FN Thomson Reuters Web of Science™ VR 1.0 PT J AU BRUIJN, JA MIHM, MC BARNHILL, RL AF BRUIJN, JA MIHM, MC BARNHILL, RL TI DESMOPLASTIC MELANOMA SO HISTOPATHOLOGY LA English DT Review DE MELANOMA; DESMOPLASTIC MELANOMA; MALIGNANT MELANOMA; SKIN ID MALIGNANT-MELANOMA; NEUROTROPIC MELANOMA; SPINDLE CELL; ELECTRON-MICROSCOPY; VARIANT; TUMORS; HEAD; NECK AB Desmoplastic melanoma is a rare tumour of which a limited number of cases have been described. The clinical and histopathological features of desmoplastic melanoma and its variants may give rise to perplexing diagnostic and therapeutic dilemmas. In the past decades, some insight has been gained into the histogenesis of these lesions and discriminating clinical and morphological features are now recognized. Review of the literature reveals an extensive list of differential diagnoses. Adequate surgical excision and close follow-up of these radioresistant, frequently-recurring tumours is strongly advocated. C1 LEIDEN UNIV,DEPT PATHOL,2300 RA LEIDEN,NETHERLANDS. MASSACHUSETTS GEN HOSP,DIV DERMATOPATHOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 34 TC 77 Z9 77 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0309-0167 J9 HISTOPATHOLOGY JI Histopathology PD MAR PY 1992 VL 20 IS 3 BP 197 EP 205 DI 10.1111/j.1365-2559.1992.tb00957.x PG 9 WC Cell Biology; Pathology SC Cell Biology; Pathology GA HK972 UT WOS:A1992HK97200001 PM 1563706 ER PT J AU MAGEE, DM SMITH, JG BLEICKER, CA CARTER, CJ BONEWALD, LF SCHACHTER, J WILLIAMS, DM AF MAGEE, DM SMITH, JG BLEICKER, CA CARTER, CJ BONEWALD, LF SCHACHTER, J WILLIAMS, DM TI CHLAMYDIA-TRACHOMATIS PNEUMONIA INDUCES INVIVO PRODUCTION OF INTERLEUKIN-1 AND INTERLEUKIN-6 SO INFECTION AND IMMUNITY LA English DT Note ID NECROSIS FACTOR-ALPHA; T-CELL ACTIVATION; BACTERIAL-INFECTION; RECOMBINANT INTERLEUKIN-1; IL-6; PATHOGENESIS; RESISTANCE; CYTOKINES; FIBROBLASTS; MOUSE AB Cytokine induction during Chlamydia trachomatis pneumonia may alter the pathogenesis or course of disease. We examined interleukin-1 (IL-1) and IL-6 production by measuring mRNA and bioactivity in murine lungs. mRNA and bioactivity for IL-1-alpha, IL-1-beta, and IL-6 increased after Chlamydia infection. These cytokines may be important in regulating host defenses against C. trachomatis. C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT MICROBIOL,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,DIV INFECT DIS,SAN ANTONIO,TX 78284. UNIV CALIF SAN FRANCISCO,DEPT LAB MED,SAN FRANCISCO,CA 94143. RP MAGEE, DM (reprint author), SAN ANTONIO STATE CHEST HOSP,DEPT RES IMMUNOL,SAN ANTONIO,TX 78223, USA. FU NIAID NIH HHS [AI 22380] NR 39 TC 36 Z9 37 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 MAR PY 1992 VL 60 IS 3 BP 1217 EP 1220 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA HH195 UT WOS:A1992HH19500071 PM 1541536 ER PT J AU WEBER, AL GRILLO, H AF WEBER, AL GRILLO, H TI TRACHEAL LESIONS - ASSESSMENT BY CONVENTIONAL FILMS, COMPUTED-TOMOGRAPHY AND MAGNETIC-RESONANCE-IMAGING SO ISRAEL JOURNAL OF MEDICAL SCIENCES LA English DT Article DE HEAD AND NECK IMAGING; TRACHEAL STENOSIS; TRACHEAL TUMORS; CT; MRI; SAGITTAL, CORONAL, OBLIQUE VIEWS ID CARCINOMA; TUMORS AB The radiological evaluation of the trachea is comprehensive and includes lateral neck and anteroposterior high kilovoltage conventional X-ray films; fluoroscopy; barium study of the esophagus; angiography for vascular lesions; computed tomography (CT), which is of great value in assessing tumors that have penetrated the wall of the trachea; and magnetic resonance imaging (MRI), especially helpful in delineating the entire length of a stenosis or a tumor because of its coronal, oblique and sagittal views. The authors describe the etiologic, anatomic and clinical aspects of tracheal stenosis, and review benign and malignant tracheal tumors together with a description of their CT and MRI characteristics. C1 MASSACHUSETTS GEN HOSP,GEN THORAC SURG UNIT,BOSTON,MA 02114. RP WEBER, AL (reprint author), MASSACHUSETTS EYE & EAR HOSP,DEPT RADIOL,243 CHARLES ST,BOSTON,MA 02114, USA. NR 39 TC 12 Z9 12 U1 0 U2 0 PU ISRAEL JOURNAL MED SCIENCES PI JERUSALEM PA 2 ETZEL ST, FRENCH HILL, JERUSALEM 97853, ISRAEL SN 0021-2180 J9 ISRAEL J MED SCI JI Isr. J. Med. Sci. PD MAR-APR PY 1992 VL 28 IS 3-4 BP 233 EP 240 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA HN831 UT WOS:A1992HN83100016 PM 1592594 ER PT J AU WEBER, AL BAKER, AS MONTGOMERY, WW AF WEBER, AL BAKER, AS MONTGOMERY, WW TI INFLAMMATORY LESIONS OF THE NECK, INCLUDING FASCIAL SPACES - EVALUATION BY COMPUTED-TOMOGRAPHY AND MAGNETIC-RESONANCE-IMAGING SO ISRAEL JOURNAL OF MEDICAL SCIENCES LA English DT Article DE HEAD AND NECK IMAGING; CT; MRI; VISCERAL SPACE; PARAPHARYNGEAL SPACE; RETROPHARYNGEAL SPACE ID JUGULAR VENOUS THROMBOSIS; VEIN-THROMBOSIS; INFECTIONS; DIAGNOSIS; ABSCESS; HEAD; FACE; FLOW AB The clinical findings that characterize inflammatory lesions of the neck are briefly presented. The technique of the major imaging methods - computed tomography (CT) and magnetic resonance inmaging (MRI) - used for the evaluation of these lesions is described as well as the radiologic appearance of abscesses, enlarged lymph nodes and cellulitis. The only advantage of MRI over CT is its multiplanar capability, sagittal sections being especially useful in the demonstration of the retropharyngeal space. C1 MASSACHUSETTS EYE & EAR HOSP,DEPT OTOLARYNGOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MED,DIV INFECT DIS,BOSTON,MA 02114. RP WEBER, AL (reprint author), MASSACHUSETTS EYE & EAR HOSP,DEPT RADIOL,243 CHARLES ST,BOSTON,MA 02114, USA. NR 25 TC 7 Z9 8 U1 0 U2 0 PU ISRAEL JOURNAL MED SCIENCES PI JERUSALEM PA 2 ETZEL ST, FRENCH HILL, JERUSALEM 97853, ISRAEL SN 0021-2180 J9 ISRAEL J MED SCI JI Isr. J. Med. Sci. PD MAR-APR PY 1992 VL 28 IS 3-4 BP 241 EP 249 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA HN831 UT WOS:A1992HN83100017 PM 1592595 ER PT J AU REIMER, P KWONG, KK WEISSKOFF, R COHEN, MS BRADY, TJ WEISSLEDER, R AF REIMER, P KWONG, KK WEISSKOFF, R COHEN, MS BRADY, TJ WEISSLEDER, R TI DYNAMIC SIGNAL INTENSITY CHANGES IN LIVER WITH SUPERPARAMAGNETIC MR CONTRAST AGENTS SO JMRI-JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE CONTRAST ENHANCEMENT; CONTRAST MEDIA, COMPARATIVE STUDIES; CONTRAST MEDIA, EXPERIMENTAL STUDIES; IRON; LIVER, MR AB The dynamic effects of three different superparamagnetic magnetic resonance (MR) contrast agents on liver signal were evaluated with an echo-planar imaging technique. The contrast agents were (a) USPIO (ultrasmall superparamagnetic iron oxide), which has a long blood half-life and was developed for MR imaging of lymph nodes and bone marrow; (b) AG (arabino-galactan)-USPIO, an asialoglycoprotein receptor-directed iron oxide with hepatocyte uptake; and (c) AMI-25, a conventional reticuloendothelial iron oxide agent. Dynamic liver signal intensity (SI) curves reflect different uptake mechanisms for the different agents. Receptor blocking experiments indicate that intracellular redistribution or clustering of the AG-USPIO (known to occur from electron microscopy studies) does not contribute to the decrease in liver SI. Monitoring liver SI over time with echo-planar imaging may provide a better understanding of the kinetics of the growing number of MR contrast agents and allow optimization of imaging protocols to exploit peak enhancement. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,DEPT RADIOL,CTR NUCL MAGNET RESONANCE,BLDG 149,13TH ST,BOSTON,MA 02129. RI Cohen, Mark/C-6610-2011 OI Cohen, Mark/0000-0001-6731-4053 FU NCI NIH HHS [P01 CA48279] NR 0 TC 27 Z9 27 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 MAR-APR PY 1992 VL 2 IS 2 BP 177 EP 181 DI 10.1002/jmri.1880020210 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA HK056 UT WOS:A1992HK05600006 PM 1562768 ER PT J AU OBARU, K DECLUE, JE HASELTINE, WA AF OBARU, K DECLUE, JE HASELTINE, WA TI AN AMINO-TERMINAL AMINO-ACID AFFECTS THE ELECTROPHORETIC MOBILITY OF THE HIV-1 NEF PROTEIN SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE HUMAN IMMUNODEFICIENCY VIRUS; NEF GENE ID HUMAN-IMMUNODEFICIENCY-VIRUS; TYPE-1; REPLICATION; ONCOGENE; CELLS; PRODUCT; REGION; GENE AB The nef protein of the BH8 clone derived from the IIIB isolate of human immunodeficiency virus 1 (HIV-1) has a molecular weight of 27,000, whereas that produced by a clone of the BRU strain of HIV-1 appears to have a molecular weight of 24,800. To determine the basis for this difference in molecular weight, a series of recombinant nef genes were made in which segments of the BH8 and BRU nef coding sequences were exchanged. The region of amino acids 35-74 caused mobility shift. In this region, the BH8 and BRU proteins differ by a single amino acid at position 54. Residue 54 of BH8 nef is an aspartic acid, whereas that of BRU is alanine. Reciprocal changes in the sequences of BH8 and BRU nef were made by site-directed mutagenesis. The results show that substitution of aspartic acid at residue 54 of BH8 to alanine results in a protein that has a molecular weight of 25,000, and substitution of the alanine at position 54 of BRU to aspartic acid results in synthesis of a 27-kDa protein. These results show that a change in amino acid 54 of the HIV-1 nef protein dramatically affects the electrophoretic mobility of the protein. Nef proteins that contain an aspartic acid at residue 54 migrate as 27-kDa proteins, whereas those that contain alanine at residue 54 migrate as 25-kDa proteins. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT HUMAN RETROVIROL,44 BINNEY ST,BOSTON,MA 02115. FU NCI NIH HHS [CA 06516]; NIAID NIH HHS [AI 24845, AI 28785] NR 19 TC 14 Z9 14 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 MAR PY 1992 VL 5 IS 3 BP 308 EP 312 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA HF287 UT WOS:A1992HF28700013 PM 1740757 ER PT J AU KATSANIS, G JACOBY, G AF KATSANIS, G JACOBY, G TI THE FREQUENCY OF EXTENDED-SPECTRUM BETA-LACTAMASES IN ISOLATES OF KLEBSIELLA PNEUMONIAE SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Letter ID RESISTANCE; PLASMID RP KATSANIS, G (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. FU NIAID NIH HHS [AI20415] NR 9 TC 7 Z9 7 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0305-7453 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD MAR PY 1992 VL 29 IS 3 BP 345 EP 346 DI 10.1093/jac/29.3.345 PG 2 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA HK795 UT WOS:A1992HK79500013 PM 1592702 ER PT J AU DAVIES, JP SINGER, G HARRIS, WH AF DAVIES, JP SINGER, G HARRIS, WH TI THE EFFECT OF A THIN COATING OF POLYMETHYLMETHACRYLATE ON THE TORSIONAL FATIGUE-STRENGTH OF THE CEMENT METAL INTERFACE SO JOURNAL OF APPLIED BIOMATERIALS LA English DT Article AB Recent studies have established that a mechanism of initiation of failure of fixation of cemented femoral components is debonding of the cement-metal interface. Other studies have shown that the torsional forces induced by stair climbing and rising from a chair are very high. Thus, the interface between the femoral prosthesis and the bone cement in total hip arthroplasty (THA) is required to transmit high torsional loads from the metal to the cement in a cyclic shear mode many times per year. These torsional loads likely contribute to the debonding. This study evaluated the efficacy of a thin layer of polymethylmethacrylate (PMMA) precoating in increasing the torsional fatigue strength of the cement-metal interface. Fatigue studies were performed on 15 specimens. Each specimen was tested with and without PMMA precoating. The PMMA precoat significantly and substantially increased the torsional fatigue strength of the cement-metal interface. Thus, PMMA precoating is likely to be a clinical advantage in maintaining the long-term integrity of the cement-prosthesis interface. C1 MASSACHUSETTS GEN HOSP,ORTHOPAED BIOMECH LAB,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,HIP & IMPLANT UNIT,BOSTON,MA 02114. NR 11 TC 32 Z9 32 U1 0 U2 1 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 SPR PY 1992 VL 3 IS 1 BP 45 EP 49 DI 10.1002/jab.770030108 PG 5 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA HD761 UT WOS:A1992HD76100007 PM 10147704 ER PT J AU JACKSON, RM RUSSELL, WJ VEAL, CF AF JACKSON, RM RUSSELL, WJ VEAL, CF TI ENDOGENOUS AND EXOGENOUS CATALASE IN REOXYGENATION LUNG INJURY SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE REEXPANSION PULMONARY EDEMA; OXIDANT LUNG INJURY; HYDROGEN PEROXIDE; LUNG TISSUE HYPOXIA ID PERFUSED RAT-LIVER; ISCHEMIA-REPERFUSION; SUPEROXIDE-DISMUTASE; HYDROGEN-PEROXIDE; PULMONARY-EDEMA; METABOLISM; HYPOXIA; OXYGEN; NEUTROPHILS; GENERATION AB Reexpansion pulmonary edema parallels reperfusion (reoxygenation) injuries in other organs in that hypoxic and hypoperfused lung tissue develops increased vascular permeability and neutrophil infiltration after reexpansion. This study investigated endogenous lung catalase activity and H2O2 production during hypoxia (produced by lung collapse) and after reoxygenation (resulting from reexpansion), in addition to assessing the effects of exogenous catalase infusion on the development of unilateral pulmonary edema after reexpansion. Lung collapse resulted in a progressive increase in endogenous catalase activity after 3 (14%) and 7 days (23%), while activities in contralateral left lungs did not change (normal left lungs averaged 180 +/- 11 units/mg DNA). Tissue from control left lungs released H2O2 into the extracellular medium at a rate calculated to be 242 +/- 34 nmol.h-1.lung-1. No significant change in extracellular release of H2O2 occurred after 7 days of right lung collapse. However, after reexpansion of the previously collapsed right lungs for 2 h, H2O2 release from both reexpanded right and contralateral left lungs significantly increased (88 and 60%, respectively) compared with controls. Infusion of exogenous catalase significantly increased plasma and lung catalase activities. Exogenous catalase infusion prevented neither the increase in lung permeability nor the infiltration with neutrophils that typically occurs in reexpanded lungs. These data indicate that lung hypoxia/reoxygenation, induced by sequential collapse and reexpansion, has specific effects on endogenous lung catalase activity and H2O2 release. However, exogenous catalase does not prevent reexpansion pulmonary edema, eliminating extracellular (but not intracellular) H2O2 as an important mediator of unilateral lung injury in this model. C1 BIRMINGHAM VET AFFAIRS MED CTR,BIRMINGHAM,AL 35233. RP JACKSON, RM (reprint author), UNIV ALABAMA,DEPT MED,DIV PULM & CRIT CARE MED,RM 323 LYONS HARRISON RES BLDG,BIRMINGHAM,AL 35294, USA. FU NHLBI NIH HHS [HL-39147] NR 32 TC 23 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 MAR PY 1992 VL 72 IS 3 BP 858 EP 864 PG 7 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA HK063 UT WOS:A1992HK06300007 PM 1568981 ER PT J AU MEZZANOTTE, WS TANGEL, DJ WHITE, DP AF MEZZANOTTE, WS TANGEL, DJ WHITE, DP TI MECHANISMS OF CONTROL OF ALAE NASI MUSCLE-ACTIVITY SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE ELECTROMYOGRAPHY; NASAL AIRWAY ID OBSTRUCTIVE SLEEP-APNEA; AIRWAY PRESSURE CHANGES; RESPIRATORY ACTIVITY; STRETCH RECEPTORS; GENIOGLOSSUS; ACTIVATION; HUMANS; RESISTANCE; RESPONSES; HYPERCAPNIA AB Human upper airway dilator muscles are clearly influenced by chemical stimuli such as hypoxia and hypercapnia. Whether in humans there are upper airway receptors capable of modifying the activity of such muscles is unclear. We studied alae nasi electromyography (EMG) in normal men in an attempt to determine 1) whether increasing negative intraluminal pressure influences the activity of the alae nasi muscle, 2) whether nasal airway feedback mechanisms modify the activity of this muscle, and 3) if so, whether these receptor mechanisms are responding to mucosal temperature/pressure changes or to airway deformation. Alae nasi EMG was recorded in 10 normal men under the following conditions: 1) nasal breathing (all potential nasal receptors exposed), 2) oral breathing (nasal receptors not exposed), 3) nasal breathing with splints (airway deformation prevented), and 4) nasal breathing after nasal anesthesia (mucosal receptors anesthetized). In addition, in a separate group, the combined effects of anesthesia and nasal splints were assessed. Under each condition, EMG activity was monitored during basal breathing, progressive hypercapnia, and inspiratory resistive loading. Under all four conditions, both load and hypercapnia produced a significant increase in alae nasi EMG, with hypercapnia producing a similar increment in EMG regardless of nasal receptor exposure. On the other hand, loading produced greater increments in EMG during nasal than during oral breathing, with combined anesthesia plus splinting producing a load response similar to that observed during oral respiration. These observations suggest that nasal airway receptors have little effect on the alae nasi response to hypercapnia but appear to mediate the alae nasi response to loading or negative airway pressure. In addition, both mucosal receptors and receptors sensitive to airway collapse or deformation appear to be present in the nose. C1 UNIV COLORADO,HLTH SCI CTR,DENVER,CO 80262. RP MEZZANOTTE, WS (reprint author), DENVER VET AFFAIRS MED CTR,NATL JEWISH CTR,DIV PULM,1055 CLERMONT ST,DENVER,CO 80220, USA. FU NHLBI NIH HHS [HL-07085] NR 42 TC 18 Z9 18 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 MAR PY 1992 VL 72 IS 3 BP 925 EP 933 PG 9 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA HK063 UT WOS:A1992HK06300017 PM 1568988 ER PT J AU MAAYAN, C CARLEY, DW AXELROD, FB GRIMES, J SHANNON, DC AF MAAYAN, C CARLEY, DW AXELROD, FB GRIMES, J SHANNON, DC TI RESPIRATORY SYSTEM STABILITY AND ABNORMAL CARBON-DIOXIDE HOMEOSTASIS SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE FAMILIAL DYSAUTONOMIA; PERIODIC BREATHING; SLEEP APNEA; CONTROL OF BREATHING; CONGENITAL CENTRAL HYPOVENTILATION SYNDROME ID FAMILIAL DYSAUTONOMIA; AUTONOMIC NEUROPATHY; SLEEP-APNEA; HYPOXIA; MODEL AB We have tested the hypothesis that interactions among eight parameters of the respiratory and cardiovascular systems that determine the loop gain (LG) of the respiratory CO2 feedback control system might account for the degree of stability or instability of breathing patterns in healthy sleeping volunteers as well as in familial dysautonomia (FD) and congenital central hypoventilation syndrome (CCHS) patients. The predictability of cycle duration was tested as well. We measured the values of CO2 sensitivity, CO2 delivery capacity in the circulation, circulation delay, mean lung volume for CO2, and mixed venous PCO2 in 8 FD patients, 2 CCHS patients, and 19 healthy controls. The values of these parameters were used in a mathematical model to compute the LG of the respiratory control system during sleep for each epoch of respiration analyzed. The strength of the ventilatory oscillations (R) was quantified using power density spectra of the ventilation time series. All subjects were studied at inspiratory O2 concentrations (FI(O2)) of 0.21 and 0.15; CCHS patients and controls were also studied at 0.12 FI(O2) to examine the effect of steady-state hypoxia on respiratory system stability. In 2 FD patients, LG was elevated at both levels of FI(O2) and periodic breathing was observed; the values of R were elevated. Elevated mixed venous PCO2 and reduced CO2 delivery capacity were chiefly responsible for the abnormally high LG observed. In three healthy volunteers, high LG and unstable patterns were associated with high chemosensitivity. The CCHS patients, however, remained stable even at 0.12 FI(O2) because LG remained equivalent to zero due to a lack of chemosensitivity. As predicted by the model, unstable breathing patterns were associated with LG approximating unity or greater regardless of which parameter caused a high LG. LG greater-than-or-equal-to 1.0 was 71% sensitive and 98% specific in predicting instability. The shape of the model was sigmoidal in the experimental observations. Furthermore the model accurately predicted the cycle duration. Understanding the integration of the parameters that govern LG may aid in elucidating the mechanisms responsible for periodic breathing and sleep apnea and may have implications for their therapy. C1 MASSACHUSETTS GEN HOSP,CHILDRENS SERV,PEDIAT PULM UNIT,FRUIT ST,BOSTON,MA 02114. NYU MED CTR,CTR DYAUTONOMIA,NEW YORK,NY 10016. UNIV ILLINOIS,COLL MED,CHICAGO,IL 60612. NR 26 TC 17 Z9 17 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 MAR PY 1992 VL 72 IS 3 BP 1186 EP 1193 PG 8 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA HK063 UT WOS:A1992HK06300053 PM 1568973 ER PT J AU LITWIN, CM BOYKO, SA CALDERWOOD, SB AF LITWIN, CM BOYKO, SA CALDERWOOD, SB TI CLONING, SEQUENCING, AND TRANSCRIPTIONAL REGULATION OF THE VIBRIO-CHOLERAE FUR GENE SO JOURNAL OF BACTERIOLOGY LA English DT Article ID ESCHERICHIA-COLI; NUCLEOTIDE-SEQUENCE; IRON REGULATION; EXPRESSION; DNA; VIRULENCE; OPERON; PROTEIN; MUTANT AB Many genes involved in the transport of iron by bacteria as well as in pathogenesis are regulated by the environmental concentration of iron, with increased expression under low-iron conditions. In Escherichia coli, transcriptional regulation by iron depends on the fur gene. A virulence gene in Vibrio cholerae (irgA) is also transcriptionally regulated by iron, and the promoter of irgA contains a dyad repeat homologous to Fur binding sites in E. coli. Southern hybridization of V. cholerae chromosomal DNA, using an internal fragment of E. coli fur as a probe, showed a single hybridizing sequence under conditions of low stringency. We derived a restriction map in the vicinity of this hybridizing sequence; overlapping PstI and HindIII fragments were identified at the center of this map. The cloned PstI fragment failed to complement an E. coli fur mutant; sequence analysis revealed an open reading frame that began just downstream of the PstI site, suggesting that the clone was not functional because it lacked its promoter. The overlapping HindIII fragment contained the intact V. cholerae fur gene with its promoter and complemented an E. coli fur mutant. DNA sequencing of the HindIII fragment demonstrated a single open reading frame of 150 amino acids that was 76% homologous to E. coli Fur. Primer extension analysis localized two promoters for the V. cholerae fur gene; no significant homology to an E. coli Fur binding site was identified for either promoter. Northern blot analysis showed that the two fur transcripts were not strongly regulated by iron. These studies identify a gene in V. cholerae homologous in both function and sequence to the fur gene of E. coli, and we have designated this gene the fur gene of V. cholerae. 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] NR 32 TC 89 Z9 91 U1 1 U2 2 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 MAR PY 1992 VL 174 IS 6 BP 1897 EP 1903 PG 7 WC Microbiology SC Microbiology GA HJ502 UT WOS:A1992HJ50200025 PM 1372314 ER PT J AU DEWHIRST, FE PASTER, BJ OLSEN, I FRASER, GJ AF DEWHIRST, FE PASTER, BJ OLSEN, I FRASER, GJ TI PHYLOGENY OF 54 REPRESENTATIVE STRAINS OF SPECIES IN THE FAMILY PASTEURELLACEAE AS DETERMINED BY COMPARISON OF 16S RIBOSOMAL-RNA SEQUENCES SO JOURNAL OF BACTERIOLOGY LA English DT Article ID DEOXYRIBONUCLEIC-ACID RELATEDNESS; RIBOSOMAL-RNA GENE; ACTINOBACILLUS-LIKE ORGANISMS; COMB-NOV; HEMOPHILUS-SOMNUS; HISTOPHILUS-OVIS; ORAL CAVITY; HAEMOPHILUS-HAEMOGLOBINOPHILUS; NUCLEOTIDE-SEQUENCE; ESCHERICHIA-COLI AB Virtually complete 16S rRNA sequences were determined for 54 representative strains of species in the family Pasteurellaceae. Of these strains, 15 were Pasteurella, 16 were Actinobacillus, and 23 were Haemophilus. A phylogenetic tree was constructed based on sequence similarity, using the Neighbor-Joining method. Fifty-three of the strains fell within four large clusters. The first cluster included the type strains of Haemophilus influenzae, H. aegyptius, H. aphrophilus, H. haemolyticus, H. paraphrophilus, H. segnis, and Actinobacillus actinomycetemcomitans. This cluster also contained A. actinomycetemcomitans FDC Y4, ATCC 29522, ATCC 29523, and ATCC 29524 and H. aphrophilus NCTC 7901. The second cluster included the type strains of A. seminis and Pasteurella aerogenes and H. somnus OVCG 43826. The third cluster was composed of the type strains of Pasteurella multocida, P. anatis, P. avium, P. canis, P. dagmatis, P. gallinarum, P. langaa, P. stomatis, P. volantium, H. haemoglobinophilus, H. parasuis, H. paracuniculus, H. paragallinarum, and A. capsulatus. This cluster also contained Pasteurella species A CCUG 18782, Pasteurella species B CCUG 19974, Haemophilus taxon C CAPM 5111, H. parasuis type 5 Nagasaki, P. volantium (H. parainfluenzae) NCTC 4101, and P. trehalosi NCTC 10624. The fourth cluster included the type strains of Actinobacillus lignieresii, A. equuli, A. pleuropneumoniae, A. suis, A. ureae, H. parahaemolyticus, H. parainfluenzae, H. paraphrohaemolyticus, H. ducreyi, and P. haemolytica. This cluster also contained Actinobacillus species strain CCUG 19799 (Bisgaard taxon 11), A. suis ATCC 15557, H. ducreyi ATCC 27722 and HD 35000, Haemophilus minor group strain 202, and H. parainfluenzae ATCC 29242. The type strain of P. pneumotropica branched alone to form a fifth group. The branching of the Pasteurellaceae family tree was quite complex. The four major clusters contained multiple subclusters. The clusters contained both rapidly and slowly evolving strains (indicated by differing numbers of base changes incorporated into the 16S rRNA sequence relative to outgroup organisms). While the results presented a clear picture of the phylogenetic relationships, the complexity of the branching will make division of the family into genera a difficult and somewhat subjective task. We do not suggest any taxonomic changes at this time. C1 FORSYTH DENT CTR,DEPT MICROBIOL,BOSTON,MA 02115. UNIV OSLO,FAC DENT,DEPT MICROBIOL,OSLO 3,NORWAY. RP DEWHIRST, FE (reprint author), FORSYTH DENT CTR,DEPT PHARMACOL,BOSTON,MA 02115, USA. FU NIDCR NIH HHS [DE-04881, DE-08303] NR 68 TC 152 Z9 157 U1 0 U2 8 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 MAR PY 1992 VL 174 IS 6 BP 2002 EP 2013 PG 12 WC Microbiology SC Microbiology GA HJ502 UT WOS:A1992HJ50200038 PM 1548238 ER PT J AU CARPENTER, JE HIPP, JA GERHART, TN RUDMAN, CG HAYES, WC TRIPPEL, SB AF CARPENTER, JE HIPP, JA GERHART, TN RUDMAN, CG HAYES, WC TRIPPEL, SB TI FAILURE OF GROWTH-HORMONE TO ALTER THE BIOMECHANICS OF FRACTURE-HEALING IN A RABBIT MODEL SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID IMMUNOREACTIVE SOMATOMEDIN-C; CHONDROCYTES; CARTILAGE; SERUM AB Standardized tibial osteotomies were created and stabilized with external fixation in twenty-seven skeletally mature rabbits. Fourteen animals were treated with a daily injection of human growth hormone (150 micrograms per kilogram of body weight), and thirteen received a daily injection of saline solution. Serial non-destructive biomechanical tests, radiography, and determinations of the levels of serum insulin-like growth-factor I were performed for all of the animals. Destructive strength-testing of the sites of osteotomy was performed at four, six, or eight weeks. Twenty-five of the twenty-seven osteotomies healed uneventfully. There were no significant differences in the serial biomechanical measurements at the sites of the healing osteotomies, in the radiographic measurements, or in the ultimate strength of the sites of the osteotomy between the two groups. The mean level of serum insulin-like growth-factor I increased 33 per cent relative to the preoperative baseline level in the group that received growth hormone and increased 10 per cent in the control group. This difference was not statistically significant. There was no significant correlation between the biomechanical properties at the sites of the osteotomies and the levels of serum insulin-like growth-factor I. Administration of growth hormone had no measurable effect on fracture-healing in this model of normal animals. It remains to be determined whether injection of growth hormone might affect healing when there is a state of deficiency of endogenous growth hormone or when there is a non-union of a fracture. C1 MASSACHUSETTS GEN HOSP,DEPT ORTHOPAED SURG,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. BETH ISRAEL HOSP,DEPT ORTHOPAED SURG,ORTHOPAED BIOMECH LAB,BOSTON,MA 02215. FU NIAMS NIH HHS [AR31068] NR 34 TC 48 Z9 49 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 MAR PY 1992 VL 74A IS 3 BP 359 EP 367 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA HM905 UT WOS:A1992HM90500006 PM 1548262 ER PT J AU TANZER, M MALONEY, WJ JASTY, M HARRIS, WH AF TANZER, M MALONEY, WJ JASTY, M HARRIS, WH TI THE PROGRESSION OF FEMORAL CORTICAL OSTEOLYSIS IN ASSOCIATION WITH TOTAL HIP-ARTHROPLASTY WITHOUT CEMENT SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID SURGICAL TI-6AL-4V; ION-IMPLANTATION; BONE-RESORPTION; REPLACEMENT; COMPONENTS; LYSIS; WEAR AB Twenty hips in twenty patients had development of femoral endosteal cortical erosion after a cementless total hip replacement with the Harris-Galante porous-coated implant. Serial anteroposterior and lateral radiographs of all of the affected femora were reviewed to determine the interval between the operation and the first recognition of the osteolytic lesion or lesions, as well as to evaluate the radiographic appearance and progression of the lesions. The twenty affected hips were followed for an average of fifty-three months (range, twenty to seventy-seven months) after the operation. Osteolysis was first noted radiographically at twelve to sixty-six months (mean, thirty-nine months) postoperatively; in most patients, it occurred around the distal portion of the prosthetic stem. Twelve (60 per cent) of the femoral components were shown to be loose, as proved either radiographically or operatively. Three of these components had been judged radiographically to be stable when the endosteal erosion had first been identified, but they had subsequently migrated. The remaining eight hips had no evidence of loosening. The osteolysis was more severe in the femora in which the component was loose than in those in which it was stable. Of the fourteen patients who were followed, twelve (86 per cent) had an increase in the size of the osteolytic lesions with time, and only one patient had some radiographic evidence of healing. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP TANZER, M (reprint author), MASSACHUSETTS GEN HOSP,ORTHOPAED BIOMECH LAB,BOSTON,MA 02114, USA. NR 27 TC 143 Z9 146 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 MAR PY 1992 VL 74A IS 3 BP 404 EP 410 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA HM905 UT WOS:A1992HM90500012 PM 1548268 ER PT J AU GINTY, DD FANGER, GR WAGNER, JA MAUE, RA AF GINTY, DD FANGER, GR WAGNER, JA MAUE, RA TI THE ACTIVITY OF CAMP-DEPENDENT PROTEIN-KINASE IS REQUIRED AT A POSTTRANSLATIONAL LEVEL FOR INDUCTION OF VOLTAGE-DEPENDENT SODIUM-CHANNELS BY PEPTIDE GROWTH-FACTORS IN PC12 CELLS SO JOURNAL OF CELL BIOLOGY LA English DT Article ID FACTOR-INDUCED INCREASE; RAT-BRAIN NEURONS; PHEOCHROMOCYTOMA CELLS; ALPHA-SUBUNIT; NEURITE OUTGROWTH; MESSENGER-RNAS; CLONED CDNA; EXPRESSION; PHOSPHORYLATION; GENE AB The synthesis and expression of voltage-dependent sodium (Na) channels is a crucial aspect of neuronal differentiation because of the central role these ion channels play in the generation of action potentials and the transfer of information in the nervous system. We have used rat pheochromocytoma (PC12) cell lines deficient in cAMP-dependent protein kinase (PKA) activity to examine the role of PKA in the induction of Na channel expression by nerve growth factor (NGF) and basic FGF (bFGF). In the parental PC12 cell line both NGF and bFGF elicit an increase in the density of functional Na channels, as determined from whole-cell patch clamp recordings. This increase does not occur in two PC12 cell lines deficient in both isozymes of PKA (PKAI and PKAII), and is strongly reduced in a third line deficient in PKAII, but not PKAI. Despite the inability of the neurotrophic factors to induce functional Na channel expression in the PKA-deficient cells, Northern blot hybridization studies and saxitoxin binding assays of intact cells indicate that NGF and bFGF are still capable of eliciting increases in both Na channel mRNA and Na channel protein in the membrane. Thus, PKA activity appears to be necessary at a posttranslational step in the synthesis and expression of functional Na channels, and thereby plays an important role in determining neuronal excitability. C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MOLEC PHARMACOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. DARTMOUTH COLL,SCH MED,DEPT PHYSIOL,PROGRAM CELLULAR & MOLEC NEUROSCI,HANOVER,NH 03755. DARTMOUTH COLL,SCH MED,DEPT PHYSIOL,PROGRAM BIOCHEM,HANOVER,NH 03755. FU NCI NIH HHS [CA40929]; NINDS NIH HHS [NS08764, NS28767] NR 55 TC 61 Z9 63 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD MAR PY 1992 VL 116 IS 6 BP 1465 EP 1473 DI 10.1083/jcb.116.6.1465 PG 9 WC Cell Biology SC Cell Biology GA HH749 UT WOS:A1992HH74900014 PM 1311713 ER PT J AU ISHIDA, Y FURUKAWA, Y DECAPRIO, JA SAITO, M GRIFFIN, JD AF ISHIDA, Y FURUKAWA, Y DECAPRIO, JA SAITO, M GRIFFIN, JD TI TREATMENT OF MYELOID LEUKEMIC-CELLS WITH THE PHOSPHATASE INHIBITOR OKADAIC ACID INDUCES CELL-CYCLE ARREST AT EITHER G1/S OR G2/M DEPENDING ON DOSE SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID PREMATURE CHROMOSOME CONDENSATION; CDC2 PROTEIN-KINASE; CONTROL GENE CDC2+; FISSION YEAST; DNA-REPLICATION; TUMOR PROMOTER; TYROSINE PHOSPHORYLATION; REGULATED EXPRESSION; H1 KINASE; MITOSIS AB The phosphatase inhibitor okadaic acid was found to induce cell cycle arrest of human myeloid leukemic cell lines HL-60 and U937 in a concentration- and time-dependent manner. Exposure to low concentrations of okadaic acid (2-8nM) for 24-48 hr caused > 70% of cells to arrest at G2/M, with up to 40% of the cells arrested in early mitosis. Cell viability decreased rapidly after 48 hr of treatment, and morphological and DNA structure analysis indicated that this was primarily due to the induction of apoptosis. The cells arrested in mitosis by 8 nM okadaic acid could be highly enriched by density gradient centrifugation and underwent apoptosis when further cultured either with or without okadaic acid, indicating that the effects of okadaic acid were irreversible. In contrast to the effects of low concentrations of okadaic acid, high concentrations (500 nM), inhibited proliferation in less than 3 hr. Remarkably, the majority of cells also entered a mitosis-like state characterized by dissolution of the nuclear membrane and condensation and partial separation of chromosomes. However, these cells had a diploid content of DNA, indicating that the cell cycle arrest occurred at G1/S with premature chromosome condensation (PCC), rather than at G2/M. If cells were first blocked at G1/S with hydroxyurea and then treated with okadaic acid, > 90% developed PCC in less than 3 hr without replicating their DNA. Caffeine was not able to induce PCC in these cells, either with or without prior inhibition of DNA synthesis. These results provide further evidence that an interacting system of cell cycle associated phosphatases and kinases control the initiation of each phase of the cell cycle in higher eukaryotes and further suggest that okadaic acid will be useful in manipulating the cell cycle of leukemic cells. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. JICHI MED SCH,INST HEMATOL,DIV HEMOPOIESIS,MINAMI KAWACHI,TOCHIGI 32904,JAPAN. FU NCI NIH HHS [CA36167, CA34183] NR 58 TC 102 Z9 103 U1 1 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD MAR PY 1992 VL 150 IS 3 BP 484 EP 492 DI 10.1002/jcp.1041500308 PG 9 WC Cell Biology; Physiology SC Cell Biology; Physiology GA HF671 UT WOS:A1992HF67100007 PM 1311329 ER PT J AU HALL, JE SCHOENFELD, DA MARTIN, KA CROWLEY, WF AF HALL, JE SCHOENFELD, DA MARTIN, KA CROWLEY, WF TI HYPOTHALAMIC GONADOTROPIN-RELEASING-HORMONE SECRETION AND FOLLICLE-STIMULATING-HORMONE DYNAMICS DURING THE LUTEAL-FOLLICULAR TRANSITION SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HUMAN MENSTRUAL-CYCLE; LUTEINIZING-HORMONE; PULSE FREQUENCY; PUBERTAL DEVELOPMENT; OVARIECTOMIZED EWES; MACACA-FASCICULARIS; GENE-EXPRESSION; INHIBIN LEVELS; CORPUS-LUTEUM; ALPHA-SUBUNIT AB To define the precise neuroendocrine characteristics of the luteal-follicular transition, 11 normal women underwent 12 frequent sampling studies at 10-min intervals for 48 h at various points during the transition from one cycle to the next. Daily blood samples captured both the preceding and subsequent LH surges, so that studies could be characterized in relation to the preceding LH peak (LH+), the subsequent LH peak (LH-), and menses (M). In the frequent sampling study, LH and FSH were measured in all samples, and estradiol (E2) and progesterone (P) were measured in 2-h pools. The frequency of pulsatile LH secretion increased 4.5-fold over an 8-day period spanning the luteal-follicular transition. This increase in LH pulse frequency was strongly related to the preceding LH peak (r = 0.82; P < 0.00001), but was not at all related to the onset of menses. When the temporal markers (i.e. LH+, LH-, and M) were removed from the analysis, LH pulse frequency was inversely related to the log of serum P (r = -0.50; P < 0.005), but not E2. FSH levels increased both within the individual studies (P < 0.005) and in the group as a whole over the duration of the luteal-follicular transition. Mean FSH rose 3.5-fold compared to less than a 2-fold increase in mean LH. As with LH pulse frequency, the increase in FSH was most strongly related to the preceding LH peak, but was also significantly associated with the subsequent LH peak and the onset of menses. The relationship between FSH and the number of days from the preceding LH peak is even better fit by a second degree polynomial, which revealed an abrupt increase in LH beginning at LH+11. With the temporal markers excluded, the increase in FSH related only to LH pulse frequency (r = 0.62; P < 0.001). FSH was not statistically related to the decreases in P or E2, which are also key variables at this stage of the menstrual cycle. We reached the following conclusions. 1) A dramatic increase in LH pulse frequency, and by inference GnRH pulse frequency, accompanies the selective rise in FSH levels during the luteal-follicular transition of the normal menstrual cycle. 2) Both the increase in GnRH pulse frequency and the rise in FSH levels during this transition are strongly related to the preceding LH peak, while the clinical marker of menses is a relatively poor indicator of these events. 3) These studies indicate a high degree of neuroendocrine regulation of this critical transition and suggest that the abrupt increase in GnRH pulse frequency per se may play a significant role in the etiology of the selective rise in FSH that is critical to normal folliculogenesis. RP HALL, JE (reprint author), MASSACHUSETTS GEN HOSP, DEPT MED, REPROD ENDOCRINE UNIT, BOSTON, MA 02114 USA. FU NCRR NIH HHS [RR-01066]; NICHD NIH HHS [HD-15080, R01 HD015788, U54 HD028138, U01 HD044417] NR 41 TC 94 Z9 94 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAR PY 1992 VL 74 IS 3 BP 600 EP 607 DI 10.1210/jc.74.3.600 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA HG332 UT WOS:A1992HG33200025 PM 1740493 ER PT J AU KAYE, TB RUBIN, RA GOLDFINE, AB RAJAMANI, K KINSLEY, BT VISCHER, UM SIMONSON, DC AF KAYE, TB RUBIN, RA GOLDFINE, AB RAJAMANI, K KINSLEY, BT VISCHER, UM SIMONSON, DC TI EFFECT OF GLYCEMIC CONTROL ON THE OVERNIGHT DEXAMETHASONE SUPPRESSION TEST IN PATIENTS WITH DIABETES-MELLITUS SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID INSULIN-DEPENDENT DIABETICS; DIAGNOSTIC-TESTS; HYPERTENSION; RESPONSES; CORTISOL; GLUCOSE AB Because many of the clinical features associated with Cushing's syndrome are frequently found in patients with diabetes mellitus, diabetic patients are often evaluated for Cushing's syndrome. The initial test for Cushing's syndrome is the 1 mg overnight dexamethasone suppression test (DST), but its value as a screening test in diabetic subjects, especially those with poor glycemic control, has been questioned. To address this issue, an overnight DST was administered to 100 subjects with diabetes. Only 7 patients failed to suppress their plasma cortisol to less than 140 nmol/L (5.0-mu-g/dL), achieving a specificity of 93%. There was no relation between acute glycemic control (as measured by the mean of 4 serum glucose values obtained before receiving dexamethasone) or chronic glycemic control (as measured by glycohemoglobin) and false positive responses to the 1 mg overnight DST. The mean of the measures of acute glycemic control of the 7 subjects who had false positive results, 14.4 +/- 2.8 mmol/L, was not significantly different than that of the 93 subjects with normal responses, 13.2 +/- 3.3 mmol/L. Similarly, the mean glycohemoglobin of the subjects with false positive results, 12.8 +/- 2.4%, was not significantly different than that of the subjects with normal responses, 12.9 +/- 2.5%. There was no correlation between plasma cortisol after dexamethasone and glycohemoglobin (r = 0.05), and only a weak correlation with the mean serum glucose (r = 0.21). We conclude that the 1 mg overnight DST is a valid screening test for Cushing's syndrome in patients with diabetes, regardless of glycemic control. C1 NEW ENGLAND DEACONESS HOSP, JOSLIN DIABET CTR, DEPT MED, 1 JOSLIN PL, BOSTON, MA 02215 USA. HARVARD UNIV, BRIGHAM & WOMENS HOSP, SCH MED, BOSTON, MA 02115 USA. FU NIDDK NIH HHS [5 P30 DK 36836] NR 23 TC 9 Z9 10 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAR PY 1992 VL 74 IS 3 BP 640 EP 644 DI 10.1210/jc.74.3.640 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA HG332 UT WOS:A1992HG33200032 PM 1740499 ER PT J AU LAWRENCE, VA TUGWELL, P GAFNI, A KOSUWON, W SPITZER, WO AF LAWRENCE, VA TUGWELL, P GAFNI, A KOSUWON, W SPITZER, WO TI ACUTE LOW-BACK-PAIN AND ECONOMICS OF THERAPY - THE ITERATIVE LOOP APPROACH SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE ACUTE NONSPECIFIC LOW-BACK PAIN; MEASUREMENT ITERATIVE LOOP; COMMUNITY HEALTH PERSPECTIVE; ECONOMIC EVALUATION ID DOUBLE-BLIND; MUSCULOSKELETAL DISORDERS; CLINICAL-TRIAL; CONSERVATIVE THERAPY; SPINAL MANIPULATION; FAMILY-PRACTICE; UNITED-STATES; MEDICAL-CARE; LUMBAR SPINE; EPIDEMIOLOGY AB We use the measurement iterative loop as a conceptual framework to examine the economics of common therapies for acute non-specific low back pain. The measurement iterative loop systematically assesses the interlocking facets of an illness from the community health perspective, including quantifying burden of illness, etiology, assessment of therapeutic effectiveness, and economic evaluation of therapies. The iterative loop reveals that: (1) burden of illness, although known to be substantial, is so far inaccurately measured, (2) little is known about such factors as provider and patient compliance: and (3) the economics of therapy can guide us in this time of clinical uncertainty when no therapy appears clearly superior. For therapies with at least some support from randomized controlled trials, bedrest appears to be economically superior. Besides burden of illness, compliance, and current therapies, future research should address such "therapeutic" options as early return to work and patient self-management. C1 AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. MCMASTER UNIV,DEPT CLIN EPIDEMIOL & BIOSTAT,HAMILTON L8S 4L8,ONTARIO,CANADA. MCGILL UNIV,DEPT EPIDEMIOL & BIOSTAT,MONTREAL H3A 2T5,QUEBEC,CANADA. RP LAWRENCE, VA (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV GEN MED,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. OI Tugwell, Peter/0000-0001-5062-0556 NR 67 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 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD MAR PY 1992 VL 45 IS 3 BP 301 EP 311 DI 10.1016/0895-4356(92)90091-Z PG 11 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA HR885 UT WOS:A1992HR88500013 PM 1533245 ER PT J AU GUNJI, H HASS, R KUFE, D AF GUNJI, H HASS, R KUFE, D TI INTERNUCLEOSOMAL DNA FRAGMENTATION DURING PHORBOL ESTER INDUCED MONOCYTIC DIFFERENTIATION AND G0/G1 ARREST SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE CELL CYCLE; DNA CLEAVAGE; RETRODIFFERENTIATION; TPA ID FMS PROTO-ONCOGENE; C-FMS; CELL-DIFFERENTIATION; LEUKEMIA-CELLS; GROWTH-FACTOR; T-CELLS; INDUCTION; APOPTOSIS; ENDONUCLEASE; ACTIVATION AB The treatment of human myeloid leukemia cell lines with phorbol esters, such as 12-O-tetradecanoylphorbol-13-acetate (TPA), is associated with loss of proliferative capacity and induction of monocytic differentiation. The present results demonstrate that treatment of asynchronous human U-937 leukemia cells with 10 nM TPA is also associated with oligonucleosomal DNA cleavage. This pattern of DNA fragmentation, which is observed in programmed cell death, was detectable in populations of TPA-treated cells that had entered a nonproliferative G0/G1 phase. Similar findings were obtained after TPA treatment of a synchronous population of G1 cells. These cells progressed through S and G2/M phases before undergoing internucleosomal DNA cleavage during G0/G1 arrest. These G0/G1 cells displayed characteristics of monocytic differentiation, including down-regulation of c-myc expression and induction of c-fms transcripts. DNA fragmentation was also studied in cells treated with 5 nM TPA for 48 h and then monitored in drug-free long-term culture. Endonucleolytic cleavage was similarly observed in the differentiated G0/G1 population. However, longer periods of culture were associated with a decrease in DNA fragmentation to undetectable levels. This effect was followed by retrodifferentiation and reentry of cells into cycle. Taken together, these findings demonstrate that internucleosomal DNA fragmentation occurs during induction of monocytic differentiation, and that both of these events are detectable in G0/G1 cells. RP GUNJI, H (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,CLIN PHARMACOL LAB,BOSTON,MA 02115, USA. RI Hass, Ralf/F-3197-2012 OI Hass, Ralf/0000-0002-2481-7547 FU NCI NIH HHS [CA-34183, CA-42802] NR 32 TC 78 Z9 78 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 MAR PY 1992 VL 89 IS 3 BP 954 EP 960 DI 10.1172/JCI115677 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA HH513 UT WOS:A1992HH51300031 PM 1541683 ER PT J AU WILSON, DB WILSON, MP AF WILSON, DB WILSON, MP TI IDENTIFICATION AND SUBCELLULAR-LOCALIZATION OF HUMAN RAB5B, A NEW MEMBER OF THE RAS-RELATED SUPERFAMILY OF GTPASES SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE GTP-BINDING PROTEIN; MEMBRANE TRAFFICKING ID GTP-BINDING-PROTEINS; MOLECULAR-CLONING; CELL-LINE; YEAST; SECRETION; TRANSPORT; VESICLES; YPT1; EXPRESSION; CALCIUM AB Members of the mammalian rab family of GTPases are associated with specific subcellular compartments, where these proteins are postulated to function in vesicular transport. By screening a human umbilical vein endothelial cell library with degenerate oligonucleotide probes, we have isolated a 1.6-kb cDNA clone encoding a 215-amino-acid protein belonging to the rab family of GTPases. This newly identified rab protein is 81% identical to human rab5, the canine counterpart of which has been localized to the plasma membrane and early endosomes. In light of this homology, we have named this new member of the GTPase superfamily "rab5b." Northern analysis using the rab5b cDNA as a probe revealed a 3.6-kb mRNA in a variety of cell types, including human umbilical vein endothelial cells, K562 erythroleukemia cells, U937 monoblastic cells, and HeLa cells. A fusion protein between glutathione-S-transferase (GST) and rab5b was expressed in bacteria and purified to homogeneity. The recombinant protein was shown to bind GTP and GDP. As is typical of other recombinant rab proteins, the rab5b-GST fusion protein displayed a low intrinsic rate of GTP hydrolysis (0.005/min). An antiserum to rab5b was prepared and used to determine the apparent molecular size and subcellular distribution of the protein. Western blotting with this antibody revealed a 25-kD protein in COS cells transfected with rab5b and in nontransfected HeLa cells. Indirect immunofluorescence and subcellular fractionation showed that rab5b localizes to the plasma membrane. We speculate that rab5b plays a role in vesicular trafficking at the plasma membrane in various cell types. C1 BRANDEIS UNIV,CTR COMPLEX SYST,GRAD DEPT BIOCHEM,WALTHAM,MA 02254. RP WILSON, DB (reprint author), BOSTON CHILDRENS HOSP,DANA FARBER CANC INST,DIV HEMATOL ONCOL,ENDERS BLDG,7TH FLOOR,BOSTON,MA 02115, USA. RI Wilson, David/K-7433-2014 OI Wilson, David/0000-0002-1826-7745 FU NHLBI NIH HHS [5P32HL-07574] NR 48 TC 32 Z9 35 U1 0 U2 1 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 MAR PY 1992 VL 89 IS 3 BP 996 EP 1005 DI 10.1172/JCI115683 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA HH513 UT WOS:A1992HH51300037 PM 1541686 ER PT J AU CLARK, GM MATHIEU, MC OWENS, MA DRESSLER, LG EUDEY, L TORMEY, DC OSBORNE, CK GILCHRIST, KW MANSOUR, EG ABELOFF, MD MCGUIRE, WL AF CLARK, GM MATHIEU, MC OWENS, MA DRESSLER, LG EUDEY, L TORMEY, DC OSBORNE, CK GILCHRIST, KW MANSOUR, EG ABELOFF, MD MCGUIRE, WL TI PROGNOSTIC-SIGNIFICANCE OF S-PHASE FRACTION IN GOOD-RISK, NODE-NEGATIVE BREAST-CANCER PATIENTS SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID DNA FLOW-CYTOMETRY; PLOIDY; SURVIVAL C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED ONCOL,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284. INST GUSTAVE ROUSSY,F-94805 VILLEJUIF,FRANCE. NICHOLS INST,SAN JUAN CAPISTRANO,CA. UNIV NEW MEXICO,CTR CANC,ALBUQUERQUE,NM 87131. HARVARD UNIV,SCH PUBL HLTH,DANA FARBER CANC INST,BOSTON,MA 02115. UNIV WISCONSIN,CTR CLIN CANC,MADISON,WI 53706. CASE WESTERN RESERVE UNIV,METROHELTH MED CTR,CLEVELAND,OH 44106. JOHNS HOPKINS UNIV HOSP,CTR ONCOL,BALTIMORE,MD 21205. FU NCI NIH HHS [CA21115, CA32102, CA23318] NR 22 TC 111 Z9 112 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 MAR PY 1992 VL 10 IS 3 BP 428 EP 432 PG 5 WC Oncology SC Oncology GA HF656 UT WOS:A1992HF65600013 PM 1740681 ER PT J AU TAKAHASHI, LK AF TAKAHASHI, LK TI DEVELOPMENTAL EXPRESSION OF DEFENSIVE RESPONSES DURING EXPOSURE TO CONSPECIFIC ADULTS IN PREWEANLING RATS (RATTUS-NORVEGICUS) SO JOURNAL OF COMPARATIVE PSYCHOLOGY LA English DT Article ID INFANT RHESUS-MONKEYS; MATERNAL AGGRESSION; HORMONAL RESPONSES; 2-WEEK-OLD RATS; SMALL RODENTS; SEPARATION; ULTRASOUNDS; BEHAVIOR; STRESS; MICE AB I examined preweanling rats' (Rattus norvegicus) expression of ultrasounds and secretion of ACTH when exposed to unfamiliar adult male rats or to their mothers. Pups at 7 days of age produced similar levels of ultrasonic vocalization near both unfamiliar males and mothers. However, these pups could discriminate familiar from unfamiliar adults because ACTH was significantly higher in pups near adult males than in those near mothers. At 14 days of age, pups avoided adult males but not their mothers; therefore, adult males represented a significant threat. Importantly, 14-day-old rats significantly reduced ultrasound production only when near adult males. Pups at 21 days of age no longer emitted ultrasounds when socially isolated or when near conspecific adults. In addition, 14- and 21-day-old rats produced similar elevated ACTH levels across stimulus conditions. Results show significant changes in preweanling rats' responses to conspecific adults. C1 WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI 53705. RP TAKAHASHI, LK (reprint author), UNIV WISCONSIN,SCH MED,DEPT PSYCHIAT,600 HIGHLAND AVE,MADISON,WI 53792, USA. FU NIMH NIH HHS [MH-43986] NR 49 TC 53 Z9 53 U1 0 U2 1 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0735-7036 J9 J COMP PSYCHOL JI J. Comp. Psychol. PD MAR PY 1992 VL 106 IS 1 BP 69 EP 77 DI 10.1037//0735-7036.106.1.69 PG 9 WC Behavioral Sciences; Psychology; Psychology, Multidisciplinary; Zoology SC Behavioral Sciences; Psychology; Zoology GA HF269 UT WOS:A1992HF26900008 PM 1313347 ER PT J AU ROBERTSON, MJ SOIFFER, RJ WOLF, SF MANLEY, TJ DONAHUE, C YOUNG, D HERRMANN, SH RITZ, J AF ROBERTSON, MJ SOIFFER, RJ WOLF, SF MANLEY, TJ DONAHUE, C YOUNG, D HERRMANN, SH RITZ, J TI RESPONSE OF HUMAN NATURAL-KILLER (NK) CELLS TO NK CELL STIMULATORY FACTOR (NKSF) - CYTOLYTIC ACTIVITY AND PROLIFERATION OF NK CELLS ARE DIFFERENTIALLY REGULATED BY NKSF SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID HIGH-DOSE INTERLEUKIN-2; RECOMBINANT INTERLEUKIN-2; ADHESION MOLECULES; HUMAN-LYMPHOCYTES; CANCER-PATIENTS; SOLID TUMORS; RECEPTOR; EXPRESSION; ACTIVATION; PARTICIPATION AB Natural killer cell stimulatory factor (NKSF) is a 70-kD heterodimeric cytokine that was initially isolated from conditioned medium of human B lymphoblastoid cell lines. The effects of recombinant NKSF on the function of human peripheral blood NK cells were examined. NKSF directly augmented the cytolytic activity of freshly isolated NK cells. Both CD56dim and CD56bright NK cells demonstrated enhanced cytotoxicity after brief exposure to NKSF. In contrast, highly purified T lymphocytes did not exhibit major histocompatibility complex-unrestricted cytotoxicity after short-term culture with NKSF. Like interleukin 2 (IL-2), NKSF augmented the lysis of NK-sensitive, NK-resistant, and antibody-coated targets. Both NKSF and IL-2 induced marked upregulation of several NK cell adhesion molecules known to participate in cytolysis, including CD2, CD11a, and CD54. However, NKSF activates NK cells through a pathway distinct from that of IL-2, since the presence of anti-IL-2 receptor (anti-IL-2R) antibodies or IL-4 did not inhibit the effects of NKSF. NKSF by itself induced very little proliferation of resting NK cells. NK cells preactivated in vitro with IL-2 demonstrated enhanced proliferation to NKSF, but the degree of proliferation was always inferior to that induced by IL-2 alone. Moreover, NKSF strongly inhibited IL-2-induced proliferation of either resting or preactivated NK cells. This inhibition was not the result of decreased IL-2R expression, because NKSF-activated NK cells expressed higher levels of both IL-2Rs p75 and p55. Furthermore, NKSF did not inhibit the proliferation of mitogen-activated T cells, indicating a selective effect on NK cell proliferation. Human NK cells expanded in vivo by prolonged continuous infusions of IL-2 remained fully responsive to NKSF. Picomolar concentrations of NKSF were as effective as nanomolar concentrations of IL-2 in augmenting the cytolytic activity of NK cells expanded in vivo by IL-2. NKSF may play an important role in the regulation of human NK cell function, and its possible use as a therapeutic cytokine deserves further investigation. C1 GENET INST,CAMBRIDGE,MA 02140. RP ROBERTSON, MJ (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,DIV TUMOR IMMUNOL,44 BINNEY ST,BOSTON,MA 02115, USA. RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NCI NIH HHS [CA-41619] NR 42 TC 377 Z9 381 U1 0 U2 4 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 MAR 1 PY 1992 VL 175 IS 3 BP 779 EP 788 DI 10.1084/jem.175.3.779 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA HF640 UT WOS:A1992HF64000016 PM 1346796 ER PT J AU GONG, JL MCCARTHY, KM TELFORD, J TAMATANI, T MIYASAKA, M SCHNEEBERGER, EE AF GONG, JL MCCARTHY, KM TELFORD, J TAMATANI, T MIYASAKA, M SCHNEEBERGER, EE TI INTRAEPITHELIAL AIRWAY DENDRITIC CELLS - A DISTINCT SUBSET OF PULMONARY DENDRITIC CELLS OBTAINED BY MICRODISSECTION SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID EPIDERMAL LANGERHANS CELLS; COLONY-STIMULATING FACTOR; LEUKOCYTE-COMMON ANTIGEN; MONOCLONAL-ANTIBODY; LYMPHOCYTES-T; ADHESION RECEPTORS; RAT LUNG; MACROPHAGES; IDENTIFICATION; HETEROGENEITY AB Dendritic cells (DC), in general, and pulmonary DC, in particular, are a heterogeneous population of cells, their phenotype and function being dependent on their anatomic location, their state of activation, and the regulatory effect of locally secreted cytokines. Using a novel microdissection technique, the epithelium from the trachea and entire air-way system was harvested, and the contained DC isolated at > 90% purity. The phenotype and function of these airway DC (ADC) was compared to DC isolated, at > 90% purity, from the parenchyma of the same lung. In contrast to lung DC (LDC), ADC did not express intercellular adhesion molecule 1 (ICAM-1) in situ, the amount of immune associated antigen (Ia) expressed was less (as determined by immunoperoxidase staining and immunopanning), and > 50% of ADC displayed Fc receptors (FcR). The majority of LDC were ICAM-1+, < 5% expressed FcR, and all were intensely Ia+. Airway DC were most numerous in tracheal epithelium, but they were also present in small numbers in the epithelium of the most distal airways. Their numbers increased in all segments of the tracheobronchial epithelium in response to the administration of IFN-gamma. ADC were consistently more effective than LDC in presenting soluble (hen egg lysozyme) and particulate (heat-killed Listeria monocytogenes) antigens to antigen-sensitized T cells. By contrast, LDC were significantly more efficient in stimulating the proliferation of nonsensitized T cells in an autologous mixed leukocyte reaction. These data suggest that in normal animals, intraepithelial DC of airways share many attributes with Langerhans cells of the skin. Interstitial LDC, by contrast, reside in an environment where they may be exposed to a different set of regulatory factors and where they have progressed to a more advanced stage of differentiation than ADC. Both groups of DC are, however, heterogeneous, reflecting the continuous turnover that these cells undergo in the lung. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,COX BLDG 5,BOSTON,MA 02114. TOKYO METROPOLITAN INST MED SCI,DEPT IMMUNOL,TOKYO 113,JAPAN. FU NHLBI NIH HHS [HL-36781] NR 47 TC 92 Z9 93 U1 0 U2 1 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 MAR 1 PY 1992 VL 175 IS 3 BP 797 EP 807 DI 10.1084/jem.175.3.797 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA HF640 UT WOS:A1992HF64000018 PM 1740664 ER PT J AU JAIN, J VALGEARCHER, VE SINSKEY, AJ RAO, A AF JAIN, J VALGEARCHER, VE SINSKEY, AJ RAO, A TI THE AP-1 SITE AT -150 BP, BUT NOT THE NF-KAPPA-B SITE, IS LIKELY TO REPRESENT THE MAJOR TARGET OF PROTEIN-KINASE-C IN THE INTERLEUKIN-2 PROMOTER SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID LYMPHOCYTE-SPECIFIC FACTORS; T-CELL ACTIVATION; ANTIGEN RECEPTOR; GENE; BINDING; EXPRESSION; ENHANCER; FOS; PROLIFERATION; TRANSCRIPTION AB Stimulation of T cells with antigen results in activation of several kinases, including protein kinase C (PKC), that may mediate the later induction of activation-related genes. We have examined the potential role of PKC in induction of the interleukin 2 (IL-2) gene in T cells stimulated through the T cell receptor/CD3 complex. We have previously shown that prolonged treatment of the untransformed T cell clone Ar-5 with phorbol esters results in downmodulation of the alpha and beta-isozymes of PKC, and abrogates induction of IL-2 mRNA and protein. Here we show that phorbol ester treatment also abolishes induction of chloramphenicol acetyltransferase activity in Ar-5 cells transfected with a plasmid containing the IL-2 promoter linked to this reporter gene. The IL-2 promoter contains binding sites for nuclear factors including NFAT-1, Oct, NF-kappa-B, and AP-1, which are all potentially sensitive to activation of PKC. We show that induction of a trimer of the NFAT and Oct sites is not sensitive to phorbol ester treatment, and that mutations in the NF-kappa-B site have no effect on inducibility of the IL-2 promoter. In contrast, mutations in the AP-1 site located at -150 bp almost completely abrogate induction of the IL-2 promoter, and appearance of an inducible nuclear factor binding to this site is sensitive to PKC depletion. Moreover, cotransfections with c-fos and c-jun expression plasmids markedly enhance induction of the IL-2 promoter in minimally stimulated T cells. Our results indicate that the AP-1 site at -150 bp represents a major, if not the only, site of PKC responsiveness in the IL-2 promoter. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOUR VIROL,MAYER BLDG,ROOM 613,44 BINNEY ST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. MIT,DEPT BIOL,CAMBRIDGE,MA 02139. FU NCI NIH HHS [CA-42471] NR 51 TC 77 Z9 77 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 MAR 1 PY 1992 VL 175 IS 3 BP 853 EP 862 DI 10.1084/jem.175.3.853 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA HF640 UT WOS:A1992HF64000024 PM 1740667 ER PT J AU LAVIZZOMOUREY, RJ SIEGLER, EL AF LAVIZZOMOUREY, RJ SIEGLER, EL TI HEARING IMPAIRMENT IN THE ELDERLY SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Review RP LAVIZZOMOUREY, RJ (reprint author), PHILADELPHIA VET AFFAIRS MED CTR,UNIV & WOODLAND AVE,PHILADELPHIA,PA 19104, USA. OI Siegler, Eugenia/0000-0001-9449-5873 FU NIA NIH HHS [K08AG0036304] NR 0 TC 3 Z9 3 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR-APR PY 1992 VL 7 IS 2 BP 191 EP 198 DI 10.1007/BF02598012 PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA HJ343 UT WOS:A1992HJ34300011 PM 1487768 ER PT J AU GELBERMAN, RH AF GELBERMAN, RH TI CARPAL-TUNNEL SYNDROME - MORPHOLOGICAL-CHANGES AFTER THE RELEASE OF THE TRANSVERSE CARPAL LIGAMENT - REPLY SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Letter RP GELBERMAN, RH (reprint author), MASSACHUSETTS GEN HOSP,WACC-427,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD MAR PY 1992 VL 17A IS 2 BP 379 EP 379 DI 10.1016/0363-5023(92)90425-O PG 1 WC Orthopedics; Surgery SC Orthopedics; Surgery GA HJ086 UT WOS:A1992HJ08600037 ER PT J AU MASUYAMA, JI BERMAN, JS CRUIKSHANK, WW MORIMOTO, C CENTER, DM AF MASUYAMA, JI BERMAN, JS CRUIKSHANK, WW MORIMOTO, C CENTER, DM TI EVIDENCE FOR RECENT AS WELL AS LONG-TERM ACTIVATION OF T-CELLS MIGRATING THROUGH ENDOTHELIAL-CELL MONOLAYERS INVITRO SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LYMPHOCYTE HOMING RECEPTOR; MONOCLONAL-ANTIBODY; SURFACE MOLECULE; CD4 CELLS; EXTRACELLULAR-MATRIX; INTEGRIN FAMILY; HELPER FUNCTION; ADHESION; LFA-1; INTERFERON AB As T cells actively extravasate from blood, they adhere to endothelium and then migrate out of the vessel with a locomotive activity. Although both adhesion and locomotion are properties associated with activated T cells, the two processes are not necessarily associated with identical activation states. Using human endothelial cells (EC) cultured to confluence on collagen gel, we examined the activation state of human peripheral blood T cells that adhere to and migrate through EC monolayers with three different methods: flow cytometric analysis of cell surface activation-related molecules, incorporation of tritiated nucleotide, and cell cycle analysis. The results were as follows. 1) Although expression of very late activation Ag integrins VLA-2 and VLA-3 by the initial blood T cell population (unseparated cells) and of adherent T cells was minimal, 40 to 45% of migrating cells were positive for VLA-2 and VLA-3. 2) The percentage of IL-2R+ cells in both unseparated and adherent cells was below 5% whereas the percentage of IL-2R+ cells among the migrating cells was 22 +/- 9% (range, 12 to 31%, n = 6). 3) Migrating cells expressed the highest CD26, whereas CD26 of adherent (nonmigrating) cells was divided into negative and high expression; in contrast, leukocyte adhesion molecule-1 (L-selectin) of both adherent and migrating cells was mostly low or negative. 4) [H-3]Uridine incorporation of migrating and adherent cells was 2.1- to 2.5-fold and 1.4- to 1.7-fold higher, respectively, than that of unseparated cells, indicating that RNA synthesis of migrating cells as well as adherent cells was enhanced. 5) Cell cycle analysis showed that 23.5% of migrating cells appeared to enter the G1 phase but not S or G2 + M phases whereas 2.2% of unseparated cells and 8.0% of adherent cells that did not migrate had an RNA content consistent with entry into G1. These results suggest that cells migrating from normal human blood through unactivated EC have been activated recently as well as showing evidence of long term activation. The activation state of migrating cells is consistent with the hypothesis that previous in vivo activation is required for cells to migrate through EC in this system. C1 BOSTON UNIV,SCH MED,CTR PULM,80 E CONCORD ST,RM K-603,BOSTON,MA 02118. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02215. FU NHLBI NIH HHS [HL-19717]; NIAID NIH HHS [AI 25930]; NIAMS NIH HHS [AR-33713] NR 50 TC 120 Z9 121 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 1 PY 1992 VL 148 IS 5 BP 1367 EP 1374 PG 8 WC Immunology SC Immunology GA HF266 UT WOS:A1992HF26600012 PM 1371526 ER PT J AU RASHID, A AUCHINCLOSS, H SHARON, J AF RASHID, A AUCHINCLOSS, H SHARON, J TI COMPARISON OF GK1.5 AND CHIMERIC RAT MOUSE GK1.5 ANTI-CD4 ANTIBODIES FOR PROLONGATION OF SKIN ALLOGRAFT SURVIVAL AND SUPPRESSION OF ALLOANTIBODY PRODUCTION IN MICE SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELL SUBSETS; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; NZB NZW F1-MICE; MONOCLONAL-ANTIBODY; GRAFT REJECTION; CYTO-TOXICITY; SEGMENTAL FLEXIBILITY; ANTI-L3T4 ANTIBODIES; IDIOTYPE CONNECTANCE; TOLERANCE INDUCTION AB GK1.5 is a rat mAb that recognizes the mouse CD4 Ag. It has been shown to deplete CD4+ cells in vivo and to be immunosuppressive. To evaluate the effect of the C region of this antibody in achieving cell depletion, chimeric antibodies, each having the rat GK1.5 V regions and one of the four mouse IgG C region isotypes, were compared with the native rat antibody. The chimeric antibodies and the native antibody were tested for their ability to mediate in vitro C-dependent cytotoxicity, in vivo cell depletion, and prolongation of allogeneic skin graft survival and suppression of alloantibody production. In vitro C-dependent cytotoxicity assays revealed that rat IgG2b and the chimeric antibodies containing mouse IgG2a, mouse IgG2b, and mouse IgG3 were effective in lysing CD4+ lymphocytes whereas mouse IgG, was ineffective. In vivo studies of CD4+ cell depletion showed that mouse IgG2a, rat IgG2b, and mouse IgG2b were effective isotypes, mouse IgG1 was less effective, and mouse IgG3 did not deplete CD4+ cells. A correlation was found between the ability of an isotype to deplete CD4+ cells in vivo and its ability to prolong the survival of skin allografts and to suppress alloantibody production. The nondepleting mouse IgG3 was ineffective in these assays. Overall the most effective mouse isotype was IgG2a which was as effective as rat IgG2b. These results indicate 1) that syngeneic isotypes of mAb can cause cell depletion and consequently the prolongation of allograft rejection and suppression of alloantibody production; 2) that not all isotypes are equally effective; and 3) that the ability of a given isotype to deplete cells in vivo does not correlate with its ability to mediate C-dependent lysis in vitro. Our results are consistent with the hypothesis that in vivo depletion of cells is mediated by opsonization and binding through the FcR. C1 BOSTON UNIV,SCH MED,DEPT PATHOL,80 E CONCORD ST,K707,BOSTON,MA 02118. BOSTON UNIV,SCH MED,HUBERT H HUMPHREY CANC RES CTR,BOSTON,MA 02118. MASSACHUSETTS GEN HOSP,DEPT SURG,TRANSPLANTAT UNIT,BOSTON,MA 02114. FU NHLBI NIH HHS [HL18646, HL36377]; NIAID NIH HHS [AI23909] NR 57 TC 31 Z9 31 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 MAR 1 PY 1992 VL 148 IS 5 BP 1382 EP 1388 PG 7 WC Immunology SC Immunology GA HF266 UT WOS:A1992HF26600014 PM 1538121 ER PT J AU ROCK, KL ROTHSTEIN, L GAMBLE, S GRAMM, C BENACERRAF, B AF ROCK, KL ROTHSTEIN, L GAMBLE, S GRAMM, C BENACERRAF, B TI CHEMICAL CROSS-LINKING OF CLASS-I MOLECULES ON CELLS CREATES RECEPTIVE PEPTIDE BINDING-SITES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HELPER LYMPHOCYTES-T; ANTIGEN PRESENTATION; SURFACE EXPRESSION; BETA-2-MICROGLOBULIN; RECOGNITION; COMPLEX; HYBRIDOMAS; PROTEIN; CHAINS; HEAVY AB Class I heterodimers on the surface of cells are generally unreceptive to binding peptides in the absence of exogenous beta-2-microglobulin. Paraformaldehyde covalently cross-links beta-2-microglobulin to class I heavy chains in situ and stabilizes empty class I heterodimers. Functionally, this cross-linking creates receptive class I peptide binding sites by acting on beta-2-microglobulin-associated molecules. The presentation of preexisting peptide-class I complexes is also enhanced. These findings support a model whereby a structural alteration, the dissociation Of beta-2-microglobulin, limits the existence of receptive class I molecules on normal cells and may control the half-life of active class I molecules. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RP ROCK, KL (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV LYMPHOCYTE BIOL,44 BINNEY ST,BOSTON,MA 02115, USA. FU NIAID NIH HHS [R01 AI20248] NR 41 TC 18 Z9 18 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 MAR 1 PY 1992 VL 148 IS 5 BP 1451 EP 1457 PG 7 WC Immunology SC Immunology GA HF266 UT WOS:A1992HF26600024 PM 1538130 ER PT J AU SIBER, GR LESZCZYNSKI, J PENACRUZ, V FERRENGARDNER, C ANDERSON, R HEMMING, VG WALSH, EE BURNS, J MCINTOSH, K GONIN, R ANDERSON, LJ AF SIBER, GR LESZCZYNSKI, J PENACRUZ, V FERRENGARDNER, C ANDERSON, R HEMMING, VG WALSH, EE BURNS, J MCINTOSH, K GONIN, R ANDERSON, LJ TI PROTECTIVE ACTIVITY OF A HUMAN RESPIRATORY SYNCYTIAL VIRUS IMMUNE GLOBULIN PREPARED FROM DONORS SCREENED BY MICRONEUTRALIZATION ASSAY SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID MONOCLONAL-ANTIBODIES; VIRAL-INFECTION; COTTON RATS; FUSION PROTEIN; YOUNG-CHILDREN; F-GLYCOPROTEIN; INFANTS; IDENTIFICATION; IMMUNOTHERAPY; RIBAVIRIN AB To explore the feasibility of preparing a human immune globulin specific for respiratory syncytial virus (RSV) by screening plasma donors, the ability of seven RSV antibody assays to identify plasma-yielding IgG with high virus-neutralizing and animal-protective activities was compared. IgG prepared from plasma units selected by microneutralization assay had significantly higher activity in protecting mice from respiratory RSV challenge than did IgGs prepared from plasmas selected by three direct ELISAs using purified F protein, G protein, or RSV-infected cell lysate, by two competitive ELISAs with RSV neutralizing monoclonal antibodies directed to the F2 or F3 epitopes of the F protein, or by plaque reduction neutralization. Relative to IgG made from unselected plasma, microneutralization-screened IgG was enriched fivefold by plaque-reduction neutralization assays done with or without complement. The microneutralization assay identified RSV antibodies with highest animal protective activity. This assay will be useful for identifying plasma donors for the preparation of a human immune globulin with high protective activity against RSV and deserves further evaluation for prediction of protective antibody concentrations in children. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV BIOSTAT & EPIDEMIOL,BOSTON,MA 02115. CHILDRENS HOSP MED CTR,DIV INFECT DIS,BOSTON,MA 02115. UNIFORMED SERV UNIV HLTH SCI,DEPT PEDIAT,BETHESDA,MD 20814. UNIV ROCHESTER,DEPT MED,ROCHESTER,NY 14627. UNIV CALIF SAN DIEGO,SCH MED,DEPT PEDIAT,LA JOLLA,CA 92093. CTR DIS CONTROL,DIV VIRAL & RICKETTSIAL DIS,ATLANTA,GA 30333. RP SIBER, GR (reprint author), DANA FARBER CANC INST,DIV INFECT DIS,MASSACHUSETTS PUBL HLTH BIOL LABS,305 SOUTH ST,BOSTON,MA 02130, USA. RI Burns, Jane/J-6167-2015 FU NIAID NIH HHS [AI-06516] NR 47 TC 73 Z9 74 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAR PY 1992 VL 165 IS 3 BP 456 EP 463 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA HE466 UT WOS:A1992HE46600008 PM 1538152 ER PT J AU ALPERT, G BALDWIN, G THOMPSON, C WAINWRIGHT, N NOVITSKY, TJ GILLIS, Z PARSONNET, J FLEISHER, GR SIBER, GR AF ALPERT, G BALDWIN, G THOMPSON, C WAINWRIGHT, N NOVITSKY, TJ GILLIS, Z PARSONNET, J FLEISHER, GR SIBER, GR TI LIMULUS ANTILIPOPOLYSACCHARIDE FACTOR PROTECTS RABBITS FROM MENINGOCOCCAL ENDOTOXIN-SHOCK SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID TUMOR-NECROSIS-FACTOR; NEGATIVE BACTERIAL SEPSIS; ANTI-LPS FACTOR; SEPTIC SHOCK; HUMAN-MONOCYTES; HORSESHOE-CRAB; LIPOPOLYSACCHARIDE FACTOR; TACHYPLEUS-TRIDENTATUS; MONOCLONAL-ANTIBODY; ANTIBIOTIC-THERAPY AB Limulus antilipopolysaccharide factor (LALF), an 11.8-kDa peptide isolated from amebocytes of Limulus polyphemus, neutralizes meningococcal lipooligosaccharide (LOS)-induced gelation of limulus amebocyte lysate. Rabbits challenged with an LD90 of LOS (10-mu-g/kg) premixed with LALF in vitro (n = 10) had significantly higher mean arterial pressure, arterial pH, serum bicarbonate concentrations, and survival (90% vs. 8%, P = .005) than did rabbits challenged with LOS alone. Relative to untreated controls, rabbits pretreated with LALF intravenously (iv) at 1.2 mg/kg (n = 21) also had significant improvements in physiologic measurements and higher survival (52% vs. 8%, P = .003). Even when LALF (1.2 mg/kg iv) was given 1/2 h after LOS challenge, animals showed significant improvements in physiologic measurements and survival (33% vs. 8% in untreated controls P = .028). LALF-treated animals also had significantly lower circulating endotoxin activity and tumor necrosis factor concentrations. Thus, LALF attenuates the toxic effects of meningococcal LOS in rabbits even when administered after LOS challenge and deserves further evaluation as a potential therapeutic agent for treating gram-negative septic shock. C1 CHILDRENS HOSP MED CTR,DANA FARBER CANC INST,DEPT MED,DIV EMERGENCY MED,INFECT DIS LAB,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT MED,CHANNING LAB,BOSTON,MA 02115. ASSOCIATES CAPE COD INC,WOODS HOLE,MA. DARTMOUTH COLL,HITCHCOCK MED CTR,DARTMOUTH MED SCH,DEPT MED,HANOVER,NH 03756. FU NIAID NIH HHS [AI-18125] NR 51 TC 56 Z9 58 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAR PY 1992 VL 165 IS 3 BP 494 EP 500 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA HE466 UT WOS:A1992HE46600013 PM 1538154 ER PT J AU BARNES, PF GRISSO, CL ABRAMS, JS BAND, H REA, TH MODLIN, RL AF BARNES, PF GRISSO, CL ABRAMS, JS BAND, H REA, TH MODLIN, RL TI GAMMA-DELTA-LYMPHOCYTES-T IN HUMAN TUBERCULOSIS SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID HEAT-SHOCK PROTEIN; MYCOBACTERIUM-TUBERCULOSIS; CELL RECEPTOR; IFN-GAMMA; ANTIGEN; IL-2; RECOGNITION; ACTIVATION; PLEURITIS; COMPLEX AB The manifestations of tuberculous infection reflect the immune response to infection. Most healthy tuberculin reactors develop protective immunity; tuberculous pleuritis reflects a resistant response manifest by mild disease, whereas advanced pulmonary and miliary tuberculosis reflect ineffective immunity. The role of gamma-delta-T cells was assessed in tuberculous infection by evaluating expansion of these cells from blood mononuclear cells after stimulation with Mycobacterium tuberculosis. After culture in vitro, the percentages of gamma-delta+ cells were significantly greater in patients with protective and resistant immunity (tuberculin reactors, 25% +/- 4%; tuberculous pleuritis, 30% +/- 7%) than in those with ineffective immunity (advanced pulmonary tuberculosis, 9% +/- 3%; miliary tuberculosis, 2% +/- 1%). In leprosy, expansion of gamma-delta+ cells was greater in immunologically resistant tuberculoid patients (32% +/- 4%) than in Mycobacterium leprae-unresponsive lepromatous patients (9% +/- 2%). M. tuberculosis-reactive gamma-delta-T cell lines produced interferon-gamma, granulocyte-macrophage colony-stimulating factor, interleukin-3, and tumor necrosis factor-alpha, cytokines that activate macrophages and may contribute to mycobacterial elimination. These findings suggest that gamma-delta-T cells contribute to immune resistance against M. tuberculosis. C1 UNIV SO CALIF,SCH MED,DERMATOL SECT,LOS ANGELES,CA 90033. UNIV CALIF LOS ANGELES,SCH MED,DIV DERMATOL,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT MICROBIOL & IMMUNOL,LOS ANGELES,CA 90024. DNAX RES INST MOLEC & CELLULAR BIOL INC,MOLEC & CELLULAR BIOL RES INST,DANA FARBER CANC INST,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT RHEUMATOL & IMMUNOL,BOSTON,MA 02115. RP BARNES, PF (reprint author), UNIV SO CALIF,SCH MED,DEPT MED,HMR 904,2025 ZONAL AVE,LOS ANGELES,CA 90033, USA. OI Modlin, Robert/0000-0003-4720-031X FU NIAID NIH HHS [AI-27285, AI-28508, AI-22553] NR 34 TC 146 Z9 148 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAR PY 1992 VL 165 IS 3 BP 506 EP 512 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA HE466 UT WOS:A1992HE46600015 PM 1538155 ER PT J AU BLANK, IH AF BLANK, IH TI INDUSTRY-FUNDED DERMATOLOGICAL RESEARCH WITHIN ACADEMIA IN THE UNITED-STATES - FISCAL AND ETHICAL CONSIDERATIONS SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Editorial Material ID UNIVERSITY-RESEARCH; BIOTECHNOLOGY RP BLANK, IH (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT DERMATOL,WELLMAN LABS PHOTOMED,BOSTON,MA 02114, USA. NR 13 TC 8 Z9 8 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAR PY 1992 VL 98 IS 3 BP 265 EP 268 DI 10.1111/1523-1747.ep12497829 PG 4 WC Dermatology SC Dermatology GA HJ638 UT WOS:A1992HJ63800001 PM 1545134 ER PT J AU NANNEY, LB YATES, RA KING, LE AF NANNEY, LB YATES, RA KING, LE TI MODULATION OF EPIDERMAL GROWTH-FACTOR RECEPTORS IN PSORIATIC LESIONS DURING TREATMENT WITH TOPICAL EGF SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID TYROSINE PHOSPHORYLATION; FACTOR-ALPHA; FACTOR BINDING; LOCALIZATION; KERATINOCYTES; ACROCHORDONS; EXPRESSION; CELLS AB Active psoriatic lesions have increased EGF/TGF-alpha receptors, historically known as the EGF-R. This increase is due to their persistence into the outer parakeratotic layers as measured by autoradiography, immunohistochemistry, and mRNA assays. When psoriatic lesions in patients resolve due to therapy with different modalities, the EGF-R persistently expressed in the outer layers of the epidermis either disappear or resume a basal location presumably due to receptor downregulation. To test whether EGF could downregulate EGF-R and biologically affect psoriatic epidermis, split-thickness skin grafts of active psoriatic lesions were sutured onto the dorsal surface of nude mice. After 3 weeks, the mice were treated daily for a 6-week period with placebo, or 10 or 50-mu-g/ml EGF. Immunostaining showed persistent EGF-R in all epidermal layers in the untreated, placebo-, and 10-mu-g/ml EGF-treated groups. Those grafts receiving a high dose of EGF (50-mu-g/ml) showed either no immunoreactive EGF-R or faint basilar staining. As an additional check for functional activity of the EGF-R, an abundant substrate for this receptor, PLC-gamma-1 was also evaluated following EGF treatment. A similar distribution and modulation pattern following treatment were observed in the grafts immunostained for PLC-gamma-1, suggesting that exogenous EGF treatment affected metabolic pathways subsequent to ligand receptor binding. Morphologic alterations characteristic of a regressing psoriatic phenotype (a decrease in acanthosis, thickness, and the resumption of the orthokeratotic mode of differentiation) were noted in those lesions receiving the 50-mu-g/ml EGF treatment. This study indicates that persistent EGF-R in psoriasis vulgaris are biologically active in vivo and may serve a pivotal role in the regulation of psoriatic lesions. C1 VANDERBILT UNIV,MED CTR,SCH MED,DEPT CELL BIOL,NASHVILLE,TN 37232. VANDERBILT UNIV,MED CTR,SCH MED,DEPT MED,DIV DERMATOL,NASHVILLE,TN 37232. US DEPT VET AFFAIRS,RES SERV,NASHVILLE,TN. RP NANNEY, LB (reprint author), VANDERBILT UNIV,MED CTR,SCH MED,DEPT PLAST SURG,MCN,S-2221,NASHVILLE,TN 37232, USA. FU NIA NIH HHS [AGAR07491]; NIAMS NIH HHS [AR26518]; NIGMS NIH HHS [GM40437] NR 35 TC 38 Z9 38 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAR PY 1992 VL 98 IS 3 BP 296 EP 301 DI 10.1111/1523-1747.ep12497963 PG 6 WC Dermatology SC Dermatology GA HJ638 UT WOS:A1992HJ63800006 PM 1545139 ER PT J AU READE, JM AF READE, JM TI EATING DISORDERS - HSU,LKG SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Book Review RP READE, JM (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. 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 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD MAR PY 1992 VL 180 IS 3 BP 213 EP 213 PG 1 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA HJ014 UT WOS:A1992HJ01400026 ER PT J AU TAKAHASHI, T NOWAKOWSKI, RS CAVINESS, VS AF TAKAHASHI, T NOWAKOWSKI, RS CAVINESS, VS TI BUDR AS AN S-PHASE MARKER FOR QUANTITATIVE STUDIES OF CYTOKINETIC BEHAVIOR IN THE MURINE CEREBRAL VENTRICULAR ZONE SO JOURNAL OF NEUROCYTOLOGY LA English DT Article ID CELL PROLIFERATION; RHESUS-MONKEY; MIGRATION; ORIGIN; CORTEX; NEOCORTEX; TIME; GOLGI; MOUSE; MICE AB BUdR incorporation into replicating DNA, detected immunohistochemically, is used as an S-phase marker in the proliferative cell populations of the cerebral wall of the mouse embryo on the 14th gestational day (E14). The analysis initiates a series of studies concerned with the cytokinetic behaviour and cell output of proliferative populations involved in neocortical histogenesis. On E14 there are two periventricular proliferative zones in the cerebral wall. These are the ventricular and subventricular zones. The ventricular zone is a pseudostratified epithelium. DNA replication occurs with the cell nucleus in the outer zone of the epithelium and mitoses at the ventricular surface. Prior applications of BUdR for studies of cytogenesis in the CNS have been extended in two principal ways: (1) basic fuchsin was used as counterstain for BUdR-negative nuclei and (2) labelling indices were determined separately in strata or bins, 10-mu-m in height, through the full depth of the ventricular zone and overlying cerebral wall. It was established that a single injection of 50-mu-g g-1 into the pregnant dam was associated with labelling of 100% of nuclei in S-phase over an interval extending from 15 min to at least 2.0 h after injection. The zone where nuclei are undergoing S-phase (S-phase zone) extends through the outer four bins of the ventricular zone. The method has high quantitative reproducibility with an SE for labelling indices in bins within the S-phase zone less than 10% of the average values. Evidence is provided that BUdR incorporation is initiated with the nucleus in the outer aspect of the S-phase zone. The efficiency of incorporation of the marker is reduced as nuclei near the end of DNA replication and move to the inner aspect of the S-phase zone. C1 UNIV MED & DENT NEW JERSEY,ROBERT WOOD JOHNSON MED SCH,DEPT NEUROSCI & CELL BIOL,PISCATAWAY,NJ 08854. RP TAKAHASHI, T (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROL,BOSTON,MA 02114, USA. RI Nowakowski, Richard/C-3217-2016 FU NINDS NIH HHS [NS12005, NS28061] NR 47 TC 204 Z9 210 U1 0 U2 4 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0300-4864 J9 J NEUROCYTOL JI J. Neurocytol. PD MAR PY 1992 VL 21 IS 3 BP 185 EP 197 DI 10.1007/BF01194977 PG 13 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA HH676 UT WOS:A1992HH67600003 PM 1373183 ER PT J AU LEIFER, D KOWALL, NW AF LEIFER, D KOWALL, NW TI THY-1 IN HIPPOCAMPUS - NORMAL ANATOMY AND NEURITIC GROWTH IN ALZHEIMERS-DISEASE SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE ALZHEIMERS DISEASE; HIPPOCAMPUS; IMMUNOHISTOCHEMISTRY; NEURITES; THY-1 ID MICROTUBULE-ASSOCIATED PROTEINS; HUMAN-BRAIN; MONOCLONAL-ANTIBODY; ADHESION MOLECULE; NERVOUS-SYSTEM; CELL-SURFACE; NEURONS; ANTIGEN; IMMUNOGLOBULIN; TAU AB Abnormal neuritic sprouting is a prominent feature of Alzheimer's disease (AD), and the Thy-1 glycoprotein has a role in neurite growth in culture. We therefore investigated the distribution of Thy-1 immunoreactivity in the hippocampus of normal elderly patients and of AD patients. Normally, Thy-1 immunoreactivity, which was more prominent in CA1 than elsewhere in the hippocampus, was located mainly in irregular patches on the perikarya of pyramidal cells, their dendrites and axons. In AD, Thy-1-immunoreactive neurons were reduced in number in CA1, and there was diffuse staining of neurofibrillary tangle-bearing pyramidal cells, but neurofibrillary tangles themselves were not immunoreactive. There was also staining of disorganized arrays of dystrophic neurites, some with spiny processes and bizarre filopodial endings. Some Thy-1 -immunoreactive dystrophic neurites entered senile plaques. The data confirm that there is extensive growth of abnormal neurites in AD and suggest that Thy-1 is involved in this process. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. RP LEIFER, D (reprint author), CHILDRENS HOSP MED CTR,DEPT NEUROL,BOSTON,MA 02115, USA. RI Kowall, Neil/G-6364-2012 OI Kowall, Neil/0000-0002-6624-0213 FU NIA NIH HHS [AG 05134]; NICHD NIH HHS [1K11 CHD00888] NR 45 TC 6 Z9 6 U1 0 U2 0 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 MAR PY 1992 VL 51 IS 2 BP 133 EP 141 DI 10.1097/00005072-199203000-00003 PG 9 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA HH070 UT WOS:A1992HH07000003 PM 1347079 ER PT J AU LOUIS, DN MEEHAN, SM FERRANTE, RJ HEDLEYWHYTE, ET AF LOUIS, DN MEEHAN, SM FERRANTE, RJ HEDLEYWHYTE, ET TI USE OF THE SILVER NUCLEOLAR ORGANIZER REGION (AGNOR) TECHNIQUE IN THE DIFFERENTIAL-DIAGNOSIS OF CENTRAL-NERVOUS-SYSTEM NEOPLASIA SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE ASTROCYTOMA; BRAIN TUMOR; GLIOSIS; MEDULLOBLASTOMA; NUCLEOLAR ORGANIZER REGION; SILVER NUCLEOLAR ORGANIZER REGION ID HUMAN BRAIN-TUMORS; MALIGNANCY; PROTEINS; CELLS; NORS AB Because the distinction between gliosis and low-grade astrocytoma may prove difficult by routine light microscopy, we evaluated the silver nucleolar organizer region (AgNOR) technique in making this distinction. The AgNOR impregnation was performed on formalin-fixed, paraffin-embedded tissue from 49 central nervous system (CNS) biopsies: eight normal brain, 14 gliosis, 14 grade 2 astrocytoma (Daumas-Duport scale), two grade 4 astrocytoma, nine medulloblastoma, one metastatic carcinoma, and one choroid plexus papilloma. Quantitative and qualitative differences were found between gliosis and low-grade astrocytomas. In gliosis, AgNOR counts averaged 1.18 +/- 0.11 (SD) AgNOR/nucleus, while in low-grade astrocytomas AgNOR counts averaged 2.22 +/- 0.39 (p < 0.001). Compound AgNOR were frequent in 9/14 grade 2 astrocytomas and in both grade 4 astrocytomas, whereas compound AgNOR were extremely rare in cases of gliosis. Quantitative and qualitative differences were also found between normal cerebellar internal granular cells and medulloblastoma cells. Cerebellar granular cells averaged 0.90 +/- 0.10 AgNOR/nucleus whereas medulloblastoma cells had an average of 4.52 +/- 0.95 (p < 0.001). Compound AgNOR were seen in all medulloblastomas but not in internal granular cells. These findings suggest that the AgNOR technique may be a useful adjunct in the diagnosis of CNS neoplasia. C1 MASSACHUSETTS GEN HOSP,CS KUBIK LAB NEUROPATHOL,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 22 TC 24 Z9 24 U1 0 U2 0 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 MAR PY 1992 VL 51 IS 2 BP 150 EP 157 DI 10.1097/00005072-199203000-00005 PG 8 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA HH070 UT WOS:A1992HH07000005 PM 1538239 ER PT J AU CURRIER, MB MURRAY, GB WELCH, CC AF CURRIER, MB MURRAY, GB WELCH, CC TI ELECTROCONVULSIVE-THERAPY FOR POSTSTROKE DEPRESSED GERIATRIC-PATIENTS SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID POSTSTROKE DEPRESSION; MOOD AB Medical records were retrospectively reviewed for 20 medically ill geriatric patients who received electroconvulsive therapy (ECT) for post-stroke depression from January 1982 to January 1991 at Massachusetts General Hospital. Of the 19 patients (95%) who improved with ECT, 7 patients (37%) suffered relapses despite maintenance anti-depressant medications. Relapses typically developed approximately 4 months after ECT. Five patients (23%) developed ECT-related medical complications. Three patients (15%) developed transient interictal confusion or amnesia. No patient experienced an exacerbation of preexisting neurologic deficits. These findings indicate that ECT is a generally well tolerated and effective treatment for depressed, medically ill post-stroke geriatric patients. C1 MASSACHUSETTS GEN HOSP,PSYCHIAT CONSULTAT SERV,BOSTON,MA 02114. NR 13 TC 53 Z9 56 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD SPR PY 1992 VL 4 IS 2 BP 140 EP 144 PG 5 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA HT257 UT WOS:A1992HT25700004 PM 1627974 ER PT J AU AMES, A LI, YY HEHER, EC KIMBLE, CR AF AMES, A LI, YY HEHER, EC KIMBLE, CR TI ENERGY-METABOLISM OF RABBIT RETINA AS RELATED TO FUNCTION - HIGH COST OF NA+ TRANSPORT SO JOURNAL OF NEUROSCIENCE LA English DT Article ID OXIDATIVE-METABOLISM; OXYGEN-CONSUMPTION; PROTEIN-SYNTHESIS; GLYCOLYSIS; STIMULATION; GLUCOSE; LIGHT; BRAIN; FLUX; PHOTORECEPTORS AB Experiments designed to examine the energy requirements of neurophysiological function were performed on isolated rabbit retina. Function was altered by photic stimulation or by function-specific drugs, and the response of energy metabolism was assessed by simultaneous measurements of O2 consumption and lactate production. In other experiments, the supply of O2 or glucose was reduced and the effect on energy metabolism and electrophysiological function was observed. Energy requirements under control conditions in darkness were high, with O2 consumption (per gm dry wt) at 11.3-mu-mol min-1, with lactate production at 14.8-mu-mol min-1, and with the derived value for glucose consumption at 9.3-mu-mol min-1 and for high-energy phosphate (approximately P) generation at 82.6-mu-mol min-1. Energy reserves were small. Removing glucose abolished the b-wave of the electroretinogram (ERG) with a t1/2 of 1 min, but did not immediately affect O2 consumption or the PIII of the ERG. Removing O2 caused increases of up to 2.7-fold in glycolysis (Pasteur effect) and caused both PIII and b-wave to fail, with a t1/2 of about 5 min. Neurotransmission through the inner retina was supported almost entirely by glycolysis, as evidenced by large increases in lactate production in response to flashing light and decreases in response to transmitter blockers (2.3-fold overall change), with no change in O2 consumption. Phototransduction, on the other hand, was normally supported by oxidative metabolism. The dark current accounted for 41% of the retina's O2 consumption. With O2 reduced, the dark current was partially supported by glycolysis, which accounts (at least in part) for the large Pasteur effect. Na+ transport by NaK ATPase accounted for about half of all energy used, as evidenced by the response to strophanthidin, that is, for 49% of the oxidative energy and 58% of the glycolytic energy. The t1/2 for the turnover of intracellular Na+ was calculated from these data to be less than 1 min. Changes in temperature caused changes in the amplitude of light-evoked electrical responses of 6.5% per degree and caused changes in both O2 consumption and glycolysis of 6.8% per degree (Q10 = 1.9). A surprisingly large fraction of oxidative energy, corresponding to about 40% of the total energy generated, could not be assigned to phototransduction, to neurotransmission, to Na+ transport for other purposes, or to vegetative metabolism. We cannot account for its usage, but it may be related to the (previously reported) rapid turnover of the gamma-phosphate of retinal GTP, the function of which also remains unknown. We conclude that most of the high-energy metabolism of retina is required to support function. Some of the most energy-demanding functions remain to be identified. RP AMES, A (reprint author), MASSACHUSETTS GEN HOSP,NEUROSURG SERV,401 WARREN BLDG,BOSTON,MA 02114, USA. FU NINDS NIH HHS [NS 25753] NR 49 TC 230 Z9 231 U1 2 U2 6 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 MAR PY 1992 VL 12 IS 3 BP 840 EP 853 PG 14 WC Neurosciences SC Neurosciences & Neurology GA HJ353 UT WOS:A1992HJ35300015 PM 1312136 ER PT J AU SCOTT, JA AF SCOTT, JA TI ANATOMIC DIVISIONS SO JOURNAL OF NUCLEAR MEDICINE LA English DT Editorial Material RP SCOTT, JA (reprint author), MASSACHUSETTS GEN HOSP,DEPT NUCL MED,BOSTON,MA 02129, USA. NR 14 TC 3 Z9 3 U1 0 U2 0 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 MAR PY 1992 VL 33 IS 3 BP 407 EP 409 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA HG330 UT WOS:A1992HG33000023 PM 1740712 ER PT J AU STORZ, G TARTAGLIA, LA AF STORZ, G TARTAGLIA, LA TI OXYR - A REGULATOR OF ANTIOXIDANT GENES SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT SYMP AT THE 75TH ANNUAL MEETING OF THE FEDERATION OF AMERICAN SOC FOR EXPERIMENTAL BIOLOGY CY APR 23, 1991 CL ATLANTA, GA SP FEDERAT AMER SOC EXPTL BIOL DE ESCHERICHIA-COLI; OXIDATIVE STRESS ID ALKYL HYDROPEROXIDE REDUCTASE; REDOX-CYCLING AGENTS; ESCHERICHIA-COLI; SALMONELLA-TYPHIMURIUM; OXIDATIVE STRESS; HYDROGEN-PEROXIDE; HEAT-SHOCK; SPONTANEOUS MUTAGENESIS; INDUCIBLE GENES; DNA DAMAGE AB The study of the bacterial response to hydrogen peroxide has given general insights into how cells defend against deleterious oxidants. Treatment of Salmonella typhimurium and Escherichia coli cells with low doses of hydrogen peroxide results in the induction of 30 proteins and resistance to killing by higher doses of hydrogen peroxide. The expression of nine of the hydrogen peroxide-inducible proteins, including the antioxidant enzymes catalase, glutathione reductase and an alkyl hydroperoxide reductase, is controlled by the positive regulator oxyR. Strains carrying deletions of the oxyR gene are hypersensitive to hydrogen peroxide and have increased levels of spontaneous mutagenesis during aerobic growth. The OxyR protein is homologous to the LysR-NodD family of bacterial regulatory proteins and binds to the promoters of oxyR-regulated genes. The oxidized, but not the reduced, form of the OxyR protein activates transcription of oxyR-regulated genes in vitro, suggesting that direct oxidation of the OxyR protein brings about a conformation change by which OxyR senses an oxidative stress signal and then activates the expression of defense activities. C1 MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. GENENTECH INC,SAN FRANCISCO,CA 94080. OI Storz, Gisela/0000-0001-6698-1241 NR 25 TC 83 Z9 84 U1 0 U2 2 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3166 J9 J NUTR JI J. Nutr. PD MAR PY 1992 VL 122 IS 3 SU S BP 627 EP 630 PG 4 WC Nutrition & Dietetics SC Nutrition & Dietetics GA HG411 UT WOS:A1992HG41100008 PM 1542022 ER PT J AU ORMEROD, LD GARSD, A ABELSON, MB KENYON, KR AF ORMEROD, LD GARSD, A ABELSON, MB KENYON, KR TI EICOSANOID MODULATION AND EPITHELIAL WOUND-HEALING KINETICS OF THE ALKALI-BURNED CORNEA SO JOURNAL OF OCULAR PHARMACOLOGY LA English DT Article AB The cyclooxygenase and lipoxygenase enzyme systems can metabolize a number of C20 polyunsaturated fatty acids. Although arachidonic acid is the usual substrate for these pathways, the eicosanoid precursor pool can be nutritionally manipulated by supplementation with alternative precursors, often generating less active or down-regulatory metabolic products. Prefeeding with gamma-linolenic acid, eicosapentaenoic acid, or a combination of both failed to influence the lag-phase, epithelial migration rate, or epithelial wound healing kinetics after either 1N or 4N NaOH alkali burning of the rabbit cornea. Initial epithelial wound healing probably does not involve eicosanoid-mediated processes. Essentially linear epithelial healing kinetics continued to closure without a late decrease in wound edge velocity. RP ORMEROD, LD (reprint author), HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,EYE RES INST,20 STANFORD ST,BOSTON,MA 02114, USA. FU NEI NIH HHS [EY05799, EY06353] NR 0 TC 1 Z9 1 U1 0 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 8756-3320 J9 J OCUL PHARMACOL PD SPR PY 1992 VL 8 IS 1 BP 53 EP 58 DI 10.1089/jop.1992.8.53 PG 6 WC Ophthalmology; Pharmacology & Pharmacy SC Ophthalmology; Pharmacology & Pharmacy GA HZ075 UT WOS:A1992HZ07500006 PM 1328428 ER PT J AU ELMER, EB EHRLICH, MG ZALESKE, DJ POLSKY, C MANKIN, HJ AF ELMER, EB EHRLICH, MG ZALESKE, DJ POLSKY, C MANKIN, HJ TI CHONDRODIASTASIS IN RABBITS - A STUDY OF THE EFFECT OF TRANSPHYSEAL BONE LENGTHENING ON CELL-DIVISION, SYNTHETIC FUNCTION, AND MICROCIRCULATION IN THE GROWTH PLATE SO JOURNAL OF PEDIATRIC ORTHOPAEDICS LA English DT Article DE CHONDRODIASTASIS; GROWTH PLATE; LENGTHENING AB The effects of chondrodiatasis on chondrocyte division, matrix synthesis, and microcirculation in rabbit growth plate were studied. The procedure did not produce any significant change in the percentage of cells labeled with tritiated thymidine, the intensity of radioactive sulfate labeling of the matrix, or the blood supply of the physis. These findings suggest that the procedure does not work by stimulating cell division, synthetic function, or vascularity of the plate, but rather by stretching the matrix passively. C1 MASSACHUSETTS GEN HOSP,PEDIAT ORTHOPAED UNIT,BOSTON,MA 02114. FU NIAMS NIH HHS [AR39380]; PHS HHS [16265] NR 0 TC 10 Z9 10 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0271-6798 J9 J PEDIATR ORTHOPED JI J. Pediatr. Orthop. PD MAR-APR PY 1992 VL 12 IS 2 BP 181 EP 190 PG 10 WC Orthopedics; Pediatrics SC Orthopedics; Pediatrics GA HE696 UT WOS:A1992HE69600008 PM 1552021 ER PT J AU HIROBE, S DOODY, DP RYAN, DP KIM, SH DONAHOE, PK AF HIROBE, S DOODY, DP RYAN, DP KIM, SH DONAHOE, PK TI ECTOPIC CLASS-II MAJOR HISTOCOMPATIBILITY ANTIGENS IN HIRSCHSPRUNGS-DISEASE AND NEURONAL INTESTINAL DYSPLASIA SO JOURNAL OF PEDIATRIC SURGERY LA English DT Article; Proceedings Paper CT 22ND ANNUAL MEETING OF THE AMERICAN PEDIATRIC SURGICAL ASSOC CY MAY 15-18, 1991 CL LAKE BUENA VISTA, FL SP AMER PEDIAT SURG ASSOC DE HIRSCHSPRUNGS DISEASE; NEURONAL INTESTINAL DYSPLASIA; CLASS-II MAJOR HISTOCOMPATIBILITY COMPLEX ID HLA-DR; MONOCLONAL-ANTIBODY; EXPRESSING CELLS; LYMPHOCYTES-T; DIFFERENTIATION; ASSOCIATION; INDUCTION; COLON C1 MASSACHUSETTS GEN HOSP,DEPT PEDIAT SURG,DIV PEDIAT SURG,WARREN BLDG,ROOM 1133,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,PEDIAT SURG RES LABS,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 31 TC 21 Z9 21 U1 0 U2 1 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 MAR PY 1992 VL 27 IS 3 BP 357 EP 363 DI 10.1016/0022-3468(92)90861-Z PG 7 WC Pediatrics; Surgery SC Pediatrics; Surgery GA HJ057 UT WOS:A1992HJ05700016 PM 1501011 ER PT J AU FINBERG, RW NEWBURGER, JW MIKATI, MA HELLER, AH BURNS, JC AF FINBERG, RW NEWBURGER, JW MIKATI, MA HELLER, AH BURNS, JC TI EFFECT OF HIGH-DOSES OF INTRAVENOUSLY ADMINISTERED IMMUNE GLOBULIN ON NATURAL-KILLER-CELL ACTIVITY IN PERIPHERAL-BLOOD SO JOURNAL OF PEDIATRICS LA English DT Article ID KAWASAKI-DISEASE; GAMMA-GLOBULIN; ENDOTHELIAL-CELLS; ACTIVATION; INJURY AB Because Kawasaki disease is a disorder characterized by lymphocyte activation and immune complex destruction of endothelial cells, we examined the effect of administration of high doses of intravenously administered immune globulin (IVIG) on a lymphocyte population with affinity for endothelial cells: the natural killer cells. We found that administration of high doses of IVIG resulted in a significant increase in the activity of natural killer cells and in the numbers of circulating CD16+ cells. Furthermore, a study of patients treated with IVIG for seizure disorders suggests that this effect of IVIG on circulating NK cells is not unique to patients with Kawasaki disease. The beneficial effect of IVIG in the treatment of Kawasaki disease may be due to the ability of IVIG to inhibit interaction between natural killer cells and endothelial cells. C1 HARVARD UNIV, SCH MED, BOSTON, MA 02115 USA. CHILDRENS HOSP MED CTR, DEPT MED, BOSTON, MA 02115 USA. CHILDRENS HOSP MED CTR, DEPT CARDIOL, BOSTON, MA 02115 USA. CHILDRENS HOSP MED CTR, DEPT NEUROL, BOSTON, MA 02115 USA. UNIV CALIF SAN DIEGO, SCH MED, DEPT PEDIAT, LA JOLLA, CA 92093 USA. RP FINBERG, RW (reprint author), HARVARD UNIV, SCH MED, DANA FARBER CANC INST, INFECT DIS LAB, 44 BINNEY ST, BOSTON, MA 02115 USA. RI Finberg, Robert/E-3323-2010; Burns, Jane/J-6167-2015 FU NHLBI NIH HHS [HL-01855, HL-34545] NR 21 TC 34 Z9 34 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD MAR PY 1992 VL 120 IS 3 BP 376 EP 380 DI 10.1016/S0022-3476(05)80900-X PG 5 WC Pediatrics SC Pediatrics GA HG940 UT WOS:A1992HG94000006 PM 1538283 ER PT J AU NATHANSON, JA AF NATHANSON, JA TI NITROVASODILATORS AS A NEW CLASS OF OCULAR HYPOTENSIVE AGENTS SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID LOWERS INTRAOCULAR-PRESSURE; NATRIURETIC FACTOR RECEPTOR; AQUEOUS-HUMOR FLOW; GUANYLATE-CYCLASE; OUTFLOW FACILITY; NITRIC-OXIDE; CYCLIC-GMP; RABBITS; IOP; BETA-2-ADRENOCEPTOR AB Because of recent evidence indicating that hormone regulation of particulate guanylate cyclase in the eye may modulate aqueous humor dynamics, we have investigated the possibility that exogenous activators of soluble guanylate cyclase may be useful in altering intraocular pressure (IOP). A variety of nitrovasodilators known to activate guanylate cyclase were evaluated for their topical effects on IOP, outflow resistance and systemic cardiovascular parameters. In both young and older rabbits, topically applied nitroglycerin (0.003-0.1 g %) rapidly lowered IOP in a dose-dependent fashion, with a peak effect at 1 to 2 hr. Topically applied 0.1% isosorbide dinitrate, sodium nitrite, hydralazine, minoxidil and sodium nitroprusside mimicked the ocular hypotensive actions of nitroglycerin. Ipsilateral effects on IOP were greater than contralateral effects and, at the doses applied, there was little or no alteration in heart rate or systemic blood pressure, or signs of ocular irritation. Higher doses (0.5-2.0 g %) of nitroglycerine, hydralazine and sodium nitroprusside were less effective in lowering IOP. Topically applied molsidomine (0.1%), a prodrug which requires hepatic metabolism to 3-morpholino-sydonimin hydrochloride for guanylate cyclase stimulatory activity, was ineffective in lowering IOP, whereas topical 0.1% 3-morpholino-sydonimin hydrochloride was effective. After chronic administration, rabbits receiving nitroglycerin showed diminished ocular response, whereas repeated doses of hydralazine (56 days) did not elicit tolerance. Tonographic studies showed that topically applied nitroglycerin and hydralazine increased the facility (decreased the resistance) of aqueous humor leaving the eye. These data indicate that topically applied nitrovasodilators can effectively lower IOP at doses which have little effect on systemic blood pressure. Because these IOP-lowering effects appear to result, to a significant degree, from local actions on the eye, further investigation of these agents in conditions of elevated intraocular pressure may be warranted. C1 HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. RP NATHANSON, JA (reprint author), MASSACHUSETTS GEN HOSP,DEPT NEUROL,NEUROPHARMACOL RES LAB,BOSTON,MA 02114, USA. FU NEI NIH HHS [EY05077] NR 75 TC 116 Z9 120 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD MAR PY 1992 VL 260 IS 3 BP 956 EP 965 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA HJ019 UT WOS:A1992HJ01900004 PM 1532035 ER PT J AU KELLER, MB LAVORI, PW BEARDSLEE, WR WUNDER, J SCHWARTZ, CE ROTH, J BIEDERMAN, J AF KELLER, MB LAVORI, PW BEARDSLEE, WR WUNDER, J SCHWARTZ, CE ROTH, J BIEDERMAN, J TI THE DISRUPTIVE BEHAVIORAL-DISORDER IN CHILDREN AND ADOLESCENTS - COMORBIDITY AND CLINICAL COURSE SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE DISRUPTIVE BEHAVIORAL DISORDER; CHILDREN; ADOLESCENTS ID ATTENTION DEFICIT DISORDER; STRUCTURED PSYCHIATRIC INTERVIEW; FOLLOW-UP; HYPERACTIVE CHILDREN; CONDUCT DISORDER; PREVALENCE; SAMPLE; PSYCHOPATHOLOGY; POPULATION; AGREEMENT AB Comorbidity, time to recovery, rate of chronicity, and probability of recurrence following recovery were studied in 51 children diagnosed with attention deficit disorder, conduct disorder, and oppositional defiant disorder. Thirty-three percent of the children had two of the above diagnoses, and one child had all three diagnoses. The mean duration of attention deficit disorder was 8 years up to the time of the interview; the mean duration of oppositional defiant disorder was 4.5 years, and the mean duration of conduct disorder was 3 years. Life-table estimates showed that 14% of the children would not have recovered 15 years after the onset of their disorder. Rates of recurrence were high following recovery from each of these disorders. C1 CHILDRENS HOSP MED CTR,DEPT PSYCHIAT,BOSTON,MA 02115. MASSACHUSETTS MENTAL HLTH CTR,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP KELLER, MB (reprint author), BROWN UNIV,DEPT PSYCHIAT & HUMAN BEHAV,PROVIDENCE,RI 02912, USA. FU NIMH NIH HHS [U01 MH025478, R0-1-MH34780-3, 2-U02-MH25475-09, R01 MH025478] NR 28 TC 18 Z9 18 U1 0 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD MAR PY 1992 VL 31 IS 2 BP 204 EP 209 DI 10.1097/00004583-199203000-00005 PG 6 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA HH094 UT WOS:A1992HH09400004 PM 1564020 ER PT J AU SPENCER, T BIEDERMAN, J WRIGHT, V DANON, M AF SPENCER, T BIEDERMAN, J WRIGHT, V DANON, M TI GROWTH DEFICITS IN CHILDREN TREATED WITH DESIPRAMINE - A CONTROLLED-STUDY SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE GROWTH DEFICITS; DESIPRAMINE; ATTENTION-DEFICIT HYPERACTIVITY DISORDER ID HYPERACTIVE-CHILDREN; FOLLOW-UP; METHYLPHENIDATE TREATMENT; NUTRITIONAL-STATUS; STIMULANT-DRUGS; IMIPRAMINE; DISORDER; BOYS; CLASSIFICATION; MALNUTRITION AB Using multiple assessment methods, growth deficits in weight and height were examined in a clinical sample of children and adolescents with attention deficit hyperactivity disorder treated chronically (mean 14 months) with desipramine (DMI) and two comparison samples of children treated chronically with methylphenidate (MPH) and a not-treated group. Although there were statistically significant weight deficits in children treated with both DMI and MPH compared with normal controls, only those treated with MPH sustained height deficits that attained statistical significance. It appears that DMI may be an appropriate alternative for patients with stimulant-associated severe suppression of growth in height. C1 MASSACHUSETTS GEN HOSP,CHILDRENS SERV,PEDIAT ENDOCRINOL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP SPENCER, T (reprint author), MASSACHUSETTS GEN HOSP,PEDIAT PSYCHOPHARMACOL UNIT ACC-725,FRUIT ST,BOSTON,MA 02114, USA. NR 56 TC 23 Z9 25 U1 3 U2 4 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD MAR PY 1992 VL 31 IS 2 BP 235 EP 243 DI 10.1097/00004583-199203000-00009 PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA HH094 UT WOS:A1992HH09400008 PM 1564024 ER PT J AU DRAKE, LA CEILLEY, RI CORNELISON, RL DOBES, WA DORNER, W GOLTZ, RW LEWIS, CW SALASCHE, SJ TURNER, MLC DORNER, W BAYLOCK, KW HANIFIN, JM HOLDER, WR JENSEN, GT AF DRAKE, LA CEILLEY, RI CORNELISON, RL DOBES, WA DORNER, W GOLTZ, RW LEWIS, CW SALASCHE, SJ TURNER, MLC DORNER, W BAYLOCK, KW HANIFIN, JM HOLDER, WR JENSEN, GT TI GUIDELINES OF CARE FOR ATOPIC-DERMATITIS SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID ECZEMA; ANTAGONIST; IGE RP DRAKE, LA (reprint author), MASSACHUSETTS GEN HOSP,WELLMAN 2,BOSTON,MA 02114, USA. NR 17 TC 15 Z9 17 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 MAR PY 1992 VL 26 IS 3 BP 485 EP 488 PG 4 WC Dermatology SC Dermatology GA HF659 UT WOS:A1992HF65900018 ER PT J AU SANFILIPPO, AJ HARRIGAN, P POPOVIC, AD WEYMAN, AE LEVINE, RA AF SANFILIPPO, AJ HARRIGAN, P POPOVIC, AD WEYMAN, AE LEVINE, RA TI PAPILLARY-MUSCLE TRACTION IN MITRAL-VALVE PROLAPSE - QUANTITATION BY 2-DIMENSIONAL ECHOCARDIOGRAPHY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID CHORDAE TENDINEAE; REPLACEMENT; DOGS; IDENTIFICATION; ABNORMALITIES; ETIOLOGY; LEAFLETS; ANNULUS; MOTION; SIZE AB Previous angiographic observations in patients with mitral valve prolapse have suggested that superior leaflet displacement results in abnormal superior tension on the papillary muscle tips that causes their superior traction or displacement. It has further been postulated that such tension can potentially affect the mechanical and electrophysiologic function of the left ventricle. The purpose of this study was to confirm and quantitate this phenomenon noninvasively by using two-dimensional echocardiography to determine whether superior displacement of the papillary muscle tips occurs and its relation to the degree of mitral leaflet displacement. Directed echocardiographic examination of the papillary muscles and mitral anulus was carried out in a series of patients with classic mitral valve prolapse and results were compared with those in a group of normal control subjects. Distance from the anulus to the papillary muscle tip was measured both in early and at peak ventricular systole. In normal subjects, this distance did not change significantly through systole, whereas in the patient group it decreased, corresponding to a superior displacement of the papillary muscle tips toward the anulus in systole (8.5 +/- 2.6 vs. 0.8 +/- 0.7 mm; p < 0.0001). This superior papillary muscle motion paralleled the superior displacement of the leaflets in individual patients (y = 1.0x + 0.8; r = 0.93) and followed a similar time course. The systolic motion of the mitral anulus toward the apex, assessed with respect to a fixed external reference, was not significantly different in the patients and control groups (14.3 +/- 4 vs. 15.5 +/- 4.4 mm; p = 0.4) and therefore could not explain the superior papillary muscle tip motion relative to the anulus in the patients with mitral valve prolapse. These results demonstrate that normal mechanisms maintain a relatively constant distance between the papillary muscle tips and the mitral anulus during systole. In classic mitral valve prolapse, superior leaflet displacement is paralleled by superior displacement of the papillary muscles that is consistent with superiorly directed forces causing their traction. Two-dimensional echocardiography can therefore be used to measure these relations and test hypotheses as to their clinical correlates in patients with mitral valve prolapse. C1 MASSACHUSETTS GEN HOSP,CARDIAC ULTRASOUND LAB,PHILLIPS HOUSE 8,BOSTON,MA 02114. AMER HEART ASSOC,DALLAS,TX. R SAMUEL MCLAUGHLIN FDN CANADA,TORONTO,ONTARIO,CANADA. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. FU NHLBI NIH HHS [HL-38176] NR 34 TC 48 Z9 49 U1 2 U2 2 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 MAR 1 PY 1992 VL 19 IS 3 BP 564 EP 571 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA HF970 UT WOS:A1992HF97000016 PM 1538011 ER PT J AU MAHONEY, J EUHARDY, R CARNES, M AF MAHONEY, J EUHARDY, R CARNES, M TI A COMPARISON OF A 2-WHEELED WALKER AND A 3-WHEELED WALKER IN A GERIATRIC POPULATION SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID FALLS AB Objective: There are few data on the effect of walkers on gait and mobility or on comparisons of different walker types. We compared a commonly used 4-legged, 2-wheeled walker and a newer 3-legged, 3-wheeled walker in measures of gait, mobility, and patient satisfaction. Design: Cross-over controlled trial. Setting: In the Physical Therapy Department of a Veterans Affairs hospital. Participants: Subjects were 15 male and female frail elderly veterans (mean age, 82 years), both inpatients and outpatients, consecutively enrolled from a sample of 35 patients referred to the Physical Therapy Department for mobility problems. Subjects met the following criteria: age 65 or over, ambulatory, no prior use of a wheeled walker, stable medical condition, and informed consent. Intervention: Subjects were evaluated without either walker and with each of the two walkers on a 15-foot walkway and a 60-foot obstacle course. Subjects were asked which walker they preferred. Outcome Measure: Outcome measures were stride length on the walkway, time on an obstacle course, and walker preference. Results: Stride length was 1.4 inches (3.6 cm) greater with the 3-wheeled walker than with the 2-wheeled walker (P = 0.016 by Wilcoxon signed-rank test). Time on the obstacle course was 16.0 seconds less with the 3-wheeled walker than the 2-wheeled walker (P = 0.002). The 3-wheeled walker was subjectively preferred. Conclusions: The 3-wheeled walker appears to have a greater positive impact on gait and mobility than the 2-wheeled walker. C1 WILLIAM S MIDDLETON MEM VET ADM MED CTR,GERIATR SECT,2500 OVERLOOK TERR,MADISON,WI 53705. UNIV WISCONSIN,DEPT MED,MADISON,WI 53706. NR 12 TC 13 Z9 13 U1 0 U2 1 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 MAR PY 1992 VL 40 IS 3 BP 208 EP 212 PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA HG945 UT WOS:A1992HG94500002 PM 1538036 ER PT J AU BEAL, MF MATSON, WR STOREY, E MILBURY, P RYAN, EA OGAWA, T BIRD, ED AF BEAL, MF MATSON, WR STOREY, E MILBURY, P RYAN, EA OGAWA, T BIRD, ED TI KYNURENIC ACID CONCENTRATIONS ARE REDUCED IN HUNTINGTONS-DISEASE CEREBRAL-CORTEX SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article DE KYNURENIC ACID; EXCITATORY AMINO ACID; HUNTINGTONS DISEASE; TRYPTOPHAN; CEREBRAL CORTEX ID D-ASPARTATE RECEPTOR; QUINOLINIC ACID; RAT-BRAIN; CEREBROSPINAL-FLUID; PARKINSONS-DISEASE; MAMMALIAN BRAIN; URIC-ACID; COMPLEX-I; D-SERINE; GLYCINE AB Huntington's disease (HD) is characterized by gradually evolving selective neuronal death. Several lines of evidence suggest that an excitotoxic mechanism may play a role. Tryptophan metabolism leads to production of quinolinic acid, an N-methyl-D-aspartate (NMDA) receptor agonist, and to kynurenic acid, an antagonist at these same receptors. We recently found increased kynurenine to kynurenic acid ratios in HD postmortem putamen and decreased kynurenic acid concentrations in cerebrospinal fluid, consistent with decreased formation of kynurenic acid in HD brain. In the present study we used HPLC with 16 sensor coulometric electrochemical detection to measure kynurenic acid and 18 other electrochemically active compounds in 6 cortical regions, caudate and cerebellum from controls, HD, Alzheimer's disease (AD), and Parkinson's disease (PD) patients. Significant reductions in kynurenic acid concentrations were found in 5 of 6 cortical regions examined. Smaller reductions of kynurenic acid in the caudate, cerebellum and frontal pole were not significant. No significant reductions were found in the AD and PD patients. Both uric acid and glutathionine were significantly reduced in several regions of HD cerebral cortex, which could signify abnormal energy metabolism in HD. Since kynurenic acid is an antagonist of excitatory amino acid receptors, a deficiency could contribute to the pathogenesis of neuronal degeneration in HD. C1 ESA INC,BEDFORD,MA 01730. HARVARD UNIV,SCH MED,BOSTON,MA 02115. HARVARD UNIV,MCLEAN HOSP,SCH MED,BRAIN TISSUE RESOURCE CTR,BELMONT,MA 02178. RP BEAL, MF (reprint author), MASSACHUSETTS GEN HOSP,DEPT NEUROL,NEUROCHEM LAB,NEUROL RES 4,BOSTON,MA 02114, USA. RI Storey, Elsdon/A-9889-2013 FU DS NIH HHS [NINCDS 16367]; NIMH NIH HHS [MHNS 31862] NR 65 TC 120 Z9 122 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD MAR PY 1992 VL 108 IS 1 BP 80 EP 87 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA HK009 UT WOS:A1992HK00900012 PM 1385624 ER PT J AU SHIPLEY, WU AF SHIPLEY, WU TI RADIATION-THERAPY SO JOURNAL OF UROLOGY LA English DT Editorial Material RP SHIPLEY, WU (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,GENITOURINARY RADIAT ONCOL UNIT,BOSTON,MA 02114, USA. NR 4 TC 2 Z9 2 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 MAR PY 1992 VL 147 IS 3 BP 929 EP 930 PN 2 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA HF976 UT WOS:A1992HF97600039 PM 1538500 ER PT J AU BIKEL, I LOEKEN, MR AF BIKEL, I LOEKEN, MR TI INVOLVEMENT OF SIMIAN VIRUS-40 (SV40) SMALL T-ANTIGEN IN TRANSACTIVATION OF SV40 EARLY AND LATE PROMOTERS SO JOURNAL OF VIROLOGY LA English DT Article ID DNA-BINDING FACTORS; PROTEIN PHOSPHATASE-2A; TUMOR-ANTIGEN; REPLICATION; TRANSFORMATION; TRANSCRIPTION; STIMULATION; EXPRESSION; INVITRO; MUTANTS AB We have previously found that simian virus 40 (SV40) small t antigen (small t) can trans activate the E2A and VA-I genes of adenovirus in plasmid DNA-transfected cells (M.R. Loeken, I. Bikel, D.M. Livingston, and J. Brady, Cell 55:1171-1177, 1988). To determine whether trans activation by small t might be involved in the SV40 productive infection cycle, we examined the effects of cotransfecting plasmids encoding small t with plasmids containing the chloramphenicol acetyltransferase (CAT) gene linked to the SV40 early or late promoter. Small t increased three- to fivefold the expression of a CAT plasmid linked to the SV40 early promoter and enhancer. Small t expression had no effect by itself on CAT activity directed by the SV40 late promoter, but small t enhanced the effect of a suboptimal concentration of a plasmid expressing large T up to 10-fold. When the concentration of the plasmid expressing large T was increased to a level at which large T alone stimulated the late promoter ninefold, the enhancement by small t was only twofold. The effects of small t on both the SV40 early and late promoters depended on sequences within the small t-unique domain, since a plasmid expressing only the first 82 amino acids common to both large T and small t was inactive. The effects of small t on early- and late-promoter-directed CAT enzyme activity was reflected in increased CAT mRNA as measured by S1 analysis. These results suggest that SV40 small t may play a role in viral infection by increasing transcription from the early promoter and from the late promoter at times when large T levels are low. C1 JOSLIN DIABET CTR,1 JOSLIN PL,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. FU NCI NIH HHS [CA24715]; NIDDK NIH HHS [DK36836] NR 33 TC 15 Z9 15 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 1992 VL 66 IS 3 BP 1489 EP 1494 PG 6 WC Virology SC Virology GA HD265 UT WOS:A1992HD26500026 PM 1310761 ER PT J AU LING, LE DRUKER, BJ CANTLEY, LC ROBERTS, TM AF LING, LE DRUKER, BJ CANTLEY, LC ROBERTS, TM TI TRANSFORMATION-DEFECTIVE MUTANTS OF POLYOMAVIRUS MIDDLE T-ANTIGEN ASSOCIATE WITH PHOSPHATIDYLINOSITOL 3-KINASE (PI 3-KINASE) BUT ARE UNABLE TO MAINTAIN WILD-TYPE LEVELS OF PI 3-KINASE PRODUCTS IN INTACT-CELLS SO JOURNAL OF VIROLOGY LA English DT Article ID KINASE-ACTIVITY; TYROSINE PHOSPHORYLATION; PROTEIN; GROWTH; RECEPTOR; VIRUS; POLYPHOSPHOINOSITIDES; INTERNALIZATION; PURIFICATION; STIMULATION AB Middle T antigen (MT) of polyomavirus causes transformation by associating with a number of cellular proteins. The association with and activation of two such proteins, phosphatidylinositol 3-kinase (PI 3-kinase) and pp60c-src, appears to be necessary for transformation by MT. The tyrosine kinase activity of MT-associated pp60c-src is significantly increased when assayed in vitro, and levels of phosphotyrosine-containing proteins are elevated in vivo. Similarly, levels of the PI 3-kinase products phosphatidylinositol-3,4-bisphosphate [PI(3,4)P2] and phosphatiylinositol-3,4,5-trisphosphate [PI(3,4,5)P3] are constitutively elevated in MT-transformed cells. However, the formation of a complete MT/cellular protein complex and the activation of tyrosine kinase are not sufficient to cause transformation, since the transformation-defective mutants 248m and dl1015 associate with all wild-type MT-associated proteins, including PI 3-kinase and pp60c-src, and neither mutant appears to be defective in MT-associated tyrosine kinase activity. Studies presented here compared (i) the amount of PI 3-kinase activity associated with the MT complex and (ii) levels of [H-3]inositol incorporation into PI 3-kinase products in cells expressing mutant or wild-type MT. The results show that dl1015 is defective in both assays, whereas 248m is defective only for incorporation of [H-3]inositol into PI(3,4,5)P2 and PI(3,4)P3. These findings identify a biochemical defect in the 248m mutant and corroborate previous results correlating transformation and elevated levels of PI 3-kinase products in vivo. In addition, they indicate that PI 3-kinase product levels are affected by factors other than simply the amount of PI 3-kinase activity associated with the MT complex. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. TUFTS UNIV,SCH MED,DEPT PHYSIOL,BOSTON,MA 02111. RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 FU NCI NIH HHS [CA 08476-03, CA 30002]; NIGMS NIH HHS [GM41890, R01 GM041890] NR 38 TC 63 Z9 64 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 MAR PY 1992 VL 66 IS 3 BP 1702 EP 1708 PG 7 WC Virology SC Virology GA HD265 UT WOS:A1992HD26500050 PM 1371171 ER PT J AU PAUL, SR BARUT, BA BENNETT, F COCHRAN, MA ANDERSON, KC AF PAUL, SR BARUT, BA BENNETT, F COCHRAN, MA ANDERSON, KC TI LACK OF A ROLE OF INTERLEUKIN-11 IN THE GROWTH OF MULTIPLE-MYELOMA SO LEUKEMIA RESEARCH LA English DT Article DE INTERLEUKIN-11; MYELOMA; INTERLEUKIN-6; HEMATOPOIESIS; LEUKEMIAS; LYMPHOMAS ID CELL; INVITRO AB Interleukin (IL) 11 is a recently described lymphokine which, like IL-6, stimulates normal hematopoietic murine and human hematopoietic progenitor cells and therefore has potential value for either enhancing hematopoiesis in disease states or augmenting hematopoietic recovery after myeloablative therapies. Since IL-6 is known to promote the growth of human myeloma, either in an autocrine or paracrine fashion, we examined the effect of IL-11 on the growth of a murine plasmacytoma cell line, human myeloma-derived cell lines, and freshly isolated human myeloma cells. Interleukin 11 does increase DNA synthesis by the murine plasmacytoma line T10 in the presence of neutralizing antibody to IL-6. However, neither human myeloma cells nor derived cell lines express IL-11 mRNA; secrete IL-11; express IL-11 cell surface receptors; or augment either DNA synthesis or Ig secretion in response to exogenous IL-11. These findings strongly suggest that IL-11 does support the growth of a murine plasmacytoma cell line but does not play a role in the growth of either freshly isolated human myeloma cells or derived cell lines. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,44 BINNEY ST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. FU NCI NIH HHS [CA50947]; NCRR NIH HHS [S07RR05526] NR 21 TC 35 Z9 35 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD MAR PY 1992 VL 16 IS 3 BP 247 EP 252 DI 10.1016/0145-2126(92)90062-C PG 6 WC Oncology; Hematology SC Oncology; Hematology GA HN414 UT WOS:A1992HN41400005 PM 1532843 ER PT J AU BIERER, MF RIGOTTI, NA AF BIERER, MF RIGOTTI, NA TI PUBLIC-POLICY FOR THE CONTROL OF TOBACCO-RELATED DISEASE SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Article ID SMOKING; CAMPAIGN; HEALTH; CONSUMPTION; TRENDS C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP BIERER, MF (reprint author), MASSACHUSETTS GEN HOSP,GEN INTERNAL MED UNIT,BOSTON,MA 02114, USA. NR 59 TC 15 Z9 15 U1 3 U2 7 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0025-7125 J9 MED CLIN N AM JI Med. Clin. N. Am. PD MAR PY 1992 VL 76 IS 2 BP 515 EP 539 PG 25 WC Medicine, General & Internal SC General & Internal Medicine GA HJ313 UT WOS:A1992HJ31300013 PM 1548973 ER PT J AU KLUMPP, TR BLOCK, CC CALIGIURI, MA RABINOWE, SN SOIFFER, RJ RITZ, J AF KLUMPP, TR BLOCK, CC CALIGIURI, MA RABINOWE, SN SOIFFER, RJ RITZ, J TI IMMUNE-MEDIATED CYTOPENIA FOLLOWING BONE-MARROW TRANSPLANTATION - CASE-REPORTS AND REVIEW OF THE LITERATURE SO MEDICINE LA English DT Review ID VERSUS-HOST DISEASE; RED-CELL APLASIA; AUTOIMMUNE-LIKE THROMBOCYTOPENIA; MAJOR ABO INCOMPATIBILITY; CHRONIC MYELOID-LEUKEMIA; ALLOGENEIC MARROW; ANTI-A; HEMOLYTIC-ANEMIA; GRAFT FAILURE; ANTIBODIES C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. TEMPLE UNIV,HLTH SCI CTR,SCH MED,DEPT MED,PHILADELPHIA,PA 19140. RP KLUMPP, TR (reprint author), TEMPLE UNIV,CTR COMPREHENS CANC,BONE MARROW TRANSPLANT PROGRAM,POB 38346,3322 N BROAD ST,PHILADELPHIA,PA 19140, USA. RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NCI NIH HHS [CA34183]; NIAID NIH HHS [AI29530] NR 103 TC 53 Z9 53 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0025-7974 J9 MEDICINE JI Medicine (Baltimore) PD MAR PY 1992 VL 71 IS 2 BP 73 EP 83 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA HK175 UT WOS:A1992HK17500002 PM 1347635 ER PT J AU HAFFNER, SM DUNN, JF KATZ, MS AF HAFFNER, SM DUNN, JF KATZ, MS TI RELATIONSHIP OF SEX HORMONE-BINDING GLOBULIN TO LIPID, LIPOPROTEIN, GLUCOSE, AND INSULIN CONCENTRATIONS IN POSTMENOPAUSAL WOMEN SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID BODY-FAT DISTRIBUTION; HIGH-DENSITY LIPOPROTEINS; DEPENDENT DIABETES-MELLITUS; CARDIOVASCULAR RISK-FACTORS; POST-MENOPAUSAL WOMEN; PREMENOPAUSAL WOMEN; ANDROGENIC ACTIVITY; POSTHEPARIN PLASMA; MEXICAN-AMERICANS; HDL-CHOLESTEROL C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV GERIATR & GERONTOL,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,CTR GERIATR RES EDUC & CLIN,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV ENDOCRINOL & METAB,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DIV CLIN EPIDEMIOL,SAN ANTONIO,TX 78284. FU NCRR NIH HHS [RR-01346]; NHLBI NIH HHS [R37HL36820, HL-24799] NR 61 TC 102 Z9 102 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD MAR PY 1992 VL 41 IS 3 BP 278 EP 284 DI 10.1016/0026-0495(92)90271-B PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA HG988 UT WOS:A1992HG98800009 PM 1542267 ER PT J AU HU, Q LEES, JA BUCHKOVICH, KJ HARLOW, E AF HU, Q LEES, JA BUCHKOVICH, KJ HARLOW, E TI THE RETINOBLASTOMA PROTEIN PHYSICALLY ASSOCIATES WITH THE HUMAN CDC2 KINASE SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CYCLE CONTROL GENE; LARGE T-ANTIGEN; CELL DIVISION CYCLE; SV40 LARGE-T; SUSCEPTIBILITY GENE; SACCHAROMYCES-CEREVISIAE; MESSENGER-RNA; HISTONE-H1 KINASE; E1A PROTEINS; RB GENE AB The protein product (pRB) of the retinoblastoma susceptibility gene functions as a negative regulator of cell proliferation, and its activity appears to be modulated by phosphorylation. Using a new panel of anti-human pRB monoclonal antibodies, we have investigated the biochemical properties of this protein. These antibodies have allowed us to detect a pRB-associated kinase that has been identified as the cell cycle-regulating kinase p34cdc2 or a closely related enzyme. Since this associated kinase phosphorylates pRB at most of the sites used in vivo, these results suggest that this kinase is one of the major regulators of pRB. The associated kinase activity follows the pattern of phosphorylation seen for pRB in vivo. The associated kinase activity is not seen in the G1 phase but appears in the S phase, and the levels continue to increase throughout the remainder of the cell cycle. C1 COLD SPRING HARBOR LAB,POB 100,COLD SPRING HARBOR,NY 11724. MASSACHUSETTS GEN HOSP,CTR CANC,BOSTON,MA 02129. FU NCI NIH HHS [CA13106] NR 85 TC 130 Z9 130 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 MAR PY 1992 VL 12 IS 3 BP 971 EP 980 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA HE838 UT WOS:A1992HE83800008 PM 1545827 ER PT J AU HU, JS OLSON, EN KINGSTON, RE AF HU, JS OLSON, EN KINGSTON, RE TI HEB, A HELIX-LOOP-HELIX PROTEIN RELATED TO E2A AND ITF2 THAT CAN MODULATE THE DNA-BINDING ABILITY OF MYOGENIC REGULATORY FACTORS SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CREATINE-KINASE GENE; IMMUNOGLOBULIN ENHANCER; MYOD FAMILY; SEQUENCE; EXPRESSION; DOMAIN; IDENTIFICATION; ACTIVATION; DISTINCT; MEMBER AB Proteins containing the basic-helix-loop-helix (B-HLH) domain have been shown to be important in regulating cellular differentiation. We have isolated a cDNA for a human B-HLH factor, denoted HEB, that shares nearly complete identity in the B-HLH domain with the immunoglobulin enhancer binding proteins encoded by the E2A and ITF2 genes (E proteins). Functional characterization of the protein expressed from this cDNA indicates that HEB is a third member of the E-protein class of B-HLH factors. HEB mRNA was found to be expressed in several tissues and cell types, including skeletal muscle, thymus, and a B-cell line. HEB, ITF2, and the E12 product of the E2A gene all bound to a similar spectrum of E-box sequences as homo-oligomers. All three factors also formed hetero-oligomers with myogenin, and the DNA-binding specificity and binding off-rates (dissociation rates) were modulated after hetero-oligomerization. Both homo- and hetero-oligomers of these proteins were able to distinguish between very closely related E-box sequences. In addition, HEB was shown to form hetero-oligomers with the E12 and ITF2 proteins. Finally, HEB was able to activate gene expression. These data demonstrate that HEB shares characteristics with other E proteins and show that HEB can interact with members of both the myogenic regulatory class and the E-protein class of B-HLH factors. HEB is therefore likely to play an important role in regulating lineage-specific gene expression. C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. UNIV TEXAS,MD ANDERSON HOSP & TUMOR INST,DEPT BIOCHEM & MOLEC BIOL,HOUSTON,TX 77030. NR 48 TC 269 Z9 272 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 MAR PY 1992 VL 12 IS 3 BP 1031 EP 1042 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA HE838 UT WOS:A1992HE83800014 PM 1312219 ER PT J AU GRAVES, RA TONTONOZ, P SPIEGELMAN, BM AF GRAVES, RA TONTONOZ, P SPIEGELMAN, BM TI ANALYSIS OF A TISSUE-SPECIFIC ENHANCER - ARF6 REGULATES ADIPOGENIC GENE-EXPRESSION SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID DIFFERENTIATION-INDUCED GENE; BINDING-PROTEIN; SV40 ENHANCER; ADIPOCYTE DIFFERENTIATION; GEL-ELECTROPHORESIS; ADIPOSE CONVERSION; MESSENGER-RNAS; MOUSE; ORGANIZATION; DETERMINANT AB The molecular basis of adipocyte-specific gene expression is not well understood. We have previously identified a 518-bp enhancer from the adipocyte P2 gene that stimulates adipose-specific gene expression in both cultured cells and transgenic mice. In this analysis of the enhancer, we have defined and characterized a 122-bp DNA fragment that directs differentiation-dependent gene expression in cultured preadipocytes and adipocytes. Several cis-acting elements have been identified and shown by mutational analysis to be important for full enhancer activity. One pair of sequences, ARE2 and ARE4, binds a nuclear factor (ARF2) present in extracts derived from many cell types. Multiple copies of these elements stimulate gene expression from a minimal promoter in preadipocytes, adipocytes, and several other cultured cell lines. A second pair of elements, ARE6 and ARE7, binds a separate factor (ARF6) that is detected only in nuclear extracts derived from adipocytes. The ability of multimers of ARE6 or ARE7 to stimulate promoter activity is strictly adipocyte specific. Mutations in the ARE6 sequence greatly reduce the activity of the 518-bp enhancer. These data demonstrate that several cis- and trans-acting components contribute to the activity of the adipocyte P2 enhancer and suggest that ARF6, a novel differentiation-dependent factor, may be a key regulator of adipogenic gene expression. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. FU NIDDK NIH HHS [DK31405] NR 35 TC 117 Z9 118 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAR PY 1992 VL 12 IS 3 BP 1202 EP 1208 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA HE838 UT WOS:A1992HE83800030 PM 1545801 ER PT J AU STEHLE, JH RIVKEES, SA LEE, JJ WEAVER, DR DEEDS, JD REPPERT, SM AF STEHLE, JH RIVKEES, SA LEE, JJ WEAVER, DR DEEDS, JD REPPERT, SM TI MOLECULAR-CLONING AND EXPRESSION OF THE CDNA FOR A NOVEL ADENOSINE-A2 RECEPTOR SUBTYPE SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID ADENOSINE RECEPTORS; PARS-TUBERALIS; RAT-BRAIN; CGS 21680; PROTEIN; BINDING AB A novel adenosine receptor subtype has been cloned from a rat brain cDNA library using a probe generated by the polymerase chain reaction. The cDNA, designated RFL9, encodes a protein of 332 amino acids. The structure of RFL9 is most similar to that of the recently cloned rat A2-adenosine receptor, with a sequence identity of 73% within the presumed seven transmembrane domains. Expression of RFL9 in COS-6M cells resulted in ligand binding and functional activity characteristics of an adenosine receptor that is coupled positively to adenylyl cyclase. Examination of the tissue distribution of RFL9 mRNA by Northern blot analysis showed a restricted distribution with highest levels expressed in large intestine, cecum, and urinary bladder; this pattern was distinct from that of either the A1- or A2- adenosine receptor mRNAs. In situ hybridization studies of RFL9 mRNA showed no specific hybridization pattern in brain, but a hybridization signal was readily observed in the hypophyseal pars tuberalis. Thus, RFL9 encodes a novel A2-adenosine receptor subtype. C1 MASSACHUSETTS GEN HOSP, CHILDRENS SERV, DEV CHRONOBIOL LAB, JACKSON 1226, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02115 USA. FU NICHD NIH HHS [KO8 HD-00924]; NIDDK NIH HHS [DK-42125] NR 31 TC 241 Z9 244 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD MAR PY 1992 VL 6 IS 3 BP 384 EP 393 DI 10.1210/me.6.3.384 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA HM714 UT WOS:A1992HM71400009 PM 1584214 ER PT J AU IONASESCU, VV TROFATTER, J HAINES, JL SUMMERS, AM IONASESCU, R SEARBY, C AF IONASESCU, VV TROFATTER, J HAINES, JL SUMMERS, AM IONASESCU, R SEARBY, C TI X-LINKED RECESSIVE CHARCOT-MARIE TOOTH NEUROPATHY - CLINICAL AND GENETIC-STUDY SO MUSCLE & NERVE LA English DT Article DE GENETIC LINKAGE; X-CHROMOSOME; CHARCOT-MARIE TOOTH NEUROPATHY ID DNA PROBES; LINKAGE; LOCALIZATION; CARRIERS AB We describe three families with X-linked recessive Charcot-Marie-Tooth (CMT) neuropathies. The disease phenotype in family 1 was characterized by infantile onset, weakness of lower legs, areflexia, pes cavus, and mental retardation (2 of 5 patients). The disease phenotype in families 2 and 3 was characterized by late onset, distal weakness, and normal intelligence. Hereditary spastic paraparesis was also present in the CMT patients of family 2. Thirty X-linked DNA markers were used for linkage studies. A maximum lod score of +3.48 was obtained by multipoint linkage analysis for the DXS16 locus mapped at Xp22.2 in family 1. In families 2 and 3, there was suggestion of linkage of Xq26 markers; the peak multipoint lod score for these 2 CMT families was 1.81, at DXS144. These results were suggestive of heterogeneity. The joint analysis including both regions (Xp22.2 and Xq26) provided evidence against homogeneity (chi-2 = 9.12, P < 0.005). C1 MASSACHUSETTS GEN HOSP,MOLEC NEUROGENET LAB,BOSTON,MA 02114. N YORK GEN HOSP,DEPT GENET,N YORK M2K 1E1,ONTARIO,CANADA. RP IONASESCU, VV (reprint author), UNIV IOWA HOSP & CLIN,DEPT PEDIAT,DIV MED GENET,IOWA CITY,IA 52242, USA. RI Haines, Jonathan/C-3374-2012; OI Searby, Charles/0000-0002-8108-8782 NR 13 TC 26 Z9 26 U1 0 U2 1 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-639X J9 MUSCLE NERVE JI Muscle Nerve PD MAR PY 1992 VL 15 IS 3 BP 368 EP 373 DI 10.1002/mus.880150317 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA HF955 UT WOS:A1992HF95500016 PM 1557086 ER PT J AU CABALKA, LM HYMAN, BT GOODLETT, CR RITCHIE, TC VANHOESEN, GW AF CABALKA, LM HYMAN, BT GOODLETT, CR RITCHIE, TC VANHOESEN, GW TI ALTERATION IN THE PATTERN OF NERVE-TERMINAL PROTEIN IMMUNOREACTIVITY IN THE PERFORANT PATHWAY IN ALZHEIMERS-DISEASE AND IN RATS AFTER ENTORHINAL LESIONS SO NEUROBIOLOGY OF AGING LA English DT Article DE ALZHEIMERS DISEASE; HIPPOCAMPAL FORMATION; PERFORANT PATHWAY; ENTORHINAL CORTEX; SYNAPTOPHYSIN; NT75; RAT ID PARKINSONISM-DEMENTIA COMPLEX; DENTATE GYRUS; HIPPOCAMPAL-FORMATION; ADULT-RAT; SENILE PLAQUES; CORTEX; PROLIFERATION; BRAIN; SYNAPTOGENESIS; REINNERVATION AB Neurons in layer II of the entorhinal cortex consistently develop neurofibrillary tangles in Alzheimer's disease (AD). Experimental neuroanatomical studies have shown that these neurons give rise to the perforant pathway, a major excitatory projection to the hippocampal formation, which terminates in a discrete pattern in the outer portion of the molecular layer of the dentate gyrus. The distribution of two nerve terminal associated proteins, synaptophysin and NT75, was studied in the molecular layer of the dentate gyrus in AD and control cases to determine whether Alzheimer neuronal pathology is associated with loss of synaptic markers. In parallel studies, the effect of ablation of the entorhinal cortex in rats was evaluated. In AD as compared to controls, a decrease in synaptophysin immunostaining was evident in the terminal zone of the perforant pathway. NT75 nerve terminal immunostaining was too weak to interpret in the human hippocampal formation. Both synaptophysin and NT75 immunoreactivity were found in association with some neuritic plaques. In rats, entorhinal lesions resulted in diminished immunoreactivity for both synaptophysin and NT75 in the perforant pathway terminal zone. These results suggest that nerve terminal protein loss is a concomitant feature of neuronal pathology in AD. C1 MASSACHUSETTS GEN HOSP,NEUROL SERV,14 FRUIT ST,BOSTON,MA 02114. UNIV IOWA,DEPT ANAT,IOWA CITY,IA 52242. RI Goodlett, Charles/C-5979-2015 OI Goodlett, Charles/0000-0002-7821-9999 FU NIA NIH HHS [AG08487]; NINDS NIH HHS [NS14944, NS23379] NR 54 TC 58 Z9 59 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD MAR-APR PY 1992 VL 13 IS 2 BP 283 EP 291 DI 10.1016/0197-4580(92)90041-U PG 9 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA HL796 UT WOS:A1992HL79600012 PM 1522944 ER PT J AU ARRIAGADA, PV GROWDON, JH HEDLEYWHYTE, ET HYMAN, BT AF ARRIAGADA, PV GROWDON, JH HEDLEYWHYTE, ET HYMAN, BT TI NEUROFIBRILLARY TANGLES BUT NOT SENILE PLAQUES PARALLEL DURATION AND SEVERITY OF ALZHEIMERS-DISEASE SO NEUROLOGY LA English DT Article; Proceedings Paper CT 43RD ANNUAL MEETING OF THE AMERICAN ACADEMY OF NEUROLOGY CY APR, 1991 CL BOSTON, MA SP AMER ACAD NEUROL ID GRADED INTELLECTUAL STATUS; PAIRED HELICAL FILAMENTS; PATHOLOGICAL-CHANGES; NEURITIC PLAQUES; DOWNS-SYNDROME; DEMENTIA; DEGENERATION; NEOCORTEX; LAMINAR; CORTEX AB We studied the accumulation of neurofibrillary tangles (NFTs) and senile plaques (SPs) in 10 Alzheimer's disease patients who had been examined during life. We counted NFTs and SPs in 13 cytoarchitectural regions representing limbic, primary sensory, and association cortices, and in subcortical neurotransmitter-specific areas. The degree of neuropathologic change was compared with the severity of dementia, as assessed by the Blessed Dementia Scale and duration of illness. We found that (1) the severity of dementia was positively related to the number of NFTs in neocortex, but not to the degree of SP deposition; (2) NFTs accumulate in a consistent pattern reflecting hierarchic vulnerability of individual cytoarchitectural fields; (3) NFTs appeared in the entorhinal cortex, CA1/subiculum field of the hippocampal formation, and the amygdala early in the disease process; and (4) the degree of SP deposition was also related to a hierarchic vulnerability of certain brain areas to accumulate SPs, but the pattern of SP distribution was different from that of NFT. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROL,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02114. FU NIA NIH HHS [AG08487, P50 AG05134] NR 42 TC 1414 Z9 1466 U1 5 U2 47 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAR PY 1992 VL 42 IS 3 BP 631 EP 639 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA HJ992 UT WOS:A1992HJ99200031 PM 1549228 ER PT J AU HANTRAYE, P BROWNELL, AL ELMALEH, D SPEALMAN, RD WULLNER, U BROWNELL, GL MADRAS, BK ISACSON, O AF HANTRAYE, P BROWNELL, AL ELMALEH, D SPEALMAN, RD WULLNER, U BROWNELL, GL MADRAS, BK ISACSON, O TI DOPAMINE FIBER DETECTION BY [C-11] CFT AND PET IN A PRIMATE MODEL OF PARKINSONISM SO NEUROREPORT LA English DT Article DE POSITRON EMISSION TOMOGRAPHY; DOPAMINE UPTAKE INHIBITOR; [C-11]-CFT; MPTP; DOPAMINE FIBER LOSS ID POSITRON EMISSION TOMOGRAPHY; UPTAKE SITES; BRAIN; DISEASE; INVIVO; BINDING; C-11-NOMIFENSINE; METABOLISM AB MONKEYS were treated on two regimens of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) injections to achieve dopamine fiber degeneration of differing severities. A rapid treatment regimen produced a severe parkinsonian syndrome, whereas an intermittent regimen did not cause locomotor symptoms to appear up to 25 weeks. High resolution PET scanning of dopamine nerve terminals revealed that the specific binding of the dopamine transporter [C-11]-WIN 35,428 ([C-11]-CFT) was diminished by 94% (caudate nucleus) and by 93% (putamen) in the symptomatic monkey. Decreases of 65 and 67% were detected in these regions in the non-symptomatic monkey. Post-mortem immunocytochemical evaluation of presumed dopamine fibers by tyrosine-hydroxylase showed similar reductions in the symptomatic animal. C1 HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. MCLEAN HOSP,NEUROREGENERAT LAB,BELMONT,MA 02178. MASSACHUSETTS GEN HOSP,DEPT NUCL RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. NEW ENGLAND REG PRIMATE RES CTR,DIV BEHAV BIOL,SOUTHBOROUGH,MA 01772. CNRS,URA 1285,F-91406 ORSAY,FRANCE. FU NCRR NIH HHS [RR00168]; NIDA NIH HHS [DA 06303]; NINDS NIH HHS [NS30064-01] NR 18 TC 87 Z9 89 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD MAR PY 1992 VL 3 IS 3 BP 265 EP 268 DI 10.1097/00001756-199203000-00013 PG 4 WC Neurosciences SC Neurosciences & Neurology GA HM185 UT WOS:A1992HM18500013 PM 1515582 ER PT J AU SHORE, JW FOSTER, CS WESTFALL, CT RUBIN, PAD AF SHORE, JW FOSTER, CS WESTFALL, CT RUBIN, PAD TI RESULTS OF BUCCAL MUCOSAL GRAFTING FOR PATIENTS WITH MEDICALLY CONTROLLED OCULAR CICATRICIAL PEMPHIGOID SO OPHTHALMOLOGY LA English DT Article ID MUCOUS-MEMBRANE; IMMUNOSUPPRESSIVE THERAPY; ENTROPION AB Eyelid surgery for patients with ocular cicatricial pemphigoid is risky when there is unchecked perioperative inflammation. The authors performed buccal mucosal grafts on 42 eyelids (23 eyes) of 17 patients with ocular cicatricial pemphigoid whose disease was controlled by systemic immunosuppression. Results were graded as: improved (12 cases, 16 eyes); satisfactory (2 cases, 2 eyes); or poor (5 patients, 5 eyes). Complications included breakthrough trichiasis, surface keratinization of the graft, blepharoptosis, phimosis, depressed eyelid blink, incomplete eyelid closure, submucosal abscess formation, and persistent nonhealing epithelial defects of the cornea. Technical errors at surgery accounted for two complications. Secondary corneal ulceration developed in two patients. The immunologic aspect of the disease flared or progressed in five patients in the postoperative period and necessitated an increase or change in systemic medication for immunosuppression. Buccal mucosal grafting shows promise in temporarily rehabilitating eyelids of some ocular cicatricial pemphigoid patients whose disease is controlled by immunosuppressive therapy. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,OCULAR IMMUNOL SERV,BOSTON,MA 02114. RP SHORE, JW (reprint author), HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,EYE PLAST & ORBIT SERV,BOSTON,MA 02114, USA. NR 21 TC 67 Z9 68 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD MAR PY 1992 VL 99 IS 3 BP 383 EP 395 PG 13 WC Ophthalmology SC Ophthalmology GA HG885 UT WOS:A1992HG88500016 PM 1565450 ER PT J AU KROUSE, JH METSON, R AF KROUSE, JH METSON, R TI BARIUM SWALLOW IS A PREDICTOR OF SALIVARY FISTULA FOLLOWING LARYNGECTOMY SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article ID SURGERY AB Pharyngocutaneous salivary fistula after laryngectomy is a serious complication that can lead to prolonged hospitalization and increased patient morbidity. A postoperative barium swallow provides the surgeon with information regarding the integrity of the pharyngeal suture line. In an attempt to determine whether this information can be used to predict or prevent salivary fistula, we reviewed the records of 109 patients who underwent total laryngectomy, including 51 who had a barium swallow before they began oral intake. Ten patients (20%) demonstrated a sinus tract originating from the pharyngeal suture line. A clinical salivary fistula developed in all four patients with a sinus tract 2 cm or longer, but in only one of six patients with a tract shorter than 2 cm. Other factors predictive of salivary fistula included tumor stage, previous radiation therapy, and the presence of concurrent postoperative complications. A single fistula developed in the 58 patients not studied with barium. Information provided by postlaryngectomy barium swallow appeared to predict, but not prevent salivary fistula formation. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02114. NR 4 TC 14 Z9 14 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD MAR PY 1992 VL 106 IS 3 BP 254 EP 257 PG 4 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA HJ155 UT WOS:A1992HJ15500010 PM 1589217 ER PT J AU NAKAMURA, S VAWTER, G SALLAN, S CHANOCK, S AF NAKAMURA, S VAWTER, G SALLAN, S CHANOCK, S TI FATAL ESOPHAGEAL ASPERGILLOMA IN A LEUKEMIC ADOLESCENT SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Note DE ASPERGILLUS; ACUTE LYMPHOBLASTIC LEUKEMIA; ESOPHAGITIS; IMMUNOCOMPROMISED HOST ID INVASIVE PULMONARY ASPERGILLOSIS; MULTIVARIATE-ANALYSIS; FUNGAL-INFECTIONS; DISEASE C1 HARVARD UNIV,CHILDRENS HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,CHILDRENS HOSP,SCH MED,DIV PEDIAT HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,CHILDRENS HOSP,SCH MED,DIV INFECT DIS,BOSTON,MA 02115. NR 17 TC 5 Z9 5 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD MAR PY 1992 VL 11 IS 3 BP 245 EP 247 PG 3 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA HH626 UT WOS:A1992HH62600018 PM 1565546 ER PT J AU WEBER, GF BRUCH, HP AF WEBER, GF BRUCH, HP TI PHARMACOLOGY OF SUPEROXIDE-DISMUTASE SO PHARMAZIE LA German DT Review ID FREE-RADICAL SCAVENGER; XANTHINE-OXIDASE; OXYGEN RADICALS; REPERFUSION ARRHYTHMIAS; BACTERICIDAL ACTIVITY; POLYETHYLENE-GLYCOL; MYOCARDIAL ISCHEMIA; MULTIPLE-SCLEROSIS; CONSCIOUS DOGS; GENERATION C1 HARVARD UNIV,SCH MED,DEPT BIOCHEM & MOLEC PHARMACOL,BOSTON,MA 02115. MED UNIV LUBECK,CHIRURG KLIN,LUBECK,GERMANY. RP WEBER, GF (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV IMMUNOPATHOL,44 BINNEY ST,BOSTON,MA 02115, USA. RI Bruch, Hans-Peter/E-7731-2010 NR 74 TC 6 Z9 6 U1 0 U2 2 PU GOVI-VERLAG GMBH PI ESCHBORN PA PHARMAZEUTISCHER VERLAG GINNHEIMER STRASSE 26, D-65760 ESCHBORN, GERMANY SN 0031-7144 J9 PHARMAZIE JI Pharmazie PD MAR PY 1992 VL 47 IS 3 BP 159 EP 167 PG 9 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA HP891 UT WOS:A1992HP89100001 PM 1615019 ER PT J AU CHIODO, LK GERETY, MB MULROW, CD RHODES, MC TULEY, MR AF CHIODO, LK GERETY, MB MULROW, CD RHODES, MC TULEY, MR TI THE IMPACT OF PHYSICAL THERAPY ON NURSING-HOME PATIENT OUTCOMES SO PHYSICAL THERAPY LA English DT Article DE GERIATRICS; LONG-TERM CARE; NURSING HOMES; PHYSICAL THERAPY ID TERM AB The objective of this retrospective study was to assess the intensity and outcome of individual components of interdisciplinary care, including physical therapy, in a teaching nursing home. Two independent reviewers abstracted records from 90 consecutive patients admitted to the nursing home. They rated intensity and outcome of each program component using a structured, standardized data-abstraction form. Program components were physical therapy, speech therapy, psychosocial therapy, medication adjustment, and other medical and nursing care. Physical therapy and medication adjustment were the most frequently received therapies. Eighty-eight percent of the patients receiving high-intensity physical therapy and 33% of the patients receiving moderate-intensity physical therapy improved. For medication adjustment, 93% and 72% of the high- and moderate-intensity groups, respectively, improved. In univariate analyses, physical therapy intensity and age were associated with improvement. Baseline function in activities of daily living and cognitive function were not associated with physical therapy outcome. A stepwise multiple logistic regression analysis revealed that only therapy intensity was associated with improved outcome. We conclude that physical therapy was efficacious for patients receiving high-intensity treatment. Advanced age, activities-of-daily-living status, and cognitive impairment were not associated with poor physical therapy outcome. C1 AUDIE L MURPHY MEM VET ADM MED CTR,GERIATR RES EDUC & CLIN CTR,7400 MERTON MINTER BLVD,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DIV GEN MED,SAN ANTONIO,TX 78284. NR 13 TC 17 Z9 17 U1 0 U2 1 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 MAR PY 1992 VL 72 IS 3 BP 168 EP 175 PG 8 WC Orthopedics; Rehabilitation SC Orthopedics; Rehabilitation GA HG871 UT WOS:A1992HG87100002 PM 1584851 ER PT J AU CHIODO, LK GERETY, MB MULROW, CD RHODES, MC TULEY, MR AF CHIODO, LK GERETY, MB MULROW, CD RHODES, MC TULEY, MR TI THE IMPACT OF PHYSICAL THERAPY ON NURSING-HOME PATIENT OUTCOMES - RESPONSE SO PHYSICAL THERAPY LA English DT Letter C1 AUDIE L MURPHY MEM VET ADM MED CTR,GERIATR RES EDUC & CLIN CTR,7400 MERTON MINTER BLVD,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DIV GEN MED,SAN ANTONIO,TX 78284. NR 0 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 MAR PY 1992 VL 72 IS 3 BP 174 EP 175 PG 2 WC Orthopedics; Rehabilitation SC Orthopedics; Rehabilitation GA HG871 UT WOS:A1992HG87100004 ER PT J AU SHIRLEY, BW HANLEY, S GOODMAN, HM AF SHIRLEY, BW HANLEY, S GOODMAN, HM TI EFFECTS OF IONIZING-RADIATION ON A PLANT GENOME - ANALYSIS OF 2 ARABIDOPSIS TRANSPARENT-TESTA MUTATIONS SO PLANT CELL LA English DT Article ID CHALCONE SYNTHASE GENE; PETUNIA-HYBRIDA; TRANSPOSABLE ELEMENTS; ANTIRRHINUM-MAJUS; FLAVONOID GENES; ZEA-MAYS; DNA; THALIANA; PROTEIN; EXPRESSION AB Ionizing radiation is known to cause chromosomal alterations such as inversions and deletions and has been used extensively for inducing mutations. In Arabidopsis, two methods for the isolation of genes identified on the basis of mutant phenotypes-genomic subtraction and chromosome walking-either rely on or are greatly facilitated by the availability of these types of mutations. This article gives a detailed characterization of ionizing radiation-induced mutations in plants. The Arabidopsis genes encoding chalcone flavanone isomerase (CHI) and dihydroflavonol 4-reductase (DFR) were cloned and found to correspond to two transparent testa loci. A CHI allele, generated by fast-neutron irradiation, consisted of an inversion within the gene. A 272-bp fragment from 38 centimorgans away on the same chromosome was transferred to one end of this inversion. A DFR allele, induced by x-irradiation, contained two deletions and an inversion of the 2.8-centimorgan intervening region. Sequence analysis of the break points in both mutants indicate that repair of radiation-induced damage involves mechanisms similar or identical to those that mediate the integration of foreign sequences into the genome. The chromosome rearrangements found in these mutants have important implications for the use of ionizing radiation-induced alleles in classical and molecular genetic experiments in plants. C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. RI Winkel, Brenda/A-6602-2008 OI Winkel, Brenda/0000-0003-3481-024X NR 66 TC 252 Z9 284 U1 6 U2 22 PU AMER SOC PLANT PHYSIOLOGISTS PI ROCKVILLE PA 15501 MONONA DRIVE, ROCKVILLE, MD 20855 SN 1040-4651 J9 PLANT CELL JI Plant Cell PD MAR PY 1992 VL 4 IS 3 BP 333 EP 347 DI 10.1105/tpc.4.3.333 PG 15 WC Biochemistry & Molecular Biology; Plant Sciences; Cell Biology SC Biochemistry & Molecular Biology; Plant Sciences; Cell Biology GA HL040 UT WOS:A1992HL04000011 PM 1354004 ER PT J AU SCHAFFNER, AR SHEEN, J AF SCHAFFNER, AR SHEEN, J TI MAIZE C4 PHOTOSYNTHESIS INVOLVES DIFFERENTIAL REGULATION OF PHOSPHOENOLPYRUVATE CARBOXYLASE GENES SO PLANT JOURNAL LA English DT Article ID ORTHO-PHOSPHATE DIKINASE; BUNDLE SHEATH-CELLS; C-4 PHOTOSYNTHESIS; SEQUENCE-ANALYSIS; MESSENGER-RNAS; HIGHER-PLANTS; EXPRESSION; LEAVES; LIGHT; TRANSCRIPTION AB Maize as a C4 plant partitions CO2 fixation in two consecutive, spatially separated steps, thus eliminating photorespiration. The crucial enzyme for primary CO2 fixation is a C4-specific phosphoenolpyruvate carboxylase (PEPC). The differential expression of the unique C4-specific gene pepcZm1 and two non-C4-specific genes, pepcZm2A and pepcZm3B, in leaf, root, and stem is reported here. It is shown, in a transient homologous system, that this tissue-specific regulation is mainly controlled by their distinct promoters. The light induction of the C4-specific pepcZm1 in illuminated etiolated (greening) leaves probably relies on light-dependent developmental changes instead of an immediate responsiveness found for other maize genes. Analyses of deleted, mutated, and hybrid promoters revealed the redundant nature of a 14mer which is repeated four times and a decisive function of the TATA box-like motif, TATTT, and the sequences directly preceding it. No consensus sequences to other photosynthetic gene promoters were uncovered. Although light induces the expression of C4 PEPC and other photosynthetic genes in maize, this co-ordination is apparently mediated through different signal transduction pathways and distinct regulatory elements. This study indicates that the acquisition of a new promoter is at least partially responsible for the C4-specific expression of pepcZm1 essential for C4 photosynthesis. C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. NR 48 TC 60 Z9 62 U1 0 U2 7 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0960-7412 J9 PLANT J JI Plant J. PD MAR PY 1992 VL 2 IS 2 BP 221 EP 232 PG 12 WC Plant Sciences SC Plant Sciences GA HJ777 UT WOS:A1992HJ77700010 PM 1302051 ER PT J AU FRANCEL, TJ VANDERKOLK, CA HOOPES, JE MANSON, PN YAREMCHUK, MJ AF FRANCEL, TJ VANDERKOLK, CA HOOPES, JE MANSON, PN YAREMCHUK, MJ TI MICROVASCULAR SOFT-TISSUE TRANSPLANTATION FOR RECONSTRUCTION OF ACUTE OPEN TIBIAL FRACTURES - TIMING OF COVERAGE AND LONG-TERM FUNCTIONAL RESULTS SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID LOWER-EXTREMITY; FREE FLAPS; MANAGEMENT; EXPERIENCE; SALVAGE; TRAUMA AB Seventy-two patients with Gustilo grade IIIB open tibial fractures were treated with free-tissues transfers. If successful free-tissue transfer for soft-tissue reconstruction is performed within 15 days of injury, the risk of major complications is 3.6 percent. Long-term retrospective follow-up (mean 42 months) revealed successful limb salvage in 93 percent, good aesthetic results in 80 percent, and patient satisfaction in 96 percent. However, 66 percent of patients exhibited significantly decreased range of motion of the ankle, 44 percent experienced swelling and edema requiring elastic support and activity modification, and 50 percent occasionally required an assistance device for ambulation. The long-term employment rate was 28 percent, and no patient returned to work after 2 years of unemployment. In contrast, 68 percent of amputees after lower extremity trauma over the same period returned to work within 2 years. Patients need to realize the disruptive nature of this injury on their family, job, and future. C1 MARYLAND INST EMERGENCY MED SERV SYST,BALTIMORE,MD. JOHNS HOPKINS UNIV,SCH MED,DIV PLAST SURG,BALTIMORE,MD 21205. MASSACHUSETTS GEN HOSP,DIV PLAST SURG,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 31 TC 137 Z9 139 U1 1 U2 7 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD MAR PY 1992 VL 89 IS 3 BP 478 EP 487 DI 10.1097/00006534-199203000-00014 PG 10 WC Surgery SC Surgery GA HG142 UT WOS:A1992HG14200015 PM 1741471 ER PT J AU BEASER, RS AF BEASER, RS TI FINE-TUNING INSULIN THERAPY SO POSTGRADUATE MEDICINE LA English DT Article ID NIDDM AB Insulin replacement programs that mimic normal physiologic patterns are becoming increasingly precise. Dr Beaser describes trends in insulin therapy for both insulin-dependent and non-insulin-dependent diabetes mellitus, discussing split-mix regimens, multiple daily injection regimens, and continuous subcutaneous insulin infusion. C1 HARVARD UNIV, SCH MED, BOSTON, MA 02115 USA. NEW ENGLAND DEACONESS HOSP, BOSTON, MA 02215 USA. RP BEASER, RS (reprint author), JOSLIN DIABET CTR, DIABET TREATMENT UNIT, 1 JOSLIN PL, BOSTON, MA 02215 USA. NR 22 TC 4 Z9 4 U1 0 U2 0 PU JTE MULTIMEDIA PI BERWYN PA 1235 WESTLAKES DR, STE 220, BERWYN, PA 19312 USA SN 0032-5481 J9 POSTGRAD MED JI Postgrad. Med. PD MAR PY 1992 VL 91 IS 4 BP 323 EP 330 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA HK951 UT WOS:A1992HK95100029 PM 1546020 ER PT J AU FUHRMAN, JA LANE, WS SMITH, RF PIESSENS, WF PERLER, FB AF FUHRMAN, JA LANE, WS SMITH, RF PIESSENS, WF PERLER, FB TI TRANSMISSION-BLOCKING ANTIBODIES RECOGNIZE MICROFILARIAL CHITINASE IN BRUGIAN LYMPHATIC FILARIASIS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE BRUGIA-MALAYI; PARASITIC NEMATODES; PCR ID ACID SEQUENCE-ANALYSIS; MALAYI MICROFILARIAE; GEL-ELECTROPHORESIS; POLYACRYLAMIDE GELS; PROTEINS; NITROCELLULOSE; DIGESTION; ANTIGENS AB Brugia malayi is a parasitic nematode that causes lymphatic filariasis in humans. The monoclonal antibody MF1, which mediates clearance of peripheral microfilaremia in a gerbil infection model, recognizes two stage-specific proteins, p70 and p75, in B. malayi microfilariae. cDNA coding for the MF1 antigen was sequenced, and the predicted protein sequence shows significant similarities to chitinases from bacteria and yeast. When microfilarial extracts and purified preparations of the MF1 antigen were tested for chitinase activity, strong bands of chitin-degrading activity comigrated in SDS/PAGE with p70 and p75 and showed a reduction-dependent mobility shift characteristic of the MF1 antigen. Thus, the MF1 antigen is microfilarial chitinase, which may function to degrade chitin-containing structures in the microfilaria or in its mosquito vector during parasite development and transmission. C1 NEW ENGLAND BIOLABS INC,BEVERLY,MA 01915. HARVARD UNIV,MICROCHEM FACIL,CAMBRIDGE,MA 02138. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,MOLEC BIOL COMP RES RESOURCE,BOSTON,MA 02115. RP FUHRMAN, JA (reprint author), HARVARD UNIV,SCH PUBL HLTH,DEPT TROP PUBL HLTH,665 HUNTINGTON AVE,BOSTON,MA 02115, USA. FU NIAID NIH HHS [AI 24858, AI 02642] NR 25 TC 97 Z9 98 U1 0 U2 0 PU NATL ACAD PRESS 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 MAR 1 PY 1992 VL 89 IS 5 BP 1548 EP 1552 DI 10.1073/pnas.89.5.1548 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA HG681 UT WOS:A1992HG68100007 PM 1542646 ER PT J AU FEDEROFF, HJ GESCHWIND, MD GELLER, AI KESSLER, JA AF FEDEROFF, HJ GESCHWIND, MD GELLER, AI KESSLER, JA TI EXPRESSION OF NERVE GROWTH-FACTOR INVIVO FROM A DEFECTIVE HERPES-SIMPLEX VIRUS-1 VECTOR PREVENTS EFFECTS OF AXOTOMY ON SYMPATHETIC-GANGLIA SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE NEUROTROPHIC FACTORS; GENE THERAPY; GENE TRANSFER ID NEUROTROPHIC FACTOR; BETA-GALACTOSIDASE; MOLECULAR-CLONING; AXONAL-TRANSPORT; GENE-TRANSFER; HSV-1 VECTOR; FACTOR NGF; NEURONS; BRAIN; SYSTEM AB Sympathetic neurons in the superior cervical ganglion (SCG) of adult rats depend on target-derived nerve growth factor (NGF) for maintenance of tyrosine hydroxylase (TH) levels and the noradrenergic neurotransmitter system. Axotomy of a SCG results in NGF deprivation, causing a decline in TH activity; continuous local application of NGF can prevent this decline in TH activity. We now report that injection of a defective herpes simplex virus 1 vector that expresses NGF (pHSVngf) into a SCG can prevent the decline in TH activity that follows axotomy. SCG of adult rats were injected with either pHSVngf virus or pNFlac virus, which expresses Escherichia coli beta-galactosidase. Analysis of RNA from pHSVngf-infected SCG indicated that the NGF gene was efficiently transcribed and processed. Furthermore, 4 days after pHSVngf injection animals underwent axotomy of the virus-injected SCG. After another 10 days, animals were sacrificed and both the injected-axotomized and contralateral control ganglia were assayed for TH activity. Axotomy of SCG injected with pNFlac virus produced a 50% decline in TH activity relative to control ganglia (P = 0.02). In contrast, SCG injected with pHSVngf virus did not show a decline in TH activity following axotomy; instead, these ganglia manifested an 18% increase in TH levels relative to control ganglia. These data demonstrate that herpes simplex virus 1 vectors can be used to modify neuronal physiology in vivo; specifically, expression of a critical gene product by neural cells that do not normally produce it has potential applications for gene therapy. C1 YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT MED,BRONX,NY 10461. YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT NEUROL,BRONX,NY 10461. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELL GROWTH & REGULAT,BOSTON,MA 02115. RP FEDEROFF, HJ (reprint author), YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT NEUROSCI,BRONX,NY 10461, USA. RI Geller, Alfred/C-6469-2012 FU NICHD NIH HHS [HD27226]; NINDS NIH HHS [NS20013, NS20778] NR 42 TC 170 Z9 174 U1 0 U2 1 PU NATL ACAD PRESS 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 MAR 1 PY 1992 VL 89 IS 5 BP 1636 EP 1640 DI 10.1073/pnas.89.5.1636 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA HG681 UT WOS:A1992HG68100025 PM 1311846 ER PT J AU NITSCH, RM BLUSZTAJN, JK PITTAS, AG SLACK, BE GROWDON, JH WURTMAN, RJ AF NITSCH, RM BLUSZTAJN, JK PITTAS, AG SLACK, BE GROWDON, JH WURTMAN, RJ TI EVIDENCE FOR A MEMBRANE DEFECT IN ALZHEIMER-DISEASE BRAIN SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE PHOSPHOLIPID METABOLISM; NEURODEGENERATION; DOWN SYNDROME; HUNTINGTON DISEASE; PARKINSON DISEASE ID NUCLEAR MAGNETIC-RESONANCE; DOWNS-SYNDROME; RAT-BRAIN; PRECURSOR; CHOLINE; PROTEIN; SPECTROSCOPY; METABOLISM; DIAGNOSIS; TISSUE AB To determine whether neurodegeneration in Alzheimer disease brain is associated with degradation of structural cell membrane molecules, we measured tissue levels of the major membrane phospholipids and their metabolites in three cortical areas from postmortem brains of Alzheimer disease patients and matched controls. Among phospholipids, there was a significant (P < 0.05) decrease in phosphatidylcholine and phosphatidylethanolamine. There were significant (P < 0.05) decreases in the initial phospholipid precursors choline and ethanolamine and increases in the phospholipid deacylation product glycerophosphocholine. The ratios of glycerophosphocholine to choline and glycerophosphoethanolamine to ethanolamine were significantly increased in all examined Alzheimer disease brain regions. The activity of the glycerophosphocholine-degrading enzyme glycerophosphocholine cholinephosphodiesterase was normal in Alzheimer disease brain. There was a near stoichiometric relationship between the decrease in phospholipids and the increase of phospholipid catabolites. These data are consistent with increased membrane phospholipid degradation in Alzheimer disease brain. Similar phospholipid abnormalities were not detected in brains of patients with Huntington disease, Parkinson disease, or Down syndrome. We conclude that the phospholipid abnormalities described here are not an epiphenomenon of neurodegeneration and that they may be specific for the pathomechanism of Alzheimer disease. C1 MIT,DEPT BRAIN & COGNIT SCI,CAMBRIDGE,MA 02139. BOSTON UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02118. RP NITSCH, RM (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROL,ACC 830,FRUIT ST,BOSTON,MA 02114, USA. FU NIA NIH HHS [AG-05134, AG-07906]; NIMH NIH HHS [MH-NS 31862] NR 32 TC 396 Z9 400 U1 2 U2 13 PU NATL ACAD PRESS 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 MAR 1 PY 1992 VL 89 IS 5 BP 1671 EP 1675 DI 10.1073/pnas.89.5.1671 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA HG681 UT WOS:A1992HG68100032 PM 1311847 ER PT J AU HALLAQ, H SMITH, TW LEAF, A AF HALLAQ, H SMITH, TW LEAF, A TI MODULATION OF DIHYDROPYRIDINE-SENSITIVE CALCIUM CHANNELS IN HEART-CELLS BY FISH OIL FATTY-ACIDS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE CARDIAC ARRHYTHMIAS; OUABAIN TOXICITY; N-3 FATTY ACIDS; EICOSAPENTAENOIC ACID; DOCOSAHEXAENOIC ACID ID VENTRICULAR CELLS; BINDING; CONTRACTION AB The highly unsaturated n - 3 fatty acids from fish oils, eicosapentaenoic acid [EPA; C20:5 (n - 3)] and docosahexaenoic acid [DHA; C22:6 (n - 3)], prevent the toxicity of high concentrations of the cardiac glycoside ouabain to isolated neonatal rat cardiac myocytes. Arachidonic acid [C20:4 (n - 6)] lacks such protective action. The protective effect of the n - 3 fatty acids is associated with their ability to prevent high levels of cytosolic free calcium from occurring in response to the ouabain. This in turn results, at least in part, from a 30% reduction in calcium influx rate induced by the n - 3 fatty acids. This protective effect is simulated by nitrendipine, a dihydropyridine inhibitor of the L-type calcium channels in cardiac myocytes. Nitrendipine (0.1 nM) alone, however, inhibits myocyte contractility, as do verapamil (10-mu-M) and diltiazem (1.0-mu-M). EPA or DHA (5-mu-M) blocks the inhibitory effects of nitrendipine but not those of verapamil or diltiazem. Bay K8644, a known dihydropyridine agonist of L-type calcium channels, produces a ouabain-like effect that is also prevented by EPA or DHA. Specific binding of [H-3]nitrendipine to intact myocytes is noncompetitively inhibited by EPA or DHA in a manner that reduces the number of high- and low-affinity binding sites (B(max)) and increases their affinities. The fish oil fatty acids prevent calcium overload from ouabain and Bay K8644. They also prevent a calcium-depleted state in the myocytes caused by the L-type calcium channel blocker nitrendipine. The protective effects or the n - 3 fatty acids appear to result from their modulatory effects on nitrendipine-sensitive L-type calcium channels. C1 BRIGHAM & WOMENS HOSP,DEPT MED,DIV CARDIOVASC,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP HALLAQ, H (reprint author), MASSACHUSETTS GEN HOSP,DEPT MED,CARDIOVASC HLTH UNIT,BOSTON,MA 02114, USA. FU NHLBI NIH HHS [HL40548]; NIDDK NIH HHS [DK38165, DK39249] NR 15 TC 156 Z9 157 U1 0 U2 5 PU NATL ACAD PRESS 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 MAR 1 PY 1992 VL 89 IS 5 BP 1760 EP 1764 DI 10.1073/pnas.89.5.1760 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA HG681 UT WOS:A1992HG68100050 PM 1371883 ER PT J AU DECAPRIO, JA FURUKAWA, Y AJCHENBAUM, F GRIFFIN, JD LIVINGSTON, DM AF DECAPRIO, JA FURUKAWA, Y AJCHENBAUM, F GRIFFIN, JD LIVINGSTON, DM TI THE RETINOBLASTOMA-SUSCEPTIBILITY GENE-PRODUCT BECOMES PHOSPHORYLATED IN MULTIPLE STAGES DURING CELL-CYCLE ENTRY AND PROGRESSION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HUMAN LYMPHOCYTES-T; SV40 LARGE-T; TRANSCRIPTION FACTOR; RB PROTEIN; EXPRESSION; DIFFERENTIATION; INVITRO; E2F AB The retinoblastoma-susceptibility gene product (RB) undergoes cell cycle-dependent phosphorylation and dephosphorylation. We characterized RB phosphorylation after mitogenic stimulation of primary human T lymphocytes, initially arrested in the G0 state. RB is phosphorylated in at least three steps when T cells are driven into the cell cycle. The first event occurs during mid G1 phase, the second during S phase, and the third in G2/M. Tryptic phosphopeptide mapping indicates that the different phosphorylation events occur, at least in part, on different residues in RB. Given the known relationship of the RB phosphorylation state to function, it is possible that RB regulates growth at multiple points in the cell cycle. RP DECAPRIO, JA (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. NR 27 TC 249 Z9 250 U1 0 U2 1 PU NATL ACAD PRESS 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 MAR 1 PY 1992 VL 89 IS 5 BP 1795 EP 1798 DI 10.1073/pnas.89.5.1795 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA HG681 UT WOS:A1992HG68100057 PM 1531876 ER PT J AU PARKER, CM CEPEK, KL RUSSELL, GJ SHAW, SK POSNETT, DN SCHWARTING, R BRENNER, MB AF PARKER, CM CEPEK, KL RUSSELL, GJ SHAW, SK POSNETT, DN SCHWARTING, R BRENNER, MB TI A FAMILY OF BETA-7 INTEGRINS ON HUMAN MUCOSAL LYMPHOCYTES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID T-CELL RECEPTOR; MONOCLONAL-ANTIBODY; INTESTINAL LYMPHOCYTES; EPITHELIAL-CELLS; LAMINA PROPRIA; IMMUNE-SYSTEM; ANTIGEN; PROTEINS; ACTIVATION; EXPRESSION AB The heterodimeric protein complex recognized by the human mucosal lymphocyte 1 (HML-1) monoclonal antibody is expressed on 95% of intraepithelial lymphocytes but on only 1-2% of peripheral blood lymphocytes [Cerf-Bensusson, N., Jarry, A., Brousse, N., Lisowska-Grospierre, B., Guy-Grand, D. & Griscelli, C. (1987) Eur. J. Immunol. 17, 1279-1285]. We purified the smaller HML-1 subunit (105 kDa under nonreducing conditions) from hairy-cell leukemia cells and determined the N-terminal amino acid sequence of this chain. The 17 residues determined were identical to the deduced amino acid sequence encoded by an integrin-beta-7 cDNA clone [Yuan, Q., Jiang, W.-M., Krissansen, G. W. & Watson, J. D. (1990) Int. Immunol. 2, 1097-1108]. Biochemical analysis of the larger HML-1 subunit (175 kDa under nonreducing conditions) suggested that it was a distinct member of the cleaved group of integrin-alpha-chains, which we designated alpha(E). The beta-7-chain also was associated with the integrin-alpha-4 subunit, suggesting that the HML-1 antigen (alpha(E)beta-7) and alpha-4-beta-7 constitute a beta-7-integrin family on mucosal lymphocytes. Interestingly, regulation of the expression of the HML-1 antigen was reciprocal to that of lymphocyte function-associated molecule 1 in the presence of transforming growth factor-beta-1. We suggest that these beta-7-integrins may play a specific role in mucosal localization or adhesion and that the expression of the HML-1 antigen might be regulated by transforming growth factor-beta-1 produced at or near epithelial tissues. C1 HARVARD UNIV,SCH MED,DEPT RHEUMATOL & IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,GRAD PROGRAM IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PEDIAT,BOSTON,MA 02114. CORNELL UNIV,DEPT MED,NEW YORK,NY 10021. THOMAS JEFFERSON UNIV,DEPT PATHOL,PHILADELPHIA,PA 19107. RP PARKER, CM (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,IMMUNOCHEM LAB,BOSTON,MA 02115, USA. NR 38 TC 229 Z9 235 U1 0 U2 1 PU NATL ACAD PRESS 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 MAR 1 PY 1992 VL 89 IS 5 BP 1924 EP 1928 DI 10.1073/pnas.89.5.1924 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA HG681 UT WOS:A1992HG68100084 PM 1542691 ER PT J AU WILENS, TE BIEDERMAN, J AF WILENS, TE BIEDERMAN, J TI THE STIMULANTS SO PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Review ID ATTENTION-DEFICIT DISORDER; MOTHER-CHILD INTERACTIONS; SUSTAINED-RELEASE METHYLPHENIDATE; AGGRESSIVE NONCOMPLIANT FEATURES; MINIMAL BRAIN-DYSFUNCTION; HYPERACTIVE-CHILDREN; GROWTH-HORMONE; TOURETTES SYNDROME; CONTROLLED TRIAL; STANDARD METHYLPHENIDATE C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP WILENS, TE (reprint author), MASSACHUSETTS GEN HOSP,DEPT CHILD PSYCHIAT ACC 725,15 PARKMAN ST,BOSTON,MA 02114, USA. NR 121 TC 193 Z9 195 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 MAR PY 1992 VL 15 IS 1 BP 191 EP 222 PG 32 WC Psychiatry SC Psychiatry GA KZ407 UT WOS:A1992KZ40700012 PM 1347939 ER PT J AU WOOD, LC COOPER, DS AF WOOD, LC COOPER, DS TI AUTOIMMUNE THYROID-DISEASE, LEFT-HANDEDNESS, AND DEVELOPMENTAL DYSLEXIA SO PSYCHONEUROENDOCRINOLOGY LA English DT Note ID CEREBRAL LATERALIZATION; BIOLOGICAL MECHANISMS; ASSOCIATIONS; HYPOTHESIS; PATHOLOGY; PROGRAM AB Autoimmune thyroid disease (ATD) (Graves' disease and Hashimoto's thyroiditis) has been one of a number of autoimmune diseases possibly associated with left-handedness, mixed dominance, and learning disability. In the present study, 74 men with ATD were compared to 24 control men with non-ATD. An increased frequency of mixed dominance and traits suggestive of dyslexia were observed in the patients with ATD. These data are consistent with a link between the development of ATD and cerebral dominance. C1 JOHNS HOPKINS UNIV,SINAI HOSP BALTIMORE,SCH MED,DIV ENDOCRINE,BALTIMORE,MD 21218. RP WOOD, LC (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,THYROID UNIT,ACC635,BOSTON,MA 02114, USA. NR 14 TC 14 Z9 14 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD MAR PY 1992 VL 17 IS 1 BP 95 EP 99 DI 10.1016/0306-4530(92)90080-Q PG 5 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA HT162 UT WOS:A1992HT16200008 PM 1609020 ER PT J AU SURMAN, OS PURTILO, R AF SURMAN, OS PURTILO, R TI REEVALUATION OF ORGAN-TRANSPLANTATION CRITERIA - ALLOCATION OF SCARCE RESOURCES TO BORDERLINE CANDIDATES SO PSYCHOSOMATICS LA English DT Article ID LIVER-TRANSPLANTATION; PATIENT; HEART AB Organ transplantation in the 1960s proceeded according to a "lifeboat" ethics formula with physicians acting as "gatekeepers." Selection of transplant recipients is now based on medical urgency and waiting time. Some candidates continue to be given low priority by virtue of psychological impairment. The three As-advanced age, acquired immune deficiency syndrome (or positive human immunodeficiency virus status), and alcoholism - also stand out as characteristics that tend to exclude candidates. Cancer is another relative or absolute contraindication to transplantation. This article focuses retrospectively on the psychosocial and medical aspects of the decision to include six patients at Massachusetts General Hospital who were selected for organ transplantation despite their borderline candidacy. The authors introduce four lines of thinking that decision-makers might use to either include or exclude marginal candidates (e.g., the physician's interpretation of what duty requires, the patient's or surrogate's wishes, cost-benefit considerations, or the need for research to improve our scientific understanding of transplantation issues) and discuss an ethical approach that supports each line of thinking. The authors conclude that not all of the ethical approaches lead practitioners and policymakers to the same conclusions regarding the optimum size of or who should be a part of the recipient pool. The future of who receives transplants and why depends at least in part on the underlying ethical considerations that are deemed appropriate as determinants of practice and policy. C1 MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,INST HLTH PROFESS,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 23 TC 23 Z9 23 U1 1 U2 3 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD SPR PY 1992 VL 33 IS 2 BP 202 EP 212 PG 11 WC Psychiatry; Psychology SC Psychiatry; Psychology GA HL357 UT WOS:A1992HL35700010 PM 1557485 ER PT J AU CREMENS, MC AF CREMENS, MC TI INTEGRATING PHARMACOTHERAPY AND PSYCHOTHERAPY - BEITMAN,BD, KLERMAN,GL SO PSYCHOSOMATICS LA English DT Book Review RP CREMENS, MC (reprint author), MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,CONSULTAT SERV,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 SPR PY 1992 VL 33 IS 2 BP 232 EP 233 PG 2 WC Psychiatry; Psychology SC Psychiatry; Psychology GA HL357 UT WOS:A1992HL35700019 ER PT J AU CREMENS, MC AF CREMENS, MC TI NEW TECHNIQUES IN THE PSYCHOTHERAPY OF OLDER PATIENTS - MEYERS,WA SO PSYCHOSOMATICS LA English DT Book Review RP CREMENS, MC (reprint author), MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,CONSULTAT SERV,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 SPR PY 1992 VL 33 IS 2 BP 233 EP 234 PG 2 WC Psychiatry; Psychology SC Psychiatry; Psychology GA HL357 UT WOS:A1992HL35700020 ER PT J AU RUMMENY, EJ WERNECKE, K SAINI, S VASSALLO, P WIESMANN, W OESTMANN, JW KIVELITZ, D REERS, B REISER, MF PETERS, PE AF RUMMENY, EJ WERNECKE, K SAINI, S VASSALLO, P WIESMANN, W OESTMANN, JW KIVELITZ, D REERS, B REISER, MF PETERS, PE TI COMPARISON BETWEEN HIGH-FIELD-STRENGTH MR IMAGING AND CT FOR SCREENING OF HEPATIC METASTASES - A RECEIVER OPERATING CHARACTERISTIC ANALYSIS SO RADIOLOGY LA English DT Article DE COMPUTED TOMOGRAPHY (CT), COMPARATIVE STUDIES; GASTROINTESTINAL TRACT, NEOPLASMS; LIVER NEOPLASMS, CT; LIVER NEOPLASMS, MR; LIVER NEOPLASMS, SECONDARY; MAGNETIC RESONANCE (MR), COMPARATIVE STUDIES ID SUPERPARAMAGNETIC IRON-OXIDE; LIVER METASTASES; ARTERIAL PORTOGRAPHY; CLINICAL-APPLICATION; DELAYED CT; CONTRAST; ULTRASOUND; CARCINOMA; CANCER; TUMORS AB The diagnostic performance of high-field-strength magnetic resonance (MR) imaging (1.5 T) for detection of liver metastases was compared with that of computed tomography (CT). All patients (n = 52) underwent preoperative screening for metastases by means of MR imaging with T1-weighted, proton-density-weighted, and T2-weighted pulse sequences and CT scanning with unenhanced, incremental dynamic bolus-enhanced, and delayed contrast medium-enhanced techniques. Diagnostic performance was evaluated by means of receiver operating characteristic analysis in which 800 images (400 with and 400 without lesions) and five readers (4,000 observations) were used; images were obtained from patients (n = 39) in whom the same anatomic levels were available for all MR imaging and CT studies. Direct comparison between the best MR imaging technique (T2-weighted spin-echo imaging [repetition time, 2,000 msec; echo time, 70 msec]) and the best CT technique (incremental dynamic bolus CT) showed a strong trend of superiority of T2-weighted MR imaging over incremental dynamic bolus CT. No highly statistically significant difference (P greater-than-or-equal-to .01), however, was found between these two techniques. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. RP RUMMENY, EJ (reprint author), UNIV MUNSTER,DEPT RADIOL,ALBERT SCHWEITZER STR 33,W-4400 MUNSTER,GERMANY. NR 45 TC 80 Z9 80 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD MAR PY 1992 VL 182 IS 3 BP 879 EP 886 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA HE860 UT WOS:A1992HE86000051 PM 1535912 ER PT J AU PRINCE, MR ATHANASOULIS, CA AF PRINCE, MR ATHANASOULIS, CA TI FLUORESCENCE-GUIDED PULSED DYE LASER-ASSISTED ANGIOPLASTY SO RADIOLOGY LA English DT Letter ID ATHEROSCLEROTIC PLAQUE; ABSORPTION RP PRINCE, MR (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114, USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD MAR PY 1992 VL 182 IS 3 BP 896 EP 897 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA HE860 UT WOS:A1992HE86000056 PM 1535916 ER PT J AU DAWSON, SL MUELLER, PR AF DAWSON, SL MUELLER, PR TI EMBOLOTHERAPY SO SEMINARS IN INTERVENTIONAL RADIOLOGY LA English DT Editorial Material RP DAWSON, SL (reprint author), MASSACHUSETTS GEN HOSP,DEPT 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 MAR PY 1992 VL 9 IS 1 BP U1 EP U1 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA HK893 UT WOS:A1992HK89300001 ER PT J AU HUTCHISON, FN BELL, NH AF HUTCHISON, FN BELL, NH TI OSTEOMALACIA AND RICKETS SO SEMINARS IN NEPHROLOGY LA English DT Review ID CHRONIC-RENAL-FAILURE; METABOLIC BONE-DISEASE; VITAMIN-D METABOLITES; SERUM 1,25-DIHYDROXYVITAMIN-D LEVELS; LINKED HYPOPHOSPHATEMIC RICKETS; ALUMINUM-RELATED OSTEODYSTROPHY; D-DEPENDENT RICKETS; PARATHYROID-HORMONE; SECONDARY HYPERPARATHYROIDISM; HEMODIALYSIS-PATIENTS C1 MED UNIV S CAROLINA,DEPT MED,CHARLESTON,SC 29425. MED UNIV S CAROLINA,DEPT PHARMACOL,CHARLESTON,SC 29425. RP HUTCHISON, FN (reprint author), RALPH H JOHNSON VET AFFAIRS MED CTR,109 BEE ST,CHARLESTON,SC 29401, USA. NR 131 TC 9 Z9 10 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9295 J9 SEMIN NEPHROL JI Semin. Nephrol. PD MAR PY 1992 VL 12 IS 2 BP 127 EP 145 PG 19 WC Urology & Nephrology SC Urology & Nephrology GA HJ369 UT WOS:A1992HJ36900007 PM 1561493 ER PT J AU GILBERT, DC AF GILBERT, DC TI CHALLENGES TO THE PRESUMPTION OF ACADEMIC AND SCIENTIFIC INTEGRITY SO SRA-JOURNAL OF THE SOCIETY OF RESEARCH ADMINISTRATORS LA English DT Editorial Material RP GILBERT, DC (reprint author), MASSACHUSETTS GEN HOSP,RES AFFAIRS,BOSTON,MA 02114, USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU SOC RESEARCH ADMINISTRATORS PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036 SN 1062-8142 J9 SRA-J SOC RES ADMIN JI SRA-J. Soc. Res. Admin. PD SPR PY 1992 VL 23 IS 4 BP 47 EP 51 PG 5 WC Business; Management SC Business & Economics GA HW854 UT WOS:A1992HW85400007 ER PT J AU ALBIN, MS HANTLER, C MITZEL, H BUNEGIN, L GROVER, F COHEN, D AF ALBIN, MS HANTLER, C MITZEL, H BUNEGIN, L GROVER, F COHEN, D TI TRANSCRANIAL DOPPLER (TCD) UTILIZATION DURING OPEN-HEART-SURGERY - FLOW CHANGES AND INCIDENCE OF AIR MICROEMBOLI SO STROKE LA English DT Meeting Abstract C1 UNIV TEXAS,AUDIE MURPHY MEM VET HOSP,HLTH SCI CTR,SAN ANTONIO,TX 78285. 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 0039-2499 J9 STROKE JI Stroke PD MAR PY 1992 VL 23 IS 3 BP 474 EP 474 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA HH219 UT WOS:A1992HH21900109 ER PT J AU OJEMANN, RG AF OJEMANN, RG TI TRAINING THE NEUROSURGEON FOR THE 21ST-CENTURY SO SURGICAL NEUROLOGY LA English DT Editorial Material C1 HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. RP OJEMANN, RG (reprint author), MASSACHUSETTS GEN HOSP,NEUROSURG SERV,BOSTON,MA 02114, USA. NR 7 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0090-3019 J9 SURG NEUROL JI Surg. Neurol. PD MAR PY 1992 VL 37 IS 3 BP 167 EP 174 DI 10.1016/0090-3019(92)90224-B PG 8 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA HG382 UT WOS:A1992HG38200001 PM 1536020 ER PT J AU JOYCE, JN LEXOW, N KIM, SJ ARTYMYSHYN, R SENZON, S LAWERENCE, D CASSANOVA, MF KLEINMAN, JE BIRD, ED WINOKUR, A AF JOYCE, JN LEXOW, N KIM, SJ ARTYMYSHYN, R SENZON, S LAWERENCE, D CASSANOVA, MF KLEINMAN, JE BIRD, ED WINOKUR, A TI DISTRIBUTION OF BETA-ADRENERGIC-RECEPTOR SUBTYPES IN HUMAN POSTMORTEM BRAIN - ALTERATIONS IN LIMBIC REGIONS OF SCHIZOPHRENICS SO SYNAPSE LA English DT Article DE CORTEX; HIPPOCAMPUS; BASAL GANGLIA; BETA1 (BETA-1) RECEPTOR; BETA2 (BETA-2) RECEPTOR ID NEUROLEPTIC-INDUCED AKATHISIA; BETA-2-ADRENERGIC RECEPTORS; SUICIDE VICTIMS; RAT-BRAIN; QUANTITATIVE AUTORADIOGRAPHY; H-3 DIHYDROALPRENOLOL; SELECTIVE INCREASES; HUMAN STRIATUM; UPTAKE SITES; BINDING AB The distribution of the beta-1 (beta-1) beta-2 (beta-2) subtypes of the beta-adrenergic receptor was examined in rat and nondiseased control human tissue. The distribution of the beta-1 and beta-2 receptors was also examined in schizophrenic cases, with additional studies in schizophrenic suicide and nonschizophrenic suicide cases. Scatchard analysis of the binding of [I-125]iodopindolol (IPIN) to cortical membranes showed a similar K(d) in human (177 pM) and rat (161 pM), but a lower maximum binding site (B(max)) in the human tissue (18.7 fmol/mg protein and 55.6 fmol/mg protein). For the autoradiographic studies [I-125]IPIN was used to visualize both subtypes (total) or was displaced with the selective beta-1-receptor antagonist ICI-89,406 to visualize beta-2 sites, or with the selective beta-2-receptor antagonist ICI-118,551 to visualize beta-1, sites. Important differences in the regional distribution of the two subtypes of the beta-adrenergic receptors were noted between rat and human. In the nucleus accumbens and ventral putamen (ventral striatum), a patchy distribution of beta-1, receptors was observed that was not evident in the rat. These patches were aligned with markers of the matrix compartment of the striatum. The schizophrenic cases showed significant increases in the labeling of the beta-1-receptor patches with [I-125]IPIN. In contrast to the frontal cortex of the nondisease controls, the parietal and temporal cortex showed a high ratio of beta-1 to beta-2 receptors and a highly laminar organization of the subtypes. [I-125]IPIN binding to beta-1 receptors was highest in the external laminae with the reverse gradient for the beta-2 subtype. The medial temporal cortex displayed an alteration in the ratio of the 2 subtypes of the beta-adrenergic receptor, with the parahippocampus and hippocampus of the human, in contrast to the rat brain, predominantly expressing the beta-2 receptor. Moreover, there were consistently higher densities of beta-2 receptors in the hippocampus of the right hemisphere than the left hemisphere of the nondisease controls. There was not a left and right hemispheric asymmetry of beta-2 receptors in the hippocampus of elderly schizophrenics or in young schizophrenics who committed suicide. The asymmetry was evident in nonschizophrenic suicides, suggesting that the lack of asymmetry in the hippocampus of schizophrenics is evident early in the disease process. Thus limbic structures show alterations in the patterning of beta-1 and beta-2 receptors in the schizophrenic cases. C1 UNIV PENN,SCH MED,DEPT PHARMACOL,PHILADELPHIA,PA 19104. NIMH,ST ELIZABETHS HOSP,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL NEUROPATHOL,BOSTON,MA 02114. RP JOYCE, JN (reprint author), UNIV PENN,SCH MED,DEPT PSYCHIAT,CHEM NEUROANAT LAB,127 CLIN RES BLDG,422 CURRIE BLVD,PHILADELPHIA,PA 19104, USA. FU NIMH NIH HHS [MH 00044, MH 43852, MH 43880] NR 61 TC 59 Z9 60 U1 2 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0887-4476 J9 SYNAPSE JI Synapse PD MAR PY 1992 VL 10 IS 3 BP 228 EP 246 DI 10.1002/syn.890100306 PG 19 WC Neurosciences SC Neurosciences & Neurology GA HF843 UT WOS:A1992HF84300005 PM 1313605 ER PT J AU ANDERSON, KC AF ANDERSON, KC TI THE ROLE OF THE BLOOD-BANK IN HEMATOPOIETIC STEM-CELL TRANSPLANTATION SO TRANSFUSION LA English DT Article ID BONE-MARROW TRANSPLANTATION; COLONY-STIMULATING FACTOR; CYTOMEGALO-VIRUS INFECTION; RECOMBINANT-HUMAN-ERYTHROPOIETIN; VERSUS-HOST DISEASE; DONOR PLATELET TRANSFUSIONS; ACUTE LYMPHOBLASTIC-LEUKEMIA; INTRAVENOUS IMMUNE GLOBULIN; ACUTE MYELOBLASTIC-LEUKEMIA; ALLOGENEIC MARROW C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. RP ANDERSON, KC (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV MED,BLOOD COMPONENT LAB,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA50947] NR 177 TC 9 Z9 9 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD MAR-APR PY 1992 VL 32 IS 3 BP 272 EP 285 DI 10.1046/j.1537-2995.1992.32392213814.x PG 14 WC Hematology SC Hematology GA HN281 UT WOS:A1992HN28100017 PM 1348379 ER PT J AU WEE, SL STROKA, DM PREFFER, FI JOLLIFFE, LK COLVIN, RB COSIMI, AB AF WEE, SL STROKA, DM PREFFER, FI JOLLIFFE, LK COLVIN, RB COSIMI, AB TI THE EFFECTS OF OKT4A MONOCLONAL-ANTIBODY ON CELLULAR-IMMUNITY OF NONHUMAN PRIMATE RENAL-ALLOGRAFT RECIPIENTS SO TRANSPLANTATION LA English DT Article ID T-CELLS; NEGATIVE SIGNAL; LYMPHOCYTES; RECEPTOR; SURVIVAL; CD4; TRANSPLANTATION; EXPRESSION; MOLECULES; REJECTION AB Significant differences in cellular responses were found among allograft recipients treated with various OKT4A mAb protocols. Recipients of multiple infusion low-dose and 2-bolus OKT4A immunosuppressive regimens regularly showed potent donor-specific cytotoxic CD8+ and CD4+ intragraft T cells and donor-reactive PBMC in MLC tests. In contrast, PBMC isolated from recipients of high-dose OKT4A therapy generally showed very weak or no response to donor-antigens during the later posttransplant periods. Furthermore, an absence of IL2-responsive intragraft cells was found to correlate with stable graft function in these recipients. We conclude that OKT4A mAb, in high doses, can block allosensitization and induce donor-specific non-responsiveness in vivo. An OKT4A-based therapy, therefore, may have the potential of inducing long-lasting donor-specific immunosuppression, or even tolerance. C1 MASSACHUSETTS GEN HOSP,IMMUNOPATHOL UNIT,BOSTON,MA 02214. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. ORTHO PHARMACEUT CORP,RARITAN,NJ 08869. RP WEE, SL (reprint author), MASSACHUSETTS GEN HOSP,DEPT SURG,TRANSPLANTAT UNIT,BOSTON,MA 02214, USA. RI Stroka, Deborah/F-1806-2013 FU NHLBI NIH HHS [HL-18646] NR 27 TC 23 Z9 24 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD MAR PY 1992 VL 53 IS 3 BP 501 EP 507 DI 10.1097/00007890-199203000-00001 PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA HJ581 UT WOS:A1992HJ58100001 PM 1532265 ER PT J AU KAWAMURA, T NIGUMA, T FECHNER, JH WOLBER, R BEESKAU, MA HULLETT, DA SOLLINGER, HW BURLINGHAM, WJ AF KAWAMURA, T NIGUMA, T FECHNER, JH WOLBER, R BEESKAU, MA HULLETT, DA SOLLINGER, HW BURLINGHAM, WJ TI CHRONIC HUMAN SKIN-GRAFT REJECTION IN SEVERE COMBINED IMMUNODEFICIENT MICE ENGRAFTED WITH HUMAN PBL FROM AN HLA-PRESENSITIZED DONOR SO TRANSPLANTATION LA English DT Article ID SCID MICE; MOUSE; LYMPHOCYTES; ALLOGRAFTS; CELLS AB Mice with severe combined immunodeficiency (C.B-17 scid [SCID]) accepted xenografts of adult human peripheral blood leukocytes injected intraperitoneally as evidenced by production of human immunoglobulin (IgG and IgM), and circulation of human leukocytes in peripheral blood. SCID mice also accepted human split-thickness skin xenografts. Passenger leukocytes present in small numbers in such skin grafts could also recirculate in host peripheral blood and make detectable levels of human immunoglobulin. To test the immunocompetence of the transferred human PBL, SCID mice received a human skin xenograft from a second donor (HLA-mismatched with the PBL donor) either before (n = 6) or after (n = 23) xenografting of PBL. Skin was monitored daily for signs of rejection, and rejection was scored by histology 3-4 weeks after the second graft (PBL or skin) was placed. Of 19 SCID injected with PBL from an HLA presensitized patient (L.G.), 7/19 (37%) rejected a subsequent HLA-mismatched skin xenograft. Two of six SCID (33%) rejected a previously established skin xenograft when PBL were administered afterward. The rejection of the human skin was chronic, of relatively late onset (3-4 weeks), and was characterized grossly by contraction, glassy surface, and thickening. Histopathologic examination showed lymphocyte infiltration into the dermis with endothelial cell cuffing and destruction of capillaries, as well as lymphocyte tagging of the basal epidermis, hyperkeratosis, lymphocyte exocytosis and single epidermal cell necrosis. Immunostaining with monoclonal antibody to human CD2 or mouse CD3 revealed that human, but not mouse T lymphocytes were tagging the dermis/epidermis junction and infiltrating the epidermis of rejecting skin grafts. We conclude that a form of human skin graft rejection may be reproduced in an SCID mouse. The immune status of the transferred cells (sensitized vs. normal) and the lymphocytes ability to recirculate in SCID peripheral blood appear to be factors limiting the rejection process. C1 UNIV WISCONSIN,DEPT SURG,600 HIGHLAND AVE,MADISON,WI 53792. WILLIAM S MIDDLETON MEM VET ADM MED CTR,DEPT PATHOL,MADISON,WI 53792. RI Fechner, John/C-5962-2016 OI Fechner, John/0000-0002-8220-7237 FU NIAID NIH HHS [AI26941]; NIDDK NIH HHS [DK31774] NR 17 TC 35 Z9 35 U1 1 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD MAR PY 1992 VL 53 IS 3 BP 659 EP 665 DI 10.1097/00007890-199203000-00032 PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA HJ581 UT WOS:A1992HJ58100032 PM 1549862 ER PT J AU KNECHTLE, SJ WANG, J BURLINGHAM, WJ BEESKAU, M SUBRAMANIAN, R SOLLINGER, HW AF KNECHTLE, SJ WANG, J BURLINGHAM, WJ BEESKAU, M SUBRAMANIAN, R SOLLINGER, HW TI THE INFLUENCE OF RS-61443 ON ANTIBODY-MEDIATED REJECTION SO TRANSPLANTATION LA English DT Note C1 UNIV WISCONSIN,SCH MED,DEPT SURG,MADISON,WI 53792. WILLIAM S MIDDLETON MEM VET ADM MED CTR,DEPT PATHOL,MADISON,WI 53705. NR 13 TC 26 Z9 26 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD MAR PY 1992 VL 53 IS 3 BP 699 EP 701 PG 3 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA HJ581 UT WOS:A1992HJ58100046 PM 1549873 ER PT J AU SZOSTAK, JW AF SZOSTAK, JW TI INVITRO GENETICS SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Article ID DNA-BINDING; NUCLEIC-ACIDS; RNA; SEQUENCES; PROTEIN; SELECTION; REPLICATION; EVOLUTION; SITE; BACTERIOPHAGE-T4 AB Understanding the basis of specificity in an intermolecular interaction is a common if difficult task; designing a specific intermolecular interaction is much more challenging. A new technique is described that has applications to both problems, at least with regard to nucleic acids. The power of this method lies in its ability to isolate extremely rare sequences with precisely specified properties from very large pools of random sequences. RP SZOSTAK, JW (reprint author), MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114, USA. NR 27 TC 155 Z9 157 U1 2 U2 8 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD MAR PY 1992 VL 17 IS 3 BP 89 EP 93 DI 10.1016/0968-0004(92)90242-2 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HJ905 UT WOS:A1992HJ90500002 PM 1384177 ER PT J AU LIPTON, SA AF LIPTON, SA TI MODELS OF NEURONAL INJURY IN AIDS - ANOTHER ROLE FOR THE NMDA RECEPTOR SO TRENDS IN NEUROSCIENCES LA English DT Editorial Material ID HUMAN IMMUNODEFICIENCY VIRUS; IMMUNE-DEFICIENCY SYNDROME; AMINO-ACID NEUROTOXICITY; RAT CEREBELLAR SLICES; PROTEIN KINASE-C; DEMENTIA COMPLEX; GLUTAMATE NEUROTOXICITY; CLINICAL-FEATURES; ENVELOPE PROTEIN; NERVOUS-SYSTEM AB As many as two-thirds of patients with acquired immunodeficiency syndrome (AIDS) eventually suffer from neurological manifestations, including dysfunction of cognition, movement and sensation. How can human immunodeficiency virus type 1 (HIV-1) result in neuronal damage if neurons themselves are not infected by the virus? In this article Stuart Lipton reviews a series of experiments from several different laboratories that offer related hypotheses accounting for neurotoxicity in the brains of AIDS patients. There is growing support for the existence of HIV- or immune-related toxins that directly or indirectly lead to the injury or demise of neurons via a potentially complex web of interactions between macrophages (or microglia), astrocytes and neurons. However, a final common pathway for neuronal susceptibility appears to be operative, similar to that observed after stroke, trauma and epilepsy. This mechanism involves voltage-dependent Ca2+ channels and NMDA receptor-operated channels, and therefore offers hope for future pharmacological intervention. C1 BETH ISRAEL HOSP,DEPT NEUROL,BOSTON,MA 02215. WOMENS HOSP MED CTR,DEPT NEUROL,LOS ANGELES,CA 90033. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02115. RP LIPTON, SA (reprint author), CHILDRENS HOSP MED CTR,DEPT NEUROL,CELLULAR & MOLEC NEUROSCI,BOSTON,MA 02115, USA. FU NEI NIH HHS [EY05477, EY09024]; NINDS NIH HHS [NS07264] NR 64 TC 259 Z9 260 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD MAR PY 1992 VL 15 IS 3 BP 75 EP 79 DI 10.1016/0166-2236(92)90013-X PG 5 WC Neurosciences SC Neurosciences & Neurology GA HF634 UT WOS:A1992HF63400001 PM 1373919 ER PT J AU DAMIANI, S KOERNER, FC DICKERSIN, GR COOK, MG EUSEBI, V AF DAMIANI, S KOERNER, FC DICKERSIN, GR COOK, MG EUSEBI, V TI GRANULAR-CELL TUMOR OF THE BREAST SO VIRCHOWS ARCHIV A-PATHOLOGICAL ANATOMY AND HISTOPATHOLOGY LA English DT Article DE BREAST; GRANULAR CELL TUMOR; MAMMOGRAPHY; ULTRASTRUCTURE; IMMUNOHISTOCHEMISTRY ID CARCINOEMBRYONIC ANTIGEN; MYOBLASTOMA; IMMUNOPEROXIDASE; CARCINOMA; PROTEIN AB Eight cases of benign granular cell tumour of the breast are reported. Seven patients were women and one was male. The age at the time of the excision ranged from 17 to 73 (average 40.1) years. All tumours were positive for S-100 protein and negative for keratin, myoglobin and gross cystic disease fluid protein. In two cases ultrastructural studies revealed findings identical to those in the previously reported cases of granular cell tumours. None of these cases were diagnosed preoperatively. In six cases the clinical and mammographic findings, and in one case the frozen section, led to an erroneous diagnosis of malignancy. The clinico-pathological features of the cases are delineated in order to draw attention to a benign condition which closely simulates malignancy. C1 UNIV BOLOGNA,OSPED BELLARIA,IST ANAT & ISTOL PATOL,VIA ALTURA 3,I-40139 BOLOGNA,ITALY. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. ROYAL SURREY CTY HOSP,DEPT PATHOL,GUILDFORD,ENGLAND. NR 36 TC 35 Z9 35 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0174-7398 J9 VIRCHOWS ARCH A JI Virchows Arch. A-Pathol. Anat. Histopathol. PD MAR PY 1992 VL 420 IS 3 BP 219 EP 226 DI 10.1007/BF01600274 PG 8 WC Anatomy & Morphology; Pathology SC Anatomy & Morphology; Pathology GA HJ928 UT WOS:A1992HJ92800003 PM 1372779 ER PT J AU LINDBERG, I LINCOLN, B RHODES, CJ AF LINDBERG, I LINCOLN, B RHODES, CJ TI FLUOROMETRIC ASSAY OF A CALCIUM-DEPENDENT, PAIRED-BASIC PROCESSING ENDOPEPTIDASE PRESENT IN INSULINOMA GRANULES SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID SECRETORY GRANULES; KEX2; SITE; CLEAVAGE; CELL; RAT C1 BRIGHAM & WOMENS HOSP,JOSLIN DIABET CTR,EP JOSLIN RES LAB,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP LINDBERG, I (reprint author), LOUISIANA STATE UNIV,MED CTR,DEPT BIOCHEM & MOLEC BIOL,NEW ORLEANS,LA 70112, USA. FU NCRR NIH HHS [S07RR05673]; NIDA NIH HHS [DA 05084, R01 DA005084]; NIDDK NIH HHS [DK36836] NR 19 TC 15 Z9 15 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 FEB 28 PY 1992 VL 183 IS 1 BP 1 EP 7 DI 10.1016/0006-291X(92)91599-L PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA HG438 UT WOS:A1992HG43800001 PM 1543479 ER PT J AU NISHIYAMA, M WANDS, JR AF NISHIYAMA, M WANDS, JR TI CLONING AND INCREASED EXPRESSION OF AN INSULIN-RECEPTOR SUBSTRATE-1-LIKE GENE IN HUMAN HEPATOCELLULAR-CARCINOMA SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID PROTEIN-KINASE; REQUIREMENTS C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. RP NISHIYAMA, M (reprint author), MASSACHUSETTS GEN HOSP,CTR CANC,MOLEC HEPATOL LAB,BOSTON,MA 02114, USA. FU NCI NIH HHS [CA-35711]; NIAAA NIH HHS [AA-08169, AA-02666] NR 11 TC 116 Z9 117 U1 0 U2 3 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 FEB 28 PY 1992 VL 183 IS 1 BP 280 EP 285 DI 10.1016/0006-291X(92)91640-C PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA HG438 UT WOS:A1992HG43800042 PM 1311924 ER PT J AU ANDERSON, P STREULI, M SAITO, H SCHLOSSMAN, S TIAN, Q AF ANDERSON, P STREULI, M SAITO, H SCHLOSSMAN, S TIAN, Q TI MOLECULAR-CLONING AND FUNCTIONAL-CHARACTERIZATION OF A CANDIDATE NUCLEOLYSIN IN THE GRANULES OF CYTOLYTIC LYMPHOCYTES SO FASEB JOURNAL LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 1 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1992 VL 6 IS 5 BP A1691 EP A1691 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA HH271 UT WOS:A1992HH27100532 ER PT J AU BOUCHER, Y JAIN, RK AF BOUCHER, Y JAIN, RK TI VENOUS-PRESSURE IN THE MAIN SOURCE OF INTERSTITIAL HYPERTENSION IN SOLID TUMORS SO FASEB JOURNAL LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1992 VL 6 IS 5 BP A2071 EP A2071 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA HH271 UT WOS:A1992HH27102735 ER PT J AU BURTON, MD KAZEMI, H AF BURTON, MD KAZEMI, H TI CETIEDIL, AN INHIBITOR OF ACETYLCHOLINE-RELEASE, DEPRESSES RESPIRATORY NEURONAL OUTPUT IN THE NEONATAL RAT SO FASEB JOURNAL LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1992 VL 6 IS 5 BP A1826 EP A1826 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA HH271 UT WOS:A1992HH27101313 ER PT J AU CARTER, EA TROP, M SCHIFFRIN, EJ AF CARTER, EA TROP, M SCHIFFRIN, EJ TI ETHANOL, INFECTIONS AND THE RESPONSE TO INJURY SO FASEB JOURNAL LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1992 VL 6 IS 5 BP A1901 EP A1901 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA HH271 UT WOS:A1992HH27101747 ER PT J AU CASTILLO, L YU, YM BRANCH, S CHAPMAN, T BURKE, JF YOUNG, VR AF CASTILLO, L YU, YM BRANCH, S CHAPMAN, T BURKE, JF YOUNG, VR TI ARGININE METABOLISM IN RELATION TO AN ARGININE-FREE INTAKE IN YOUNG MEN SO FASEB JOURNAL LA English DT Meeting Abstract C1 MIT,CAMBRIDGE,MA 02139. SHRINERS BURN INST,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1992 VL 6 IS 5 BP A1943 EP A1943 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA HH271 UT WOS:A1992HH27101993 ER PT J AU DAHLBERG, CGW QUINN, DA BONVENTRE, JP JOSEPH, PM THOMPSON, BT HALES, CA AF DAHLBERG, CGW QUINN, DA BONVENTRE, JP JOSEPH, PM THOMPSON, BT HALES, CA TI EGF CAUSES INTRACELLULAR ALKALINIZATION OF BOVINE PULMONARY-ARTERY SMOOTH-MUSCLE CELLS IN PART VIA STIMULATION OF NA+/H+ EXCHANGE SO FASEB JOURNAL LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,PULM CRIT CARE UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,RENAL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1992 VL 6 IS 5 BP A1603 EP A1603 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA HH271 UT WOS:A1992HH27100020 ER PT J AU DENEKE, SM BUKOWSKI, DM LAWRENCE, RA JENKINSON, SG AF DENEKE, SM BUKOWSKI, DM LAWRENCE, RA JENKINSON, SG TI COMPARISON OF CYSTINE TRANSPORT IN LUNG TYPE-II EPITHELIAL-CELLS AND PULMONARY-ARTERY ENDOTHELIAL-CELLS SO FASEB JOURNAL 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 FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1992 VL 6 IS 5 BP A1737 EP A1737 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA HH271 UT WOS:A1992HH27100798 ER PT J AU FLESCHER, E LEDBETTER, JA SCHIEVEN, GL FOSSUM, D TALAL, N AF FLESCHER, E LEDBETTER, JA SCHIEVEN, GL FOSSUM, D TALAL, N TI OXIDATIVE STRESS SUPPRESSES HUMAN T-CELL SIGNAL TRANSDUCTION SO FASEB JOURNAL LA English DT Meeting Abstract C1 BRISTOL MYERS SQUIBB PHARM RES INST,SEATTLE,WA 98121. 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 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1992 VL 6 IS 5 BP A1714 EP A1714 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA HH271 UT WOS:A1992HH27100664 ER PT J AU FRUMAN, DA KLEE, CB BIERER, BE BURAKOFF, SJ AF FRUMAN, DA KLEE, CB BIERER, BE BURAKOFF, SJ TI FK506 AND CSA INHIBIT CALCINEURIN PHOSPHATASE-ACTIVITY IN LYMPHOCYTES-T SO FASEB JOURNAL LA English DT Meeting Abstract C1 BRIGHAM & WOMENS HOSP,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NCI,BIOCHEM LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1992 VL 6 IS 5 BP A1692 EP A1692 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA HH271 UT WOS:A1992HH27100538 ER PT J AU HOOP, B BURTON, MD SOTOARAPE, I LIEBOVITCH, L KAZEMI, H AF HOOP, B BURTON, MD SOTOARAPE, I LIEBOVITCH, L KAZEMI, H TI FRACTAL ANALYSIS OF SPONTANEOUS BRAIN-STEM VENTILATORY OUTPUT SO FASEB JOURNAL LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. COLUMBIA UNIV COLL PHYS & SURG,NEW YORK,NY 10032. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1992 VL 6 IS 5 BP A2013 EP A2013 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA HH271 UT WOS:A1992HH27102395 ER PT J AU HUGHES, CCW JAIN, J RAO, A POBER, JS AF HUGHES, CCW JAIN, J RAO, A POBER, JS TI COSTIMULATION OF T-CELL ACTIVATION BY ENDOTHELIAL-CELLS MAY INVOLVE AUGMENTED C-FOS SYNTHESIS SO FASEB JOURNAL LA English DT Meeting Abstract C1 YALE UNIV,SCH MED,NEW HAVEN,CT 06536. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. RI Hughes, Christopher/F-7510-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1992 VL 6 IS 5 BP A1892 EP A1892 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA HH271 UT WOS:A1992HH27101691 ER PT J AU HUTCHISON, WG SPENCE, CR HALES, CA AF HUTCHISON, WG SPENCE, CR HALES, CA TI FURFURALDEHYDE, THE MAJOR COMPONENT OF COTTON SMOKE, DOES NOT CAUSE ACUTE PULMONARY-EDEMA IN SHEEP SO FASEB JOURNAL LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,PULM & CRIT CARE UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1992 VL 6 IS 5 BP A1818 EP A1818 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA HH271 UT WOS:A1992HH27101265 ER PT J AU JOSEPH, PM HALES, CA AF JOSEPH, PM HALES, CA TI ACROLEIN STIMULATES PGE2 AND 6-KETO-PGF1-ALPHA RELEASE FROM CULTURED PULMONARY VASCULAR ENDOTHELIAL-CELLS SO FASEB JOURNAL 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 FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1992 VL 6 IS 5 BP A1818 EP A1818 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA HH271 UT WOS:A1992HH27101268 ER PT J AU KRANZ, DM HOLMAN, PO HUANG, M TAN, KN ROTH, ME AF KRANZ, DM HOLMAN, PO HUANG, M TAN, KN ROTH, ME TI GERMLINE TRANSCRIPTS FROM SOME T-CELL RECEPTOR VARIABLE REGION GENES MAY ENCODE PROTEINS WITH NOVEL FUNCTIONS SO FASEB JOURNAL LA English DT Meeting Abstract C1 UNIV ILLINOIS,URBANA,IL 61801. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1992 VL 6 IS 5 BP A1976 EP A1976 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA HH271 UT WOS:A1992HH27102179 ER PT J AU LEUNIG, M GUTMANN, R FEYH, J GOETZ, AE MESSMER, K KASTENBAUER, E JAIN, RK AF LEUNIG, M GUTMANN, R FEYH, J GOETZ, AE MESSMER, K KASTENBAUER, E JAIN, RK TI INTERSTITIAL FLUID PRESSURE MEASURED IN HUMAN SQUAMOUS-CELL CARCINOMAS OF HEAD AND NECK REGION SO FASEB JOURNAL LA English DT Meeting Abstract C1 UNIV MUNICH,KLINIKUM GROSSHADERN,W-8000 MUNICH 70,GERMANY. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1992 VL 6 IS 5 BP A2079 EP A2079 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA HH271 UT WOS:A1992HH27102783 ER PT J AU LEUNIG, M GOETZ, AE DELLIAN, M ZETTERER, G GAMARRA, F MESSMER, K JAIN, RK AF LEUNIG, M GOETZ, AE DELLIAN, M ZETTERER, G GAMARRA, F MESSMER, K JAIN, RK TI POSSIBLE CORRELATION BETWEEN INTERSTITIAL FLUID PRESSURE AND THERAPEUTIC RESPONSE FOLLOWING TUMOR TREATMENT BY HYPERTHERMIA SO FASEB JOURNAL LA English DT Meeting Abstract C1 UNIV MUNICH,KLINIKUM GROSSHADERN,W-8000 MUNICH 70,GERMANY. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1992 VL 6 IS 5 BP A2079 EP A2079 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA HH271 UT WOS:A1992HH27102780 ER PT J AU MACLEAN, JA SU, Z GUO, Y WONG, JT AF MACLEAN, JA SU, Z GUO, Y WONG, JT TI ANTI-CD3-ANTI-CD25 (CD3,25) BISPECIFIC MONOCLONAL-ANTIBODY (BSMAB) - TARGETING OF ACTIVATED T-CELLS INVITRO SO FASEB JOURNAL LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1992 VL 6 IS 5 BP A2008 EP A2008 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA HH271 UT WOS:A1992HH27102369 ER PT J AU MELDER, RJ JAIN, RK AF MELDER, RJ JAIN, RK TI EFFECT OF IL2 AND ANTI-CYTOSKELETAL AGENTS ON NK CELL RIGIDITY SO FASEB JOURNAL LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1992 VL 6 IS 5 BP A2080 EP A2080 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA HH271 UT WOS:A1992HH27102787 ER PT J AU ORSON, FM THOMAS, DW MCSHAN, WM AF ORSON, FM THOMAS, DW MCSHAN, WM TI DIRECT DETECTION OF IL2R-ALPHA PROMOTER SPECIFIC OLIGONUCLEOTIDE BINDING TO GENOMIC DNA SO FASEB JOURNAL LA English DT Meeting Abstract C1 BAYLOR COLL MED,DEPT VET AFFAIRS MED CTR,HOUSTON,TX 77030. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1992 VL 6 IS 5 BP A1715 EP A1715 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA HH271 UT WOS:A1992HH27100669 ER PT J AU PEARSON, DA ABRAHAM, VS SACHS, DH HARTY, MW SYKES, M AF PEARSON, DA ABRAHAM, VS SACHS, DH HARTY, MW SYKES, M TI SELECTIVE-INHIBITION OF CD4 GRAFT-VS-HOST ACTIVITY IN IL-2-TREATED MICE SO FASEB JOURNAL LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02129. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1992 VL 6 IS 5 BP A1693 EP A1693 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA HH271 UT WOS:A1992HH27100543 ER PT J AU RAO, A JAIN, J MCCAFFREY, PG VALGEARCHER, VE AF RAO, A JAIN, J MCCAFFREY, PG VALGEARCHER, VE TI THE TRANSCRIPTION FACTOR AP-1 FOS JUN IS A COMPONENT OF NF-AT THE NUCLEAR FACTOR OF ACTIVATED T-CELLS SO FASEB JOURNAL LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR VIROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1992 VL 6 IS 5 BP A1642 EP A1642 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA HH271 UT WOS:A1992HH27100247 ER PT J AU RODEWALD, HR MOINGEON, P LUCICH, JL DOSIOU, C LOPEZ, P REINHERZ, EL AF RODEWALD, HR MOINGEON, P LUCICH, JL DOSIOU, C LOPEZ, P REINHERZ, EL TI DIRECT LINKAGE BETWEEN LYMPHOCYTE-T AND NATURAL-KILLER (NK) CELL LINEAGES AS REVEALED BY DEVELOPMENT OF EARLY FETAL THYMOCYTES INVITRO AND INVIVO SO FASEB JOURNAL LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,IMMUNOBIOL LAB,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,FLOW CYTOMETRY FACIL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1992 VL 6 IS 5 BP A1977 EP A1977 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA HH271 UT WOS:A1992HH27102185 ER PT J AU SANCHO, J KAMOUN, M CHOI, MS DASGUPTA, JD CHATILA, T GEHA, R TERHORST, C AF SANCHO, J KAMOUN, M CHOI, MS DASGUPTA, JD CHATILA, T GEHA, R TERHORST, C TI STIMULATION OF T-CELLS THROUGH THE TCR-CD3-COMPLEX INDUCES TYROSINE PHOSPHORYLATION OF A 70 KDA POLYPEPTIDE-CHAIN ASSOCIATED WITH THE CD3-ZETA CHAIN SO FASEB JOURNAL LA English DT Meeting Abstract C1 BETH ISRAEL HOSP,BOSTON,MA 02215. HOSP UNIV PENN,PHILADELPHIA,PA 19104. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. CHILDRENS HOSP,PHILADELPHIA,PA 19104. RI Sancho, Jaime/O-3228-2013 OI Sancho, Jaime/0000-0003-3852-7951 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1992 VL 6 IS 5 BP A1982 EP A1982 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA HH271 UT WOS:A1992HH27102216 ER PT J AU SCHINI, VB SCOTTBURDEN, T DURANTE, W ELIZONDO, E SCHAFER, A VANHOUTTE, PM AF SCHINI, VB SCOTTBURDEN, T DURANTE, W ELIZONDO, E SCHAFER, A VANHOUTTE, PM TI EICOSAPENTAENOIC ACID (EPA) ENHANCES THE ACTIVITY OF NITRIC-OXIDE SYNTHASE EVOKED BY INTERLEUKIN-1-BETA(IL-1-BETA) IN CULTURED SMOOTH-MUSCLE CELLS FROM HUMAN AORTA SO FASEB JOURNAL LA English DT Meeting Abstract C1 BAYLOR COLL MED,CTR EXPTL THERAPEUT,HOUSTON,TX 77030. HOUSTON VA MED CTR,HOUSTON,TX 77030. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1992 VL 6 IS 5 BP A1732 EP A1732 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA HH271 UT WOS:A1992HH27100769 ER PT J AU SHIMOUCH, A BLOCH, DB JANSSENS, SP BLOCH, KD AF SHIMOUCH, A BLOCH, DB JANSSENS, SP BLOCH, KD TI CAMP DECREASES EXPRESSION OF GENES ENCODING SOLUBLE GUANYLATE-CYCLASE SUBUNITS IN RFL-6 RAT LUNG FIBROBLASTS SO FASEB JOURNAL LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1992 VL 6 IS 5 BP A1847 EP A1847 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA HH271 UT WOS:A1992HH27101433 ER PT J AU THOMAS, LJ YEH, ETH AF THOMAS, LJ YEH, ETH TI DEFICIENT TRANSMEMBRANE SIGNAL TRANSDUCTION IN T-CELL GLYCOSYLATION MUTANTS SO FASEB JOURNAL LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,DEPT MED,ARTHRITIS UNIT,BOSTON,MA 02115. NR 2 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1992 VL 6 IS 5 BP A1986 EP A1986 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA HH271 UT WOS:A1992HH27102236 ER PT J AU VINK, J THOMAS, L BRUIJIN, JA MIHM, MC BYERS, HR AF VINK, J THOMAS, L BRUIJIN, JA MIHM, MC BYERS, HR TI ROLE OF BETA-1 INTEGRINS IN ORGAN SPECIFIC ADHESION OF HUMAN-MELANOMA CELLS-INVITRO SO FASEB JOURNAL LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,DIV DERMATOPATHOL,BOSTON,MA 02114. LEIDEN UNIV,DEPT PATHOL,2300 RA LEIDEN,NETHERLANDS. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1992 VL 6 IS 5 BP A1929 EP A1929 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA HH271 UT WOS:A1992HH27101910 ER PT J AU VIVIER, E ROCHET, N ACKERLY, M PETRINI, J KOCHAN, JP ANDERSON, P AF VIVIER, E ROCHET, N ACKERLY, M PETRINI, J KOCHAN, JP ANDERSON, P TI ASSOCIATION OF SIGMA-RELATED DIMERS WITH FC-GAMMA-RIIIA AND CD3 - TCR COMPLEXES SO FASEB JOURNAL LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. HOFFMANN LA ROCHE INC,NUTLEY,NJ 07110. RP VIVIER, E (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1992 VL 6 IS 5 BP A1691 EP A1691 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA HH271 UT WOS:A1992HH27100527 ER PT J AU WONG, JT CURIEL, T SCHOOLEY, R WALKER, B AF WONG, JT CURIEL, T SCHOOLEY, R WALKER, B TI ANTI-HIV CTL ACTIVITIES AND P24 SECRETION OF T-CELL SUBSETS PROPAGATED WITH BISPECIFIC MONOCLONAL-ANTIBODIES (BSMAB) SO FASEB JOURNAL LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1992 VL 6 IS 5 BP A1726 EP A1726 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA HH271 UT WOS:A1992HH27100734 ER PT J AU XIA, W TSAO, T PINTO, C KRADIN, R AF XIA, W TSAO, T PINTO, C KRADIN, R TI IA+ DENDRITIC CELLS BIND AVIDLY TO FIBRONECTIN AND DISPLAY IFN-GAMMA-DEPENDENT BINDING TO LAMININ SO FASEB JOURNAL LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1992 VL 6 IS 5 BP A1706 EP A1706 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA HH271 UT WOS:A1992HH27100618 ER PT J AU ZHANG, ZJ SHOELSON, S MILLER, A WEINER, HL AF ZHANG, ZJ SHOELSON, S MILLER, A WEINER, HL TI INSULITIS IS SUPPRESSED IN NOD MICE BY ORAL-ADMINISTRATION OF INSULIN PEPTIDES AND GLUCAGON SO FASEB JOURNAL LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,JOSLIN DIABET CTR,BOSTON,MA 02115. NR 1 TC 11 Z9 11 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1992 VL 6 IS 5 BP A1693 EP A1693 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA HH271 UT WOS:A1992HH27100540 ER PT J AU ISOBE, M YAGITA, H OKUMURA, K IHARA, A AF ISOBE, M YAGITA, H OKUMURA, K IHARA, A TI SPECIFIC ACCEPTANCE OF CARDIAC ALLOGRAFT AFTER TREATMENT WITH ANTIBODIES TO ICAM-1 AND LFA-1 SO SCIENCE LA English DT Article ID ADHESION MOLECULE-1 ICAM-1; CELL-ASSOCIATED ANTIGEN; MEDIATED CYTO-TOXICITY; MONOCLONAL-ANTIBODY; IMMUNE-SYSTEM; ACTIVATION; LIGAND; INHIBITION; RECEPTORS; MALA-2 AB An indefinite survival of cardiac allografts between fully incompatible mice strains was observed when monoclonal antibodies (MAbs) to intercellular adhesion molecule-1 (ICAM-1) and leukocyte function-associated antigen-1 (LFA-1) were simultaneously administered after the transplantation for 6 days. Mice with long-term surviving cardiac allografts accepted skin grafts from the donor-strain but rejected skin grafts from a third-party strain. Because MAbs to ICAM-1 or LFA-1 alone were insufficient for prolonged tolerance, the two MAbs probably acted synergistically to induce specific unresponsiveness. Thus, ICAM-1-LFA-1 adhesion participates in the induction of allograft rejection and MAbs may be useful as therapeutic agents. C1 MASSACHUSETTS GEN HOSP,CARDIAC UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,PATHOL RES LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. JUNTENDO UNIV,SCH MED,DEPT IMMUNOL,TOKYO 113,JAPAN. NR 26 TC 771 Z9 776 U1 0 U2 2 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD FEB 28 PY 1992 VL 255 IS 5048 BP 1125 EP 1127 DI 10.1126/science.1347662 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA HF632 UT WOS:A1992HF63200040 PM 1347662 ER PT J AU MILLER, DM SHEN, MM SHAMU, CE BURGLIN, TR RUVKUN, G DUBOIS, ML GHEE, M WILSON, L AF MILLER, DM SHEN, MM SHAMU, CE BURGLIN, TR RUVKUN, G DUBOIS, ML GHEE, M WILSON, L TI C-ELEGANS UNC-4 GENE ENCODES A HOMEODOMAIN PROTEIN THAT DETERMINES THE PATTERN OF SYNAPTIC INPUT TO SPECIFIC MOTOR NEURONS SO NATURE LA English DT Article ID NEMATODE CAENORHABDITIS-ELEGANS; TRANSPOSABLE ELEMENT; NERVOUS-SYSTEM; CELL LINEAGES; DROSOPHILA; HOMEOBOX; EXPRESSION; PRODUCT AB THE creation of neural circuits depends on the formation of synapses between specific sets of neurons. Little is known, however, of the molecular mechanisms governing synaptic choice. A mutation in the unc-4 gene alters the pattern of synaptic input to one class of motor neurons in the Caenorhabditis elegans ventral nerve cord. In unc-4(e120), the presynaptic partners of VA motor neurons are replaced with interneurons appropriate to motor neurons of the VB class. This change in neural specificity is not accompanied by any detectable effects on neuronal morphology or process extension 1,2. We show that the absence of a functional unc-4 gene product accounts for the mutant phenotype. The unc-4 gene encodes a homeodomain protein and thus is likely to function as a transcription factor. The limited effect of the unc-4 null mutation on cell fate may mean that unc-4 regulates the expression of a small number of target genes and that the products of these genes are directly involved in the choice of synaptic partners. C1 MRC,MOLEC BIOL LAB,CAMBRIDGE CB2 2QH,ENGLAND. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. RP MILLER, DM (reprint author), DUKE UNIV,MED CTR,DEPT CELL BIOL,DURHAM,NC 27710, USA. RI Shen, Michael/C-7546-2009 OI Shen, Michael/0000-0002-4042-1657 NR 40 TC 138 Z9 140 U1 1 U2 4 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD FEB 27 PY 1992 VL 355 IS 6363 BP 841 EP 845 DI 10.1038/355841a0 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA HF636 UT WOS:A1992HF63600061 PM 1347150 ER PT J AU ELLINGTON, AD SZOSTAK, JW AF ELLINGTON, AD SZOSTAK, JW TI SELECTION INVITRO OF SINGLE-STRANDED-DNA MOLECULES THAT FOLD INTO SPECIFIC LIGAND-BINDING STRUCTURES SO NATURE LA English DT Article ID EVOLUTION; POLYMERASE AB WE have isolated a set of ligand-binding DNA sequences from a large pool of random sequence DNAs by selection and amplification in vitro, using similar methods to those described for the isolation of ligand-binding RNAs 1. The ligand-DNA interactions are both sequence- and ligand-specific, and are dependent on proper folding of the single-stranded DNA. Some ligands led to the isolation of more DNA sequences than RNA sequences, and vice versa. Analysis of individual sequences reveals that ligand binding is DNA-specific; RNAs of identical sequence could not interact with the same ligands. Ligand-binding DNAs might be more suitable than RNAs as potential pharmacological reagents 2-4 because of the greater stability of DNA. The apparent primacy of RNA in the early evolution of life 5-7 may have been due to its availability rather than to its functional superiority. RP ELLINGTON, AD (reprint author), MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114, USA. NR 12 TC 406 Z9 423 U1 11 U2 84 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD FEB 27 PY 1992 VL 355 IS 6363 BP 850 EP 852 DI 10.1038/355850a0 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA HF636 UT WOS:A1992HF63600064 PM 1538766 ER PT J AU FINKELSTEIN, JS NEER, RM BILLER, BMK CRAWFORD, JD KLIBANSKI, A AF FINKELSTEIN, JS NEER, RM BILLER, BMK CRAWFORD, JD KLIBANSKI, A TI OSTEOPENIA IN MEN WITH A HISTORY OF DELAYED PUBERTY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID BONE-MINERAL CONTENT; IDIOPATHIC HYPOGONADOTROPIC HYPOGONADISM; DUAL PHOTON-ABSORPTIOMETRY; ALKALINE-PHOSPHATASE; PHYSICAL-ACTIVITY; TOTAL-BODY; DENSITY; OSTEOPOROSIS; WOMEN; MASS AB Background and Methods. The effect of delayed puberty on peak bone mineral density in men is unknown. To determine whether such a delay reduces normal peak bone density and leads to osteopenia during adulthood, we measured radial bone mineral density by single-photon absorptiometry and spinal bone mineral density by dual-energy x-ray absorptiometry in 23 men who had a history of constitutionally delayed puberty and 21 men who underwent normal puberty. Their mean ages were 26 and 24 years, respectively. The groups were matched for other factors known to affect bone mass. Results. The mean (+/- SD) radial bone mineral density was significantly lower in the men with a history of delayed puberty than in the normal men (0.73 +/- 0.07 vs. 0.80 +/- 0.05 g per square centimeter; P < 0.0002). Spinal bone mineral density was also significantly lower in the men with delayed puberty than in the normal men (1.03 +/- 0.10 vs. 1.13 +/- 0.11 g per square centimeter; P < 0.003). Radial bone density was at least 1 SD below the mean value for the normal men in 15 of the 23 men with a history of delayed puberty, and spinal bone density was similarly decreased in 10 of the 23. Conclusions. Adult men with a history of constitutionally delayed puberty have decreased radial and spinal bone mineral density. These findings suggest that the timing of puberty is an important determinant of peak bone density in men. Because the peak bone mineral density achieved during young adulthood is a major determinant of bone density in later life, men in whom puberty was delayed may be at increased risk for osteoporotic fractures when they are older. C1 MASSACHUSETTS GEN HOSP,DEPT MED,NEUROENDOCRINE UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PEDIAT,BOSTON,MA 02114. RP FINKELSTEIN, JS (reprint author), MASSACHUSETTS GEN HOSP,DEPT MED,ENDOCRINE UNIT,BULFINCH 3,BOSTON,MA 02114, USA. FU NCRR NIH HHS [RR-1066]; NICHD NIH HHS [HD-21204] NR 40 TC 300 Z9 304 U1 0 U2 2 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD FEB 27 PY 1992 VL 326 IS 9 BP 600 EP 604 DI 10.1056/NEJM199202273260904 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA HF633 UT WOS:A1992HF63300004 PM 1734250 ER PT J AU SEMIGRAN, MJ DINSMORE, RE KING, ME BLAND, EF WHITE, PD SCULLY, RE BROOKS, DR NEWTON, JR AF SEMIGRAN, MJ DINSMORE, RE KING, ME BLAND, EF WHITE, PD SCULLY, RE BROOKS, DR NEWTON, JR TI WIDE-COMPLEX TACHYCARDIA IN A 65-YEAR-OLD WOMAN WITHOUT PREVIOUS EVIDENCE OF CARDIAC DISEASE - TRUE ANEURYSM OF LEFT-VENTRICLE, CONGENITAL SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Discussion ID CORONARY-ARTERY SURGERY; MYOCARDIAL-INFARCTION; SURGICAL-TREATMENT; NATURAL-HISTORY; PSEUDOANEURYSM; RECOGNITION; DIAGNOSIS; DIVERTICULUM; ARRHYTHMIAS C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP SEMIGRAN, MJ (reprint author), MASSACHUSETTS GEN HOSP,MED,BOSTON,MA 02114, USA. NR 48 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 FEB 27 PY 1992 VL 326 IS 9 BP 624 EP 633 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA HF633 UT WOS:A1992HF63300008 ER PT J AU BHANDARI, B GRANDALIANO, G ABBOUD, H AF BHANDARI, B GRANDALIANO, G ABBOUD, H TI PLATELET DERIVED GROWTH-FACTOR (PDGF) A-CHAIN AND B-CHAIN GENE-EXPRESSION IN HUMAN MESANGIAL CELLS - MESSENGER-RNA ABUNDANCE, TRANSCRIPTION AND MESSENGER-RNA STABILITY SO FASEB JOURNAL LA English DT Meeting Abstract C1 AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX 78284. RI Grandaliano, Giuseppe/G-2963-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 26 PY 1992 VL 6 IS 4 BP A1077 EP A1077 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA HG719 UT WOS:A1992HG71900820 ER PT J AU BOYLE, LA PANDOLFI, F SCOTT, S KURNICK, JT AF BOYLE, LA PANDOLFI, F SCOTT, S KURNICK, JT TI FIBROBLASTS MEDIATE PRESERVATION OF LYMPHOCYTE VIABILITY AND FUNCTION SO FASEB JOURNAL LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 26 PY 1992 VL 6 IS 4 BP A941 EP A941 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA HG719 UT WOS:A1992HG71900025 ER PT J AU CHOWANSKI, Z HARMATZ, P WEISSCARRINGTON, P CARTER, E DASCOLI, J CUNNINGHAM, J AF CHOWANSKI, Z HARMATZ, P WEISSCARRINGTON, P CARTER, E DASCOLI, J CUNNINGHAM, J TI THE EFFECT OF DIETARY COPPER (CU) AND SEVERE THERMAL-INJURY ON MURINE SYSTEMIC AND MUCOSAL IMMUNE-RESPONSE SO FASEB JOURNAL LA English DT Meeting Abstract C1 SHRINERS BURN INST,BOSTON,MA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. UNIV MASSACHUSETTS,AMHERST,MA 01003. WESTSIDE VET ADM MED CTR,CHICAGO,IL. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 26 PY 1992 VL 6 IS 4 BP A1096 EP A1096 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA HG719 UT WOS:A1992HG71900926 ER PT J AU DUPONTVERSTEEGDEN, EE FREVALDENHOVEN, AM MCCARTER, RJ KATZ, MS AF DUPONTVERSTEEGDEN, EE FREVALDENHOVEN, AM MCCARTER, RJ KATZ, MS TI ELEVATED LEVELS OF ALBUMIN IN MUSCLES OF MDX MICE SO FASEB JOURNAL LA English DT Meeting Abstract C1 UNIV TEXAS,HLTH SCI CTR,DEPT PHYSIOL,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,GRECC,SAN ANTONIO,TX 78284. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 26 PY 1992 VL 6 IS 4 BP A963 EP A963 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA HG719 UT WOS:A1992HG71900155 ER PT J AU FREEDMAN, A MUNRO, JM NADLER, L AF FREEDMAN, A MUNRO, JM NADLER, L TI REGULATION OF NORMAL B-CELL PROLIFERATION BY FOLLICULAR DENDRITIC CELLS SO FASEB JOURNAL LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 26 PY 1992 VL 6 IS 4 BP A1410 EP A1410 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA HG719 UT WOS:A1992HG71902744 ER PT J AU GWOSDOW, AR OCONNELL, NA SPENCER, JA KUMAR, MSA ABOUSAMRA, AB AF GWOSDOW, AR OCONNELL, NA SPENCER, JA KUMAR, MSA ABOUSAMRA, AB TI INTERLEUKIN-1 INDUCES CORTICOSTERONE RELEASE BY ADRENERGIC-STIMULATION FROM THE RAT ADRENAL-GLAND SO FASEB JOURNAL LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. SHRINERS BURN INST,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 26 PY 1992 VL 6 IS 4 BP A1186 EP A1186 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA HG719 UT WOS:A1992HG71901443 ER PT J AU HAHN, WC ROSENSTEIN, Y CALVO, V BURAKOFF, SJ BIERER, BE AF HAHN, WC ROSENSTEIN, Y CALVO, V BURAKOFF, SJ BIERER, BE TI CHANGING THE TERMINAL AMINO-ACID OF CD2 ABROGATES TCR REGULATION OF CD2 AVIDITY AND LIMITS T-CELL RESPONSIVENESS SO FASEB JOURNAL LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 26 PY 1992 VL 6 IS 4 BP A1224 EP A1224 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA HG719 UT WOS:A1992HG71901663 ER PT J AU HORWITZ, JI TOMPKINS, RG YARMUSH, ML AF HORWITZ, JI TOMPKINS, RG YARMUSH, ML TI IMMOBILIZED IL-2 PRESERVES THE VIABILITY OF AN IL-2 DEPENDENT CELL-LINE SO FASEB JOURNAL LA English DT Meeting Abstract C1 MIT,DEPT CHEM ENGN,CAMBRIDGE,MA 02139. MASSACHUSETTS GEN HOSP,SURG SERV,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 26 PY 1992 VL 6 IS 4 BP A1079 EP A1079 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA HG719 UT WOS:A1992HG71900828 ER PT J AU KANDIL, O FISHMAN, JA ROSE, RM REMOLD, HG AF KANDIL, O FISHMAN, JA ROSE, RM REMOLD, HG TI UP-REGULATION OF INTERLEUKIN-6 (IL-6) IN HIV-INFECTED HUMAN MACROPHAGES COINFECTED WITH PNEUMOCYSTIS-CARINII (PC) SO FASEB JOURNAL LA English DT Meeting Abstract C1 HARVARD UNIV,NEW ENGLAND DEACONESS HOSP,SCH MED,BOSTON,MA 02215. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,BOSTON,MA 02115. HARVARD UNIV,MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 2 Z9 2 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 26 PY 1992 VL 6 IS 4 BP A1156 EP A1156 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA HG719 UT WOS:A1992HG71901268 ER PT J AU KERSTEN, CM KURNICK, JT RUBIN, RH MCCLUSKEY, RT AF KERSTEN, CM KURNICK, JT RUBIN, RH MCCLUSKEY, RT TI BACTERIAL-ANTIGEN SPECIFIC LYMPHOCYTES-T IN HUMAN PYELONEPHRITIS SO FASEB JOURNAL LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 26 PY 1992 VL 6 IS 4 BP A1070 EP A1070 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA HG719 UT WOS:A1992HG71900776 ER PT J AU KORTY, PE TEDDER, TF SHEVACH, EM AF KORTY, PE TEDDER, TF SHEVACH, EM TI IDENTIFICATION OF THE LIGANDS FOR THE CD59 AND LY-6A.2 CELL-SURFACE ANTIGENS SO FASEB JOURNAL LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NIAID,LI,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 26 PY 1992 VL 6 IS 4 BP A1224 EP A1224 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA HG719 UT WOS:A1992HG71901664 ER PT J AU KRADIN, R XIA, W PIKE, M AF KRADIN, R XIA, W PIKE, M TI PULMONARY DENDRITIC CELLS SHOW ENHANCED MOTILITY IN RESPONSE TO INTERLEUKIN-2 SO FASEB JOURNAL LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 26 PY 1992 VL 6 IS 4 BP A1409 EP A1409 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA HG719 UT WOS:A1992HG71902736 ER PT J AU KURNICK, JT CHATILA, MK HAWES, GE GROVE, BH WAITKIS, R STRUJK, L VANDENELSEN, P AF KURNICK, JT CHATILA, MK HAWES, GE GROVE, BH WAITKIS, R STRUJK, L VANDENELSEN, P TI PCR ANALYSIS OF SYNOVIAL INFILTRATING LYMPHOCYTES SHOWS CLUSTERING OF TCR V-REGION USAGE IN ARTHRITIS SO FASEB JOURNAL LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. LEIDEN UNIV,DEPT IMMUNOHEMATOL,2300 RA LEIDEN,NETHERLANDS. LEIDEN UNIV,BLOOD BANK,2300 RA LEIDEN,NETHERLANDS. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 26 PY 1992 VL 6 IS 4 BP A1119 EP A1119 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA HG719 UT WOS:A1992HG71901058 ER PT J AU MENU, E HAHN, WC BOTHWELL, ALM SIMS, PJ BIERER, BE AF MENU, E HAHN, WC BOTHWELL, ALM SIMS, PJ BIERER, BE TI OVERLAPPING BUT NONIDENTICAL BINDING-SITES ON CD2 FOR CD58 AND A 2ND LIGAND, CD59 SO FASEB JOURNAL LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. YALE UNIV,SCH MED,NEW HAVEN,CT 06510. OKLAHOMA MED RES FDN,OKLAHOMA CITY,OK 73104. RI MENU, Elisabeth/B-2886-2010 OI MENU, Elisabeth/0000-0001-8844-9328 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 26 PY 1992 VL 6 IS 4 BP A1224 EP A1224 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA HG719 UT WOS:A1992HG71901661 ER PT J AU MOLINA, IJ KENNEY, DM ROSEN, FS REMOLDODONNELL, E AF MOLINA, IJ KENNEY, DM ROSEN, FS REMOLDODONNELL, E TI LONG-TERM ALLOSPECIFIC T-CELL LINES AS A TOOL TO DEFINE DEFECTS IN THE WISKOTT-ALDRICH SYNDROME SO FASEB JOURNAL LA English DT Meeting Abstract C1 CHILDRENS HOSP MED CTR,CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 26 PY 1992 VL 6 IS 4 BP A1120 EP A1120 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA HG719 UT WOS:A1992HG71901068 ER PT J AU NAGLERANDERSON, C MCNAIR, LA CRADOCK, A AF NAGLERANDERSON, C MCNAIR, LA CRADOCK, A TI SELF REACTIVE, GAMMA-DELTA T-CELL RECEPTOR+, LYMPHOCYTES FROM THE INTESTINAL EPITHELIUM OF WEANLING MICE SO FASEB JOURNAL LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,MUCOSAL IMMUNOL LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02129. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 26 PY 1992 VL 6 IS 4 BP A1408 EP A1408 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA HG719 UT WOS:A1992HG71902733 ER PT J AU SOTOARAPE, I BEAGLE, J BURTON, M KAZEMI, H AF SOTOARAPE, I BEAGLE, J BURTON, M KAZEMI, H TI ROLE OF GLUTAMATE IN CENTRAL VENTILATORY OUTPUT AND IN THE HYPOXIC VENTILATORY RESPONSE IN THE RAT SO FASEB JOURNAL LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,PULM & CRIT CARE UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 26 PY 1992 VL 6 IS 4 BP A1508 EP A1508 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA HG719 UT WOS:A1992HG71903310 ER PT J AU SUNDAY, ME PATIDAR, K WILLETT, CG AF SUNDAY, ME PATIDAR, K WILLETT, CG TI ALTERED REGULATION OF C-MYC PROTOONCOGENE AND RB AND P53 TUMOR SUPPRESSOR GENES IN A HAMSTER MODEL OF PRENEOPLASTIC LUNG INJURY SO FASEB JOURNAL LA English DT Meeting Abstract C1 BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 26 PY 1992 VL 6 IS 4 BP A1029 EP A1029 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA HG719 UT WOS:A1992HG71900541 ER PT J AU SYKES, M BODINE, DM MOULTON, AD PEARSON, DA NIENHUIS, AW SACHS, DH AF SYKES, M BODINE, DM MOULTON, AD PEARSON, DA NIENHUIS, AW SACHS, DH TI TOLERANCE INDUCTION USING AUTOLOGOUS BONE-MARROW MODIFIED WITH AN ALLOGENEIC CLASS-I MHC GENE SO FASEB JOURNAL LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114. NHLBI,CLIN HEMATOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 26 PY 1992 VL 6 IS 4 BP A1405 EP A1405 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA HG719 UT WOS:A1992HG71902719 ER PT J AU TOMERA, JF KUKULKA, SP LILFORD, K AF TOMERA, JF KUKULKA, SP LILFORD, K TI BURN TRAUMA-INDUCED INTERACTIONS OF THE FORMS OF H-3 INOSITOL IN SKELETAL-MUSCLE SO FASEB JOURNAL LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT ANAESTHESIOL,BOSTON,MA 02115. SHRINERS BURN INST,ANESTHESIA SERV,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 26 PY 1992 VL 6 IS 4 BP A959 EP A959 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA HG719 UT WOS:A1992HG71900134 ER PT J AU VENEGAS, JG TSUZAKI, K SIMON, B HALES, CA AF VENEGAS, JG TSUZAKI, K SIMON, B HALES, CA TI APEX-TO-BASE DIFFERENCES IN REGIONAL GAS-TRANSPORT DURING HFV ARE CAUSED BY REGIONAL LUNG-TO-CHEST WALL COUPLING SO FASEB JOURNAL LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 26 PY 1992 VL 6 IS 4 BP A1513 EP A1513 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA HG719 UT WOS:A1992HG71903341 ER PT J AU VOGT, JA YU, YM FISCHMAN, A CHAPMAN, TE TOMPKINS, RT BURKE, JF AF VOGT, JA YU, YM FISCHMAN, A CHAPMAN, TE TOMPKINS, RT BURKE, JF TI DETERMINATION OF KREBS-CYCLE PARAMETERS IN RABBIT LIVER BY C-13-NMR SPECTROSCOPY SO FASEB JOURNAL LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. SHRINERS BURN UNIT,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 26 PY 1992 VL 6 IS 4 BP A1519 EP A1519 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA HG719 UT WOS:A1992HG71903377 ER PT J AU WHITEHEAD, AS DEBEER, MC STEEL, DM RITS, M LELIAS, JM LANE, WS DEBEER, FC AF WHITEHEAD, AS DEBEER, MC STEEL, DM RITS, M LELIAS, JM LANE, WS DEBEER, FC TI IDENTIFICATION OF NOVEL MEMBERS OF THE SERUM AMYLOID-A PROTEIN SUPERFAMILY AS CONSTITUTIVE APOLIPOPROTEINS OF HIGH-DENSITY-LIPOPROTEIN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID C-REACTIVE PROTEIN; NUCLEOTIDE-SEQUENCE; MESSENGER-RNAS; GENE FAMILY; SAA; MOUSE; INDUCTION; NITROCELLULOSE; INFLAMMATION; METABOLISM AB A novel serum amyloid A protein (SAA) has been identified as a normal apolipoprotein component of non-acute phase high density lipoprotein. This novel SAA has been designated "constitutive" SAA (C-SAA) to distinguish it from "acute phase" SAA (A-SAA). C-SAA was partially sequenced, and immunochemical analyses indicated that it constitutes a distinct subclass of apolipoproteins within the SAA superfamily. A C-SAA cDNA clone was isolated from a human liver library and sequenced. The clone predicts a pre-C-SAA molecule of 130 residues from which an 18-residue leader peptide is cleaved. The 112-residue mature molecule is 8 residues longer than human A-SAA; the size difference is due to the presence of an octapeptide between positions 70 and 77 that is not found in the corresponding region of human A-SAA. Paradoxically, octapeptides of similar composition are found at similar positions in the A-SAAs of a number of other species. The C-SAA octapeptide specifies the first two residues of a NSS tripeptide, the only potential N-linked glycosylation site in the molecule. Studies indicate that approximately 50% of these sites are glycosylated, thereby giving rise to two size classes, 14 and 19 kDa, of C-SAA in vivo. Human acute phase liver contains little C-SAA mRNA relative to the levels of A-SAA mRNA, and the treatment of PLC/PRF/5 hepatoma cells with monocyte-conditioned medium does not induce C-SAA mRNA concentrations to detectable levels, in contrast to the massive induction of A-SAA mRNA observed. C-SAA is therefore not a major acute phase reactant. C1 UNIV KENTUCKY,ALBERT B CHANDLER MED CTR,DEPT MED,MN614,800 ROSE ST,LEXINGTON,KY 40536. CHILDRENS HOSP MED CTR,DEPT IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. CTR BLOOD RES,BOSTON,MA 02115. DEPT VET AFFAIRS MED CTR,LEXINGTON,KY 40511. HARVARD UNIV,HARVARD MICROCHEM FACIL,CAMBRIDGE,MA 02138. BETH ISRAEL HOSP,DEPT HEMATOL & ONCOL,BOSTON,MA 02215. FU PHS HHS [2T32A107306] NR 47 TC 143 Z9 146 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 25 PY 1992 VL 267 IS 6 BP 3862 EP 3867 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HE607 UT WOS:A1992HE60700050 PM 1740433 ER PT J AU SUNDSETH, SS ALBERTA, JA WAXMAN, DJ AF SUNDSETH, SS ALBERTA, JA WAXMAN, DJ TI SEX-SPECIFIC, GROWTH HORMONE-REGULATED TRANSCRIPTION OF THE CYTOCHROME-P450 2C11 AND 2C12 GENES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RAT-LIVER CYTOCHROME-P-450; INVITRO TRANSCRIPTION; BINDING-PROTEIN; C-FOS; EXPRESSION; PITUITARY; ALPHA-2U-GLOBULIN; HEPATOCYTES; SECRETION; GLAND AB Growth hormone (GH) differentially regulates the expression of several male-specific and female-specific liver cytochrome P450 mRNAs as a function of its sex-dependent ultradian secretory pattern. Pulsatile GH release stimulates expression of the male-specific P450 2C11, while a continuous GH secretion pattern suppresses expression of 2C11 and stimulates the expression of the female-specific P450 2C12. To help define the level at which GH regulates the expression of 2C11 and 2C12 mRNA, liver nuclear RNA samples isolated from rats differing in GH status were analyzed for 2C11 and 2C12 hnRNAs by hybridization to 2C11 and 2C12 gene-specific exonic oligonucleotide probes, as well as exon/intron junction probes. The 2C11 and 2C12 hnRNAs were found to be responsive to circulating GH profiles in a manner indistinguishable from the corresponding mature, cytoplasmic mRNAs, with no 2C12 mRNA precursors found in untreated male or hypophysectomized female liver nuclei, and no 2C11 mRNA precursors in untreated female or hypophysectomized male liver nuclei. Thus, transport of 2C11 and 2C12 RNA to the cytoplasm and cytoplasmic mRNA stability are unlikely to be important GH-regulated control points for sex-specific P450 RNA expression. Run-on transcription analysis further established that GH regulates the sex-specific expression of the 2C11 and 2C12 genes at the level of transcript initiation. Transcription was also shown to be the major step for regulation of the male-specific P450 2A2 RNA, whose expression, unlike 2C11, is not obligatorily dependent on pulsatile GH release. In vitro footprinting analysis of 2C11 and 2C12 promoter fragments incubated with liver nuclear proteins isolated from rats differing in GH status revealed several sex- and GH-dependent differences in DNase cleavage patterns ("hypersensitivity sites"), demonstrating that GH can regulate specific protein-DNA interactions in the 5'-flanking sequences of these two genes. In vitro transcription assays driven by 2C11 and 2C12 5'-flanking DNA sequences fused to TATAA box-G-less cassette template constructs did not, however, faithfully mimic the sex-specific transcription of the 2C11 and 2C12 genes, indicating that additional cis-elements or trans-acting factors may be required to achieve the transcriptional regulation of these genes that occurs in vivo. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,JF-525,44 BINNEY ST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. FU NIDDK NIH HHS [DK-33765, R01 DK033765] NR 58 TC 120 Z9 120 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 25 PY 1992 VL 267 IS 6 BP 3907 EP 3914 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HE607 UT WOS:A1992HE60700057 PM 1740438 ER PT J AU SUNDSETH, SS WAXMAN, DJ AF SUNDSETH, SS WAXMAN, DJ TI SEX-DEPENDENT EXPRESSION AND CLOFIBRATE INDUCIBILITY OF CYTOCHROME-P450 4A FATTY-ACID OMEGA-HYDROXYLASES - MALE SPECIFICITY OF LIVER AND KIDNEY CYP4A2 MESSENGER-RNA AND TISSUE-SPECIFIC REGULATION BY GROWTH-HORMONE AND TESTOSTERONE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PEROXISOMAL BETA-OXIDATION; RAT-LIVER; ARACHIDONIC-ACID; GENE-EXPRESSION; LAURIC ACID; TRANSCRIPTIONAL REGULATION; PHENOBARBITAL INDUCTION; RENAL CYTOCHROME-P-450; COMPLEMENTARY-DNA; P-450 FORMS AB The induction of liver cytochrome P450 4A-catalyzed fatty acid omega-hydroxylase activity by clofibrate and other peroxisome proliferators has been proposed to be causally linked to the ensuing proliferation of peroxisomes in rat liver. Since female rats are less responsive than males to peroxisome proliferation induced by clofibrate, the influence of gender and hormonal status on the basal and clofibrate-inducible expression of the 4A P450s was examined. Northern blot analysis using gene-specific oligonucleotide probes revealed that in the liver, P450 4A1 and 4A3 mRNAs are induced to a much greater extent in male as compared to female rats following clofibrate treatment, whereas P450 4A2 mRNA is altogether absent from female rat liver. Male-specific expression of P450 4A2 mRNA was also observed in kidney. Western blot analysis indicated that a similar sex dependence characterizes both the basal expression and the clofibrate inducibility of the corresponding P450 4A proteins. This suggests that the lower responsiveness of female rats to clofibrate-induced peroxisome proliferation may reflect the lower inducibility of the P450 4A fatty acid hydroxylase enzymes in this sex. Investigation of the contribution of pituitary-dependent hormones to the male-specific expression of 4A2 revealed that this P450 mRNA is fully suppressed in liver following exposure to the continuous plasma growth hormone profile that characterizes adult female rats; in this and other regards liver P450 4A2 is regulated in a manner that is similar, but not identical to, P450 3A2, a male-specific testosterone 6 beta-hydroxylase. In contrast, kidney 4A2 expression, although also male-specific, was not suppressed by continuous growth hormone treatment, but was regulated by pathways that, in part, involve testosterone as a positive regulator. The male-specific expression of liver and kidney P450 4A2 is thus under the control of distinct pituitary-dependent hormones acting in a tissue-specific manner. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,RM JF-525,44 BINNEY ST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. FU NIDDK NIH HHS [DK 33765, R01 DK033765] NR 60 TC 193 Z9 194 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 25 PY 1992 VL 267 IS 6 BP 3915 EP 3921 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HE607 UT WOS:A1992HE60700058 PM 1740439 ER PT J AU STGEORGEHYSLOP, PH OHNO, H GUSELLA, JF MCKEITHAN, T AF STGEORGEHYSLOP, PH OHNO, H GUSELLA, JF MCKEITHAN, T TI THE BCL3 LOCUS ON CHROMOSOME-19 DISPLAYS AN INFORMATIVE MICROSATELLITE POLYMORPHISM SO NUCLEIC ACIDS RESEARCH LA English DT Note C1 UNIV CHICAGO,DEPT PATHOL,CHICAGO,IL 60687. UNIV CHICAGO,DEPT MED,CHICAGO,IL 60687. MASSACHUSETTS GEN HOSP,MOLEC NEUROGENET LAB,BOSTON,MA 02114. RP STGEORGEHYSLOP, PH (reprint author), UNIV TORONTO,DEPT MED & NEUROL,TANZ NEUROSCI BLDG,6 QUEENS PK CRESCENT,TORONTO M5S 1A8,ONTARIO,CANADA. FU NCI NIH HHS [CA49207]; NHGRI NIH HHS [HG00317] NR 3 TC 9 Z9 9 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD FEB 25 PY 1992 VL 20 IS 4 BP 927 EP 927 DI 10.1093/nar/20.4.927 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HG350 UT WOS:A1992HG35000060 PM 1542596 ER PT J AU KWIATKOWSKI, DJ GUSELLA, JF AF KWIATKOWSKI, DJ GUSELLA, JF TI DINUCLEOTIDE REPEAT POLYMORPHISM AT THE D9S112 LOCUS (9Q31-34) SO NUCLEIC ACIDS RESEARCH LA English DT Note C1 MASSACHUSETTS GEN HOSP, NEUROGENET LAB, BOSTON, MA 02114 USA. RP KWIATKOWSKI, DJ (reprint author), BRIGHAM & WOMENS HOSP, DIV EXPTL MED, 221 LONGWOOD AVE, BOSTON, MA 02115 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD FEB 25 PY 1992 VL 20 IS 4 BP 930 EP 930 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HG350 UT WOS:A1992HG35000066 ER PT J AU KWIATKOWSKI, DJ GUSELLA, JF AF KWIATKOWSKI, DJ GUSELLA, JF TI DINUCLEOTIDE REPEAT POLYMORPHISM AT THE D9S115 LOCUS (9Q31-34) SO NUCLEIC ACIDS RESEARCH LA English DT Note C1 MASSACHUSETTS GEN HOSP, NEUROGENET LAB, BOSTON, MA 02114 USA. RP KWIATKOWSKI, DJ (reprint author), BRIGHAM & WOMENS HOSP, DIV EXPTL MED, 221 LONGWOOD AVE, BOSTON, MA 02115 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD FEB 25 PY 1992 VL 20 IS 4 BP 930 EP 930 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HG350 UT WOS:A1992HG35000067 ER PT J AU KWIATKOWSKI, DJ GUSELLA, JF AF KWIATKOWSKI, DJ GUSELLA, JF TI DINUCLEOTIDE REPEAT POLYMORPHISM AT THE D9S116 LOCUS (9Q31-34) SO NUCLEIC ACIDS RESEARCH LA English DT Note C1 MASSACHUSETTS GEN HOSP, NEUROGENET LAB, BOSTON, MA 02114 USA. RP KWIATKOWSKI, DJ (reprint author), BRIGHAM & WOMENS HOSP, DIV EXPTL MED, 221 LONGWOOD AVE, BOSTON, MA 02115 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD FEB 25 PY 1992 VL 20 IS 4 BP 931 EP 931 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HG350 UT WOS:A1992HG35000068 ER PT J AU KWIATKOWSKI, DJ GUSELLA, JF AF KWIATKOWSKI, DJ GUSELLA, JF TI DINUCLEOTIDE REPEAT POLYMORPHISM AT THE D9S118 LOCUS (9Q31-34) SO NUCLEIC ACIDS RESEARCH LA English DT Note C1 MASSACHUSETTS GEN HOSP, NEUROGENET LAB, BOSTON, MA 02114 USA. RP KWIATKOWSKI, DJ (reprint author), BRIGHAM & WOMENS HOSP, DIV EXPTL MED, 221 LONGWOOD AVE, BOSTON, MA 02115 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD FEB 25 PY 1992 VL 20 IS 4 BP 932 EP 932 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HG350 UT WOS:A1992HG35000070 ER PT J AU KWIATKOWSKI, DJ GUSELLA, JF AF KWIATKOWSKI, DJ GUSELLA, JF TI DINUCLEOTIDE REPEAT POLYMORPHISM AT THE D9S119 LOCUS (9Q22-34) SO NUCLEIC ACIDS RESEARCH LA English DT Note C1 MASSACHUSETTS GEN HOSP, NEUROGENET LAB, BOSTON, MA 02114 USA. RP KWIATKOWSKI, DJ (reprint author), BRIGHAM & WOMENS HOSP, DIV EXPTL MED, 221 LONGWOOD AVE, BOSTON, MA 02115 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD FEB 25 PY 1992 VL 20 IS 4 BP 932 EP 932 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HG350 UT WOS:A1992HG35000071 ER PT J AU KWIATKOWSKI, DJ GUSELLA, JF AF KWIATKOWSKI, DJ GUSELLA, JF TI DINUCLEOTIDE REPEAT POLYMORPHISM AT THE D9S121 LOCUS (9Q31-34) SO NUCLEIC ACIDS RESEARCH LA English DT Note C1 MASSACHUSETTS GEN HOSP, NEUROGENET LAB, BOSTON, MA 02114 USA. RP KWIATKOWSKI, DJ (reprint author), BRIGHAM & WOMENS HOSP, DIV EXPTL MED, 221 LONGWOOD AVE, BOSTON, MA 02115 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD FEB 25 PY 1992 VL 20 IS 4 BP 933 EP 933 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HG350 UT WOS:A1992HG35000073 ER PT J AU KWIATKOWSKI, DJ GUSELLA, JF AF KWIATKOWSKI, DJ GUSELLA, JF TI DINUCLEOTIDE REPEAT POLYMORPHISM AT THE D9S120 LOCUS (9Q31-34) SO NUCLEIC ACIDS RESEARCH LA English DT Note C1 MASSACHUSETTS GEN HOSP, NEUROGENET LAB, BOSTON, MA 02114 USA. RP KWIATKOWSKI, DJ (reprint author), BRIGHAM & WOMENS HOSP, DIV EXPTL MED, 221 LONGWOOD AVE, BOSTON, MA 02115 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD FEB 25 PY 1992 VL 20 IS 4 BP 933 EP 933 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HG350 UT WOS:A1992HG35000072 ER PT J AU KWIATKOWSKI, DJ GUSELLA, JF AF KWIATKOWSKI, DJ GUSELLA, JF TI DINUCLEOTIDE REPEAT POLYMORPHISM AT THE D9S123 LOCUS (9Q31-34) SO NUCLEIC ACIDS RESEARCH LA English DT Note C1 MASSACHUSETTS GEN HOSP, NEUROGENET LAB, BOSTON, MA 02114 USA. RP KWIATKOWSKI, DJ (reprint author), BRIGHAM & WOMENS HOSP, DIV EXPTL MED, 221 LONGWOOD AVE, BOSTON, MA 02115 USA. NR 1 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD FEB 25 PY 1992 VL 20 IS 4 BP 934 EP 934 DI 10.1093/nar/20.4.934 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HG350 UT WOS:A1992HG35000074 ER PT J AU MCCLATCHEY, AI VANDENBERGH, P PERICAKVANCE, MA RASKIND, W VERELLEN, C MCKENNAYASEK, D RAO, K HAINES, JL BIRD, T BROWN, RH GUSELLA, JF AF MCCLATCHEY, AI VANDENBERGH, P PERICAKVANCE, MA RASKIND, W VERELLEN, C MCKENNAYASEK, D RAO, K HAINES, JL BIRD, T BROWN, RH GUSELLA, JF TI TEMPERATURE-SENSITIVE MUTATIONS IN THE III-IV-CYTOPLASMIC LOOP REGION OF THE SKELETAL-MUSCLE SODIUM-CHANNEL GENE IN PARAMYOTONIA-CONGENITA SO CELL LA English DT Article ID RAT-BRAIN; ALPHA-SUBUNIT; FUNCTIONAL EXPRESSION; CDNA SEQUENCE; CLONED CDNA; INACTIVATION; DROSOPHILA; MYOTONIA AB Paramyotonia congenita (PMC), a dominant disorder featuring cold-induced myotonia (muscle stiffness), has recently been genetically linked to a candidate gene, the skeletal muscle sodium channel gene SCN4A. We have now established that SCN4A is the disease gene in PMC by identifying two different single-base coding sequence alterations in PMC families. Both mutations affect highly conserved residues in the III-IV cytoplasmic loop, a portion of the sodium channel thought to pivot in response to membrane depolarization, thereby blocking and inactivating the channel. Abnormal function of this cytoplasmic loop therefore appears to produce the Na+ current abnormality and the unique temperature-sensitive clinical phenotype in this disorder. C1 MASSACHUSETTS GEN HOSP,DAY NEUROMUSCULAR RES,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02129. CATHOLIC UNIV LOUVAIN,CLIN UNIV ST LUC,DEPT NEUROL,B-1200 BRUSSELS,BELGIUM. DUKE UNIV,DEPT MED,DIV NEUROSURG,DURHAM,NC 27706. UNIV WASHINGTON,DEPT MED,SEATTLE,WA 98195. UNIV CONNECTICUT,CTR HLTH,DEPT NEUROL,FARMINGTON,CT 06032. SEATTLE VET AFFAIRS HOSP,DIV NEUROL,SEATTLE,WA 98195. RP MCCLATCHEY, AI (reprint author), MASSACHUSETTS GEN HOSP,MOLEC NEUROGENET LAB,BOSTON,MA 02129, USA. RI Haines, Jonathan/C-3374-2012 FU NINDS NIH HHS [NS26630, NS22224, NS24279] NR 44 TC 212 Z9 213 U1 0 U2 7 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD FEB 21 PY 1992 VL 68 IS 4 BP 769 EP 774 DI 10.1016/0092-8674(92)90151-2 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA HF440 UT WOS:A1992HF44000016 PM 1310898 ER PT J AU MOERTEL, CG LEFKOPOULO, M LIPSITZ, S HAHN, RG KLAASSEN, D AF MOERTEL, CG LEFKOPOULO, M LIPSITZ, S HAHN, RG KLAASSEN, D TI STREPTOZOCIN DOXORUBICIN, STREPTOZOCIN FLUOROURACIL, OR CHLOROZOTOCIN IN THE TREATMENT OF ADVANCED ISLET-CELL CARCINOMA SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID PHASE-I; THERAPY; TABLES AB Background. The combination of streptozocin and fluorouracil has become the standard therapy for advanced islet-cell carcinoma. However, doxorubicin has also been shown to be active against this type of tumor, as has chlorozotocin, a drug that is structurally similar to streptozocin but less frequently causes vomiting. Methods. In this multicenter trial, we randomly assigned 105 patients with advanced islet-cell carcinoma to receive one of three treatment regimens: streptozocin plus fluorouracil, streptozocin plus doxorubicin, or chlorozotocin alone. The 31 patients in whom the disease did not respond to treatment were crossed over to chlorozotocin alone or to one of the combination regimens. Results. Streptozocin plus doxorubicin was superior to streptozocin plus fluorouracil in terms of the rate of tumor regression, measured objectively (69 percent vs. 45 percent, P = 0.05), and the length of time to tumor progression (median, 20 vs. 6.9 months; P = 0.001). Streptozocin plus doxorubicin also had a significant advantage in terms of survival (median, 2.2 vs. 1.4 years; P = 0.004) that was accentuated when we considered long-term survival (> 2 years). Chlorozotocin alone produced a 30 percent regression rate, with the length of time to tumor progression and the survival time equivalent to those observed with streptozocin plus fluorouracil. Crossover therapy after the failure of either chlorozotocin alone or one of the combination regimens produced an overall response rate of only 17 percent, and the responses were transient. Toxic reactions to all regimens included vomiting, which was least severe with chlorozotocin; hematologic depression; and, with long-term therapy, renal insufficiency. Conclusions. The combination of streptozocin and doxorubicin is superior to the current standard regimen of streptozocin plus fluorouracil in the treatment of advanced islet-cell carcinoma. Chlorozotocin alone is similar in efficacy to streptozocin plus fluorouracil, but it produces fewer gastrointestinal side effects than the regimens containing streptozocin. It therefore merits study as a constituent of combination drug regimens. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. CANC CONTROL AGCY,VANCOUVER V5Z 3J3,BC,CANADA. RP MOERTEL, CG (reprint author), MAYO CLIN & MAYO FDN,ROCHESTER,MN 55905, USA. FU NCI NIH HHS [CA 15947, CA 13650, CA 23318] NR 15 TC 506 Z9 513 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 FEB 20 PY 1992 VL 326 IS 8 BP 519 EP 523 DI 10.1056/NEJM199202203260804 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA HD658 UT WOS:A1992HD65800004 PM 1310159 ER PT J AU FERNANDEZDELCASTILLO, C HARRINGER, W WARSHAW, AL VLAHAKES, GJ KOSKI, G ZASLAVSKY, AM RATTNER, DW AF FERNANDEZDELCASTILLO, C HARRINGER, W WARSHAW, AL VLAHAKES, GJ KOSKI, G ZASLAVSKY, AM RATTNER, DW TI PANCREATIC INJURY AFTER CARDIOPULMONARY BYPASS - REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP FERNANDEZDELCASTILLO, C (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 4 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 FEB 20 PY 1992 VL 326 IS 8 BP 573 EP 574 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA HD658 UT WOS:A1992HD65800023 ER PT J AU PODOLSKY, DK AF PODOLSKY, DK TI INFLAMMATORY BOWEL-DISEASE - REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP PODOLSKY, DK (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 FEB 20 PY 1992 VL 326 IS 8 BP 575 EP 575 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA HD658 UT WOS:A1992HD65800026 ER PT J AU SHOELSON, SE LU, ZX PARLAUTAN, L LYNCH, CS WEISS, MA AF SHOELSON, SE LU, ZX PARLAUTAN, L LYNCH, CS WEISS, MA TI MUTATIONS AT THE DIMER, HEXAMER, AND RECEPTOR-BINDING SURFACES OF INSULIN INDEPENDENTLY AFFECT INSULIN INSULIN AND INSULIN-RECEPTOR INTERACTIONS SO BIOCHEMISTRY LA English DT Article ID STRUCTURALLY ABNORMAL INSULIN; MUTANT HUMAN INSULIN; BIOLOGICAL-ACTIVITY; CIRCULAR-DICHROISM; MONOMERIC INSULINS; SHORTENED INSULIN; INVITRO POTENCY; SIDE-CHAIN; ANALOGS; H-1-NMR AB Mutagenesis of the dimer- and hexamer-forming surfaces of insulin yields analogues with reduced tendencies to aggregate and dramatically altered pharmacokinetic properties. We recently showed that one such analogue, HisB10 --> Asp, ProB28 --> Lys, LysB29 --> Pro human insulin (DKP-insulin), has enhanced affinity for the insulin receptor and is useful for studying the structure of the insulin monomer under physiologic solvent conditions [Weiss, M. A., Hua, Q. X., Lynch, C. S., Frank, B. H., & Shoelson, S. E. (1991) Biochemistry 30, 7373-7389]. DKP-insulin retains native secondary and tertiary structure in solution and may therefore provide an appropriate baseline for further studies of related analogues containing additional substitutions within the receptor-binding surface of insulin. To test this, we prepared a family of DKP analogues having potency-altering substitutions at the B24 and B25 positions using a streamlined approach to enzymatic semisynthesis which negates the need for amino-group protection. For comparison, similar analogues of native human insulin were prepared by standard semisynthetic methods. The DKP analogues show a reduced tendency to self-associate, as indicated by H-1-NMR resonance line widths. In addition, CD spectra indicate that (with one exception) the native insulin fold is retained in each analogue; the exception, PheB24 --> Gly, induces similar perturbations in both native insulin and DKP-insulin backgrounds. Notably, analogous substitutions exhibit parallel trends in receptor-binding potency over a wide range of affinities: D-PheB24 > unsubstituted > GlyB24 > SerB24 > AlaB25 > LeuB25 > SerB25, whether the substitution was in a native human or DKP-insulin background. Such 'template independence" reflects an absence of functional interactions between the B24 and B25 sites and additional substitutions in DKP-insulin and demonstrates that mutations in discrete surfaces of insulin have independent effects on protein structure and function. In particular, the respective receptor-recognition (PheB24, PheB25), hexamer-forming (HisB10), and dimer-forming (ProB28, LysB29) surfaces of insulin may be regarded as independent targets for protein design. DKP-insulin provides an appropriate biophysical model for defining structure-function relationships in a monomeric template. C1 BRIGHAM & WOMENS HOSP,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MOLEC PHARMACOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. RP SHOELSON, SE (reprint author), BRIGHAM & WOMENS HOSP,JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02115, USA. FU NIDDK NIH HHS [DK-36836] NR 73 TC 66 Z9 67 U1 2 U2 10 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD FEB 18 PY 1992 VL 31 IS 6 BP 1757 EP 1767 DI 10.1021/bi00121a025 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HE194 UT WOS:A1992HE19400025 PM 1737029 ER PT J AU SEVILLA, DC WAGNER, NB PEGUES, R PECK, SL MIKAT, EM IDEKER, RE HUTCHINS, G REIMER, KA HACKEL, DB SELVESTER, RH WAGNER, GS AF SEVILLA, DC WAGNER, NB PEGUES, R PECK, SL MIKAT, EM IDEKER, RE HUTCHINS, G REIMER, KA HACKEL, DB SELVESTER, RH WAGNER, GS TI CORRELATION OF THE COMPLETE VERSION OF THE SELVESTER QRS SCORING SYSTEM WITH QUANTITATIVE ANATOMIC FINDINGS FOR MULTIPLE LEFT-VENTRICULAR MYOCARDIAL INFARCTS SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID SIZE; FAILURE AB The correlation between myocardial infarct size estimated by the complete version of the Selvester QRS scoring system and that documented by pathoanatomic studies has been reported for single anterior, inferior and posterolateral infarcts. Although previous studies described electrocardiographic changes in patients with multiple infarcts, no quantitative documentation of the ability of such changes to estimate the total amount of left ventricular infarction has been reported. This study of 32 patients with anatomically documented multiple infarcts shows a significant correlation between QRS-estimated and anatomically documented sizes (r = 0.44; p = 0.01), which is less than that previously reported for single infarcts in the anterior, inferior and posterolateral locations. Several of the 54 electrocardiographic criteria were never satisfied. Criteria for posterior infarction were seldom present, suggesting "cancellation effect" of coexisting anterior infarction. These results will be the basis for future modification of QRS criteria for estimating myocardial infarct size. C1 DUKE UNIV,MED CTR,DEPT PATHOL,BOX 3636,DURHAM,NC 27710. BARNES HOSP,MULTICTR INVEST LIMITAT INFARCT SIZE STUDY GRP,ST LOUIS,MO 63110. DUKE UNIV,MED CTR,DEPT MED,DURHAM,NC 27710. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. JOHNS HOPKINS UNIV HOSP,BALTIMORE,MD 21205. UNIV TEXAS,PARKLAND MEM HOSP,HLTH SCI CTR,DALLAS,TX 75230. NR 17 TC 25 Z9 25 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 FEB 15 PY 1992 VL 69 IS 5 BP 465 EP 469 DI 10.1016/0002-9149(92)90987-A PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA HD943 UT WOS:A1992HD94300008 PM 1736608 ER PT J AU BLOCK, PC PALACIOS, IF BLOCK, EH TUZCU, EM GRIFFIN, B AF BLOCK, PC PALACIOS, IF BLOCK, EH TUZCU, EM GRIFFIN, B TI LATE (2-YEAR) FOLLOW-UP AFTER PERCUTANEOUS BALLOON MITRAL VALVOTOMY SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID STENOSIS; VALVULOPLASTY; COMMISSUROTOMY; CATHETER; VALVE; MECHANISM AB Percutaneous balloon mitral valvotomy (PBMV) compares well with surgical commissurotomy, showing comparable improvement in symptoms and catheterization-proven valve are early after the procedure. This study reports the New York Heart Association class, mitral valve area calculated by echocardiography, and the results of transseptal cardiac catheterization 2 years after PBMV. The data are compared with the status immediately before and after PBMV. Forty-one patients returned to enter the study (mean follow-up time 24 +/- 3 months). All patients were evaluated clinically by the same investigator who had seen them at the time of PBMV. Transseptal cardiac catheterization and echocardiographic analysis (2-dimensional and Doppler echocardiography) were performed on the same day. At follow-up, 17 patients were class I, 20 were class II, and 4 were class III. Although the mitral valve area calculated by cardiac catheterization increased significantly from immediately before to immediately after PBMV there was a decrease in the calculated mitral valve area at 2-year follow-up. Echocardiographic analysis did not show as large an increase in mitral area, immediately after PBMV, and no significant decrease in mitral valve area at 2 years (before PBMV planimetry 1.1 +/- 0.1 cm2; immediately after 1.8 +/- 0.1 [p < 0.05]; follow-up 1.6 +/- 0.1 [p = not significant compared with immediately after PBMV]). Doppler halftime measurements were similar. PBMV is effective therapy with good midterm results for selected patients with mitral stenosis. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP BLOCK, PC (reprint author), ST VINCENT HOSP & MED CTR,INST HEART,9155 SW BARNES RD,SUITE 230,PORTLAND,OR 97225, USA. NR 16 TC 46 Z9 47 U1 0 U2 1 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 FEB 15 PY 1992 VL 69 IS 5 BP 537 EP 541 DI 10.1016/0002-9149(92)91000-T PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA HD943 UT WOS:A1992HD94300021 PM 1736620 ER PT J AU HEBERT, LE SCHERR, PA BECKETT, LA FUNKENSTEIN, HH ALBERT, MS CHOWN, MJ EVANS, DA AF HEBERT, LE SCHERR, PA BECKETT, LA FUNKENSTEIN, HH ALBERT, MS CHOWN, MJ EVANS, DA TI RELATION OF SMOKING AND ALCOHOL-CONSUMPTION TO INCIDENT ALZHEIMERS-DISEASE SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE AGED; ALCOHOL DRINKING; ALZHEIMERS DISEASE; EPIDEMIOLOGY; INCIDENCE; RISK FACTORS; SMOKING ID RISK-FACTORS; COMMUNITY POPULATION; DRINKING; HEALTH; MEN AB The authors examined the effects of smoking and alcohol use in a prospective community-based study of incident Alzheimer's disease. Two in-home interviews of the total elderly population of East Boston, Massachusetts, conducted in 1982 and 1985 were used to sample individuals for clinical evaluation for Alzheimer's disease. A total of 513 persons underwent detailed clinical evaluation including neurologic, neuropsychologic, and psychiatric evaluation to diagnose Alzheimer's disease. In weighted logistic regression controlled for age, sex, and education, the estimated odds ratio of Alzheimer's disease was 0.7 (95% confidence interval 0.3-1.4) for ever smokers compared with never smokers. For 40 pack-years of smoking, the odds ratio of Alzheimer's disease was 0.8 (95% confidence interval 0.6-1.1). Consumption of 1 oz (30 ml) of alcohol per day was associated with an odds ratio of 1.1 (95% confidence interval 0.8-1.5). These results suggest that recent mild-to-moderate consumption of alcohol is not substantially related to incidence of Alzheimer's disease and that smoking does not increase risk of the disease. C1 RUSH PRESBYTERIAN ST LUKES MED CTR,CTR RES HLTH & AGING,1653 W CONGRESS PKWY,CHICAGO,IL 60612. HARVARD UNIV,SCH PUBL HLTH,DEPT HLTH POLICY & MANAGEMENT,BOSTON,MA 02115. CTR DIS CONTROL,NATL CTR CHRON DIS PREVENT & HLTH PROMOT,AGING BRANCH,ATLANTA,GA 30333. BRIGHAM & WOMENS HOSP,DEPT MED,DIV NEUROL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02114. BRIGHAM & WOMENS HOSP,DEPT MED,CHANNING LAB,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. FU NIA NIH HHS [N01-AG-O-2107, AG05362, N01-AG-1-2106] NR 27 TC 86 Z9 87 U1 1 U2 8 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD FEB 15 PY 1992 VL 135 IS 4 BP 347 EP 355 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA HT763 UT WOS:A1992HT76300003 PM 1550089 ER PT J AU HAINES, JL YAN, WL BOUSTANY, RM JEWELL, A JULIER, C BREAKEFIELD, XO GUSELLA, JF AF HAINES, JL YAN, WL BOUSTANY, RM JEWELL, A JULIER, C BREAKEFIELD, XO GUSELLA, JF TI LINKAGE ANALYSIS IN JUVENILE NEURONAL CEROID LIPOFUSCINOSIS SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article; Proceedings Paper CT 3RD INTERNATIONAL CONF ON THE NEURONAL CEROID LIPOFUSCINOSES ( BATTEN DISEASE ) CY MAY 30-JUN 01, 1990 CL INDIANAPOLIS, IN SP MARCH DIMES BIRTH DEFECTS FDN, NINCDS, CHILDRENS BRAIN DIS FDN, MERRELL DOW RES LAB, LILLY RES LABS, INDIANAPOLIS UNIV SCH MED DE BATTEN DISEASE; NCL; HOMOGENEITY; CHROMOSOME-16 ID DISEASE AB Neuronal ceroid lipofuscinosis (NCL, Batten disease) is an autosomal recessive disease characterized by progressive mental retardation, cortical atrophy, seizures, and retinal degeneration. Several subtypes have been delineated on the basis of age-at-onset and histological characteristics; the most common is the juvenile (JNCL) form. Recently, the gene for JNCL was shown to reside on chromosome 16 through linkage studies to the haptoglobin locus and anonymous DNA markers using numerous European families. We have now examined 8 families from North America with JNCL for linkage to markers in 16q21-23. Results in 3 families tend to support linkage to chromosome 16; 3 families remained uninformative, and 2 families produced negative lod scores in this region. A test of homogeneity was suggestive, but could not significantly reject the null hypothesis of homogeneity. We are continuing to collect families, particularly those with multiple living affecteds, and are identifying other probes in this region. Given close localization on chromosome 16 for JNCL, molecular strategies, including candidate gene strategies, are being explored. C1 DUKE UNIV,MED CTR,DIV PEDIAT NEUROL,DURHAM,NC 27710. RP HAINES, JL (reprint author), MASSACHUSETTS GEN HOSP,MOLEC NEUROGENET LAB,BLDG 149,6TH FLOOR,BOSTON,MA 02129, USA. RI Haines, Jonathan/C-3374-2012 FU NINDS NIH HHS [P01 NS 24279-05] NR 12 TC 11 Z9 11 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD FEB 15 PY 1992 VL 42 IS 4 BP 542 EP 545 DI 10.1002/ajmg.1320420424 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA HF152 UT WOS:A1992HF15200023 PM 1609835 ER PT J AU DANIEL, PF SAULS, DL BOUSTANY, RMN AF DANIEL, PF SAULS, DL BOUSTANY, RMN TI EVIDENCE FOR PROCESSING OF DOLICHOL-LINKED OLIGOSACCHARIDES IN PATIENTS WITH NEURONAL CEROID-LIPOFUSCINOSIS SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article; Proceedings Paper CT 3RD INTERNATIONAL CONF ON THE NEURONAL CEROID LIPOFUSCINOSES ( BATTEN DISEASE ) CY MAY 30-JUN 01, 1990 CL INDIANAPOLIS, IN SP MARCH DIMES BIRTH DEFECTS FDN, NINCDS, CHILDRENS BRAIN DIS FDN, MERRELL DOW RES LAB, LILLY RES LABS, INDIANAPOLIS UNIV SCH MED DE DOLICHYL PYROPHOSPHORYL OLIGOSACCHARIDES; BATTEN DISEASE; FIBROBLASTS; BRAIN; N-METHYLDEOXYNOJIRIMYCIN; GLUCOSIDASE-I; OLIGOSACCHARIDE PROCESSING ID ALPHA-D-MANNOSIDASE; ENDOPLASMIC-RETICULUM; PYROPHOSPHORYL OLIGOSACCHARIDES; PHOSPHORYLATED DOLICHOL; DIPHOSPHO-DOLICHOL; CATABOLIC PATHWAY; RAT-LIVER; GOLGI; CHROMATOGRAPHY; METHYLATION AB In agreement with reports from other laboratories, we have shown that patients with the juvenile or late infantile forms of neuronal ceroid-lipofuscinosis (NCL) have greatly increased levels (5-fold to 20-fold) of dolichyl pyrophosphoryl oligosaccharides in their cerebral gray matter. Oligosaccharides containing 2 GlcNAc residues and 3 to 9 mannose residues were liberated by mild acid hydrolysis. The oligosaccharide profile given by brain tissue from 2 patients with infantile NCL was markedly different from that of late infantile and juvenile NCL brain, with Man9GlcNAc2 as the most abundant component and decreasing amounts of Man8- Man7- and Man6GlcNAc2. By contrast, Man5GlcNAc2 was the most abundant oligosaccharide present in all juvenile NCL brain samples analyzed. Both the susceptibility of the isolated Man5GlcNAc2 to endoglucosaminidase H digestion and permethylation analysis clearly indicated that it is not an intermediate in the biosynthesis of Glc3Man9GlcNAc2-PP-dolichol but has undergone catabolism, probably either in the endoplasmic reticulum or in the Golgi apparatus. Treatment of cultured skin fibroblasts for 7 days with N-methyldeoxynojirimycin, a potent inhibitor of the endoplasmic reticulum processing enzymes glucosidase I and II, resulted in an accumulation of the same Man5GlcNAc2-PP-dolichol species that was elevated in juvenile NCL brain. The level in untreated fibroblasts was undetectable, suggesting that inhibition of processing glucosidases has interfered with the regulation and compartmentalization of lipid-linked oligosaccharides. C1 HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. RP DANIEL, PF (reprint author), EUNICE KENNEDY SHRIVER CTR MENTAL RETARDAT INC,DEPT BIOCHEM,200 TRAPELO RD,WALTHAM,MA 02254, USA. FU NINDS NIH HHS [NS 24279] NR 27 TC 8 Z9 8 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD FEB 15 PY 1992 VL 42 IS 4 BP 586 EP 592 DI 10.1002/ajmg.1320420432 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA HF152 UT WOS:A1992HF15200031 PM 1609840 ER PT J AU EMANUEL, LL EMANUEL, E AF EMANUEL, LL EMANUEL, E TI ADVANCE DIRECTIVES SO ANNALS OF INTERNAL MEDICINE LA English DT Letter C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. RP EMANUEL, LL (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 1 TC 3 Z9 3 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD FEB 15 PY 1992 VL 116 IS 4 BP 348 EP 348 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA HD546 UT WOS:A1992HD54600029 PM 1733399 ER PT J AU DATTA, R IMAMURA, K GOLDMAN, SJ DIANOUX, AC KUFE, DW SHERMAN, ML AF DATTA, R IMAMURA, K GOLDMAN, SJ DIANOUX, AC KUFE, DW SHERMAN, ML TI FUNCTIONAL EXPRESSION OF THE MACROPHAGE COLONY-STIMULATING FACTOR RECEPTOR IN HUMAN THP-1 MONOCYTIC LEUKEMIA-CELLS SO BLOOD LA English DT Article ID TUMOR-NECROSIS-FACTOR; FMS PROTO-ONCOGENE; FACTOR GENE-EXPRESSION; HEMATOPOIETIC