SAN JOSE,CA 95128. STANFORD UNIV,SCH MED,DIV INFECT DIS & GEOG MED,STANFORD,CA 94305. UNIV ALABAMA,CTR COMPREHENS CANC,DIV BIOSTAT,BIRMINGHAM,AL 35294. UNIV ALABAMA,DEPT MED,DIV INFECT DIS,BIRMINGHAM,AL 35294. UNIV MICHIGAN,SCH MED,VET AFFAIRS MED CTR,DEPT INTERNAL MED,DIV INFECT DIS,ANN ARBOR,MI. VET AFFAIRS MED CTR,MED SERV,DIV INFECT DIS,TUCSON,AZ. UNIV ARIZONA,DEPT MED,TUCSON,AZ. AUDIE L MURPHY MEM VET ADM MED CTR,DIV INFECT DIS,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. BOSTON UNIV,SCH MED,DEPT MED,DIV INFECT DIS,BOSTON,MA 02118. UNIV CALIF SAN DIEGO,DEPT MED,DIV PULM MED,SAN DIEGO,CA 92103. DUKE UNIV,DEPT MED,DIV INFECT DIS,DURHAM,NC. OI Denning, David/0000-0001-5626-2251 FU NIAID NIH HHS [N01-AI-15082] NR 20 TC 370 Z9 376 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9343 J9 AM J MED JI Am. J. Med. PD AUG PY 1994 VL 97 IS 2 BP 135 EP 144 DI 10.1016/0002-9343(94)90023-X PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA PB686 UT WOS:A1994PB68600006 PM 8059779 ER PT J AU PROVENZALE, JM SCHWARZSCHILD, MA AF PROVENZALE, JM SCHWARZSCHILD, MA TI HEMIBALLISMUS SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article DE BASAL GANGLIA; BRAIN, ABSCESS; ACQUIRED IMMUNODEFICIENCY SYNDROME (AIDS); RADIOLOGIC-CLINICAL CORRELATIONS; MOVEMENT ID HEMICHOREA-HEMIBALLISMUS; MOVEMENT-DISORDERS; BASAL GANGLIA; INFARCTION; NUCLEUS; CHOREA; MONKEY C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. RP PROVENZALE, JM (reprint author), DUKE UNIV,MED CTR,DEPT RADIOL,BOX 3808,DURHAM,NC 27710, USA. NR 29 TC 14 Z9 14 U1 0 U2 1 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 AUG PY 1994 VL 15 IS 7 BP 1377 EP 1382 PG 6 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA PB622 UT WOS:A1994PB62200031 PM 7976952 ER PT J AU DALKARA, T MORIKAWA, E PANAHIAN, N MOSKOWITZ, MA AF DALKARA, T MORIKAWA, E PANAHIAN, N MOSKOWITZ, MA TI BLOOD FLOW-DEPENDENT FUNCTIONAL RECOVERY IN A RAT MODEL OF FOCAL CEREBRAL-ISCHEMIA SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE ISCHEMIC PENUMBRA; CEREBRAL BLOOD FLOW; NITRIC OXIDE; L-ARGININE ID NITRIC-OXIDE; L-ARGININE; ARTERY OCCLUSION; BRAIN ISCHEMIA; INFARCTION; MECHANISMS; PATHOPHYSIOLOGY; THRESHOLDS; NIMODIPINE; PENUMBRA AB The reduction in focal infarct volume after L-arginine has been attributed to an increase in regional cerebral blood flow (rCBF) within ischemic tissue. We tested the hypothesis that L-arginine-induced rCBF increases precede the recovery of spontaneous electrical activity [electrocorticogram (ECoG)] in spontaneously hypertensive rats subjected to middle cerebral artery (MCA) occlusion. ECoG was recorded from the penumbral region of parietal cortex by a glass microelectrode inserted into 1-mm(3) cortical tissue from which blood flow was sampled by laser-Doppler flowmetry. rCBF dropped to 21 +/- 8% of the preischemic level, and ECoG was depressed by 64 +/- 13% after distal MCA occlusion. L-Arginine infusion (300 mg/kg iv) increased rCBF in 14 out of 18 rats, and ECoG significantly recovered in seven rats in which rCBF exceeded 31% of preischemic flow. Increases in rCBF anticipated the functional improvement in every case. Saline (n = 6) or D-arginine (12 = 5) administration was ineffective. These data demonstrate that increasing rCBF can promote functional recovery in the ischemic brain and suggest that early administration of L-arginine or other vasodilators may enhance tissue survival by increasing rCBF. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,STROKE RES LAB,NEUROSURG SERV,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,STROKE RES LAB,NEUROL SERV,BOSTON,MA 02114. RI Moskowitz, Michael/D-9916-2011 FU NINDS NIH HHS [NS-10828, NS-26361] NR 31 TC 54 Z9 55 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD AUG PY 1994 VL 267 IS 2 BP H678 EP H683 PN 2 PG 6 WC Physiology SC Physiology GA PC441 UT WOS:A1994PC44100035 PM 8067423 ER PT J AU IRIKURA, K MAYNARD, KI LEE, WS MOSKOWITZ, MA AF IRIKURA, K MAYNARD, KI LEE, WS MOSKOWITZ, MA TI L-NNA DECREASES CORTICAL HYPEREMIA AND BRAIN CGMP LEVELS FOLLOWING CO2 INHALATION IN SPRAGUE-DAWLEY RATS SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE NITRIC OXIDE; N-G-NITRO-L-ARGININE; REGIONAL CEREBRAL BLOOD FLOW; GUANOSINE 3',5'-CYCLIC MONOPHOSPHATE; HYPERCAPNIA; CRANIAL WINDOW; LASER-DOPPLER FLOWMETRY ID CEREBRAL BLOOD-FLOW; NITRIC-OXIDE; GUANYLATE-CYCLASE; HYPERCAPNIA; ACTIVATION; RELAXATION; NUCLEUS AB The role of nitric oxide (NO) in the response to 5% CO2 inhalation was investigated by measuring 1) regional cerebral blood flow (rCBF) by laser-Doppler flowmetry and pial vessel diameter through a closed cranial window after topical N-G-nitro-L-arginine (L-NNA, 1 mM), and 2) the time-dependent changes in brain guanosine 3',5'-cyclic monophosphate (cGMP) levels after L-NNA (10 mg/kg ip). When L-NNA (but not N-G-nitro-D-arginine) was applied topically for 30 or 60 min, the response to hypercapnia was significantly attenuated. A correlation was found between inhibition of brain NO synthase (NOS) activity and the rCBF response (r = 0.77; P < 0.01). However, L-NNA applied 15 min before hypercapnia did not attenuate the increase in rCBF but did attenuate the dilation to topical acetylcholine. Inhalation of CO2 (5%) elevated brain cGMP levels by 20-25%, and L-NNA reduced this response. These data from the rat suggest that 1) a product of NOS activity is associated with hypercapnic hyperemia and the attendant increase in brain cGMP levels, and 2) hypercapnic blood flow changes may not be dependent on endothelial NOS activity within pial vessels. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,NEUROSURG SERV,STROKE RES LAB,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,NEUROL SERV,STROKE RES LAB,BOSTON,MA 02114. RI Moskowitz, Michael/D-9916-2011 FU NINDS NIH HHS [NS-26361, NS-10828] NR 29 TC 42 Z9 42 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD AUG PY 1994 VL 267 IS 2 BP H837 EP H843 PN 2 PG 7 WC Physiology SC Physiology GA PC441 UT WOS:A1994PC44100053 PM 8067440 ER PT J AU LITALIEN, GJ CHANDRASEKAR, NR LAMURAGLIA, GM PEVEC, WC DHARA, S WARNOCK, DF ABBOTT, WM AF LITALIEN, GJ CHANDRASEKAR, NR LAMURAGLIA, GM PEVEC, WC DHARA, S WARNOCK, DF ABBOTT, WM TI BIAXIAL ELASTIC PROPERTIES OF RAT ARTERIES IN-VIVO - INFLUENCE OF VASCULAR WALL CELLS ON ANISOTROPY SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE COMPLIANCE; BIAXIAL ELASTICITY; VASCULAR TONE ID MECHANICAL-PROPERTIES; CAROTID-ARTERY; INVITRO; BEHAVIOR; SEGMENTS; LASER AB There is no consensus as to the degree of arterial anisotropy or to its relationship to vascular cell function. Given the relevance of the isotropic assumption in formulating elasticity models, reliable measures of biaxial displacements are needed. In this study, a video motion analyzer (VMA) was used to describe the biaxial in vivo dynamic elasticity of 22 carotid arteries and 5 abdominal aortas in 27 rats. The influence of vascular cell function was also examined by subjecting six rats to a photosensitive drug, chloroaluminum sulfonated phthalocyanine (CASPc), which is focally cytotoxic on activation by laser. Circumferential compliance (C-circ) was greater than longitudinal compliance (C-long) for all vessels. Compliance pressure curves were nonlinear, and biaxial displacements were in phase. The circumferential elastic modulus was less than the longitudinal modulus at common stresses. CASPc + laser reduced C-circ but not C-long, thus altering Poisson's ratio. In conclusion, rat arteries are biaxially, nonlinearly elastic and anisotropic in vivo. Vascular cells modulate Poisson's ratio by influencing C-circ. C1 MASSACHUSETTS GEN HOSP,WELLMAN LABS PHOTOMED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP LITALIEN, GJ (reprint author), MASSACHUSETTS GEN HOSP,DIV VASC RES,VASC BIOL RES LAB,15 PARKMAN ST,ACC-458,FRUIT ST,BOSTON,MA 02114, USA. FU NHLBI NIH HHS [HL-02583] NR 24 TC 17 Z9 17 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD AUG PY 1994 VL 267 IS 2 BP H574 EP H579 PN 2 PG 6 WC Physiology SC Physiology GA PC441 UT WOS:A1994PC44100023 PM 8067413 ER PT J AU LOPEZ, JJ LORELL, BH INGELFINGER, JR WEINBERG, EO SCHUNKERT, H DIAMANT, D TANG, SS AF LOPEZ, JJ LORELL, BH INGELFINGER, JR WEINBERG, EO SCHUNKERT, H DIAMANT, D TANG, SS TI DISTRIBUTION AND FUNCTION OF CARDIAC ANGIOTENSIN AT(1)-RECEPTOR AND AT(2)-RECEPTOR SUBTYPES IN HYPERTROPHIED RAT HEARTS SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE ANGIOTENSIN II RECEPTOR; CARDIAC HYPERTROPHY; ANGIOTENSINS; RECEPTOR SUBTYPES ID LEFT-VENTRICULAR HYPERTROPHY; CONVERTING ENZYME-INHIBITION; II RECEPTOR ANTAGONISTS; ACTIVE ANTIHYPERTENSIVE AGENT; PRESSURE-OVERLOAD HYPERTROPHY; CALCIUM CURRENT; EXPRESSION; IDENTIFICATION; MYOCARDIUM; DUP-753 AB To determine distribution and function of cardiac angiotensin (ANG) II receptor AT(1) and AT(2) subtypes in left ventricular (LV) hypertrophy (LVH), ANG II (10(-8) M) was infused into isolated rat hearts with hypertrophy from aortic banding and into sham-operated controls. ANG II was infused alone or in the presence of ATL inhibitor [losartan (10(-5) M) or CL-329167 (10(-7) M)] or AT(2) inhibitor [CG-42112A (10(-8) M)]. ANG II alone caused less increase in coronary vascular resistance (CVR) in LVH compared with. control hearts (19 vs. 39%; P < 0.01), although baseline CVR was higher in LVH hearts. This was prevented by AT(1) but not AT(2) antagonists. ANG II also increased LV end-diastolic pressure in LVH hearts, signifying decreased diastolic relaxation that was prevented by AT(1) but not AT(2) inhibition. Characterization of ANG II binding sites in LV membrane preparations revealed similar dissociation constants between groups (1.6 +/- 0.95 vs. 2.2 +/- 2.0 nM; not significant) but lower maximum binding capacity in the LVH group (21.1 +/- 5.9 vs. 33.5 +/- 3.0 fmol/mg protein; P < 0.05). Competition assays demonstrated that control left ventricles contain predominantly the AT(1) subtype (68.8 +/- 20%), whereas LVH ventricles contain primarily the putative AT(2) subtype (59.8% +/- 10.8%; P < 0.05). This suggests that receptor subtype redistribution occurs in LVH with AT(1) subtype downregulation. Nonetheless, the AT(1) subtype mediates the effects of ANG II on coronary tone and diastolic dysfunction in pressure-overload hypertrophy. C1 BETH ISRAEL HOSP,DEPT MED,DIV CARDIOVASC,BOSTON,MA 02215. HARVARD UNIV,CHARLES A DANA RES INST,THORNDIKE LAB,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA 02215. MASSACHUSETTS GEN HOSP,CHILDRENS SERV,PEDIAT RENAL RES LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. FU NHLBI NIH HHS [HL-28939, HL-43131, HL-48455] NR 35 TC 176 Z9 177 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD AUG PY 1994 VL 267 IS 2 BP H844 EP H852 PN 2 PG 9 WC Physiology SC Physiology GA PC441 UT WOS:A1994PC44100054 PM 8067441 ER PT J AU GLASSMAN, PA BELL, RM TRANQUADA, RE AF GLASSMAN, PA BELL, RM TRANQUADA, RE TI THE 1966 ENACTMENT OF MEDICARE - ITS EFFECT ON DISCHARGES FROM LOS-ANGELES COUNTY-OPERATED HOSPITALS SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Note AB The effect of Medicare on two public hospitals in Los Angeles County was analyzed by examining the percentage of patients 65 years of age and older among all discharges from 1958 through 1971. At Harbor General Hospital, discharges of elderly patients had dropped from 21.7% to 7.9% by late 1966; at Los Angeles County General Hospital, discharges decreased from 15.3% to 10.7% between 1966 and 1967. Monitoring public hospitals' demographic changes after enacting a national health plan may provide information on patients' and providers' acceptance of insurance and on resources needed by public hospitals to care for those left without coverage. C1 RAND CORP,SANTA MONICA,CA. UNIV SO CALIF,SCH MED,LOS ANGELES,CA. UNIV SO CALIF,SCH PUBL ADM,LOS ANGELES,CA 90089. RP GLASSMAN, PA (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,DIV GEN INTERNAL MED 691-W111G,WILSHIRE & SAWTELLE BLVD,LOS ANGELES,CA 90073, USA. NR 10 TC 1 Z9 1 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD AUG PY 1994 VL 84 IS 8 BP 1325 EP 1327 DI 10.2105/AJPH.84.8.1325 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PC266 UT WOS:A1994PC26600026 PM 8059897 ER PT J AU LEVINE, SM ANZUETO, A PETERS, JI CRONIN, T SAKO, EY JENKINSON, SC BRYAN, CL AF LEVINE, SM ANZUETO, A PETERS, JI CRONIN, T SAKO, EY JENKINSON, SC BRYAN, CL TI MEDIUM-TERM FUNCTIONAL RESULTS OF SINGLE-LUNG TRANSPLANTATION FOR END-STAGE OBSTRUCTIVE LUNG-DISEASE SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID PULMONARY-DISEASE; EMPHYSEMA; EXERCISE; CORTICOSTEROIDS; RESPONSES; DIAPHRAGM; MYOPATHY; HEART AB Controversy has surrounded the use of single-lung transplantation (SLT) for the treatment of endstage obstructive lung disease. In recent years, several transplant centers have performed SLT for such indications. In this report, we describe functional results in patients undergoing SLT for obstructive lung disease, twenty-two followed over one year and 10 over two years. Data include pulmonary function testing, gas exchange, quantitative ventilation and perfusion to the lung graft, and results of symptom-limited graded cycle exercise testing after SLT. Our results show improvement in obstructive dysfunction FEV(1) 0.49 +/- 0.13 L (16 +/- 4% predicted) pre-SLT to 1.71 +/- 0.43 L (57 +/- 12% predicted) 3 mo after SLT, FEV(1)/FVC 0.30 +/- 0.07 pre-SLT to 0.75 +/- 0.09 3 mo after SLT, and improvement in arterial oxygenation, PaO2 58 +/- 10 mm Hg pre SLT to PaO2 86 +/- 13 mm Hg 3 mo post-SLT. In addition, these improvements were sustained up to 1 to 2 yr post-SLT. The majority of ventilation and perfusion go to the new lung graft. After SLT, patients have reduced maximum oxygen consumption (VO(2)max 40 to 60% predicted) but do not have ventilatory limitation to exercise and can carry out daily activities without compromise. We conclude that SLT is a viable medium-term therapeutic option for endstage obstructive lung disease. The long-term future of this technique remains to be determined. C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED PULM DIS CRIT CARE,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT SURG CARDIOTHORAC SURG,SAN ANTONIO,TX 78284. RP LEVINE, SM (reprint author), AUDIE L MURPHY MEM VET ADM MED CTR,PULM DIS SECT 111E,7400 MERTON MINTER BLVD,SAN ANTONIO,TX 78284, USA. NR 39 TC 54 Z9 55 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD AUG PY 1994 VL 150 IS 2 BP 398 EP 402 PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA PB286 UT WOS:A1994PB28600017 PM 8049821 ER PT J AU SLANETZ, PJ WHITMAN, GJ SHEPARD, JAO CHEW, FS AF SLANETZ, PJ WHITMAN, GJ SHEPARD, JAO CHEW, FS TI NODULAR PULMONARY AMYLOIDOSIS SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Note ID LOWER RESPIRATORY-TRACT; BIOPSY C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 5 TC 5 Z9 6 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 AUG PY 1994 VL 163 IS 2 BP 296 EP 296 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA QE289 UT WOS:A1994QE28900012 PM 8037018 ER PT J AU KAZEROONI, EA BHALLA, M SHEPARD, JAO MCLOUD, TC AF KAZEROONI, EA BHALLA, M SHEPARD, JAO MCLOUD, TC TI ADENOSQUAMOUS CARCINOMA OF THE LUNG - RADIOLOGIC APPEARANCE SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID FEATURES; CANCER AB OBJECTIVE. To our knowledge, the imaging features of pulmonary adenosquamous carcinoma, a form of bronchogenic carcinoma with a greater propensity for metastases at the time of diagnosis and a poorer prognosis than other forms of bronchogenic carcinoma, have not been reported, Accordingly, we studied the radiologic appearance of this tumor to describe the findings and discern if there are features that distinguish it from other bronchogenic carcinomas. MATERIALS AND METHODS. Clinical and radiologic features of 30 cases of adenosquamous carcinoma were reviewed. Chest radiographs were available in all cases and CT scans were available in 23. In cases without CT scans, planar tomograms were reviewed in five cases and MR images were reviewed in one. Tumors were defined by location, morphology, and TNM classification. RESULTS. The tumors measured 0.6-6.5 cm in diameter (mean, 2.8 cm) on CT scans or chest radiographs. One tumor not seen even in retrospect on CT scans or chest radiographs was found at autopsy. Twenty-five tumors were solid and four were cavitary, Five tumors were central and 25 were peripheral, including one tumor of the superior sulcus of the lung and the tumor not seen at imaging. Tumor margins were poorly defined in 19 and spiculated in 10. Four large masses had heterogeneous attenuation on CT scans; one had punctate calcification. Fifty-three percent of tumors were peripheral nodules 1-3 cm in diameter, Results of fine-needle aspiration of 18 masses indicated malignant tumors in 16 cases, but adenosquamous carcinoma in only two. Evidence of previous lung injury, including tumor in or next to scar, pneumoconiosis, radiation fibrosis, and interstitial fibrosis, was found on CT scans, chest radiographs, and/or pathology in half the patients. CONCLUSION. The radiologic findings of adenosquamous lung carcinoma are a spectrum, typically a peripheral solitary nodule, less commonly a central hilar mass or tumor of the superior sulcus. Scar or fibrosis within the lungs suggests that adenosquamous carcinoma, just as adenocarcinoma, may arise in scarred lung parenchyma. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. RP KAZEROONI, EA (reprint author), UNIV MICHIGAN HOSP,DEPT RADIOL,1500 E MED CTR DR,ANN ARBOR,MI 48109, USA. NR 17 TC 14 Z9 15 U1 0 U2 1 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 AUG PY 1994 VL 163 IS 2 BP 301 EP 306 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA QE289 UT WOS:A1994QE28900014 PM 8037019 ER PT J AU GAZELLE, GS SAINI, S HAHN, PF GOLDBERG, MA HALPERN, EF AF GAZELLE, GS SAINI, S HAHN, PF GOLDBERG, MA HALPERN, EF TI MR-IMAGING OF THE LIVER AT 1.5-T - VALUE OF SIGNAL AVERAGING IN SUPPRESSING MOTION ARTIFACTS SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID HEPATIC METASTASES; PULSE SEQUENCE; CONTRAST AB OBJECTIVE. Prior reports have suggested that signal averaging is not as effective as phase reordering for suppressing motion-related artifacts on T1-weighted spin-echo MR imaging of the liver at high field strengths. We hypothesized that with shorter TEs, signal averaging could be effective, and therefore undertook this study to compare signal averaging with phase reordering at 1.5 T. SUBJECTS AND METHODS. Thirty consecutive patients underwent MR imaging of the liver at 1.5 T with two if-weighted spin-echo pulse sequences. In one sequence we used signal averaging and in the other we used phase reordering as the primary motion suppression techniques. For each patient, the order in which these sequences were performed was randomized; TR (400-500 msec), TE (11-12 msec), and field of view (32-34 cm) remained constant. Images were analyzed quantitatively for liver signal-to-noise ratio (SNR), liver-spleen contrast-to-noise ratio (CNR), and liver-lesion CNR (in 16 patients with focal liver lesions), as well as qualitatively (three observers, blinded to technique) for overall image quality. RESULTS. Signal averaging resulted in images with significantly greater liver SNR, liver-spleen CNR, and liver-lesion CNR than did phase reordering (p = .0001, .002, and .02, respectively), All observers showed a preference for the signal-averaged images. For one observer, this preference was statistically significant; for the others, it was not. CONCLUSION. Signal averaging can be an effective means of suppressing motion-related artifacts on T1-weighted MR images of the liver obtained at 1.5 T. RP GAZELLE, GS (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIOL,32 FRUIT ST,BOSTON,MA 02114, USA. NR 9 TC 6 Z9 6 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 AUG PY 1994 VL 163 IS 2 BP 335 EP 337 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA QE289 UT WOS:A1994QE28900020 PM 8037025 ER PT J AU BOLAND, GW LEE, MJ LEUNG, J MUELLER, PR AF BOLAND, GW LEE, MJ LEUNG, J MUELLER, PR TI PERCUTANEOUS CHOLECYSTOSTOMY IN CRITICALLY ILL PATIENTS - EARLY RESPONSE AND FINAL OUTCOME IN 82 PATIENTS SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID ACUTE CHOLECYSTITIS; GALLBLADDER AB OBJECTIVE. Patients in the intensive care unit are at increased risk of developing acute calculous and acalculous cholecystitis. Diagnosis based on clinical and sonographic findings is difficult in the presence of severe intercurrent disease, We did a study to evaluate the efficacy of percutaneous cholecystostomy as a diagnostic and therapeutic maneuver in 82 patients in the intensive care unit who had persistent unexplained sepsis. SUBJECTS AND METHODS. Eighty-two patients with unexplained sepsis underwent percutaneous cholecystostomy after a complete clinical, laboratory, and radiologic search showed no source of sepsis outside the gallbladder. All patients were febrile, 65 had an increased WBC count, and 37 were receiving vasopressors, Sonographic abnormalities included a distended gallbladder (71 patients), sludge (63 patients), gallstones (26 patients), wall thickening (34 patients), pericholecystic fluid (25 patients), and Murphy's sign (19 patients). RESULTS. Sonographic findings were not helpful in predicting response to percutaneous cholecystostomy, A dramatic improvement in clinical condition was observed in 48 patients (59%) within 48 hr. Signs of improvement included defervescence (41 patients), discontinuance of vasopressors (26 patients), and reduction in WBC count (33 patients). No clinical response was observed in 34 patients (41%). No complications related to catheter insertion occurred. CONCLUSION. Because acute cholecystitis is difficult to diagnose in patients in the intensive care unit, percutaneous cholecystostomy serves as a diagnostic and therapeutic maneuver in patients with unexplained sepsis when the gallbladder is the suspected source of sepsis. A response rate to percutaneous cholecystostomy of 59% was seen in this study. The gallbladder was cleared as a potential source of sepsis in the remaining patients. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 12 TC 74 Z9 76 U1 0 U2 1 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 AUG PY 1994 VL 163 IS 2 BP 339 EP 342 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA QE289 UT WOS:A1994QE28900021 PM 8037026 ER PT J AU GOLDBERG, MA PIVOVAROV, M MAYOSMITH, WW BHALLA, MP BLICKMAN, JG BRAMSON, RT BOLAND, GWL LLEWELLYN, HJ HALPERN, E AF GOLDBERG, MA PIVOVAROV, M MAYOSMITH, WW BHALLA, MP BLICKMAN, JG BRAMSON, RT BOLAND, GWL LLEWELLYN, HJ HALPERN, E TI APPLICATION OF WAVELET COMPRESSION TO DIGITIZED RADIOGRAPHS SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID IRREVERSIBLE IMAGE COMPRESSION; DIAGNOSTIC-ACCURACY AB OBJECTIVE. Image data compression is an enabling technology for teleradiology and picture archive and communication systems. Compression decreases the time and cost of image transmission and the requirements for image storage. Wavelets, discovered in 1987, constitute a new compression technique that has been described in radiologic publications but, to our knowledge, no previous studies of its use have been reported. The purpose of this study was to demonstrate the application of wavelet-based compression technology to digitized radiographs. MATERIALS AND METHODS. Twelve radiographs with abnormal findings were digitized, compressed, and decompressed by using a new wavelet-based lossy compression algorithm. Images were compressed at ratios from 10:1 to 60:1. Seven board-certified radiologists reviewed images on a two-headed, high-resolution (2K x 2K) diagnostic workstation. Paired original and compressed/decompressed images were presented in random order. Reviewers adjusted contrast and magnification to judge whether image degradation was present, and if so, whether it was of diagnostic significance. Quantitative error measures were tabulated. RESULTS. Reviewers found no clinically relevant degradation below a compression ratio of 30:1. Skeletal radiographs appeared more sensitive to compression than did chest or abdominal radiographs, but the trend was not statistically significant. Quantitative error measures increased gradually with compression ratio. CONCLUSION. On the basis of subjective assessment of image quality and the computational efficiency of the algorithm, wavelet-based techniques appear promising for the compression of digitized radiographs. The results of this initial experience can be used to design appropriate observer performance studies. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP GOLDBERG, MA (reprint author), HARVARD UNIV,SCH MED,DEPT RADIOL,32 FRUIT ST,BOSTON,MA 02114, USA. NR 19 TC 85 Z9 85 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 AUG PY 1994 VL 163 IS 2 BP 463 EP 468 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA QE289 UT WOS:A1994QE28900048 PM 8037051 ER PT J AU SZYFELBEIN, WM YOUNG, RH SCULLY, RE AF SZYFELBEIN, WM YOUNG, RH SCULLY, RE TI CYSTIC STRUMA-OVARII - A FREQUENTLY UNRECOGNIZED TUMOR - A REPORT OF 20 CASES SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE OVARY; STRUMA; CYSTIC AB Twenty cases of cystic struma ovarii in women aged 23 to 83 (average, 46) years are described. The patients had the usual signs and symptoms of an adnexal mass. The tumors, all of which were unilateral and confined to the ovary, ranged from 2 to 19 (average, 13.5) cm in greatest dimension. Eighteen were multilocular, two unilocular. They were typically filled with clear to green-brown fluid. Microscopic examination showed cysts of various sizes separated by fibrous septa, which in many areas appeared nonspecific, but in all the cases contained at least small numbers of thyroid follicles. The cysts were typically lined by nonspecific-appearing, flat to cuboidal epithelial cells. The paucity of thyroid follicles in many areas and the nonspecific appearance of the epithelial cells lining the cysts often caused the diagnosis of struma ovarii to be overlooked. Clues to the correct diagnosis, in addition to the thyroid follicles in the septa, included the presence of larger areas of typical struma in a few cases and the association with a dermoid cyst in three cases. Immunohistochemical staining for thyroglobulin confirmed the nature of the tumor in all three cases in which it was performed. The diagnosis of cystic struma should be entertained when examining a multilocular or unilocular cystic ovarian neoplasm whose features are not obviously those of another tumor type, and a careful search for thyroid follicles should be undertaken to establish the diagnosis. In problematic cases, immunohistochemical staining for thyroglobulin may be required to establish the diagnosis. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RP SZYFELBEIN, WM (reprint author), MASSACHUSETTS GEN HOSP,DEPT PATHOL WARREN 2,JAMES HOMER WRIGHT PATHOL LABS,BOSTON,MA, USA. NR 10 TC 34 Z9 38 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD AUG PY 1994 VL 18 IS 8 BP 785 EP 788 DI 10.1097/00000478-199408000-00004 PG 4 WC Pathology; Surgery SC Pathology; Surgery GA NZ050 UT WOS:A1994NZ05000004 PM 8037292 ER PT J AU EBLE, JN ROSENBERG, AE YOUNG, RH AF EBLE, JN ROSENBERG, AE YOUNG, RH TI RETROPERITONEAL XANTHOGRANULOMA IN A PATIENT WITH ERDHEIM-CHESTER DISEASE SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Note DE ERDHEIM-CHESTER DISEASE; XANTHOGRANULOMA; RETROPERITONEUM; KIDNEY ID INFLAMMATORY FIBROUS HISTIOCYTOMA AB A case of Erdheim-Chester disease with retroperitoneal and renal sinus xanthogranuloma that occurred in a 50-year-old woman is presented. The 12 previously reported cases of Erdheim-Chester disease associated with retroperitoneal xanthogranuloma are reviewed and compared with 13 sporadic cases of retroperitoneal xanthogranuloma. Retroperitoneal xanthogranuloma is distinguished from inflammatory malignant fibrous histiocytoma by its lack of neutrophils, inconspicuous vascularity, lack of nuclear atypia, and abundant collagen. It is distinguished from inflammatory fibrosarcoma by its numerous foamy histiocytes, relative lack of plasma cells, and lack of nuclear atypia; it is distinguished from retroperitoneal fibrosis principally by its many foamy histiocytes, lack of plasma cells, and lack of vasculitis. C1 INDIANA UNIV,SCH MED,INDIANAPOLIS,IN. HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP EBLE, JN (reprint author), RICHARD L ROUDEBUSH VET AFFAIRS MED CTR,1481 W 10TH ST,INDIANAPOLIS,IN 46202, USA. NR 45 TC 33 Z9 35 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD AUG PY 1994 VL 18 IS 8 BP 843 EP 848 DI 10.1097/00000478-199408000-00012 PG 6 WC Pathology; Surgery SC Pathology; Surgery GA NZ050 UT WOS:A1994NZ05000012 PM 8037299 ER PT J AU CLEMENT, PB GRANAI, CO YOUNG, RH SCULLY, RE AF CLEMENT, PB GRANAI, CO YOUNG, RH SCULLY, RE TI ENDOMETRIOSIS WITH MYXOID CHANGE - A CASE SIMULATING PSEUDOMYXOMA PERITONEI SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Note DE ENDOMETRIOSIS; MYXOID CHANGE; PSEUDOMYXOMA PERITONEI; ADENOCARCINOMA ID UTERUS-LIKE MASS; CLINICOPATHOLOGICAL ANALYSIS; OVARY; ENDOMYOMETRIOSIS AB After a diagnosis of endocervical adenocarcinoma was made on examination of a curettage specimen, a 46-year-old woman underwent laparotomy for the purpose of radical hysterectomy. After frozen section of a biopsy specimen obtained from a nodule 2 cm in diameter on the posterior surface of the cervix was interpreted as adenocarcinoma, consistent with pseudomyxoma peritonei, the planned hysterectomy was abandoned; only biopsies of the pelvic and para-aortic lymph nodes and a bilateral salpingo-oophorectomy were performed. Permanent sections of the nodule revealed pools of almost acellular mucin, myxoid fibrous tissue, and typical endometriotic glands and stroma. Similar findings were associated with endometriotic foci in the serosa of a fallopian tube and adjacent to a pelvic lymph node. There was no evidence of adenocarcinoma in any of the specimens. A radical hysterectomy was performed subsequently, and pathological examination of the uterus revealed a superficially invasive adenocarcinoma of the cervix without evidence of extrauterine spread. The diagnosis of endometriosis associated with myxoid change was confirmed in residual cul-de-sac tissue. The patient was alive with no clinical evidence of tumor 6.5 years later. This case illustrates that rare cases of endometriosis can be associated with striking degrees of myxoid change, a finding that should not be confused with mucinous adenocarcinoma on microscopic examination. C1 UNIV BRITISH COLUMBIA,VANCOUVER,BC,CANADA. VINCENT MEM HOSP,DEPT GYNECOL,BOSTON,MA. MASSACHUSETTS GEN HOSP,JAMES HOMER WRIGHT PATHOL LABS,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RP CLEMENT, PB (reprint author), VANCOUVER GEN HOSP,DEPT PATHOL,855 W 12TH AVE,VANCOUVER V5Z 1M9,BC,CANADA. NR 10 TC 17 Z9 17 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD AUG PY 1994 VL 18 IS 8 BP 849 EP 853 DI 10.1097/00000478-199408000-00013 PG 5 WC Pathology; Surgery SC Pathology; Surgery GA NZ050 UT WOS:A1994NZ05000013 PM 8037300 ER PT J AU MOHSENIFAR, Z STEIN, M DELILLY, J MAHLER, ME MANDELKERN, M WILLIAMS, AJ AF MOHSENIFAR, Z STEIN, M DELILLY, J MAHLER, ME MANDELKERN, M WILLIAMS, AJ TI REGIONAL METABOLIC DEPENDENCY IN OBSTRUCTIVE SLEEP-APNEA SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article DE SLEEP APNEA; OXYGEN-SUPPLY DEPENDENCY; POSITRON-EMISSION TOMOGRAPHY SCANNING ID POSITIVE AIRWAY PRESSURE; GLUCOSE-UTILIZATION; HEMODYNAMICS AB Abnormalities of oxygen use occur in obstructive sleep apnea, as do impaired cerebral perfusion and alterations of cerebral function. In this case study, the authors quantitated the local cerebral glucose metabolic rate in two patients with obstructive sleep apnea (one with and one without oxygen supply dependency) and assessed cerebral glucose use by increasing oxygen delivery through passive leg elevation. Obstructive sleep apnea was confirmed by visual analysis of nocturnal pulse oximetry traces in two patients and its severity assessed from the respiratory disturbance index and minimum oxygen saturation. Awake local cerebral glucose metabolic rate (mu M/min/100 g) was determined by positron-emission tomography using [18F]2-Fluoro-2-Deoxy-D-Glucose at baseline and on the following day during passive leg elevation. Conditions otherwise were unchanged. The patient with global oxygen supply dependency exhibited a significant increase in the local cerebral glucose metabolic rate. In contrast, the patient without global supply dependency had no change in the local cerebral glucose metabolic rate. These case studies demonstrate the first evidence of improvement in regional metabolic consumption in response to increased oxygen delivery and in the presence of global oxygen supply dependency. C1 W LOS ANGELES VA MED CTR,MED SERV,LOS ANGELES,CA. W LOS ANGELES VA MED CTR,RES SERV,LOS ANGELES,CA. UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA. UNIV CALIF IRVINE,DEPT PHYS,IRVINE,CA 92717. RP MOHSENIFAR, Z (reprint author), CEDARS SINAI MED CTR,DIV PULM MED,8700 BEVERLY BLVD,ROOM 6732,LOS ANGELES,CA 90048, USA. NR 21 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0002-9629 J9 AM J MED SCI JI Am. J. Med. Sci. PD AUG PY 1994 VL 308 IS 2 BP 75 EP 78 DI 10.1097/00000441-199408000-00001 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA PA658 UT WOS:A1994PA65800001 PM 8042657 ER PT J AU LEE, PY FLETCHER, WS SULLIVAN, ES VETTO, JT AF LEE, PY FLETCHER, WS SULLIVAN, ES VETTO, JT TI COLORECTAL-CANCER IN YOUNG-PATIENTS - CHARACTERISTICS AND OUTCOME SO AMERICAN SURGEON LA English DT Article; Proceedings Paper CT 36th Annual Meeting of the Midwest-Surgical-Association CY AUG 08-11, 1993 CL LINCOLNSHIRE, IL SP MIDWEST SURG ASSOC ID PATIENTS LESS; CARCINOMA; COLON; RECTUM; AGE; ADENOCARCINOMA; SURVEILLANCE; PROGNOSIS; COLITIS; ADULTS AB Controversy still exists regarding the features and prognosis of colorectal cancer in young patients. We reviewed the records of 62 patients 40 years of age and younger with adenocarcinoma of the colon and rectum, treated and followed at our institution between 1968 and 1991. These patients represented 3.1 per cent of our total colorectal patient population during that time period. Their mean age was 34.5 years old, with the youngest patient being 18 years of age. Modified Dukes stages at presentation were 8 per cent A, 20 per cent B, 23 per cent C, and 48 per cent 15. Underlying inflammatory bowel disease was present in 21 per cent of patients and was proportionately distributed between high (C and D) and low (A and B) stages. Half of the stage D patients had high grade lesions, compared with only 20 per cent of lower stage patients (P = 0.037). All but two patients had operative exploration; 36 (60%) had complete resection Of all gross disease. With a mean follow-up of 98.2 months, the 5-year overall survival for stage A disease was 100 per cent, but dropped to 85, 40, and 7 per cent for stages B, C and D, respectively. Compared to published figures for the general population, younger patients with colon and rectal cancer tend to present at a more advanced stage, but have similar stage-related survival. C1 PORTLAND VET AFFAIRS MED CTR,PORTLAND,OR. NR 33 TC 62 Z9 66 U1 0 U2 0 PU SOUTHEASTERN SURGICAL CONGRESS PI ATLANTA PA 1776 PEACHTREE RD, NW., SUITE 410N, ATLANTA, GA 30309-2352 SN 0003-1348 J9 AM SURGEON JI Am. Surg. PD AUG PY 1994 VL 60 IS 8 BP 607 EP 612 PG 6 WC Surgery SC Surgery GA NY413 UT WOS:A1994NY41300011 PM 8030817 ER PT J AU GOUDSOUZIAN, NG DENMAN, W MATTA, E AF GOUDSOUZIAN, NG DENMAN, W MATTA, E TI MIVACURIUM AFTER ATRACURIUM IN CHILDREN SO ANESTHESIA AND ANALGESIA LA English DT Article ID OXIDE-NARCOTIC ANESTHESIA; VECURONIUM; HALOTHANE; PHARMACOKINETICS; PANCURONIUM; INFUSION; INFANTS AB The effect of mivacurium after atracurium was evaluated in 36 children anesthetized with halothane-nitrous oxide-oxygen by measuring the force of contraction of the adductor pollicis during train-of-four stimulation at 0.1 Hz. The children were evaluated in two main groups. In Group 1 the effect of bolus doses of mivacurium after equipotent repeat doses of atracurium were evaluated. When the first twitch of the train-of-four response (T1) had recovered to 25% of control after a tracheally intubating dose of atracurium, a repeat dose of atracurium was given, on subsequent recovery to 25%, an equipotent dose of mivacurium was administered. In Group 2 when T1 had recovered to >10% from 0.5 mg/kg atracurium, a mivacurium infusion was started; the initial infusion rate was 4 mu g.kg(-1).min(-1) with adjustments made to maintain 90%-99% depression of T1. Patients were allowed to recover spontaneously from the effect of the relaxants. RP GOUDSOUZIAN, NG (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ANESTHESIA,BOSTON,MA 02114, USA. NR 15 TC 6 Z9 6 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 AUG PY 1994 VL 79 IS 2 BP 345 EP 349 PG 5 WC Anesthesiology SC Anesthesiology GA NZ337 UT WOS:A1994NZ33700026 PM 7639377 ER PT J AU HUNCHAREK, M KLASSEN, H KLASSEN, M AF HUNCHAREK, M KLASSEN, H KLASSEN, M TI SPLENIC ARTERY ANEURYSM AND UPPER GASTROINTESTINAL-BLEEDING IN A NULLIPAROUS WOMAN - A CASE-HISTORY SO ANGIOLOGY LA English DT Note ID MANAGEMENT AB An eighty-three-year-old nulliparous woman hospitalized for orthopedic surgery developed postoperative upper gastrointestinal bleeding and hypotension resulting in her death. Postmortem examination revealed a ruptured splenic artery aneurysm. This is the second reported case of gastrointestinal bleeding due to ruptured splenic artery aneurysm in a nulliparous woman and the first such case resulting in death. The incidence, pathophysiology, clinical presentation, and diagnosis of splenic artery aneurysm are discussed. C1 HARVARD UNIV,CAMBRIDGE HOSP,SCH MED,DEPT MED,CAMBRIDGE,MA 02138. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02114. NR 9 TC 2 Z9 2 U1 0 U2 0 PU WESTMINSTER PUBL INC PI GLEN HEAD PA 708 GLEN COVE AVE, GLEN HEAD, NY 11545 SN 0003-3197 J9 ANGIOLOGY JI Angiology PD AUG PY 1994 VL 45 IS 8 BP 733 EP 735 DI 10.1177/000331979404500809 PG 3 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PB113 UT WOS:A1994PB11300009 PM 8048783 ER PT J AU DOHN, MN WEINBERG, WG TORRES, RA FOLLANSBEE, SE CALDWELL, PT SCOTT, JD GATHE, JC HAGHIGHAT, DP SAMPSON, JH SPOTKOV, J DERESINSKI, SC MEYER, RD LANCASTER, DJ FRAME, PT MOHSENIFAR, Z BUCKLEY, RM CHEUNG, T HYLAND, R CHAN, C LANG, W MILDVAN, D GREENBERG, SB CRAVEN, D HIRSCH, M ELSADR, W JOSEPH, P HARDY, D BROWN, N ROGERS, M AF DOHN, MN WEINBERG, WG TORRES, RA FOLLANSBEE, SE CALDWELL, PT SCOTT, JD GATHE, JC HAGHIGHAT, DP SAMPSON, JH SPOTKOV, J DERESINSKI, SC MEYER, RD LANCASTER, DJ FRAME, PT MOHSENIFAR, Z BUCKLEY, RM CHEUNG, T HYLAND, R CHAN, C LANG, W MILDVAN, D GREENBERG, SB CRAVEN, D HIRSCH, M ELSADR, W JOSEPH, P HARDY, D BROWN, N ROGERS, M TI ORAL ATOVAQUONE COMPARED WITH INTRAVENOUS PENTAMIDINE FOR PNEUMOCYSTIS-CARINII PNEUMONIA IN PATIENTS WITH AIDS SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE PENTAMIDINE; ATOVAQUONE; PNEUMONIA, PNEUMOCYSTIS CARINII; ACQUIRED IMMUNODEFICIENCY SYNDROME ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; TRIMETHOPRIM-SULFAMETHOXAZOLE; CLINDAMYCIN PRIMAQUINE; RANDOMIZED TRIAL; 566C80; EFFICACY; THERAPY; DAPSONE AB Objective: To test the hypothesis that the therapeutic success rate of oral atovaquone is not worse than that of intravenous pentamidine in the primary treatment of mild and moderate Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome and to detect differences in the toxicity rates of the two treatments. Design: Patients were randomly assigned to receive 21 days of open-label therapy with either atovaquone, 750 mg orally with meals three times daily, or intravenous pentamidine, 3 to 4 mg per kg body weight once daily. Setting: Multicenter study including university and community treatment facilities. Patients: Patients with human immunodeficiency virus infection and clinical presentations consistent with mild or moderate P. carinii pneumonia were eligible. For efficacy and safety analyses, patients with histologically confirmed P. carinii pneumonia were emphasized. Measurements: Patients were monitored by clinical and laboratory evaluations for therapeutic efficacy and adverse events during the acute treatment phase and for 8 weeks after therapy was discontinued. C1 INFECT DIS RES CONSORTIUM GEORGIA, ATLANTA, GA USA. ST VINCENTS HOSP & MED CTR, NEW YORK, NY 10011 USA. DAVIES MED CTR, INST HIV RES & TREATMENT, SAN FRANCISCO, CA USA. BURROUGHS WELLCOME CO, RES TRIANGLE PK, NC 27709 USA. PK PLAZA MED CTR, HOUSTON, TX USA. UNIV CALIF IRVINE, IRVINE MED CTR, ORANGE, CA 92668 USA. RES & EDUC GRP, PORTLAND, OR USA. KAISER FDN HOSP, HARBOR CITY, CA USA. AIDS CLIN RES CONSORTIUM, REDWOOD CITY, CA USA. CEDARS SINAI MED CTR, LOS ANGELES, CA 90048 USA. REG MED CTR, MEMPHIS, TN USA. PENN HOSP, PHILADELPHIA, PA 19107 USA. MT SINAI MED CTR, NEW YORK, NY 10029 USA. WELLESLEY COLL HOSP, TORONTO M4Y 1J3, ON, CANADA. VIRX INC, SAN FRANCISCO, CA USA. BETH ISRAEL MED CTR, NEW YORK, NY 10003 USA. BAYLOR COLL MED, HOUSTON, TX 77030 USA. BOSTON CITY HOSP, BOSTON, MA 02118 USA. MASSACHUSETTS GEN HOSP, BOSTON, MA 02114 USA. HARLEM HOSP MED CTR, NEW YORK, NY 10037 USA. SUMMIT MED CTR, OAKLAND, CA USA. UNIV CALIF LOS ANGELES, LOS ANGELES, CA USA. RP DOHN, MN (reprint author), UNIV CINCINNATI, COLL MED, DEPT INTERNAL MED, DIV PULM CRIT CARE, POB 670564, CINCINNATI, OH 45267 USA. NR 23 TC 65 Z9 67 U1 0 U2 2 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD AUG 1 PY 1994 VL 121 IS 3 BP 174 EP 180 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA NY338 UT WOS:A1994NY33800003 PM 7880228 ER PT J AU EBERLEIN, TJ AF EBERLEIN, TJ TI CURRENT MANAGEMENT OF CARCINOMA OF THE BREAST SO ANNALS OF SURGERY LA English DT Review ID RECONSTRUCTION FOLLOWING MASTECTOMY; SURGICAL ADJUVANT BREAST; GROWTH-FACTOR RECEPTOR; HER-2 NEU ONCOGENE; INTRADUCTAL CARCINOMA; RADIATION-THERAPY; CANCER PATIENTS; CONSERVING SURGERY; LOBULAR CARCINOMA; RANDOMIZED TRIAL AB Objective An in-depth retrospective review of the multidisciplinary approach to the management of carcinoma of the breast was done. The author reviewed previous trials and treatment from the past to the present. The indications and contraindications of surgical procedures, radiation therapy, systemic chemotherapy, and hormonal therapy are discussed. Summary Background Data Carcinoma of the breast is one of the most common malignancies treated by the practicing general or oncologic surgeon. The disease is best treated using a multidisciplinary approach, combining the efforts of surgery, radiation therapy, and systemic treatments. Understanding the indications and contraindications for each of these modalities will provide the practicing surgeon the most up-to-date algorithms for the management of his/her patient. Conclusions The author provides a comprehensive analysis of the multidisciplinary approach to the management of carcinoma of the breast. It emphasizes the results of previous trials and discusses future controversies and areas for study. C1 HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,CTR BREAST EVALUAT,BOSTON,MA 02115. RP EBERLEIN, TJ (reprint author), BRIGHAM & WOMENS HOSP,DIV SURG ONCOL,BIOL CANC THERAPY PROGRAM,75 FRANCIS ST,BOSTON,MA 02115, USA. NR 151 TC 26 Z9 28 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD AUG PY 1994 VL 220 IS 2 BP 121 EP 136 DI 10.1097/00000658-199408000-00003 PG 16 WC Surgery SC Surgery GA PA499 UT WOS:A1994PA49900003 PM 8053734 ER PT J AU FOITZIK, T MITHOFER, K FERRARO, MJ FERNANDEZDELCASTILLO, C LEWANDROWSKI, KB RATTNER, DW WARSHAW, AL AF FOITZIK, T MITHOFER, K FERRARO, MJ FERNANDEZDELCASTILLO, C LEWANDROWSKI, KB RATTNER, DW WARSHAW, AL TI TIME-COURSE OF BACTERIAL-INFECTION OF THE PANCREAS AND ITS RELATION TO DISEASE SEVERITY IN A RODENT MODEL OF ACUTE NECROTIZING PANCREATITIS SO ANNALS OF SURGERY LA English DT Article ID GUT; TRANSLOCATION; NECROSIS; SEPSIS; MICE AB Background Bacterial infection of pancreatic necrosis is thought to be a major determinant of outcome in acute necrotizing pancreatitis. The determinants and possibilities for prophylaxis are unknown and difficult to study in humans. Objective The time course of bacterial infection oi the pancreas in a rodent model of acute necrotizing pancreatitis was characterized. The authors ascertained if there is a correlation with the degree of necrosis. Methods Acute pancreatitis (AP) of graded severity was induced under sterile conditions by an intravenous infusion of cerulein (5 mu g/kg/hr) for 6 hours (mild AP), or a combination of intravenous cerulein with an intraductal infusion of 10-mM glycodeoxycholic acid (0.2 mL for 2 min for moderate AP, 0.5 mL for 10 min for severe AP). Sham-operated animals (intravenous and intraductal NaCl 0.9%) served as controls. Ninety-six hours after induction, animals were killed for quantitative bacterial examination and histologic scoring of necrosis. In addition, groups of animals with severe AP were investigated at 12, 24, 48, 96, and 144 hours. Results No significant pancreatic necrosis was found in control animals (0.3 +/- 0.1) or animals with mild AP (0.6 +/- 0.1) killed at 96 hours. Necrosis scores were 1.1 +/- 0.2 for animals with moderate AP and 1.9 +/- 0.2 for animals with severe AP. Control animals did not develop significant bacterial infection of the pancreas (greater than or equal to 10(3) CFU/g). At 96 hours, the prevalence of infection was 37.5% in animals with mild AP and 50% in animals with moderate AP. In animals with severe AP, infection of the pancreas increased from 33% in the first 24 hours to 75% between 48 and 96 hours (p < 0.05). The bacterial counts and the number of different species increased with time and was maximal (> 10(11) CFU/g) at 96 hours. Conclusion Bacterial infection of the pancreas in rodent AP increases during the first several days, and its likelihood correlates with the severity of the disease. This model, which closely mimics the features of human acute pancreatitis, provides a unique opportunity to study the pathogenesis of infected necrosis and test therapeutic strategies. C1 MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 23 TC 34 Z9 36 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD AUG PY 1994 VL 220 IS 2 BP 193 EP 198 DI 10.1097/00000658-199408000-00011 PG 6 WC Surgery SC Surgery GA PA499 UT WOS:A1994PA49900011 PM 8053741 ER PT J AU AKINS, CW BUCKLEY, MJ DAGGETT, WM HILGENBERG, AD VLAHAKES, GJ TORCHIANA, DF AUSTEN, WG AF AKINS, CW BUCKLEY, MJ DAGGETT, WM HILGENBERG, AD VLAHAKES, GJ TORCHIANA, DF AUSTEN, WG TI REOPERATIVE CORONARY GRAFTING - CHANGING PATIENT PROFILES, OPERATIVE INDICATIONS, TECHNIQUES, AND RESULTS SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 30th Annual Meeting of the Society-of-Thoracic-Surgeons CY JAN 31-FEB 02, 1994 CL NEW ORLEANS, LA SP SOC THORAC SURGEONS ID SAPHENOUS-VEIN GRAFTS; ARTERY BYPASS; SURGERY; DISEASE; ATHEROSCLEROSIS; ANGIOPLASTY; MORTALITY AB To assess the changing trends in patient profiles, operative indications and techniques, and their impact on the results of reoperative myocardial revascularization, we reviewed the records of 750 consecutive patients who had an isolated first reoperation for coronary artery disease at the Massachusetts General Hospital from 1977 to 1992. The patients were chronologically grouped into three equal cohorts of 250 patients. Our assessment over time revealed a significantly (p < 0.03) increased incidence of the following: older age, peripheral vascular disease, grafts at the first revascularization, longer operative interval, interval infarctions and angioplasties, and congestive heart failure and unstable angina requiring greater use of preoperative intraaortic balloon pumping. At catheterization significantly more left main coronary disease, lower ejection fractions, and more patent but diseased grafts were found. The reoperations were significantly done more urgently, with more grafts placed and a greater use of mammary artery grafting. Despite these increased risks over time, median postoperative hospital stay was significantly shortened (p < 0.001), though hospital mortality (5.3%) and perioperative myocardial infarction (6.3%) did not change significantly. Significant multivariate predictors of hospital death were nonelective operation, perioperative myocardial infarction, prior myocardial infarction, and mammary artery grafting at the initial operation. RP AKINS, CW (reprint author), MASSACHUSETTS GEN HOSP,DEPT SURG,CARDIAC SURG UNIT,WHITE 503,BOSTON,MA 02114, USA. NR 23 TC 29 Z9 31 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD AUG PY 1994 VL 58 IS 2 BP 359 EP 365 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA PD589 UT WOS:A1994PD58900016 PM 8067832 ER PT J AU ALSTON, TA DAMBRA, MN AF ALSTON, TA DAMBRA, MN TI NEUTRALIZATION OF HEPARIN BY TRASYLOL - REPLY SO ANNALS OF THORACIC SURGERY LA English DT Letter RP ALSTON, TA (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ANESTHESIA,BOSTON,MA 02114, USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD AUG PY 1994 VL 58 IS 2 BP 605 EP 606 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA PD589 UT WOS:A1994PD58900082 ER PT J AU KANG, SW BARNHILL, RL MIHM, MC FITZPATRICK, TB SOBER, AJ AF KANG, SW BARNHILL, RL MIHM, MC FITZPATRICK, TB SOBER, AJ TI MELANOMA RISK IN INDIVIDUALS WITH CLINICALLY ATYPICAL NEVI SO ARCHIVES OF DERMATOLOGY LA English DT Article ID MALIGNANT MELANOMAS; DYSPLASTIC NEVUS AB Background and Design: A lack of consensus as to the clinical and histologic characteristics of dysplastic nevi has resulted in the recommendation to abandon the term dysplastic nevus for the more descriptive atypical nevus or atypical mole. The significance of the presence of one or more such lesions, histologic features notwithstanding, has not been carefully examined. The risk of melanoma was assessed in individuals with atypical nevi monitored regularly in our Pigmented Lesion Clinic. Any patient enrolled in this subspecialty clinic between 1980 and 1985 without the diagnosis of melanoma who had at least one sufficiently atypical-appearing nevus and who was followed up for a minimum of 5 years was entered in the study. Results: A total of 155 such individuals were identified. The mean (+/- SEM) age of the patients at first evaluation was 26+/-1 years. The group was followed for 7+/-1 years. The male-female ratio was 1:1. A family history of melanoma was present in 71 subjects (46%). Of the 155 patients, two developed melanoma. The thickness of the tumors in both patients was less than or equal to 0.8 mm. Twenty-five patients (16%), including the two with melanoma, had at least one nevus removed that showed severe nuclear atypia''. Conclusions: The risk of melanoma in individuals with atypical nevi is significantly greater than expected. The elevated risk was demonstrated even though careful, regular evaluations and removal of more atypical lesions were performed. This study provides evidence that, compared with no surveillance, the meticulous monitoring of patients with clinically atypical nevi is more likely to result in the detection of melanoma at thin stages, with an attendant improved prognosis. C1 MASSACHUSETTS GEN HOSP,DEPT DERMATOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT DERMATOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. NR 11 TC 54 Z9 54 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 AUG PY 1994 VL 130 IS 8 BP 999 EP 1001 DI 10.1001/archderm.130.8.999 PG 3 WC Dermatology SC Dermatology GA PC020 UT WOS:A1994PC02000005 PM 8053717 ER PT J AU NOGITA, T WONG, TY OHARA, K MIZUSHIMA, J MIHM, MC KAWASHIMA, M AF NOGITA, T WONG, TY OHARA, K MIZUSHIMA, J MIHM, MC KAWASHIMA, M TI ATYPICAL MELANOSIS OF THE FOOT - A REPORT OF 3 CASES IN JAPANESE POPULATIONS SO ARCHIVES OF DERMATOLOGY LA English DT Article ID ACRAL LENTIGINOUS MELANOMA; MALIGNANT-MELANOMA; INSITU AB Background: Acral lentiginous melanoma is the most common type of malignant melanoma in the Japanese population. In most instances, classic acral lentiginous melanoma or acral lentiginous melanoma in situ can be readily distinguished from other benign pigmented lesions by virtue of its atypical clinical appearance. Observation: We present three cases of seemingly malignant pigmented lesions on the foot, all arising in Japanese females. Clinically, the lesions are characterized by irregular borders and variegated pigmentation closely mimicking those of acral lentiginous melanoma in situ. However, the histologic findings revealed only focal slight melanocytic hyperplasia with minimal cytologic atypia along the basal layer. Despite the malignant clinical features, thorough histologic examination failed to disclose any area with significant melanocytic atypia or evidence of malignancy. Conclusions: To the best of our knowledge, similar lesions with the clinical appearance of melanoma in situ and completely lacking histologic evidence of malignancy have not been reported. We, therefore, prefer to designate these lesions as atypical melanosis of the foot to highlight the clinically apparent atypical findings and to distinguish them from malignant melanoma in situ of the foot. C1 MASSACHUSETTS GEN HOSP,DIV DERMATOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. TORANOMON GEN HOSP,DEPT DERMATOL,TOKYO,JAPAN. RP NOGITA, T (reprint author), TOKYO WOMENS MED COLL,DEPT DERMATOL,SHINJUKU KU,8-1 KAWADACHO,TOKYO 162,JAPAN. NR 23 TC 20 Z9 20 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 AUG PY 1994 VL 130 IS 8 BP 1042 EP 1045 DI 10.1001/archderm.130.8.1042 PG 4 WC Dermatology SC Dermatology GA PC020 UT WOS:A1994PC02000013 PM 8053702 ER PT J AU LOUIS, DN SEIZINGER, BR AF LOUIS, DN SEIZINGER, BR TI GENETIC-BASIS OF NEUROLOGICAL TUMORS SO BAILLIERES CLINICAL NEUROLOGY LA English DT Article ID GROWTH-FACTOR RECEPTOR; NEUROFIBROMATOSIS TYPE-1 GENE; VONHIPPEL-LINDAU DISEASE; CENTRAL-NERVOUS-SYSTEM; BILATERAL ACOUSTIC NEUROFIBROMATOSIS; PRIMITIVE NEUROECTODERMAL TUMORS; HUMAN-MALIGNANT ASTROCYTOMA; RENAL-CELL CARCINOMA; HUMAN GLIOMAS INVIVO; HUMAN BRAIN-TUMORS C1 BRISTOL MYERS SQUIBB,PHARMACEUT RES INST,ONCOL DRUG DISCOVERY,PRINCETON,NJ 08543. RP LOUIS, DN (reprint author), MASSACHUSETTS GEN HOSP,MOLEC NEUROONCOL LAB,BOSTON,MA 02114, USA. FU NCI NIH HHS [CA09144, CA57683] NR 86 TC 13 Z9 13 U1 0 U2 1 PU BAILLIERE TINDALL PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0961-0421 J9 BAILLIERE CLIN NEUR JI Baillieres Clin. Neurol. PD AUG PY 1994 VL 3 IS 2 BP 335 EP 352 PG 18 WC Clinical Neurology SC Neurosciences & Neurology GA PA631 UT WOS:A1994PA63100008 PM 7952851 ER PT J AU RAM, PA WAXMAN, DJ AF RAM, PA WAXMAN, DJ TI DEHYDROEPIANDROSTERONE 3-BETA-SULFATE IS AN ENDOGENOUS ACTIVATOR OF THE PEROXISOME-PROLIFERATION PATHWAY - INDUCTION OF CYTOCHROME-P-450 4A AND ACYL-COA OXIDASE MESSENGER-RNAS IN PRIMARY RAT HEPATOCYTE CULTURE AND INHIBITORY EFFECTS OF CA2+-CHANNEL BLOCKERS SO BIOCHEMICAL JOURNAL LA English DT Article ID HORMONE RECEPTOR SUPERFAMILY; ACID OMEGA-HYDROXYLASE; BETA-OXIDATION; FATTY-ACIDS; CLOFIBRIC ACID; RETINOIC ACID; LIVER; GENE; EXPRESSION; IDENTIFICATION AB The role of steroids related to the adrenal androgen dehydroepiandrosterone (5-androstene-3 beta-ol-17-one; DHEA) in regulating the expression of peroxisomal and cytochrome P-450 4A (CYP4A) enzymes active in fatty acid metabolism was assessed using a primary rat hepatocyte culture system. Exposure of hepatocytes to the peroxisome proliferator, clofibric acid (10-250 mu M), for 48-96 h led to substantial increases in CYP4A protein, CYP4A1, CYP4A2 and CYP4A3 mRNAs, and the mRNAs encoding both forms of peroxisomal acyl-CoA oxidase (ACOX-I and ACOX-II), as judged by Northern-blot analysis using gene-specific oligonucleotide probes. Although DHEA treatment in vivo is effective in inducing these mRNAs in rat liver, it had no effect in the cultured hepatocytes. In contrast, treatment of the cells with DHEA 3 beta-sulphate (DHEA-S; 10-250 mu M) stimulated major increases in CYP4A and ACOX mRNA levels. Examination of several analogues indicated a preference for 3 beta-sulphate over 17 beta-sulphated steroids and the (i)nactivity of a 3 alpha-hydroxy-17 beta-sulphate derivative (DHEA-S > 5-androstene-3 beta,17 beta-diol 3-sulphate similar to 5 alpha-androstene-3 beta-ol-17-one 3-sulphate > 5-androstene-3 beta, 17 beta-diol 17-sulphate similar to 5 beta androstane-3 alpha-ol-17-one 3-sulphate much greater than 5 alpha-androstane-3 alpha,17 beta-diol 17-sulphate). Induction of CYP4A mRNAs by either DHEA-S or clofibric acid was partially blocked by structurally diverse Ca2+-channel antagonists (nicardipine nifedipine and diltiazem; 50 mu M), suggesting that both the steroidal and fibrate classes of CYP4A inducers stimulate peroxisomal-proliferative responses via a Ca2+-dependent pathway. Retinoic acid alone slightly induced CYP4A mRNAs but did not enhance the induction by clofibrate or DHEA-S. As DHEA-S corresponds to a physiologically important major circulating androgen, these findings suggest that it may serve as an endogenous regulator of hepatic peroxisome enzyme levels, They further suggest that Ca2+-channel blockers may be useful pharmacological tools for the further study of the underlying cellular mechanisms whereby endogenous steroids and fibrate drugs induce peroxisome proliferation, and the relationship of these events to activation of the peroxisome proliferator-activated receptor. C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. FU NIDDK NIH HHS [DK 33765] NR 57 TC 32 Z9 32 U1 0 U2 1 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD AUG 1 PY 1994 VL 301 BP 753 EP 758 PN 3 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PB311 UT WOS:A1994PB31100017 PM 8053899 ER PT J AU MUNN, LL MELDER, RJ JAIN, RK AF MUNN, LL MELDER, RJ JAIN, RK TI ANALYSIS OF CELL FLUX IN THE PARALLEL-PLATE FLOW CHAMBER - IMPLICATIONS FOR CELL CAPTURE STUDIES SO BIOPHYSICAL JOURNAL LA English DT Article ID ADHESION; LEUKOCYTES; STRENGTH AB The parallel plate flow chamber provides a controlled environment for determinations of the shear stress at which cells in suspension can bind to endothelial cell monolayers. By decreasing the flow rate of cell-containing media over the monolayer and assessing the number of cells bound at each wall shear stress, the relationship between shear force and binding efficiency can be determined. The rate of binding should depend on the delivery of cells to the surface as well as the intrinsic cell-surface interactions; thus, only if the cell flux to the surface is known can the resulting binding curves be interpreted correctly. We present the development and validation of a mathematical model based on the sedimentation rate and velocity profile in the chamber for the delivery of cells from a flowing suspension to the chamber surface. Our results show that the flux depends on the bulk cell concentration, the distance from the entrance point, and the flow rate of the cell-containing medium. The model was then used in a normalization procedure for experiments in which T cells attach to TNF-alpha-stimulated HUVEC monolayers, showing that a threshold for adhesion occurs at a shear stress of about 3 dyn/cm(2). C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,BOSTON,MA 02114. RI Munn, Lance/L-3950-2016 OI Munn, Lance/0000-0003-0698-7232 NR 21 TC 68 Z9 71 U1 0 U2 6 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD AUG PY 1994 VL 67 IS 2 BP 889 EP 895 PG 7 WC Biophysics SC Biophysics GA NY823 UT WOS:A1994NY82300042 PM 7948702 ER PT J AU AVALOS, BR BROUDY, VC CESELSKI, SK DRUKER, BJ GRIFFIN, JD HAMMOND, WP AF AVALOS, BR BROUDY, VC CESELSKI, SK DRUKER, BJ GRIFFIN, JD HAMMOND, WP TI ABNORMAL RESPONSE TO GRANULOCYTE-COLONY-STIMULATING FACTOR (G-CSF) IN CANINE CYCLIC HEMATOPOIESIS IS NOT CAUSED BY ALTERED G-CSF RECEPTOR EXPRESSION SO BLOOD LA English DT Article ID NEUTROPENIA; NEUTROPHILS; INTERLEUKIN-3; CELLS C1 OHIO STATE UNIV,ARTHUR G JAMES CANC HOSP & RES INST,COLUMBUS,OH. UNIV WASHINGTON,DEPT MED,DIV HEMATOL,SEATTLE,WA 98195. PROVIDENCE MED CTR,SEATTLE,WA. OREGON HLTH SCI UNIV,DIV HEMATOL & MED ONCOL,PORTLAND,OR 97201. DANA FARBER CANC INST,DIV CELLULAR & MOLEC BIOL,BOSTON,MA. DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA. RP AVALOS, BR (reprint author), OHIO STATE UNIV,DEPT INTERNAL MED,DIV BONE MARROW TRANSPLANTAT,303 E DOAN HALL,410 W 10TH AVE,COLUMBUS,OH 43210, USA. FU NCI NIH HHS [CA01422]; NHLBI NIH HHS [HL01812]; NIDDK NIH HHS [DK44194] NR 29 TC 11 Z9 11 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 AUG 1 PY 1994 VL 84 IS 3 BP 789 EP 794 PG 6 WC Hematology SC Hematology GA NZ250 UT WOS:A1994NZ25000016 PM 7519075 ER PT J AU SOIFFER, RJ MURRAY, C GONIN, R RITZ, J AF SOIFFER, RJ MURRAY, C GONIN, R RITZ, J TI EFFECT OF LOW-DOSE INTERLEUKIN-2 ON DISEASE RELAPSE AFTER T-CELL-DEPLETED ALLOGENEIC BONE-MARROW TRANSPLANTATION SO BLOOD LA English DT Article ID VERSUS-HOST DISEASE; CHRONIC MYELOGENOUS LEUKEMIA; NATURAL-KILLER-CELLS; ACUTE LYMPHOBLASTIC-LEUKEMIA; RECOMBINANT INTERLEUKIN-2; PHASE-I; RESIDUAL DISEASE; CANCER-PATIENTS; CLINICAL-TRIAL; SOLID TUMORS C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV BIOSTAT,BOSTON,MA 02115. RP SOIFFER, RJ (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,44 BINNEY ST,BOSTON,MA 02115, USA. RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NCI NIH HHS [CA41619]; PHS HHS [A129530] NR 50 TC 116 Z9 118 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 AUG 1 PY 1994 VL 84 IS 3 BP 964 EP 971 PG 8 WC Hematology SC Hematology GA NZ250 UT WOS:A1994NZ25000041 PM 8043878 ER PT J AU FERRARA, JLM AF FERRARA, JLM TI PARADIGM SHIFT FOR GRAFT-VERSUS-HOST DISEASE SO BONE MARROW TRANSPLANTATION LA English DT Editorial Material ID NECROSIS-FACTOR-ALPHA RP FERRARA, JLM (reprint author), CHILDRENS HOSP,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115, USA. NR 7 TC 27 Z9 27 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD AUG PY 1994 VL 14 IS 2 BP 183 EP 184 PG 2 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA PE172 UT WOS:A1994PE17200001 PM 7994229 ER PT J AU TEPLER, I ELIAS, A KALISH, L SHULMAN, L STRAUSS, G SKARIN, A LYNCH, T LEVITT, D RESTA, D DEMETRI, G GAYNES, L SCHNIPPER, L AF TEPLER, I ELIAS, A KALISH, L SHULMAN, L STRAUSS, G SKARIN, A LYNCH, T LEVITT, D RESTA, D DEMETRI, G GAYNES, L SCHNIPPER, L TI EFFECT OF RECOMBINANT HUMAN INTERLEUKIN-3 ON HEMATOLOGICAL RECOVERY FROM CHEMOTHERAPY-INDUCED MYELOSUPPRESSION SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE INTERLEUKIN 3; IL-3; NSCLC; MYELOSUPPRESSION; PHASE I/II CLINICAL TRIAL ID COLONY-STIMULATING FACTOR; TRANSITIONAL-CELL-CARCINOMA; BONE-MARROW FAILURE; PHASE-I; PROGENITOR CELLS; GROWTH-FACTORS; GM-CSF; LUNG-CANCER; MACROPHAGE; HEMATOPOIESIS AB Patients with non-small-cell lung cancer (NSCLC) were treated with ICE chemotherapy (ifosfamide 2000 mg/m(2), days 1-3; carboplatin 300 mg/m(2), day 1; etoposide 75 mg/m(2), days 1-3) intravenously (i.v.) during the first 3 d of a maximum of four 28 d treatment cycles. Interleukin-3 (IL-3) was administered in cycles 2 and 4 as a daily subcutaneous (s.c.) injection on days 5-18. Cohorts of three patients were treated at dosage levels of 0.5, 1.25, 2.5, 5.0, 10.0 and 15.0 mu g/kg/d. At 15.0 mu g/kg/d a 'flu-like' syndrome of myalgias, arthralgias and fatigue was considered dose-limiting. Other toxicities were headache, fever, urticaria, arrhythmia, chills and flushing. Subsequently, nine patients were added to the group receiving 10 mu g/kg/d. 27 patients received IL-3 after their second course of ICE. At 10 and 15 mu g/kg/d, IL-3 in cycle 2 was associated with enhanced haematological recovery. Depth of neutrophil nadir and days of neutropenia (ANC < 0.5 x 10(9)/l) were reduced in 9/13 patients and in 8/11 patients, respectively. No effect was seen on platelet nadir or days of thrombocytopenia. IL-3 was well tolerated up to 10 mu g/kg/d when given as a daily s.c. injection. Results suggest IL-3 as a potential adjunct to chemotherapy, and further studies to explore administration of IL-3 in combination with other cytokines in this setting are warranted. C1 DANA FARBER CANC INST,BOSTON,MA. BRIGHAM & WOMENS HOSP,BOSTON,MA. HARVARD UNIV,SCH MED,HARVARD COMMUNITY HLTH PLAN,BOSTON,MA. SANDOZ PHARMACEUT CORP,CYTOKINE DEV UNIT,E HANOVER,NJ. RP TEPLER, I (reprint author), BETH ISRAEL HOSP,330 BROOKLINE AVE,BOSTON,MA 02215, USA. NR 43 TC 18 Z9 19 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD AUG PY 1994 VL 87 IS 4 BP 678 EP 686 DI 10.1111/j.1365-2141.1994.tb06723.x PG 9 WC Hematology SC Hematology GA PB740 UT WOS:A1994PB74000002 PM 7986706 ER PT J AU KENNEY, DM REID, R PARENT, DW ROSEN, FS REMOLDODONNELL, E AF KENNEY, DM REID, R PARENT, DW ROSEN, FS REMOLDODONNELL, E TI EVIDENCE IMPLICATING CALPAIN (CA2+-DEPENDENT NEUTRAL PROTEASE) IN THE DESTRUCTIVE THROMBOCYTOPENIA OF THE WISKOTT-ALDRICH SYNDROME SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE PLATELET; CALPAIN; THROMBOCYTOPENIA; WISKOTT-ALDRICH SYNDROME ID LYMPHOCYTE SURFACE SIALOGLYCOPROTEIN; CALCIUM-DEPENDENT PROTEASE; PLATELET PLASMA-MEMBRANE; SIALOPHORIN CD43; ACTIVATION; EXPRESSION; ABNORMALITIES; PROTEINS; CLEAVAGE; SIZE AB The Wiskott-Aldrich syndrome (WAS) is an inherited platelet/T-lymphocyte disease characterized by small platelets, thrombocytopenia and immunodeficiency. Because degradative events have a significant role, we directly examined calpain (Ca2+-dependent neutral protease), a prominent protease in the affected cells, by functional and antigenic quantitation. Calpain activity in platelets of seven WAS patients was decreased to 59 +/- 3.7% (P < 0.01) relative to platelets of 11 normals. Platelets of two patients with immune thrombocytopenia had normal calpain activity. By immunoblotting, mu-procalpain, the mu-calpain species in resting (unstimulated) blood cells, was decreased in platelets of nine WAS patients to 58 +/- 14.6% (P < 0.01) relative to paired normals. In contrast, mu-procalpain levels in lymphocytes of seven WAS patients did not differ from normal lymphocytes. Normal platelets and lymphocytes have different mechanisms for Ca2+-dependent mu-procalpain activation. On addition of ionophore and Ca2+ to stirred platelets, 80 kD mu-procalpain was rapidly (0.5 min) and quantitatively converted to 76 kD active mu-calpain; this process was the same in WAS platelets. In lymphocytes, mu-procalpain activation was slow, only partially complete (40 min), and the active species was 78 kD. The marked depletion of calpain in WAS platelets demonstrated in this study may result from inappropriate stimulation of platelets and be related to the severe thrombocytopenia that characterizes this disease. C1 CHILDRENS HOSP,DIV IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. RP KENNEY, DM (reprint author), CTR BLOOD RES,800 HUNTINGTON AVE,BOSTON,MA 02115, USA. FU NHLBI NIH HHS [HL29583]; NIAID NIH HHS [AI31541]; NIGMS NIH HHS [GM37298] NR 54 TC 17 Z9 17 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 AUG PY 1994 VL 87 IS 4 BP 773 EP 781 DI 10.1111/j.1365-2141.1994.tb06737.x PG 9 WC Hematology SC Hematology GA PB740 UT WOS:A1994PB74000016 PM 7986718 ER PT J AU HARRIS, WH AF HARRIS, WH TI TOTAL HIP-REPLACEMENT - CEMENT VERSUS CEMENTLESS RESOLUTION SO BULLETIN ON THE RHEUMATIC DISEASES LA English DT Article ID 10-YEAR FOLLOW-UP; ARTHROPLASTIES; COMPONENTS C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP HARRIS, WH (reprint author), MASSACHUSETTS GEN HOSP,DEPT ORTHOPAED SURG,BOSTON,MA 02114, USA. NR 27 TC 1 Z9 1 U1 0 U2 0 PU ARTHRITIS FOUNDATION PI ATLANTA PA 1314 SPRING STREET NW, ATLANTA, GA 30309 SN 0007-5248 J9 B RHEUM DIS JI Bull. Rheum. Dis. PD AUG PY 1994 VL 43 IS 5 BP 1 EP 4 PG 4 WC Rheumatology SC Rheumatology GA PD772 UT WOS:A1994PD77200001 PM 7921064 ER PT J AU CONSTABLE, JD AF CONSTABLE, JD TI THE STATE OF BURN CARE - PAST, PRESENT AND FUTURE SO BURNS LA English DT Article RP CONSTABLE, JD (reprint author), MASSACHUSETTS GEN HOSP,CTR AMBULATORY CARE,BOSTON,MA 02114, USA. NR 0 TC 4 Z9 5 U1 0 U2 0 PU BUTTERWORTH-HEINEMANN LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0305-4179 J9 BURNS JI Burns PD AUG PY 1994 VL 20 IS 4 BP 316 EP 324 DI 10.1016/0305-4179(94)90059-0 PG 9 WC Critical Care Medicine; Dermatology; Surgery SC General & Internal Medicine; Dermatology; Surgery GA NY256 UT WOS:A1994NY25600005 PM 7945820 ER PT J AU FOLLIS, F MILLER, K SCREMIN, OU PETT, S KESSLER, R WERNLY, J AF FOLLIS, F MILLER, K SCREMIN, OU PETT, S KESSLER, R WERNLY, J TI NMDA RECEPTOR BLOCKADE AND SPINAL-CORD ISCHEMIA DUE TO AORTIC CROSS-CLAMPING IN THE RAT MODEL SO CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES LA English DT Article ID CARDIAC-ARREST; MK-801; INJURY; BRAIN; PARAPLEGIA; ANTAGONIST; GLUTAMATE; PROTECTS; DAMAGE; PAPAVERINE AB Recent brain research proposes that, during ischemia, synaptically released excitatory amino acid neurotransmitters accumulate at toxic concentrations with ensuing neuronal death. Their action is mediated by the receptor subtype N-methyl-D-aspartate (NMDA). The protective effect of NMDA receptor blockade with intrathecal MgSO4 and MK-801 was investigated during spinal cord ischemia induced by aortic occlusion of 12 minutes. Male Sprague-Dawley rats, 250-300g, underwent intrathecal administration of 20 mu L of normal saline (SA n = 16), MgSO4 1M (MG n = 16), or MK-801, 25 mM solutions (MK n = 16) in a randomized order. After 2 hours, the animals underwent occlusion of the thoracic aorta and subclavian arteries for 12 min. An additional control group (CO n = 16) underwent occlusion for 12 minutes, without intrathecal injection. The animals were scored according to their functional performance (LS = lesion score) each day for four days by a blinded observer. Mean LS were calculated for each group at a given day. Treatment and control groups were not different at day 1 (P = 0.302). Group MG was improved from groups SA (P = < 0.0039) and CO (P = < 0.0048) at day 4. This study demonstrates that although intrathecal NMDA receptor blockade with MgSO, or MK-801 does not prevent paraplegia due to spinal cord ischemia in the rat, it could however influence the rate of recovery after ischemic injury. C1 UNIV NEW MEXICO,DEPT THORAC & CARDIOTHORAC SURG,ALBUQUERQUE,NM 87131. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,SCH MED,DEPT PHYSIOL,LOS ANGELES,CA 90024. FU NCRR NIH HHS [MO1 RR00997, SO7 RR-05583-25] NR 31 TC 24 Z9 26 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 AUG PY 1994 VL 21 IS 3 BP 227 EP 232 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA PC596 UT WOS:A1994PC59600007 PM 8000978 ER PT J AU CASTRESANA, JS BARRIOS, C GOMEZ, L KREICBERGS, A AF CASTRESANA, JS BARRIOS, C GOMEZ, L KREICBERGS, A TI NO ASSOCIATION BETWEEN C-MYC AMPLIFICATION AND TP53 MUTATION IN SARCOMA TUMORIGENESIS SO CANCER GENETICS AND CYTOGENETICS LA English DT Article ID TUMOR SUPPRESSOR GENES; P53 MUTATIONS; POINT MUTATION; POLYMORPHISMS; LEUKEMIA; LYMPHOMA AB Oncogenes and tumor suppressor genes coparticipate in sarcoma tumorigenesis. We tested 43 sarcomas for c-myc amplification by Southern blot and molecular hybridization techniques and TP53 mutations by the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) technique and direct sequencing of the PCR products. We found eight tumors with c-myc amplification and five different tumors with TP53 mutations but no tumors harbor both c-myc and TP53 alterations. We suggest that c-myc amplification and TP53 mutations do not seem to coparticipate in the tumorigenesis of sarcomas. C1 KAROLINSKA HOSP & INST,DEPT TUMOR PATHOL,S-10401 STOCKHOLM,SWEDEN. KAROLINSKA HOSP & INST,DEPT ORTHOPED,S-10401 STOCKHOLM,SWEDEN. MASSACHUSETTS GEN HOSP,MOLEC NEUROONCOL LAB,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,NEUROSURG SERV,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02129. OI Castresana, Javier S./0000-0002-2373-482X NR 14 TC 12 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0165-4608 J9 CANCER GENET CYTOGEN JI Cancer Genet. Cytogenet. PD AUG PY 1994 VL 76 IS 1 BP 47 EP 49 DI 10.1016/0165-4608(94)90070-1 PG 3 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA PE587 UT WOS:A1994PE58700011 PM 8076351 ER PT J AU LI, FP MONTESANO, R AF LI, FP MONTESANO, R TI INTERACTIONS OF CANCER SUSCEPTIBILITY GENES AND ENVIRONMENTAL CARCINOGENS - AMERICAN-ASSOCIATION-FOR-CANCER-RESEARCH (AACR) INTERNATIONAL-AGENCY-FOR-RESEARCH-ON-CANCER (IARC) JOINT CONFERENCE SO CANCER RESEARCH LA English DT Editorial Material C1 INT AGCY RES CANC,F-69372 LYON,FRANCE. RP LI, FP (reprint author), DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02155, USA. NR 0 TC 7 Z9 7 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 AUG 1 PY 1994 VL 54 IS 15 BP 4243 EP 4247 PG 5 WC Oncology SC Oncology GA NZ246 UT WOS:A1994NZ24600049 PM 8033156 ER PT J AU ROELKE, M SMITH, AJC PALACIOS, IF AF ROELKE, M SMITH, AJC PALACIOS, IF TI THE TECHNIQUE AND SAFETY OF TRANSSEPTAL LEFT-HEART CATHETERIZATION - THE MASSACHUSETTS-GENERAL-HOSPITAL EXPERIENCE WITH 1,279 PROCEDURES SO CATHETERIZATION AND CARDIOVASCULAR DIAGNOSIS LA English DT Article DE TRANSSEPTAL LEFT HEART CATHETERIZATION ID TRANS-SEPTAL CATHETERIZATION; CARDIAC-CATHETERIZATION; LEFT ATRIAL; COMPLICATIONS; VALVE AB With the introduction of interventional procedures such as percutaneous mitral valvuloplasty and radiofrequency ablation of left-sided bypass tracts, there has been renewed interest in the technique of transseptal left heart catheterization. We review our experience with 1,279 transseptal catheterizations performed over the last 10 years. The most common indications for transseptal catheterization included direct measurement of left atrial pressure or access to the left ventricle in patients with prosthetic aortic or mitral valves, and in patients undergoing percutaneous mitral valvuloplasty. A total of 17 major complications occurred (1.3%), including cardiac tamponade (15 patients, 1.2%), systemic emboli (1 patient, 0.08%), and death secondary to aortic perforation (0.08%). We conclude that when performed by experienced operators, transseptal left heart catheterization is associated with low morbidity and mortality. (C) 1994 Wiley-Liss, Inc. RP ROELKE, M (reprint author), MASSACHUSETTS GEN HOSP,CARDIAC UNIT,CARDIAC CATHETERIZAT LAB,FRUIT ST,BOSTON,MA 02114, USA. NR 34 TC 79 Z9 80 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 0098-6569 J9 CATHETER CARDIO DIAG JI Catheter. Cardiovasc. Diagn. PD AUG PY 1994 VL 32 IS 4 BP 332 EP 339 DI 10.1002/ccd.1810320409 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PC738 UT WOS:A1994PC73800008 PM 7987913 ER PT J AU DUBINETT, SM HUANG, M LICHTENSTEIN, A MCBRIDE, WH WANG, JY MARKOVITZ, G KELLEY, D GRODY, WW MINTZ, LE DHANANI, S AF DUBINETT, SM HUANG, M LICHTENSTEIN, A MCBRIDE, WH WANG, JY MARKOVITZ, G KELLEY, D GRODY, WW MINTZ, LE DHANANI, S TI TUMOR-NECROSIS-FACTOR-ALPHA PLAYS A CENTRAL ROLE IN INTERLEUKIN-2-INDUCED PULMONARY VASCULAR LEAK AND LYMPHOCYTE ACCUMULATION SO CELLULAR IMMUNOLOGY LA English DT Article ID ALVEOLAR MACROPHAGES; RECOMBINANT INTERLEUKIN-2; PASSIVE-IMMUNIZATION; HEMODYNAMIC-CHANGES; ENDOTHELIAL-CELLS; INTERFERON-GAMMA; GENE-EXPRESSION; ADVANCED CANCER; SEPTIC SHOCK; LUNG INJURY AB Administration of interleukin-2 (IL-2) leads to pulmonary vascular leak. This form of pulmonary edema has previously been postulated to be due to the in vivo induction of tumor necrosis factor-alpha (TNF-alpha). To determine whether TNF-alpha plays a role in IL-2-induced pulmonary vascular leak, we performed in situ hybridization of lung sections and reverse transcriptase-polymerase chain reaction of bronchoalveolar lavage macrophages from IL-2-challenged mice. The results confirm an in situ upregulation of TNF-alpha mRNA expression in the lungs associated with vascular leak. In addition, a significant increase in TNF-alpha protein production was found in the lung following IL2 administration, as measured by TNF-alpha-specific ELISA of lung supernatants (P = 0.028). Intravenous administration ofa soluble TNF receptor significantly diminished 1L-2-induced pulmonary vascular leak (P = 0.006). These findings confirm a central role for TNF-alpha in mediating the pulmonary vascular leak associated with IL-2 toxicity, (C) 1994 Academic Press, Inc. C1 UNIV CALIF LOS ANGELES,DIV MED ONCOL,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,DIV RADIAT ONCOL,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,DIV MOLEC PATHOL,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,MED RES SERV,LOS ANGELES,CA 90073. RP DUBINETT, SM (reprint author), UNIV CALIF LOS ANGELES,DIV PULM & CRIT CARE MED,WADSWORTH PULM IMMUNOL LAB,LOS ANGELES,CA 90024, USA. FU NCI NIH HHS [CA09120] NR 40 TC 44 Z9 45 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD AUG PY 1994 VL 157 IS 1 BP 170 EP 180 DI 10.1006/cimm.1994.1214 PG 11 WC Cell Biology; Immunology SC Cell Biology; Immunology GA NZ093 UT WOS:A1994NZ09300015 PM 8039244 ER PT J AU HUNCHAREK, M AF HUNCHAREK, M TI MILIARY MESOTHELIOMA SO CHEST LA English DT Note AB Metastases in pleural mesothelioma usually occur late in the disease process. Diffuse involvement of the lung parenchyma is rare. A patient with miliary pulmonary parenchymal involvement with malignant mesothelioma is described. To our knowledge, this represents the first such case reported. RP HUNCHAREK, M (reprint author), MASSACHUSETTS GEN HOSP,CTR CANC,DEPT RADIAT ONCOL,BOSTON,MA, USA. NR 4 TC 10 Z9 10 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 AUG PY 1994 VL 106 IS 2 BP 605 EP 606 DI 10.1378/chest.106.2.605 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA PC341 UT WOS:A1994PC34100055 PM 7774346 ER PT J AU MORENO, PR FALK, E PALACIOS, IF NEWELL, JB FUSTER, V FALLON, JT AF MORENO, PR FALK, E PALACIOS, IF NEWELL, JB FUSTER, V FALLON, JT TI MACROPHAGE INFILTRATION IN ACUTE CORONARY SYNDROMES - IMPLICATIONS FOR PLAQUE RUPTURE SO CIRCULATION LA English DT Article DE PLAQUES; MYOCARDIAL INFARCTION; ANGINA; MACROPHAGES ID ATHEROSCLEROTIC PLAQUES; COLLAGENASE; STROMELYSIN; EXPRESSION AB Background Rupture of atherosclerotic plaques is probably the most important mechanism underlying the sudden onset of acute coronary syndromes. Macrophages may release lytic enzymes that degrade the fibrous cap and therefore produce rupture of the atherosclerotic plaque. This study was designed to quantify macrophage content in coronary plaque tissue from patients with stable and unstable coronary syndromes. Methods and Results Hematoxylin and eosin and immunostaining with anti-human macrophage monoclonal antibody (PC-M1) were performed. Computerized planimetry was used to analyze 26 atherectomy specimens comprising 524 pieces of tissue from 8 patients with chronic stable angina, 8 patients with unstable angina, and 10 patients with non-Q-wave myocardial infarction. Total plaque area was 417+/-87 mm(2)X10(-2) in patients with stable angina, 601+/-157 mm(2)X10(-2) in patients with unstable angina, and 499+/-87 mm(2)X10(-2) in patients with non-Q-wave myocardial infarction (P=NS). The macrophagerich area was larger in plaques from patients with unstable angina (61+/- mm(2)X10(-2)) and non-Q-wave myocardial infarction (87+/-32 mm(2)X10(-2)) than in plaques from patients with stable angina (14+/-5 mm(2)X10(-2)) (P=.024). The percentage of the total plaque area occupied by macrophages was also larger in patients with unstable angina (13.3+/-5.6%) and non-Q-wave myocardial infarction (14.6+/-4.6%) than in patients with stable angina (3.14+/-1%) (P=.018). Macrophage-rich sclerotic tissue was largest in patients with non-Q-wave myocardial infarction (67+/-30 mm(2)X10(-2)) and unstable angina (55+/-19 mm(2)X10(-2)) than in patients with stable angina (11.51+/-4.1 mm(2)X10(-2)) (P=.046). Macrophage-rich atheromatous gruel was also largest in patients with non-Q-wave myocardial infarction (15+/-4 mm(2)X10(-2)) than in patients with unstable angina (3.3+/-1.7 mm(2)X10(-2)) or stable angina (2.4+/-1.2 mm(2)X10(-2)) (P=.026). Conclusions Macrophage-rich areas are more frequently found in patients with unstable angina and non-Q-wave myocardial infarction. This suggests that macrophages are a marker of unstable atherosclerotic plaques and may play a significant role in the pathophysiology of acute coronary syndromes. C1 MASSACHUSETTS GEN HOSP,CARDIAC UNIT,CARDIOVASC PATHOL RES LAB,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RI Falk, Erling/A-7475-2015; Fuster, Valentin/H-4319-2015 OI Falk, Erling/0000-0001-8566-9974; Fuster, Valentin/0000-0002-9043-9986 NR 17 TC 804 Z9 844 U1 4 U2 16 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD AUG PY 1994 VL 90 IS 2 BP 775 EP 778 PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PA963 UT WOS:A1994PA96300019 PM 8044947 ER PT J AU MAILHAC, A BADIMON, JJ FALLON, JT FERNANDEZORTIZ, A MEYER, B CHESEBRO, JH FUSTER, V BADIMON, L AF MAILHAC, A BADIMON, JJ FALLON, JT FERNANDEZORTIZ, A MEYER, B CHESEBRO, JH FUSTER, V BADIMON, L TI EFFECT OF AN ECCENTRIC SEVERE STENOSIS ON FIBRIN(OGEN) DEPOSITION ON SEVERELY DAMAGED VESSEL WALL IN ARTERIAL THROMBOSIS - RELATIVE CONTRIBUTION OF FIBRIN(OGEN) AND PLATELETS SO CIRCULATION LA English DT Article DE FIBRIN(OGEN); THROMBOSIS; STENOSIS ID UNSTABLE ANGINA-PECTORIS; MYOCARDIAL-INFARCTION; ISCHEMIC DEATH; SHEAR RATE; FLOW; MODEL; FIBRINOGEN; DISEASE; HEPARIN; ATHEROSCLEROSIS AB Background Coronary thrombosis is a dynamic process dependent on the pathologi Methods and Results We investigated the effect of a severe (80%) eccentric stenosis on fibrin(ogen) interaction with a deeply damaged vessel wall, its relation to platelet deposition in thrombus formation, and the influence of time on thrombus growth. Porcine I-125-fibrinogen and autologous In-111-platelets were injected into pigs instrumented for extracorporeal circulation and treated with low-dose heparin (aPTT ratio <1.5) that has been previously shown and herein confirmed not to affect platelet and/or fibrin(ogen) attachment. Tunica media, as a model of severely injured vessel wall, was mounted in a tubular perfusion chamber containing an eccentric axisymmetric sinusoidal stenosis obstructing the lumen and exposed for 1, 5, and 10 minutes to perfusing blood. A shear rate of 424 s(-1) at the laminar, parallel parabolic local how perfused segments one to two orders of magnitude greater at the apex of the stenosis. Fibrin(ogen) deposition, its axial distribution with respect to the apex, and its relation to platelet deposition were determined by an ex vivo analysis of the test substrates. Fibrin(ogen) and platelet deposition were both significantly higher at the apex of the stenosis than at either the prestenotic or poststenotic area at all the studied perfusion times (P<.02). However, fibrin(ogen) deposition demonstrated a significantly smaller degree of increase from the prestenotic area to the apex as well as a smaller degree of decrease from the latter to the poststenotic region, compared with platelet deposition (P<.05). Although both fibrin(ogen) and platelet deposition increased over time, the ratio of fibrin(ogen) to platelets showed a progressive decrease that became significant from 5 to 10 minutes (P<.03) at either low or high shear rate. The rate of platelet deposition was relatively constant; however, fibrin(ogen) deposition progressively decreased, especially at the apex. Conclusions On severely damaged vessel wall, fibrin(ogen) and platelet deposition is maximal at the apex of the stenosis where shear rate is extremely high and parallel streamlines are deformed. Nevertheless, fibrin(ogen) deposition is significantly less dependent on high shear rate than is platelet deposition, and the pattern is not influenced by time. Finally, fibrin(ogen) deposition appears to be predominant in the thrombus layers adjacent to a severely damaged vessel wall regardless of the local shear stress levels and flow conditions. C1 HARVARD UNIV, MASSACHUSETTS GEN HOSP,SCH MED, CARDIOVASC BIOL RES LAB,CARDIAC UNIT, BOSTON, MA USA. RI BADIMON, LINA/O-4711-2014; Fuster, Valentin/H-4319-2015; Fernandez-Ortiz, Antonio/B-2227-2017 OI BADIMON, LINA/0000-0002-9162-2459; Fuster, Valentin/0000-0002-9043-9986; Fernandez-Ortiz, Antonio/0000-0002-3239-1910 FU NHLBI NIH HHS [HL-38933] NR 43 TC 104 Z9 104 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD AUG PY 1994 VL 90 IS 2 BP 988 EP 996 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PA963 UT WOS:A1994PA96300047 PM 8044972 ER PT J AU WINKELMAN, J ALTSCHULER, C GLENN, G LAESSIG, R GOLDSTEIN, D WERNER, M WILDING, P SILVERSTEIN, M KAMPA, I FIREMAN, B DAWSON, N MALKUS, H WITTE, D ROSMAN, A GARBER, C HOLTZMAN, N AF WINKELMAN, J ALTSCHULER, C GLENN, G LAESSIG, R GOLDSTEIN, D WERNER, M WILDING, P SILVERSTEIN, M KAMPA, I FIREMAN, B DAWSON, N MALKUS, H WITTE, D ROSMAN, A GARBER, C HOLTZMAN, N TI JAPANESE HEALTH-CARE SYSTEM - IN-VITRO DIAGNOSTIC-TESTS AND REIMBURSEMENTS - DISCUSSION SO CLINICAL CHEMISTRY LA English DT Discussion C1 ST JOSEPHS HOSP,MILWAUKEE,WI. MED COLL WISCONSIN,MILWAUKEE,WI 53226. WISCONSIN STATE LAB HYG,MADISON,WI. GEORGE WASHINGTON UNIV,MED CTR,WASHINGTON,DC 20052. HOSP UNIV PENN,PHILADELPHIA,PA 19104. MAYO CLIN & MAYO FDN,DEPT MED,DIV AREA GEN INTERNAL MED,ROCHESTER,MN 55905. MAYO CLIN & MAYO FDN,DEPT HLTH SCI RES,CLIN EPIDEMIOL SECT,ROCHESTER,MN 55905. CASE WESTERN RESERVE UNIV,CLEVELAND,OH. YALE NEW HAVEN MED CTR,NEW HAVEN,CT 06504. BRONX VET AFFAIRS MED CTR,CTR ALCOHOL RES & TREATMENT,NEW YORK,NY 10468. CUNY MT SINAI SCH MED,NEW YORK,NY 10468. JOHNS HOPKINS MED INST,BALTIMORE,MD 21205. KAISER PERMANENTE MED CTR,LOS ANGELES,CA. RP WINKELMAN, J (reprint author), HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT CLIN LABS,ADM LAB,75 FRANCIS ST,BOSTON,MA 02115, USA. 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 AUG PY 1994 VL 40 IS 8 BP 1668 EP 1670 PG 3 WC Medical Laboratory Technology SC Medical Laboratory Technology GA PA073 UT WOS:A1994PA07300052 ER PT J AU TALAL, N AF TALAL, N TI CONCLUDING REMARKS - AUTOGENES AND ONCOGENES SO CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY LA English DT Editorial Material ID FAS MESSENGER-RNA; LPR MICE; AUTOIMMUNE-DISEASE; APOPTOSIS; EXPRESSION; INSERTION; ANTIGEN; GENES; ETN C1 AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX. RP TALAL, N (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT MED,CLIN IMMUNOL SECT,SAN ANTONIO,TX 78284, USA. FU NIDCR NIH HHS [DEO 9311] NR 15 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0090-1229 J9 CLIN IMMUNOL IMMUNOP JI Clin. Immunol. Immunopathol. PD AUG PY 1994 VL 72 IS 2 BP 208 EP 209 DI 10.1006/clin.1994.1132 PG 2 WC Immunology; Pathology SC Immunology; Pathology GA PB324 UT WOS:A1994PB32400013 PM 8050195 ER PT J AU LEE, YS GUINAN, E AF LEE, YS GUINAN, E TI NEW CYTOKINES WITH THROMBOPOIETIC ACTIVITY - POTENTIAL ROLE IN THERAPY SO CLINICAL IMMUNOTHERAPEUTICS LA English DT Review ID COLONY-STIMULATING FACTOR; STEM-CELL FACTOR; RECOMBINANT HUMAN INTERLEUKIN-3; LEUKEMIA INHIBITORY FACTOR; C-KIT LIGAND; INVITRO HUMAN MEGAKARYOCYTOPOIESIS; HEMATOPOIETIC GROWTH-FACTORS; CONGENITAL AMEGAKARYOCYTIC THROMBOCYTOPENIA; BONE-MARROW; GM-CSF AB The use of growth factors to stimulate haemopoietic proliferation in various clinical conditions such as renal failure-associated anaemia, post-chemotherapy cytopenia and enhancement of bone marrow engraftment has been well described. Of the 3 haemopoietic lineages, the use of growth factors has been most beneficial in the erythroid and myeloid compartments. Currently, there are no cytokines available specifically for the purpose of stimulating thrombopoiesis. However, expanding knowledge of haemopoiesis in general and megakaryocytopoiesis in particular has led to an appreciation of the fact that multiple growth factors with overlapping or specific activities are involved in various stages of megakaryocyte proliferation and differentiation. Although application of early acting, multilineage cytokines such as interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF) and stem cell factor (SCF) has resulted in significant augmentation of thrombopoiesis in vitro, little such activity has been seen in vivo. The IL-3/GM-CSF fusion protein PIXY-321 (pixykine), also active in vitro, similarly has limited thrombopoietic effect in vivo. On the other hand, interleukin-6 (IL-6) and, in early studies, interleukin-11 (IL-11), which both augment IL-3-dependent progenitor proliferation and have significant megakaryocytopoietic activity in vitro, produce a more pronounced thrombopoietic effect. Further analyses and trials will be required to establish proper cytokine dosages, regimens and combinations in order to achieve maximal platelet enhancement. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PEDIAT ONCOL,44 BINNEY ST,BOSTON,MA 02115. CHILDRENS HOSP MED CTR,DEPT HEMATOL,BOSTON,MA 02115. NR 102 TC 2 Z9 2 U1 0 U2 0 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 1172-7039 J9 CLIN IMMUNOTHER JI Clin. Immunother. PD AUG PY 1994 VL 2 IS 2 BP 100 EP 108 PG 9 WC Immunology; Pharmacology & Pharmacy SC Immunology; Pharmacology & Pharmacy GA PA706 UT WOS:A1994PA70600004 ER PT J AU HIBBERD, PL RUBIN, RH AF HIBBERD, PL RUBIN, RH TI CLINICAL ASPECTS OF FUNGAL INFECTION IN ORGAN TRANSPLANT RECIPIENTS SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID RENAL-ALLOGRAFT RECIPIENTS; ORTHOTOPIC LIVER-TRANSPLANTATION; PNEUMOCYSTIS-CARINII INFECTION; CYTOMEGALO-VIRUS DISEASE; TRIMETHOPRIM-SULFAMETHOXAZOLE; HEART-LUNG; CARDIAC TRANSPLANTATION; INVASIVE ASPERGILLOSIS; CYCLOSPORINE; KETOCONAZOLE AB Fungal infections following solid organ transplantation remain a major cause of morbidity and mortality. Candida species and Aspergillus fumigatus continue to account for the majority of these infections, although the attack rate is higher among recipients of organs other than kidneys because those patients receive more immunosuppressive therapy. Although amphotericin B remains the drug of choice for treatment of invasive aspergillosis, its toxicity profile limits its widespread use. Recent experience suggests that fluconazole may be a safe and effective alternative for the treatment of fungal infections caused by Candida species or Cryptococcus neoformans. Prevention of fungal infections remains one of the most important goals in the field of transplantation. New approaches-such as the use of ''preemptive therapy,'' or prophylaxis, for patients at greatest risk of developing infection-may assist in attainment of this goal. C1 MASSACHUSETTS GEN HOSP,TRANSPLANT UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. HARVARD UNIV,MIT,CTR EXPTL PHARMACOL & THERAPEUT,DIV HLTH SCI & TECHNOL,CAMBRIDGE,MA 02139. RP HIBBERD, PL (reprint author), MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,32 FRUIT ST,BOSTON,MA 02114, USA. NR 65 TC 57 Z9 58 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD AUG PY 1994 VL 19 SU 1 BP S33 EP S40 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA PC397 UT WOS:A1994PC39700006 PM 7948569 ER PT J AU HUQUE, T BRAND, JG AF HUQUE, T BRAND, JG TI NITRIC-OXIDE SYNTHASE ACTIVITY OF THE TASTE ORGAN OF THE CHANNEL CATFISH, ICTALURUS-PUNCTATUS SO COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY B-BIOCHEMISTRY & MOLECULAR BIOLOGY LA English DT Article DE NITRIC OXIDE SYNTHASE; TASTE ORGAN; ICTALURUS PUNCTATUS ID L-ARGININE; BINDING; CEREBELLUM; CYCLASE; SYSTEM; CELLS AB The constitutive nitric oxide synthase activity of the catfish taste organ (barbel) was characterized, using the conversion of L-[H-3]arginine to L-[H-3]citrulline as the index of enzyme activity. The enzyme was dependent on Ca2+ (but not calmodulin) and NADPH (but not FAD). Activity was moderately enhanced by tetrahydrobiopterin. Kinetic parameters were K-m = 22 mu M and V-max = 25 pmol/min/mg. The enzyme was inhibited by N-G-monomethyl-L-arginine (half-maximally at 3 mu M) and N-G-nitro-L-arginine (half-maximally at 50 mu M), and also by sodium nitroprusside and superoxide dismutase. In the presence of millimolar levels of the taste stimulus L-alanine, nitric oxide synthase activity was increased by up to 3-fold, with activation of the enzyme being reversed by N-G-monomethyl-L-arginine. There was no activation of guanylyl cyclase by L-alanine. These data indicate that a constitutive nitric oxide synthase activity is present in the catfish taste organ and that, therefore, nitric oxide may have a role in the biochemical mechanisms underlying taste perception. C1 UNIV PENN,VET AFFAIRS MED CTR,PHILADELPHIA,PA 19104. UNIV PENN,SCH DENT MED,DEPT BIOCHEM,PHILADELPHIA,PA 19104. RP HUQUE, T (reprint author), MONELL CHEM SENSES CTR,3500 MARKET ST,PHILADELPHIA,PA 19104, USA. NR 23 TC 11 Z9 12 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0305-0491 J9 COMP BIOCHEM PHYS B JI Comp. Biochem. Physiol. B-Biochem. Mol. Biol. PD AUG PY 1994 VL 108 IS 4 BP 481 EP 486 DI 10.1016/0305-0491(94)90101-5 PG 6 WC Biochemistry & Molecular Biology; Zoology SC Biochemistry & Molecular Biology; Zoology GA PK631 UT WOS:A1994PK63100010 ER PT J AU GARCIA, C SALADINO, R THOMPSON, C HAMMER, B PARSONNET, J WAINWRIGHT, N NOVITSKY, T FLEISHER, GR SIBER, G AF GARCIA, C SALADINO, R THOMPSON, C HAMMER, B PARSONNET, J WAINWRIGHT, N NOVITSKY, T FLEISHER, GR SIBER, G TI EFFECT OF A RECOMBINANT ENDOTOXIN-NEUTRALIZING PROTEIN ON ENDOTOXIN-SHOCK IN RABBITS SO CRITICAL CARE MEDICINE LA English DT Article DE ENDOTOXIN; LIPOPOLYSACCHARIDE; TUMOR NECROSIS FACTOR; SHOCK; SEPSIS; GRAM-NEGATIVE BACTERIA; ESCHERICHIA COLI; INFECTION; ANIMAL MODEL; CRITICAL ILLNESS ID TUMOR-NECROSIS-FACTOR; NEGATIVE BACTERIAL SEPSIS; LIMULUS ANTILIPOPOLYSACCHARIDE FACTOR; ESCHERICHIA-COLI; SEPTIC SHOCK; MONOCLONAL-ANTIBODY; FACTOR-ALPHA; MENINGOCOCCAL ENDOTOXIN; HORSESHOE-CRAB; IGG ANTIBODY AB Objectives: Limulus anti-lipopolysaccharide factor, an 11.8-kilodalton peptide isolated from amebocytes of Limulus polyphemus inhibits the biologic activities of endotoxin in vitro, including gelation of Limulus amebocyte lysate. A recombinant version of limulus anti-lipopolysaccharide factor, termed endotoxin neutralizing protein, has now been expressed in yeast. Endotoxin-neutralizing protein was evaluated for its potential prophylactic and therapeutic effects in rabbits challenged with Escherichia coli endotoxin. Design: Controlled animal trial. Setting: Animal research laboratory. Subjects: A total of 112 New Zealand white rabbits were studied. Interventions: Rabbits were challenged with an LD80 dose of E. coli endotoxin (100 mu g/kg); control animals (n = 52) were treated with saline solution at the time of endotoxin challenge; experimental animals received endotoxin-neutralizing protein 2.5 mg/kg prechallenge (n 20), 5.0 mg/kg prechallenge (n = 20), or 5.0 mg/kg 30 mins postchallenge (n = 20). C1 HARVARD UNIV,CHILDRENS HOSP,SCH MED,DEPT MED,DIV EMERGENCY MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,INFECT DIS LAB,BOSTON,MA 02115. DARTMOUTH HITCHCOCK MED CTR,DEPT MED,DIV INFECT DIS,LEBANON,NH. ASSOCIATES CAPE COD INC,WOODS HOLE,MA. RI Hammer, Brian/I-7282-2013 FU NIAID NIH HHS [AI18125] NR 41 TC 25 Z9 25 U1 0 U2 0 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 AUG PY 1994 VL 22 IS 8 BP 1211 EP 1218 DI 10.1097/00003246-199408000-00003 PG 8 WC Critical Care Medicine SC General & Internal Medicine GA PA247 UT WOS:A1994PA24700003 PM 8045139 ER PT J AU KACMAREK, RM MANG, H BARKER, N CYCYKCHAPMAN, MC AF KACMAREK, RM MANG, H BARKER, N CYCYKCHAPMAN, MC TI EFFECTS OF DISPOSABLE OR INTERCHANGEABLE POSITIVE END-EXPIRATORY PRESSURE VALVES ON WORK OF BREATHING DURING THE APPLICATION OF CONTINUOUS POSITIVE AIRWAY PRESSURE SO CRITICAL CARE MEDICINE LA English DT Article DE POSITIVE END-EXPIRATORY PRESSURE; WORK OF BREATHING; CONTINUOUS POSITIVE AIRWAY PRESSURE; LUNG MODEL; LUNGS; CRITICAL ILLNESS; RESPIRATORY THERAPY; MECHANICAL VENTILATION; ARTIFICIAL RESPIRATION; APPARATUS AND INSTRUMENTS ID FLOW RESISTANCE; INSPIRATORY WORK; SYSTEMS; DEVICES AB Objective: To determine which of a series of disposable or interchangeable positive end-expiratory pressure (PEEP) devices functions with the least imposition of inspiratory and expiratory work during continuous positive airway pressure. Design: Prospective laboratory evaluation performed on a lung model. Setting: Research laboratory at a university medical center. Interventions: A spontaneously breathing lung model, created from a training test lung and a volume ventilator, were used to simulate a patient spontaneously breathing at a tidal volume of 0.4 L, peak inspiratory flow of 40 L/ min, an inspiration/expiration ratio of 1:2, and a respiratory rate of 20 breaths/min. Ten PEEP valves attached to a continuous high-flow system were evaluated. Measurements and Main Results: Ah of the PEEP valves studied imposed high levels of both inspiratory and expiratory work of breathing. The BE-171 and BE-142 valves (Instrumentation Industries) imposed the least amount of inspiratory work. In general, imposed inspiratory work accounted for similar to 70% to 80% of total imposed work of breathing. Conclusions: All of the disposable/interchangeable PEEP valves that were studied imposed a considerable amount of both inspiratory and expiratory work, even when the continuous flow provided exceeded the peak inspiratory flow demands of the lung model. The primary reason for the high imposed work levels is the high gas-flow resistance of all of the valves studied. C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIOL,BOSTON,MA 02114. UNIV ERLANGEN NURNBERG,DEPT ANESTHESIOL,W-8520 ERLANGEN,GERMANY. UNIV ERLANGEN NURNBERG,RESP CARE SERV,W-8520 ERLANGEN,GERMANY. RP KACMAREK, RM (reprint author), MASSACHUSETTS GEN HOSP,RESP CARE SERV,ELLISON 4,BOSTON,MA, USA. NR 13 TC 11 Z9 11 U1 0 U2 0 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 AUG PY 1994 VL 22 IS 8 BP 1219 EP 1226 DI 10.1097/00003246-199408000-00004 PG 8 WC Critical Care Medicine SC General & Internal Medicine GA PA247 UT WOS:A1994PA24700004 PM 8045140 ER PT J AU HOO, GWS SANTIAGO, S WILLIAMS, AJ AF HOO, GWS SANTIAGO, S WILLIAMS, AJ TI NASAL MECHANICAL VENTILATION FOR HYPERCAPNIC RESPIRATORY-FAILURE IN CHRONIC OBSTRUCTIVE PULMONARY-DISEASE - DETERMINANTS OF SUCCESS AND FAILURE SO CRITICAL CARE MEDICINE LA English DT Article DE ARTIFICIAL RESPIRATION; CHRONIC OBSTRUCTIVE PULMONARY DISEASE; HYPERCAPNIA; INTENSIVE CARE UNITS; INTERMITTENT POSITIVE PRESSURE VENTILATION; MECHANICAL VENTILATION; RESPIRATORY INSUFFICIENCY; TIDAL VOLUME; CRITICAL ILLNESS; PULMONARY EMERGENCIES; SEVERITY OF ILLNESS INDEX ID POSITIVE PRESSURE VENTILATION; FACE MASK; ACUTE EXACERBATIONS; COPD; COMPLICATIONS; SUPPORT; SYSTEM AB Objectives: To evaluate the efficacy of nasal mechanical ventilation in patients with chronic obstructive pulmonary disease and hypercapnic respiratory failure and to identify predictors of success or failure of nasal mechanical ventilation. Design: Prospective case series. Setting: Medical intensive care unit in Veterans Administration Medical Center. Patients: Twelve chronic obstructive pulmonary disease patients treated during 14 episodes of hypercapnic respiratory failure. Interventions: Nasal mechanical ventilation in addition to conventional therapy to treat hypercapnic respiratory failure. Patients underwent nasal mechanical ventilation for at least 30 mins, or longer if the therapy was tolerated. Responses to therapy and arterial blood gases were monitored. Measurements and Main Results: Half of the episodes were successfully treated with nasal mechanical ventilation. There were no differences in age, prior pulmonary function, baseline arterial blood gases, admission arterial blood gases, or respiratory rate between those patients successfully treated and those patients who failed nasal mechanical ventilation. Unsuccessfully treated patients appeared to have a greater severity of illness than successfully treated patients, as indicated by a higher Acute Physiology and Chronic Health Evaluation II score (mean 21 +/- 4 [SD] vs. 15 +/- 4; p = .02). Unsuccessfully treated patients were edentulous, had pneumonia or excess secretions, and had pursed-lip breathing, factors that prevented adequate mouth seal and contributed to greater mouth leaks than in successfully treated patients (the mean volume of the mouth leak was 314 +/- 107 vs. 100 +/- 70 mL; p < .01). Successfully treated patients were able to adapt more rapidly to the nasal mask and ventilator, with greater and more rapid reduction in Paco(2), correction of pH, and reduction in respiratory rate. Conclusions: Patients who failed nasal mechanical ventilation appeared to have a greater severity of illness; they were unable to minimize the amount of mouth leak (because of lack of teeth, secretions, or breathing pattern) and were unable to coordinate with the ventilator. These features may allow identification of poor candidates for nasal mechanical ventilation, avoiding unnecessary delays in endotracheal intubation and mechanical ventilation. C1 W LOS ANGELES VET AFFAIRS MED CTR,RES SERV,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA. RP HOO, GWS (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,MED SERV,PULM & CRIT CARE SECT W111Q,WILSHIRE & SAWTELLE BLVD,LOS ANGELES,CA 90073, USA. NR 23 TC 92 Z9 96 U1 1 U2 1 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 AUG PY 1994 VL 22 IS 8 BP 1253 EP 1261 PG 9 WC Critical Care Medicine SC General & Internal Medicine GA PA247 UT WOS:A1994PA24700009 ER PT J AU SCHULZ, JB BEAL, MF AF SCHULZ, JB BEAL, MF TI MITOCHONDRIAL DYSFUNCTION IN MOVEMENT-DISORDERS SO CURRENT OPINION IN NEUROLOGY LA English DT Article ID COMPLEX-I DEFICIENCY; RESPIRATORY-CHAIN ACTIVITY; ELECTRON-TRANSPORT CHAIN; PARKINSONS-DISEASE; HUNTINGTONS-DISEASE; HUMAN BRAIN; SKELETAL-MUSCLE; DNA; AGE; DEFECT AB A major theory regarding the mechanism of neuronal degeneration in several movement disorders is that mitochondrial defects may play a role. Biochemical studies in Parkinson's disease, Huntington's disease, multiple system atrophy, and idiopathic dystonia have shown defects in enzymes of oxidative phosphorylation in postmortem brain tissue, platelets, muscle, or lymphocytes. The basal ganglia and substantia nigra are also particularly susceptible to the accumulation of age-dependent mitochondrial DNA deletions, which may contribute to the delayed onset of movement disorders. The 1-methyl-4-phenyl 1,2,3,6-tetrahydro-pyridine model of Parkinson's disease involves conversion to 1-methyl-4-phenylpyridinium, which then inhibits complex I of the electron transport chain. Our studies show that the complex II inhibitor 3-nitropropionic acid can closely replicate the neurochemical, histologic, and clinical features of Huntington's disease. The mechanism of neuronal death in both these models may be slow excitotoxicity. Both direct biochemical studies and animal models of movement disorders therefore suggest that mitochondrial dysfunction may play a direct role in their pathogenesis. C1 MASSACHUSETTS GEN HOSP,NEUROL SERV,WARREN 408,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RI Schulz, Jorg/D-9786-2012 OI Schulz, Jorg/0000-0002-8903-0593 FU NINDS NIH HHS [NS 10828, NS 31579]; PHS HHS [16367] NR 61 TC 74 Z9 74 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 1350-7540 J9 CURR OPIN NEUROL JI Curr. Opin. Neurol. PD AUG PY 1994 VL 7 IS 4 BP 333 EP 339 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA PA834 UT WOS:A1994PA83400010 PM 7952242 ER PT J AU CHAPMAN, KB SZOSTAK, JW AF CHAPMAN, KB SZOSTAK, JW TI IN-VITRO SELECTION OF CATALYTIC RNAS SO CURRENT OPINION IN STRUCTURAL BIOLOGY LA English DT Article ID COMPLEMENTARY-STRAND RNA; INVITRO SELECTION; HAIRPIN RIBOZYME; EVOLUTION; TEMPLATE; LIGANDS; ENZYME AB In vitro selection techniques are poised to allow a rapid expansion of the study of catalysis by RNA enzymes (ribozymes). This truly molecular version of genetics has already been applied to the study of the structures of known ribozymes and to the tailoring of their catalytic activity to meet specific requirements of substrate specificity or reaction conditions. During the past year, in vitro selection has been successfully used to isolate novel RNA catalysts from random sequence pools. RP CHAPMAN, KB (reprint author), MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114, USA. NR 22 TC 50 Z9 50 U1 1 U2 3 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0959-440X J9 CURR OPIN STRUC BIOL JI Curr. Opin. Struct. Biol. PD AUG PY 1994 VL 4 IS 4 BP 618 EP 622 DI 10.1016/S0959-440X(94)90227-5 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QB256 UT WOS:A1994QB25600020 PM 11539575 ER PT J AU KAHN, CR AF KAHN, CR TI INSULIN ACTION, DIABETOGENES, AND THE CAUSE OF TYPE-II DIABETES SO DIABETES LA English DT Review ID RECEPTOR TYROSINE KINASE; PHOSPHATIDYLINOSITOL 3-KINASE ACTIVITY; HUMAN SKELETAL-MUSCLE; PROTEIN S6 KINASE; ENDOGENOUS SUBSTRATE PHOSPHORYLATION; SERINE THREONINE KINASES; GROWTH-FACTOR; BETA-SUBUNIT; SIGNAL-TRANSDUCTION; GLUCOSE-TRANSPORT C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. RP KAHN, CR (reprint author), JOSLIN DIABET CTR,ROOM 620,1 JOSLIN PL,BOSTON,MA 02215, USA. FU NIDDK NIH HHS [DK-31036, DK-33201] NR 236 TC 703 Z9 718 U1 5 U2 44 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD AUG PY 1994 VL 43 IS 8 BP 1066 EP 1084 PG 19 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NZ022 UT WOS:A1994NZ02200018 PM 8039601 ER PT J AU JAVITT, JC AIELLO, LP CHIANG, YP FERRIS, FL CANNER, JK GREENFIELD, S AF JAVITT, JC AIELLO, LP CHIANG, YP FERRIS, FL CANNER, JK GREENFIELD, S TI PREVENTIVE EYE CARE IN PEOPLE WITH DIABETES IS COST-SAVING TO THE FEDERAL-GOVERNMENT - IMPLICATIONS FOR HEALTH-CARE REFORM SO DIABETES CARE LA English DT Article ID TREATING RETINOPATHY; 4-YEAR INCIDENCE; DIAGNOSIS; MELLITUS; AGE; PHOTOCOAGULATION; PROGRESSION; PREVALENCE; SEVERITY; DISEASE AB OBJECTIVE - Diabetic retinopathy, which leads to macular edema and retinal neovascularization, is the leading cause of blindness among working-age Americans. Previous research has demonstrated significant cost savings associated with detection of eye disease in Americans with type I diabetes. However, detection and treatment of eye disease among those with type II diabetes was previously thought not to be test-saving. Our purpose was to estimate the current and potential federal savings resulting from the screening and treatment of retinopathy in patients with type II diabetes, based on recently available data concerning efficacy of treating both macular edema and neovascularization along with new data on federal budgetary costs of blindness. RESEARCH DESIGN AND METHODS - We used computer modeling, incorporating data from population-based epidemiological studies and multicenter clinical trials. Monte Carlo simulation was used, combined with sensitivity analysis and present value analysis of cost savings. RESULTS - Screening and treatment for eye disease in patients with type II diabetes generates annual savings of $247.9 million to the federal budget and 53,986 person-years of sight, even at current suboptimal (60%) levels of care. If all patients with type II diabetes receive recommended care, the predicted net savings (discounted at 5%) exceeds $472.1 million and 94,304 person-years of sight. Nearly all savings are associated with detection and treatment of diabetic macular edema. Enrolling each additional person with type II diabetes into currently recommended ophthalmological care results in an average net savings of $975/person, even if all costs of care are borne by the federal government. CONCLUSIONS - Our analysis indicates that prevention programs aimed at improving eye care for patients with diabetes not only reduce needless vision loss but also will provide a financial return on the investment of public funds. C1 JOHNS HOPKINS UNIV, WILMER OPHTHALMOL INST, BALTIMORE, MD 21218 USA. JOSLIN DIABET CTR, BEETHAM EYE INST, BOSTON, MA 02215 USA. NEI, OFF BIOMETRY, BETHESDA, MD 20892 USA. TUFTS UNIV NEW ENGLAND MED CTR, INST HLTH, DIABET PORT PROJECT, BOSTON, MA 02111 USA. RP JAVITT, JC (reprint author), GEORGETOWN UNIV, MED CTR, CTR SIGHT, WORTHEN CTR EYE CARE RES, 3800 RESERVOIR RD NW, WASHINGTON, DC 20007 USA. FU AHRQ HHS [P01-HS08005]; NEI NIH HHS [R21-EY07744, R0I-EYO8805] NR 52 TC 210 Z9 212 U1 0 U2 7 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD AUG PY 1994 VL 17 IS 8 BP 909 EP 917 DI 10.2337/diacare.17.8.909 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NY359 UT WOS:A1994NY35900023 PM 7956643 ER PT J AU LANG, J NISHIMOTO, I OKAMOTO, T WELLER, U WOLLHEIM, CB AF LANG, J NISHIMOTO, I OKAMOTO, T WELLER, U WOLLHEIM, CB TI HETEROTRIMERIC G-PROTEINS MEDIATE DIRECT INHIBITION OF EXOCYTOSIS IN INSULIN-SECRETING CELL-LINES SO DIABETOLOGIA LA English DT Meeting Abstract C1 UNIV GENEVA,DIV BIOCHIM CLIN,GENEVA,SWITZERLAND. HARVARD UNIV,MASSACHUSETTS GEN HOSP EAST,BOSTON,MA. UNIV MAINZ,INST MED MIKROBIOL,MAINZ,GERMANY. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 37 SU 1 BP A76 EP A76 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PB881 UT WOS:A1994PB88100292 ER PT J AU JEAN, A REISS, A DESROCHERS, M DUBOIS, S TROTTIER, E TROTTIER, Y WIRTANEN, L ADESNIK, M WAXMAN, DJ ANDERSON, A AF JEAN, A REISS, A DESROCHERS, M DUBOIS, S TROTTIER, E TROTTIER, Y WIRTANEN, L ADESNIK, M WAXMAN, DJ ANDERSON, A TI RAT-LIVER CYTOCHROME-P450 2B3 - STRUCTURE OF THE CYP2B3 GENE AND IMMUNOLOGICAL IDENTIFICATION OF A CONSTITUTIVE P450 2B3-LIKE PROTEIN IN RAT-LIVER SO DNA AND CELL BIOLOGY LA English DT Article ID PHENOBARBITAL-INDUCIBLE CYTOCHROME-P-450; POLYMERASE CHAIN-REACTION; MESSENGER-RNA; ALPHA-1-FETOPROTEIN GENE; TRANSCRIPTION FACTORS; NUCLEOTIDE-SEQUENCE; CODING SEQUENCES; MAMMALIAN-CELLS; NUCLEAR FACTOR; BINDING-SITES AB The cytochrome P450 2B subfamily in the rat contains an estimated eight to eleven members at the genomic level. Synthesis in the liver of the prototypic forms P450 2B1 and P450 2B2 is dramatically induced by phenobarbital. The 1.9-kb mRNA for P450 2B3, a third member of the P450 2B subfamily, is constitutively present in rat liver but is not inducible by phenobarbital. We have now cloned and sequenced exonic sequences corresponding to the entire 2B3 mRNA and determined their exon-intron structure, which is identical to that of CYP2B1/CYP2B2 and other CYP2B genes. A putative CYP2B3 transcription start site was identified and CYP2B3 5'- and 3'-flanking sequences were compared to those of CYP2B1 and CYP2B2. CYP2B3, like CYP2B1 and CYP2B2, has a modified TATA box preceding the transcription start site and lacks the canonical polyadenylation signal preceding the poly(A) site. A 2B3 expression vector, pMT2-2B3, directed the synthesis in COS-1 cells of an similar to 50-kD protein detectable on Western blots with a polyclonal antibody and with one of four monoclonal antibodies raised against 2B1 but not with a polyclonal antibody raised against P450 PB6. The 2B3 protein migrated with a slightly higher electrophoretic mobility than 2B1 acid comigrated with a protein detected by anti-2B1 antibodies in liver microsomes from untreated rats. The results indicate that a 2B3-like protein is present in rat liver and that it is distinct from P450 PB6 and other known constitutive rat hepatic P450s. C1 NYU,MED CTR,DEPT CELL BIOL,NEW YORK,NY 10016. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. UNIV LAVAL,DEPT BIOL,QUEBEC CITY G1K 7P4,PQ,CANADA. UNIV LAVAL,HOTEL DIEU,CTR RECH CANCEROL,QUEBEC CITY G1R 2J6,PQ,CANADA. RI Trottier, Yvon/H-8852-2016 FU NIDDK NIH HHS [DK33765]; NIGMS NIH HHS [GM-30701] NR 82 TC 19 Z9 19 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD AUG PY 1994 VL 13 IS 8 BP 781 EP 792 DI 10.1089/dna.1994.13.781 PG 12 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA PE756 UT WOS:A1994PE75600001 PM 8068203 ER PT J AU CLOUSTON, PD KIERS, L ZUNIGA, G CROS, D AF CLOUSTON, PD KIERS, L ZUNIGA, G CROS, D TI QUANTITATIVE-ANALYSIS OF THE COMPOUND MUSCLE ACTION-POTENTIAL IN EARLY ACUTE INFLAMMATORY DEMYELINATING POLYNEUROPATHY SO ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY LA English DT Article DE COMPOUND MUSCLE ACTION POTENTIAL; DEMYELINATION; GUILLAIN-BARRE SYNDROME; POLYNEUROPATHY ID GUILLAIN-BARRE-SYNDROME; PROXIMAL CONDUCTION BLOCK; ELECTRODIAGNOSTIC ABNORMALITIES; PROGNOSTIC VALUE; PATTERNS; NERVE; SENSITIVITY AB We quantitated the size and configuration of compound muscle action potentials (CMAPs) in 266 nerves (66 median, 67 ulnar, 71 tibial and 62 peroneal) of 72 patients with acute inflammatory demyelinating polyneuropathy (AIDP) initially studied within 19 days of symptom onset. Results were compared with criteria for CMAP abnormalities, including criteria for abnormal negative peak duration and desynchronisation, derived from a control population of 50 median, ulnar, tibial and peroneal nerves. Other motor conduction abnormalities including minimal F response latency were also examined. We also analysed patterns of CMAP abnormality, peak disability and outcome for AIDP patients who had at least 3 motor nerves evaluated at first electrophysiologic study. Amongst AIDP nerves, low-amplitude of the distal CMAP, usually with prolonged distal latency, was much more common than an abnormal fall in CMAP amplitude between stimulus sites. Using our CMAP criteria more than half of these low amplitude distal responses showed prolonged negative peak duration or desynchronisation or both, consistent with demyelination. Of the 47 AIDP patients who had 3 or more motor nerves initially studied, 37 (78.7%) had at least 1 motor nerve with a distal CMAP showing evidence of temporal dispersion. In addition, those with at least 75% of motor nerves showing a pattern of low amplitude of the distal CMAP without a further significant fall in amplitude between stimulus sites had greater peak disability and a poorer outcome. Assessment of temporal dispersion of the distal CMAP should be included in electrophysiologic criteria for acute demyelination. In addition, for some patients with AIDP patterns of CMAP amplitude abnormality amongst motor nerves are present early in the illness and may provide prognostic information. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,ELECTROMYOG LAB,BOSTON,MA 02114. NR 32 TC 28 Z9 28 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0013-4694 J9 ELECTROEN CLIN NEURO JI Electroencephalogr. Clin. Neurophysiol. PD AUG PY 1994 VL 93 IS 4 BP 245 EP 254 DI 10.1016/0168-5597(94)90026-4 PG 10 WC Engineering, Biomedical; Clinical Neurology SC Engineering; Neurosciences & Neurology GA PE752 UT WOS:A1994PE75200001 PM 7521284 ER PT J AU KIERS, L CLOUSTON, P ZUNIGA, G CROS, D AF KIERS, L CLOUSTON, P ZUNIGA, G CROS, D TI QUANTITATIVE STUDIES OF F-RESPONSES IN GUILLAIN-BARRE-SYNDROME AND CHRONIC INFLAMMATORY DEMYELINATING POLYNEUROPATHY SO ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY LA English DT Article DE F WAVES; DEMYELINATING NEUROPATHY; GUILLAIN-BARRE SYNDROME; CHRONIC INFLAMMATORY DEMYELINATING POLYNEUROPATHY ID ACUTE IDIOPATHIC POLYNEURITIS; ELECTRODIAGNOSTIC ABNORMALITIES; CONDUCTION-VELOCITY; PROXIMAL CONDUCTION; EVOKED-POTENTIALS; PROGNOSTIC VALUE; WAVE; NERVE; CHRONODISPERSION; NEUROPATHIES AB We examined F wave mean and minimum latency, mean and maximum amplitude, duration, persistence and chronodispersion in 241 nerves from 78 patients with Guillain-Barre syndrome (GBS) and 162 nerves from 43 patients with chronic inflammatory demyelinating polyneuropathy (CIDP). Results were compared with normal criteria derived from 72 median, 73 ulnar and 73 tibial control nerves, to determine the relative diagnostic sensitivity of the various F wave parameters. F wave abnormalities were found in 92% and 95% of nerves of patients with GBS and CIDP respectively. Absence of F responses or prolongation of minimum and mean latency were the most frequent abnormalities in both groups. Forty-five (11.2%) nerves overall had absent F responses with normal compound muscle action potential (CMAP) amplitudes and no significant fall between stimulus sites, consistent with isolated proximal conduction block. Forty-four nerves (23.7% of nerves in which F waves were present) fulfilled minimum F latency criteria for acquired demyelination. Eighty-one (20.1%) nerves had normal conventional motor nerve conduction studies and abnormal F responses, not all of which were identified by assessing only F absence or minimum-latency. Severity of F wave abnormalities did not correlate with clinical outcome. Our findings confirm the high frequency of proximal nerve lesions in early GBS and CIDP, not all of which are associated with distal motor conduction abnormalities, and suggest that assessment of multiple F wave parameters, in particular chronodispersion, mean latency and mean amplitude (in addition to absence and minimum latency), increases the yield of F wave studies. C1 MASSACHUSETTS GEN HOSP,CLIN NEUROPHYSIOL LABS,BOSTON,MA 02114. NR 40 TC 50 Z9 52 U1 1 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0013-4694 J9 ELECTROEN CLIN NEURO JI Electroencephalogr. Clin. Neurophysiol. PD AUG PY 1994 VL 93 IS 4 BP 255 EP 264 DI 10.1016/0168-5597(94)90027-2 PG 10 WC Engineering, Biomedical; Clinical Neurology SC Engineering; Neurosciences & Neurology GA PE752 UT WOS:A1994PE75200002 PM 7521285 ER PT J AU DULGEROFF, AJ HERSHMAN, JM AF DULGEROFF, AJ HERSHMAN, JM TI MEDICAL THERAPY FOR DIFFERENTIATED THYROID-CARCINOMA SO ENDOCRINE REVIEWS LA English DT Review ID TUMOR-NECROSIS-FACTOR; DOXORUBICIN PLUS CISPLATIN; CELL-MEDIATED-IMMUNITY; SERUM THYROGLOBULIN; RADIOACTIVE IODINE; CONCISE COMMUNICATION; I-131 THERAPY; IMMUNOLOGICAL ASPECTS; PAPILLARY CARCINOMA; HOSPITAL EXPERIENCE C1 W LOS ANGELES VET AFFAIRS MED CTR,DIV ENDOCRINOL & METAB W111D,LOS ANGELES,CA 90073. RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X NR 121 TC 56 Z9 58 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD AUG PY 1994 VL 15 IS 4 BP 500 EP 515 PG 16 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PD217 UT WOS:A1994PD21700007 PM 7988483 ER PT J AU SCHNEYER, AL RZUCIDLO, DA SLUSS, PM CROWLEY, WF AF SCHNEYER, AL RZUCIDLO, DA SLUSS, PM CROWLEY, WF TI CHARACTERIZATION OF UNIQUE BINDING-KINETICS OF FOLLISTATIN AND ACTIVIN OR INHIBIN IN SERUM SO ENDOCRINOLOGY LA English DT Article ID FOLLICULAR-FLUID; GRANULOSA-CELLS; GROWTH-FACTOR; PROTEIN; EXPRESSION; PITUITARY; RECEPTOR; CLONING; KINASE; BETA AB Serum binding proteins (BPs) have been identified for several peptide and protein hormones, and their presence has significant implications for the biological action of the hormone. Follistatin (FS) has been identified as an activin- and inhibin-BP in tissues, serum, and follicular fluid of several species, including humans. In this study, the binding kinetics of FS for activin and inhibin were characterized in human serum using gel filtration chromatography and compared to those of pure recombinant hormones using chromatography and a new solid phase assay. When complexed with radiolabeled activin or inhibin, FS eluted at a volume corresponding to a mol wt range of 67,000-150,000, an elution volume identical to the lower mol wt BP peak observed in serum. Furthermore, kinetic analyses of recombinant FS binding to activin using a solid phase assay revealed that 1) the FS-activin interaction is of high affinity, similar to or exceeding that estimated for activin binding to its receptor; 2) binding to activin is essentially irreversible at physiological pH; and 3) the potency of inhibin is approximately 500- to 1000-fold lower than that of activin in the FS binding assay. The lack of FS-[I-125]activin complex reversibility observed in the solid phase assay was confirmed using a modified gel filtration chromatography protocol. Thus, preincubation of pure FS or serum with unlabeled activin for 2 h eliminated all binding of subsequently added labeled activin despite a much longer incubation period. However, when labeled activin was incubated with FS for 2 h, subsequent addition of unlabeled activin or inhibin was unable to displace labeled activin from FS, again demonstrating a lack of reversibility. Finally, to map this high affinity interaction, overlapping synthetic peptides were used to compete with labeled activin for FS binding. Two potential contact sites between FS and activin were identified, one near the N-terminus (amino acids 15-29) and the other near the C-terminus (amino acids 99-116). Given its apparently irreversible nature, high affinity, and ability to neutralize activin's biological activity, FS is quite different from the typical hormone-BP. These unique properties of FS undoubtedly attest to the potency of activin in many physiological and developmental settings and, therefore, to the importance of BPs, such as FS for regulating activin's bioactivity, distribution, and/or clearance. C1 MASSACHUSETTS GEN HOSP, NATL CTR INFERTIL RES, BOSTON, MA 02114 USA. RP SCHNEYER, AL (reprint author), MASSACHUSETTS GEN HOSP, REPROD ENDOCRINE UNIT, BHX-5, BOSTON, MA 02114 USA. FU NICHD NIH HHS [U54-HD-29164, R01 HD015788, T32 HD007396] NR 35 TC 131 Z9 136 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD AUG PY 1994 VL 135 IS 2 BP 667 EP 674 DI 10.1210/en.135.2.667 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NZ288 UT WOS:A1994NZ28800025 PM 8033815 ER PT J AU SYKES, M KHAN, A SACHS, DH TOMITA, Y AF SYKES, M KHAN, A SACHS, DH TOMITA, Y TI BONE-MARROW TRANSPLANTATION FOR THE INDUCTION OF CORD-BLOOD TRANSPLANTATION TOLERANCE SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1994 VL 22 IS 8 BP 677 EP 677 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA PB368 UT WOS:A1994PB36800001 ER PT J AU PHARR, PN OGAWA, M HOFBAUER, A LONGMORE, G AF PHARR, PN OGAWA, M HOFBAUER, A LONGMORE, G TI NEITHER AN ACTIVATED ERYTHROPOIETIN NOR A CSF-1 RECEPTOR-INDUCED THE DIFFERENTIATION OF PLURIPOTENT PROGENITORS SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 VET AFFAIRS MED CTR,RALPH H JOHNSON DEPT,CHARLESTON,SC 29403. MED UNIV S CAROLINA,DEPT MED,CHARLESTON,SC 29425. WASHINGTON UNIV,SCH MED,DIV HEMATOL ONCOL,ST LOUIS,MO 63110. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1994 VL 22 IS 8 BP 685 EP 685 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA PB368 UT WOS:A1994PB36800030 ER PT J AU REDDY, SV SINGER, FR ROODMAN, GD AF REDDY, SV SINGER, FR ROODMAN, GD TI HEMATOPOIETIC PRECURSORS FROM PATIENTS WITH PAGETS-DISEASE (PD) OF BONE EXPRESS MEASLES-VIRUS NUCLEOCAPSID (MVN) MESSENGER-RNA SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 UNIV TEXAS SAN ANTONIO, SAN ANTONIO, TX 78285 USA. AUDIE L MURPHY MEM VET ADM MED CTR, SAN ANTONIO, TX 78284 USA. ST JOHNS MED CTR, SANTA MONICA, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X EI 1873-2399 J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1994 VL 22 IS 8 BP 686 EP 686 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA PB368 UT WOS:A1994PB36800034 ER PT J AU EPPERLY, M ANDO, K GREENBERGER, JS AF EPPERLY, M ANDO, K GREENBERGER, JS TI EXPRESSION OF TRANSGENES FOR CYCLIN-D2 OR CYCLIN-D3 RESULTS IN AN INCREASED RADIORESISTANCE IN 32D-CL-3 CELLS SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 UNIV PITTSBURGH,MED CTR,DEPT RADIAT ONCOL,PITTSBURGH,PA. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NR 1 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1994 VL 22 IS 8 BP 699 EP 699 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA PB368 UT WOS:A1994PB36800082 ER PT J AU EMERY, DW SABLINSKI, T SHULMAN, S FOLEY, A SHIMADA, H SACHS, DH LEGUERN, C AF EMERY, DW SABLINSKI, T SHULMAN, S FOLEY, A SHIMADA, H SACHS, DH LEGUERN, C TI RETROVIRUS VECTOR EXPRESSION FOLLOWING BONE-MARROW TRANSDUCTION AND TRANSPLANTATION IN MINIATURE SWINE SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,TRANSPLANTAT BIOL RES CTR,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1994 VL 22 IS 8 BP 700 EP 700 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA PB368 UT WOS:A1994PB36800085 ER PT J AU EMANUEL, PD BUSQUE, L GILLILAND, DG PRCHAL, JT SOKOL, IM BELICKOVA, M CASTLEBERRY, RP AF EMANUEL, PD BUSQUE, L GILLILAND, DG PRCHAL, JT SOKOL, IM BELICKOVA, M CASTLEBERRY, RP TI EVIDENCE OF CLONALITY IN JUVENILE CHRONIC MYELOGENOUS LEUKEMIA (JCML) - ANALYSIS BY VARIOUS TECHNIQUES SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 UNIV ALABAMA,BIRMINGHAM,AL. BRIGHAM & WOMENS HOSP,DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1994 VL 22 IS 8 BP 771 EP 771 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA PB368 UT WOS:A1994PB36800347 ER PT J AU EPPERLY, M HALLAHAN, DE KUFE, DW WEICHSELBAUM, R GREENBERGER, JS AF EPPERLY, M HALLAHAN, DE KUFE, DW WEICHSELBAUM, R GREENBERGER, JS TI MANGANESE SUPEROXIDE-DISMUTASE TRANSGENE INCREASES THE RADIORESISTANCE OF HEMATOPOIETIC PROGENITOR-CELL LINES SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 PITTSBURGH CANC INST,DEPT RADIAT ONCOL,PITTSBURGH,PA 15213. DANA FARBER CANC INST,BOSTON,MA. UNIV CHICAGO,DEPT RADIAT ONCOL,CHICAGO,IL 60637. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1994 VL 22 IS 8 BP 790 EP 790 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA PB368 UT WOS:A1994PB36800419 ER PT J AU EDER, M ERNST, TJ GANSER, A HOELZER, D GRIFFIN, JD AF EDER, M ERNST, TJ GANSER, A HOELZER, D GRIFFIN, JD TI A LOW-AFFINITY HUMAN GM-CSF ALPHA/BETA CHIMERIC RECEPTOR INDUCES GM-CSF DEPENDENT PROLIFERATION IN A MURINE CELL-LINE SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 UNIV FRANKFURT,DEPT HEMATOL,W-6000 FRANKFURT,GERMANY. DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA. HARVARD UNIV,SCH MED,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1994 VL 22 IS 8 BP 806 EP 806 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA PB368 UT WOS:A1994PB36800480 ER PT J AU FRIM, DM WULLNER, U BEAL, MF ISACSON, O AF FRIM, DM WULLNER, U BEAL, MF ISACSON, O TI IMPLANTED NGF-PRODUCING FIBROBLASTS INDUCE CATALASE AND MODIFY ATP LEVELS BUT DO NOT AFFECT GLUTAMATE-RECEPTOR BINDING OR NMDA RECEPTOR EXPRESSION IN THE RAT STRIATUM SO EXPERIMENTAL NEUROLOGY LA English DT Article ID NERVE GROWTH-FACTOR; NEUROTROPHIC FACTOR PREVENTS; BIOLOGICALLY DELIVERED NGF; EXCITATORY AMINO-ACIDS; EXCITOTOXIC LESIONS; NEURONAL DEATH; MITOCHONDRIAL DYSFUNCTION; NUCLEOTIDE-SEQUENCE; FACTOR FAMILY; CELL-DEATH AB Neurotrophic factors, in particular NGF, have been shown to potently protect against glutamate-receptor-mediated toxicity. In order to further investigate the mechanism of this protection, we investigated the in vivo effects of fibroblasts, genetically modified to secrete NGF and implanted near the striatum, on striatal excitatory amino acid binding and receptor expression, on the induction of the peroxidative enzyme catalase, and on cellular energy metabolism in the striatum. Seven days after implantation into the corpus callosum of either a genetically altered NGF-producing (NGF[+]) or unaltered parental (NGF[-]) fibroblast cell-line, there is a time point at which NGF[C] cells have been shown to prevent exitotoxic insults. At that time point after implantation, we found that NGF[c] grafts caused a marked increase in catalase mRNA expression in and around the NGF[+] grafts. The NGF[+] grafts also reduced basal levels of striatal ATP when compared to the effects of NGF[+] grafts. No changes were observed in [H-3]glutamate binding and NMDA receptor mRNA expression. We conclude that effects of NGF[+] fibroblast grafts on glutamate receptor mediated toxicity are not by direct effects on glutamate receptors or glutamate binding, but rather appear to be a process involving enzymatic induction and modification of cellular energy stores. The observed increase in catalase mRNA suggests that peroxidative metabolism may be involved in these NGF-mediated effects. (C) 1994 Academic Press, Inc. C1 MCLEAN HOSP, NEUROREGENERAT LAB, BELMONT, MA 02178 USA. MASSACHUSETTS GEN HOSP, NEUROL SERV, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, NEUROSURG SERV, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA USA. FU NINDS NIH HHS [NS10828, NS29178, NS30064] NR 58 TC 28 Z9 28 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 EI 1090-2430 J9 EXP NEUROL JI Exp. Neurol. PD AUG PY 1994 VL 128 IS 2 BP 172 EP 180 DI 10.1006/exnr.1994.1125 PG 9 WC Neurosciences SC Neurosciences & Neurology GA PE963 UT WOS:A1994PE96300002 PM 8076661 ER PT J AU DYNLACHT, BD FLORES, O LEES, JA HARLOW, E AF DYNLACHT, BD FLORES, O LEES, JA HARLOW, E TI DIFFERENTIAL REGULATION OF E2F TRANSACTIVATION BY CYCLIN CDK2 COMPLEXES SO GENES & DEVELOPMENT LA English DT Article DE E2F-1 DP-1; CYCLIN-KINASE COMPLEX; IN VITRO TRANSCRIPTION; CELL CYCLE REGULATION ID RETINOBLASTOMA GENE-PRODUCT; TRANSCRIPTION FACTOR E2F; RNA POLYMERASE-II; CELL-CYCLE REGULATION; INITIATION FACTOR-IIB; REGION 1A PROTEINS; HUMAN MYC PROMOTER; BINDING PROTEIN; DEPENDENT KINASES; DNA-BINDING AB The mammalian transcription factor E2F plays a critical role in the expression of genes required for cellular proliferation. To understand how E2F is regulated, we have developed a reconstituted in vitro transcription assay. Using this E2F-responsive assay, we can demonstrate that E2F-mediated transcription can be directly repressed by the tumor suppressor protein pRB. This inhibition is abolished by phosphorylation of pRB with either cyclin A/cdk2 or cyclin E/cdk2. However, these cyclin/kinase complexes exhibit differences in the ability to phosphorylate E2F. Only cyclin A/cdk2 can phosphorylate E2F effectively, and this phosphorylation abolishes its ability to bind DNA and mediate trans-activation. Thus, this in vitro transcriptional assay allows activation and inactivation of E2F transcription, and our findings demonstrate how transcriptional regulation of E2F can be linked to cell cycle-dependent activation of kinases. C1 TULARIK INC,S SAN FRANCISCO,CA 94080. MIT,CTR CANC RES,DEPT BIOL,CAMBRIDGE,MA 02139. RP DYNLACHT, BD (reprint author), MASSACHUSETTS GEN HOSP,CTR CANC,BOSTON,MA 02129, USA. NR 94 TC 339 Z9 343 U1 1 U2 3 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0890-9369 J9 GENE DEV JI Genes Dev. PD AUG 1 PY 1994 VL 8 IS 15 BP 1772 EP 1786 DI 10.1101/gad.8.15.1772 PG 15 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA PB104 UT WOS:A1994PB10400004 PM 7958856 ER PT J AU KIM, SK HAINES, JL BERSON, EL DRYJA, TP AF KIM, SK HAINES, JL BERSON, EL DRYJA, TP TI NONALLELIC HETEROGENEITY IN AUTOSOMAL-DOMINANT RETINITIS-PIGMENTOSA WITH INCOMPLETE PENETRANCE SO GENOMICS LA English DT Note C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BERMAN GUND & HOWE LABS,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,MOLEC NEUROGENET UNIT,BOSTON,MA 02129. RI Haines, Jonathan/C-3374-2012 FU NEI NIH HHS [EY00169, EY08683] NR 4 TC 2 Z9 2 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD AUG PY 1994 VL 22 IS 3 BP 659 EP 660 DI 10.1006/geno.1994.1446 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA PC816 UT WOS:A1994PC81600025 PM 8001983 ER PT J AU KNAPP, RC AF KNAPP, RC TI REFLECTIONS ON OVARIAN-CANCER - A 33-YEAR EXPERIENCE SO GYNECOLOGIC ONCOLOGY LA English DT Article ID SERUM CA-125 LEVELS; PREOPERATIVE EVALUATION; MONOCLONAL-ANTIBODY; CA 125; CARCINOMA; MASSES; TUMORS C1 BRIGHAM & WOMENS HOSP,DEPT GYNECOL & GYNECOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. RP KNAPP, RC (reprint author), HARVARD UNIV,SCH MED,DEPT GYNECOL,BOSTON,MA 02115, USA. NR 37 TC 2 Z9 2 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD AUG PY 1994 VL 54 IS 2 BP 124 EP 129 DI 10.1006/gyno.1994.1180 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA PC290 UT WOS:A1994PC29000003 PM 8063234 ER PT J AU CAREY, K AF CAREY, K TI COST ALLOCATION PATTERNS BETWEEN HOSPITAL INPATIENT AND OUTPATIENT DEPARTMENTS SO HEALTH SERVICES RESEARCH LA English DT Article DE COST ALLOCATION; OUTPATIENT SERVICE; COST FUNCTION ID PROSPECTIVE PAYMENT SYSTEM; PERFORMANCE; COMPETITION; PRODUCTIVITY; CONTAINMENT; OWNERSHIP; OUTPUT; LABOR AB Objective. This study examines changes in hospitals' cost allocation patterns between inpatient and outpatient departments in response to the implementation of the prospective payment system. Data Sources and Study Settings. The analysis was carried out using data for 3,961 hospitals obtained from the Medicare Cost Reports and from the American Hospital Association for the years 1984 through 1988. Study Design. A total operating cost function was estimated on the two outputs of discharges and outpatient visits. The estimation results were instrumental in disaggregating costs into inpatient and outpatient components. This was done cross sectionally for each of the five years. Principal Findings. Comparison of this cost breakdown with that of hospital revenue provides evidence of distinct patterns in which nonteaching, rural, and small hospitals increasingly allocated greater costs to outpatient departments than did large, urban, and teaching hospitals. Conclusions. The results suggest that small rural hospitals turned to the outpatient side in the face of tough economic challenges over the period of study. Because differences in cost allocation patterns occur by particular hospital category, analyses that rely on accounting cost or revenue data in order to identify cost differences among those same categories may come to erroneous conclusions. In particular, because teaching hospitals apportion costs more heavily on the inpatient side, cost allocation differences cause upward bias in the PPS medical education adjustment. RP CAREY, K (reprint author), US DEPT VET AFFAIRS,MANAGEMENT SCI GRP,200 SPRINGS RD,BEDFORD,MA 01730, USA. NR 42 TC 8 Z9 8 U1 2 U2 5 PU HEALTH ADMINISTRATION PRESS PI MELROSE PARK PA C/O FOUNDATION AMER COLL HEALTHCARE EXECUTIVES 1951 CORNELL AVE, MELROSE PARK, IL 60160 SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD AUG PY 1994 VL 29 IS 3 BP 275 EP 292 PG 18 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA PD813 UT WOS:A1994PD81300002 PM 8063566 ER PT J AU GILL, JI GULLEY, ML AF GILL, JI GULLEY, ML TI IMMUNOGLOBULIN AND T-CELL RECEPTOR GENE REARRANGEMENT SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; POLYMERASE CHAIN-REACTION; MINIMAL RESIDUAL DISEASE; B-CELLS; LYMPHOPROLIFERATIVE DISORDERS; CLONAL REARRANGEMENT; HODGKINS-DISEASE; MALIGNANT-LYMPHOMA; REGION GENES; BETA-GENE C1 UNIV TEXAS,HLTH SCI CTR,DEPT PATHOL,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX. FU NCI NIH HHS [KO8-CA01615] NR 66 TC 19 Z9 19 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD AUG PY 1994 VL 8 IS 4 BP 751 EP 770 PG 20 WC Oncology; Hematology SC Oncology; Hematology GA PD162 UT WOS:A1994PD16200012 PM 7961289 ER PT J AU CLARE, N HANSEN, K AF CLARE, N HANSEN, K TI CYTOGENETICS IN THE DIAGNOSIS OF HEMATOLOGIC MALIGNANCIES SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; ACUTE NONLYMPHOCYTIC LEUKEMIA; ACUTE MYELOID-LEUKEMIA; ACUTE PROMYELOCYTIC LEUKEMIA; BONE-MARROW TRANSPLANTATION; NON-HODGKINS-LYMPHOMA; DENOVO MYELODYSPLASTIC SYNDROME; ACUTE MEGAKARYOCYTIC LEUKEMIA; POLYMERASE CHAIN-REACTION C1 AUDIE L MURPHY MEM VET ADM MED CTR,HEMATOL LAB,SAN ANTONIO,TX 78284. RP CLARE, N (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT PATHOL,CYTOGENET LAB,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. NR 99 TC 9 Z9 9 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD AUG PY 1994 VL 8 IS 4 BP 785 EP 807 PG 23 WC Oncology; Hematology SC Oncology; Hematology GA PD162 UT WOS:A1994PD16200014 PM 7961291 ER PT J AU NISHIZAKI, Y KAUNITZ, JD ODA, M GUTH, PH AF NISHIZAKI, Y KAUNITZ, JD ODA, M GUTH, PH TI IMPAIRMENT OF GASTRIC-MUCOSAL DEFENSES MEASURED IN-VIVO IN CIRRHOTIC RATS SO HEPATOLOGY LA English DT Article ID ALKALINE-PHOSPHATASE ACTIVITY; PORTAL-HYPERTENSION; BLOOD-FLOW; INTRACELLULAR PH; LIVER-CIRRHOSIS; VASCULAR ECTASIAS; HUMAN-SERUM; INJURY; CELL; PROSTAGLANDIN-E2 AB Patients with cirrhosis have an increased incidence of gastric ulcers and erosions. We evaluated the effect of carbon tetrachloride-induced cirrhosis on rat gastric mucosal defense mechanisms using our recently developed in vivo fluorescence microscopy technique. Cirrhotic rats had increased portal vein pressure, increased serum aminotransferase concentrations and decreased serum albumin concentrations. We noted significantly more spontaneous gross gastric lesions in the cirrhotic rats. In vivo microscopic measurements revealed that cirrhotic rats had (a) a significantly thinner gastric mucous gel layer, (b) a much greater decrease in surface mucosal cell intracellular pH in response to an acid load, (c) decreased gastric mucosal blood how and (d) decreased surface cell viability. We conclude that spontaneous gastric mucosal lesions in cirrhotic rats may be related to more rapid penetration of acid through a thinner gastric mucous gel layer and a lower mucosal blood flow. These changes are associated with a decreased ability of the surface cells to maintain intracellular pH homeostasis, increased initial gastric surface cell acidification, decreased surface cell viability and a lower blood flow that probably is inadequate to remove the increased acid. C1 UNIV CALIF LOS ANGELES,W LOS ANGELES VET AFFAIRS MED CTR,MED SERV,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,W LOS ANGELES VET AFFAIRS MED CTR,RES SERV,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,CTR ULCER RES & EDUC,DEPT MED,LOS ANGELES,CA 90073. KEIO UNIV,SCH MED,DEPT INTERNAL MED,TOKYO 160,JAPAN. NR 45 TC 18 Z9 18 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD AUG PY 1994 VL 20 IS 2 BP 445 EP 452 DI 10.1016/0270-9139(94)90198-8 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PA130 UT WOS:A1994PA13000025 PM 8045506 ER PT J AU WEI, MX TAMIYA, T CHASE, M BOVIATSIS, EJ CHANG, TKH KOWALL, NW HOCHBERG, FH WAXMAN, DJ BREAKEFIELD, XO CHIOCCA, EA AF WEI, MX TAMIYA, T CHASE, M BOVIATSIS, EJ CHANG, TKH KOWALL, NW HOCHBERG, FH WAXMAN, DJ BREAKEFIELD, XO CHIOCCA, EA TI EXPERIMENTAL TUMOR-THERAPY IN MICE USING THE CYCLOPHOSPHAMIDE-ACTIVATING CYTOCHROME-P450 2B1 GENE SO HUMAN GENE THERAPY LA English DT Article ID POLYMERASE CHAIN-REACTION; THYMIDINE KINASE GENES; MALIGNANT BRAIN-TUMORS; INDUCED RAT-LIVER; GLIOMA-CELLS; INTRATHECAL 4-HYDROPEROXYCYCLOPHOSPHAMIDE; CYTOSINE DEAMINASE; CONTROLLED RELEASE; ANTITUMOR-ACTIVITY; EXPRESSION AB Most malignant tumors of the central nervous system do not respond well to chemotherapy. The anticancer drug cyclophosphamide (CPA) is largely ineffective against these neoplasms as its-conversion to DNA-alkylating, cytotoxic metabolites is restricted primarily to the liver and these metabolites do not readily cross the blood-brain barrier. Here, we show that brain tumor cells can be sensitized to the cytotoxic effects of CPA, both in culture and in vivo, by introduction of the hepatic enzyme responsible for the activation of CPA, cytochrome P450 2B1. Stable transfection of rat C6 glioma cells with the P450 2B1 gene rendered the cultured tumor cells sensitive to CPA. Further, C6 cells bearing this gene were more sensitive than parental cells to the cytotoxic action of CPA when grown subcutaneously in the flanks of athymic mice. Murine fibroblasts producing a retrovirus vector encoding P450 2B1 and expressing this enzyme were then prepared and grafted into the brains of athymic mice seeded with rat C6 gliomas. Intrathecal administration of CPA prevented the development of meningeal neoplasia and led to partial regression of the parenchymal tumor mass. By contrast, C6 glioma-bearing mice receiving fibroblasts expressing the Escherichia coli lacZ gene and CPA exhibited extensive meningeal tumors and parenchymal solid brain tumors. The in situ activation of CPA by cytochrome P450 2B1 provides a novel approach not only for brain tumor gene therapy, but also for negative, drug-conditional selection of other defined cell populations. C1 MASSACHUSETTS GEN HOSP E, DEPT NEUROL, MOLEC NEUROGENET UNIT, BOSTON, MA 02129 USA. HARVARD UNIV, SCH MED, NEUROSCI PROGRAM, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DANA FARBER CANC INST, DEPT BIOL CHEM & MOLEC PHARMACOL, BOSTON, MA 02114 USA. BEDFORD VET ADM, BEDFORD, MA 01730 USA. BOSTON UNIV, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, DEPT NEUROL, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, DEPT SURG, NEUROSURG SERV, BOSTON, MA 02114 USA. RI Kowall, Neil/G-6364-2012 OI Kowall, Neil/0000-0002-6624-0213 FU NCI NIH HHS [NCI CA49248]; NINDS NIH HHS [NINDS NS24279] NR 61 TC 138 Z9 143 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 EI 1557-7422 J9 HUM GENE THER JI Hum. Gene Ther. PD AUG PY 1994 VL 5 IS 8 BP 969 EP 978 DI 10.1089/hum.1994.5.8-969 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA PD826 UT WOS:A1994PD82600006 PM 7948146 ER PT J AU PAKZABAN, P GELLER, AI ISACSON, O AF PAKZABAN, P GELLER, AI ISACSON, O TI EFFECT OF EXOGENOUS NERVE GROWTH-FACTOR ON NEUROTOXICITY OF AND NEURONAL GENE DELIVERY BY A HERPES-SIMPLEX AMPLICON VECTOR IN THE RAT-BRAIN SO HUMAN GENE THERAPY LA English DT Article ID BETA-GALACTOSIDASE; VIRUS-1 VECTOR; EXPRESSION; THERAPY; MUTANTS; LATENCY; INVITRO; CELLS; PHYSIOLOGY; INVIVO AB We have previously shown that local destruction of neural tissue by wild-type herpes simplex virus type 1 (HSV-1) is attenuated by intracerebral infusion of nerve growth factor (NGF). To investigate the effect of NGF on the extent of neurolysis and efficacy of neuronal gene transfer mediated by an HSV-1 amplicon vector system in vivo, rats were stereotaxically injected in the striatum with an amplicon preparation, pHSVlac. This amplicon contains the Escherichia coli lacZ gene under the transcriptional control of the HSV-1 immediate early 4/5 promoter and is packaged by an HSV-1 helper virus carrying a deletion in the immediate early 3 gene. Vector injection was followed by continuous intracerebral infusion of NGF-beta (total dose 5 mu g) or vehicle solution over 7 days. Animals were sacrificed at the end of the 7-day infusion period for histological analysis of the brains. A distinct zone of inflammation and necrosis surrounded the injection site in all vector-inoculated animals. The volume of striatal tissue destruction was significantly smaller in NGF-treated animals (1.27 +/- 0.19 mm(3); mean +/- SEM) than in the vehicle-treated controls (2.16 +/- 0.37 mm(3); P < 0.05 by t-test). Immunohistochemical staining for HSV and beta-galactosidase (beta-Gal) in vehicle-treated animals revealed that many striatal cells harbored HSV antigens 3,678 +/- 636), but only a small number expressed the reporter gene at 7 days post-injection (294 +/- 60). NGF infusion did not significantly affect the number of HSV-immunoreactive cells (4,224 +/- 618), or the number of cells expressing beta-Gal (330 +/- 72) at this time. In some animals in both groups, a disseminated pattern of HSV immunoreactivity and reporter gene expression was seen throughout the brain. We conclude that exogenous NGF reduces the local cytopathologic effects of this HSV-1-derived vector in the rat striatum, but does not affect the number of HSV-immunoreactive cells or the short-term expression of the transgene. C1 MCLEAN HOSP, NEUROREGENERAT LAB, BELMONT, MA 02178 USA. MASSACHUSETTS GEN HOSP, NEUROSURG SERV, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, NEUROL SERV, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, PROGRAM NEUROSCI, BOSTON, MA 02114 USA. CHILDRENS HOSP, DIV ENDOCRINOL, BOSTON, MA 02115 USA. RI Geller, Alfred/C-6469-2012 FU NINDS NIH HHS [NS29178, NINDS 5T32 NS07340, NS30064] NR 33 TC 38 Z9 39 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 EI 1557-7422 J9 HUM GENE THER JI Hum. Gene Ther. PD AUG PY 1994 VL 5 IS 8 BP 987 EP 995 DI 10.1089/hum.1994.5.8-987 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA PD826 UT WOS:A1994PD82600008 PM 7948148 ER PT J AU DORIA, A WARRAM, JH RICH, SS KROLEWSKI, AS AF DORIA, A WARRAM, JH RICH, SS KROLEWSKI, AS TI ANGIOTENSIN I-CONVERTING ENZYME (ACE) - ESTIMATION OF DNA HAPLOTYPES IN UNRELATED INDIVIDUALS USING DENATURING GRADIENT GEL BLOTS SO HUMAN GENETICS LA English DT Article ID INSERTION DELETION POLYMORPHISM; FRAGMENT-LENGTH-POLYMORPHISMS; GENOMIC DNA; SEQUENCE POLYMORPHISMS; GENE; SUBSTITUTIONS; FREQUENCIES; MUTATIONS; HALF; LOCI AB The angiotensin I-converting enzyme (ACE) gene (17q23) is a candidate gene for essential hypertension and related diseases, but investigation of its role in human pathology is hampered by a lack of identified polymorphisms. Currently, a 287-bp insertion/deletion (I/D) RFLP in intron 16 represents the only one known. Additional polymorphisms for the ACE gene would make most families informative for linkage studies and would allow haplotypes to be assigned in association studies. To increase the information provided by the ACE gene, we used a sensitive screening technique, denaturing gradient gel electrophoresis (DGGE) blots, to identify polymorphisms and combined this with gene counting to identify haplotypes. Five independent polymorphisms, restriction fragment melting polymorphisms (RFMPs), were identified by four probes (encompassing half of the ACE cDNA) in digests produced by three restriction enzymes (DdeI, RsaI, and AluI). One RFMP has three alleles while the others have two alleles. In a sample of 67 unrelated control subjects, minor allele frequencies ranged from 0.12 to 0.49. A significant level of linkage disequilibrium was found for all pairs of markers. The four most informative RFMPs, taken in combination, define 24 potential haplotypes. Based on gene counting, 11 of the 24 are rare or nonexistent in this population, and the estimated heterozygosity of the remaining 13 haplotypes approaches 80%. Under these conditions for the ACE locus, phase-unknown genotypes could be assigned to haplotype pairs in unrelated subjects with reasonable certainty. Thus, using DGGE blot technique for identifying numerous DNA polymorphisms in a candidate locus, in combination with gene counting, one can often identify DNA haplotypes for both related and unrelated study subjects at a candidate locus. These markers in the ACE gene should be useful for clinical and epidemiologic studies of the role of ACE in human disease. C1 HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,DEPT MED,DIV RES,BOSTON,MA 02215. UNIV MINNESOTA,DEPT LAB MED & PATHOL,MINNEAPOLIS,MN 55455. UNIV MINNESOTA,INST HUMAN GENET,MINNEAPOLIS,MN 55455. FU NIDDK NIH HHS [R01 DK 41526, P30 DK 36836] NR 32 TC 17 Z9 17 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD AUG PY 1994 VL 94 IS 2 BP 117 EP 123 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA NZ381 UT WOS:A1994NZ38100002 PM 8045557 ER PT J AU DORIA, A JI, L WARRAM, JH KROLEWSKI, AS AF DORIA, A JI, L WARRAM, JH KROLEWSKI, AS TI DDEI POLYMORPHISM IN THE AGTR1 GENE SO HUMAN MOLECULAR GENETICS LA English DT Note ID RECEPTOR C1 HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02215. FU NIDDK NIH HHS [R01 DK 41526] NR 3 TC 32 Z9 36 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD AUG PY 1994 VL 3 IS 8 BP 1444 EP 1444 DI 10.1093/hmg/3.8.1444 PG 1 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA PC827 UT WOS:A1994PC82700048 PM 7987340 ER PT J AU BOSTWICK, DG ALGABA, F AMIN, MB AYALA, A EBLE, J GOLDSTEIN, N HELPAP, B HUMPHREY, P GRIGNON, D JONES, EC MCNEAL, J MONTIRONI, R QIAN, J RO, J SRIGLEY, J TETU, B TRONCOSO, P TRUE, L WHEELER, T YOUNG, RH AF BOSTWICK, DG ALGABA, F AMIN, MB AYALA, A EBLE, J GOLDSTEIN, N HELPAP, B HUMPHREY, P GRIGNON, D JONES, EC MCNEAL, J MONTIRONI, R QIAN, J RO, J SRIGLEY, J TETU, B TRONCOSO, P TRUE, L WHEELER, T YOUNG, RH TI CONSENSUS STATEMENT ON TERMINOLOGY - RECOMMENDATION TO USE ATYPICAL ADENOMATOUS HYPERPLASIA IN-PLACE OF ADENOSIS OF THE PROSTATE SO HUMAN PATHOLOGY LA English DT Letter C1 FDN PUIGVERT,BARCELONA,SPAIN. HENRY FORD HOSP,DETROIT,MI 48202. UNIV TEXAS,MD ANDERSON CANC CTR,HOUSTON,TX. RICHARD L ROUDEBUSH VET AFFAIRS MED CTR,INDIANAPOLIS,IN 46202. INDIANA UNIV,INDIANAPOLIS,IN 46204. CEDARS SINAI MED CTR,LOS ANGELES,CA 90048. UNIV FREIBURG,ACAD HOSP,SINGEN,GERMANY. BARNES HOSP,ST LOUIS,MO 63110. WASHINGTON UNIV,SCH MED,ST LOUIS,MO. HARPER GRACE HOSP,DETROIT,MI 48201. WAYNE STATE UNIV,DETROIT,MI. UNIV BRITISH COLUMBIA,VANCOUVER,BC,CANADA. STANFORD UNIV,MED CTR,STANFORD,CA 94305. UNIV ANCONA,ANCONA,ITALY. BEIJING FRIENDSHIP HOSP,BEIJING,PEOPLES R CHINA. UNIV TORONTO,SUNNYBROOK HLTH SCI CTR,TORONTO,ON,CANADA. HOTEL DIEU QUEBEC,QUEBEC CITY,PQ,CANADA. UNIV WASHINGTON,SEATTLE,WA 98195. BAYLOR COLL MED,HOUSTON,TX 77030. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RP BOSTWICK, DG (reprint author), MAYO CLIN & MAYO FDN,200 1ST ST SW,ROCHESTER,MN 55905, USA. NR 2 TC 6 Z9 6 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD AUG PY 1994 VL 25 IS 8 BP 840 EP 840 DI 10.1016/0046-8177(94)90258-5 PG 1 WC Pathology SC Pathology GA PC663 UT WOS:A1994PC66300020 PM 7520021 ER PT J AU WALUNAS, TL LENSCHOW, DJ BAKKER, CY LINSLEY, PS FREEMAN, GJ GREEN, JM THOMPSON, CB BLUESTONE, JA AF WALUNAS, TL LENSCHOW, DJ BAKKER, CY LINSLEY, PS FREEMAN, GJ GREEN, JM THOMPSON, CB BLUESTONE, JA TI CTLA-4 CAN FUNCTION AS A NEGATIVE REGULATOR OF T-CELL ACTIVATION SO IMMUNITY LA English DT Article ID LYMPHOCYTES-T; COUNTER-RECEPTOR; CD28; EXPRESSION; ANTIBODY; ANTIGEN; MOLECULE; LIGAND; MOUSE; PROLIFERATION AB CD28 and CTLA-4 are related glycoproteins found on T cells. Ligation of CD28 following antigen receptor engagement provides a costimulatory signal required for T cell activation. Anti-CTLA-4 antibodies were generated to examine the role of the CTLA-4 receptor on murine T cells. Expression of CTLA-4 as a homodimer is up-regulated 2-3 days following T cell activation. Anti-CTLA-4 antibodies and Fab fragments augmented T cell proliferation in an allogeneic MLR. However, when optimal costimulation and Fc cross-linking were present, anti-CTLA-4 MAbs inhibited T cell proliferation. Together, these results suggest that the MAb may obstruct the interaction of CTLA-4 with its natural ligand and block a negative signal, or directly signal T cells to down-regulate immune function. C1 UNIV CHICAGO,DEPT MED,CHICAGO,IL 60637. UNIV CHICAGO,HOWARD HUGHES MED INST,CHICAGO,IL 60637. BRISTOL MYERS SQUIBB CO,PHARMACEUT RES INST,SEATTLE,WA 98121. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. RP WALUNAS, TL (reprint author), UNIV CHICAGO,COMM IMMUNOL,CHICAGO,IL 60637, USA. FU NCI NIH HHS [CA40216]; NIAID NIH HHS [P01 AI35294, AI35225] NR 36 TC 1207 Z9 1241 U1 5 U2 21 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 1074-7613 J9 IMMUNITY JI Immunity PD AUG PY 1994 VL 1 IS 5 BP 405 EP 413 DI 10.1016/1074-7613(94)90071-X PG 9 WC Immunology SC Immunology GA PK168 UT WOS:A1994PK16800009 PM 7882171 ER PT J AU SETHNA, MP VANPARIJS, L SHARPE, AH ABBAS, AK FREEMAN, GJ AF SETHNA, MP VANPARIJS, L SHARPE, AH ABBAS, AK FREEMAN, GJ TI A NEGATIVE REGULATORY FUNCTION OF B7 REVEALED IN B7-1 TRANSGENIC MICE SO IMMUNITY LA English DT Article ID T-CELL CLONES; CTLA-4 COUNTER-RECEPTOR; ACTIVATION ANTIGEN-B7; CD28; COSTIMULATION; PROLIFERATION; EXPRESSION; INDUCTION; ADHESION; PREVENTS AB To analyze the functions of T cell costimulators in vivo, we have constructed a transgenic mouse strain that constitutively expresses murine B7-1 on mature B cells. Antibody responses to T-dependent hapten-protein conjugates and serum immunoglobulin levels are markedly depressed in B7-1 transgenic mice. This immune deficiency is not due to an intrinsic B cell defect, as antibody responses to T-independent hapten conjugates are normal. Furthermore, treatment with anti-B7-1 restores the capacity of transgenic mice to respond to hapten-protein conjugates, demonstrating that the deficient antibody responses are directly attributable to the expression of B7-1. These results suggest that the temporally regulated expression of costimulators such as B7-1 may contribute to either initiation or down-regulation (feedback inhibition) of T-dependent immune responses in vivo, and that the inhibitory function is dominant in transgenic mice that constitutively express high levels of this costimulator. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. DANA FARBER CANC INST,DEPT MED,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. RP SETHNA, MP (reprint author), BRIGHAM & WOMENS HOSP,DEPT PATHOL,DIV IMMUNOL RES,75 FRANCIS ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA40216]; NIAID NIH HHS [P01AI35297, R01AI22802] NR 27 TC 85 Z9 85 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 1074-7613 J9 IMMUNITY JI Immunity PD AUG PY 1994 VL 1 IS 5 BP 415 EP 421 DI 10.1016/1074-7613(94)90072-8 PG 7 WC Immunology SC Immunology GA PK168 UT WOS:A1994PK16800010 PM 7533646 ER PT J AU TYAN, ML AF TYAN, ML TI H-2-ASSOCIATED CLEFT-PALATE (CP) SUSCEPTIBILITY GENES SO IMMUNOGENETICS LA English DT Letter ID CHROMOSOME-17; MAPS; H-2 RP TYAN, ML (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,11301 WILSHIRE BLVD,LOS ANGELES,CA 90073, USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0093-7711 J9 IMMUNOGENETICS JI Immunogenetics PD AUG PY 1994 VL 40 IS 4 BP 315 EP 315 PG 1 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA PE479 UT WOS:A1994PE47900017 PM 8082901 ER PT J AU KLEIN, BS CHATURVEDI, S HOGAN, LH JONES, JM NEWMAN, SL AF KLEIN, BS CHATURVEDI, S HOGAN, LH JONES, JM NEWMAN, SL TI ALTERED EXPRESSION OF SURFACE PROTEIN WI-1 IN GENETICALLY RELATED STRAINS OF BLASTOMYCES-DERMATITIDIS THAT DIFFER IN VIRULENCE REGULATES RECOGNITION OF YEASTS BY HUMAN MACROPHAGES SO INFECTION AND IMMUNITY LA English DT Article ID HISTOPLASMA-CAPSULATUM; PHASE VARIATION; POLYACRYLAMIDE GELS; ANTIGENIC VARIATION; MECHANISM; MUTATION; INVITRO; INVIVO; CELLS; GENES AB The molecular basis for pathogenicity and virulence of the dimorphic fungus Blastomyces dermatitidis remains unknown. WI-1 is a major cell wall protein of B. dermatitidis yeasts and is a recognition target of both humoral and cell-mediated immunity. As an initial study to determine if WI-1 might be linked to virulence of B. dermatitidis, we quantified WI-1 expression on three genetically related strains that differ in their virulence for mice: wild-type virulent ATCC strain 26199, mutant ATCC strain 60915 (which is 10,000-fold reduced in virulence), and mutant ATCC strain 60916 (which is avirulent). Two principal alterations in WI-1 expression were observed in the mutants. First, the mutants express more WI-1 on their surface, as quantified by flow cytometry with monoclonal antibody to WI-1 and by radioimmunoassay, but the WI-1 on their cell wall is less extractable than that on the wild-type strain. Second, the mutants shed less WI-1 during culture and demonstrate impaired professing of shed WI-1. Surface alterations in WI-1 were accompanied by significant differences in the binding of the virulent and mutant strains to human monocyte-derived macrophages. Attachment of yeasts to macrophages paralleled and was proportional to the expression of WI-1. Compared with wild-type yeasts, both mutants bound to macrophages more rapidly and in two- to threefold-greater magnitude. Furthermore, about 75% of yeast binding to macrophages was inhibited by a Fab anti-WI-1 monoclonal antibody. These results suggest that altered WI-1 expression on attenuated and avirulent mutant B. dermatitidis yeasts greatly facilitates macrophage recognition and binding of yeasts and, in turn, may contribute to more rapid ingestion and killing in the host. C1 UNIV WISCONSIN HOSP & CLIN,SCH MED,DEPT INTERNAL MED,MADISON,WI 53792. UNIV WISCONSIN HOSP & CLIN,SCH MED,DEPT MED MICROBIOL & IMMUNOL,MADISON,WI 53792. WILLIAM S MIDDLETON MEM VET ADM MED CTR,RES SERV,MADISON,WI 53705. UNIV CINCINNATI,COLL MED,DEPT INTERNAL MED,DIV INFECT DIS,CINCINNATI,OH 45267. RP KLEIN, BS (reprint author), UNIV WISCONSIN HOSP & CLIN,SCH MED,DEPT PEDIAT,600 HIGHLAND AVE,K4-434,MADISON,WI 53792, USA. FU NIAID NIH HHS [AI-31479, AI-00905, AI-23985] NR 28 TC 29 Z9 29 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD AUG PY 1994 VL 62 IS 8 BP 3536 EP 3542 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA NY872 UT WOS:A1994NY87200064 PM 8039924 ER PT J AU HIROSE, T KOBATA, T NOJIMA, Y SCHLOSSMAN, SF MORIMOTO, C AF HIROSE, T KOBATA, T NOJIMA, Y SCHLOSSMAN, SF MORIMOTO, C TI 3H11, A UNIQUE CELL-SURFACE MOLECULE INVOLVED IN THE FUNCTION OF THE CD45RA(+) SUBSET OF CD4+ CELLS SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE CD45RA(+) T CELLS; IMMUNOREGULATION; PWM-DRIVEN B CELL IGG SYNTHESIS; T CELL CO-STIMULATION ID DIFFERENTIATION ANTIGENS HB-10; LEUKOCYTE-COMMON ANTIGEN; HUMAN LYMPHOCYTES-T; MONOCLONAL-ANTIBODIES; HELPER-INDUCER; IMMUNOREGULATORY FUNCTIONS; ACTIVATION; RECEPTOR; EXPRESSION; SUBPOPULATIONS AB We have developed a mAb anti-3H11 by immunizing mice with a T cell line derived from the Callithrix jacchus (common marmoset). Anti-3H11 is reactive with similar to 48% of unfractionated T cells, 62% of CD4(+) cells and 39% of CD8(+) cells. Among CD4 cells, anti-3H11 preferentially reacts with the CD45RA(+) T cell subset. The majority of helper activity for pokeweed mitogen (PWM)-driven B cell IgG synthesis and T cell response to recall antigen such as tetanus toroid was found within the 3H11-CD4 cell population, whereas anti-3H11(+)CD4(+) cells provided poor helper function for PWM-driven B cell IgG synthesis and were more responsive to concanavalin A and autologous mixed lymphocyte reaction. Biochemical characterization showed that anti-3H11 precipitated a single protein band with a relative molecular weight of 32,000 from I-125-surface labeled cell lysate. Biochemical, phenotypic and functional studies revealed that the 3H11 molecule appeared to be different from previously established molecules on the T cell surface. Interestingly, addition of anti 3H11 to the combination of CD4 and B cells in the presence of CD8 cells but not to the combination of CD4 and B cells resulted in enhancement of the suppression of PWM-driven B cell IgG synthesis. Moreover, anti-3H11 had a co-mitogenic effect on T cells via the CD2 and CD3 pathways, and this co-mitogenic activity is restricted to the CD45RA(+) T cells. Taken together, our results show that the 3H11 molecule is a novel antigen which may play an important role in the activation and function of the CD45RA(+) subset of T cells. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,DIV TUMOR IMMUNOL,BOSTON,MA 02115. FU NIAID NIH HHS [AI-29530, AI-12069]; NIAMS NIH HHS [AR-33713] NR 50 TC 2 Z9 2 U1 0 U2 0 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 AUG PY 1994 VL 6 IS 8 BP 1133 EP 1142 DI 10.1093/intimm/6.8.1133 PG 10 WC Immunology SC Immunology GA PC837 UT WOS:A1994PC83700005 PM 7981142 ER PT J AU CHEN, JZ MA, A YOUNG, F ALT, FW AF CHEN, JZ MA, A YOUNG, F ALT, FW TI IL-2 RECEPTOR-ALPHA CHAIN EXPRESSION DURING EARLY B-LYMPHOCYTE DIFFERENTIATION SO INTERNATIONAL IMMUNOLOGY LA English DT Note DE ACTIVATED B CELLS IG; IMMATURE B CELLS; MATURE B CELLS; PRE-B; PRO-B; RAG; REARRANGEMENT; THYMOCYTE DIFFERENTIATION ID T-CELL DEVELOPMENT; IMMUNOGLOBULIN GENE REARRANGEMENT; INTERLEUKIN-2 RECEPTORS; DEFICIENT MICE; TAC ANTIGEN; GAMMA-CHAIN; STEM-CELLS; BETA-CHAIN; BINDING; MOUSE AB The IL-2/IL-2 receptor (IL-2R) has been studied intensively because of its potential function in the development and regulation of the immune system. The IL-2R alpha chain has been shown to be expressed on CD4(-)CD8(-) thymocytes and activated T and a cells. In this report, we show that IL-2R alpha is also expressed on precursor a cells in the bone marrow. Its expression is initiated by functional rearrangement and expression of Ig mu heavy chain gene and is dawn-regulated when immature a cells mature and express IgD. Its potential function in early B cell differentiation is discussed in comparison with its role in thymocyte differentiation. C1 HARVARD UNIV,CHILDRENS HOSP,SCH MED,HOWARD HUGHES MED INST,DEPT GENET,BOSTON,MA 02115. CTR BLOOD RES,BOSTON,MA 02115. FU NIAID NIH HHS [U01 AI31541, AI20047] NR 39 TC 42 Z9 42 U1 0 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 AUG PY 1994 VL 6 IS 8 BP 1265 EP 1268 DI 10.1093/intimm/6.8.1265 PG 4 WC Immunology SC Immunology GA PC837 UT WOS:A1994PC83700020 PM 7981152 ER PT J AU KLOEN, P JENNINGS, CL GEBHARDT, MC SPRINGFIELD, DS MANKIN, HJ AF KLOEN, P JENNINGS, CL GEBHARDT, MC SPRINGFIELD, DS MANKIN, HJ TI EXPRESSION OF TRANSFORMING GROWTH-FACTOR-BETA (TGF-BETA) RECEPTORS, TGF-BETA-1 AND TGF-BETA-2 PRODUCTION AND AUTOCRINE GROWTH-CONTROL IN OSTEOSARCOMA CELLS SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID HUMAN OSTEOGENIC-SARCOMA; INHIBITORY RESPONSES; CARCINOMA-CELLS; BINDING; FACTOR-BETA-1; MORPHOLOGY; MEMBRANE; INVITRO; FAMILY; MG-63 AB Transforming growth factor-beta (TGF-beta) is a polypeptide with multiple physiological functions. Isoforms of this growth factor have important roles in control of the cell cycle, in regulation of cell-cell interactions and in growth and development. Malignant transformation has been shown to be associated with increased expression of TGF-beta. Since bone is the largest storage site and producer of TGF-beta, we speculated on the existence of an autocrine mechanism in osteosarcoma, a malignant bone tumor. Expression of TGF-beta cell surface receptors, effects on growth of TGF-beta and TGF-beta antibodies and production of 2 TGF-beta isoforms were studied in a panel of 7 osteosarcoma cell lines. In contrast to most previous reports on the effects of TGF-beta on osteosarcoma cell growth, we found a mitogenic effect of TGF-beta 1 in 4 of 7 osteosarcoma cell lines. Receptor profiles for TGF-beta were aberrant in 5 of the 7 cell lines tested, and production of TGF-beta 1 and TGF-beta 2 varied among cell lines. Addition of anti-TGF-beta antagonized the effects of endogenous TGF-beta. Our results suggest a potential role of TGF-beta in autocrine growth control of osteosarcoma cells. (C) 1994 Wiley-Liss, Inc. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ORTHOPED SURG,ORTHOPED RES LABS,BOSTON,MA 02114. RP KLOEN, P (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,ORTHOPED ONCOL SERV,BOSTON,MA 02114, USA. NR 32 TC 33 Z9 34 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD AUG 1 PY 1994 VL 58 IS 3 BP 440 EP 445 DI 10.1002/ijc.2910580323 PG 6 WC Oncology SC Oncology GA NZ276 UT WOS:A1994NZ27600022 PM 8050825 ER PT J AU DISLER, DG MARR, DS ROSENTHAL, DI AF DISLER, DG MARR, DS ROSENTHAL, DI TI ACCURACY OF VOLUME MEASUREMENTS OF COMPUTED-TOMOGRAPHY AND MAGNETIC-RESONANCE-IMAGING PHANTOMS BY 3-DIMENSIONAL RECONSTRUCTION AND PRELIMINARY CLINICAL-APPLICATION SO INVESTIGATIVE RADIOLOGY LA English DT Article DE 3-DIMENSIONAL; RECONSTRUCTION; REFORMATION; VOLUME; THRESHOLDING ID VALIDATION; SARCOMA; SYSTEM AB RATIONALE AND OBJECTIVES. Using an independent three-dimensional workstation, the accuracy of volume measurements of phantoms was assessed using three-dimensional reconstruction of two-dimensional computed tomography (CT) and magnetic resonance (MR) images. METHODS. Round, cylindrical, and irregularly shaped high-contrast phantoms of known volume were imaged in a water bath. The effect of object contrast on volume estimation was tested using phantoms of known volume diluted serially with a contrast agent. The effect of changing field of view and slice thickness was assessed. A clinical application was performed, in which nine shoulders were injected with a known quantity of contrast material, to test the accuracy of the technique in vivo. RESULTS. A strong paired correlation (r = .99) between estimated and true volumes was obtained for high-contrast phantoms ranging from 17 to 128 mL. The weighted average absolute error was 1.42 mL (MR) and 3.50 mL (CT). Accuracy of the serially diluted 27-mL phantoms was essentially unaffected by contrast differences greater than 133 units (MR) and 102 units (CT). The weighted average absolute error was 1.33 mL (MR) and 1.56 mL (CT). Changing field of view had no effect on accuracy, but increasing the slice thickness resulted in overestimation of volume. The mean error for the clinical application was 4.4% (range: 1.7%-8.3%). CONCLUSION. Under certain circumstances, three-dimensional reconstructive volume estimation can be a convenient and accurate method for volume determination. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 17 TC 60 Z9 60 U1 1 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0020-9996 J9 INVEST RADIOL JI Invest. Radiol. PD AUG PY 1994 VL 29 IS 8 BP 739 EP 745 DI 10.1097/00004424-199408000-00002 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PE811 UT WOS:A1994PE81100002 PM 7960623 ER PT J AU BROWN, HD KOSSLYN, SM BREITER, HC BAER, L JENIKE, MA AF BROWN, HD KOSSLYN, SM BREITER, HC BAER, L JENIKE, MA TI CAN PATIENTS WITH OBSESSIVE-COMPULSIVE DISORDER DISCRIMINATE BETWEEN PERCEPTS AND MENTAL IMAGES - A SIGNAL-DETECTION ANALYSIS SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Article ID DEFICITS; CHECKERS AB Signal detection analysis was used to test three hypotheses for repetitive thoughts and behaviors characteristic of obsessive-compulsive disorder (OCD). Patients might have (a) low sensitivity for the difference between having seen something or having imagined seeing it, (b) a high criterion for this discrimination, or (c) difficulty associating context with information in memory. Subjects judged viewed words or imagined words and later indicated which were actually seen. Patients with OCD discriminated seen from imaged words significantly better than normal control subjects, as evidenced by higher d' scores on a recognition memory task. Groups did not differ in response criterion, beta, used to decide whether words had been seen or imaged. Implications for the study of OCD from an information-processing perspective are discussed. C1 MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP BROWN, HD (reprint author), HARVARD UNIV,DEPT PSYCHOL,33 KIRKLAND ST,CAMBRIDGE,MA 02138, USA. NR 34 TC 59 Z9 60 U1 2 U2 2 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0021-843X J9 J ABNORM PSYCHOL JI J. Abnorm. Psychol. PD AUG PY 1994 VL 103 IS 3 BP 445 EP 454 DI 10.1037//0021-843X.103.3.445 PG 10 WC Psychology, Clinical; Psychology, Multidisciplinary SC Psychology GA PA425 UT WOS:A1994PA42500004 PM 7930043 ER PT J AU HEFLE, SL LEMANSKE, RF BUSH, RK AF HEFLE, SL LEMANSKE, RF BUSH, RK TI ADVERSE REACTION TO LUPINE-FORTIFIED PASTA SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE LEGUME; HYPERSENSITIVITY; CROSS-REACTION; LUPINE ID MAJOR COMPONENT PROTEINS; LEGUME BOTANICAL FAMILY; ATOPIC-DERMATITIS; FOOD HYPERSENSITIVITY; CROSS-ALLERGENICITY; PEANUT ALLERGEN; CHILDREN; IDENTIFICATION; CHALLENGES; SERA AB A 5-year-old girl with peanut sensitivity experienced urticaria and angioedema after ingesting a spaghetti-like pasta fortified with sweet lupine seed flour The pasta was extracted and used in immunologic studies in patients with peanut sensitivity to determine whether such individuals are at similar risk. Results of skin prick tests with the lupine pasta extract were positive in five of seven subjects; these patients also reported a history of adverse reactions to green peas. In direct RAST studies IgE binding from pooled sera from patients with peanut sensitivity to the lupine pasta extract was 7 times that of a nonallergic control serum, and individual serum samples demonstrated binding from 1 to 6 times that of the negative control. Direct RAST studies of lupine seed flour with serum samples from patients with peanut allergy demonstrated IgE binding 1 to 11 times that of the negative control. Immunoblotting studies of electrophoretically separated pasta extract and lupine seed flour proteins showed IgE-binding protein bands at approximately 21 kd and in the range of 35 to 55 kd molecular weight We conclude that some peanut-sensitive patients may be at risk for adverse reactions to lupine. C1 WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI 53705. UNIV WISCONSIN,CTR CLIN SCI,DEPT MED,MADISON,WI. UNIV WISCONSIN,FOOD RES INST,MADISON,WI 53706. NR 26 TC 80 Z9 82 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD AUG PY 1994 VL 94 IS 2 BP 167 EP 172 DI 10.1016/0091-6749(94)90036-1 PG 6 WC Allergy; Immunology SC Allergy; Immunology GA PC926 UT WOS:A1994PC92600005 PM 8064069 ER PT J AU WONG, JT RIPPLE, RE MACLEAN, JA MARKS, DR BLOCH, KJ AF WONG, JT RIPPLE, RE MACLEAN, JA MARKS, DR BLOCH, KJ TI VANCOMYCIN HYPERSENSITIVITY - SYNERGISM WITH NARCOTICS AND DESENSITIZATION BY A RAPID CONTINUOUS INTRAVENOUS PROTOCOL SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE VANCOMYCIN; HYPERSENSITIVITY; DESENSITIZATION; THRESHOLD; NARCOTIC ID RED-MAN SYNDROME; HISTAMINE-RELEASE; BACTERICIDAL ACTIVITY; SLOW INFUSION; PHARMACOKINETICS; PROPHYLAXIS; ALLERGY AB Background: We examined the clinical spectrum of patients with persistent adverse reactions to vancomycin, assessed contributing factors, and evaluated the efficacy and safety of a rapid continuous intravenous ''desensitization'' protocol in these patients. Methods: Seven patients with serious staphylococcal infections resistant to beta-lactam antibiotics whose adverse reactions to vancomycin persisted despite slowing of the vancomycin infusion and pretreatment with H-1-antihistamine were studied. All seven patients underwent a rapid continuous intravenous desensitization protocol with multiple small increases in vancomycin concentration tightly regulated with a syringe pump. Results: Most of the seven patients safely achieved, during the first day, a vancomycin infusion rate (VIR) sufficient, or close to sufficient, to provide the desired vancomycin dose. In three patients there appeared to be a threshold VIR beyond which adverse reactions were repeatedly elicited; these reactions abated when the VIR was slightly lowered. Narcotic administration was found to adversely affect treatment with vancomycin. After concurrent narcotic administration was discontinued in three patients, they and the other four patients successfully completed the full course of treatment with vancomycin. Conclusion: Patients whose adverse reactions to vancomycin did not respond to slowing of the infusion rate and additional H-1-antihistamines can be safely treated with a rapid continuous intravenous desensitization protocol and discontinuance of narcotic administration. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,GEN MED SERV,ALLERGY UNIT,BOSTON,MA 02114. RP WONG, JT (reprint author), MASSACHUSETTS GEN HOSP,GEN MED SERV,CLIN IMMUNOL UNIT,COX 5,BOSTON,MA 02114, USA. NR 25 TC 38 Z9 38 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD AUG PY 1994 VL 94 IS 2 BP 189 EP 194 DI 10.1016/0091-6749(94)90039-6 PG 6 WC Allergy; Immunology SC Allergy; Immunology GA PC926 UT WOS:A1994PC92600008 PM 7914900 ER PT J AU JANSSENS, SP MUSTO, SW HUTCHISON, WG SPENCE, C WITTEN, M JUNG, W HALES, CA AF JANSSENS, SP MUSTO, SW HUTCHISON, WG SPENCE, C WITTEN, M JUNG, W HALES, CA TI CYCLOOXYGENASE AND LIPOXYGENASE INHIBITION BY BW-755C REDUCES ACROLEIN SMOKE-INDUCED ACUTE LUNG INJURY SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE PERMEABILITY EDEMA; THROMBOXANE; LEUKOTRIENES ID SULFIDOPEPTIDE LEUKOTRIENES; LEUKOCYTE ADHESION; INHALATION INJURY; ARACHIDONIC-ACID; VASCULAR INJURY; SYNTHETIC SMOKE; PULMONARY-EDEMA; SHEEP; METABOLITES; THROMBOXANE AB Inhalation of smoke containing acrolein, the most common toxin in urban fires after carbon monoxide, causes vascular injury with noncardiogenic pulmonary edema containing potentially edematogenic eicosanoids such as thromboxane (Tx) B-2, leukotriene (LT) B-2, and the sulfidopeptide LTs (LTC(4), LTD(4), and LTE(4)). To determine which eicosanoids are important in the acute lung injury, we pretreated sheep with BW-755C (a combined cyclooxygenase and lipoxygenase inhibitor), U-63557A (a specific Tx synthetase inhibitor), or indomethacin (a cyclooxygenase inhibitor) before a 10-min exposure to a synthetic smoke containing carbon particles (4 mu m) with acrolein and compared the results with those from control sheep that received only carbon smoke. Acrolein smoke induced a fall in arterial Po-2 and rises in peak inspiratory pressure, main pulmonary arterial pressure, pulmonary vascular resistance, lung lymph flow, and the blood-free wet-to-dry weight ratio. BW-755C delayed the rise in peak inspiratory pressure and prevented the fall in arterial Po-2, the rise in lymph flow, and the rise in wet-to-dry weight ratio. Neither indomethacin nor U-63557A prevented the increase in lymph flow or wet-to-dry weight ratio, although they did blunt and delay the rise in airway pressure and did prevent the rises in pulmonary arterial pressure and pulmonary vascular resistance. Thus, cyclooxygenase products, probably Tx, are responsible for the pulmonary hypertension after acrolein smoke and to some extent for the increased airway resistance but not the pulmonary edema. Prevention of high-permeability pulmonary edema after smoke with BW-755C suggests that LTB(4) may be etiologic, as previous work has eliminated LTC(4), LTD(4), and LTE(4). C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP JANSSENS, SP (reprint author), MASSACHUSETTS GEN HOSP,DEPT MED,PULM & CRIT CARE UNIT,BOSTON,MA 02114, USA. FU FIC NIH HHS [1FO5 TW04379-01]; NHLBI NIH HHS [HL-36829, HL-07354] NR 33 TC 28 Z9 29 U1 0 U2 1 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 AUG PY 1994 VL 77 IS 2 BP 888 EP 895 PG 8 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA PB787 UT WOS:A1994PB78700055 PM 8002544 ER PT J AU SUEN, HC LOSTY, PD DONAHOE, PK SCHNITZER, JJ AF SUEN, HC LOSTY, PD DONAHOE, PK SCHNITZER, JJ TI ACCURATE METHOD TO STUDY STATIC VOLUME-PRESSURE RELATIONSHIPS IN SMALL FETAL AND NEONATAL ANIMALS SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Note DE FETAL RATS; NEONATAL RATS; RESPIRATORY SYSTEM COMPLIANCE ID PULMONARY SURFACTANT; NEWBORN MAMMALS; LUNG AB We designed an accurate method to study respiratory static volume-pressure relationships in small fetal and neonatal animals on the basis of Archimedes' principle. Our method eliminates the error caused by the compressibility of air (Boyle's law) and is sensitive to a volume change of as little as 1 mu l. Fetal and neonatal rats during the period of rapid lung development from clay 19.5 of gestation (term = day 22) to day 3.5 postnatum were studied. The absolute lung volume at a transrespiratory pressure of 30-40 cmH(2)O increased 28-fold from 0.036 +/- 0.006 (SE) to 0.994 +/- 0.042 mi, the volume per gram of lung increased 14-fold from 0.39 +/- 0.07 to 5.59 +/- 0.66 ml/g, compliance increased 12-fold from 2.3 +/- 0.4 to 27.3 +/- 2.7 mu l/cmH(2)O, and specific compliance increased B-fold from 24.9 +/- 4.5 to 152.3 +/- 22.8 mu l.cmH(2)O(-1).g lung(-1). This technique, which allowed us to compare changes during late gestation and the early neonatal period in small rodents, can be used to monitor and evaluate pulmonary functional changes after in utero pharmacological therapies in experimentally induced abnormalities such as pulmonary hypoplasia, surfactant deficiency, and congenital diaphragmatic hernia. C1 MASSACHUSETTS GEN HOSP,PEDIAT SURG SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,PEDIAT SURG RES LABS,GEN THORAC SURG UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02114. NR 14 TC 6 Z9 6 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 AUG PY 1994 VL 77 IS 2 BP 1036 EP 1043 PG 8 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA PB787 UT WOS:A1994PB78700074 PM 8002489 ER PT J AU LAM, MS LITWIN, CM CARROLL, PA CALDERWOOD, SB AF LAM, MS LITWIN, CM CARROLL, PA CALDERWOOD, SB TI VIBRIO-CHOLERAE FUR MUTATIONS ASSOCIATED WITH LOSS OF REPRESSOR ACTIVITY - IMPLICATIONS FOR THE STRUCTURAL-FUNCTIONAL RELATIONSHIPS OF FUR SO JOURNAL OF BACTERIOLOGY LA English DT Article ID UPTAKE REGULATION PROTEIN; ESCHERICHIA-COLI; TRANSCRIPTIONAL REGULATION; IRON TRANSPORT; NUCLEOTIDE-SEQUENCE; MOLECULAR-CLONING; VIRULENCE GENE; DNA FRAGMENTS; SIDEROPHORE; EXPRESSION AB We used the Vibrio cholerae Fur protein as a model of iron-sensitive repressor proteins in gram-negative bacteria. Utilizing manganese mutagenesis, we isolated twelve independent mutations in V. cholerae fur that resulted in partial or complete loss of Fur repressor function. The mutant fur genes were recovered by PCR and sequenced; 11 of the 12 contained point mutations (two of which were identical), and one contained a 7-bp insertion that resulted in premature truncation of Fur. All of the mutants, except that containing the prematurely truncated Fur, produced protein by Western blot (immunoblot) analysis, although several had substantially smaller amounts of Fur and two made an immunoreactive protein that migrated more rapidly on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Nine of the 11 point mutations altered amino acids that are identical in all of the fur genes sequenced so far, suggesting that these amino acids may play important structural or functional roles in Fur activity. Eight of the point mutations occurred in the amino terminal half of Fur, which is thought to mediate DNA binding; most of these mutations occurred in conserved amino acids that have been previously suggested to play a role in the interaction between adjacent alpha-helices of the protein. Three of the point mutations occurred in the carboxy-terminal half of Fur, which is thought to bind iron. One mutation at histidine-90 was associated with complete loss of Fur function; this amino acid is within a motif previously suggested as being involved in iron binding by Fur. The fur allele mutant at histidine-90 interfered with iron regulation by wild-type fur in the same cell when the mutant allele was present at higher copy number; wild-type fur was dominant over all other fur mutant alleles studied. These results are analyzed with respect to previous models of the structure and function of Fur as an iron-sensitive repressor. C1 MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOLEC GENET,BOSTON,MA 02115. OI Litwin, Christine/0000-0002-4311-7714 FU NIAID NIH HHS [AI27329, AI34968] NR 45 TC 30 Z9 31 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD AUG PY 1994 VL 176 IS 16 BP 5108 EP 5115 PG 8 WC Microbiology SC Microbiology GA PA426 UT WOS:A1994PA42600040 PM 8051024 ER PT J AU YOGANATHAN, AP LEMMON, JD KIM, YH WALKER, PG LEVINE, RA VESIER, CC AF YOGANATHAN, AP LEMMON, JD KIM, YH WALKER, PG LEVINE, RA VESIER, CC TI A COMPUTATIONAL STUDY OF A THIN-WALLED 3-DIMENSIONAL LEFT-VENTRICLE DURING EARLY SYSTOLE SO JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME LA English DT Article ID MITRAL-VALVE; BLOOD-FLOW; MOTION; HEART; MECHANISM; DOGS AB A numerical study was conducted to solve the three-dimensional Navier-Stokes equations for time-dependent flow in a compliant thin-walled, anatomically correct left ventricle during early systole. Model parameters were selected so that the simulation results could be compared to clinical data. The results produced endocardial wall motion which was consistent with human heart data, and velocity fields consistent with those occurring in a normally-contracting left ventricle. During isovolumetric contraction the posterior wall moved basally and posteriorly, while the septal wall moved apically and anteriorly. During ejection, the short axis of the left ventricle decreased 1.1 mm and the long axis increased 4.2 mm. At the end of the isovolumetric contraction, most of the flow field was moving form the apex toward the base with recirculation regions at the small pocket formed by the concave anterior leaflet, adjacent to the septal wall and near the left ventricular posterior wall. Fluid velocities in the outflow tract matched NMR data to within 10 percent. The results were also consistent with clinical measurements of mitral valve-papillary muscle apparatus displacement, and changes in the mitral valve annular area. The results of the present study show that the thin-walled, three-dimensional left ventricular model simulates observed normal heart phenomena. Validation of this model permits further studies to be performed which involve altered ventricular function due to a variety of cardiac diseases. C1 GEORGIA INST TECHNOL,SCH MECH ENGN,CARDIOVASC FLUID MECH LAB,ATLANTA,GA 30332. MASSACHUSETTS GEN HOSP,CARDIAC ULTRASOUND LAB,BOSTON,MA 02114. RP YOGANATHAN, AP (reprint author), GEORGIA INST TECHNOL,SCH CHEM,CARDIOVASC FLUID MECH LAB,ATLANTA,GA 30332, USA. NR 22 TC 19 Z9 20 U1 0 U2 1 PU ASME-AMER SOC MECHANICAL ENG PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 SN 0148-0731 J9 J BIOMECH ENG-T ASME JI J. Biomech. Eng.-Trans. ASME PD AUG PY 1994 VL 116 IS 3 BP 307 EP 314 DI 10.1115/1.2895735 PG 8 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA PD367 UT WOS:A1994PD36700011 PM 7799632 ER PT J AU GOETZ, DD SMITH, EJ HARRIS, WH AF GOETZ, DD SMITH, EJ HARRIS, WH TI THE PREVALENCE OF FEMORAL OSTEOLYSIS ASSOCIATED WITH COMPONENTS INSERTED WITH OR WITHOUT CEMENT IN TOTAL HIP REPLACEMENTS - A RETROSPECTIVE MATCHED-PAIR SERIES SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID ARTHROPLASTY; PROSTHESES; FAILURE AB The prevalence of femoral osteolysis in hips in which a femoral component had been inserted without cement was compared with that in hips with a cemented component, in a retrospective matched-pair study of the results of primary total hip arthroplasties; all patients had received the same type of acetabular component. Forty-one hips in thirty-nine patients who had a Harris-Galante porous-coated total hip prosthesis without cement were matched by age, sex, weight, duration of follow-up, and diagnosis with forty-one hips in thirty-eight patients who had a hybrid total hip reconstruction; the hybrid reconstruction consisted of the same acetabular component and a Precoat femoral component inserted with a so-called third-generation cementing technique. All of the operations were done by the same surgeon, who used the same operative approach and the same course of postoperative rehabilitation. All of the patients were followed for at least four years (mean, six years). Osteolysis developed in twelve (29 per cent) of the hips that had a femoral component without cement compared with none of the hips that had a cemented component (p < 0.0002). At the latest follow-up examination, none of the femoral components that had been inserted with cement were loose and none had been revised, while eight (20 per cent) of the femoral components that had been inserted without cement were loose and five (12 per cent) had been revised. This retrospective matched-pair study controlled for many of the variables associated with a comparison of the rates of femoral osteolysis in separate series of femoral components fixed with and without cement. The matched-pair study permitted direct comparison of just two factors: the type of fixation of the femoral component and the femoral component itself. Access of particulate debris to the periprosthetic interface is essential for the development of femoral osteolysis. The prevalence of femoral osteolysis was significantly higher after the fixation without cement under the conditions of this matched-pair study. These data thus support the concepts that polyethylene debris has less access to the periprosthetic interface after femoral fixation with the third-generation techniques of cementing and that that type of cementing provided protection against femoral osteolysis, for the duration of the study, compared with fixation of the femoral stem without cement. C1 MASSACHUSETTS GEN HOSP,ORTHOPAED BIOMECH LAB,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT ORTHOPAED SURG,HIP & IMPLANT UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 57 TC 137 Z9 141 U1 0 U2 2 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 AUG PY 1994 VL 76A IS 8 BP 1121 EP 1129 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA PC507 UT WOS:A1994PC50700002 PM 8056792 ER PT J AU SCULLY, SP MOTT, MP TEMPLE, HT OKEEFE, RJ ODONNELL, RJ MANKIN, HJ AF SCULLY, SP MOTT, MP TEMPLE, HT OKEEFE, RJ ODONNELL, RJ MANKIN, HJ TI LATE RECURRENCE OF GIANT-CELL TUMOR OF BONE - A REPORT OF 4 CASES SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Note RP SCULLY, SP (reprint author), MASSACHUSETTS GEN HOSP,ORTHOPAED ONCOL UNIT,GRAY 606,BOSTON,MA 02114, USA. NR 14 TC 34 Z9 35 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 AUG PY 1994 VL 76A IS 8 BP 1231 EP 1233 PG 3 WC Orthopedics; Surgery SC Orthopedics; Surgery GA PC507 UT WOS:A1994PC50700013 PM 8056803 ER PT J AU BROWN, RA GELBERMAN, RH SELLER, JG FURCOLO, D ABRAHAMSSON, SO WEILAND, AJ URBANIAK, JR SCHOENFELD, DA AF BROWN, RA GELBERMAN, RH SELLER, JG FURCOLO, D ABRAHAMSSON, SO WEILAND, AJ URBANIAK, JR SCHOENFELD, DA TI UNTITLED - REPLY SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Letter C1 LUND UNIV,DEPT HAND SURG,MALMO,SWEDEN. HOSP SPECIAL SURG,NEW YORK,NY 10021. DUKE UNIV,MED CTR,DEPT SURG,DIV ORTHOPAED SURG,DURHAM,NC 27710. MASSACHUSETTS GEN HOSP,CTR BIOSTAT,BOSTON,MA 02114. RP BROWN, RA (reprint author), MASSACHUSETTS GEN HOSP,DEPT ORTHOPAED SURG,WACC-527,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 76A IS 8 BP 1272 EP 1272 PG 1 WC Orthopedics; Surgery SC Orthopedics; Surgery GA PC507 UT WOS:A1994PC50700019 ER PT J AU BROWN, RA GELBERMAN, RH SEILER, JG FURCOLO, D ABRAHAMSSON, SO WEILAND, AJ URBANIAK, JR SCHOENFELD, DA AF BROWN, RA GELBERMAN, RH SEILER, JG FURCOLO, D ABRAHAMSSON, SO WEILAND, AJ URBANIAK, JR SCHOENFELD, DA TI UNTITLED - REPLY SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Letter C1 LUND UNIV,DEPT HAND SURG,MALMO,SWEDEN. HOSP SPECIAL SURG,NEW YORK,NY 10021. DUKE UNIV,MED CTR,DEPT SURG,DIV ORTHOPAED SURG,DURHAM,NC 27710. MASSACHUSETTS GEN HOSP,CTR BIOSTAT,BOSTON,MA 02114. RP BROWN, RA (reprint author), MASSACHUSETTS GEN HOSP,DEPT ORTHOPAED SURG,WACC-527,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 76A IS 8 BP 1273 EP 1274 PG 2 WC Orthopedics; Surgery SC Orthopedics; Surgery GA PC507 UT WOS:A1994PC50700023 ER PT J AU BROWN, RA GELBERMAN, RH SEILER, JG FURCOLO, D ABRAHAMSSON, SO WEILAND, AJ URBANIAK, JR SCHOENFELD, DA AF BROWN, RA GELBERMAN, RH SEILER, JG FURCOLO, D ABRAHAMSSON, SO WEILAND, AJ URBANIAK, JR SCHOENFELD, DA TI UNTITLED - REPLY SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Letter C1 LUND UNIV,DEPT HAND SURG,MALMO,SWEDEN. HOSP SPECIAL SURG,NEW YORK,NY 10021. DUKE UNIV,MED CTR,DEPT SURG,DIV ORTHOPAED SURG,DURHAM,NC 27710. MASSACHUSETTS GEN HOSP,CTR BIOSTAT,BOSTON,MA 02114. RP BROWN, RA (reprint author), MASSACHUSETTS GEN HOSP,DEPT ORTHOPAED SURG,WACC-527,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 76A IS 8 BP 1273 EP 1273 PG 1 WC Orthopedics; Surgery SC Orthopedics; Surgery GA PC507 UT WOS:A1994PC50700021 ER PT J AU BROWN, RA GELBERMAN, RH SEILER, JG FURCOLO, D ABRAHAMSSON, SO WEILAND, AJ URBANIAK, JR SCHOENFELD, DA AF BROWN, RA GELBERMAN, RH SEILER, JG FURCOLO, D ABRAHAMSSON, SO WEILAND, AJ URBANIAK, JR SCHOENFELD, DA TI UNTITLED - REPLY SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Letter C1 LUND UNIV,DEPT HAND SURG,MALMO,SWEDEN. HOSP SPECIAL SURG,NEW YORK,NY 10021. DUKE UNIV,MED CTR,DEPT SURG,DIV ORTHOPAED SURG,DURHAM,NC 27710. MASSACHUSETTS GEN HOSP,CTR BIOSTAT,BOSTON,MA 02114. RP BROWN, RA (reprint author), MASSACHUSETTS GEN HOSP,DEPT ORTHOPAED SURG,WACC-527,BOSTON,MA 02114, USA. NR 10 TC 0 Z9 0 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 AUG PY 1994 VL 76A IS 8 BP 1274 EP 1275 PG 2 WC Orthopedics; Surgery SC Orthopedics; Surgery GA PC507 UT WOS:A1994PC50700025 ER PT J AU TEICHER, BA SOTOMAYOR, EA DUPUIS, NP KUSUMOTO, T MENON, K AF TEICHER, BA SOTOMAYOR, EA DUPUIS, NP KUSUMOTO, T MENON, K TI REDUCED OXYGENATION IN A RAT MAMMARY-CARCINOMA AFTER CHEMO-THERAPY OR RADIATION-THERAPY AND REOXYGENATION WITH PERFLUBRON EMULSION/CARBOGEN BREATHING SO JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY LA English DT Article DE POSTCHEMOTHERAPY REOXYGENATION; POSTRADIATION THERAPY OXYGENATION; PERFLUBRON EMULSION CARBOGEN BREATHING ID MELPHALAN ANTITUMOR-ACTIVITY; FLUOSOL-DA 20-PERCENT; GRADE BRAIN-TUMORS; CYTO-TOXICITY; CELL-CARCINOMA; BLOOD-FLOW; PHASE-I/II; X-RAYS; ADJUVANT; ENHANCEMENT AB Rat 13672 mammary carcinoma tumors were grown subcutaneously in the hind legs of female Fischer 344 rats to a volume of about 1 cm(3). Tumor oxygenation was measured using an Eppendorf PO2 histograph. Tumor oxygen measurements were made under four conditions: (a) normal air breathing, (b) carbogen breathing, (c) after intravenous administration of a perflubron emulsion (8 ml/kg) with air breathing and (d) after intravenous administration of a perflubron emulsion (8 ml/kg) with carbogen breathing. Tumor oxygenation was examined without treatment or 24 h and 48 h after treatment with cyclophosphamide (300 mg/kg, i.p.) or cisplatin (8 mg/kg, i.p.] or after the fifth dose of a daily regimen of 3-Gy irradiation (5x3 Gy). Under normal air-breathing conditions 49% of the tumor had a PO2 less than or equal to 670 Pa (5 mm Hg). The degree of hypoxia in the tumors increased after each treatment such that 24 h after treatment 65%-85% of the oxygen readings were less than or equal to 670 Pa and 48 h after treatment 60%-74% of the oxygen readings were less than or equal to 670 Pa. Administration of the perflubron emulsion/carbogen atmosphere increased the oxygen content of the tumors both without treatment and after each of the treatments. A knowledge of tumor oxygen content over the course of treatment and the ability to increase tumor oxygen should allow for the development of more rational treatment combinations and better treatment outcomes. C1 HARVARD UNIV,SCH MED,JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. RP TEICHER, BA (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [P01-CA19589] NR 31 TC 12 Z9 12 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0171-5216 J9 J CANCER RES CLIN JI J. Cancer Res. Clin. Oncol. PD AUG PY 1994 VL 120 IS 10 BP 593 EP 598 DI 10.1007/BF01212813 PG 6 WC Oncology SC Oncology GA PF421 UT WOS:A1994PF42100005 PM 7929530 ER PT J AU SUGITA, K NOJIMA, Y TACHIBANA, K SOIFFER, RJ MURRAY, C SCHLOSSMAN, SF RITZ, J MORIMOTO, C AF SUGITA, K NOJIMA, Y TACHIBANA, K SOIFFER, RJ MURRAY, C SCHLOSSMAN, SF RITZ, J MORIMOTO, C TI PROLONGED IMPAIRMENT OF VERY LATE ACTIVATING ANTIGEN-MEDIATED T-CELL PROLIFERATION VIA THE CD3 PATHWAY AFTER T-CELL-DEPLETED ALLOGENEIC BONE-MARROW TRANSPLANTATION SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE VLA ANTIGEN; ALLO-BMT; CD3 PATHWAY; EXTRACELLULAR MATRIX PROTEINS; TYROSINE PHOSPHORYLATION ID TYROSINE PHOSPHORYLATION; LYMPHOCYTE-T; INFECTIOUS COMPLICATIONS; IMMUNOGLOBULIN-SYNTHESIS; PHOSPHOLIPASE C-GAMMA-1; MONOCLONAL-ANTIBODY; SIGNAL TRANSDUCTION; RECEPTOR COMPLEX; INTEGRIN FAMILY; HELPER-INDUCER AB One of the major obstacles in allogeneic bone marrow transplantation (allo-BMT) is prolonged T cell dysfunction resulting in a variety of infectious complications in the months to years after hematologic engraftment. We previously showed that immobilized extracellular matrix (ECM) proteins such as fibronectin (FN), the CS-I domain of FN, or collagen (CO) acted synergistically with immobilized anti-CD3 to induce T cell proliferation. In addition, the comitogenic effect of ECMs could be mimicked by immobilized mAb reactive with a common beta 1 chain (CD29) of very late activating (VLA) antigens which include ECM receptors. Since the interaction of T cells with ECMs appears to play an important role in the process of T cell reconstitution following allo-BMT, we examined the expression of VLA antigens (alpha 1-alpha 6, beta 1) and their functional roles in CD3-mediated T cell proliferation at various times after T cell depleted allo-BMT. VLA beta 1 as well as VLA alpha 4, alpha 5, and alpha 6 expression was lower than normal controls during the first 3 mo after allo-BMT and auto-BMT, whereas these expressions returned to normal levels by 4 mo after allo-BMT and auto-BMT. Although alpha 1 and alpha 2 were not expressed on lymphocytes from normal controls, these antigens were expressed on lymphocytes at the detectable levels (5-15%) from patients after allo-BMT and auto-BMT. Both CD29 and CD3 were expressed at normal levels on lymphocytes from patients >3 mo after allo-BMT, whereas T cell interaction with ECM through VLA proteins or crosslinking of VLA beta 1 expressed by T cells with anti-CD29 mAb results in poor induction of CD3-mediated T cell proliferation for a prolonged period (>1 yr) after allo-BMT. In contrast, T cell proliferation induced by crosslinking of anti-CD2 or anti-CD26 with anti-CD3 was almost fully recovered by 1 yr post-allo-BMT. After autologous BMT, impaired VLA-mediated T cell proliferation via the CD3 pathway after auto-BMT returned to normal levels within 1 yr despite no significant difference in CD3 and CD29 expression following either allo- or auto-BMT. The adhesion of T cells from post-allo-BMT patients to FN-coated plate was normal or increased compared to that of normal controls. Moreover, the induction of the tyrosine phosphorylation of pp105 protein by the ligation of VLA molecules was not impaired in allo-BMT patients. These results suggest that there are some other defects in the process of VLA-mediated signal transduction in such patients. Our results imply that disturbance of VLA function could explain, at least in part, the persistent immunoincompetent state after allo-BMT and may be involved in susceptibility to opportunistic infections after allo-BMT. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,DIV TUMOR IMMUNOL,BOSTON,MA 02115. RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NIAID NIH HHS [AI12609, AI29530]; NIAMS NIH HHS [AR33713] NR 51 TC 14 Z9 15 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD AUG PY 1994 VL 94 IS 2 BP 481 EP 488 DI 10.1172/JCI117359 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA PA250 UT WOS:A1994PA25000005 PM 7518837 ER PT J AU RUSSELL, ME UTANS, U WALLACE, AF LIANG, P ARCECI, RJ KARNOVSKY, MJ WYNER, LR YAMASHITA, Y TARN, C AF RUSSELL, ME UTANS, U WALLACE, AF LIANG, P ARCECI, RJ KARNOVSKY, MJ WYNER, LR YAMASHITA, Y TARN, C TI IDENTIFICATION AND UP-REGULATION OF GALACTOSE N-ACETYLGALACTOSAMINE MACROPHAGE LECTIN IN RAT CARDIAC ALLOGRAFTS WITH ARTERIOSCLEROSIS SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE ARTERIOSCLEROSIS; ASIALOGLYCOPROTEINS; CARDIAC TRANSPLANTATION; GENE EXPRESSION; REJECTION ID EXPERIMENTAL GRAFT ARTERIOSCLEROSIS; HEART; PROTEIN-1; RECEPTOR; BINDING; CELLS; CDNA AB Using differential mRNA display to uncover potential mediators associated with chronic rejection, me identified a cDNA fragment induced in Lewis to F344 rat cardiac allografts with arteriosclerosis but not Lewis syngrafts. The full-length cDNA (1.4 kb) isolated from a rat cardiac allograft cDNA library was 99% identical to galactose/N-acetylgalactosamine (Gal/GalNAc) macrophage lectin, a cell-surface receptor. This cDNA hybridized in Northern analysis with total RNA from eight cardiac allografts but not with host hearts, syngrafts, or other organs. There was a significant allograft-specific increase in transcript levels measured by reverse transcriptase PCR at days 7, 14, 28, and 75 in comparison with paired F344 host hearts (subject to same circulation but histologically normal), day-0 hearts, and syngrafts (P < 0.008, n = 4 at each time). Transcript levels in cardiac allografts were higher than those in paired host spleens (a major source of inflammatory cells) (P < 0.0001), indicating the localized nature of Gal/GalNAc lectin induction. By in situ hybridization and immunostaining, Gal/GalNAc lectin expression localized to a subset of inflammatory cells in cardiac allografts. These findings link Gal/GalNAc macrophage lectin to the chronic rejection process, as a possible mediator of macrophage infiltration. C1 BRIGHAM & WOMENS HOSP,DIV CARDIOVASC,BOSTON,MA 02115. CHILDRENS HOSP,DIV PEDIAT HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RP RUSSELL, ME (reprint author), HARVARD UNIV,SCH PUBL HLTH,CARDIOVASC BIOL LAB,665 HUNTINGTON AVE,BOSTON,MA 02115, USA. FU NHLBI NIH HHS [HL-43318] NR 22 TC 52 Z9 52 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD AUG PY 1994 VL 94 IS 2 BP 722 EP 730 DI 10.1172/JCI117391 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA PA250 UT WOS:A1994PA25000037 PM 8040327 ER PT J AU GRIBBEN, JG AF GRIBBEN, JG TI ATTAINMENT OF MOLECULAR REMISSION - A WORTHWHILE GOAL SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID POLYMERASE CHAIN-REACTION; NON-HODGKINS-LYMPHOMA; CHROMOSOMAL TRANSLOCATION T(14-18); BONE-MARROW TRANSPLANTATION; B-CELL LYMPHOMA; FOLLICULAR LYMPHOMAS; PERIPHERAL-BLOOD; RESIDUAL CELLS; BCL-2 GENE; CLUSTER REGION RP GRIBBEN, JG (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. NR 33 TC 18 Z9 18 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 AUG PY 1994 VL 12 IS 8 BP 1532 EP 1534 PG 3 WC Oncology SC Oncology GA PA257 UT WOS:A1994PA25700002 PM 8040663 ER PT J AU ATKINS, MB OBOYLE, KR SOSMAN, JA WEISS, GR MARGOLIN, KA ERNEST, ML KAPPLER, K MIER, JW SPARANO, JA FISHER, RI ECKARDT, JR PEREIRA, C ARONSON, FR AF ATKINS, MB OBOYLE, KR SOSMAN, JA WEISS, GR MARGOLIN, KA ERNEST, ML KAPPLER, K MIER, JW SPARANO, JA FISHER, RI ECKARDT, JR PEREIRA, C ARONSON, FR TI MULTIINSTITUTIONAL PHASE-II TRIAL OF INTENSIVE COMBINATION CHEMOIMMUNOTHERAPY FOR METASTATIC MELANOMA SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ACTIVATED KILLER-CELLS; HIGH-DOSE CISPLATIN; MALIGNANT-MELANOMA; ALPHA-INTERFERON; INTERLEUKIN-2; CHEMOTHERAPY; DACARBAZINE; TAMOXIFEN; THERAPY; REGIMEN C1 CYTOKINE WORKING GRP,BOSTON,MA. ALBERT EINSTEIN MED CTR,MONTEFIORE MED CTR,NEW YORK,NY. LOYOLA UNIV,MED CTR,MAYWOOD,IL 60153. UNIV TEXAS,AUDIE L MURPHY MEM VET ADM MED CTR,CTR HLTH SCI,SAN ANTONIO,TX. CITY HOPE NATL MED CTR,DUARTE,CA. UNIV CALIF SAN FRANCISCO,MED CTR,SAN FRANCISCO,CA 94143. RP ATKINS, MB (reprint author), TUFTS UNIV,NEW ENGLAND MED CTR,DIV HEMATOL ONCOL,BOX 245,BOSTON,MA 02111, USA. FU NCRR NIH HHS [M01-RR00054, M01-RR00079] NR 39 TC 106 Z9 107 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 AUG PY 1994 VL 12 IS 8 BP 1553 EP 1560 PG 8 WC Oncology SC Oncology GA PA257 UT WOS:A1994PA25700006 PM 8040667 ER PT J AU LABBATE, LA POLLACK, MH OTTO, MW TESAR, GM ROSENBAUM, JF AF LABBATE, LA POLLACK, MH OTTO, MW TESAR, GM ROSENBAUM, JF TI THE RELATIONSHIP OF ALPRAZOLAM AND CLONAZEPAM DOSE TO STEADY-STATE CONCENTRATION IN PLASMA SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Note ID PANIC DISORDER; PHARMACOKINETICS; AGORAPHOBIA; KINETICS AB This report addresses the correlation between dose and concentration of both alprazolam and clonazepam in plasma. Patients were 43 participants in a double-blind, placebo-controlled study of alprazolam and clonazepam for the treatment of panic disorder. The concentration of clonazepam in plasma was linearly related with dose, measured as milligrams per day (R = 0.724; F = 24.2; p = 0.0001) or milligrams per kilogram per day (R = 0.863; F = 58.3; p = 0.0001). The correlation between drug concentration and daily dose of alprazolam was also significant (R = 0.60; F = 9.5; p = 0.007), although the correlation between dose measured as milligrams per kilogram per day and drug level was not significant (R = 0.361; F = 2.4; p = 0.14). This replicates previous findings that, for each additional milligram per day dose of alprazolam, there is a corresponding increase of approximately 10 ng/ml in the plasma and presents preliminary data that, for each added 1 mg/day dose of clonazepam, there is approximately an increase of 12 ng/ml in the plasma. For both drugs, however, there may be considerable variation in level in plasma for a given dose. Weight-adjusted clonazepam concentration may be more predictable than weight-adjusted alprazolam concentration. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CLIN PSYCHOPHARMACOL UNIT,BOSTON,MA. CLEVELAND CLIN FDN,DEPT PSYCHIAT,CLEVELAND,OH 44195. RP LABBATE, LA (reprint author), WALTER REED ARMY MED CTR,DEPT PSYCHIAT,WASHINGTON,DC 20307, USA. NR 15 TC 9 Z9 9 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD AUG PY 1994 VL 14 IS 4 BP 274 EP 276 PG 3 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA NX836 UT WOS:A1994NX83600008 PM 7962684 ER PT J AU ALTSHULER, LL PIERRE, JM WIRSHING, WC AMES, D AF ALTSHULER, LL PIERRE, JM WIRSHING, WC AMES, D TI SERTRALINE AND AKATHISIA SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Letter ID FLUOXETINE RP ALTSHULER, LL (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,11301 WILSHIRE BLVD,LOS ANGELES,CA 90073, USA. NR 7 TC 22 Z9 22 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD AUG PY 1994 VL 14 IS 4 BP 278 EP 279 DI 10.1097/00004714-199408000-00010 PG 2 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA NX836 UT WOS:A1994NX83600010 PM 7962686 ER PT J AU AMES, D WIRSHING, WC COKELY, HT LO, LL AF AMES, D WIRSHING, WC COKELY, HT LO, LL TI THE NATURAL COURSE OF PSEUDOTUMOR CEREBRI IN LITHIUM-TREATED PATIENTS SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Letter ID CARBONATE C1 W LOS ANGELES VET AFFAIRS MED CTR,PSYCHIAT SERV,LOS ANGELES,CA. UNIV CALIF LOS ANGELES,MED CTR,LOS ANGELES,CA 90024. RP AMES, D (reprint author), UNIV CALIF LOS ANGELES,SCH MED,DEPT PSYCHIAT & BIOBEHAV SCI,LOS ANGELES,CA 90024, USA. NR 6 TC 5 Z9 5 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD AUG PY 1994 VL 14 IS 4 BP 286 EP 287 PG 2 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA NX836 UT WOS:A1994NX83600016 PM 7962691 ER PT J AU CHEMTOB, CM HAMADA, RS ROITBLAT, HL MURAOKA, MY AF CHEMTOB, CM HAMADA, RS ROITBLAT, HL MURAOKA, MY TI ANGER, IMPULSIVITY, AND ANGER CONTROL IN COMBAT-RELATED POSTTRAUMATIC-STRESS-DISORDER SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article ID VIETNAM-ERA VETERANS; GENERAL-POPULATION; DEPRESSION; SCALE AB Empirical evidence of a relationship between combat-related PTSD and increased anger is lacking. In this study, 24 veterans of the Vietnam War with posttraumatic stress disorder (PTSD) scored significantly higher on an Anger factor comprising multiple measures of anger than did comparison groups of 23 well-adjusted Vietnam combat veterans and 12 noncombat Vietnam-era veterans with psychiatric diagnoses. In contrast, the 3 groups did not differ significantly on orthogonal factors, one of which comprised cognitive impulsivity measures and the other of which reflected motor impulsivity. Changes in heart rate in response to provocation loaded positively on the Anger factor and negatively on the 2 Impulsivity factors. Concurrent depression and trait anxiety did not have an effect on level of anger in individuals with PTSD. These empirical findings support and extend the clinical evidence regarding PTSD and anger. C1 UNIV HAWAII,HONOLULU,HI 96822. RP CHEMTOB, CM (reprint author), US DEPT VET AFFAIRS,RES & DEV 151,STRESS DISORDERS RES LAB,POB 50188,HONOLULU,HI 96850, USA. NR 34 TC 104 Z9 105 U1 0 U2 6 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0022-006X J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD AUG PY 1994 VL 62 IS 4 BP 827 EP 832 DI 10.1037/0022-006X.62.4.827 PG 6 WC Psychology, Clinical SC Psychology GA PD281 UT WOS:A1994PD28100020 PM 7962887 ER PT J AU JELLINEK, MS AF JELLINEK, MS TI MANAGED CARE - GOOD OR BAD-NEWS FOR CHILDREN SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Note C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP JELLINEK, MS (reprint author), MASSACHUSETTS GEN HOSP,CHILD PSYCHIAT SERV,BOSTON,MA 02114, USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0196-206X J9 J DEV BEHAV PEDIATR JI J. Dev. Behav. Pediatr. PD AUG PY 1994 VL 15 IS 4 BP 273 EP 274 PG 2 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA PC011 UT WOS:A1994PC01100008 PM 7798373 ER PT J AU GOLDFELD, AE TSAI, E KINCAID, R BELSHAW, PJ SCHRIEBER, SL STROMINGER, JL RAO, A AF GOLDFELD, AE TSAI, E KINCAID, R BELSHAW, PJ SCHRIEBER, SL STROMINGER, JL RAO, A TI CALCINEURIN MEDIATES HUMAN TUMOR-NECROSIS-FACTOR-ALPHA GENE INDUCTION IN STIMULATED T-CELLS AND B-CELLS SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Note ID CYCLOSPORINE-A; NUCLEAR FACTOR; LYMPHOCYTES-T; NF-AT; ACTIVATION; FK506; TRANSCRIPTION; IDENTIFICATION; MECHANISMS; EXPRESSION AB The tumor necrosis factor alpha (TNF-alpha) gene is rapidly transcribed in activated T cells via a calcium-dependent pathway that does not require de novo protein synthesis, but is completely blocked by the immunosuppressive drugs cyclosporin A (CsA) and FK506. Here we show that calcineurin phosphatase activity is both necessary and sufficient for TNF-alpha gene transcription in T cells, and identify the factor that binds to the kappa 3 element of the the TNF-alpha gene promoter as the target for calcineurin action. The ability of analogues of CsA and FK506 to block calcineurin phosphatase activity correlates completely with their ability to inhibit induction of TNF-alpha mRNA, induction of a TNF-alpha promoter reporter plasmid in transiently transfected T cells, and induction of the kappa 3 binding factor in an electrophoretic mobility shift assay. Moreover, a cDNA encoding the constitutively active form of calcineurin is sufficient to activate the TNF-alpha promoter and the kappa 3 element. TNF-alpha gene transcription is also highly inducible, CsA-sensitive, and protein synthesis-independent in B cells stimulated through their surface immunoglobulin receptors. Using the panel of CsA and FK506 analogues, we show that calcineurin participates in the induction of TNF-alpha transcription in activated B cells. These results extend our previous demonstration that the kappa 3 binding factor is related to NFATp, the preexisting subunit of nuclear factor of activated T cells, and suggest that calcineurin-mediated modification of the kappa 3 binding factor in T cells is of key importance in the induction of TNF-alpha transcription. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR VIROL,BOSTON,MA 02114. HARVARD UNIV,DEPT CHEM,CAMBRIDGE,MA 02138. HUMAN GENOME SCI,ROCKVILLE,MD 20850. RP GOLDFELD, AE (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,44 BINNEY ST,BOSTON,MA 02114, USA. FU NCI NIH HHS [CA-58735, CA-42471]; NIGMS NIH HHS [GM-38627] NR 26 TC 88 Z9 88 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD AUG 1 PY 1994 VL 180 IS 2 BP 763 EP 768 DI 10.1084/jem.180.2.763 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA NZ385 UT WOS:A1994NZ38500042 PM 8046352 ER PT J AU TOMITA, Y KHAN, A SYKES, M AF TOMITA, Y KHAN, A SYKES, M TI ROLE OF INTRATHYMIC CLONAL DELETION AND PERIPHERAL ANERGY IN TRANSPLANTATION TOLERANCE INDUCED BY BONE-MARROW TRANSPLANTATION IN MICE CONDITIONED WITH A NONMYELOABLATIVE REGIMEN SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; T-CELL TOLERANCE; MIXED ALLOGENEIC CHIMERAS; CYCLOPHOSPHAMIDE-INDUCED TOLERANCE; NONLETHAL PREPARATIVE REGIMEN; MONOCLONAL-ANTIBODIES; NEGATIVE SELECTION; I-E; EXTRATHYMIC TOLERANCE; ENCODED ANTIGENS AB We have investigated the mechanism of tolerance induced by allogeneic bone marrow transplantation (BMT) in mice conditioned with a nonmyeloablative regimen. Permanent mixed chimerism and skin allograft tolerance were achieved when recipient B10 (H-2(b)) mice were pre-treated with anti-CD4 and anti-CD8 mAbs, thymic irradiation, and 3 Gy whole body irradiation, followed by injection of B10.A (H-2(a)) bone marrow cells. V beta 11(+) T cells are normally deleted in I-E(+) B10.A mice, but not in I-E(-) B10 mice. In spleens of mixed B10.A-->B10 chimeras, V beta 11(+) B10 T cells were reduced but detectable in the first 6 wk after BMT, and later became undetectable. Splenic V beta 11+ T cells were unresponsive to receptor cross-linking with V beta 11-specific mAb, demonstrating anergy. B10 V beta 11(+) T cells were also detected in spleens of mice that were thymectomized before BMT. In PBL of chimeras, V beta 11(+) T cells were undetectable for at least 1.5 yr. Thymocyte chimerism and extensive clonal deletion of mature V beta 11(+) B10 thymocytes were observed as early as 10 days post-BMT and at all subsequent time points in thymi of mixed chimeras. Rare I-E(+) donor cells were detected in day 10 thymi, and these increased progressively in frequency at later times. In chimeras prepared in the reciprocal strain combination, B10-->B10.A, B10 donor V beta 11(+) T cells were undetectable in PBL. Together, our results implicate both central clonal deletion and peripheral clonal anergy in tolerance induced with our regimen. A very low number of intrathymic donor cells or low density of Ag expression is sufficient to mediate extensive clonal deletion of thymocytes that recognize donor Ags. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,TRANSPLANTAT BIOL RES CTR,SURG SERV,BOSTON,MA 02129. FU NHLBI NIH HHS [R01HL49915] NR 64 TC 258 Z9 262 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 AUG 1 PY 1994 VL 153 IS 3 BP 1087 EP 1098 PG 12 WC Immunology SC Immunology GA NY342 UT WOS:A1994NY34200019 PM 8027542 ER PT J AU SMITH, CV SABLINSKI, T ARN, JS MYERS, DE ROSENGARD, BR UCKUN, FM SACHS, DH AF SMITH, CV SABLINSKI, T ARN, JS MYERS, DE ROSENGARD, BR UCKUN, FM SACHS, DH TI IN-VIVO TREATMENT WITH MONOCLONAL-ANTIBODIES DIRECTED AGAINST CD4 AND CD8 ANTIGENS IN MINIATURE SWINE SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE CD4; CD8; MINIATURE SWINE; MONOCLONAL ANTIBODIES; TRANSPLANTATION ID MAJOR HISTOCOMPATIBILITY COMPLEX; BONE-MARROW TRANSPLANTATION; RENAL-ALLOGRAFT RECIPIENTS; POKEWEED ANTIVIRAL PROTEIN; KIDNEY-TRANSPLANTATION; TOLERANCE INDUCTION; CLASS-I; INVIVO; CELLS; SURVIVAL AB Two monoclonal antibodies (mAb) with specificities for mature T-cell subsets in miniature swine have been characterized previously. Antibody 74-12-4 recognizes the porcine CD4 accessory molecule and 76-2-11 is specific for the CD8 molecule. We have now examined the effects of in vivo administration of 74-12-4 and 76-2-11 on several parameters of transplantation immunity. No prolongation of class I disparate skin or kidney graft survival was observed in animals treated with either mAb alone or with a combination of both. In addition, in vivo treatment with these mAbs, in combination with subtherapeutic total body irradiation, failed to permit engraftment of allogeneic bone marrow. These therapeutic failures were thought likely to be a consequence of the fact that 74-12-4 coats, but does not deplete, CD4 cells in vivo. Because there are numerous anti-human mAbs that likewise fail to deplete in vivo, we have used 74-12-4 as a prototype to further manipulations aimed at achieving depletion. We attempted to eliminate 74-12-4-coated cells in two animals by subsequent administration of a hyperimmune pig anti-mouse Ig serum. In both such treated animals, administration of this serum produced surprisingly rapid clearance of 74-12-4 from the circulation and caused uncoating of CD4 cells, but no significant cell elimination was detected by flow cytometry. We have also prepared an anti-porcine-CD4 immunotoxin by conjugating 74-12-4 to the ribosome inhibitory plant toxin, pokeweed antiviral protein. This immunotoxin led to significant but not complete CD4 cell depletion from the peripheral blood in four of four treated animals. Further manipulations and possibly development of new anti-porcine CD4 mAbs may therefore be required to achieve complete depletion and successful mAb-mediated modification of transplantation responses. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,TRANSPLANTAT BIOL RES CTR,SURG SERV,BOSTON,MA 02129. FU NCI NIH HHS [R01 CA55553-02] NR 41 TC 3 Z9 3 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD AUG PY 1994 VL 16 IS 2 BP 105 EP 114 DI 10.1097/00002371-199408000-00004 PG 10 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA PG913 UT WOS:A1994PG91300004 PM 7804525 ER PT J AU LEWIS, SE RAO, MS SYMES, AJ DAUER, WT FINK, JS LANDIS, SC HYMAN, SE AF LEWIS, SE RAO, MS SYMES, AJ DAUER, WT FINK, JS LANDIS, SC HYMAN, SE TI COORDINATE REGULATION OF CHOLINE-ACETYLTRANSFERASE, TYROSINE-HYDROXYLASE, AND NEUROPEPTIDE MESSENGER-RNAS BY CILIARY NEUROTROPHIC FACTOR AND LEUKEMIA INHIBITORY FACTOR IN CULTURED SYMPATHETIC NEURONS SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE NEUROTRANSMITTER EXPRESSION; CILIARY NEUROTROPHIC FACTOR; CHOLINERGIC DIFFERENTIATION FACTOR; LEUKEMIA INHIBITORY FACTOR; DEPOLARIZATION; NEUROPEPTIDE ID VASOACTIVE-INTESTINAL-PEPTIDE; NEUROTRANSMITTER PLASTICITY INVIVO; SUPERIOR CERVICAL-GANGLION; CELL CONDITIONED MEDIUM; GENE-RELATED PEPTIDE; RAT SWEAT GLANDS; SUBSTANCE-P; DIFFERENTIATION FACTOR; DEVELOPMENTAL-CHANGES; RECEPTOR COMPONENT AB The neurotransmitter phenotype switch that occurs in cultures of rat superior cervical ganglion neurons after treatment with leukemia inhibitory factor or ciliary neurotrophic factor is a useful model permitting investigation of the mechanisms of cytokine-mediated differentiation. Recently the actions of leukemia inhibitory factor and ciliary neurotrophic factor have been linked through their interactions with related receptor complexes. Here we compare the effects of these two cytokines on gene expression in sympathetic neuronal cultures and begin to investigate their mechanisms. We report that, as has been shown for leukemia inhibitory factor, ciliary neurotrophic factor regulates peptides and classical transmitters in these cultures at the mRNA level. In addition, we find that the induction of substance P mRNA by these cytokines is rapid, dependent on protein synthesis, and occurs in 40-50% of superior cervical ganglion neurons in dissociated culture. C1 HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,MOLEC NEUROBIOL LAB,BOSTON,MA. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02114. CASE WESTERN RESERVE UNIV,DEPT NEUROSCI,CLEVELAND,OH 44106. RI Symes, Aviva/S-7471-2016 OI Symes, Aviva/0000-0003-2557-9939 FU NICHD NIH HHS [HD25681]; NIMH NIH HHS [MH 00892]; NINDS NIH HHS [NS 29767] NR 66 TC 66 Z9 66 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 1994 VL 63 IS 2 BP 429 EP 438 PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA NZ017 UT WOS:A1994NZ01700005 PM 7518494 ER PT J AU GLASS, J GRUBER, ML CHER, L HOCHBERG, FH AF GLASS, J GRUBER, ML CHER, L HOCHBERG, FH TI PREIRRADIATION METHOTREXATE CHEMOTHERAPY OF PRIMARY CENTRAL-NERVOUS-SYSTEM LYMPHOMA - LONG-TERM OUTCOME SO JOURNAL OF NEUROSURGERY LA English DT Article DE PRIMARY CENTRAL NERVOUS SYSTEM; TUMOR; LYMPHOMA; CHEMOTHERAPY; METHOTREXATE; WHOLE-BRAIN RADIATION THERAPY ID HIGH-DOSE METHOTREXATE; PRIMARY MALIGNANT-LYMPHOMA; NON-HODGKINS-LYMPHOMA; COMBINED MODALITY THERAPY; PRIMARY CNS LYMPHOMA; ADJUVANT CHEMOTHERAPY; LEUCOVORIN RESCUE; RADIATION-THERAPY; SURVIVAL; BRAIN AB The treatment of primary central nervous system lymphoma with chemotherapy prior to whole-brain radiation therapy (WBRT) has improved outcome considerably in this previously fatal disease. Complete or partial responses to intravenous methotrexate (3.5 gm/sq m with leucovorin rescue every 3 weeks for two to four cycles) were seen in 12 of 13 patients originally treated. A total of 25 patients (including the original 13) have now been treated with one to six cycles of methotrexate every 10 to 21 days prior to WBRT. Twenty-two had partial or complete responses, with a median duration of response of 32 months. Median survival time was 33 months (42.5 months in those responding to therapy). Nine patients are alive and without evidence of disease 9 to 122 months following therapy. Acute and long-term toxicities were minimal. Systemic methotrexate administration prior to WBRT is well tolerated and produces long-term survival. C1 UNIV CALIF LOS ANGELES,DEPT NEUROSURG,LOS ANGELES,CA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROL,BOSTON,MA. RP GLASS, J (reprint author), TEMPLE UNIV,CTR COMPREHENS CANC,CTR BRAIN TUMOR,POB 38346,3322 N BROAD ST,PHILADELPHIA,PA 19140, USA. NR 34 TC 208 Z9 216 U1 1 U2 2 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD AUG PY 1994 VL 81 IS 2 BP 188 EP 195 DI 10.3171/jns.1994.81.2.0188 PG 8 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA NY086 UT WOS:A1994NY08600006 PM 8027800 ER PT J AU TATTER, SB BORGES, LF LOUIS, DN AF TATTER, SB BORGES, LF LOUIS, DN TI CENTRAL NEUROCYTOMAS OF THE CERVICAL SPINAL-CORD SO JOURNAL OF NEUROSURGERY LA English DT Note DE CENTRAL NEUROCYTOMA; SYNAPTOPHYSIN; SPINAL CORD NEOPLASM; DIFFERENTIAL DIAGNOSIS ID DYSEMBRYOPLASTIC NEUROEPITHELIAL TUMOR; INTRAVENTRICULAR NEUROCYTOMA; DIFFERENTIATION; HEMORRHAGE; ADULTS AB Central neurocytoma is a neuronal neoplasm that occurs supratentorially in the lateral or third ventricles. The authors report the clinical, neuroradiological, and neuropathological features of two neurocytomas arising in the spinal cord of two men, aged 65 and 49 years. The patients presented with progressive neurological deficits referable to the cervical spinal cord. Magnetic resonance imaging revealed isodense intramedullary spinal cord tumors at the C3-4 level. Both tumors were initially misdiagnosed as gliomas. In Case 1 the correct diagnosis was made after electron microscopy revealed neuronal features. Immunostaining in Case 2 revealed that tumor cells were positive for synaptophysin and negative for glial fibrillary acidic protein, strongly indicating a neuronal tumor. It is suggested that this spinal cord neoplasm be included under the designation ''central neurocytoma.'' C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL NEUROPATHOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,NEUROSURG SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 24 TC 85 Z9 92 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD AUG PY 1994 VL 81 IS 2 BP 288 EP 293 DI 10.3171/jns.1994.81.2.0288 PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA NY086 UT WOS:A1994NY08600021 PM 8027814 ER PT J AU HAMBERG, LM HUNTER, GJ ALPERT, NM CHOI, NC BABICH, JW FISCHMAN, AJ AF HAMBERG, LM HUNTER, GJ ALPERT, NM CHOI, NC BABICH, JW FISCHMAN, AJ TI THE DOSE UPTAKE RATIO AS AN INDEX OF GLUCOSE-METABOLISM - USEFUL PARAMETER OR OVERSIMPLIFICATION SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE PET-FDG; DUR; GLUCOSE METABOLISM; COMPARTMENTAL ANALYSIS; LUNG CANCER; DIAGNOSTIC IMAGING ID POSITRON EMISSION TOMOGRAPHY; FDG-PET; CANCER; FLUORINE-18-FLUORODEOXYGLUCOSE; ONCOLOGY; VALUES; HEAD AB The dose uptake ratio (DUR) has been used as a quantitative index of glucose metabolism for tumor classification and monitoring response to treatment. In order to provide consistent results, DUR measurements should be made when the concentration of tracer has reached a plateau. The time of this plateau cannot be identified from a single static acquisition, Methods: In this study, we investigated the changes in DUR as a function of time in eight patients with stage iii lung cancer. All patients underwent a quantitative dynamic F-18-FDG PET study before and after treatment and the data were analyzed with a three-compartment model. Using the fitted model parameters, the DUR was predicted at the plateau and intermediate times. Results: Tumor concentrations of F-18-FDG did not reach a plateau within the 90 min of imaging in any of the pre-treatment studies and only in one case post-treatment. The average time to reach 95% of the plateau value pre-treatment was 298 +/- 42 min (range: 130-500 min); in post-treatment, it was 154 +/- 31 min (range: 65-240 min). The difference between the plateau DUR and the 60-min value was 46% +/- 6% pre-treatment and 17% +/- 5% post-treatment. Conclusions: These data indicate that DUR can vary widely with the time of measurement and that DUR should be interpreted with caution in any individual patient. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 19 TC 283 Z9 290 U1 0 U2 6 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD AUG PY 1994 VL 35 IS 8 BP 1308 EP 1312 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PA676 UT WOS:A1994PA67600014 PM 8046485 ER PT J AU ZACHAZEWSKI, JE FELDER, CR KNORTZ, K THEIN, L QUILLEN, WS AF ZACHAZEWSKI, JE FELDER, CR KNORTZ, K THEIN, L QUILLEN, WS TI COMPETENCE REVALIDATION STUDY - A DESCRIPTION OF ADVANCED CLINICAL-PRACTICE IN SPORTS PHYSICAL THERAPY SO JOURNAL OF ORTHOPAEDIC & SPORTS PHYSICAL THERAPY LA English DT Article DE SPORTS CLINICAL SPECIALIST; BOARD CERTIFICATION; COMPETENCE AB The first board-certified sports clinical specialists (SCSs) obtained their specialty credentials in 1986. A history of the development process is provided. The Sports Specialty Council and American Board of Physical Therapy Specialties are responsible for maintaining currency in the examination. Therefore, a review of current practice standards was conducted in 1992. The purpose of this article is to present an overview of the methodology and results of the survey. Complete details are found in the document entitled ''Description of Advanced Clinical Practice: Sports Physical Therapy'' (DACP), which is available through the Sports Physical Therapy Section. A random sample of 2,000 members of the Sports Physical Therapy Section and all clinical specialists certified at the time (N = 49) were surveyed. A total of 507 members (25.3%) and 49 SCSs (100%) returned the questionnaire. The domain of knowledge required by the SCS was divided into nine different areas, with multiple competency statements in each area. Respondents rated each competency statement on three scales: importance, entry-level preparation, and frequency of use. A panel of content area experts then reviewed the results to develop the final competencies and examination blueprint. These competency statements will form the basis of the SCS examination and be implemented in 1995. Competency and examination revision is a constantly evolving process, and this document should serve as a guide for further revisions. RP ZACHAZEWSKI, JE (reprint author), MASSACHUSETTS GEN HOSP,INST HLTH PROFESS,101 MERRIMAC ST,BOSTON,MA 02114, USA. NR 0 TC 2 Z9 2 U1 1 U2 4 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0190-6011 J9 J ORTHOP SPORT PHYS JI J. Orthop. Sports Phys. Ther. PD AUG PY 1994 VL 20 IS 2 BP 110 EP 124 PG 15 WC Orthopedics; Rehabilitation; Sport Sciences SC Orthopedics; Rehabilitation; Sport Sciences GA NY792 UT WOS:A1994NY79200008 PM 7920602 ER PT J AU BREUER, CK TARBELL, NJ MAUCH, PM WEINSTEIN, HJ MORRISSEY, M NEUBERG, D SHAMBERGER, RC AF BREUER, CK TARBELL, NJ MAUCH, PM WEINSTEIN, HJ MORRISSEY, M NEUBERG, D SHAMBERGER, RC TI THE IMPORTANCE OF STAGING LAPAROTOMY IN PEDIATRIC HODGKINS-DISEASE SO JOURNAL OF PEDIATRIC SURGERY LA English DT Article; Proceedings Paper CT 1993 Annual Meeting of the Section on Surgery of the American-Academy-of-Pediatrics CY OCT 29-31, 1993 CL WASHINGTON, DC SP AMER ACAD PEDIAT DE HODGKINS DISEASE; STAGING LAPAROTOMY ID COMPUTED-TOMOGRAPHY; STANFORD EXPERIENCE; PROGNOSTIC FACTORS; MOPP CHEMOTHERAPY; 2ND MALIGNANCIES; COMPLICATIONS; CHILDREN; LYMPHANGIOGRAPHY; IRRADIATION; MANAGEMENT C1 CHILDRENS HOSP,DANA FARBER CANC INST,DEPT SURG,BOSTON,MA 02115. CHILDRENS HOSP,DANA FARBER CANC INST,DEPT RADIAT THERAPY,BOSTON,MA 02115. CHILDRENS HOSP,DANA FARBER CANC INST,DEPT PEDIAT,DIV HEMATOL ONCOL,BOSTON,MA 02115. CHILDRENS HOSP,DANA FARBER CANC INST,DEPT STAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. NR 51 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 0022-3468 J9 J PEDIATR SURG JI J. Pediatr. Surg. PD AUG PY 1994 VL 29 IS 8 BP 1085 EP 1089 DI 10.1016/0022-3468(94)90284-4 PG 5 WC Pediatrics; Surgery SC Pediatrics; Surgery GA PB516 UT WOS:A1994PB51600027 PM 7965511 ER PT J AU NIEDERMAN, R AF NIEDERMAN, R TI IS GUIDED TISSUE REGENERATION REALLY GUIDED TISSUE REGENERATION SO JOURNAL OF PERIODONTOLOGY LA English DT Letter ID EXPERIMENTAL FURCATION DEFECTS; PERIODONTAL-LIGAMENT; CEMENTUM-LIKE; BONE; INVITRO; CELLS RP NIEDERMAN, R (reprint author), FORSYTH DENT CTR,140 FENWAY,BOSTON,MA 02115, USA. OI niederman, richard/0000-0001-6674-1774 NR 16 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD PERIODONTOLOGY PI CHICAGO PA 737 NORTH MICHIGAN AVENUE, SUITE 800, CHICAGO, IL 60611-2690 SN 0022-3492 J9 J PERIODONTOL JI J. Periodont. PD AUG PY 1994 VL 65 IS 8 BP 804 EP 804 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA PC617 UT WOS:A1994PC61700012 PM 7965559 ER PT J AU FIORONI, L FAVA, M GENAZZANI, AD FACCHINETTI, F GENAZZANI, AR AF FIORONI, L FAVA, M GENAZZANI, AD FACCHINETTI, F GENAZZANI, AR TI LIFE EVENTS IMPACT IN PATIENTS WITH SECONDARY AMENORRHEA SO JOURNAL OF PSYCHOSOMATIC RESEARCH LA English DT Article ID FUNCTIONAL HYPOTHALAMIC-AMENORRHEA; LUTEINIZING-HORMONE; SECRETION; WOMEN AB To evaluate the relationship between stressful life events and the onset of secondary amenorrhoea Paykel's semi-structured interview for Recent Life Events was administered to patients affected by secondary amenorrhea and also to healthy volunteers. The number, quality, and objective negative impact of life events were compared among different hormonal subtypes of secondary amenorrhoea and healthy normally menstruating women, as a control group. The number of life events in amenorrhoeic patients (N = 131) was significantly greater than those observed in the control group (N = 64) (45.9 vs 32.8%). Moreover, where only hypothalamic hypogonadotrophic amenorrhoea was considered, the occurrence of life events was significantly higher (59.8%) than in hyperandrogenic (26.6%) or in normogonadotrophic (20.4%) patients. The most prevalent events among hypothalamic hypogonadotrophic amenorrhoeic patients were those classified as 'undesirable', 'uncontrolled' and with 'Objective Negative Impact'. The present study supports the hypothesis of a cause-effect relationship between stressful personal life events and the onset of secondary amenorrhoea of hypogonadotrophic subtype. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02114. RP FIORONI, L (reprint author), UNIV MODENA,SCH MED,OSTETR P GINECOL CLIN,VIA POZZO 71,I-41100 MODENA,ITALY. RI Facchinetti, Fabio/K-9929-2014 OI Facchinetti, Fabio/0000-0003-4694-9564 NR 21 TC 13 Z9 13 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0022-3999 J9 J PSYCHOSOM RES JI J. Psychosomat. Res. PD AUG PY 1994 VL 38 IS 6 BP 617 EP 622 DI 10.1016/0022-3999(94)90059-0 PG 6 WC Psychiatry SC Psychiatry GA PE091 UT WOS:A1994PE09100015 PM 7990070 ER PT J AU DENARDO, BA TUCKER, LB MILLER, LC SZER, IS SCHALLER, JG ALARIO, A FRASER, P MCCARTHY, P MILLS, J SULLIVAN, J SUNDEL, R ZEMEL, L AF DENARDO, BA TUCKER, LB MILLER, LC SZER, IS SCHALLER, JG ALARIO, A FRASER, P MCCARTHY, P MILLS, J SULLIVAN, J SUNDEL, R ZEMEL, L TI DEMOGRAPHY OF A REGIONAL PEDIATRIC RHEUMATOLOGY PATIENT POPULATION SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE EPIDEMIOLOGY; PEDIATRICS; DIFFERENTIAL DIAGNOSIS ID JUVENILE PSORIATIC-ARTHRITIS; ANKYLOSING-SPONDYLITIS; REITERS-SYNDROME; CRITERIA; DERMATOMYOSITIS; POLYMYOSITIS; EPIDEMIOLOGY; PREVALENCE; CHILDHOOD; CHILDREN AB Objective. To examine the descriptive epidemiology of a regional cohort of children with rheumatic disease, and to document the variety and frequency of diseases encountered among pediatric rheumatology centers. Methods. Pediatric rheumatology centers in southern New England participated in a prospective multicenter patient registry. All outpatients attending clinics at 8 pediatric rheumatology centers were enrolled as subjects during the 8-year period of study (n = 4585). Diagnostic criteria defined the rheumatic disease cases which were determined by clinical examination by a pediatric rheumatologist, and record linkage was achieved to avoid duplication of subjects. Results. Rheumatic conditions were diagnosed in 1742 subjects. Juvenile rheumatoid arthritis (JRA) was the most frequently encountered rheumatic condition (53%), followed by spondyloarthropathy syndromes (13%), vasculitis (10%), systemic lupus erythematosus (SLE) (6%), isolated Raynaud's phenomenon (5%), dermatomyositis/polymyositis (DM/PM) (5%), and scleroderma (2%). The mean annual incidence of JRA, spondyloarthropathy syndromes, SLE and DM/PM among children referred to pediatric rheumatology centers in Massachusetts was 4.0, 2.0, 0.3 and 0.4 per 100,000 children at risk, respectively. Nonrheumatic conditions were diagnosed in 2843 subjects, among which musculoskeletal conditions were most frequent (56%) followed by infectious disorders (18%), psychogenic disorders (3%), fever of unknown origin (2%), and abnormal immune serology without a specific diagnosis (2%). Conclusion. The use of a multicenter patient registry was successful in allowing the collection of descriptive epidemiologic data on a large and well defined sample of children with rare disorders. C1 FLOATING HOSP CHILDREN,DEPT PEDIAT,BOSTON,MA. TUFTS UNIV,SCH MED,BOSTON,MA 02111. UNIV SO CALIF,SCH MED,LOS ANGELES,CA. RHODE ISL HOSP,PROVIDENCE,RI 02902. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. YALE NEW HAVEN MED CTR,NEW HAVEN,CT 06520. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. UNIV MASSACHUSETTS,MED CTR,BOSTON,MA 02125. NEWINGTON CHILDRENS HOSP,NEWINGTON,CT. RP DENARDO, BA (reprint author), FLOATING HOSP CHILDREN,DIV PEDIAT RHEUMATOL,750 WASHINGTON ST,BOX 286,BOSTON,MA 02111, USA. OI Sundel, Robert/0000-0002-0083-5695 FU PHS HHS [MCJ253443, MCJ255012, MCJ255064] NR 46 TC 76 Z9 78 U1 0 U2 1 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO ON M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD AUG PY 1994 VL 21 IS 8 BP 1553 EP 1561 PG 9 WC Rheumatology SC Rheumatology GA PA712 UT WOS:A1994PA71200032 PM 7983664 ER PT J AU DONAHUE, DM LEE, ME SUEN, HC QUERTERMOUS, T WAIN, JC AF DONAHUE, DM LEE, ME SUEN, HC QUERTERMOUS, T WAIN, JC TI RESIDENT RESEARCH AWARD - PULMONARY HYPOXIA INCREASES ENDOTHELIN-1 GENE-EXPRESSION IN SHEEP SO JOURNAL OF SURGICAL RESEARCH LA English DT Article ID VASOCONSTRICTOR SUBSTANCE; INHIBITORS; DOGS; MECHANISM; CELLS AB The hypoxic pulmonary vasoconstrictor response (HPVR) is a physiologic mechanism for directing pulmonary blood flow to nonhypoxic regions of the lung. The mechanism of this response remains unclear. To investigate the role of endothelin-1 (ET-1), a potent vasoconstrictor produced by vascular endothelium, in HPVR an in vivo model of alveolar hypoxia was developed. When one lung in an anesthetized sheep was made hypoxic, the static ET-1 mRNA levels in lung tissue increased in proportion to the observed decrease in pulmonary blood flow (Q(p)) to that lung. With reversal of hypoxia, Q(p) and ET-1 levels returned to baseline. This relationship between alveolar hypoxia and ET-1 mRNA levels suggests a role for ET-1 in the local pulmonary response to hypoxia. (C) 1994 Academic Press, Inc. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,THORAC SURG UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CARDIAC UNIT,BOSTON,MA 02114. RP DONAHUE, DM (reprint author), HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02114, USA. NR 24 TC 19 Z9 20 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD AUG PY 1994 VL 57 IS 2 BP 280 EP 283 DI 10.1006/jsre.1994.1145 PG 4 WC Surgery SC Surgery GA PA253 UT WOS:A1994PA25300009 PM 8028336 ER PT J AU PERKELL, JS HILLMAN, RE HOLMBERG, EB AF PERKELL, JS HILLMAN, RE HOLMBERG, EB TI GROUP-DIFFERENCES IN MEASURES OF VOICE PRODUCTION AND REVISED VALUES OF MAXIMUM AIR-FLOW DECLINATION RATE SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article AB In previous reports, aerodynamic and acoustic measures of voice production were presented for groups of normal male and female speakers [Holmberg et al., J. Acoust. Soc. Am. 84, 511-529 (1988); J. Voice 3, 294-305 (1989)] that were used as norms in studies of voice disorders [Hillman et al., J. Speech Hear, Res. 32, 373-392 (1989); J. Voice 4, 52-63 (1990)]. Several of the measures were extracted from glottal airflow waveforms that were derived by inverse filtering a high-time-resolution oral airflow signal. Recently, the methods have been updated and a new study of additional subjects has been conducted. This report presents previous (1988) and current (1993) group mean values of sound pressure level, fundamental frequency, maximum airflow declination rate, ac flow, peak flow, minimum flow, ac-dc ratio, inferred subglottal air pressure, average flow, and glottal resistance. Statistical tests indicate overall group differences and differences for values of several individual parameters between the 1988 and 1993 studies. Some inter-study differences in parameter values may be due to sampling effects and minor methodological differences; however, a comparative test of 1988 and 1993 inverse filtering algorithms shows that some lower 1988 values of maximum flow declination rate were due at least in part to excessive low-pass filtering in the 1988 algorithm. The observed differences should have had a negligible influence on the conclusions of our studies of voice disorders. C1 MASSACHUSETTS EYE & EAR INFIRM,VOICE & SPEECH LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02115. RP PERKELL, JS (reprint author), MIT,ELECTR RES LAB,ROOM 36-591,50 VASSAR ST,CAMBRIDGE,MA 02139, USA. FU NIDCD NIH HHS [DC00266] NR 7 TC 20 Z9 20 U1 0 U2 1 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD AUG PY 1994 VL 96 IS 2 BP 695 EP 698 DI 10.1121/1.410307 PN 1 PG 4 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA PB503 UT WOS:A1994PB50300007 PM 7930069 ER PT J AU DUNBAR, SF MARKS, LB SOBER, AJ ROSENBERG, A SUIT, HD AF DUNBAR, SF MARKS, LB SOBER, AJ ROSENBERG, A SUIT, HD TI CONNECTIVE-TISSUE TUMORS IN PATIENTS WITH CUTANEOUS MELANOMA SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID CLEAR CELL-SARCOMA; MALIGNANT-MELANOMA; CANCERS; RISK AB Background: A possible relation between cutaneous melanoma and connective tissue tumors has been described. Objective: After the observation that a group of our patients had both cutaneous melanoma and a soft tissue sarcoma, we elected to review this formally. Eleven patients with both diagnoses were identified and are described. Methods: A computer search through the Medical Records Department and the Tumor Registry of the Massachusetts General Hospital identified seven men and four women with the diagnoses of melanoma and malignant bone or soft tissue sarcoma. The medical records and pathology specimens of all tumors were reviewed. Results: In three patients, the two tumors were diagnosed within 1 year of each other, in seven, the diagnosis of melanoma was made first, and in one, melanoma was diagnosed after the connective tissue lesion. The interval between the two diagnoses ranged up to 13 years. Although the locations and types of melanoma were typical, some of the connective tissue tumors were unusual; there were two sacral chordomas. In two instances, the melanoma and connective tissue tumor were anatomically close; the sarcoma developed at the edge of the resection of the prior melanoma in one patient. None of the tumors developed in previously irradiated tissues, and in no instance did the second tumor appear to be caused by the therapy received for the first. None of the patients had a family history of melanoma. Four patients had other cancers in addition to the melanoma and connective tissue tumor. Conclusion: Although these patients were seen in a referral center, it is our impression (based on the total number of patients with connective tissue tumors seen and the incidence of melanoma in the general population) that observing 11 patients with both types of tumors is greater than would be expected by chance. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT DERMATOL,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,BOSTON,MA. DUKE UNIV,CTR CANC,DEPT RADIAT ONCOL,DURHAM,NC. NR 22 TC 6 Z9 6 U1 0 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 AUG PY 1994 VL 31 IS 2 BP 216 EP 219 PN 1 PG 4 WC Dermatology SC Dermatology GA NZ589 UT WOS:A1994NZ58900008 PM 8040404 ER PT J AU NOGITA, T WONG, TY HIDANO, A MIHM, MC KAWASHIMA, M AF NOGITA, T WONG, TY HIDANO, A MIHM, MC KAWASHIMA, M TI PEDUNCULATED LIPOFIBROMA - A CLINICOPATHOLOGICAL STUDY OF 32 CASES SUPPORTING A SIMPLIFIED NOMENCLATURE SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID SUPERFICIALIS AB Thirty-two cases are described of a relatively rare form of benign connective tissue proliferation characterized by ectopic fatty tissue in the dermis. The lesions usually appear as large, solitary, slow-growing, pedunculated to dome-shaped, skin-colored nodules or plaques showing predilection for the buttock and upper thigh. Other areas involved include the back, shoulder, knee, neck, and ear. Twenty patients were women and 12 were men, 19 to 78 years of age (mean, 46.9 years). The size of the lesions ranged from 4 to 69 mm (mean, 49 mm). Histologically, the lesions were characterized by the presence of mature adipose tissue infiltrating around the periadnexal adventitial dermis and between adnexal structures and admiring with dense stromal collagen. Marked deposition of mucopolysaccarides was noted in the majority of the lesions. Clinical follow-up in all 32 patients showed no evidence of recurrence. Because of their distinctive clinicopathologic features, we prefer to designate these lesions as solitary, pedunculated lipofibroma. In addition, seven of the patients had diabetes mellitus, suggesting a possible relation between the two conditions. C1 MASSACHUSETTS GEN HOSP,DIV DERMATOPATHOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RP NOGITA, T (reprint author), TOKYO WOMENS MED COLL,DEPT DERMATOL,SHINGUKU KU,8-1 KAWADACHO,TOKYO 162,JAPAN. NR 14 TC 9 Z9 10 U1 0 U2 0 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 AUG PY 1994 VL 31 IS 2 BP 235 EP 240 PN 1 PG 6 WC Dermatology SC Dermatology GA NZ589 UT WOS:A1994NZ58900013 PM 8040407 ER PT J AU SAGIE, A SCHWAMMENTHAL, E PADIAL, LR VAZQUEZ, JA WEYMAN, AE LEVINE, RA AF SAGIE, A SCHWAMMENTHAL, E PADIAL, LR VAZQUEZ, JA WEYMAN, AE LEVINE, RA TI DETERMINANTS OF FUNCTIONAL TRICUSPID REGURGITATION IN INCOMPLETE TRICUSPID-VALVE CLOSURE - DOPPLER COLOR-FLOW STUDY OF 109 PATIENTS SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID TWO-DIMENSIONAL ECHOCARDIOGRAPHY; CONTINUOUS-WAVE DOPPLER; MITRAL REGURGITATION; QUANTITATIVE ASSESSMENT; DILATED CARDIOMYOPATHY; NONINVASIVE ESTIMATION; ANULAR DILATATION; PRESSURE; QUANTIFICATION; HEART AB Objectives. The aim of this study was to investigate the association between the pattern of incomplete tricuspid valve closure and the presence of tricuspid regurgitation and to identify factors that determine the severity of regurgitation associated with this pattern. Background. The incomplete tricuspid valve closure pattern (defined as apical displacement of the leaflets) has been described by two dimensional echocardiography. However, whether this pattern is universally associated with tricuspid regurgitation and the determinants of severity of regurgitation in its presence have not been studied by Doppler color flow mapping. Methods. We identified 109 consecutive patients (mean age 62 +/- 17 years) with incomplete tricuspid valve closure who were studied by Doppler color flow mapping. We measured the linear apical displacement of the coaptation point from the tricuspid annulus and the area of displacement between the leaflets and annulus. Right atrial, ventricular and annular dimensions were measured and compared with those in a group of normal subjects. Results. Tricuspid regurgitation was present in all patients with the incomplete closure pattern; it was mild in 14%, moderate in 19% and severe in 67%. Apical displacement was significantly greater (p < 0.02) in those with severe regurgitation than in those with mild regurgitation or in normal subjects. Tricuspid annulus dilation was the only independent predictor of severity of regurgitation. The right ventricle was not significantly dilated in 32% of patients, and right ventricular systolic pressure was not correlated with the severity of regurgitation and was < 30 mm Hg in 11% of patients. Conclusions. Tricuspid regurgitation was associated with incomplete tricuspid valve closure in all patients studied and was moderate to severe in 86%. Impaired coaptation is best reflected by the displacement area between the leaflets and the annulus. High pulmonary pressure and significant right ventricular dilation are not prerequisites for functional tricuspid regurgitation. Annular dilation is the most consistent and important determinant of this lesion. C1 MASSACHUSETTS GEN HOSP,DEPT MED,CARDIAC ULTRASOUND LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 43 TC 88 Z9 91 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD AUG PY 1994 VL 24 IS 2 BP 446 EP 453 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PH376 UT WOS:A1994PH37600026 PM 8034882 ER PT J AU SEMIGRAN, MJ THAIK, CM FIFER, MA BOUCHER, CA PALACIOS, IF DEC, GW AF SEMIGRAN, MJ THAIK, CM FIFER, MA BOUCHER, CA PALACIOS, IF DEC, GW TI EXERCISE CAPACITY AND SYSTOLIC AND DIASTOLIC VENTRICULAR-FUNCTION AFTER RECOVERY FROM ACUTE DILATED CARDIOMYOPATHY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID CONGESTIVE HEART-FAILURE; ANAEROBIC THRESHOLD; EJECTION FRACTION; MYOCARDITIS; PERFORMANCE; DYSFUNCTION; DISEASE; BIOPSY; ADULT AB Objectives. This study was undertaken to determine whether abnormalities in exercise capacity or ventricular function persist after recovery from acute dilated cardiomyopathy. Background. Persistent ventricular structural abnormalities could cause abnormalities in exercise capacity or ventricular function. Methods. The results of rest and exercise first-pass radionuclide ventriculography in 18 patients who were seen within 6 months of the onset of dilated cardiomyopathy and subsequently had a normal rest left ventricular ejection fraction were compared with those of age- and gender-matched control subjects. Results. Patients were studied 144 +/- 34 (mean +/- SEM) days after the onset of left ventricular dysfunction at a time when heart failure symptoms had resolved. Patients with myocyte necrosis, as assessed by endomyocardial biopsy (n = 13) or antimyosin scintigraphy (n = 12), recovered more rapidly than did those without necrosis. Oxygen consumption both at peak exercise (17.7 +/- 1.2 vs. 26.1 +/- 1.5 ml/kg per min, p < 0.05) and at the anaerobic threshold (11.1 +/- 0.5 vs. 17.1 +/- 1.3 ml/kg per min, p < 0.05) was lower in the patients who had recovered from cardiomyopathy than in control subjects. Rest and exercise end-systolic and end-diastolic left ventricular volumes were greater in the patients than in the control subjects, although stroke volumes were similar. Left ventricular filling at rest was lower at diastolic filling intervals of 40% and 90%, and rest and exercise left ventricular early peak filling rate normalized for end diastolic volume was slower in the patients than in the control subjects. At long-term follow-up of 1,082 +/- 206 days, two patients had a return of heart failure symptoms and a decrease in left ventricular ejection fraction. Conclusions. Despite the apparent normalization of rest left ventricular ejection fraction, patients who have recovered from dilated cardiomyopathy have abnormalities in aerobic exercise capacity and in left ventricular systolic and diastolic performance. C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP SEMIGRAN, MJ (reprint author), MASSACHUSETTS GEN HOSP,DEPT MED,CARDIAC UNIT,BULFINCH 211,BOSTON,MA 02114, USA. NR 30 TC 6 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD AUG PY 1994 VL 24 IS 2 BP 462 EP 470 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PH376 UT WOS:A1994PH37600028 PM 8034884 ER PT J AU GROVER, FL COHEN, DJ OPRIAN, C HENDERSON, WG SETHI, G HAMMERMEISTER, KE JOHNSON, R BIRDWELL, A SETHI, GK HALUZA, M KIM, T VITEK, ME CRAWFORD, M FOLLAND, ED KHURI, S HWANG, M MILLER, DC RAHIMTOOLA, S DEYKIN, D GOLD, J HUANG, P AF GROVER, FL COHEN, DJ OPRIAN, C HENDERSON, WG SETHI, G HAMMERMEISTER, KE JOHNSON, R BIRDWELL, A SETHI, GK HALUZA, M KIM, T VITEK, ME CRAWFORD, M FOLLAND, ED KHURI, S HWANG, M MILLER, DC RAHIMTOOLA, S DEYKIN, D GOLD, J HUANG, P TI DETERMINANTS OF THE OCCURRENCE OF AND SURVIVAL FROM PROSTHETIC VALVE ENDOCARDITIS - EXPERIENCE OF THE VETERANS AFFAIRS COOPERATIVE STUDY ON VALVULAR HEART-DISEASE SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID MANAGEMENT; REPLACEMENT AB For the determination of the risk factors associated with the development of and death caused by prosthetic valve endocarditis, data were reviewed from 66 patients who were prospectively entered into the Veterans Affairs Cooperative Study on Valvular Heart Disease and in whom prosthetic valve endocarditis subsequently developed. Data were recorded at 13 medical centers between October 1977 and September 1982 in patients randomized to receive a mechanical valve (Bjork-Shiley spherical disc, n = 510 patients) or a bioprosthetic valve (Hancock porcine heterograft, n = 522 patients). The average rate of prosthetic valve endocarditis development was 0.8% per year over an average follow-up period of 7.7 years. Of the 66 patients in whom prosthetic valve endocarditis developed (5.8%), 15 cases occurred within 2 months of operation (early) and 51 occurred after operation Gate). The most significant preoperative predictor of prosthetic valve endocarditis was active endocarditis at the time of operation (7.4% versus 0.9%) (p = 0.001). Early prosthetic valve endocarditis occurred more frequently in patients who underwent operation for multivalvular disease (p = 0.023). Significantly related perioperative variables were coma, prolonged mechanical ventilation, deep postoperative wound infection, postoperative jaundice, ventricular tachycardia, ventricular fibrillation, and replacement of more than one valve (p < 0.05). Multivariate predictors were hypoxia (p = 0.001), preoperative endocarditis (p = 0.003), preoperative valve lesion (p = 0.020), and resident surgeon (p = 0.05). Significant preoperative variables predictive of late prosthetic valve endocarditis were mitral stenosis and mixed mitral stenosis-regurgitation. The only multivariate predictor of late prosthetic valve endocarditis was superficial wound infection (p = 0.004). Of deaths attributable to prosthetic valve endocarditis, 41% occurred in patients treated with antibiotics alone, 48% occurred in patients treated with surgical intervention and antibiotics, and death resulted in both patients who received no treatment. No difference was found in the risk of early or late postoperative prosthetic valve endocarditis developing in patients receiving the mechanical valve versus those receiving the bioprosthetic valve. C1 UNIV COLORADO,HLTH SCI CTR,DEPT VET AFFAIRS MED CTR,CARDIOTHORAC SURG SECT,DENVER,CO. UNIV COLORADO,HLTH SCI CTR,DEPT VET AFFAIRS MED CTR,CARDIOL SECT,DENVER,CO. UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX. UNIV ARIZONA,HLTH SCI CTR,DEPT VET AFFAIRS MED CTR,TUCSON,AZ. DEPT VET AFFAIRS MED CTR,COOPERAT STUDIES PROGRAM,COORDINATING CTR,HINES,IL. NR 27 TC 76 Z9 80 U1 0 U2 2 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD AUG PY 1994 VL 108 IS 2 BP 207 EP 214 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA PB114 UT WOS:A1994PB11400002 PM 8041168 ER PT J AU PALMER, MT TURNEY, SZ AF PALMER, MT TURNEY, SZ TI TRACHEAL RUPTURE AND ATLANTOOCCIPITAL DISLOCATION - CASE-REPORT SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Note ID ATLANTOOCCIPITAL DISLOCATION; CERVICAL-SPINE; BLUNT TRAUMA; INJURIES; MANAGEMENT; FRACTURES; SURVIVAL AB Blunt trauma associated with tracheal rupture (TR) or atlanto-occipital dislocation (AOD) occurs rarely. Survival after sustaining either injury is even more uncommon. We describe a case of a patient who remarkably survived both injuries concurrently. C1 MARYLAND INST EMERGENCY MED SERV SYST,22 S GREENE ST,BALTIMORE,MD 21201. MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. NR 33 TC 17 Z9 19 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1079-6061 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD AUG PY 1994 VL 37 IS 2 BP 314 EP 317 DI 10.1097/00005373-199408000-00025 PG 4 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA PC952 UT WOS:A1994PC95200025 PM 8064933 ER PT J AU MCDOUGAL, WS AF MCDOUGAL, WS TI URINARY-TRACT RECONSTRUCTION SO JOURNAL OF UROLOGY LA English DT Editorial Material RP MCDOUGAL, WS (reprint author), MASSACHUSETTS GEN HOSP,DEPT UROL,BOSTON,MA, USA. NR 1 TC 3 Z9 3 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 AUG PY 1994 VL 152 IS 2 BP 343 EP 344 PN 1 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA NW329 UT WOS:A1994NW32900013 PM 8015067 ER PT J AU PALAZZO, JP PETERSEN, RO YOUNG, RH SCULLY, RE AF PALAZZO, JP PETERSEN, RO YOUNG, RH SCULLY, RE TI DEOXYRIBONUCLEIC-ACID FLOW-CYTOMETRY OF TESTICULAR LEYDIG-CELL TUMORS SO JOURNAL OF UROLOGY LA English DT Article DE TESTICULAR NEOPLASMS; LEYDIG CELL TUMOR; DNA; FLOW CYTOMETRY ID TESTIS AB We analyzed by flow cytometry the deoxyribonucleic acid content of 13 paraffin embedded, formalin-fixed Leydig cell tumors of the testis. Of the tumors 10 were clinically benign (9 diploid and 1 aneuploid) and 3 were malignant (aneuploid) The benign aneuploid tumor showed moderate cellular atypia and a low mitotic count (less than 2 per 10 high power fields). Our study suggests that the majority of Leydig cell tumors are diploid and the less common malignant tumors are typically aneuploid, and that deoxyribonucleic acid flow cytometric findings can be useful as a prognostic indicator in these tumors. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,JAMES HOMER WRIGHT PATHOL LABS,BOSTON,MA. RP PALAZZO, JP (reprint author), THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT PATHOL,PHILADELPHIA,PA 19107, USA. NR 14 TC 10 Z9 11 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 AUG PY 1994 VL 152 IS 2 BP 415 EP 417 PN 1 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA NW329 UT WOS:A1994NW32900030 PM 8015084 ER PT J AU ATALA, A KIM, W PAIGE, KT VACANTI, CA RETIK, AB AF ATALA, A KIM, W PAIGE, KT VACANTI, CA RETIK, AB TI ENDOSCOPIC TREATMENT OF VESICOURETERAL REFLUX WITH A CHONDROCYTE-ALGINATE SUSPENSION SO JOURNAL OF UROLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the Section on Urology of the American-Academy-of-Pediatrics CY OCT 30-NOV 01, 1993 CL WASHINGTON, DC SP AMER ACAD PEDIAT DE VESICOURETERAL REFLUX; ENDOSCOPY; CHONDROITIN; ALGINATES ID URINARY-INCONTINENCE; POLYTETRAFLUOROETHYLENE INJECTION; PERIURETHRAL INJECTION; TEFLON-INJECTION; MIGRATION; CHILDREN; POLYMERS AB Injection of polytetrafluoroethylene (Teflon) or collagen has been used in the endoscopic treatment of vesicoureteral reflux. Although the principle of an endoscopic treatment is valid, there are concerns regarding the long-term safety and effectiveness of these substances. In search of a different injectable material we conducted experiments using chondrocytes in a biodegradable polymer solution for the treatment of vesicoureteral reflux in an animal model. Reflux was created in 4 mini-pigs and confirmed with a cystogram. Cartilage was obtained from the auricular surface of each animal. Chondrocytes were harvested and expanded in vitro. The cells were individually quantitated and concentrated to 40 million cells per cc. The cell suspensions were mixed with a sodium alginate and calcium sulfate solution. Each pig was injected unilaterally in the subureteral region with the autologous chondrocyte suspension. The opposite ureter served as an internal control in all animals. Cystograms showed resolution of reflux in the treated side and persistence of reflux in the opposite untreated side in each instance. Excretory urograms revealed no evidence of obstruction. Histological examination of the subureteral region demonstrated cartilage. Autologous chondrocytes can be readily harvested, expanded in vitro and injected cystoscopically. The cells survive and form a cartilage nidus that is nonantigenic. This system is able to correct reflux without any evidence of obstruction. C1 CHILDRENS HOSP,DEPT PLAST SURG,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT ANESTHESIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RP ATALA, A (reprint author), CHILDRENS HOSP,DIV UROL,300 LONGWOOD AVE,BOSTON,MA 02115, USA. OI Atala, Anthony/0000-0001-8186-2160 NR 23 TC 208 Z9 218 U1 0 U2 8 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-5347 J9 J UROLOGY JI J. Urol. PD AUG PY 1994 VL 152 IS 2 BP 641 EP 643 PN 2 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA NW330 UT WOS:A1994NW33000015 PM 8021988 ER PT J AU BENBRAHIM, A LITALIEN, GJ MILINAZZO, BB WARNOCK, DF DHARA, S GERTLER, JP ORKIN, RW ABBOTT, WM AF BENBRAHIM, A LITALIEN, GJ MILINAZZO, BB WARNOCK, DF DHARA, S GERTLER, JP ORKIN, RW ABBOTT, WM TI A COMPLIANT TUBULAR DEVICE TO STUDY THE INFLUENCES OF WALL STRAIN AND FLUID SHEAR-STRESS ON CELLS OF THE VASCULAR WALL SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID HUMAN-ENDOTHELIAL-CELLS; SMOOTH-MUSCLE CELLS; MESSENGER-RNA LEVELS; COLLAGEN PRODUCTION; FLOW; INVITRO; HYPERPLASIA; DEFORMATION; MODULATION; BEHAVIOR AB Purpose: Cellular constituents of the blood vessel wail are continuously subjected, in vivo, to both mechanical and hemodynamic forces, which elicit structural and biologic responses. We have developed a compliant tubular system, the vascular simulating device (VSD), that reproduces these forces, while supporting the attachment and the experimental manipulation of endothelial and smooth muscle cells. Methods: The VSD consists of a compliant silicone rubber tube coupled to a pump system, which permits the simultaneous application of known levels of pressure and how, to vascular wall cells cultured on the inner surface of the tube. Seeded cells can be monitored visually under phase contrast or fluorescent optics, as well as harvested and analyzed for biologic responses. Results: The elastic modulus and compliance of the silicone rubber tube are similar to those of canine and human arteries. Endothelial and smooth muscle cells cultured on the lumenal surface of the tubes remain attached and viable after subjecting them to physiologic pulsatile flow and cyclic strain. Conclusion: The VSD makes it possible to approximate, in vitro, those forces encountered by vascular wall cells, in vivo and therefore may make it possible to determine whether specific combinations of mechanical and hemodynamic forces are causally associated with specific vascular diseases. C1 MASSACHUSETTS GEN HOSP,DIV VASC SURG,VASC SURG LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. FU NHLBI NIH HHS [R1 HL 34780-8] NR 37 TC 35 Z9 36 U1 0 U2 6 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 AUG PY 1994 VL 20 IS 2 BP 184 EP 194 PG 11 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA PB112 UT WOS:A1994PB11200004 PM 8040941 ER PT J AU DAVISON, JK CAMBRIA, RP VIERRA, DJ COLUMBIA, MA KOUSTAS, G AF DAVISON, JK CAMBRIA, RP VIERRA, DJ COLUMBIA, MA KOUSTAS, G TI EPIDURAL COOLING FOR REGIONAL SPINAL-CORD HYPOTHERMIA DURING THORACOABDOMINAL ANEURYSM REPAIR SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID EXPERIENCE; PARAPLEGIA; RISK AB Purpose: We investigated the feasibility of achieving regional hypothermia of the spinal cord with an infusion of iced (4 degrees C) saline solution administered into an epidural catheter while monitoring cerebral spinal fluid (CSF) temperature in eight patients undergoing thoracic or thoracoabdominal aneurysm resection. Methods: As part of the anesthetic management, an epidural catheter was placed at T11-12, and a subarachnoid thermistor catheter was placed at L3-4. Approximately 30 minutes before aortic cross-clamping, iced (4 degrees C) saline solution was infused into the epidural catheter until CSF temperature decreased to approximately 25 degrees C. The infusion was then adjusted to maintain this temperature until the aorta was unclamped. The subarachnoid catheter was also used to measure CSP pressure and provide for CSF drainage. Surgery was performed in all patients with a clamp-and-sew technique with selective intercostal vessel reattachment. Results: Infusion of a mean volume of 489 ml (range 80 to 1700 ml) of iced saline solution into the epidural space before aortic cross-clamping led to a decrease in mean CSP temperature to 26.9 degrees C (range 25 degrees to 28.8 degrees C) in 15 to 90 minutes. During cross-clamping and aortic replacement the mean CSF temperature was maintained between 25.2 degrees to 27.6 degrees C and, with discontinuation of the infusion, returned to within 1 degrees C of body core temperature by the end of the procedure. Body core temperature was not significantly affected by the epidural infusion. Mean CSF pressure increased during the epidural infusion but could be reduced by removing saline solution from the epidural space. No postoperative neurologic deficits were observed. Conclusion: Epidural cooling appears to be a satisfactory method of achieving regional spinal cord hypothermia in patients requiring resection of thoracic or thoracoabdominal aortic aneurysms. C1 MASSACHUSETTS GEN HOSP,DEPT VASC SURG,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RP DAVISON, JK (reprint author), MASSACHUSETTS GEN HOSP,DEPT ANAESTHESIA,32 FRUIT ST,BOSTON,MA 02114, USA. NR 15 TC 65 Z9 66 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 AUG PY 1994 VL 20 IS 2 BP 304 EP 310 PG 7 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA PB112 UT WOS:A1994PB11200019 PM 8040956 ER PT J AU ROBEN, P MOORE, JP THALI, M SODROSKI, J BARBAS, CF BURTON, DR AF ROBEN, P MOORE, JP THALI, M SODROSKI, J BARBAS, CF BURTON, DR TI RECOGNITION PROPERTIES OF A PANEL OF HUMAN RECOMBINANT FAB FRAGMENTS TO THE CD4 BINDING-SITE OF GP120 THAT SHOW DIFFERING ABILITIES TO NEUTRALIZE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 SO JOURNAL OF VIROLOGY LA English DT Article ID COMBINATORIAL ANTIBODY LIBRARIES; MONOCLONAL-ANTIBODIES; ENVELOPE GLYCOPROTEIN; SURFACE GLYCOPROTEIN; HIV-1 GLYCOPROTEINS; CHIMPANZEES; EPITOPES; INDIVIDUALS; PROTECTION; GP160 AB Six recombinant human Fab fragments that were derived from the same human immunodeficiency virus type 1 (HIV-1)-infected individual and are directed against the CD4 binding site (CD4bs) of the gp120 envelope glycoprotein were studied. A range of neutralizing activity against the HIV-1 (HXBc2) isolate was observed, with Fab b12 exhibiting the greatest potency among the Fabs tested. The neutralizing potency of Fab b12 was better than that of monoclonal whole antibodies directed against the third variable (V3) region of gp120. To explore the basis for the efficient neutralizing activity of b12, the recognition of a panel of HIV-1 gp120 mutants by the six Fabs was studied. The patterns of sensitivity to particular gp120 amino acid changes were similar for all six Fabs to those seen for anti-CD4bs monoclonal antibodies derived from HIV-1-infected individuals by conventional means. In addition, recognition by Fab b12 demonstrated an atypical sensitivity to changes in the V1 and V2 variable regions. Next, the binding of the Fabs to monomeric gp120 and to the envelope glycoprotein complex was examined. Neither the binding properties of the b12 Fab to monomeric gp120 nor the ability of the Fab to compete with soluble CD4 for monomeric gp120 binding appeared to account for the greater neutralizing potency. However, both quantitative and qualitative differences between the binding of b12 and that of less potent Fabs to the cell surface envelope glycoprotein complex were observed. Relative to less potently neutralizing Fabs, Fab b12 exhibited a higher affinity for a subpopulation of cell surface envelope glycoproteins, the conformation of which was best approximated by the mature gp120 glycoprotein. Apparently, subtle differences in the gp120 epitope recognized allow some members of the group of anti-CD4bs antibodies to bind to the functionally relevant envelope glycoprotein complex and to neutralize virus more efficiently. C1 Scripps Res Inst, DEPT IMMUNOL, LA JOLLA, CA 92037 USA. SCRIPPS RES INST, DEPT MOLEC BIOL, LA JOLLA, CA 92037 USA. NYU, SCH MED, AARON DIAMOND AIDS RES CTR, NEW YORK, NY 10016 USA. HARVARD UNIV, SCH MED, DANA FARBER CANC INST, DIV HUMAN RETROVIROL, BOSTON, MA 02115 USA. FU NIAID NIH HHS [AI36082-01, AI24755, P30 AI27742-04] NR 44 TC 386 Z9 395 U1 2 U2 6 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 AUG PY 1994 VL 68 IS 8 BP 4821 EP 4828 PG 8 WC Virology SC Virology GA NW978 UT WOS:A1994NW97800012 PM 7518527 ER PT J AU LODGE, R GOTTLINGER, H GABUZDA, D COHEN, EA LEMAY, G AF LODGE, R GOTTLINGER, H GABUZDA, D COHEN, EA LEMAY, G TI THE INTRACYTOPLASMIC DOMAIN OF GP41 MEDIATES POLARIZED BUDDING OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 IN MDCK CELLS SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; EPITHELIAL-CELLS; CYTOPLASMIC DOMAIN; ENVELOPE GLYCOPROTEIN; EXPRESSION; INFECTION; PROTEIN; PARTICLES; RECEPTOR; HIV-1 AB Human immunodeficiency virus type 1 (HIV-1) has been shown to exhibit a specific basolateral release in polarized epithelial cells. Previous investigators have used vaccinia virus recomi,inants expressing HIV proteins to demonstrate that virus release is nonpolarized in the absence of viral envelope glycoproteins. In this study, we developed a transient expression system which allows the use of Madin-Darby canine kidney polarized epithelial cells directly grown on semipermeable membranes. This procedure allowed us to investigate polarized HIV viral budding following introduction of proviral DNA constructs. Expression of env gene products in trans demonstrated the ability to polarize env-negative viruses in a dose dependent manner. The targeting signal for polarized virus release was shown to be present in the envelope gp41 transmembrane protein and absent from the gp120 portion of env. At least part of this signal is within the gp41 intracytoplasmic domain. Mutants of the p17(gag) matrix protein were shown to be nonpolarized only when unable to interact with the envelope glycoproteins. Together, these data are consistent with a model of polarized virus budding in which capsid proteins, lacking a targeting signal, are targeted for specific basolateral release via an interaction of p17 with the envelope glycoprotein containing the polarization signal in its intracytoplasmic domain. C1 UNIV MONTREAL,DEPT MICROBIOL & IMMUNOL,MONTREAL H3C 3J7,PQ,CANADA. UNIV MONTREAL,RECH & TRANSPORT MEMBRANAIRE GRP,MONTREAL H3C 3J7,PQ,CANADA. DANA FARBER CANC INST,DIV HUMAN RETROVIROL,BOSTON,MA 02115. RI Lemay, Guy/B-2165-2008 FU NIAID NIH HHS [AI01017] NR 38 TC 136 Z9 137 U1 2 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 AUG PY 1994 VL 68 IS 8 BP 4857 EP 4861 PG 5 WC Virology SC Virology GA NW978 UT WOS:A1994NW97800016 PM 8035484 ER PT J AU MAMMANO, F OHAGEN, A HOGLUND, S GOTTLINGER, HG AF MAMMANO, F OHAGEN, A HOGLUND, S GOTTLINGER, HG TI ROLE OF THE MAJOR HOMOLOGY REGION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 IN VIRION MORPHOGENESIS SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; GAG GENE; MATRIX PROTEIN; POSTTRANSLATIONAL MODIFICATIONS; MUTATIONAL ANALYSIS; PARTICLE RELEASE; HTLV-III; PRECURSOR; EXPRESSION; RNA AB Retroviral capsid (CA) proteins contain a uniquely conserved stretch of 20 amino acids which has been named the major homology region (MHR). To examine the role of this region in human immunodeficiency virus type 1 morphogenesis and replication, four highly conserved positions in the MHR were individually altered by site-directed mutagenesis. Conservative substitution of two invariant residues (glutamine 155 and glutamic acid 159) abolished viral replication and significantly reduced the particle-forming ability of the mutant gag gene products. Conservative substitution of the third invariant residue in the MHR (arginine 167) or of an invariably aromatic residue (tyrosine 164) had only a moderate effect. However, removal of the extended side chains of these amino acids by substitution with alanine prevented viral replication and affected virion morphogenesis. The replacement of tyrosine 164 with alanine substantially impaired viral particle production. By contrast, the substitution of arginine 167 with alanine had only a two- to threefold effect on particle yield but led to the formation of aberrant core structures. The MHR mutants which were severely defective for particle production had a dominant negative effect on particle formation by the wild-type Gag product. The role of the MHR in the incorporation of the Gag-Pol precursor was examined by expressing the Gag and Gag-Pol polyproteins individually from separate plasmids. Only when the two precursor polyproteins were coexpressed did processed Gag and Pol products appear in the external medium. The appearance of these products was unaffected or only moderately affected by substitutions in the MHR of the Gag-Pol precursor, suggesting that the mutant Gag-Pol precursors were efficiently incorporated into viral particles. The results of this study indicate that specific residues within the MHR are required both for human immunodeficiency virus type 1 particle assembly and for the correct assembly of the viral core. However, mutant Gag and Gag-Pol polyproteins with substitutions in the MHR retained the ability to interact with wild-type Gag protein. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HUMAN RETROVIROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. BIOMED CTR,DEPT BIOCHEM,S-75123 UPPSALA,SWEDEN. OI Mammano, Fabrizio/0000-0002-9193-7696 FU NCI NIH HHS [CA06516]; NIAID NIH HHS [AI28691, AI29873] NR 53 TC 210 Z9 211 U1 0 U2 4 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 AUG PY 1994 VL 68 IS 8 BP 4927 EP 4936 PG 10 WC Virology SC Virology GA NW978 UT WOS:A1994NW97800024 PM 8035491 ER PT J AU HELIN, K HARLOW, E AF HELIN, K HARLOW, E TI HETERODIMERIZATION OF THE TRANSCRIPTION FACTORS E2F-1 AND DP-1 IS REQUIRED FOR BINDING TO THE ADENOVIRUS E4 (ORF6/7) PROTEIN SO JOURNAL OF VIROLOGY LA English DT Article ID RETINOBLASTOMA GENE-PRODUCT; TYPE-16 E7 PROTEIN; DNA-BINDING; CELL-CYCLE; E2F-CYCLIN-A COMPLEX; GROWTH-REGULATION; MESSENGER-RNA; S-PHASE; TRANSACTIVATION; ASSOCIATION AB Adenovirus infection leads to E1A-dependent activation of the transcription factor E2F. E2F has recently been identified in complexes with cellular proteins such as the retinoblastoma protein (pRB) and the two pRB family members p107 and p130. E1A dissociates E2F from these cellular proteins, and another viral protein, E4 (ORF6/7), can bind to E2F. The binding of E4 to E2F induces the formation of a stable DNA-binding complex containing the two proteins, and stimulation of the adenovirus E2 early promoter can occur. Recent studies have shown that E2F is the combined activity of several proteins, and we demonstrate here that heterodimerization of two of these proteins, E2F-1 and DP-1, is required for stable binding to E4. This complex is formed independently of DNA binding and requires the C-terminal 20 amino acids of E4. Furthermore, the binding is dependent on a region of E2F-1 between amino acids 284 and 358. This region of E2F-1 is conserved in E2F-2 and E2F-3, and deletion of this region drastically reduces the transcriptional activity of the molecule without affecting DP-1 binding, suggesting that this region of the E2F transcription factors is involved in regulating their activity. Our experiments also demonstrate that pRB binding to the E2F-1/DP-1 heterodimer prevents the formation of an E2F-1/DP-1/E4 complex. C1 MASSACHUSETTS GEN HOSP,CTR CANC,BOSTON,MA 02129. RP HELIN, K (reprint author), DANISH CANC SOC,DIV CANC BIOL,STRANDBLVD 49,DK-2100 COPENHAGEN O,DENMARK. NR 62 TC 50 Z9 50 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 AUG PY 1994 VL 68 IS 8 BP 5027 EP 5035 PG 9 WC Virology SC Virology GA NW978 UT WOS:A1994NW97800036 PM 8035503 ER PT J AU OBRIEN, WA MAO, SH CAO, YZ MOORE, JP AF OBRIEN, WA MAO, SH CAO, YZ MOORE, JP TI MACROPHAGE-TROPIC AND T-CELL LINE-ADAPTED CHIMERIC STRAINS OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 DIFFER IN THEIR SUSCEPTIBILITIES TO NEUTRALIZATION BY SOLUBLE CD4 AT DIFFERENT TEMPERATURES SO JOURNAL OF VIROLOGY LA English DT Note ID ENVELOPE V3 LOOP; GLYCOPROTEIN GP120; HOST-RANGE; HIV-1; IDENTIFICATION; DETERMINANT; INFECTION; AFFINITY; GENE; SENSITIVITY AB Molecular clones of three macrophage-tropic and three T-cell line-adapted strains of human immunodeficiency virus type 1 (HIV-1) were used to explore the mechanism of HIV-1 resistance to neutralization by soluble CD4 (sCD4). The three macrophage-tropic viruses, each possessing the V3 and flanking regions of JR-FL, were all resistant to sCD4 neutralization under the standard conditions of a short preincubation of the virus and sCD4 at 37 degrees C prior to inoculation of peripheral blood mononuclear cells. In contrast, the three T-cell line-adapted viruses, NL4-3 and two chimeras possessing the V3 and flanking regions of NL4-3 in the envelope background of JR-FL, were all sCD4 sensitive under these conditions. Sensitivity to sCD4 neutralization at 37 degrees C corresponded with rapid, sCD4-induced gp120 shedding from the viruses. However, when the incubation temperature of the sCD4 and virus was reduced to 4 degrees C, the three macrophage-tropic viruses shed gp120 and became more sensitive to sCD4 neutralization. In contrast, the rates of sCD4 induced gp120 shedding and virus neutralization were reduced for the three T-cell line-adapted viruses at 4 degrees C. Thus, HIV resistance to sCD4 is a conditional phenomenon; macrophage-tropic and T-cell line-adapted strains can be distinguished by the temperature dependencies of their neutralization by sCD4. The average density of gp120 molecules on the macrophage-tropic viruses exceeded by about fourfold that on the T-cell line-adapted viruses, suggesting that HIV growth in T-cell lines may select for a destabilized envelope glycoprotein complex. Further studies of early events in HIV-1 infection should focus on primary virus strains. C1 NYU,SCH MED,AARON DIAMOND AIDS RES CTR,NEW YORK,NY. RP OBRIEN, WA (reprint author), UNIV CALIF LOS ANGELES,W LOS ANGELES VET AFFAIRS MED CTR,DEPT MED,691-111F,WILTSHIRE & SAWTELLE,LOS ANGELES,CA 90073, USA. FU NIAID NIH HHS [AI 28697-03, AI 29894-04, AI27742-04] NR 34 TC 56 Z9 56 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD AUG PY 1994 VL 68 IS 8 BP 5264 EP 5269 PG 6 WC Virology SC Virology GA NW978 UT WOS:A1994NW97800062 PM 8035523 ER PT J AU STRACK, S AF STRACK, S TI RELATING MILLONS BASIC PERSONALITY STYLES AND HOLLANDS OCCUPATIONAL TYPES SO JOURNAL OF VOCATIONAL BEHAVIOR LA English DT Article ID ADJECTIVE CHECK LIST; SAMPLE; SCALES AB This study examined the relation between Millon's (1983) basic personality styles and Holland's (1985a) occupational types. Subjects were 75 men and 77 women college students who completed the Personality Adjective Check List (Strack, 1987, 1991b), a measure of Millon's basic personalities designed for use with normal adults, and the Self-Directed Search (SDS; Holland, 1985c, 1987). Pearson and canonical correlation analyses were conducted separately for men and women. Bivariate correlations were typically modest, ranging from -.34 to .46 across sexes. Two significant canonical variates emerged for both men and women. Meaningful associations were found for essentially all of Millon's basic personalities and Holland's types, although the pattern was different for men and women. Millon and Holland appeared most similar along dimensions of social dominance-submissiveness and emotionality (neuroticism)-restraint (conscientiousness). RP STRACK, S (reprint author), US DEPT VET AFFAIRS,PSYCHOL SERV 116B,OUTPATIENT CLIN,351 E TEMPLE ST,LOS ANGELES,CA 90012, USA. NR 38 TC 10 Z9 11 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0001-8791 J9 J VOCAT BEHAV JI J. Vocat. Behav. PD AUG PY 1994 VL 45 IS 1 BP 41 EP 54 DI 10.1006/jvbe.1994.1025 PG 14 WC Psychology, Applied SC Psychology GA PA234 UT WOS:A1994PA23400003 ER PT J AU BERGERSWEENEY, J BERGER, UV SHARMA, M PAUL, CA AF BERGERSWEENEY, J BERGER, UV SHARMA, M PAUL, CA TI EFFECTS OF CARBON DIOXIDE-INDUCED ANESTHESIA ON CHOLINERGIC PARAMETERS IN RAT-BRAIN SO LABORATORY ANIMAL SCIENCE LA English DT Article ID ACETYLCHOLINESTERASE; ACETYLTRANSFERASE AB We report that acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) activities in rat brain were virtually identical whether the rat was anesthetized with carbon dioxide (CO2) before decapitation or decapitated without prior sedation. The AChE and ChAT activities were measured in three brain regions: the hippocampus, cerebral cortex, and cerebellum. Enzyme activities varied significantly by brain region, with the highest values in the hippocampus and the lowest values in the cerebellum. Enzyme activities, however, did not vary with the method of euthanasia, either CO2-induced anesthesia prior to decapitation or decapitation without anesthesia. These data suggest that CO2-induced anesthesia prior to decapitation does not alter activities of these cholinergic markers in rat hippocampus, cerebral cortex, and cerebellum. This method of euthanasia eliminates the need to capture a conscious animal, which reduces stress to the animal and the experimenter. C1 MASSACHUSETTS GEN HOSP,MOLEC & DEV NEUROSCI LAB,BOSTON,MA 02129. RP BERGERSWEENEY, J (reprint author), WELLESLEY COLL,DEPT BIOL SCI,WELLESLEY,MA 02181, USA. NR 15 TC 29 Z9 29 U1 1 U2 1 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI CORDOVA PA 70 TIMBERCREEK DR, SUITE 5, CORDOVA, TN 38018 SN 0023-6764 J9 LAB ANIM SCI JI Lab. Anim. Sci. PD AUG PY 1994 VL 44 IS 4 BP 369 EP 371 PG 3 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA PD469 UT WOS:A1994PD46900014 PM 7983851 ER PT J AU LEUNIG, M YUAN, F BERK, DA GERWECK, LE JAIN, RK AF LEUNIG, M YUAN, F BERK, DA GERWECK, LE JAIN, RK TI METHODS IN LABORATORY INVESTIGATION - ANGIOGENESIS AND GROWTH OF ISOGRAFTED BONE - QUANTITATIVE IN-VIVO ASSAY IN NUDE-MICE SO LABORATORY INVESTIGATION LA English DT Article DE DORSAL SKIN FOLD CHAMBER; INTRAVITAL MICROSCOPY; BONE TRANSPLANTATION; OXYTETRACYCLINE ID ISCHEMIA-REPERFUSION INJURY; STRIATED-MUSCLE; TRANSPLANTATION; GRAFTS; MICROHEMODYNAMICS; CARTILAGE; BIOLOGY; INVIVO; MATRIX; REFLOW AB BACKGROUND: Understanding the regulation of vascularization and formation of bone after skeletal trauma is essential for the development of methods to promote healing. The lack of information on the biology of bone healing led us to establish an experimental model that facilitates the in vivo assessment of angiogenesis and growth of bone. EXPERIMENTAL DESIGN: Fresh, cryopreserved (frozen in the presence or absence of 10% dimethyl sulfoxide (DMSO)) or boiled neonatal femora were transplanted into dorsal skin fold chambers in adult mice of the identical strain, and angiogenesis and growth were monitored over 16 days. Computerized analysis of brightfield and epifluorescence images was employed to characterize the process of angiogenesis. Bone formation was quantified in vivo by the use of oxytetracycline. RESULTS: Reperfusion of pre-existing blood vessels of the graft was observed only in fresh transplanted femora, whereas femora of all experimental groups elicited angiogenic response from the host tissue. The rank order of the angiogenic response was: fresh > cryopreservation with DMSO > cryopreservation without DMSO > boiled. Growth of femora was completely abolished after cryopreservation or boiling. Only fresh transplanted femora increased in length (95 mu m/day) and in cartilage diameter (41 mu m/day). CONCLUSIONS: Our study demonstrates that (a) angiogenesis and growth of transplanted femora can be chronically assessed using in vivo microscopy; (b) the introduction of oxytetracycline for in vivo fluorescence microscopy allows the differential quantification of bone and cartilage growth; and (c) cryoprotection using DMSO enhances restoration of angiogenic potency after freezing. We consider this assay an excellent experimental model to study in vivo effects of agents or procedures that potentially modulate angiogenesis and growth of bone. RP LEUNIG, M (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,STEELE LAB,BOSTON,MA 02114, USA. RI Yuan, Fan/A-1287-2011; Berk, David/A-4863-2012; Leunig, Michael/E-7951-2017 OI Berk, David/0000-0002-3855-6886; Leunig, Michael/0000-0002-2036-5416 FU NCI NIH HHS [R35-CA-56591] NR 37 TC 43 Z9 46 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD AUG PY 1994 VL 71 IS 2 BP 300 EP 307 PG 8 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA PE977 UT WOS:A1994PE97700018 PM 7521447 ER PT J AU METSON, R DALLOW, RL SHORE, JW AF METSON, R DALLOW, RL SHORE, JW TI ENDOSCOPIC ORBITAL DECOMPRESSION SO LARYNGOSCOPE LA English DT Article ID DYSTHYROID OPHTHALMOPATHY; SURGERY AB Exophthalmos from Graves' disease can result in visual disability and cosmetic deformity. Surgical treatment of this disorder is now possible through an intranasal endoscopic approach that allows removal of the medial orbital wall and floor without an external incision. Endoscopic orbital decompression was performed on 22 orbits in 14 patients for treatment of progressive exophthalmos. Local anesthesia was used in five cases. Sixteen procedures involved a concurrent lateral orbital decompression performed through an external approach. There were no intraoperative or postoperative complications. Visual acuity remained stable or improved in all cases. Proptosis was reduced an average of 3.2 +/- 1.1 mm (range 2 to 4.5 mm) by endoscopic decompression alone. When a lateral decompression was also performed, proptosis was reduced by an additional 2.4 mm, for an average improvement of 5.6 +/- 1.7 mm (range 2 to 8 mm). Endoscopic orbital decompression appears to be a safe technique for the treatment of exophthalmos that can be performed effectively with the patient under general or local anesthesia. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OTOLARYNGOL,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,BOSTON,MA. NR 15 TC 73 Z9 75 U1 0 U2 1 PU LARYNGOSCOPE CO PI ST LOUIS PA 10 S BROADWAY 14TH FLOOR, ST LOUIS, MO 63102-1741 SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD AUG PY 1994 VL 104 IS 8 BP 950 EP 957 PN 1 PG 8 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA PB529 UT WOS:A1994PB52900008 PM 8052080 ER PT J AU BOADA, FE CHRISTENSEN, JD HUANGHELLINGER, FR REESE, TG THULBORN, KR AF BOADA, FE CHRISTENSEN, JD HUANGHELLINGER, FR REESE, TG THULBORN, KR TI QUANTITATIVE IN-VIVO TISSUE SODIUM CONCENTRATION MAPS - THE EFFECTS OF BIEXPONENTIAL RELAXATION SO MAGNETIC RESONANCE IN MEDICINE LA English DT Note DE QUANTITATIVE MR; SODIUM CONCENTRATION; SODIUM IMAGING; BIEXPONENTIAL TRANSVERSE RELAXATION ID MAGNETIC-RESONANCE; NA-23; T2; ECHO; NMR AB The biexponential relaxation behavior of the sodium nucleus affects the accuracy of quantitative measurement of in vivo tissue sodium concentration (TSC). Theoretical analysis and in vivo experimental results are used to demonstrate the extent of the large bias in the measured TSC that arises when the relaxation behavior in vivo differs significantly from that of the calibration standards which is when a significant fraction of the total sodium signal decays with a relaxation time much shorter than the echo time (TE) used for imaging. This bias can be as large as 20% for measurements of TSC in a normal rat brain with TE = 2 ms. Our findings indicate that shortening the echo time (TE < 0.5 ms) by projection imaging is a reliable means of obtaining accurate in vivo estimates for TSC using MR. C1 MASSACHUSETTS GEN HOSP,CTR NMR,BOSTON,MA. RI Thulborn, Keith/D-9183-2015 OI Thulborn, Keith/0000-0001-6197-4296 FU NCI NIH HHS [R01CA63661]; NHLBI NIH HHS [R01HL45176] NR 16 TC 42 Z9 42 U1 1 U2 1 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 AUG PY 1994 VL 32 IS 2 BP 219 EP 223 DI 10.1002/mrm.1910320210 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NZ793 UT WOS:A1994NZ79300009 PM 7968444 ER PT J AU LEVINE, K SHANE, HC WHARTON, RH AF LEVINE, K SHANE, HC WHARTON, RH TI WHAT IF - A PLEA TO PROFESSIONALS TO CONSIDER THE RISK-BENEFIT RATIO OF FACILITATED COMMUNICATION SO MENTAL RETARDATION LA English DT Editorial Material C1 CHILDRENS HOSP MED CTR,SPEECH LANGUAGE PATHOL SERV,COMMUN ENHANCEMENT CLIN,BOSTON,MA 02115. SPAULDING REHABIL HOSP,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP LEVINE, K (reprint author), CHILDRENS HOSP MED CTR,CTR DEV EVALUAT,INST COMMUNITY INCLUS,300 LONGWOOD AVE,BOSTON,MA 02115, USA. NR 14 TC 10 Z9 10 U1 0 U2 1 PU AMER ASSOC MENTAL RETARDATION PI WASHINGTON PA 444 N CAPITOL ST, NW, STE 846, WASHINGTON, DC 20001-1512 SN 0047-6765 J9 MENT RETARD JI Ment. Retard. PD AUG PY 1994 VL 32 IS 4 BP 300 EP 304 PG 5 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA PC279 UT WOS:A1994PC27900007 PM 7968563 ER PT J AU LEVINE, K SHANE, HC WHARTON, RH AF LEVINE, K SHANE, HC WHARTON, RH TI RESPONSE TO COMMENTARIES ON RISKS OF FACILITATED COMMUNICATION SO MENTAL RETARDATION LA English DT Editorial Material C1 SPAULDING REHABIL HOSP,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. CHILDRENS HOSP MED CTR,SPEECH LANGUAGE PATHOL SERV,COMMUN ENHANCEMENT CLIN,BOSTON,MA 02115. RP LEVINE, K (reprint author), CHILDRENS HOSP MED CTR,CTR DEV EVALUAT,INST COMMUNITY INCLUS,300 LONGWOOD AVE,BOSTON,MA 02115, USA. NR 4 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC MENTAL RETARDATION PI WASHINGTON PA 444 N CAPITOL ST, NW, STE 846, WASHINGTON, DC 20001-1512 SN 0047-6765 J9 MENT RETARD JI Ment. Retard. PD AUG PY 1994 VL 32 IS 4 BP 317 EP 318 PG 2 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA PC279 UT WOS:A1994PC27900012 ER PT J AU SHIRRA, MK ZHU, Q HUANG, HC PALLAS, D HANSEN, U AF SHIRRA, MK ZHU, Q HUANG, HC PALLAS, D HANSEN, U TI ONE EXON OF THE HUMAN LSF GENE INCLUDES CONSERVED REGIONS INVOLVED IN NOVEL DNA-BINDING AND DIMERIZATION MOTIFS SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TRANSCRIPTION FACTOR CP2; PRE-MESSENGER-RNA; MOLECULAR-CLONING; PROTEINS; PROMOTER; EXPRESSION; ELEMENT; IDENTIFICATION; ACTIVATION; MECHANISM AB The transcription factor LSF, identified as a HeLa protein that binds the simian virus 40 late promoter, recognizes direct repeats with a center-to-center spacing of 10 bp. The characterization of two human cDNAs, representing alternatively spliced mRNAs, provides insight into the unusual DNA-binding and oligomerization properties of LSF. The sequence of the full-length LSF is identical to that of the transcription factors alpha CP2 and LBP-1c and has similarity to the Drosophila transcription Factor Elf-1/NTF-1. Using an epitope-counting method, we show that LSF binds DNA as a homodimer. LSF-ID, which is identical to LBP-1d, contains an in-frame internal deletion of 51 amino acids resulting from alternative mRNA splicing. Unlike LSF, LSF-ID did not bind LSF DNA-binding sites. Furthermore, LSF-ID did not affect the binding of LSF to DNA, suggesting that the two proteins do not interact. Of three short regions with a high degree of homology between LSF and Elf-1/NTF-1, LSF-ID lacks two, which are predicted to form P-strands. Double amino acid substitutions in each of these regions eliminated specific DNA-binding activity, similarly to the LSF-ID deletion. The dimerization potential of these mutants was measured both by the ability to inhibit the binding of LSF to DNA and by direct protein-protein interaction studies. Mutations in one homology region, but not the other, functionally eliminated dimerization. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV MOLEC GENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOLEC GENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT CELLULAR & MOLEC BIOL,BOSTON,MA 02115. FU NCI NIH HHS [CA38038, CA45285, R01 CA057327] NR 41 TC 52 Z9 53 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD AUG PY 1994 VL 14 IS 8 BP 5076 EP 5087 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA NY429 UT WOS:A1994NY42900006 PM 8035790 ER PT J AU MOLNAR, G CROZAT, A PARDEE, AB AF MOLNAR, G CROZAT, A PARDEE, AB TI IMMEDIATE-EARLY GENE EGR-1 REGULATES THE ACTIVITY OF THE THYMIDINE KINASE PROMOTER AT THE G(0)-TO-G(1) TRANSITION OF THE CELL-CYCLE SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ZINC FINGER PROTEIN; MESSENGER-RNA; BINDING-PROTEINS; GROWTH-FACTORS; DNA-SEQUENCES; JUN ENCODES; G1/S PHASE; TRANSCRIPTION; EXPRESSION; REPRESSION AB Production of thymidine kinase (TK) protein parallels the onset of DNA synthesis during the cell cycle. This process is regulated at transcriptional, posttranscriptional, and translational levels to cause a 40- to 50-fold increase in cytosolic enzymatic activity as cells progress from G(1) to S phase. Transcriptional activation of the mouse TK gene through the cell cycle is dependent upon previously characterized cis elements of the proximal promoter, called MT1, MT2, and MT3, that bind at least two different complexes: TKE during the transition of cells from quiescence (G(0)) to G(1), and Yi later at the G(1)/S boundary. To identify the transcription factors involved in this regulation, we screened a mouse fibroblast cDNA expression library with a labeled MT3 oligonucleotide probe and isolated a clone that encodes Egr-1, an immediate-early transcription factor, whose expression is regulated by serum or growth factors during the G(0)-to-G(1) transition when cells reenter the cell cycle. Electrophoretic mobility shift assays demonstrate that Egr-1 is involved in the TKE complex that binds to the MT3 element and that expression of Egr-1 induces transcription of a mouse TK-chloramphenicol acetyltransferase reporter in transient transfections. These results suggest a role for Egr-1 in regulating expression of the TK gene at the G(0)-to-G(1) transition. RP MOLNAR, G (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELL GROWTH & REGULAT,44 BINNEY ST,BOSTON,MA 02115, USA. NR 43 TC 82 Z9 83 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 AUG PY 1994 VL 14 IS 8 BP 5242 EP 5248 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA NY429 UT WOS:A1994NY42900023 PM 8035803 ER PT J AU DUMAS, B HARDING, HP CHOI, HS LEHMANN, KA CHUNG, M LAZAR, MA MOORE, DD AF DUMAS, B HARDING, HP CHOI, HS LEHMANN, KA CHUNG, M LAZAR, MA MOORE, DD TI A NEW ORPHAN MEMBER OF THE NUCLEAR HORMONE-RECEPTOR SUPERFAMILY CLOSELY-RELATED TO REV-ERB SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID RETINOID-X-RECEPTOR; YA SUBUNIT GENE; CONTROLLING INDUCIBLE EXPRESSION; PROLIFERATOR-ACTIVATED RECEPTOR; PLANAR AROMATIC-COMPOUNDS; STEROIDOGENIC FACTOR-I; THYROID-HORMONE; TRANSCRIPTION FACTOR; RESPONSIVE ELEMENT; PHENOLIC ANTIOXIDANTS AB We have isolated complementary DNA clones encoding a novel orphan member of the nuclear receptor superfamily, termed BD73. This protein shows strong amino acid sequence similarity to the previously described Rev-ErbA alpha. Unlike Rev-Erb, in which the opposite strand of the C-terminal coding region encodes the C-terminal portion of a variant thyroid hormone receptor isoform, the opposite strand of the C-terminal coding region of BD73 does not have any extensive open reading frames. BD73 messenger RNA is expressed in a wide variety of tissues and cell lines. In quiescent HepG2 cells, BD73 messenger RNA levels are strongly induced by planar aromatic antioxidants. Like Rev-Erb, BD73 binds as a monomer to a DNA sequence which consists of a specific A/T-rich sequence upstream of the consensus hexameric half-site specified by the P box of the DNA-binding domain. Amino acid sequence comparisons suggest that the A box sequence, which has been suggested to mediate monomer binding by other superfamily members, lies closer to the DNA-binding domain in BD73 and Rev-Erb than in other receptors. Under the conditions examined, neither BD73 nor Rev-Erb activated reporters containing multiple copies of their common binding site. Thus, these two orphans may require an as yet unidentified ligand or other signal for such activation. Together, BD73 and Rev-Erb define a subgroup orphan receptors that bind as monomers to a half-site flanked by a specific and extended A/T-rich sequence. C1 MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. ROUSSEL UCLAF,F-93230 ROMAINVILLE,FRANCE. UNIV PENN,SCH MED,DEPT MED,DIV ENDOCRINOL,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,DEPT GENET,PHILADELPHIA,PA 19104. UNIV UTAH,ECCLES INST,DEPT HUMAN GENET,SALT LAKE CITY,UT 84112. FU NIDDK NIH HHS [DK-45586]; NIGMS NIH HHS [GM-08216] NR 49 TC 87 Z9 88 U1 1 U2 3 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD AUG PY 1994 VL 8 IS 8 BP 996 EP 1005 DI 10.1210/me.8.8.996 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PB576 UT WOS:A1994PB57600005 PM 7997240 ER PT J AU FRIEDLAND, RP MAJOCHA, RE RENO, JM LYLE, LR MAROTTA, CA AF FRIEDLAND, RP MAJOCHA, RE RENO, JM LYLE, LR MAROTTA, CA TI DEVELOPMENT OF AN ANTI-A-BETA MONOCLONAL-ANTIBODY FOR IN-VIVO IMAGING OF AMYLOID ANGIOPATHY IN ALZHEIMERS-DISEASE SO MOLECULAR NEUROBIOLOGY LA English DT Article; Proceedings Paper CT Symposium on Transmissible and Nontransmissible Neurodegenerative Disorders CY FEB 28-MAR 05, 1993 CL OCHO RIOS, JAMAICA SP INT BRAIN RES ORG, UNIV GOTEBORG, UNIV WEST INDIES DE ALZHEIMERS DISEASE; AMYLOID ANGIOPATHY; IN VIVO DIAGNOSIS; MONOCLONAL ANTIBODIES; SINGLE PHOTON EMISSION TOMOGRAPHY ID PLAQUE CORE PROTEIN; CONGOPHILIC ANGIOPATHY; PRECURSOR; DIAGNOSIS; THERAPY; INVIVO; CORTEX; BRAIN AB We evaluated the efficacy of murine monoclonal antibodies (MAbs) targeted to the A beta amyloid of Alzheimer's disease for development of procedures for the in vivo identification of amyloid angiopathy (AA). MAbs to A beta were prepared and screened for effectiveness in visualizing AA and neuritic plaques in postmortem AD brain sections. They were assessed again after enzymatic cleavage to produce Fab fragments and after labeling with technetium-99m (Tc-99m) using a diamide dimercaptide ligand system. Modified and radiolabeled Fab fragments retained activity and specificity toward amyloid-laden blood vessels and neuritic plaques. A highly specific murine MAb, 10H3, was identified and characterized that fulfills criteria necessary for the development of an in vivo diagnostic imaging agent. Toxicity studies in rats showed the MAb to be safe. Biodistribution studies in mice demonstrated desirable properties for use as an imaging agent. Expansion and adaptation of these strategies may provide the methods and materials for the noninvasive analysis of AA in living patients, and permit assessment of the contribution of AA to the clinical and pathological features of AD. C1 MASSACHUSETTS GEN HOSP,NEUROBIOL LAB,BOSTON,MA. BROWN UNIV,DEPT PSYCHIAT,PROVIDENCE,RI. MALLINCKRODT MED INC,ST LOUIS,MO. NEORX CORP,SEATTLE,WA. RP FRIEDLAND, RP (reprint author), CASE WESTERN RESERVE UNIV,DEPT NEUROL,2074 ABINGTON RD,CLEVELAND,OH 44106, USA. RI Friedland, Robert/A-2834-2010 OI Friedland, Robert/0000-0001-5721-1843 FU NIA NIH HHS [AG08012, P01 AG02126] NR 30 TC 24 Z9 24 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 SN 0893-7648 J9 MOL NEUROBIOL JI Mol. Neurobiol. PD AUG-DEC PY 1994 VL 9 IS 1-3 BP 107 EP 113 DI 10.1007/BF02816109 PG 7 WC Neurosciences SC Neurosciences & Neurology GA PW290 UT WOS:A1994PW29000012 PM 7888086 ER PT J AU WILLIAMS, BO REMINGTON, L ALBERT, DM MUKAI, S BRONSON, RT JACKS, T AF WILLIAMS, BO REMINGTON, L ALBERT, DM MUKAI, S BRONSON, RT JACKS, T TI COOPERATIVE TUMORIGENIC EFFECTS OF GERMLINE MUTATIONS IN RB AND P53 SO NATURE GENETICS LA English DT Article ID WILD-TYPE P53; CELL LUNG-CANCER; RETINOBLASTOMA SUSCEPTIBILITY GENE; TUMOR-SUPPRESSOR GENE; LARGE T-ANTIGEN; TRANSGENIC MICE; BREAST-CANCER; CYCLE CONTROL; PINEAL ORGAN; APOPTOSIS AB The tumour suppressor genes Rb and p53 are mutated in several types of human cancer, and many tumour types carry mutations in both genes. To study how these genes normally function, we and others have created mouse strains with Rb and p53 mutations. Here we describe the phenotypic effects of combined germline mutations in these two tumour suppressor genes. Mice mutant for both genes have reduced viability and exhibit novel pathology including pinealoblastomas, islet cell tumours, bronchial epithelial hyperplasia and retinal dysplasia. These data indicate that mutations in Rb and p53 can cooperate in the transformation of certain cell types in the mouse. C1 MIT,CTR CANC RES,DEPT BIOL,CAMBRIDGE,MA 02139. UNIV WISCONSIN,DEPT OPHTHALMOL,MADISON,WI 53792. HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,BOSTON,MA 02114. TUFTS UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02111. TUFTS UNIV,SCH VET MED,DEPT PATHOL,BOSTON,MA 02111. RI Williams, Bart/A-3539-2013 OI Williams, Bart/0000-0002-5261-5301 NR 58 TC 305 Z9 308 U1 0 U2 1 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD AUG PY 1994 VL 7 IS 4 BP 480 EP 484 DI 10.1038/ng0894-480 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA PA832 UT WOS:A1994PA83200013 PM 7951317 ER EF