GROWTH-FACTORS; MARROW-DERIVED MACROPHAGES; FACTOR-I CSF-1; MESSENGER-RNA; KINASE-C; POSTTRANSCRIPTIONAL REGULATION; MONONUCLEAR PHAGOCYTES C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,CLIN PHARMACOL LAB,44 BINNEY ST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. GENET INST,DEPT PRECLIN BIOL,CAMBRIDGE,MA. FU NCI NIH HHS [P01 CA34183, K08 CA01902] NR 58 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 0006-4971 J9 BLOOD JI Blood PD FEB 15 PY 1992 VL 79 IS 4 BP 904 EP 912 PG 9 WC Hematology SC Hematology GA HD660 UT WOS:A1992HD66000010 PM 1531307 ER PT J AU ODA, A DALEY, JF CABRAL, C KANG, J SMITH, M SALZMAN, EW AF ODA, A DALEY, JF CABRAL, C KANG, J SMITH, M SALZMAN, EW TI HETEROGENEITY IN FILAMENTOUS ACTIN CONTENT AMONG INDIVIDUAL HUMAN BLOOD-PLATELETS SO BLOOD LA English DT Article ID FLOW-CYTOMETRY; ADENOSINE-DIPHOSPHATE; ACTIVATION; SHAPE; POLYMERIZATION; MOBILIZATION; MEMBRANE; PLASMA; SIGNAL; SIZE C1 BETH ISRAEL HOSP,DEPT SURG,330 BROOKLINE AVE,BOSTON,MA 02215. BETH ISRAEL HOSP,DEPT MED,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. FU NHLBI NIH HHS [HL-38820, HL-344014] NR 35 TC 25 Z9 25 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 FEB 15 PY 1992 VL 79 IS 4 BP 920 EP 927 PG 8 WC Hematology SC Hematology GA HD660 UT WOS:A1992HD66000012 PM 1737100 ER PT J AU CLINTON, SK IMREY, PB MANGIAN, HJ NANDKUMAR, S VISEK, WJ AF CLINTON, SK IMREY, PB MANGIAN, HJ NANDKUMAR, S VISEK, WJ TI THE COMBINED EFFECTS OF DIETARY-FAT, PROTEIN, AND ENERGY-INTAKE ON AZOXYMETHANE-INDUCED INTESTINAL AND RENAL CARCINOGENESIS SO CANCER RESEARCH LA English DT Article ID MICE FED 10-PERCENT; PLASMA AMINO-ACIDS; MALE F344 RATS; ENVIRONMENTAL FACTORS; COLON CARCINOGENESIS; RESTRICTED DIET; TUMOR-INCIDENCE; CALORIC-INTAKE; BREAST-CANCER; END PRODUCTS AB Two 3 x 3 factorial experiments were conducted to examine the effects of dietary protein (8, 16, and 32% of energy from casein) and dietary fat (12, 24, and 48% of energy from corn oil) on the initiation and promotion of azoxymethane-induced carcinogenesis in rats. For the initiation study, 33 weanling male Sprague-Dawley rats were randomized to each of nine diets fed ad libitum. Azoxymethane was administered s.c. between the fourth to sixth weeks of feeding, providing a total dose of 6 mg/100 g body weight. All rats were subsequently fed a common diet containing 16% energy from protein and 24% energy from fat for an additional 30 to 38 weeks. For the promotion study, all rats were fed a common diet containing 16% of energy from protein and 12% of energy from fat until the completion of azoxymethane administration, when 33 rats were randomized to each of nine diets varying in fat and protein content and fed these diets until sacrifice. Low-protein diets during the initiation phase were associated with increased risk of renal adenocarcinomas (P < 0.001) and mesenchymal (P = 0.005) malignancies. No other statistically significant relationships were found between the levels of dietary fat or protein and the prevalence of malignant lesions of the small intestine, colon, or kidney in either the initiation or promotion study (although polypoid adenocarcinoma of the colon increased suggestively from 13 to 19 to 26% of rats with increasing dietary protein during initiation). Results of a multiple logistic regression analysis, combining both studies, showed that ad libitum energy intake was significantly associated with intestinal carcinogenesis. The odds of finding an intestinal adenocarcinoma increased by 6.2 +/- 2.6% (SE) for each additional kilocalorie of mean daily ad libitum intake (P = 0.014). The quintile of rats which consumed the least averaged 60 kcal/day, while the most voracious quintile averaged 74 kcal/day. This 14 kcal/day difference in mean ad libitum intake corresponded to more than a doubling (146% increase) of the odds of developing an intestinal adenocarcinoma. These studies suggest that ad libitum energy intake is a critical factor modulating experimental colon carcinogenesis. C1 UNIV ILLINOIS,COLL MED,DEPT MED INFORMAT SCI,URBANA,IL 61801. UNIV ILLINOIS,COLL MED,DEPT HLTH & SAFETY STUDIES,URBANA,IL 61801. UNIV ILLINOIS,COLL MED,DEPT STAT,URBANA,IL 61801. UNIV ILLINOIS,COLL MED,DEPT MED,DIV NUTR SCI,URBANA,IL 61801. RP CLINTON, SK (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,CLIN PHARMACOL LAB,44 BINNEY ST,BOSTON,MA 02115, USA. OI Imrey, Peter/0000-0002-0533-4603 FU NCI NIH HHS [CA33796] NR 60 TC 29 Z9 29 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD FEB 15 PY 1992 VL 52 IS 4 BP 857 EP 865 PG 9 WC Oncology SC Oncology GA HD163 UT WOS:A1992HD16300017 PM 1737347 ER PT J AU RUBIN, E KHARBANDA, S GUNJI, H WEICHSELBAUM, R KUFE, D AF RUBIN, E KHARBANDA, S GUNJI, H WEICHSELBAUM, R KUFE, D TI CIS-DIAMMINEDICHLOROPLATINUM(II) INDUCES C-JUN EXPRESSION IN HUMAN MYELOID-LEUKEMIA CELLS - POTENTIAL INVOLVEMENT OF A PROTEIN KINASE-C-DEPENDENT SIGNALING PATHWAY SO CANCER RESEARCH LA English DT Article ID TUMOR PLATINUM-COMPOUNDS; DNA-DAMAGING AGENTS; TRANSCRIPTIONAL REGULATION; MAMMALIAN-CELLS; FOS; INDUCTION; REPAIR; MECHANISM; ARREST; DEATH AB cis-Diamminedichloroplatinum(II) (CDDP) is a chemotherapeutic agent known to inhibit DNA, RNA, and protein synthesis. The cytotoxicity of this drug is thought to result from the formation of DNA intrastrand cross-links. The present work demonstrates that treatment of human myeloid leukemia cells (HL-60, U-937, and KG-1) with CDDP is associated with increased expression of the c-jun gene and that this effect is related to activation by a transcriptional mechanism. The results also demonstrate that treatment with CDDP is associated with increases in protein kinase C (PKC) activity. Furthermore, the finding that pretreatment with H7, an inhibitor of PKC, abrogates the effect of CDDP on c-jun expression suggested the involvement of PKC in this process. Down-regulation of PKC by prolonged pretreatment with 12-O-tetradecanoylphorbol-13-acetate was also associated with inhibition of CDDP-induced c-jun expression. The results further demonstrate that there is a temporal relationship between the CDDP-induced increase in c-jun expression and the occurrence of internucleosomal DNA cleavage characteristic of programmed cell death. These findings suggest that c-jun may be involved in the cellular response to DNA-damaging agents, such as CDDP, and that this effect may be mediated by a PKC-dependent pathway. RP RUBIN, E (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,CLIN PHARMACOL LAB,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA 34183, CA 42802] NR 39 TC 86 Z9 86 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 FEB 15 PY 1992 VL 52 IS 4 BP 878 EP 882 PG 5 WC Oncology SC Oncology GA HD163 UT WOS:A1992HD16300020 PM 1737349 ER PT J AU ROBERTS, WG HASAN, T AF ROBERTS, WG HASAN, T TI ROLE OF NEOVASCULATURE AND VASCULAR-PERMEABILITY ON THE TUMOR RETENTION OF PHOTODYNAMIC AGENTS SO CANCER RESEARCH LA English DT Article ID LOW-DENSITY LIPOPROTEINS; PHOTOFRIN-II; HISTOCHEMICAL-LOCALIZATION; SULFONATED PHTHALOCYANINE; CELLULAR-UPTAKE; NORMAL TISSUE; CHLORIN E6; BLOOD-FLOW; THERAPY; INVIVO AB A variety of photodynamic sensitizers (chloroaluminum sulfonated phthalocyanine, tetraphenyl porphine sulfonate, mono-L-aspartyl chlorin e6, Photofrin, chlorin e6, and Uroporphyrin dihydrochloride I) were characterized by their ability to be retained in EMT-6 tumors growing in BALB/c mice. Two properties uniquely associated with tumors, proliferating neovasculature and vascular permeability, were tested for their relative importance in retaining the photosensitizer. A chick embryo model was used to compare photosensitizer uptake/retention in proliferating and nonproliferating neovasculature with retention in proliferating nonvascular tissue. Our results provide evidence that photosensitizers which are preferentially retained by tumors have a selective affinity for proliferating neovasculature. The chloroaluminum sulfonated phthalocyanine and tetraphenyl porphine sulfonate compounds possess the greatest affinity for proliferating neovasculature relative to nonvascular tissue, while the phthalocyanine has the largest tumor/normal differential in vivo of all the photosensitizers tested. Chlorin e6 and uroporphyrin dihydrochloride I were the only photosensitizers which were not retained in greater amounts by tumor tissues relative to normal tissues. Using a delayed-type hypersensitivity reaction, extended and constant vascular permeability was induced in BALB/c mice. Vascular permeability was quantitated by Evans blue extraction from the delayed-type hypersensitivity sites. Interestingly, leaky vessels alone did not result in photosensitizer retention, as seen with tumors. These data demonstrate that tumor-retained photosensitizers possess a selective affinity for proliferating neovasculature and that vascular permeability alone is not sufficient to retain these sensitizers. C1 MASSACHUSETTS GEN HOSP,DEPT DERMATOL,WELLMAN LABS PHOTOMED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. FU NIAMS NIH HHS [R01 AR23595]; NIGMS NIH HHS [GM13763-02] NR 56 TC 71 Z9 75 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD FEB 15 PY 1992 VL 52 IS 4 BP 924 EP 930 PG 7 WC Oncology SC Oncology GA HD163 UT WOS:A1992HD16300027 PM 1371089 ER PT J AU RAM, PA WAXMAN, DJ AF RAM, PA WAXMAN, DJ TI THYROID-HORMONE STIMULATION OF NADPH P450 REDUCTASE EXPRESSION IN LIVER AND EXTRAHEPATIC TISSUES - REGULATION BY MULTIPLE MECHANISMS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MESSENGER RIBONUCLEIC-ACID; RAT-LIVER; MALIC ENZYME; GROWTH-HORMONE; CYTOCHROME-P-450 REDUCTASE; TRANSCRIPTIONAL ACTIVATION; GENE-EXPRESSION; BINDING-SITES; RNA LEVEL; TRIIODOTHYRONINE AB The role of thyroid hormone in regulating the expression of the flavoprotein NADPH cytochrome P450 reductase was studied in adult rats. Depletion of circulating thyroid hormone by hypophysectomy, or more selectively, by treatment with the anti-thyroid drug methimazole led to a 75-85% depletion of hepatic microsomal P450 reductase activity and protein in both male and female rats. Thyroxine substantially restored P450 reductase activity at a dose that rendered the thyroid-depleted rats euthyroid. Microsomal P450 reductase activity in several extrahepatic tissues was also dependent on thyroid hormone, but to a lesser extent than in liver (30-50% decrease in kidney, adrenal, lung, and heart but not in testis from hypothyroid rats). Hepatic P450 reductase mRNA levels were also decreased in the hypothyroid state, indicating that the loss of P450 reductase activity is not a consequence of the associated decreased availability of the FMN and FAD cofactors of P450 reductase. Parallel analysis of S14 mRNA, which has been studied extensively as a model thyroid-regulated liver gene product, indicated that P450 reductase and S14 mRNA respond similarly to these changes in thyroid state. In contrast, while the expression of S14 and several other thyroid hormone-dependent hepatic mRNAs is stimulated by feeding a high carbohydrate, fat-free diet, hepatic P450 reductase expression was not increased by this lipogenic diet. Injection of hypothyroid rats with T3 at a supraphysiologic, receptor-saturating dose stimulated a major induction of hepatic P450 reductase mRNA that was detectable 4 h after the T3 injection, and peaked at approximately 650% of euthyroid levels by 12 h. However, this same treatment stimulated a biphasic increase in P450 reductase protein and activity that required 3 days to reach normal euthyroid levels. T3 treatment of euthyroid rats also stimulated a major induction of P450 reductase mRNA that was maximal (12-fold increase) by 12 h, but in this case no major increase in P450 reductase protein or activity was detectable over a 3-day period. Together, these studies establish that thyroid hormone regulates P450 reductase expression by pretranslational mechanisms. They also suggest that other regulatory mechanisms, which may involve changes in P450 reductase protein stability and/or changes in the translational efficiency of its mRNA, are likely to occur. C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NR 42 TC 81 Z9 82 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 FEB 15 PY 1992 VL 267 IS 5 BP 3294 EP 3301 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HD154 UT WOS:A1992HD15400075 PM 1737785 ER PT J AU MUKHOPADHYAY, NK PRICE, DJ KYRIAKIS, JM PELECH, S SANGHERA, J AVRUCH, J AF MUKHOPADHYAY, NK PRICE, DJ KYRIAKIS, JM PELECH, S SANGHERA, J AVRUCH, J TI AN ARRAY OF INSULIN-ACTIVATED, PROLINE-DIRECTED SERINE THREONINE PROTEIN-KINASES PHOSPHORYLATE THE P70-S6 KINASE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MYELIN BASIC-PROTEIN; EPIDERMAL GROWTH-FACTOR; S6 KINASE; TYROSINE KINASE; CELL-DIVISION; YEAST; IDENTIFICATION; PURIFICATION; RECEPTOR; MATURATION AB This study characterizes the insulin-activated serine/threonine protein kinases in H4 hepatoma cells active on a 37-residue synthetic peptide (called the SKAIPS peptide) corresponding to a putative autoinhibitory domain in the carboxyl-terminal tail of the p70 S6 kinase as well as on recombinant p70 S6 kinase. Three peaks of insulin-stimulated protein kinase active on both these substrates are identified as two (possibly three) isoforms of the 40-45-kDa erk/microtubule-associated protein (MAP)-2 kinase family and a 150-kDa form of cdc2. Although distinguishable in their substrate specificity, these protein kinases together with the p54 MAP-2 kinase share a major common specificity determinant reflected in the SKAIPS peptide: the requirement for a proline residue immediately carboxyl-terminal to the site of Ser/Thr phosphorylation. In addition, however, at least one peak of insulin-stimulated protein kinase active on recombinant p70, but not on the SKAIPS peptide, is present although not yet identified. MPF/cdc2 phosphorylates both rat liver p70 S6 kinase and recombinant p70 S6 kinase exclusively at a set of Ser/Thr residues within the putative autoinhibitory (SKAIPS peptide) domain. erk/MAP kinase does not phosphorylate rat liver p70 S6 kinase, but readily phosphorylates recombinant p70 S6 kinase at sites both within and in addition to those encompassed by the SKAIPS peptide sequences. Although the tryptic P-32-peptides bearing the cdc2 and erk/MAP kinase phosphorylation sites co-migrate with a subset of the sites phosphorylated in situ in insulin-stimulated cells, phosphorylation of the p70 S6 kinase by these proline-directed protein kinases in vitro does not reproducibly activate p70 S6 kinase activity. Thus, one or more erk/MAP kinases and cdc2 are likely to participate in the insulin-induced phosphorylation of the p70 S6 kinase. In addition to these kinases, however, phosphorylation of the p70 S6 kinase by other as yet unidentified protein kinases is necessary to recapitulate the multisite phosphorylation required for activation of the p70 S6 kinase. C1 MASSACHUSETTS GEN HOSP,DIABET UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,MED SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. UNIV BRITISH COLUMBIA,BIOMED RES CTR,VANCOUVER V6T 1Z3,BC,CANADA. FU NHLBI NIH HHS [HL07680]; PHS HHS [41762, 17776] NR 64 TC 202 Z9 203 U1 0 U2 4 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 FEB 15 PY 1992 VL 267 IS 5 BP 3325 EP 3335 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HD154 UT WOS:A1992HD15400080 PM 1737788 ER PT J AU NELSON, C RABB, H ARNAOUT, MA AF NELSON, C RABB, H ARNAOUT, MA TI GENETIC CAUSE OF LEUKOCYTE ADHESION MOLECULE DEFICIENCY - ABNORMAL SPLICING AND A MISSENSE MUTATION IN A CONSERVED REGION OF CD18 IMPAIR CELL-SURFACE EXPRESSION OF BETA-2 INTEGRINS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PLATELET GLYCOPROTEIN-IIIA; POLYMERASE CHAIN-REACTION; AMINO-ACID-SEQUENCE; LEU-CAM DEFICIENCY; MESSENGER-RNA; FIBRONECTIN RECEPTOR; EPITHELIAL-CELLS; SUBUNIT; LFA-1; COMMON AB Patients with leukocyte adhesion molecule (CD11/CD18, beta-2 integrins) deficiency have structural defects in the common beta-subunit (CD18), which prevent heterodimer formation and normal cell surface expression' of these receptors, leading to life-threatening bacterial infections. To elucidate the nature of these defects in a patient with partial (type II) deficiency, abnormal CD18 cDNA clones were isolated, using the polymerase chain reaction to amplify the patient's B cell-derived cDNAs. Sequence analysis revealed two mutant alleles. cDNA clones, representing a maternal allele, contained both a 12-base pair insertion resulting in an in-frame addition of four amino acids between P247 and E248 and a C1756 --> T nucleotide transition, resulting in an R586 --> W substitution in the normal CD18 protein. The in-frame insertion arose by a single nucleotide C --> A transversion in the 3' terminus of an intron, generating an aberrant splice acceptor site. Other cDNA clones contained an A1052 --> G nucleotide transition not present in either parent which resulted in an N351 --> S substitution. To determine the functional importance of these changes, cDNA encoding a normal alpha-chain (CD11b) was cotransfected into COS with CD18 cDNAs encoding for wild-type, maternal mutant allele, or CD18 containing N351 --> S substitution. Immunostaining of transfectants with anti-CD18 monoclonal antibodies revealed no cell surface expression of the maternal mutant CD18, and 22% surface expression of N351 --> S CD18. Both the insertion and the N351 --> S mutations occurred in a 250 amino acid extracellular region of CD18 that is highly conserved among beta-integrins supporting a role for this region in heterodimer formation. C1 MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,LEUKOCYTE BIOL & INFLAMMAT PROGRAM,RENAL UNIT,BOSTON,MA 02114. NR 38 TC 35 Z9 36 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 FEB 15 PY 1992 VL 267 IS 5 BP 3351 EP 3357 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HD154 UT WOS:A1992HD15400083 PM 1346613 ER PT J AU KOYASU, S MCCONKEY, DJ CLAYTON, LK ABRAHAM, S YANDAVA, B KATAGIRI, T MOINGEON, P YAMAMOTO, T REINHERZ, EL AF KOYASU, S MCCONKEY, DJ CLAYTON, LK ABRAHAM, S YANDAVA, B KATAGIRI, T MOINGEON, P YAMAMOTO, T REINHERZ, EL TI PHOSPHORYLATION OF MULTIPLE CD3-ZETA TYROSINE RESIDUES LEADS TO FORMATION OF PP21 INVITRO AND INVIVO - STRUCTURAL-CHANGES UPON T-CELL RECEPTOR STIMULATION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ANTIGEN RECEPTOR; ZETA-CHAIN; MOLECULAR-CLONING; ETA-CHAIN; POSSIBLE IDENTIFICATION; SIGNAL TRANSDUCTION; DISULFIDE LINKAGE; KINASE P56LCK; COMPLEX; GENE AB T lymphocyte activation resulting from antigen recognition involves a protein tyrosine kinase pathway which triggers phosphorylation of several cellular substrates including the CD3-zeta subunit of the T cell receptor (TCR) to form pp21. The homologous TCR-associated protein, CD3-eta, is an alternatively spliced product of the same gene locus as CD3-zeta. CD3-eta lacks one of six cytoplasmic tyrosine residues (Tyr-132) found in CD3-zeta and is itself not phosphorylated. Site-directed mutagenesis in conjunction with in vitro and in vivo phosphorylation studies herein demonstrates that Tyr-132 is required for the formation of pp21. Moreover, the differential phosphorylation of CD3-zeta versus CD3-eta is not due to a selective association of the known TCR-associated protein tyrosine kinase, p59fyn; p59fyn but not p56lck or p62yes is associated with each of the three TCR isoforms containing CD3-zeta-2, CD3-eta-2, or CD3-zeta-eta. This association occurs through components of the TCR complex distinct from CD3-zeta or CD3-eta. In addition we show that pp21 formation is not only dependent on Tyr-132 but results from concomitant phosphorylation of other CD3-zeta residues including Tyr-121. Mutation of Tyr-90, -121, or -132 does not alter primary signal transduction as shown by the ability of individual CD3-zeta Tyr --> Phe mutants to produce interleukin-2 upon TCR stimulation. Thus, the substantial structural changes in CD3-zeta upon TCR stimulation as reflected by alteration in its mobility in sodium dodecyl sulfate-polyacrylamide gel electrophoresis may affect subsequent events such as receptor desensitization, receptor movement, and/or protein associations. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. UNIV TOKYO,INST MED SCI,MINATO KU,TOKYO 108,JAPAN. RP KOYASU, S (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,IMMUNOBIOL LAB,BOSTON,MA 02115, USA. RI Koyasu, Shigeo/J-5583-2015 OI Koyasu, Shigeo/0000-0001-9585-3038 FU NIAID NIH HHS [AI21226, AI19807, AI31269] NR 56 TC 61 Z9 61 U1 0 U2 7 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 FEB 15 PY 1992 VL 267 IS 5 BP 3375 EP 3381 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HD154 UT WOS:A1992HD15400086 PM 1531339 ER PT J AU MICHALEK, MT BENACERRAF, B ROCK, KL AF MICHALEK, MT BENACERRAF, B ROCK, KL TI THE CLASS-II MHC-RESTRICTED PRESENTATION OF ENDOGENOUSLY SYNTHESIZED OVALBUMIN DISPLAYS CLONAL VARIATION, REQUIRES ENDOSOMAL LYSOSOMAL PROCESSING, AND IS UP-REGULATED BY HEAT-SHOCK SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELL RECOGNITION; ANTIGEN-PRESENTING CELLS; B-LYMPHOMA CELLS; INFLUENZA-VIRUS; LYMPHOCYTES-T; ENDOPLASMIC-RETICULUM; SIGNAL SEQUENCE; PROTEIN; HEMAGGLUTININ; DEGRADATION AB LB27.4 cells (a B lymphoblastoid APC) were transfected with a plasmid containing an OVA cDNA. Functional analysis of six independent clones yielded three patterns of MHC-restricted presentation of the endogenously synthesized OVA. A clone displayed either: 1) strong class I and class II-restricted presentation, 2) strong class I but little or no class II-restricted presentation or, 3) only a modest class I-restricted presentation. There was no clonal variation in class II-restricted presentation of exogenous Ag or in the amount of surface class I or II molecules. Heat shock increased the presentation of endogenous but not exogenous Ag with class II These results indicate that an endogenously synthesized Ag both constitutively and during heat shock can gain access to the class II, MHC-restricted, presentation pathway. The amount of OVA synthesized by a cell correlated with whether OVA-class II complexes were detected. However, the amount of OVA secreted into the extracellular fluid was not sufficient to sensitize APC, which suggests that endogenously synthesized OVA enters the class II pathway of Ag presentation by an intracellular route rather than by an extracellular/reuptake route. Also, the functional and quantitative analysis of the clones suggests that endogenously synthesized OVA was presented more efficiently with class I as compared to class II-MHC molecules. Leupeptin and chloroquine inhibited the class II-restricted presentation of endogenously synthesized OVA. Together these results indicate that endogenously synthesized OVA can gain access to an endosomal/lysosomal lysosomal compartment via an intracellular route and be processed and presented in association with class II-MHC molecules. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RP MICHALEK, MT (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV LYMPHOCYTE BIOL,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA 46967]; NIAID NIH HHS [AI 20248] NR 55 TC 53 Z9 53 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 FEB 15 PY 1992 VL 148 IS 4 BP 1016 EP 1024 PG 9 WC Immunology SC Immunology GA HD975 UT WOS:A1992HD97500006 PM 1737924 ER PT J AU SEN, J BOSSU, P BURAKOFF, SJ ABBAS, AK AF SEN, J BOSSU, P BURAKOFF, SJ ABBAS, AK TI T-CELL SURFACE MOLECULES REGULATING NONCOGNATE LYMPHOCYTE-B ACTIVATION - ROLE OF CD2 AND LFA-1 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID FUNCTION-ASSOCIATED ANTIGEN-3; LYMPHOKINE RESPONSIVENESS; MONOCLONAL-ANTIBODIES; COGNATE INTERACTIONS; MURINE CD2; PROLIFERATION; INDUCTION; DIFFERENTIATION; HETEROGENEITY; STIMULATION AB A central event in humoral responses is the Ag-mediated interaction of Th cells and B cells. This interaction leads to the activation of both cell types and results in cytokine secretion by the T cells and proliferation and secretion of Ig by the B cells. The proliferative and differentiative responses of B cells are dependent on contact-mediated signals and cytokines provided by the activated Th cells. Although the role of cytokines in B cell activation and differentiation is understood, the nature of the signals delivered by the activated Th cells and the molecules involved in this process are not known. In this study we have examined Ag-mediated "cognate" T-B cell interactions as well as B cell activation induced by contact with preactivated and fixed Th lymphocytes. Our results indicate that both the T cell surface molecules lymphocyte function associated Ag-1 and CD2 are important in the activation of T cells by Ag presented by B lymphocytes. This indicates that B cells have similar characteristics as other APC. However, once the T cells are activated, contact-mediated stimulation of resting B lymphocytes (the noncognate phase) is dependent on CD2 but not lymphocyte function associated Ag-1. Two lines of evidence indicate this; first, it is inhibited by blocking of CD2 on the T cells and, second, such stimulation is not efficiently mediated by a CD2- Th cell line. Thus, CD2 plays an obligatory role at several discrete stages of T cell-mediated activation of resting B lymphocytes. C1 HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RP SEN, J (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,D1604,44 BINNEY ST,BOSTON,MA 02115, USA. RI Bosso, Paola/E-4832-2014 OI Bosso, Paola/0000-0002-1432-0078 FU NIAID NIH HHS [AI 22802, AI 31868] NR 31 TC 32 Z9 32 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 FEB 15 PY 1992 VL 148 IS 4 BP 1037 EP 1042 PG 6 WC Immunology SC Immunology GA HD975 UT WOS:A1992HD97500009 PM 1346620 ER PT J AU JAIN, J VALGEARCHER, VE RAO, A AF JAIN, J VALGEARCHER, VE RAO, A TI ANALYSIS OF THE AP-1 SITES IN THE IL-2 PROMOTER SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LEUCINE ZIPPER PROTEINS; LYMPHOCYTE-SPECIFIC FACTORS; C-FOS PROMOTER; DNA-BINDING; INTERLEUKIN-2 GENE; ANTIGEN RECEPTOR; JUN PROTEINS; KAPPA-B; PROTO-ONCOGENE; T-CELLS AB We have investigated the role of the two AP-1 sites, located at approximately -150 and -180 bp relative to the transcription start site, in induction of the IL-2 promoter through the TCR/CD3 complex. We show that only the proximal (-150 bp) AP-1 site is functional in vitro, as judged by its ability to bind nuclear proteins from T cells stimulated with Ag or anti-CD3-epsilon. The inducible nuclear proteins binding to this site have the characteristics of AP-1, as judged by their kinetics of induction, the ability to compete and be competed efficiently by a metallothionein AP-1 site oligonucleotide, and their reaction with antibodies to Fos and Jun proteins. Mutations in the proximal AP-1 site greatly diminish or abrogate induction of the IL-2 promoter, indicating that the site is also functional in vivo. Although the distal (-180 bp) AP-1 site is incapable of direct binding to nuclear proteins from activated T cells, a mutation in this site diminishes IL-2 promoter induction, suggesting that this site may also be functional in vivo. Cotransfection of a 5' IL-2-chloramphenicol acetyltransferase plasmid with c-Fos and/or c-Jun enhances the induction of IL-2-chloramphenicol acetyltransferase activity, confirming that the IL-2 promoter contains a functional AP-1 site. Both AP-1 sites may be targets for c-Fos action, as inferred from the results of experiments in which c-Fos was cotransfected with internal deletion mutants of the IL-2 promoter lacking either AP-1 site. Northern analysis indicates that mRNAs for at least six members of the Fos/Jun family (c-fos,fosB,fra-1, c-jun, junB, and junD) are expressed in activated Ar-5 cells; thus the AP-1 sites of the IL-2 promoter may bind different dimeric Fos/Jun complexes at different times after T cell activation, perhaps mediating both positive and negative regulation of the IL-2 promoter. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR VIROL,MAYER BLDG,ROOM 628,44 BINNEY ST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. MIT,DEPT BIOL,CAMBRIDGE,MA 02139. FU NCI NIH HHS [CA42471] NR 60 TC 167 Z9 168 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 FEB 15 PY 1992 VL 148 IS 4 BP 1240 EP 1250 PG 11 WC Immunology SC Immunology GA HD975 UT WOS:A1992HD97500037 PM 1737937 ER PT J AU PARK, EC FINLEY, D SZOSTAK, JW AF PARK, EC FINLEY, D SZOSTAK, JW TI A STRATEGY FOR THE GENERATION OF CONDITIONAL MUTATIONS BY PROTEIN DESTABILIZATION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE PROTEOLYSIS; UBIQUITIN; FUSION PROTEINS; MATING TYPE ID N-END RULE; YEAST; LOCUS; SITE; HML AB Conditional mutations such as temperature-sensitive (ts) mutations are important for the analysis of protein function but are often difficult, or impossible, to obtain. Here we present a simple method for generating conditional mutations based on the use of a protein-destabilizing genetic element in combination with systems allowing the induction and repression of gene expression. This genetic cassette can be fused to other protein-coding sequences, and once transcription is turned off and synthesis of the gene product ceases, the preexisting protein is rapidly degraded. We have applied this method to the analysis of the yeast ARD1 gene product, a subunit of an N-terminal acetyltransferase, and show that a complete loss of ARD1 product can be achieved in less than one generation. Despite the rapid loss of ARD1 protein, there is a prolonged delay in the expression of the ard1 mutant phenotype, suggesting that the acetylated substrates of ARD1 are metabolically stable and/or exert a long-lasting effect on processes such as the repression of the silent mating type cassettes. C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT CELLULAR & MOLEC PHYSIOL,BOSTON,MA 02115. RP PARK, EC (reprint author), MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114, USA. NR 15 TC 55 Z9 55 U1 3 U2 3 PU NATL ACAD PRESS 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 FEB 15 PY 1992 VL 89 IS 4 BP 1249 EP 1252 DI 10.1073/pnas.89.4.1249 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA HE606 UT WOS:A1992HE60600021 PM 1311090 ER PT J AU MOINGEON, P LUCICH, JL MCCONKEY, DJ LETOURNEUR, F MALISSEN, B KOCHAN, J CHANG, HC RODEWALD, HR REINHERZ, EL AF MOINGEON, P LUCICH, JL MCCONKEY, DJ LETOURNEUR, F MALISSEN, B KOCHAN, J CHANG, HC RODEWALD, HR REINHERZ, EL TI CD3-ZETA DEPENDENCE OF THE CD2 PATHWAY OF ACTIVATION IN LYMPHOCYTES-T AND NATURAL-KILLER-CELLS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE SIGNAL TRANSDUCTION; ACCESSORY MOLECULES; INTERLEUKIN-2 PRODUCTION; CA2+ MOBILIZATION ID ERYTHROCYTE BINDING-PROTEIN; RECEPTOR ZETA-CHAIN; FC-GAMMA RECEPTOR; ANTIGEN RECEPTOR; IGG FC; EXPRESSION; COMPLEX; CD16; SURFACE; RECOGNITION AB In T lymphocytes, signal transduction through the CD2 adhesion molecule requires surface expression of the CD3-Ti T-cell receptor (TCR) complex. In contrast, in natural killer (NK) cells, CD2 functions in the absence of a TCR. Because the TCR on T lymphocytes and the CD16 low-affinity IgG Fc receptor (Fc-gamma receptor type III) complex on NK cells share a common CD3-zeta subunit, we reasoned that CD3-zeta may be critical for CD2 signaling in T lymphocytes and NK cells. Here we show that transfection of a cDNA encoding a transmembrane form of CD16 into TCR- variants of the Jurkat T-cell line results in CD16 expression in association with endogenous CD3-zeta homodimers and restores CD2 signaling function. To test directly the role of CD3-zeta in CD2 triggering, we then transfected human CD2 into each of two murine T-T hybridomas that express TCRs containing either a full-length CD3-zeta subunit or a truncated CD3-zeta subunit incapable of transducing signals. Despite expression of equivalent surface levels of TCR, CD2-mediated signaling is seen only in the T cells containing wild-type CD3-zeta. These findings show that (i) CD16 on NK cells is functionally equivalent to the TCR on T lymphocytes for coupling CD2 to signaling pathways and (ii) CD2 signal transduction depends upon the CD3-zeta subunit of the TCR complex and, by inference, the CD3-zeta subunit of the CD16 complex. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. CNRS,INSERM,CTR IMMUNOL,F-13288 MARSEILLE 9,FRANCE. HOFFMANN LA ROCHE INC,DEPT MOLEC GENET,NUTLEY,NJ 07110. RP MOINGEON, P (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,IMMUNOBIOL LAB,BOSTON,MA 02115, USA. NR 36 TC 97 Z9 97 U1 0 U2 3 PU NATL ACAD PRESS 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 FEB 15 PY 1992 VL 89 IS 4 BP 1492 EP 1496 DI 10.1073/pnas.89.4.1492 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA HE606 UT WOS:A1992HE60600072 PM 1346934 ER PT J AU REED, GL AF REED, GL TI GENERATION OF SPECIES-SPECIFIC, RAT MONOCLONAL-ANTIBODIES THAT BIND TO THE KAPPA-CHAIN OF MOUSE IMMUNOGLOBULIN SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE MONOCLONAL ANTIBODY; 2ND ANTIBODY; IMMUNOGLOBULIN-KAPPA CHAIN; PLASMA HUMAN; PLASMA RABBIT; AFFINITY; IMMUNOASSAY AB Large numbers of mouse monoclonal antibodies (MAbs) with exquisite binding specificities have become available. However the study of these primary antibodies in biological fluids by second, anti-mouse antibody techniques, has been confounded by the large quantity of other animal immunoglobulin which is often present in these fluids. To overcome this problem, we have derived high affinity rat MAbs which bind specifically to the antigen binding fragments (Fab) of mouse antibody and display minimal or no crossreactivity with human or rabbit immunoglobulin at the concentrations which are usually found in plasma. Equilibrium binding studies demonstrated that these antibodies had binding affinity constants for mouse Fab that ranged from 4.3 x 10(8) to 4.1 x 10(9) M-1. All of these rat MAbs bound to the kappa chain of mouse immunoglobulin, though competition binding studies amongst these MAbs indicated that they probably recognized three different epitopes. Because of their specificity and affinity, these rat anti-mouse kappa MAbs may be useful in a wide variety of experimental biological systems both in vitro and in vivo. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP REED, GL (reprint author), MASSACHUSETTS GEN HOSP,MED SERV,CARDIAC UNIT,JACKSON 14,BOSTON,MA 02114, USA. FU NHLBI NIH HHS [HL-02348] NR 12 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD FEB 14 PY 1992 VL 147 IS 1 BP 111 EP 117 PG 7 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA HE947 UT WOS:A1992HE94700014 PM 1371795 ER PT J AU SPIES, T CERUNDOLO, V COLONNA, M CRESSWELL, P TOWNSEND, A DEMARS, R AF SPIES, T CERUNDOLO, V COLONNA, M CRESSWELL, P TOWNSEND, A DEMARS, R TI PRESENTATION OF VIRAL-ANTIGEN BY MHC CLASS-I MOLECULES IS DEPENDENT ON A PUTATIVE PEPTIDE TRANSPORTER HETERODIMER SO NATURE LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; TOXIC LYMPHOCYTES-T; HLA-B ANTIGENS; ASSOCIATION; PROTEIN; RECOGNITION; PATHWAY; INVITRO; REGION; CELLS AB MAJOR histocompatibility complex (MHC) class I molecules present peptides derived from the endogenous protein pool to cytotoxic T lymphocytes, which can thus recognize intracellular antigen 1-3 . This pathway may depend on a transporter (PSF1) (refs 4-6) to mediate entry of the cytosolic peptides into a pre-Golgi compartment where they bind to class I heavy chains and promote their stable assembly with beta-2-microglobulin 7-12. There is, however, only indirect support for this function of PSF1 (ref. 6). Here we show that PSF1 is necessary for the efficient assembly of class I molecules and enables them to present a peptide epitope derived from endogenously synthesized viral antigen. Immunochemical and genetic data demonstrate that the PSF1 polypeptide is associated with a complementary transporter chain, which is polymorphic and is encoded by the PSF2 gene 13, which is closely linked to PSF1. C1 JOHN RADCLIFFE HOSP,INST MOLEC MED,OXFORD OX3 9DU,ENGLAND. IST NAZL RIC CANC,I-16132 GENOA,ITALY. YALE UNIV,SCH MED,IMMUNOBIOL SECT,NEW HAVEN,CT 06510. UNIV WISCONSIN,GENET LAB,MADISON,WI 53706. RP SPIES, T (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR VIROL,44 BINNEY ST,BOSTON,MA 02115, USA. OI Cerundolo, Vincenzo/0000-0003-0040-3793; Townsend, Alain/0000-0002-3702-0107; Colonna, Marco/0000-0001-5222-4987 NR 28 TC 316 Z9 316 U1 0 U2 1 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD FEB 13 PY 1992 VL 355 IS 6361 BP 644 EP 646 DI 10.1038/355644a0 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA HD547 UT WOS:A1992HD54700058 PM 1538752 ER PT J AU HAMILTON, JD HARTIGAN, PM SIMBERKOFF, MS DAY, PL DIAMOND, GR DICKINSON, GM DRUSANO, GL EGORIN, MJ GEORGE, WL GORDIN, FM HAWKES, CA JENSEN, PC KLIMAS, NG LABRIOLA, AM LAHART, CJ OBRIEN, WA OSTER, CN WEINHOLD, KJ WRAY, NP ZOLLAPAZNER, SB AF HAMILTON, JD HARTIGAN, PM SIMBERKOFF, MS DAY, PL DIAMOND, GR DICKINSON, GM DRUSANO, GL EGORIN, MJ GEORGE, WL GORDIN, FM HAWKES, CA JENSEN, PC KLIMAS, NG LABRIOLA, AM LAHART, CJ OBRIEN, WA OSTER, CN WEINHOLD, KJ WRAY, NP ZOLLAPAZNER, SB TI A CONTROLLED TRIAL OF EARLY VERSUS LATE TREATMENT WITH ZIDOVUDINE IN SYMPTOMATIC HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION - RESULTS OF THE VETERANS AFFAIRS COOPERATIVE STUDY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID PLACEBO-CONTROLLED TRIAL; AIDS-RELATED COMPLEX; DOUBLE-BLIND; AZIDOTHYMIDINE AZT; CLINICAL-TRIALS; EFFICACY; TOXICITY; PATIENT; HIV AB Background. Zidovudine is recommended for asymptomatic and early symptomatic human immunodeficiency virus (HIV) infection. The best time to initiate zidovudine treatment remains uncertain, however, and whether early treatment improves survival has not been established. Methods. We conducted a multicenter, randomized, double-blind trial that compared early zidovudine therapy (beginning at 1500 mg per day) with late therapy in HIV-infected patients who were symptomatic and had CD4+ counts between 0.2 x 10(9) and 0.5 x 10(9) cells per liter (200 to 500 per cubic millimeter) at entry. Those assigned to late therapy initially received placebo and began zidovudine when their CD4+ counts fell below 0.2 x 10(9) per liter (200 per cubic millimeter) or when the acquired immunodeficiency syndrome (AIDS) developed. Results. During a mean follow-up period of more than two years, there were 23 deaths in the early-therapy group (n = 170) and 20 deaths in the late-therapy group (n = 168) (P = 0.48; relative risk [late vs. early], 0.81; 95 percent confidence interval, 0.44 to 1.59). In the early-therapy group, 28 patients progressed to AIDS, as compared with 48 in the late-therapy group (P = 0.02; relative risk, 1.76; 95 percent confidence interval, 1.1 to 2.8). Early therapy increased the time until CD4+ counts fell below 0.2 x l0(9) per liter (200 per cubic millimeter), and it produced more conversions from positive to negative for serum p24 antigen. Early therapy was associated with more anemia, leukopenia, nausea, vomiting, and diarrhea, whereas late therapy was associated with more skin rash. Conclusions. In symptomatic patients with HIV infection, early treatment with zidovudine delays progression to AIDS, but in this controlled study it did not improve survival, and it was associated with more side effects. C1 DEPT VET AFFAIRS MED CTR,BALTIMORE,MD. DEPT VET AFFAIRS MED CTR,HOUSTON,TX. DEPT VET AFFAIRS MED CTR,LOS ANGELES,CA. DEPT VET AFFAIRS MED CTR,MIAMI,FL. DEPT VET AFFAIRS MED CTR,NEW YORK,NY. DEPT VET AFFAIRS MED CTR,SAN FRANCISCO,CA. DEPT VET AFFAIRS MED CTR,WASHINGTON,DC. VET AFFAIRS COORDINATING CTR,W HAVEN,CT. VET AFFAIRS COORDINATING CTR,ALBUQUERQUE,NM. DUKE UNIV,DURHAM,NC 27706. WALTER REED ARMY MED CTR,WASHINGTON,DC. RP HAMILTON, JD (reprint author), DEPT VET AFFAIRS MED CTR,508 FULTON ST,DURHAM,NC 27705, USA. NR 18 TC 330 Z9 330 U1 0 U2 3 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD FEB 13 PY 1992 VL 326 IS 7 BP 437 EP 443 DI 10.1056/NEJM199202133260703 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA HD164 UT WOS:A1992HD16400003 PM 1346337 ER PT J AU WARSHAW, AL FERNANDEZDELCASTILLO, C AF WARSHAW, AL FERNANDEZDELCASTILLO, C TI PANCREATIC-CARCINOMA SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID MALIGNANT OBSTRUCTIVE-JAUNDICE; NEEDLE ASPIRATION BIOPSY; ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY; SERUM IMMUNOREACTIVE ELASTASE; HORMONE-RELEASING HORMONE; POLYPEPTIDE ANTIGEN TPA; PAST MEDICAL HISTORY; PHASE-II TRIAL; DUCTAL ADENOCARCINOMA; DIABETES-MELLITUS C1 HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. RP WARSHAW, AL (reprint author), MASSACHUSETTS GEN HOSP,SURG SERV,ACC-336,BOSTON,MA 02114, USA. NR 187 TC 1271 Z9 1303 U1 3 U2 31 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 FEB 13 PY 1992 VL 326 IS 7 BP 455 EP 465 DI 10.1056/NEJM199202133260706 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA HD164 UT WOS:A1992HD16400006 PM 1732772 ER PT J AU GUSTAFSON, ML LEE, MM SCULLY, RE MONCURE, AC HIRAKAWA, T GOODMAN, A MUNTZ, HG DONAHOE, PK MACLAUGHLIN, DT FULLER, AF AF GUSTAFSON, ML LEE, MM SCULLY, RE MONCURE, AC HIRAKAWA, T GOODMAN, A MUNTZ, HG DONAHOE, PK MACLAUGHLIN, DT FULLER, AF TI MULLERIAN INHIBITING SUBSTANCE AS A MARKER FOR OVARIAN SEX-CORD TUMOR SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Note ID GRANULOSA-CELL TUMORS; ANNULAR TUBULES; RADIOIMMUNOASSAY; ESTRADIOL; SERUM; GENE C1 MASSACHUSETTS GEN HOSP,PEDIAT SURG RES LAB,WARREN 11,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,VINCENT RES LAB,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PEDIAT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT OBSTET & GYNECOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. OI Lee, Mary/0000-0002-7204-4884 FU NCI NIH HHS [5 RO1 CA17393] NR 25 TC 92 Z9 94 U1 0 U2 2 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD FEB 13 PY 1992 VL 326 IS 7 BP 466 EP 471 DI 10.1056/NEJM199202133260707 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA HD164 UT WOS:A1992HD16400007 PM 1732773 ER PT J AU KUTER, I HARRIS, NL AXELROD HARMON, DC AF KUTER, I HARRIS, NL AXELROD HARMON, DC TI A 57-YEAR-OLD MAN WITH A 20-YEAR HISTORY OF EPISODIC HEADACHE, FLUSHING, HYPOTENSION, AND OCCASIONAL SYNCOPE - SYSTEMIC MASTOCYTOSIS SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Discussion ID MAST-CELL ACTIVATION; CARCINOID-SYNDROME; BONE-MARROW; IDIOPATHIC ANAPHYLAXIS; URTICARIA PIGMENTOSA; PHEOCHROMOCYTOMA; DISEASE; MANAGEMENT; DIAGNOSIS; LOCALIZATION C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP KUTER, I (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 54 TC 5 Z9 5 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 FEB 13 PY 1992 VL 326 IS 7 BP 472 EP 481 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA HD164 UT WOS:A1992HD16400008 ER PT J AU ALEXANDERBRIDGES, M BUGGS, C GIERE, L DENARO, M KAHN, B WHITE, M SUKHATME, V NASRIN, N AF ALEXANDERBRIDGES, M BUGGS, C GIERE, L DENARO, M KAHN, B WHITE, M SUKHATME, V NASRIN, N TI MODELS OF INSULIN ACTION ON METABOLIC AND GROWTH-RESPONSE GENES SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE PHOSPHORYLATION; IRE-A; EGR-1; GAPDH; GENE TRANSCRIPTION; INSULIN ID GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE; S6 KINASE; PROTEIN; POLYPEPTIDE; RECEPTOR; CELLS AB In ongoing studies aimed at elucidating the mechanism of insulin action on the expression of genes that modulate glucose utilization and cell growth, we have focused on the inductive effect of insulin on transcription of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and the early growth response gene, Egr-1. Insulin acutely stimulates the expression of both genes in 3T3 adipocytes; however, in primary adipocytes, chronic insulin exposure has opposing effects on the expression of these genes. GAPDH mRNA is decreased in the epididymal fat cells of diabetic animals and is increased over control levels when insulin is replaced, while Egr-1 mRNA levels are increased in diabetic animals. These observations, coupled with the finding that insulin-stimulated Egr-1 gene transcription is impaired in a Chinese hamster ovarian (CHO) cell line that displays normal metabolic responses but impaired ability to regulate DNA synthesis, support the conclusion that insulin regulation of Egr-1, a growth response gene, and GAPDH, a metabolic response gene, are mediated by distinct pathways. We present evidence that supports the role of protein phosphorylation in mediating the effect of insulin on activation of Egr-1 and GAPDH gene transcription. RP ALEXANDERBRIDGES, M (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,HOWARD HUGHES MED INST,DIABET UNIT,WELLMAN 306,BOSTON,MA 02114, USA. NR 11 TC 27 Z9 27 U1 0 U2 3 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD FEB 12 PY 1992 VL 109 IS 2 BP 99 EP 105 PG 7 WC Cell Biology SC Cell Biology GA HH867 UT WOS:A1992HH86700002 PM 1625685 ER PT J AU GOLDSTEIN, BJ ZHANG, WR HASHIMOTO, N KAHN, CR AF GOLDSTEIN, BJ ZHANG, WR HASHIMOTO, N KAHN, CR TI APPROACHES TO THE MOLECULAR-CLONING OF PROTEIN-TYROSINE PHOSPHATASES IN INSULIN-SENSITIVE TISSUES SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE INSULIN ACTION; PROTEIN-TYROSINE PHOSPHATASES; INSULIN RESISTANCE; PROTEIN PHOSPHORYLATION; INSULIN RECEPTOR ID LEUKOCYTE-COMMON ANTIGEN; HUMAN-PLACENTA; PERMEABILIZED ADIPOCYTES; XENOPUS OOCYTES; KINASE-ACTIVITY; BETA-SUBUNIT; RECEPTOR; DEPHOSPHORYLATION; PHOSPHORYLATION; CELL AB The intrinsic tyrosyl kinase activity of the insulin receptor is regulated by a balance between insulin-induced receptor autophosphorylation, which stimulates the receptor kinase, and enzymatic dephosphorylation of the receptor, which deactivates its kinase activity. The cellular protein-tyrosine phosphatase (PTPase) enzymes responsible for reversing the activated state of the insulin receptor have not been characterized. Our laboratory is interested in identifying and cloning the specific PTPase(s) that regulate the phosphorylation state of the insulin receptor. This chapter will summarize the design and results of our initial molecular cloning studies to identify specific PTPases in insulin-sensitive tissues that may have a potential physiological role in insulin action and clinical insulin resistance. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT MED,BOSTON,MA 02115. RP GOLDSTEIN, BJ (reprint author), JOSLIN DIABET CTR,DIV RES,1 JOSLIN PL,BOSTON,MA 02215, USA. FU NIDDK NIH HHS [DK43396, DK36836, DK33201] NR 33 TC 12 Z9 12 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD FEB 12 PY 1992 VL 109 IS 2 BP 107 EP 113 PG 7 WC Cell Biology SC Cell Biology GA HH867 UT WOS:A1992HH86700003 PM 1625676 ER PT J AU ROY, RJ GOSSELIN, P ANZIVINO, MJ MOORE, DD GUERIN, SL AF ROY, RJ GOSSELIN, P ANZIVINO, MJ MOORE, DD GUERIN, SL TI BINDING OF A NUCLEAR-PROTEIN TO THE RAT GROWTH-HORMONE SILENCER ELEMENT SO NUCLEIC ACIDS RESEARCH LA English DT Article ID NEGATIVE REGULATORY ELEMENTS; TISSUE-SPECIFIC EXPRESSION; FACTOR-I; GENE-EXPRESSION; TRANSCRIPTIONAL SILENCER; 3-HYDROXY-3-METHYLGLUTARYL-COENZYME-A REDUCTASE; FACTOR-1-LIKE PROTEINS; COLLAGEN PROMOTER; POSITIVE ACTIVITY; DNA RECOGNITION AB The rat growth hormone (rGH) gene is uniquely expressed in a subset of cells from the anterior pituitary. This strongly cell type specific expression is controlled by both cis-acting positive sequences that bind the pituitary specific transcription factor Pit-1 and cis-acting negative regulatory elements that lie upstream of the Pit-1 sites. The negative elements act to prevent expression of the gene in inappropriate cell types. Here we report that the most proximal rGH silencer element is specifically bound by a protein found in a number of rGH non-expressing cell types and which exerts a negative regulatory effect through the recognition of this rGH element in transient transfection assays. The sequence recognized by this protein is similar to sequences of several other negative regulatory elements as well as to the consensus binding site for the transcription factor NF1. However, the 45 KDa molecular weight identified for this protein does not correspond to any of the sizes previously reported for NF1 suggesting that it is likely to represent a new member amongst this family of transcription factors. C1 MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. UNIV LAVAL,FAC MED,DEPT PHYSIOL,QUEBEC CITY G1K 7P4,QUEBEC,CANADA. RP ROY, RJ (reprint author), CHU LAVAL,CTR RECH ENDOCRINOL MOLEC,2705 BLVD LAURIER,QUEBEC CITY G1V 4G2,QUEBEC,CANADA. NR 54 TC 37 Z9 37 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD FEB 11 PY 1992 VL 20 IS 3 BP 401 EP 408 DI 10.1093/nar/20.3.401 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HE570 UT WOS:A1992HE57000003 PM 1741274 ER PT J AU PRENTICE, HL AF PRENTICE, HL TI HIGH-EFFICIENCY TRANSFORMATION OF SCHIZOSACCHAROMYCES-POMBE BY ELECTROPORATION SO NUCLEIC ACIDS RESEARCH LA English DT Article RP MASSACHUSETTS GEN HOSP, DEPT MOLEC BIOL, BOSTON, MA 02114 USA. NR 7 TC 210 Z9 212 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD FEB 11 PY 1992 VL 20 IS 3 BP 621 EP 621 DI 10.1093/nar/20.3.621 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HE570 UT WOS:A1992HE57000048 PM 1741305 ER PT J AU JENNE, JW AF JENNE, JW TI PHARMACOKINETICS AND DRUG-MONITORING - A CITATION-CLASSIC COMMENTARY ON PHARMACOKINETICS OF THEOPHYLLINE - APPLICATION TO ADJUSTMENT OF CLINICAL DOSE OF AMINOPHYLLINE BY JENNE,J.W., WYSE,E., ROOD,F.S. AND MCDONALD,F.M. SO CURRENT CONTENTS/CLINICAL MEDICINE LA English DT Article ID METABOLITES; SERUM RP JENNE, JW (reprint author), US DEPT VET AFFAIRS,EDWARD HINES JR HOSP,HINES,IL 60141, USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU INST SCI INFORM INC PI PHILADELPHIA PA 3501 MARKET ST, PHILADELPHIA, PA 19104 SN 0891-3358 J9 CC/CLIN MED PD FEB 10 PY 1992 IS 6 BP 10 EP 10 PG 1 WC Multidisciplinary Sciences; Social Sciences, Interdisciplinary SC Science & Technology - Other Topics; Social Sciences - Other Topics GA HA328 UT WOS:A1992HA32800001 ER PT J AU PARDEE, AB AF PARDEE, AB TI A GROWTH-CONTROL EVENT DEFECTIVE IN TUMORS - A CITATION-CLASSIC COMMENTARY ON A RESTRICTION POINT FOR CONTROL OF NORMAL ANIMAL-CELL PROLIFERATION BY PARDEE,A.B. SO CURRENT CONTENTS/LIFE SCIENCES LA English DT Article ID CYCLE RP PARDEE, AB (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115, USA. NR 7 TC 0 Z9 0 U1 3 U2 5 PU INST SCI INFORM INC PI PHILADELPHIA PA 3501 MARKET ST, PHILADELPHIA, PA 19104 SN 0011-3409 J9 CC/LIFE SCI PD FEB 10 PY 1992 IS 6 BP 11 EP 11 PG 1 WC Multidisciplinary Sciences; Social Sciences, Interdisciplinary SC Science & Technology - Other Topics; Social Sciences - Other Topics GA HA329 UT WOS:A1992HA32900002 ER PT J AU DURKOP, H LATZA, U HUMMEL, M EITELBACH, F SEED, B STEIN, H AF DURKOP, H LATZA, U HUMMEL, M EITELBACH, F SEED, B STEIN, H TI MOLECULAR-CLONING AND EXPRESSION OF A NEW MEMBER OF THE NERVE GROWTH-FACTOR RECEPTOR FAMILY THAT IS CHARACTERISTIC FOR HODGKINS-DISEASE SO CELL LA English DT Article ID TUMOR-NECROSIS-FACTOR; STERNBERG-REED CELLS; MONOCLONAL-ANTIBODY; POINT MUTATIONS; LYMPHOID-CELLS; KI-1 ANTIGEN; PROTEIN; LINES; TRANSLOCATION; EFFICIENCY AB In man, Hodgkin's disease (HD) represents the most frequent lymphoma entity whose pathogenesis is still unknown. In order to contribute to the characterization of the molecular mechanisms of this disease, cDNAs coding for the HD characteristic antigen CD30 were cloned from expression libraries of the human HUT-102 cell line using the monoclonal antibodies Ki-1 and Ber-H2. The open reading frame of the cDNA that can be translated from two mRNA species of 2.6 kb, and 3.8 kb, respectively, predicts a 595 amino acid protein with leader, extracellular, single transmembrane, and intracellular domains. When expressed in COS-1 cells, the cDNA presented properties comparable to native CD30 antigen. The CD30 extracellular domain proved to be homologous to members of the nerve growth factor receptor superfamily. Six cysteine-rich motifs could be recognized within the putative ligand-binding domain. C1 FREE UNIV BERLIN,KLINIKUM STEGLITZ,INST PATHOL,W-1000 BERLIN 45,GERMANY. MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. NR 63 TC 546 Z9 554 U1 3 U2 8 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD FEB 7 PY 1992 VL 68 IS 3 BP 421 EP 427 DI 10.1016/0092-8674(92)90180-K PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA HD398 UT WOS:A1992HD39800004 PM 1310894 ER PT J AU BARNES, TM BURGLIN, TR AF BARNES, TM BURGLIN, TR TI PRUNE FUNCTION SO NATURE LA English DT Letter ID DROSOPHILA C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. RP BARNES, TM (reprint author), MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114, USA. NR 10 TC 4 Z9 4 U1 0 U2 0 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD FEB 6 PY 1992 VL 355 IS 6360 BP 504 EP 505 DI 10.1038/355504b0 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA HC526 UT WOS:A1992HC52600036 PM 1741029 ER PT J AU WOODS, BT HEDLEYWHYTE, ET GROWDON, JH MCKEE, AC CHIN, JK AF WOODS, BT HEDLEYWHYTE, ET GROWDON, JH MCKEE, AC CHIN, JK TI A 67-YEAR-OLD MAN WITH APHASIA AND MEMORY LOSS, FOLLOWED BY PROGRESSIVE DEMENTIA - PICKS LOBAR ATROPHY (PICKS DISEASE) SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Discussion ID PHOSPHORYLATED NEUROFILAMENT EPITOPES; GERSTMANN-STRAUSSLER SYNDROME; CREUTZFELDT-JAKOB DISEASE; ALZHEIMERS-DISEASE; NEUROFIBRILLARY TANGLES; AMYLOID PROTEIN; BODIES; PARKINSONISM; GENETICS; VARIANT C1 MCLEAN HOSP,CTR BRAIN IMAGING,BELMONT,MA 02178. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP WOODS, BT (reprint author), MCLEAN HOSP,DEPT NEUROL,BELMONT,MA 02178, USA. NR 37 TC 9 Z9 9 U1 0 U2 1 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD FEB 6 PY 1992 VL 326 IS 6 BP 397 EP 405 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA HC386 UT WOS:A1992HC38600008 ER PT J AU SUIT, H URIE, M AF SUIT, H URIE, M TI PROTON-BEAMS IN RADIATION-THERAPY SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Review ID INTRACRANIAL ARTERIOVENOUS-MALFORMATIONS; UVEAL MELANOMAS; SURVIVAL RATES; CHONDROSARCOMA; IRRADIATION; CHORDOMA; SKULL; BASE AB The rationale for study of proton radiation therapy is that, for some anatomic sites and tumors, the treatment volume is smaller; i.e., there is less irradiation of nontarget tissue while the target is included in three dimensions at each treatment session. As a result, the dose to the target can be raised. The consequence is that the tumor control probability improves and the frequency and severity of treatment-related morbidity decrease. These results come about from the physical fact that the proton range in tissue is finite; in comparison, absorption of photons is an exponential function and, hence, some dose is received for the full-beam path through the body. Accordingly, the dose deep to the target for proton treatments can be zero for each beam path. This situation provides a virtually certain means of improving the treatment outcome for selected categories of patients. Experience to date with proton radiation therapy has been quite limited. As of June 1991, the total number of proton radiation-treated patients was 11 763 from the various centers. Of that number, approximately 46% and 32% have been treated for small benign intracranial lesions (principally pituitary adenomas and arteriovenous malformations) and for tumors of the eve, respectively. Thus, only some 2500 patients have been treated for all other tumor types. The results from three centers and approximately 2800 patients with uveal melanoma are that the local control rate was 96% (for failures in-field, marginal, and in other parts of the eye). The local control results for chondrosarcomas and chordomas of the skull base are 91% and 65%, respectively. These percentages compare with some 35% achieved with conventional treatment. Experience with arteriovenous malformations indicates that control of bleeding and disappearance of the lesion are comparable to those achieved by other procedures. The developments from the proton therapy programs have contributed greatly to radiation treatment planning, e.g., the first three-dimensional treatment planning system put into regular clinical use (uveal melanoma), beam's eve view, digital-reconstructed radiograph, dose-volume histograms, and definitions of the uncertainty in dose around any defined point. The potential for clinical gains is high. In May 1991, the Proton Radiation Oncology (Group was formed to design, supervise, and coordinate clinical trials and to assist in data analysis. The efficacy of proton radiation therapy will be compared with that of photon therapy of the very highest technology. RP SUIT, H (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,BOSTON,MA 02114, USA. FU NCI NIH HHS [CA-23219] NR 31 TC 92 Z9 94 U1 2 U2 6 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 FEB 5 PY 1992 VL 84 IS 3 BP 155 EP 164 DI 10.1093/jnci/84.3.155 PG 10 WC Oncology SC Oncology GA HG727 UT WOS:A1992HG72700009 PM 1311773 ER PT J AU HOLDEN, SA TEICHER, BA ARA, G HERMAN, TS COLEMAN, CN AF HOLDEN, SA TEICHER, BA ARA, G HERMAN, TS COLEMAN, CN TI ENHANCEMENT OF ALKYLATING AGENT ACTIVITY BY SR-4233 IN THE FSAIIC MURINE FIBROSARCOMA SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID HAMSTER OVARY CELLS; DNA CROSS-LINKING; SENSITIZER MISONIDAZOLE; CYTO-TOXICITY; MELPHALAN; INVIVO; RADIATION; INVITRO; CHEMOSENSITIZATION; RADIOSENSITIVITY AB Background: The most commonly used antineoplastic drugs are more cytotoxic toward normally oxygenated tumor cells than toward hypoxic tumor cells. Purpose and Methods: To examine the ability of SR-4233, a new cytotoxic agent, to overcome the resistance of hypoxic tumor cells to antitumor alkylating agents, we tested the cytotoxic effect of SR-4233 alone and in combination with varying doses of cisplatin (CDDP), cyclophosphamide (CPM), carmustine (BCNU), or melphalan L-PAM) on tumor cells and bone marrow cells isolated from C3H/FeJ mice bearing the FSaIIC fibrosarcoma. Results: When SR-4233 alone was given, tumor cell killing was limited. When SR-4233 was administered just before single-dose treatment with CDDP, CPM, BCNU, or L-PAM, however, marked dose enhancement leading to increased cytotoxic effects on tumor cells and on bone marrow cells was observed. Similar experiments with tumor cell subpopulations, selected by Hoechst 33342 dye diffusion, confirmed that while cytotoxicity to both bright (oxygenated) and dim (hypoxic) cells was increased by combining each alkylating agent with SR-4233, the enhancement of the effect was relatively greater in the subpopulation of dim cells. The delay in the growth of tumors in animals treated with the combination of SR-4233 and CDDP, CPM, or L-PAM was 1.6-fold to 5.3-fold greater than that in animals treated with each alkylating agent alone. Conclusion: Our results suggest that SR-4233 may have the potential to improve the clinical efficacy of commonly used antitumor alkylating agents. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115. JOINT CTR RADIAT THERAPY,BOSTON,MA. FU NCI NIH HHS [P01CA-19589] NR 39 TC 48 Z9 48 U1 0 U2 0 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 FEB 5 PY 1992 VL 84 IS 3 BP 187 EP 193 DI 10.1093/jnci/84.3.187 PG 7 WC Oncology SC Oncology GA HG727 UT WOS:A1992HG72700013 PM 1542129 ER PT J AU BLAZERYOST, BL WATANABE, M HAVERTY, TP ZIYADEH, FN AF BLAZERYOST, BL WATANABE, M HAVERTY, TP ZIYADEH, FN TI ROLE OF INSULIN AND IGF1 RECEPTORS IN PROLIFERATION OF CULTURED RENAL PROXIMAL TUBULE CELLS SO BIOCHIMICA ET BIOPHYSICA ACTA LA English DT Article DE KIDNEY GROWTH; MITOGENESIS; EPIDERMAL GROWTH FACTOR; COMPETITIVE BINDING ASSAY; (MOUSE CORTICAL TUBULE) ID GROWTH-FACTOR-I; SERUM-FREE MEDIUM; KIDNEY EPITHELIAL-CELLS; HUMAN-FIBROBLASTS; HYBRID RECEPTORS; DEFINED MEDIUM; SOMATOMEDIN-C; RAT; TRANSPORT; LINE AB We have used a murine proximal tubule cell line (MCT cells) to determine the presence and binding characteristics of insulin and IGF1 receptors and to correlate these parameters with the concentration-response relationships for ligand-induced cellular proliferation. Separate insulin and IGF1 receptors were identified by equilibrium binding assays. Half-maximal displacement of either peptide occurred at 3-10 nM; crossover binding to the alternate receptor occurred with a 10- to 100-fold lower affinity. Peptide effects on cellular proliferation were determined by measuring [H-3]thymidine incorporation. Both insulin and IGF1 stimulate thymidine incorporation in a dose-dependent manner with similar increases above the basal level. The estimated half-maximal stimulation (EC50) occurred at 4 nM for IGF1 and 8 nM for insulin. A comparison of the receptor binding affinities with the dose-response relationships for [H-3]thymidine incorporation reveals that each growth factor appears to be exerting its effect via binding to its own receptor. Therefore, in this cell line, physiologic concentrations of either insulin or IGF1 can modulate cellular growth. To our knowledge this is the first demonstration of mitogenic effect which may be modulated by ligand binding to the insulin receptor in proximal tubule epithelia. C1 UNIV PENN,SCH MED,PHILADELPHIA,PA 19104. RP BLAZERYOST, BL (reprint author), VET AFFAIRS MED CTR,DEPT MED,DIV RENAL ELECTROLYTE,ROOM A303R,UNIV & WOODLAND AVES,PHILADELPHIA,PA 19104, USA. FU NIDDK NIH HHS [DK-39565] NR 42 TC 19 Z9 19 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-3002 J9 BIOCHIM BIOPHYS ACTA PD FEB 3 PY 1992 VL 1133 IS 3 BP 329 EP 335 DI 10.1016/0167-4889(92)90055-G PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA HD987 UT WOS:A1992HD98700013 PM 1310625 ER PT J AU STEIN, PD ATHANASOULIS, C GREENSPAN, RH HENRY, JW AF STEIN, PD ATHANASOULIS, C GREENSPAN, RH HENRY, JW TI RELATION OF PLAIN CHEST RADIOGRAPHIC FINDINGS TO PULMONARY ARTERIAL-PRESSURE AND ARTERIAL BLOOD-OXYGEN LEVELS IN PATIENTS WITH ACUTE PULMONARY-EMBOLISM SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article AB Abnormalities of the plain chest radiograph of 123 patients with acute pulmonary embolism (PE) and no prior cardiac or pulmonary disease were related to the pulmonary arterial mean pressure, the partial pressure of oxygen in arterial blood, and the alveolar-arterial oxygen gradient. Patients with either a prominent central pulmonary artery or cardiomegaly had higher pulmonary arterial mean pressures than did patients with atelectasis, a pulmonary parenchymal abnormality or pleural effusion (p < 0.001). These radiographic findings give clues to the severity of pulmonary hypertension in acute PE and suggest that pulmonary infarction or hemorrhage is associated with less severe PE. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. YALE UNIV,NEW HAVEN,CT 06520. RP STEIN, PD (reprint author), HENRY FORD HEART & VASC INST,2799 W GRAND BLVD,DETROIT,MI 48202, USA. FU NHLBI NIH HHS [N01-HR-34009, N01-HR-34012, N01-HR-34008] NR 7 TC 22 Z9 23 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 FEB 1 PY 1992 VL 69 IS 4 BP 394 EP 396 DI 10.1016/0002-9149(92)90240-Y PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA HB248 UT WOS:A1992HB24800019 PM 1734655 ER PT J AU FLOTTE, TJ PASTELLEVY, C GRAEMECOOK, F PREFFER, F BELL, DA AF FLOTTE, TJ PASTELLEVY, C GRAEMECOOK, F PREFFER, F BELL, DA TI DNA FLOW-CYTOMETRY OF PRIMARY TUMORS AND THEIR SKIN METASTASES - CORRELATION OF DNA HISTOGRAMS SO AMERICAN JOURNAL OF DERMATOPATHOLOGY LA English DT Article DE DNA; FLOW CYTOMETRY; METASTASIS; SKIN ID RENAL-CELL CARCINOMA; THYROID-CARCINOMA; HETEROGENEITY; PATTERNS; CANCER; PLOIDY; INDEX AB The purpose of this study was to determine whether quantification of DNA content would demonstrate conserved patterns in primary tumors and their metastases and to learn whether this technique would be useful in determining if a tumor was metastatic from a previous primary tumor or represented a new neoplasm. The study comprised of all cases nonmelanoma metastatic skin lesions in which the primary tumor was also resected at this hospital between the years 1984 and 1990 (22 cases). Both the primary and metastatic lesions were examined by the deparaffinized flow cytometric technique for DNA content. DNA-ancuploid tumors were considered to correlate if the DNA indices (ratio of ancuploid to diploid peak channels) were within 10%. Thirty-four tumors were DNA-aneuploid; eight tumors were DNA-diploid. We found agreement in 20 of 22 cases (agree-aneuploid: 16 cases; agree-diploid: four cases). In six of our cases the histograms of the primary and the metastatic lesions did not correlate when only one block was examined; however, when three blocks from each site were studied, we found concordance of DNA indices in four cases. There was disagreement in two of 22 cases (disagree-different DNA indices: two cases). In both of these cases, only one block of the primary tumor was available for examination, and the histograms were of marginal quality. This study demonstrates that the histogram pattern (aneuploid versus diploid) of DNA content is highly conserved between primary and metastatic tumors. There was 91% agreement between DNA indices of primary tumors and their metastases (20 of 22 cases) using a 10% correlation criterion. These data indicate that flow cytometric DNA analysis offers supportive information but not diagnostic confirmation of the origin of a metastatic lesion. C1 HARVARD UNIV,SCH MED,DEPT DERMATOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RP FLOTTE, TJ (reprint author), MASSACHUSETTS GEN HOSP,DEPT PATHOL,FRUIT ST,BOSTON,MA 02114, USA. NR 26 TC 2 Z9 2 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 FEB PY 1992 VL 14 IS 1 BP 19 EP 23 DI 10.1097/00000372-199202000-00003 PG 5 WC Dermatology SC Dermatology GA HC322 UT WOS:A1992HC32200003 PM 1510211 ER PT J AU ZIEGLER, JW TODRES, ID AF ZIEGLER, JW TODRES, ID TI INTUBATION OF NEWBORNS SO AMERICAN JOURNAL OF DISEASES OF CHILDREN LA English DT Letter ID NASOTRACHEAL INTUBATION; ATROPINE; NEONATE RP ZIEGLER, JW (reprint author), MASSACHUSETTS GEN HOSP,ELLISON 3,BOSTON,MA 02114, USA. NR 5 TC 22 Z9 23 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0002-922X J9 AM J DIS CHILD JI Am. J. Dis. Child. PD FEB PY 1992 VL 146 IS 2 BP 147 EP 149 PG 3 WC Pediatrics SC Pediatrics GA HC690 UT WOS:A1992HC69000004 PM 1733141 ER PT J AU RAEHL, CL BOND, CA PITTERLE, ME AF RAEHL, CL BOND, CA PITTERLE, ME TI PHARMACEUTICAL SERVICES IN UNITED-STATES HOSPITALS IN 1989 SO AMERICAN JOURNAL OF HOSPITAL PHARMACY LA English DT Article DE ADMINISTRATION; CLINICAL PHARMACY; DATA COLLECTION; DRUG DISTRIBUTION SYSTEMS; EDUCATION, PHARMACEUTICAL; GEOGRAPHY; MANPOWER; PHARMACEUTICAL SERVICES; PHARMACY, INSTITUTIONAL, HOSPITAL; STAFF DEVELOPMENT; UNITED-STATES ID ASHP NATIONAL SURVEY; CARE AB The results of a spring 1989 national survey of hospital-based pharmacy services are reported. The study group (n = 2112) comprised half of U.S. acute-care general surgical or medical hospitals with 50 or more licensed beds. Pharmacy directors were asked about their hospital's provision of 14 clinical pharmacy services. The survey had a response rate of 56% (1174 usable responses). Provision levels varied significantly with the pharmacy drug delivery system for 14 services, pharmacy director's education for 12 services, hospital teaching affiliation for 12 services, hospital ownership for 9 services, hospital size for 9 services, and geographic region for 5 services. The following percentages of respondents offered specific services: drug-use evaluation, 90%; inservice education, 66%; adverse drug reaction (ADR) management, 46%; drug therapy monitoring, 41%; pharmacokinetic consultations, 40%; parenteral-enteral nutrition team participation, 28%; patient medication counseling, 26%; drug therapy protocol management, 25%; cardiopulmonary resuscitation (CPR) team participation, 25%; clinical research, 22%; drug information, 16%; participation in medical rounds, 13%; poison information, 9%; and medication histories, 2%. Pharmacist staffing requirements for clinical services usually centralized within the department were highest for drug information and poison information. Within hospitals offering the services, four of nine patient-specific services were potentially available to more than half the patients: ADR management, CPR team participation, drug therapy monitoring, and nutrition team participation. Drug therapy protocol management required the most pharmacist staff time. Only one service, pharmacokinetic consultations, was justified by more than half of the providers of that service. Respondents expected all the services to undergo net growth during 1989-90. The 1989 National Clinical Pharmacy Services Survey showed that provision of clinical pharmacy services varied with the pharmacy drug delivery system, pharmacy director's education, hospital teaching affiliation, hospital ownership, hospital size, and geographic region. C1 WILLIAM S MIDDLETON MEM VET ADM MED CTR,ARRHYTHMIA CLIN,MADISON,WI 53705. RP RAEHL, CL (reprint author), UNIV WISCONSIN,SCH PHARM,MADISON,WI 53706, USA. NR 24 TC 46 Z9 46 U1 0 U2 0 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 SN 0002-9289 J9 AM J HOSP PHARM JI Am. J. Hosp. Pharm. PD FEB PY 1992 VL 49 IS 2 BP 323 EP 346 PG 24 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA HB963 UT WOS:A1992HB96300009 PM 1553999 ER PT J AU BOND, CA PITTERLE, ME RAEHL, CL AF BOND, CA PITTERLE, ME RAEHL, CL TI COST OF INPATIENT PHARMACEUTICAL SERVICES IN UNITED-STATES HOSPITALS IN 1989 SO AMERICAN JOURNAL OF HOSPITAL PHARMACY LA English DT Article DE ADMINISTRATION; CLINICAL PHARMACY; COSTS; DATA COLLECTION; DRUG DISTRIBUTION SYSTEMS; DRUG INFORMATION; EDUCATION, PHARMACEUTICAL; GEOGRAPHY; PHARMACEUTICAL SERVICES; PHARMACISTS, HOSPITAL; PHARMACY, INSTITUTIONAL, HOSPITAL; SUBSTITUTION; UNITED-STATES ID CLINICAL PHARMACY; CASE-MIX; DRUG; SEVERITY; ILLNESS; CARE AB The results of a spring 1989 national survey of hospital-based pharmacy services are reported; this article focuses on the cost structure of services. A questionnaire was sent to 2112 hospitals, comprising half of U.S. acute-care general medical or surgical hospitals with 50 or more licensed beds. Cost results were evaluated both as unadjusted data and as data adjusted with the case mix index (CMI). The survey had a response rate of 56% (1174 usable responses). Both pharmacy cost information and the CMI were obtained for 1000 hospitals. Mean +/- S.D. unadjusted medication costs per occupied bed were $6744 +/- $3048 and varied significantly with geographic region. Mean +/- S.D. pharmacist salary costs per full-time equivalent (FTE) were $38,432 +/- $8,550 and differed with geographic region, hospital ownership, the pharmacy drug delivery system, and the pharmacy director's education. Pharmacist salary costs associated with centrally based clinical pharmacy services ranged from a high of $60 per occupied bed per year for drug information services to a low of $15 for inservice education. The state with the highest mean +/- S.D. pharmacist annual salary per FTE was California ($45,900 +/- $11,037); the state with the lowest annual salary was Indiana ($29,637 +/- $7,110). A 1989 survey of clinical pharmacy services provided comprehensive data on complex cost structures. C1 WILLIAM S MIDDLETON MEM VET ADM MED CTR,ARRHYTHMIA CLIN,MADISON,WI 53705. RP BOND, CA (reprint author), UNIV WISCONSIN,SCH PHARM,MADISON,WI 53706, USA. NR 38 TC 10 Z9 10 U1 0 U2 0 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 SN 0002-9289 J9 AM J HOSP PHARM JI Am. J. Hosp. Pharm. PD FEB PY 1992 VL 49 IS 2 BP 347 EP 367 PG 21 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA HB963 UT WOS:A1992HB96300010 PM 1554000 ER PT J AU CLINTON, SK UNDERWOOD, R HAYES, L SHERMAN, ML KUFE, DW LIBBY, P AF CLINTON, SK UNDERWOOD, R HAYES, L SHERMAN, ML KUFE, DW LIBBY, P TI MACROPHAGE COLONY-STIMULATING FACTOR GENE-EXPRESSION IN VASCULAR CELLS AND IN EXPERIMENTAL AND HUMAN ATHEROSCLEROSIS SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID LOW-DENSITY-LIPOPROTEIN; SMOOTH-MUSCLE CELLS; HUMAN-ENDOTHELIAL-CELLS; TUMOR NECROSIS FACTOR; FACTOR CSF-1; MESSENGER-RNA; CHOLESTEROL DEPOSITION; MOLECULAR-CLONING; GROWTH-FACTOR; BETA-TUBULIN AB The infiltration of monocytes into the vascular wall and their transformation into lipid-laden foam cells characterizes early atherogenesis. Macrophages are also present in more advanced human atherosclerotic plaques and can produce many mediators that may contribute to lesion formation and progression. Macrophage colony-stimulating factor (MCSF) enhances the proliferation and differentiation of monocyte progenitors and is required for the survival and activation of mature monocytes and macrophages. The authors therefore examined the expression of the MCSF gene in cultured human vascular endothelial (EC) and smooth muscle cells (SMC) as well as in atheromatous lesions from rabbits and humans. Growth arrested EC and SMC contain a low level of MCSF mRNA. Bacterial lipopolysaccharide (LPS), recombinant human interleukin-1-alpha (IL-1-alpha) or tumor necrosis factor alpha (TNF-alpha) induced MCSF mRNA accumulation in a concentration-dependent manner in both EC and SMC. These stimuli induced large increases in MCSF mRNA with peak induction between 4-8 hours after treatment. LPS, IL-1-alpha, and TNF-alpha stimulated EC and SMC also showed increased fluorescent antibody staining for MCSF protein and released immunoreactive MCSF in a time-dependent manner. In contrast, phorbol 12-myristate 13-acetate (PMA) was a less potent inducer of MCSF gene expression and iron-oxidized low-density lipoproteins (ox-LDL) did not increase consistently MCSF mRNA or the synthesis and secretion of immunoreactive protein. Northern analysis of mRNA isolated from the atheromatous aorta of rabbits fed a 1% cholesterol diet for 10 weeks showed elevated MCSF mRNA compared with controls. Immunostaining of atheromatous arterial lesions of rabbits demonstrated MCSF protein in association with initimal SMC as well as macrophages. Furthermore, polymerase chain reaction (PCR) analysis of MCSF mRNA in human atheromata showed higher levels than found in nonatherosclerotic arteries and veins. Since the authors found no mRNA for the MCSF receptor, c-fms, in cultured EC or SMC macrophages are likely the primary target for MCSF within atheromatous vessels. The authors therefore investigated the effects of MCSF on monocyte functions related to foam cell development. Treatment of cultured human monocytes with recombinant human MCSF (10(3) U/ml, 72 hr) led to the accumulation of mRNA for the acetyl-LDL (scavenger) receptor and apolipoprotein E (apo E). These studies establish that vascular EC and SMC produce substantial MCSF in response to a variety of stimuli. The local production of MCSF during atherogenesis may contribute to macrophage survival and proliferation or activate specific macrophage functions such as expression of the scavenger receptor and secretion of apo E. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DIV CARDIOVASC,VASC MED & ATHEROSCLEROSIS UNIT,BOSTON,MA 02115. GENET INST,CAMBRIDGE,MA. RP CLINTON, SK (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,CLIN PHARMACOL LAB,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA 34813]; NHLBI NIH HHS [HL 34636] NR 72 TC 277 Z9 287 U1 0 U2 12 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD FEB PY 1992 VL 140 IS 2 BP 301 EP 316 PG 16 WC Pathology SC Pathology GA HE071 UT WOS:A1992HE07100008 PM 1739124 ER PT J AU BURSTEN, SL HARRIS, WE RESCH, K LOVETT, DH AF BURSTEN, SL HARRIS, WE RESCH, K LOVETT, DH TI LIPID-A ACTIVATION OF GLOMERULAR MESANGIAL CELLS - MIMICRY OF THE BIOACTIVE LIPID, PHOSPHATIDIC-ACID SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE ACYL TRANSFERASE; DIACYLGLYCEROL ID LIPOPOLYSACCHARIDE-BINDING PROTEINS; VASCULAR ENDOTHELIAL-CELLS; GRAM-NEGATIVE ENDOTOXIN; ESCHERICHIA-COLI; BACTERIAL LIPOPOLYSACCHARIDES; MONOSACCHARIDE PRECURSORS; MURINE SPLENOCYTES; ARACHIDONIC-ACID; RAT-LIVER; ACYLTRANSFERASE AB Lipid A, the active component of bacterial endotoxin, stimulates multiple cell types, including glomerular mesangial cells (MC), and yet the molecular mechanisms of cell activation remain unclear. Lipid A, in its monosaccharyl form, structurally resembles the biologically active lipid phosphatidic acid (PA). Given this, it was postulated that lipid A activates cells by acting as a structural and functional mimetic of PA. Lipid A was found to specifically stimulate an MC lyso-PA acyl transferase activity, leading to enhanced synthesis of sn-2-unsaturated forms of PA. Sn-2-unsaturated PA itself, in contrast to sn-2-saturated PA, also stimulated the lyso-PA acyl transferase activity, a positive feedback feature previously noted with lyso-lecithin acyl transferase. Structure-function correlations demonstrated that the phosphate moieties in both PA and lipid A were necessary to feedback stimulation of lyso-PA acyl transferase (AT), as dephosphorylated lipid A and 2-unsaturated 1,2-sn-diacylglycerol had no stimulatory effect on lyso-PA AT. The biologic relevance of the lipid A and PA-mediated increases in lyso-PA acyl transferase activity was shown, whereby limited exposure to these lipids rapidly induced identical MC morphologic and functional alterations characteristic of cellular activation. By mimicking the stimulatory action of PA, per se, on lyso-PA acyl transferase activity, lipid A may initiate a positive feedback cycle of acylation, yielding increased amounts of PA enriched in unsaturated fatty acids. This newly synthesized PA may subsequently act as the proximal mediator of cellular activation. C1 UNIV WASHINGTON,SEATTLE VET AFFAIRS MED CTR,DEPT MED,SEATTLE,WA 98108. HANOVER MED SCH,MOLEK PHARMAKOL ABT,W-3000 HANNOVER 61,GERMANY. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO VET AFFAIRS MED CTR,DEPT MED,SAN FRANCISCO,CA 94121. NR 45 TC 24 Z9 24 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 FEB PY 1992 VL 262 IS 2 BP C328 EP C338 PN 1 PG 11 WC Physiology SC Physiology GA HF161 UT WOS:A1992HF16100009 PM 1539625 ER PT J AU FRONTONI, S OHMAN, L HAYWOOD, JR DEFRONZO, RA ROSSETTI, L AF FRONTONI, S OHMAN, L HAYWOOD, JR DEFRONZO, RA ROSSETTI, L TI INVIVO INSULIN ACTION IN GENETIC MODELS OF HYPERTENSION SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE GLYCOGEN SYNTHESIS; INSULIN CLAMP; INSULIN SENSITIVITY; GLYCOLYSIS ID STIMULATED-GLUCOSE-UPTAKE; OBESE ZUCKER RATS; BLOOD-PRESSURE; DIABETIC RATS; DEPENDENT DIABETICS; SKELETAL-MUSCLE; RESISTANCE; SENSITIVITY; METABOLISM; HYPERINSULINEMIA AB Insulin resistance has been described in nonobese subjects with essential hypertension. At present it is unknown whether hypertension per se may lead to the onset of insulin resistance. To examine this question we studied in vivo insulin action in two rat models of genetic hypertension. Four groups of conscious rats were studied: Milan hypertensive (MHS), Milan normotensive (MNS), spontaneously hypertensive (SHR), and Wistar-Kyoto (WKY). Mean arterial pressure was increased in SHR vs. WKY in both the fed (184 +/- 5 vs. 126 +/- 6 mmHg; P < 0.001) and fasting (160 +/- 5 vs. 129 +/- 5; P < 0.001) states. During high-dose insulin clamps, total body glucose uptake (mg.kg-1.min-1) was similar in MNS (28.7 +/- 1.4) vs. MHS (33.6 +/- 3.0) and in WKY (34.6 +/- 1.8) vs. SHR (35.7 +/- 2.4). During low-dose insulin clamps, suppression of hepatic glucose production (3.5 +/- 0.6 vs. 3.0 +/- 0.5 mg.kg-1.min-1) and stimulation of glycolysis (12.9 +/- 0.8 vs. 14.4 +/- 1.5 mg.kg-1.min-1) were similar in WKY vs. SHR, whereas glucose uptake (24.6 +/- 1.9 vs. 18.3 +/- 1.2 mg.kg-1.min-1; P < 0.01) and muscle glycogenic rate (10.2 +/- 1.1 vs. 6.5 +/- 1.1 mg.kg-1.min-1; P < 0.05) were increased in SHR vs. WKY. In conclusion, 1) feeding markedly augments blood pressure in hypertensive but not in normotensive rats, and 2) hepatic and muscle insulin sensitivity are normal or increased in two different rat models of genetic hypertension. These results provide evidence that high blood pressure per se does not invariably lead to the development of insulin resistance. C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT PHARMACOL,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. RI FRONTONI, SIMONA/J-4893-2012 NR 46 TC 47 Z9 47 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 FEB PY 1992 VL 262 IS 2 BP E191 EP E196 PN 1 PG 6 WC Physiology SC Physiology GA HF161 UT WOS:A1992HF16100044 PM 1539644 ER PT J AU CASTELLINO, P SOLINI, A LUZI, L BARR, JG SMITH, DJ PETRIDES, A GIORDANO, M CARROLL, C DEFRONZO, RA AF CASTELLINO, P SOLINI, A LUZI, L BARR, JG SMITH, DJ PETRIDES, A GIORDANO, M CARROLL, C DEFRONZO, RA TI GLUCOSE AND AMINO-ACID-METABOLISM IN CHRONIC-RENAL-FAILURE - EFFECT OF INSULIN AND AMINO-ACIDS SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE PROTEIN METABOLISM ID DIETARY-PROTEIN INTAKE; LEUCINE METABOLISM; CLAMP TECHNIQUE; CHRONIC UREMIA; BETA-CELL; MUSCLE; RESISTANCE; DEFECTS; PLASMA; INSUFFICIENCY AB The effects of hyperinsulinemia and hyperaminoacidemia on glucose and amino acid metabolism were examined in 16 control and 13 chronic renal failure (CRF) patients under two conditions: 1) euglycemic hyperinsulinemia and 2) amino acid infusion. All studies were performed with continuous indirect calorimetry and [1-C-14]leucine infusion. In CRF patients insulin-mediated whole body glucose metabolism was reduced by 35% (4.41 +/- 0.50 vs. 6.76 +/- 0.73 mg.kg-1.min-1, P < 0.01), primarily due to a decrease in nonoxidative glucose disposal (1.70 +/- 0.70 vs. 4.32 +/- 0.60 mg.kg-1.min-1, P < 0.01); glucose oxidation was similar in both groups. In the postabsorptive state total leucine turnover (1.56 +/- 0.06 vs. 1.75 +/- 0.06), leucine oxidation (0.25 +/- 0.01 vs. 0.30 +/- 0.01), and nonoxidative leucine disposal (1.29 +/- 0.06 vs. 1.40 +/- 0.07-mu-mol.kg-1.min-1) were reduced in CRF vs. control subjects (all P < 0.05). In response to hyperinsulinemia, endogenous leucine flux (index of proteolysis), leucine oxidation, nonoxidative leucine disposal (NOLD) (index of protein synthesis), and net leucine flux into protein were similar in CRF and control subjects. In contrast, the ability of hyperaminoacidemia to enhance NOLD (1.54 +/- 0.11 vs. 2.10 +/- 0.10-mu-mol.kg-1.min-1, P < 0.01) and net leucine balance (0.27 +/- 0.05 vs. 0.41 +/- 0.05, P < 0.05) was reduced in CRF patients. In summary, in patients with CRF 1) basal leucine turnover and oxidation are reduced, 2) insulin-mediated suppression of proteolysis and net leucine flux into protein are normal, 3) amino acid-induced stimulation of protein synthesis and net flux of leucine into protein are impaired, and 4) insulin-mediated stimulation of glucose metabolism is reduced because of diminished nonoxidative glucose disposal. These results demonstrate a clear-cut dissociation between the effects of insulin on glucose vs. amino acid-protein metabolism, and an impairment in amino acid-induced stimulation of protein anabolism. C1 UNIV TEXAS,HLTH SCI CTR,DIV NEPHROL,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284. NAPLES UNIV,IST MED INTERNA & NEFROL,I-80134 NAPLES,ITALY. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. RI Luzi, Livio/M-2696-2016; Solini, Anna/K-4666-2016 OI Luzi, Livio/0000-0003-3183-0552; Solini, Anna/0000-0002-7855-8253 FU NCRR NIH HHS [RR-01346] NR 40 TC 64 Z9 65 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 FEB PY 1992 VL 262 IS 2 BP F168 EP F176 PN 2 PG 9 WC Physiology SC Physiology GA HF163 UT WOS:A1992HF16300073 PM 1539681 ER PT J AU SABOLIC, I CULIC, O LIN, SH BROWN, D AF SABOLIC, I CULIC, O LIN, SH BROWN, D TI LOCALIZATION OF ECTO-ATPASE IN RAT-KIDNEY AND ISOLATED RENAL CORTICAL MEMBRANE-VESICLES SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE IMMUNOFLUORESCENCE; IMMUNOGOLD; ENDOTHELIAL CELLS; PROXIMAL TUBULE; ANTI-ECTO-ADENOSINE-TRIPHOSPHATASE ANTIBODIES ID BRUSH-BORDER MEMBRANES; AORTIC ENDOTHELIAL-CELLS; LATERAL PLASMA-MEMBRANES; ADENOSINE-TRIPHOSPHATASE; EXTRACELLULAR ATP; ADENINE-NUCLEOTIDES; RABBIT NEPHRON; CORTEX; CALCIUM; THROMBOMODULIN AB Brush-border (BBMV) and basolateral membrane vesicles (BLMV) from rat renal cortex exhibit an ecto-ATPase activity that is distinct from other ATPases. We have examined the cellular and regional distribution of this enzyme in rat kidney using antibodies against rat liver ecto-ATPase. In isolated vesicles, the distribution shown by biochemical assays of ATPase activity was confirmed by immunocytochemistry and Western blotting. Indirect immunofluorescence and immunogold labeling showed that brush borders of the S1 and S3 segments of the proximal tubule (PT) were stained, but the S2 segment was negative. Staining was most intense in the S3 segment. The luminal membrane of the initial part of the thin descending limb of Henle also showed a marked staining. Surprisingly, basolateral plasma membranes of PT had no detectable staining. However, the plasma membrane of endothelial cells was heavily stained, both in larger vessels and in peritubular capillaries. Using an antibody against rat thrombomodulin, a marker for endothelial cell plasma membranes, we showed that preparations of BBMV, BLMV, and endocytic vesicles are all contaminated with these membranes. This may explain, at least partially, the biochemically measured ecto-ATPase activity in renal cortical membrane vesicles. Finally, no specific staining in the kidney was found using polyclonal antipeptide antibodies against the "long form" of liver ecto-ATPase, either by immunocytochemistry or by Western blotting. This indicates either that there is no long isoform of the ecto-ATPase in the kidney or that the intracellular domains of the long form are different in the two tissues. C1 HARVARD MED SCH,BOSTON,MA 02129. UNIV TEXAS,MD ANDERSON CANC CTR,DEPT MOLEC PATHOL,HOUSTON,TX 77030. RP SABOLIC, I (reprint author), MASSACHUSETTS GEN HOSP,DEPT PATHOL,RENAL UNIT,149 13TH ST,8TH FLOOR,BOSTON,MA 02129, USA. FU NIDDK NIH HHS [DK-38452] NR 38 TC 54 Z9 54 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 FEB PY 1992 VL 262 IS 2 BP F217 EP F228 PN 2 PG 12 WC Physiology SC Physiology GA HF163 UT WOS:A1992HF16300079 PM 1311523 ER PT J AU RIGOTTI, NA BOURNE, D ROSEN, A LOCKE, JA SCHELLING, TC AF RIGOTTI, NA BOURNE, D ROSEN, A LOCKE, JA SCHELLING, TC TI WORKPLACE COMPLIANCE WITH A NO-SMOKING LAW - A RANDOMIZED COMMUNITY INTERVENTION TRIAL SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID WORKSITES; POLICIES AB Background. Compliance with state and local laws restricting smoking in public places and workplaces has not been systematically evaluated. Methods. We assessed workplace compliance with a comprehensive no-smoking law adopted in Brookline, Mass, and tested whether mailing information to businesses increased awareness of and compliance with the law. We conducted a random sample telephone survey of 299 businesses (87% response rate). Self-reported compliance was validated by direct observations. Results. One year after its adoption, the law was popular with businesses. The prevalence of smoking restrictions, smoking policies, and no-smoking signs was 80%, 59%, and 40%, respectively. One third of businesses banned smoking. Full compliance with the law was low, however, because few businesses posted a copy of their smoking policy as required. The mailing increased employers' awareness of the law. Employers' sent the mailing also reported better compliance, but this was not confirmed by direct observations. Conclusions. The law was popular and contributed to a high prevalence of workplace smoking restrictions. Different interpretations of the law by policymakers and businesses seemed to explain why formal compliance was low. The mailing increased awareness of, but not compliance with, the law. C1 BOSTON UNIV,SCH MED,GEN INTERNAL MED SECT,BOSTON,MA 02118. ARKANSAS HLTH DEPT,LITTLE ROCK,AR. PUBL HLTH,BROOKLINE,MA. UNIV MARYLAND,DEPT ECON,COLLEGE PK,MD 20742. RP RIGOTTI, NA (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,GEN INTERNAL MED UNIT,FRUIT ST,BOSTON,MA 02114, USA. NR 18 TC 16 Z9 16 U1 2 U2 3 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 FEB PY 1992 VL 82 IS 2 BP 229 EP 235 DI 10.2105/AJPH.82.2.229 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA HL398 UT WOS:A1992HL39800015 PM 1739153 ER PT J AU STOMPER, PC CONNOLLY, JL AF STOMPER, PC CONNOLLY, JL TI MAMMOGRAPHIC FEATURES PREDICTING AN EXTENSIVE INTRADUCTAL COMPONENT IN EARLY-STAGE INFILTRATING DUCTAL CARCINOMA SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID PRIMARY RADIATION-THERAPY; II BREAST-CANCER; MASTECTOMY; INSITU; RADIOTHERAPY; EXCISION; TRIAL AB Several studies have shown that the presence of an extensive intraductal component in patients with infiltrating ductal carcinoma is a major factor for predicting local recurrence after breast-conserving surgery and radiotherapy. A prospective study of 101 consecutive mammograms in patients with stage I or II infiltrating ductal carcinoma was performed to determine the predictive values of mammographic features in determining the presence or absence of an extensive intraductal component. Thirty-five (35%) of the lesions contained a pathologically verified extensive intraductal component. Sixty-five percent (22/34) of lesions showing mammographic evidence of calcifications with or without a mass were associated with an extensive intraductal component (p < .001). Lesions with calcifications greater than 3 cm in extent were significantly (p < .05) more likely to have an extensive intraductal component (9/10; 90%) than those with calcifications less than 3 cm in extent (13/24; 54%). Only 17% (8/46) of patients in whom mammograms showed only a mass or architectural distortion and 24% (5/21) of patients who had a mass palpable clinically or who had normal findings on mammograms had lesions with an extensive intraductal component. We conclude that infiltrating ductal carcinomas associated with calcifications on mammography, especially if the calcifications are extensive, are likely to be associated with an extensive intraductal component. Carcinomas without calcifications that show masses or architectural distortion on mammography, or carcinomas with palpable masses and normal findings on mammography, are unlikely to have an extensive intraductal component. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT DIAGNOST RADIOL,BOSTON,MA 02115. HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02215. NR 17 TC 32 Z9 32 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 FEB PY 1992 VL 158 IS 2 BP 269 EP 272 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA HB058 UT WOS:A1992HB05800006 PM 1309620 ER PT J AU CHEW, FS CRENSHAW, WB AF CHEW, FS CRENSHAW, WB TI IDIOPATHIC TUMORAL CALCINOSIS SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP CHEW, FS (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,32 FRUIT ST,BOSTON,MA 02114, USA. NR 2 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 FEB PY 1992 VL 158 IS 2 BP 330 EP 330 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA HB058 UT WOS:A1992HB05800020 PM 1729793 ER PT J AU CULLEN, DJ NEMESKAL, AR COOPER, JB ZASLAVSKY, A DWYER, MJ AF CULLEN, DJ NEMESKAL, AR COOPER, JB ZASLAVSKY, A DWYER, MJ TI EFFECT OF PULSE OXIMETRY, AGE, AND ASA PHYSICAL STATUS ON THE FREQUENCY OF PATIENTS ADMITTED UNEXPECTEDLY TO A POSTOPERATIVE INTENSIVE-CARE UNIT AND THE SEVERITY OF THEIR ANESTHESIA-RELATED COMPLICATIONS SO ANESTHESIA AND ANALGESIA LA English DT Article AB Unanticipated intensive care unit admission (UIA) associated with anesthesia served as an outcome measure to assess the quality of anesthesia care in a large teaching hospital. We characterized the patient population and types of problems associated with UIAs, attempted to identify patterns of care that could have led to specific adverse outcomes, and determined if a specific intervention, pulse oximetry, reduced UIAs. During a consecutive 65-wk period (July 1985-September 1986), 17,093 surgical patients were expected to enter the recovery room and then return to floor care. Seventy-one patients (0.42%) experienced a UIA from either the recovery room or operating room, and the circumstances of their admissions were analyzed in detail. After introduction of pulse oximetry in all anesthetizing locations (not including the recovery room) in the 29th week, the overall rate of UIAs and, specifically, the rate of UIA to rule out myocardial infarction, decreased significantly. Increasing ASA physical status (ASA-PS) and age significantly increased the probability of UIA. UIA patients with ASA-PS III/IV had a significantly higher acuity in the intensive care unit and were far more likely to die during their hospitalization than ASA-PS I/II patients. Retrospective review of UIAs alone did not identify patterns of care requiring remediation, which leads us to question the utility of UIAs as a generic screen for quality assurance. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP CULLEN, DJ (reprint author), MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114, USA. NR 13 TC 53 Z9 53 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 FEB PY 1992 VL 74 IS 2 BP 181 EP 188 PG 8 WC Anesthesiology SC Anesthesiology GA HB064 UT WOS:A1992HB06400002 PM 1731535 ER PT J AU ECKHARDT, WF PATAFIO, O CIGARROA, FG AF ECKHARDT, WF PATAFIO, O CIGARROA, FG TI A RETAINED ESOPHAGEAL STETHOSCOPE AS A POTENTIAL CAUSE OF SMALL-BOWEL OBSTRUCTION SO ANESTHESIA AND ANALGESIA LA English DT Article C1 HARVARD UNIV,SCH MED,DEPT ANESTHESIA,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. RP ECKHARDT, WF (reprint author), MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,FRUIT ST,BOSTON,MA 02114, USA. NR 9 TC 2 Z9 2 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 FEB PY 1992 VL 74 IS 2 BP 300 EP 302 PG 3 WC Anesthesiology SC Anesthesiology GA HB064 UT WOS:A1992HB06400024 PM 1731554 ER PT J AU LEVINE, RL ROZENTAL, JM NICKLES, RJ AF LEVINE, RL ROZENTAL, JM NICKLES, RJ TI BLOOD-FLOW ASYMMETRY IN CAROTID OCCLUSIVE DISEASE SO ANGIOLOGY LA English DT Article ID CEREBROVASCULAR-DISEASE; ANGIOGRAPHIC FINDINGS; CEREBRAL PERFUSION; INHALATION; ISCHEMIA AB Patterns of anterior border zone (ABZ) and middle cerebral artery (MCA) cerebral blood flow (CBF) asymmetry were readily seen during both normocapnic room air (RA) and induced hypercapnic (CO2) inhalation using fluoromethane and a multislic, high-resolution positron scanner. Wilcoxon two-sample rank testing showed symptomatic-over-nonsymptomatic CBF ratios for unilateral greater than 75% carotid stenosis patients (n = 8) to be 1.05 +/- 0.07 (p < 0.008 as compared with control of 0.97 +/- 0.02) ABZ RA, 0.98 +/- 0.11 ABZ Co2, 0.98 +/- 0.04 MCA RA, and 0.98 +/- 0.06 MCA CO2. Unilateral carotid occlusion patients (n = 8) had ratios of 0.90 +/- 0.16 ABZ RA, 0.81 +/- 0.19 (p < 0.002) ABZ CO2, 0.90 +/- 0.12 and 0.89 +/- 0.13 for MCA RA and CO2, respectively (both p < 0.008 as compared with control 0.99). These preliminary results suggest an upgrade of autoregulation (ie, very high ratio) in the ABZ of high-grade stenosis patients during normocapnia. CBF was preferentially higher on the symptomatic side and then either did not increase or paradoxically fell in response to hypercapnia. In comparison, carotid occlusion patients had low ABZ and MCA ratios during normocapnia, also unable to increase with hypercapnia. The fall in ratios from normocapnia to hypercapnia indicates that these areas, already subject to maximal vasodilation, fail to increase CBF or actually become hypoperfused following induced hypercapnia. These results aid in understanding the concept of "hemodynamic significance." C1 WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI 53705. UNIV WISCONSIN,DEPT MED PHYS RADIOL,MADISON,WI 53706. RP LEVINE, RL (reprint author), UNIV WISCONSIN,SCH MED,DEPT NEUROL,H6-571 CLIN SCI CTR,600 HIGHLAND AVE,MADISON,WI 53792, USA. NR 18 TC 9 Z9 9 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 FEB PY 1992 VL 43 IS 2 BP 100 EP 109 DI 10.1177/000331979204300203 PG 10 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA HF157 UT WOS:A1992HF15700003 PM 1536470 ER PT J AU TROUTON, TG BARRY, JJ ALLEN, JD ADGEY, AAJ AF TROUTON, TG BARRY, JJ ALLEN, JD ADGEY, AAJ TI FAILURE OF COUNTERSHOCK-TYPE PULSES INVITRO TO ADVERSELY ALTER MITOCHONDRIAL OXIDATIVE-PHOSPHORYLATION SO ANNALS OF EMERGENCY MEDICINE LA English DT Article DE COUNTERSHOCK; MYOCARDIAL INJURY; MITOCHONDRIA AB Study objective: The aim of the study was to investigate a potential mechanism of myocardial injury after DC countershock. The effect of countershock-type electrical discharges on rabbit heart mitochondrial oxygen consumption was measured in vitro using a novel respiration cell. Measurements and main results: Mitochondria were isolated from the hearts of adult Dutch and New Zealand White rabbits. Single rectangular shocks (voltage gradients 20 to 80 V/cm; 5 ms duration) caused no significant changes in state 3 oxygen consumption in standard incubation medium. Single and multiple defibrilator shocks (critically damped sine waveform; 5 ms duration) with peak voltage gradients of 242 to 659 V/cm similarly had no significant effect on state 3 oxygen consumption. Conclusion: At voltage gradients similar to and greater than those causing myocardial cell injury and necrosis, electrical discharges do not directly depress mitochondrial function. Therefore, the reduction in mitochondrial oxygen consumption observed following transthoracic shocks in vivo may invoke other mechanisms (eg. intracellular calcium influx, high circulating noradrenaline, or free radical formation in the intact heart). RP TROUTON, TG (reprint author), MASSACHUSETTS GEN HOSP,MASSACHUSETTS EYE & EAR INFIRM,DEPT CARDIOL,32 FRUIT ST,BOSTON,MA 02114, USA. NR 0 TC 9 Z9 9 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD FEB PY 1992 VL 21 IS 2 BP 132 EP 136 DI 10.1016/S0196-0644(05)80146-5 PG 5 WC Emergency Medicine SC Emergency Medicine GA HB580 UT WOS:A1992HB58000004 PM 1739197 ER PT J AU RYAN, ET PAK, PH DESANCTIS, RW AF RYAN, ET PAK, PH DESANCTIS, RW TI MYOCARDIAL-INFARCTION MIMICKED BY ACUTE CHOLECYSTITIS SO ANNALS OF INTERNAL MEDICINE LA English DT Note DE MYOCARDIAL INFARCTION; CHOLECYSTITIS; ELECTROCARDIOGRAPHY; CHOLECYSTECTOMY; DIAGNOSIS, DIFFERENTIAL ID ELECTROCARDIOGRAPHIC CHANGES; DISEASE AB We describe a patient with acute cholecystitis whose presenting symptoms and electrocardiographic results mimicked anterior myocardial infarction. Electrocardiographic ST-segment elevations persisted despite angiographically normal coronary arteries and normal cardiac enzyme values. Removal of an acutely inflamed gallbladder resulted in resolution of electrocardiographic abnormalities. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP RYAN, ET (reprint author), MASSACHUSETTS GEN HOSP,DIV INFECT DIS,FRUIT ST,BOSTON,MA 02114, USA. NR 10 TC 18 Z9 18 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD FEB 1 PY 1992 VL 116 IS 3 BP 218 EP 220 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA HB356 UT WOS:A1992HB35600007 PM 1728205 ER PT J AU BEAL, MF AF BEAL, MF TI DOES IMPAIRMENT OF ENERGY-METABOLISM RESULT IN EXCITOTOXIC NEURONAL DEATH IN NEURODEGENERATIVE ILLNESSES SO ANNALS OF NEUROLOGY LA English DT Review ID AMYOTROPHIC-LATERAL-SCLEROSIS; POSITRON EMISSION TOMOGRAPHY; CYTOCHROME-C-OXIDASE; SOMATOSTATIN-NEUROPEPTIDE-Y; OXIDOREDUCTASE COMPLEX-I; RAGGED-RED FIBERS; MITOCHONDRIAL ELECTRON-TRANSPORT; EXPERIMENTAL THIAMINE-DEFICIENCY; IDIOPATHIC PARKINSONS-DISEASE; CYANIDE-INDUCED PARKINSONISM AB The etiology of nerve cell death in neuronal degenerative diseases is unknown, but it has been hypothesized that excitotoxic mechanisms may play a role. Such mechanisms may play a role in diseases such as Huntington's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Alzheimer's disease. In these illnesses, the slowly evolving neuronal death is unlikely to be due to a sudden release of glutamate, such as occurs in ischemia. One possibility, however, is that a defect in mitochondrial energy metabolism could secondarily lead to slow excitotoxic neuronal death, by making neurons more vulnerable to endogenous glutamate. With reduced oxidative metabolism and partial cell membrane depolarization, voltage-dependent N-methyl-D-aspartate (NMDA) receptor ion channels would be more easily activated. In addition, several other processes involved in buffering intracellular calcium may be impaired. Recent studies in experimental animals showed that mitochondrial toxins can result in a pattern of neuronal degeneration closely resembling that seen in Huntington's disease, which can be blocked with NMDA antagonists. NMDA antagonists also block neuronal degeneration induced by 1-methyl-4-phenylpyridium, which has been implicated in experimental models of Parkinson's disease. The delayed onset of neurodegenerative illnesses could be related to the progressive impairment of mitochondrial oxidative phosphorylation, which accompanies normal aging. If defective mitochondrial energy metabolism plays a role in cell death in neurodegenerative disorders, potential therapeutic strategies would be to use excitatory amino acid antagonists or agents to bypass bioenergetic defects. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP BEAL, MF (reprint author), MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114, USA. FU NINDS NIH HHS [NS10828]; PHS HHS [16367] NR 174 TC 861 Z9 868 U1 6 U2 39 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD FEB PY 1992 VL 31 IS 2 BP 119 EP 130 DI 10.1002/ana.410310202 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA HC497 UT WOS:A1992HC49700001 PM 1349466 ER PT J AU HILGENBERG, AD LOGAN, DL AKINS, CW BUCKLEY, MJ DAGGETT, WM VLAHAKES, GJ TORCHIANA, DF AF HILGENBERG, AD LOGAN, DL AKINS, CW BUCKLEY, MJ DAGGETT, WM VLAHAKES, GJ TORCHIANA, DF TI BLUNT INJURIES OF THE THORACIC AORTA SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 27TH ANNUAL MEETING OF THE SOC OF THORACIC SURGEONS CY FEB 18-20, 1991 CL SAN FRANCISCO, CA SP SOC THORAC SURGEONS ID SPINAL-CORD INJURY; 10-YEAR EXPERIENCE; TRAUMATIC RUPTURE; TRANSECTION; DISRUPTION; PREVENTION; OPERATION; REPAIR; TEARS; RISK AB We managed 51 patients with thoracic aortic injuries caused by blunt trauma between 1977 and 1990. Forty-nine injuries were located in the upper descending aorta and one each in the ascending aorta and aortic arch. Three patients arrived moribund and underwent thoracotomy for resuscitation, and all died. The diagnosis was confirmed by aortography in 48. One patient died of aortic rupture, 1 died of hypoxemia, and 1 refused operation and died. Forty-four patients had aortic repair, 42 with graft insertion. Gott shunts were placed in 23 with 3 cases of paraplegia (13%). Simple cross-clamping was used in 19 with 1 case of paraplegia (5.2%). We found statistically significant differences between the cross-clamp times of patients without paraplegia compared with those in whom paraplegia developed in both the shunt and no-shunt groups. Logistic regression analysis showed that the only factor significantly associated with paraplegia was cross-clamp time. There were two postoperative deaths (4.4%). Seven patients had medical therapy initially and aortic repair was delayed to allow other injuries to stabilize. Before aortic repair, 18 patients had intraarterial pressure monitoring and 34 received beta-blockers or antihypertensive drugs. We conclude that aortic repair with graft insertion is usually successful in nonmoribund patients, simple cross-clamping is associated with a relatively low risk of paraplegia, the incidence of paraplegia is directly associated with the duration of cross-clamp time, and selected patients can be managed medically while awaiting aortic repair. C1 HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. RP HILGENBERG, AD (reprint author), MASSACHUSETTS GEN HOSP,DEPT THORAC SURG,SURG CARDIOVASC UNIT,32 FRUIT ST,BOSTON,MA 02114, USA. NR 16 TC 59 Z9 59 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 FEB PY 1992 VL 53 IS 2 BP 233 EP 239 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA HB907 UT WOS:A1992HB90700007 PM 1731662 ER PT J AU MATHISEN, DJ AF MATHISEN, DJ TI BRONCHOGENIC-CARCINOMA WITH CHEST-WALL INVASION - REPLY SO ANNALS OF THORACIC SURGERY LA English DT Letter RP MATHISEN, DJ (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD FEB PY 1992 VL 53 IS 2 BP 364 EP 364 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA HB907 UT WOS:A1992HB90700042 ER PT J AU SRINIVAS, L SHALINI, VK SHYLAJA, M AF SRINIVAS, L SHALINI, VK SHYLAJA, M TI TURMERIN - A WATER-SOLUBLE ANTIOXIDANT PEPTIDE FROM TURMERIC [CURCUMA-LONGA] SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID INDUCED DNA DAMAGE; TUMOR PROMOTION; OXYGEN RADICALS; PEROXIDATION; PROTECTION; PROTEINS; ASSAY C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM,JOSLIN RES LAB,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,JOSLIN RES LAB,BOSTON,MA 02115. RP SRINIVAS, L (reprint author), CENT FOOD TECHNOL RES INST,DEPT NUTR & FOOD SAFETY,MYSORE 570013,KARNATAKA,INDIA. NR 30 TC 70 Z9 73 U1 0 U2 5 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD FEB 1 PY 1992 VL 292 IS 2 BP 617 EP 623 DI 10.1016/0003-9861(92)90040-4 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA GY858 UT WOS:A1992GY85800040 PM 1731625 ER PT J AU GOLDBERG, NS ESTERLY, NB ROTHMAN, KF FALLON, JD CROPLEY, TG SZANIAWSKI, W GLASSMAN, M AF GOLDBERG, NS ESTERLY, NB ROTHMAN, KF FALLON, JD CROPLEY, TG SZANIAWSKI, W GLASSMAN, M TI PERIANAL PSEUDOVERRUCOUS PAPULES AND NODULES IN CHILDREN SO ARCHIVES OF DERMATOLOGY LA English DT Article AB Background. - Pseudoverrucous papules and nodules were originally described as a reaction to irritation in association with urostomies. These changes have not been described as occuring on the perianal skin or around colostomies. Observations. - Five children had remarkably similar-appearing papules and nodules of the perianal and suprapubic skin. The rash consisted of more than a dozen 2- to 8-mm shiny, smooth, red, moist, flat-topped, round lesions. This peculiar and striking reaction appears to be the result of encopresis or urinary incontinence. Biopsy specimens reveal reactive acanthosis or psoriasiform spongiotic dermatitis. The lesions regress when the irritating factor is removed. Conclusions. - Recognition of this entity is important because pseudoverrucous papules and nodules may mimic more serious dermatoses and unnecessary workup may be initiated. Although this reaction involving perianal skin has not been reported previously, we believe it is not uncommon. C1 NEW YORK MED COLL,DEPT PEDIAT,DIV GASTROENTEROL,VALHALLA,NY 10595. MED COLL WISCONSIN,DEPT PEDIAT,MILWAUKEE,WI 53226. MED COLL WISCONSIN,DEPT DERMATOL,MILWAUKEE,WI 53226. UNIV MASSACHUSETTS,MED CTR,DEPT MED,DIV DERMATOL,WORCESTER,MA 01605. MASSACHUSETTS GEN HOSP,DEPT DERMATOL,BOSTON,MA 02114. RP GOLDBERG, NS (reprint author), NEW YORK MED COLL,DEPT DERMATOL,VALHALLA,NY 10595, USA. NR 4 TC 30 Z9 30 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD FEB PY 1992 VL 128 IS 2 BP 240 EP 242 DI 10.1001/archderm.128.2.240 PG 3 WC Dermatology SC Dermatology GA HC996 UT WOS:A1992HC99600013 PM 1739304 ER PT J AU COMPTON, CC AF COMPTON, CC TI THE DELAYED POSTBURN BLISTER - A COMMONPLACE BUT COMMONLY OVERLOOKED PHENOMENON SO ARCHIVES OF DERMATOLOGY LA English DT Editorial Material ID GROWTH-FACTOR-BETA; CULTURED EPITHELIAL AUTOGRAFTS; HUMAN KERATINOCYTES; EPIDERMOLYSIS BULLOSA; IV COLLAGEN; FLUID; INTERLEUKIN-1; MELANOCYTES; EXPRESSION; INHIBITOR RP COMPTON, CC (reprint author), MASSACHUSETTS GEN HOSP,DEPT PATHOL,WARREN 2,15 FRUIT ST,BOSTON,MA 02114, USA. NR 45 TC 3 Z9 3 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 FEB PY 1992 VL 128 IS 2 BP 249 EP 252 PG 4 WC Dermatology SC Dermatology GA HC996 UT WOS:A1992HC99600015 PM 1739305 ER PT J AU FLOTTE, TJ AF FLOTTE, TJ TI IMMUNODERMATOPATHOLOGY SO ARCHIVES OF DERMATOLOGY LA English DT Editorial Material ID SYSTEMIC LUPUS-ERYTHEMATOSUS; DERMATOSIS C1 MASSACHUSETTS GEN HOSP, DEPT PATHOL, BOSTON, MA 02114 USA. RP FLOTTE, TJ (reprint author), MASSACHUSETTS GEN HOSP, DEPT DERMATOL, BOSTON, MA 02114 USA. NR 11 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0003-987X EI 1538-3652 J9 ARCH DERMATOL JI Arch. Dermatol. PD FEB PY 1992 VL 128 IS 2 BP 252 EP 253 DI 10.1001/archderm.128.2.252 PG 2 WC Dermatology SC Dermatology GA HC996 UT WOS:A1992HC99600016 PM 1739306 ER PT J AU BARSKY, AJ WYSHAK, G KLERMAN, GL AF BARSKY, AJ WYSHAK, G KLERMAN, GL TI PSYCHIATRIC COMORBIDITY IN DSM-III-R HYPOCHONDRIASIS SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID DIAGNOSTIC INTERVIEW SCHEDULE; PRIMARY CARE; SOMATIZATION DISORDER; MEDICAL OUTPATIENTS; PANIC DISORDER; SELF-REPORT; DEPRESSION; PREVALENCE; QUESTIONNAIRE; COMMUNITY AB Forty-two DSM-III-R hypochondriacs from a general medical clinic were compared with a random sample of 76 outpatients from the same setting. Patients completed a research battery that included a structured diagnostic interview (Diagnostic Interview Schedule) and self-report questionnaires to measure personality disorder caseness, functional impairment, and hypochondriacal symptoms. Psychiatric morbidity in the hypochondriacal sample significantly exceeded that of the comparison sample. Hypochondriacs had twice as many lifetime Axis I diagnoses, twice as many Diagnostic Interview Schedule symptoms, and three times the level of personality disorder caseness as the comparison group. Of the hypochondriacal sample, 88% had one or more additional Axis I disorders, the overlap being greatest with depressive and anxiety disorders. One fifth of the hypochondriacs had somatization disorder, but the two conditions appeared to be phenomenologically distinct. Hypochondriacal patients with coexisting anxiety and/or depressive disorder (secondary hypochondriasis) did not differ greatly from hypochondriacal patients without these comorbid conditions (primary hypochondriasis). Because the nature of hypochondriasis remains unclear and requires further study, we suggest that its nosologic status not be altered in DSM-IV. C1 MASSACHUSETTS GEN HOSP,PSYCHIAT SERV & PRIMARY CARE PROGRAM,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. CORNELL UNIV,MED CTR,COLL MED,DEPT PSYCHIAT,NEW YORK,NY 10021. HARVARD UNIV,SCH PUBL HLTH,CTR POPULAT STUDIES,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,BOSTON,MA 02115. FU NIMH NIH HHS [MH 40487] NR 70 TC 142 Z9 143 U1 4 U2 11 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD FEB PY 1992 VL 49 IS 2 BP 101 EP 108 PG 8 WC Psychiatry SC Psychiatry GA HC800 UT WOS:A1992HC80000002 PM 1550462 ER PT J AU BAXTER, LR MAZZIOTTA, JC PAHL, JJ GRAFTON, ST STGEORGEHYSLOP, P HAINES, JL GUSELLA, JF SZUBA, MP SELIN, CE GUZE, BH PHELPS, ME AF BAXTER, LR MAZZIOTTA, JC PAHL, JJ GRAFTON, ST STGEORGEHYSLOP, P HAINES, JL GUSELLA, JF SZUBA, MP SELIN, CE GUZE, BH PHELPS, ME TI PSYCHIATRIC, GENETIC, AND POSITRON EMISSION TOMOGRAPHIC EVALUATION OF PERSONS AT RISK FOR HUNTINGTONS-DISEASE SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID AFFECTIVE-DISORDER; GLUCOSE-METABOLISM; LINKAGE; FAMILIES; FEATURES; SITES AB We examined chorea-free subjects at risk for Huntington's disease (n = 52) for lifetime psychiatric diagnoses, present mood, genetic marker status, and caudate glucose metabolic rates with positron emission tomography. Based on previous work, a caudate-ipsilateral hemisphere ratio less than 1.15 was defined as abnormal and predictive of Huntington's disease. None of three methods used to segregate subjects into groups more and less likely to develop Huntington's disease gave significant group rate differences for any formal psychiatric diagnoses. On present mood testing, however, subjective "anger/hostility" was significantly higher in those likely, compared with those less likely, to develop Huntington's disease, as determined by all three methods. C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT PSYCHIAT & BIOBEHAV SCI,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT NEUROL,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT RADIOL SCI,DIV NUCL MED & BIOPHYS,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,NUCL MED LAB,LOS ANGELES,CA 90024. MASSACHUSETTS GEN HOSP,MOLEC NEUROGENET LAB,BOSTON,MA 02114. RI Haines, Jonathan/C-3374-2012 FU NCRR NIH HHS [RR00865]; NINDS NIH HHS [NS16367, P01-NS-15654] NR 34 TC 28 Z9 29 U1 4 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD FEB PY 1992 VL 49 IS 2 BP 148 EP 154 PG 7 WC Psychiatry SC Psychiatry GA HC800 UT WOS:A1992HC80000008 PM 1532304 ER PT J AU KWAK, HW DAMICO, DJ AF KWAK, HW DAMICO, DJ TI EVALUATION OF THE RETINAL TOXICITY AND PHARMACOKINETICS OF DEXAMETHASONE AFTER INTRAVITREAL INJECTION SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID GLUCOSE-TRANSPORT SYSTEM; INTRAOCULAR INJECTION; TRIAMCINOLONE ACETONIDE; GLUTAMINE-SYNTHETASE; ENDOPHTHALMITIS; CELLS; ADIPOCYTES; INHIBITION AB The intravitreal injection of steroids may be potentially useful in the treatment of endophthalmitis and other ocular inflammatory diseases. The retinal toxicity and intraocular turnover of aqueous solutions of dexamethasone sodium phosphate in doses ranging from 440 to 4000-mu-g were evaluated in the rabbit; evaluation was also performed for a 0.1-mL injection of a commercially available preparation (dexamethasone phosphate [Decadron] injection, 4 mg/mL). After the 440-mu-g dose, a transient increase in staining of the Muller cells was observed, which normalized after 2 days. Progressively higher doses resulted in an increasing spectrum of disorganization in Muller and other retinal cells. The half-life of the intravitreally injected drug was 3.48 hours. These findings suggest a primary interference in Muller cell function, possibly through dexamethasone-induced alterations in retinal glutamate or glucose metabolism. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,243 CHARLES ST,BOSTON,MA 02114. HARVARD UNIV,SCH MED,RETINA SERV,BOSTON,MA 02115. HARVARD UNIV,SCH MED,HOWE LAB OPHTHALMOL,BOSTON,MA 02115. NR 34 TC 114 Z9 123 U1 1 U2 9 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 FEB PY 1992 VL 110 IS 2 BP 259 EP 266 PG 8 WC Ophthalmology SC Ophthalmology GA HD624 UT WOS:A1992HD62400033 PM 1736876 ER PT J AU WAXMAN, DJ AZAROFF, L AF WAXMAN, DJ AZAROFF, L TI PHENOBARBITAL INDUCTION OF CYTOCHROME-P-450 GENE-EXPRESSION SO BIOCHEMICAL JOURNAL LA English DT Review ID ADULT-RAT-HEPATOCYTES; LIVER MICROSOMAL CYTOCHROME-P-450; TISSUE-SPECIFIC EXPRESSION; PRIMARY MONOLAYER-CULTURE; P450 MESSENGER-RNAS; SYNTHETIC OLIGODEOXYRIBONUCLEOTIDE PROBES; N-NITROSODIMETHYLAMINE DEMETHYLASE; GLUCOCORTICOID RESPONSE ELEMENT; POST-TRANSCRIPTIONAL REGULATION; HORMONE RECEPTOR SUPERFAMILY C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MOLEC PHARMACOL,BOSTON,MA 02115. RP WAXMAN, DJ (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,ROOM JF-525,44 BINNEY ST,BOSTON,MA 02115, USA. FU NIDDK NIH HHS [DK33765] NR 223 TC 515 Z9 524 U1 2 U2 11 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD FEB 1 PY 1992 VL 281 BP 577 EP 592 PN 3 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HD762 UT WOS:A1992HD76200001 PM 1536639 ER PT J AU SAITO, H STREULI, M KRUEGER, NX ITOH, M TSAI, AYM AF SAITO, H STREULI, M KRUEGER, NX ITOH, M TSAI, AYM TI CD45 AND A FAMILY OF RECEPTOR-LINKED PROTEIN TYROSINE PHOSPHATASES SO BIOCHEMICAL SOCIETY TRANSACTIONS LA English DT Article ID LEUKOCYTE-COMMON ANTIGEN; PRE-MESSENGER RNA; HUMAN-PLACENTA; RABBIT KIDNEY; PURIFICATION; T200; CDNA; GLYCOPROTEIN; ORGANIZATION; EXPRESSION RP SAITO, H (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA-51132]; NIAID NIH HHS [AI-26598] NR 33 TC 14 Z9 14 U1 0 U2 0 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0300-5127 J9 BIOCHEM SOC T JI Biochem. Soc. Trans. PD FEB PY 1992 VL 20 IS 1 BP 165 EP 169 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HG453 UT WOS:A1992HG45300033 PM 1321749 ER PT J AU GROSSBARD, ML FREEDMAN, AS RITZ, J CORAL, F GOLDMACHER, VS ELISEO, L SPECTOR, N DEAR, K LAMBERT, JM BLATTLER, WA TAYLOR, JA NADLER, LM AF GROSSBARD, ML FREEDMAN, AS RITZ, J CORAL, F GOLDMACHER, VS ELISEO, L SPECTOR, N DEAR, K LAMBERT, JM BLATTLER, WA TAYLOR, JA NADLER, LM TI SEROTHERAPY OF B-CELL NEOPLASMS WITH ANTI-B4-BLOCKED RICIN - A PHASE-I TRIAL OF DAILY BOLUS INFUSION SO BLOOD LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; A-CHAIN IMMUNOTOXIN; METASTATIC MALIGNANT-MELANOMA; AUTOLOGOUS BONE-MARROW; NON-HODGKINS-LYMPHOMA; MONOCLONAL-ANTIBODY; CYTO-TOXICITY; THERAPY; RECONSTITUTION; ANTIGENS C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOSTAT,BOSTON,MA 02115. IMMUNOGEN INC,CAMBRIDGE,MA. RP GROSSBARD, ML (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,44 BINNEY ST,BOSTON,MA 02115, USA. RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NCI NIH HHS [CA34183, CA55207] NR 36 TC 164 Z9 164 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 FEB 1 PY 1992 VL 79 IS 3 BP 576 EP 585 PG 10 WC Hematology SC Hematology GA HB533 UT WOS:A1992HB53300006 PM 1370636 ER PT J AU KUTER, DJ GMINSKI, DM ROSENBERG, RD AF KUTER, DJ GMINSKI, DM ROSENBERG, RD TI TRANSFORMING GROWTH-FACTOR-BETA INHIBITS MEGAKARYOCYTE GROWTH AND ENDOMITOSIS SO BLOOD LA English DT Article ID EMBRYONIC KIDNEY-CELLS; PLATELET ALPHA-GRANULES; COLONY FORMATION; MURINE MEGAKARYOCYTES; TGF-BETA; THROMBOPOIETIC ACTIVITY; HUMAN ERYTHROPOIETIN; HUMAN INTERLEUKIN-6; STIMULATORY FACTOR; PROGENITOR CELLS C1 MIT, DEPT BIOL, CAMBRIDGE, MA 02139 USA. MASSACHUSETTS GEN HOSP, DEPT MED, HEMATOL ONCOL UNIT, BOSTON, MA 02114 USA. HARVARD UNIV, BETH ISRAEL HOSP, SCH MED, DEPT MED, BOSTON, MA 02215 USA. RP KUTER, DJ (reprint author), MIT, WHITAKER COLL, DEPT BIOL, 77 MASSACHUSETTS AVE, CAMBRIDGE, MA 02139 USA. FU NHLBI NIH HHS [HL 39753] NR 57 TC 69 Z9 70 U1 0 U2 0 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 FEB 1 PY 1992 VL 79 IS 3 BP 619 EP 626 PG 8 WC Hematology SC Hematology GA HB533 UT WOS:A1992HB53300011 PM 1732007 ER PT J AU KOENIGSMANN, M GRIFFIN, JD DICARLO, J CANNISTRA, SA AF KOENIGSMANN, M GRIFFIN, JD DICARLO, J CANNISTRA, SA TI MYELOID AND ERYTHROID PROGENITOR CELLS FROM NORMAL BONE-MARROW ADHERE TO COLLAGEN TYPE-I SO BLOOD LA English DT Article ID ARG-GLY-ASP; INTEGRIN FAMILY; ADHESION; INHIBITION; RECEPTORS; CULTURES; BINDING; FIBROBLASTS; FIBRONECTIN; EXPRESSION C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,44 BINNEY ST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV MED ONCOL,BOSTON,MA 02115. FU NCI NIH HHS [CA 42802, CA 36167, CA 34183] NR 36 TC 65 Z9 65 U1 0 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 FEB 1 PY 1992 VL 79 IS 3 BP 657 EP 665 PG 9 WC Hematology SC Hematology GA HB533 UT WOS:A1992HB53300016 PM 1370640 ER PT J AU BRACH, MA HERRMANN, F KUFE, DW AF BRACH, MA HERRMANN, F KUFE, DW TI ACTIVATION OF THE AP-1 TRANSCRIPTION FACTOR BY ARABINOFURANOSYLCYTOSINE IN MYELOID-LEUKEMIA CELLS (RETRACTED ARTICLE. SEE VOL 93, PG. 3573, 1999) SO BLOOD LA English DT Article ID NECROSIS-FACTOR-ALPHA; C-JUN; DNA-SYNTHESIS; GENE-EXPRESSION; PROTO-ONCOGENE; 1-BETA-D-ARABINOFURANOSYLCYTOSINE INCORPORATION; MAMMALIAN-CELLS; ARA-CTP; INHIBITORS; ELEMENTS C1 HARVARD UNIV, SCH MED,DANA FARBER CANC INST,CLIN PHARMACOL LAB, 44 BINNEY ST, BOSTON, MA 02115 USA. UNIV FREIBURG, DEPT HEMATOL & ONCOL, W-7800 FREIBURG, GERMANY. FU NCI NIH HHS [CA29431] NR 45 TC 46 Z9 47 U1 3 U2 6 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 FEB 1 PY 1992 VL 79 IS 3 BP 728 EP 734 PG 7 WC Hematology SC Hematology GA HB533 UT WOS:A1992HB53300025 PM 1310062 ER PT J AU VECSEI, L MILLER, J MACGARVEY, U BEAL, MF AF VECSEI, L MILLER, J MACGARVEY, U BEAL, MF TI KYNURENINE AND PROBENECID INHIBIT PENTYLENETETRAZOL-INDUCED AND NMDLA-INDUCED SEIZURES AND INCREASE KYNURENIC ACID CONCENTRATIONS IN THE BRAIN SO BRAIN RESEARCH BULLETIN LA English DT Article DE KYNURENIC ACID; KYNURENINE; NMDLA; PENTYLENETETRAZOL; PROBENECID SEIZURES ID INSENSITIVE GLYCINE RECEPTOR; QUINOLINIC ACID; RAT HIPPOCAMPUS; HUNTINGTONS-DISEASE; MAMMALIAN BRAIN; ANTAGONIST; IDENTIFICATION; SITE; NEUROTOXICITY; CONVULSIONS AB Kynurenine is a direct precursor of kynurenic acid, the only known endogenous antagonist of excitatory amino acid receptors in the brain. Kynurenine administered intraperitoneally (150, 450, 900 mg/kg) 2 h before pentylenetetrazol injection dose-dependently increased the time to seizures, the time to death and the survivorship of mice. Kynurenine dose-dependently increased the time to seizures and the time to death in mice with NMDLA-induced seizures. Kynurenine, 900 mg/kg, was equally efficacious to diazepam, 2 mg/kg. Probenecid dose-dependently increased the time to seizures, the time to death and the survivorship of mice with pentylenetetrazol-induced seizures. Probenecid had no significant effects on NMDLA-induced seizures, although the time to death was prolonged in the NMDLA 500 mg/kg group. Probenecid potentiated the effects of kynurenine in these tests. Both probenecid and kynurenine significantly increased kynurenine and kynurenic acid concentrations in mouse cerebral cortex and striatum. These findings suggest that kynurenine (metabolized to kynurenic acid) has anticonvulsant effects, and probenecid potentiates these effects in mice. C1 HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114. RI Vecsei, Laszlo/B-2066-2010 OI Vecsei, Laszlo/0000-0001-8037-3672 FU PHS HHS [16367] NR 39 TC 77 Z9 79 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0361-9230 J9 BRAIN RES BULL JI Brain Res. Bull. PD FEB PY 1992 VL 28 IS 2 BP 233 EP 238 DI 10.1016/0361-9230(92)90184-Y PG 6 WC Neurosciences SC Neurosciences & Neurology GA GZ884 UT WOS:A1992GZ88400012 PM 1596743 ER PT J AU BECH, P ALLERUP, P MAIER, W ALBUS, M LAVORI, P AYUSO, JL AF BECH, P ALLERUP, P MAIER, W ALBUS, M LAVORI, P AYUSO, JL TI THE HAMILTON SCALES AND THE HOPKINS SYMPTOM CHECKLIST (SCL-90) - A CROSS-NATIONAL VALIDITY STUDY IN PATIENTS WITH PANIC DISORDERS SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Article ID RELIABILITY; SENSITIVITY AB The HRSD, HRSA, SCL-90 scales were psychometrically investigated in a cross-national sample of patients with varieties of non-psychotic symptoms of anxiety and depression. Across the cultural backgrounds the scores obtained from the original versions of these scales are not sufficient statistics. However, latent structure analysis has identified homogeneous subscales for depression (the HRSD) and for discomfort (an SCL subscale). High concurrent validity was found between the subscales of depression, anxiety and discomfort. In international research, inhomogeneity among scale items can be confounded with group differences which are usually ascribed to drug differences. C1 UNIV MAINZ,DEPT PSYCHIAT,W-6500 MAINZ,GERMANY. UNIV MUNICH,CLIN,PSYCHIAT,W-8000 MUNICH 2,GERMANY. MASSACHUSETTS GEN HOSP,BIOSTAT UNIT,BOSTON,MA 02114. UNIV MADRID,DEPT PSYCHIAT,MADRID 3,SPAIN. RP BECH, P (reprint author), FREDERIKSBERG GEN HOSP,DEPT PSYCHIAT,DK-3400 HILLEROD,DENMARK. NR 18 TC 46 Z9 47 U1 0 U2 3 PU ROYAL COLLEGE OF PSYCHIATRISTS PI LONDON PA BRITISH JOURNAL OF PSYCHIATRY 17 BELGRAVE SQUARE, LONDON, ENGLAND SW1X 8PG SN 0007-1250 J9 BRIT J PSYCHIAT JI Br. J. Psychiatry PD FEB PY 1992 VL 160 BP 206 EP 211 DI 10.1192/bjp.160.2.206 PG 6 WC Psychiatry SC Psychiatry GA HE676 UT WOS:A1992HE67600008 PM 1540760 ER PT J AU STACEYCLEAR, A AF STACEYCLEAR, A TI GYNECOMASTIA SO BRITISH JOURNAL OF SURGERY LA English DT Letter RP STACEYCLEAR, A (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG ONCOL,BOSTON,MA 02114, USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0007-1323 J9 BRIT J SURG JI Br. J. Surg. PD FEB PY 1992 VL 79 IS 2 BP 182 EP 183 DI 10.1002/bjs.1800790239 PG 2 WC Surgery SC Surgery GA HE525 UT WOS:A1992HE52500036 PM 1555077 ER PT J AU MARGOLIS, HC MORENO, EC AF MARGOLIS, HC MORENO, EC TI KINETICS OF HYDROXYAPATITE DISSOLUTION IN ACETIC, LACTIC, AND PHOSPHORIC-ACID SOLUTIONS SO CALCIFIED TISSUE INTERNATIONAL LA English DT Article DE HYDROXYAPATITE; ENAMEL; DISSOLUTION; KINETICS; CARIES ID CARIES-SUSCEPTIBLE INDIVIDUALS; HUMAN PLAQUE FLUID; CALCIUM HYDROXYAPATITE; ENAMEL DEMINERALIZATION; MOLECULAR-WEIGHT; CRYSTAL-GROWTH; DENTAL ENAMEL; ORGANIC-ACIDS; CONSTANT PH; CHEMISTRY AB The present study was undertaken in an attempt to relate the kinetics of hydroxyapatite dissolution to solution parameters, under experimental conditions relevant to the dental caries process. Thus, the dissolution of hydroxyapatite was studied in acetic, lactic, and dilute phosphoric acid solutions having initial pH values from 4 to 6. Rates of dissolution and the corresponding degree of saturation with respect to hydroxyapatite were determined at various times throughout the dissolution process. Rates of dissolution of all solutions were found to decrease with increasing degree of solution saturation and were greater in solutions with lower initial values of pH. However, rates of dissolution in partially saturated phosphoric acid solutions (without added organic acid) were at least one order of magnitude lower than those observed in the organic acid buffers with the same initial pH, over the same range of saturation values. The data obtained are consistent with a surface-controlled dissolution model in which the rate of dissolution is dependent upon the degree of saturation and the sum of the activities of the acidic species in solution, i.e., phosphoric and organic acids. These results suggest that in order to assess the cariogenic potential of a given medium (e.g., plaque fluid), one must determine both the degree of saturation with respect to the dissolving mineral and the activities of acidic species in solution. RP MARGOLIS, HC (reprint author), FORSYTH DENT CTR,140 FENWAY,BOSTON,MA 02115, USA. FU NIDCR NIH HHS [DE-07493, DE-03187, DE-07009] NR 30 TC 63 Z9 63 U1 2 U2 29 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 FEB PY 1992 VL 50 IS 2 BP 137 EP 143 DI 10.1007/BF00298791 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA HA139 UT WOS:A1992HA13900011 PM 1315186 ER PT J AU FISHER, CM AF FISHER, CM TI CONCERNING THE MECHANISM OF RECOVERY IN STROKE HEMIPLEGIA SO CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES LA English DT Article ID ADULT MONKEYS; INFARCTION AB Two patients with pure motor hemiplegia were regaining strength in the affected limbs when a pure motor stroke developed on the opposite side. At the same time as the new hemiplegia appeared, the recovering side became re-paralyzed, suggesting that activity in the contralateral corticospinal tract had participated in the recovery process. Pathological studies were confirmatory. The literature pertaining to contralateral motor compensation is reviewed. RP FISHER, CM (reprint author), MASSACHUSETTS GEN HOSP,NEUROL SERV,FRUIT ST,BOSTON,MA 02114, USA. NR 32 TC 98 Z9 101 U1 0 U2 2 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 FEB PY 1992 VL 19 IS 1 BP 57 EP 63 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA HE012 UT WOS:A1992HE01200009 PM 1562908 ER PT J AU MACKLIS, RM MAUCH, PM BURAKOFF, SJ SMITH, BR AF MACKLIS, RM MAUCH, PM BURAKOFF, SJ SMITH, BR TI LYMPHOID IRRADIATION RESULTS IN LONG-TERM INCREASES IN NATURAL-KILLER-CELLS IN PATIENTS TREATED FOR HODGKINS-DISEASE SO CANCER LA English DT Article ID PERIPHERAL-BLOOD; RHEUMATOID-ARTHRITIS; TRANSPLANTATION; LYMPHOCYTES; POPULATIONS; REMISSION; TLI AB Therapeutic lymphoid irradiation has been shown to produce profound long-term alterations in lymphocyte subpopulations and immunologic responsiveness. Dual immunofluorescence flow cytometry and functional cytolytic assays were used to investigate the effects of lymphoid irradiation either alone or in combination with chemotherapy on T-cell and natural killer (NK) cell populations in the blood of patients treated for Hodgkin's disease. Patients treated with mantle and paraaortic lymphoid irradiation show significant increases in the proportion of cells bearing the NK cell phenotypic marker Leu-11 (CD16). These patients also display proportionately increased cytotoxicity against K562 tumor targets in vitro. A sizable number of these NK cells label dimly with Leu-2 (CD8) although they lack the pan-T-cell marker Leu-4 (CD3). The emergence after lymphoid irradiation of this population of Leu-11+2+ NK cells may lead to an apparent decrease in the ratio of helper to suppressor T-cells, although the actual ratio of these T-cell subsets generally is normal. These changes persist for years after the completion of radiation therapy. It was concluded that lymphoid irradiation may produce profound changes in NK cell populations in patients treated for Hodgkin's disease; the clinical significance of these changes is unclear. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PEDIAT ONCOL,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DIV HEMATOL,BOSTON,MA 02115. RP MACKLIS, RM (reprint author), HARVARD JOINT CTR RADIAT THERAPY,50 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [1-PO1-CA39542]; NIAID NIH HHS [R01-AI23346] NR 26 TC 18 Z9 19 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD FEB 1 PY 1992 VL 69 IS 3 BP 778 EP 783 DI 10.1002/1097-0142(19920201)69:3<778::AID-CNCR2820690327>3.0.CO;2-E PG 6 WC Oncology SC Oncology GA HB111 UT WOS:A1992HB11100026 PM 1730127 ER PT J AU LEBLANC, GA SUNDSETH, SS WEBER, GF WAXMAN, DJ AF LEBLANC, GA SUNDSETH, SS WEBER, GF WAXMAN, DJ TI PLATINUM ANTICANCER DRUGS MODULATE P-450 MESSENGER-RNA LEVELS AND DIFFERENTIALLY ALTER HEPATIC DRUG AND STEROID-HORMONE METABOLISM IN MALE AND FEMALE RATS SO CANCER RESEARCH LA English DT Article ID GROWTH-HORMONE; CIS-PLATINUM; PITUITARY REGULATION; CISPLATIN; EXPRESSION; MONOOXYGENASE; ENZYMES; LIVER; 6-BETA-HYDROXYLASE; CYTOCHROMES-P-450 AB Treatment of male rats with the anticancer drug cisplatin leads to feminization of the profile of cytochromes P-450 and other microsomal enzymes involved in steroid hormone and drug metabolism (G. A. Le-Blanc, and D. J. Waxman, J. Biol. Chem., 263:15732-15739, 1988). The present study uses the rat model to evaluate the differential effects of cisplatin treatment on liver microsomal enzymes between genders, and also examines whether the modulation of enzyme activities by cisplatin and its analogues involves changes in P-450 gene expression. While cisplatin treatment of male rats caused a severalfold increase in female-predominant hepatic enzymes, including testosterone 5-alpha-reductase and testosterone 7-alpha-hydroxylase (P450 form 2A1), it partially decreased the expression of these enzymes in females. The reduced expression of these estrogen-dependent enzymes in females may derive from the loss of circulating estradiol that was shown to occur in response to cisplatin treatment. Analysis of mRNA levels of individual P-450 forms revealed that the effects of cisplatin on P-450-catalyzed steroid hydroxylase activities in both male and female rats are primarily operative through the drug's effects on P-450 mRNA expression. P-450-dependent cyclo-phosphamide activation was significantly compromised in male rats after cisplatin administration; however, this activity was not altered in cisplatin-induced females. This sex-dependent effect of cisplatin was due to its suppression of P-450 form 2C11, a male-specific P-450 that is a major contributor to microsomal cyclophosphamide bioactivation in male rat liver. The clinically active cisplatin analogue iproplatin elicited effects very similar to those of cisplatin, while carboplatin and transplatin did not have significant effects on hepatic P-450 expression. Together, these findings demonstrate that the response of rat liver to cisplatin-induced changes in hepatic P-450 enzyme profiles and cyclophosphamide bioactivation capacity differs between the sexes, and in addition, these effects can be minimized by use of carboplatin in place of cisplatin. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,ROOM JF-525,44 BINNEY ST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. N CAROLINA STATE UNIV,DEPT TOXICOL,RALEIGH,NC 27695. FU NCI NIH HHS [CA-49248, 1F32-CA08259] NR 49 TC 66 Z9 66 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 FEB 1 PY 1992 VL 52 IS 3 BP 540 EP 547 PG 8 WC Oncology SC Oncology GA HB184 UT WOS:A1992HB18400007 PM 1732040 ER PT J AU TAMAKI, T KANAKURA, Y KURIU, A IKEDA, H MITSUI, H YAGURA, H MATSUMURA, I DRUKER, B GRIFFIN, JD KANAYAMA, Y YONEZAWA, T AF TAMAKI, T KANAKURA, Y KURIU, A IKEDA, H MITSUI, H YAGURA, H MATSUMURA, I DRUKER, B GRIFFIN, JD KANAYAMA, Y YONEZAWA, T TI SURFACE IMMUNOGLOBULIN-MEDIATED SIGNAL TRANSDUCTION INVOLVES RAPID PHOSPHORYLATION AND ACTIVATION OF THE PROTOONCOGENE PRODUCT RAF-1 IN HUMAN B-CELLS SO CANCER RESEARCH LA English DT Article ID COLONY-STIMULATING FACTOR; PROTEIN TYROSINE PHOSPHORYLATION; KINASE-ACTIVITY; LYMPHOCYTE-B; MEMBRANE IMMUNOGLOBULIN; ANTIGEN RECEPTOR; C-RAF; TRANSLOCATION; INTERLEUKIN-3; GROWTH AB The protooncogene product, Raf-1, is a serine/threonine kinase and has been implicated as an intermediate in signal transduction mechanisms. We examined neoplastic and normal B cells for phosphorylation and activation of Raf-1 protein in response to anti-immunoglobulin antibody (anti-Ig). Anti-Ig induced rapid phosphorylation of Raf-1 protein in both neoplastic B-cells of hairy cell leukemia and normal tonsillar B-cells which proliferated well in response to anti-Ig. The increase in phosphorylation was due primarily to an increase in phosphoserine. The immune complex kinase assay using Histone V-S as an exogenous substrate also showed an increase in Raf-1-associated kinase activity. An inhibitor of protein kinase C, H7, inhibited the proliferation as well as the Raf-1 phosphorylation in response to the proliferative signal of anti-Ig. Further, downregulation of protein kinase C by the treatment with 12-phorbol 13-myristic acid significantly abrogated the induction of Raf-1 phosphorylation. These results suggest that, in human B-cells, Raf-1 protein may be involved in the signal transduction pathway mediated by surface immunoglobulin, and that it may be, at least partially, phosphorylated by activated PKC. C1 OSAKA UNIV,SCH MED,DEPT INTERNAL MED 2,1-1-50 FUKUSHIMA,FUKUSHIMA KU,OSAKA 553,JAPAN. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 17 TC 15 Z9 15 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 FEB 1 PY 1992 VL 52 IS 3 BP 566 EP 570 PG 5 WC Oncology SC Oncology GA HB184 UT WOS:A1992HB18400011 PM 1732044 ER PT J AU MOSKOWITZ, MA AF MOSKOWITZ, MA TI INTERPRETING VESSEL DIAMETER CHANGES IN VASCULAR HEADACHES SO CEPHALALGIA LA English DT Editorial Material ID EXTRACEREBRAL CIRCULATION; RELEASE; GR43175; HUMANS RP MOSKOWITZ, MA (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114, USA. RI Moskowitz, Michael/D-9916-2011 NR 22 TC 15 Z9 15 U1 0 U2 2 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0333-1024 J9 CEPHALALGIA JI Cephalalgia PD FEB PY 1992 VL 12 IS 1 BP 5 EP 7 DI 10.1046/j.1468-2982.1992.1201005.x PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA HH541 UT WOS:A1992HH54100007 PM 1559258 ER PT J AU LEVINE, SM JENKINSON, SG BRYAN, CL ANZUETO, A ZAMORA, CA GIBBONS, WJ CALHOON, JH TRINKLE, JK AF LEVINE, SM JENKINSON, SG BRYAN, CL ANZUETO, A ZAMORA, CA GIBBONS, WJ CALHOON, JH TRINKLE, JK TI VENTILATION-PERFUSION INEQUALITIES DURING GRAFT-REJECTION IN PATIENTS UNDERGOING SINGLE LUNG TRANSPLANTATION FOR PRIMARY PULMONARY-HYPERTENSION SO CHEST LA English DT Article AB We report herein data on single lung transplant (SLT) recipients with primary pulmonary hypertension (PPH). One patient did well following surgery but died on the 30th postoperative day due to cytomegalovirus pneumonia. The remaining two patients initially did well with unlimited exercise tolerance following transplantation, but then developed marked dyspnea on exertion and hypoxemia on postoperative days 144 and 120, respectively. Pulmonary function testing showed marked deterioration of function and transbronchial lung biopsy specimens revealed acute graft rejection in one patient and evidence of chronic graft rejection in the second patient. Quantitative ventilation-perfusion lung scanning demonstrated a marked decrease in ventilation to the transplanted lung in both cases associated with only a mild decrease in perfusion. This V/Q mismatch resulted in markedly decreased arterial oxygen saturations, widened alveolar-arterial oxygen gradients, and clinically debilitating dyspnea. We conclude that rejection may result in significant V/Q mismatch and hypoxemia in PPH patients undergoing SLT, which may limit the use of this specific type of surgery for PPH. C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV PULM DIS,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT SURG,DIV CARDIOTHORAC SURG,SAN ANTONIO,TX 78284. RP LEVINE, SM (reprint author), AUDIE L MURPHY MEM VET ADM MED CTR,PULM DIS SECT,SAN ANTONIO,TX 78284, USA. FU NHLBI NIH HHS [HL-30556] NR 11 TC 55 Z9 55 U1 0 U2 1 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 SN 0012-3692 J9 CHEST JI Chest PD FEB PY 1992 VL 101 IS 2 BP 401 EP 405 DI 10.1378/chest.101.2.401 PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA HC557 UT WOS:A1992HC55700026 PM 1735262 ER PT J AU STEIN, PD ATHANASOULIS, C ALVAI, A GREENSPAN, RH HALES, CA SALTZMAN, HA VREIM, CE TERRIN, ML WEG, JG AF STEIN, PD ATHANASOULIS, C ALVAI, A GREENSPAN, RH HALES, CA SALTZMAN, HA VREIM, CE TERRIN, ML WEG, JG TI COMPLICATIONS AND VALIDITY OF PULMONARY ANGIOGRAPHY IN ACUTE PULMONARY-EMBOLISM SO CIRCULATION LA English DT Article DE ANGIOGRAPHY; ARTERIOGRAPHY; CATHETERIZATION; PULMONARY EMBOLISM ID CARDIAC ANGIOGRAPHY; CONTRAST AGENT; CINEANGIOGRAPHY; TRIAL AB Background. The Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) addressed the value of ventilation/perfusion scans in acute pulmonary embolism (PE). The present study evaluates the risks and diagnostic validity of pulmonary angiography in 1,111 patients who underwent angiography in PIOPED. Methods and Results. Complications were death in five (0.5%), major nonfatal complications in nine (1%), and less significant or minor in 60 (5%). More fatal or major nonfatal complications occurred in patients from the medical intensive care unit than elsewhere: five of 122 (4%) versus nine of 989 (1%) (p < 0.02). Pulmonary artery pressure, volume of contrast material, and presence of PE did not significantly affect the frequency of complications. Renal dysfunction, either major (requiring dialysis) or less severe, occurred in 13 of 1,111 (1%). Patients who developed renal dysfunction after angiography were older than those who did not have renal dysfunction: 74 +/- 13 years versus 57 +/- 17 years (p < 0.001). Angiograms were nondiagnostic in 35 of 1,111 (3%), and studies were incomplete in 12 of 1,111 (1%), usually because of a complication. Surveillance after negative angiograms showed PE in four of 675 (0.6%). Angiograms, interpreted on the basis of consensus readings, resulted in an unchallenged diagnosis in 96%. Conclusions. The risks of pulmonary angiography were sufficiently low to justify it as a diagnostic tool in the appropriate clinical setting. Clinical judgment is probably the most important consideration in the assessment of risk. C1 MARYLAND MED RES INST,BALTIMORE,MD. DUKE UNIV,DURHAM,NC 27706. YALE UNIV,NEW HAVEN,CT 06520. UNIV PENN,PHILADELPHIA,PA 19104. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. UNIV MICHIGAN,ANN ARBOR,MI 48109. NIH,BETHESDA,MD 20892. RP STEIN, PD (reprint author), HENRY FORD HEART & VASC INST,2799 W GRAND BLVD,DETROIT,MI 48202, USA. FU NHLBI NIH HHS [N01-HR-34007, N01-HR-34008, N01-HR-34009] NR 21 TC 488 Z9 501 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 FEB PY 1992 VL 85 IS 2 BP 462 EP 468 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA HC293 UT WOS:A1992HC29300005 PM 1735144 ER PT J AU ISOBE, M NARULA, J SOUTHERN, JF STRAUSS, HW KHAW, BA HABER, E AF ISOBE, M NARULA, J SOUTHERN, JF STRAUSS, HW KHAW, BA HABER, E TI IMAGING THE REJECTING HEART - INVIVO DETECTION OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II ANTIGEN INDUCTION SO CIRCULATION LA English DT Article DE TRANSPLANTATION; SCINTIGRAPHY; CYCLOSPORINE; MHC REJECTION ID CARDIAC ALLOGRAFT-REJECTION; IN-111 ANTIMYOSIN FAB; DONOR CLASS-I; MHC ANTIGENS; MONOCLONAL-ANTIBODY; KIDNEY ALLOGRAFTS; EXPRESSION; RAT; TRANSPLANTATION; INTERFERON AB Background. Mice with abdominal heterotopic heart transplants were studied to determine whether scintigraphic detection of an increase in major histocompatibility complex (MHC) class II antigen expression could be used as a noninvasive method for diagnosing early rejection. Methods and Results. Allografts from C3H/He (H2k) donors were transplanted into BALB/c (H2(d)) recipients (n = 18). Two of the 18 allografted mice were treated with cyclosporine (15 mg/kg/day), and two isografted mice served as controls. Each mouse was injected intravenously with 100-mu-Ci of In-111-labeled anti-MHC class II monoclonal antibodies (10-2-16 and 14-4-4S) 24 hours before scintigraphy. After imaging, the mice were killed for tissue counting and histopathology. Radiotracer uptake in the grafts reflected the severity of rejection as determined by histopathological criteria. The percent injected dose per gram of tissue in excised grafts was 4.8 +/- 1.8 (mean +/- SD) for normal grafts (n = 8), 11.1 +/- 9.7 for grafts with grade IA rejection (n = 3, NS), 18.0 +/- 3.8 for grafts with grade IIIA rejection (n = 4, p < 0.001 versus normal), 18.7 +/- 3.2 for grafts with grade IIIB rejection (n = 3, p < 0.001 versus normal), and 22.6 +/- 5.4 for grafts with severe rejection (grade IV) (n = 3, p < 0.001 versus normal). Rejecting allografts with lymphocyte infiltration but without significant myocyte necrosis could be identified by this scintigraphic method. In the BALB/c donor-C57BL/6 (H2b, IE-) recipient combination, rejecting allografts were visualized by 14-4-4S (anti-IE(k,d,p,r)) antibody but not by 10-2-16 (anti-IA(k,r,s,f) antibody. This difference shows that class II antigens induced on donor hearts are solely responsible for the antibody uptake in positive scintigrams of rejecting allografts. Conclusions. We conclude that In-111-labeled anti-MHC class II antigen antibody imaging is a sensitive and noninvasive method for detecting cardiac allograft rejection. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,DIV NUCL MED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP ISOBE, M (reprint author), MASSACHUSETTS GEN HOSP,DEPT PATHOL,CARDIAC UNIT,JACKSON 14,BOSTON,MA 02114, USA. NR 42 TC 33 Z9 33 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 FEB PY 1992 VL 85 IS 2 BP 738 EP 746 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA HC293 UT WOS:A1992HC29300032 PM 1735166 ER PT J AU TAUBMAN, MB ROLLINS, BJ POON, M MARMUR, J GREEN, RS BERK, BC NADALGINARD, B AF TAUBMAN, MB ROLLINS, BJ POON, M MARMUR, J GREEN, RS BERK, BC NADALGINARD, B TI JE MESSENGER-RNA ACCUMULATES RAPIDLY IN AORTIC INJURY AND IN PLATELET-DERIVED GROWTH-FACTOR STIMULATED VASCULAR SMOOTH-MUSCLE CELLS SO CIRCULATION RESEARCH LA English DT Article DE VASCULAR SMOOTH MUSCLE; VESSEL INJURY; GROWTH FACTORS; CYTOKINES; GENE EXPRESSION ID PROTEIN KINASE-C; HUMAN ATHEROSCLEROTIC PLAQUES; COMPETENCE GENE-JE; ANGIOTENSIN-II; CYCLIC-AMP; SWISS 3T3-CELLS; FOS GENE; INDEPENDENT PATHWAYS; MITOGENIC RESPONSE; MOLECULAR-CLONING AB The early response to vascular injury is characterized by migration of inflammatory cells, including monocytes, and platelets to the damaged vessel wall. These inflammatory cells may serve as a source of growth factors and cytokines that stimulate vascular smooth muscle cell (VSMC) migration and proliferation associated with intimal hyperplasia. JE is a platelet-derived growth factor (PDGF)-inducible "early" gene that encodes a monocyte chemoattractant and, as such, could play an important role in inflammation. We now report that JE mRNA levels are increased in intact aorta after balloon injury. The time course of this increase, with maximal levels at 4 hours, is similar to that seen in PDGF-treated cultured rat aortic VSMCs. The accumulation of JE mRNA in cultured VSMCs is accompanied by a marked increase in the secretion of JE protein. The elevation of JE mRNA levels in VSMCs shows specificity for PDGF, because angiotensin II, alpha-thrombin, and epidermal growth factor fail to increase JE mRNA levels. In contrast to 3T3 fibroblasts, the accumulation of JE mRNA in VSMCs in response to PDGF is predominantly due to an increase in JE mRNA stability. The accumulation of JE mRNA in VSMCs stimulated by PDGF appears to occur via a novel pathway(s) independent of Ca2+ mobilization, Na+-H+ exchange, protein kinase C activation, or elevation in cAMP levels. These findings suggest that VSMCs may take part in the early inflammatory response after injury through the production of JE, a potent monocyte chemoattractant. Finally, our data suggest that JE may be a marker for PDGF-specific effects on VSMCs, both in vitro and in vivo. Thus, in addition to direct effects on VSMC growth and migration, PDGF may play a role in the early inflammatory response after vascular injury by inducing chemoattractants, such as that encoded by JE. C1 CUNY MT SINAI SCH MED,DEPT MED,DIV MOLEC MED,NEW YORK,NY 10029. CUNY MT SINAI SCH MED,DEPT PEDIAT,NEW YORK,NY 10029. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. EMORY UNIV,SCH MED,DIV CARDIOL,ATLANTA,GA 30322. CHILDRENS HOSP MED CTR,DEPT CARDIOL,MOLEC & CELLULAR CARDIOL LAB,BOSTON,MA 02115. RP TAUBMAN, MB (reprint author), CUNY MT SINAI SCH MED,BROOKDALE CTR MOLEC BIOL,BOX 1126,1 GUSTAVE L LEVY PL,NEW YORK,NY 10029, USA. FU NCI NIH HHS [CA-48675]; NHLBI NIH HHS [HL-43302] NR 69 TC 146 Z9 152 U1 0 U2 4 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7330 J9 CIRC RES JI Circ.Res. PD FEB PY 1992 VL 70 IS 2 BP 314 EP 325 PG 12 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA HC554 UT WOS:A1992HC55400011 PM 1735132 ER PT J AU PANDIAN, MR MORGAN, CH CARLTON, E SEGRE, GV AF PANDIAN, MR MORGAN, CH CARLTON, E SEGRE, GV TI MODIFIED IMMUNORADIOMETRIC ASSAY OF PARATHYROID HORMONE-RELATED PROTEIN - CLINICAL-APPLICATION IN THE DIFFERENTIAL-DIAGNOSIS OF HYPERCALCEMIA SO CLINICAL CHEMISTRY LA English DT Note DE CANCER; SAMPLE HANDLING; REFERENCE VALUES ID HUMORAL HYPERCALCEMIA; MALIGNANCY; PEPTIDE; SERUM AB We have developed a sensitive, specific solid-phase immunoradiometric assay (IRMA) of parathyroid hormonerelated protein (PTH-RP) with use of affinity-purified poly-clonal immunoglobulins. Antibodies recognizing PTH-RP(37-74) are immobilized to a polystyrene bead to "capture" analytes from the sample; antibodies to epitopes within the 1-36 amino acid region of PTH-RP are labeled with I-125. This IRMA recognizes PTH-RP(1-74) and PTH-RP(1-86) equivalently, but does not detect N-terminal or C-terminal fragments of PTH-RP, intact human parathyrin (PTH), or fragments of PTH. PTH-RP is not stable in plasma at 3-5-degrees-C or room temperature, but a mixture of aprotinin (500 kallikrein units/L) and leupeptin (2.5 mg/L) improves PTH-RP stability in blood samples. In plasma collected in the presence of these protease inhibitors from normal volunteers and patients with various disorders of calcium metabolism, PTH-RP concentrations were above normal (> 1.5 pmol/L) in 91% (42 of 46) of patients with hypercalcemia associated with nonhematological malignancy. In plasma from patients with other hypercalcemic conditions (e.g., primary hyperparathyroidism, sarcoidosis, and vitamin D excess), PTH-RP was undetectable. Above-normal concentrations of PTH-RP and total calcium decreased to normal in a patient with an ovarian cyst adenocarcinoma after surgical removal of the tumor. We conclude that PTH-RP is related to and probably the causative agent of hypercalcemia in most patients with cancer, and that measurements of PTH-RP are useful in the diagnosis and management of patients with tumor-associated hypercalcemia. C1 MASSACHUSETTS GEN HOSP,DEPT MED,ENDOCRINE UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP PANDIAN, MR (reprint author), NICHOLS INST,26441 VIA ANZA,SAN JUAN CAPISTRANO,CA 92675, USA. NR 18 TC 86 Z9 87 U1 0 U2 2 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 FEB PY 1992 VL 38 IS 2 BP 282 EP 288 PG 7 WC Medical Laboratory Technology SC Medical Laboratory Technology GA HF057 UT WOS:A1992HF05700018 PM 1371724 ER PT J AU BRANCA, AA EHRLICH, HP KELLEY, SF RITENBERG, T LONGMUIR, M OHLSEN, J JEWELL, LS DOBIASH, MA PATT, LM TRACHY, RE AF BRANCA, AA EHRLICH, HP KELLEY, SF RITENBERG, T LONGMUIR, M OHLSEN, J JEWELL, LS DOBIASH, MA PATT, LM TRACHY, RE TI ACCELERATION OF HEALING OF RAT EXCISION WOUNDS BY TRIPEPTIDE-COPPER COMPLEX SO CLINICAL RESEARCH LA English DT Meeting Abstract C1 PROCYTE CORP,KIRKLAND,WA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0009-9279 J9 CLIN RES JI Clin. Res. PD FEB PY 1992 VL 40 IS 1 BP A75 EP A75 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA HA103 UT WOS:A1992HA10300407 ER PT J AU ALBIN, MS BUNEGIN, L DUKE, ES RITTER, RR PAGE, CP AF ALBIN, MS BUNEGIN, L DUKE, ES RITTER, RR PAGE, CP TI ANATOMY OF A DEFECTIVE BARRIER - SEQUENTIAL GLOVE LEAK DETECTION IN A SURGICAL AND DENTAL ENVIRONMENT SO CRITICAL CARE MEDICINE LA English DT Article DE LATEX RUBBER; GLOVE, SURGICAL; FLUORESCEINS; INFECTIONS, VIRAL, BACTERIAL; HUMAN IMMUNODEFICIENCY VIRUS; HEPATITIS-B VIRUS; CONDOMS; MICROSCOPY; FOOD AND DRUG ADMINISTRATION; SURGERY ID HEPATITIS-B VIRUS; RUBBER GLOVES; LATEX GLOVES; PERFORATIONS; CONTAMINATION; SURGEONS; FAILURE AB Objectives: a) To determine the frequency of perforations in latex surgical gloves before, during, and after surgical and dental procedures; b) to evaluate the topographical distribution of perforations in latex surgical gloves after surgical and dental procedures; and c) to validate methods of testing for latex surgical glove patency. Design: Multitrial tests under in vitro conditions and a prospective sequential patient study using consecutive testing. Setting: An outpatient dental clinic at a university dental school, the operating suite in a medical school affiliated with the Veteran's Hospital, and a biomechanics laboratory. Personnel: Surgeons, scrub nurses, and dental technicians participating in 50 surgical and 50 dental procedures. Methods: We collected 679 latex surgical gloves after surgical procedures and tested them for patency by using a water pressure test. We also employed an electronic glove leak detector before donning, after sequential time intervals, and upon termination of 47 surgical (sequential surgical), 50 dental (sequential dental), and in three orthopedic cases where double gloving was used. The electronic glove leak detector was validated by using electronic point-by-point surface probing, fluorescein dye diffusion, as well as detecting glove punctures made with a 27-gauge needle. Results: The random study indicated a leak rate of 33.0% (224 out of 679) in latex surgical gloves; the sequential surgical study demonstrated patency in 203 out of 347 gloves (58.5%); the sequential dental study showed 34 leaks in the 106 gloves used (32.1%); and with double gloving, the leak rate decreased to 25.0% (13 of 52 gloves tested). While the allowable FDA defect rate for unused latex surgical gloves is 1.5%, we noted defect rates in unused gloves of 5.5% in the sequential surgical, 1.9% in the sequential dental, and 4.0% in our electronic glove leak detector validating study. In the sequential surgical study, 52% of the leaks had occurred by 75 mins, and in the sequential dental study, 75% of the leaks developed by 30 mins. In terms of the anatomical localization, the thumb and forefinger accounted for more than 60% of the defects. There were no differences in the frequency of glove leaks between the left and right hand. Leak rates were highest for the surgeon (52%), followed by the first assistant (29%) and the scrub nurse (25%). No false negatives were noted using the electronic glove leak detector; one false positive was seen out of 225 gloves tested (0.44%), as noted in our validation studies. Conclusions: Significantly high glove leak rates were noted after surgical and dental procedures, indicating that the present day latex surgical gloves can become an incompetent barrier once they are used. Unused latex surgical gloves demonstrated a higher rate of defects than allowed by the Food and Drug Administration standards, indicating substantial non-compliance of quality control standards by manufacturers as well as inadequate governmental oversight. Double gloving, or the use of thicker latex surgical gloves, would probably reduce the frequency of glove leaks. Latex surgical gloves should be tested for patency before use and during surgical and dental procedures. C1 UNIV TEXAS,HLTH SCI CTR,DEPT SURG,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,SCH MED,CLIN RES FACIL,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,SCH DENT,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,ANESTHESIA SERV,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SURG SERV,SAN ANTONIO,TX 78284. RP ALBIN, MS (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT ANESTHESIOL,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. NR 57 TC 35 Z9 35 U1 1 U2 4 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 FEB PY 1992 VL 20 IS 2 BP 170 EP 184 DI 10.1097/00003246-199202000-00006 PG 15 WC Critical Care Medicine SC General & Internal Medicine GA HC983 UT WOS:A1992HC98300006 PM 1737454 ER PT J AU HYMAN, BT TANZI, RE AF HYMAN, BT TANZI, RE TI AMYLOID, DEMENTIA AND ALZHEIMERS-DISEASE SO CURRENT OPINION IN NEUROLOGY AND NEUROSURGERY LA English DT Article ID PROTEASE NEXIN-II; PRECURSOR PROTEIN; DOMAIN; BRAIN; ALPHA-1-ANTICHYMOTRYPSIN; NEUROFILAMENT; PLAQUES; SENILE; CORE AB Senile plaques (SP) and neurofibrillary tangles (NFT) are the major histopathological changes that occur in Alzheimer's disease (AD). How these two different types of lesions are related to each other and to the dementia of AD is unknown. Recent studies lead to paradoxical conclusions: NFT and neuronal alterations such as synapse loss are much more closely related to the symptoms of dementia than are SP. However, mutations in the beta-amyloid protein of SP have been found in some patients with familial AD, suggesting that an abnormality in amyloid causes the development of SP, NFT and AD dementia. Examination of transgenic animals that produce amyloid precursor protein (APP), or altered forms of APP, may lead to the development of an animal model of AD, and ultimately to answers that link amyloid production to neuronal alterations, and cognitive impairments. RP HYMAN, BT (reprint author), MASSACHUSETTS GEN HOSP,DEPT NEUROL,NEUROL SERV,FRUIT ST,BOSTON,MA 02114, USA. FU NIA NIH HHS [AGO8487]; NINDS NIH HHS [NS30428] NR 47 TC 35 Z9 35 U1 12 U2 12 PU CURRENT SCIENCE LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0951-7383 J9 CURR OPIN NEUROL NEU PD FEB PY 1992 VL 5 IS 1 BP 88 EP 93 PG 6 WC Neurosciences SC Neurosciences & Neurology GA HH015 UT WOS:A1992HH01500017 PM 1623244 ER PT J AU CHEN, JT STARK, DD AF CHEN, JT STARK, DD TI MAGNETIC-RESONANCE TECHNIQUES AND ARTIFACTS - EDITORIAL REVIEW SO CURRENT OPINION IN RADIOLOGY LA English DT Review AB One area in which MR imaging can use improvement is the reduction of artifacts due to various physiologic motions during imaging. These artifacts degrade images and can cause misleading interpretations. This paper reviews some of the recent technical advances directed to remove these artifacts, as well as other techniques that improve MR imaging quality in general. RP CHEN, JT (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CURRENT SCIENCE PI PHILADELPHIA PA 400 MARKET STREET,SUITE 750 ATTN:SARAH WHEALEN/SUB MGR, PHILADELPHIA, PA 19106 SN 1040-869X J9 CURR OPIN RADIOL PD FEB PY 1992 VL 4 IS 1 BP 13 EP 15 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA HD519 UT WOS:A1992HD51900002 PM 1739592 ER PT J AU WEBER, AL AF WEBER, AL TI IMAGING OF THE SALIVARY-GLANDS SO CURRENT OPINION IN RADIOLOGY LA English DT Review AB Salivary gland diseases are very common disorders and require radiologic evaluation. Several radiologic methods are used for assessment of these diseases. Conventional films of the parotid and submandibular glands demonstrate opaque stones in the duct system, whereas sialography depicts nonopaque stones, provides additional information on the position of the stones, and differentiates it from other calcific densities near the duct system, as well as providing information concerning ectasia of the ducts. CT has been used for evaluating mass lesions and extraglandular inflammatory disease, including abscesses. CT also depicts stones that may not be visible on conventional films. MR imaging has become an important modality in the diagnosis and definition of benign and malignant tumors and cysts and it will probably replace CT as the primary imaging modality for the assessment of these lesions. Gadolinium may be used in the examination, especially if a malignant tumor is suspected (because of irregularity and intraglandular extension). RP WEBER, AL (reprint author), MASSACHUSETTS GEN HOSP,MASSACHUSETTS EYE & EAR INFIRM,DEPT RADIOL,243 CHARLES ST,BOSTON,MA 02114, USA. NR 0 TC 14 Z9 14 U1 0 U2 0 PU CURRENT SCIENCE PI PHILADELPHIA PA 400 MARKET STREET,SUITE 750 ATTN:SARAH WHEALEN/SUB MGR, PHILADELPHIA, PA 19106 SN 1040-869X J9 CURR OPIN RADIOL PD FEB PY 1992 VL 4 IS 1 BP 117 EP 122 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA HD519 UT WOS:A1992HD51900017 PM 1739589 ER PT J AU SINGER, DE NATHAN, DM ANDERSON, KM WILSON, PWF EVANS, JC AF SINGER, DE NATHAN, DM ANDERSON, KM WILSON, PWF EVANS, JC TI ASSOCIATION OF HBA1C WITH PREVALENT CARDIOVASCULAR-DISEASE IN THE ORIGINAL COHORT OF THE FRAMINGHAM-HEART-STUDY SO DIABETES LA English DT Article ID HIGH-DENSITY-LIPOPROTEIN; GLYCOSYLATED HEMOGLOBIN; GLUCOSE-TOLERANCE; RISK-FACTORS; INSULIN RESISTANCE; DIABETES-MELLITUS; RETINOPATHY; INDIVIDUALS; PLASMA; ATHEROSCLEROSIS AB We studied the cross-sectional relationship between HbA1c and cardiovascular disease (CVD) in the survivors of the original cohort of the Framingham Heart Study (n = 1045). HbA1c was significantly related to prevalent CVD among women but not men. HbA1c was also related to hypertension and to the ratio of total to high-density lipoprotein cholesterol levels. In regression analyses that controlled for these and other potential risk factors, HbAc remained significantly related to CVD among women. The relative odds of CVD increased 1.39-fold (95% confidence interval 1.06-1.83) for increases in HbA1c of 1% (e.g., for HbA1c from 5 to 6%). The relationship was not weakened when known diabetic subjects or subjects taking 13-blocker or thiazide medications were excluded from analysis. In contrast, there was no significant relationship between "casual" blood glucose and prevalent CVD. Our results reveal a strong, significant, independent association between hyperglycemia, measured by HbA1c, and CVD among older women. C1 MASSACHUSETTS GEN HOSP,DEPT MED,DIABET UNIT,BOSTON,MA 02114. NHLBI,FRAMINGHAM HEART STUDY,FRAMINGHAM,MA. HARVARD UNIV,SCH MED,DEPT HLTH CARE POLICY,BOSTON,MA 02115. BOSTON UNIV HOSP,MED CTR,SCH MED,EVANS MEM DEPT CLIN RES,PREVENT MED & EPIDEMIOL SECT,BOSTON,MA 02218. RP SINGER, DE (reprint author), MASSACHUSETTS GEN HOSP,GEN INTERNAL MED UNIT,BULFINCH 1,BOSTON,MA 02114, USA. NR 43 TC 215 Z9 217 U1 1 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD FEB PY 1992 VL 41 IS 2 BP 202 EP 208 DI 10.2337/diabetes.41.2.202 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA HA610 UT WOS:A1992HA61000012 PM 1733810 ER PT J AU JAMEEL, N PUGH, JA MITCHELL, BD STERN, MP AF JAMEEL, N PUGH, JA MITCHELL, BD STERN, MP TI DIETARY-PROTEIN INTAKE IS NOT CORRELATED WITH CLINICAL PROTEINURIA IN NIDDM SO DIABETES CARE LA English DT Article ID URINARY ALBUMIN EXCRETION; DIABETIC NEPHROPATHY; MEXICAN-AMERICANS; NATURAL-HISTORY; MICROALBUMINURIA; GLOMERULOPATHY; PATHOGENESIS; HYPERTENSION AB OBJECTIVE - To determine whether dietary protein intake is correlated with clinical proteinuria in subjects with non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS - Cross-sectional analysis of data obtained from the San Antonio Heart Study, a population-based survey of diabetes and cardiovascular risk factors. Subjects were enrolled in two phases: phase 1 between 1979 and 1982 and phase 2 between 1984 and 1988. This study was based on 376 NIDDM subjects who had both urinalysis and complete dietary protein intake information available. Dietary protein intake was measured by 24-h dietary recall in phase 1 and by food-frequency questionnaire in phase 2. An early-morning spot urine was obtained from study subjects. Clinical proteinuria was defined as greater-than-or-equal-to 1 on Ames Albustix test. RESULTS - In phase 1, the subjects with negative or trace proteinuria had a mean protein intake of 79.9 g/day compared with 72. 1 g/day for subjects with greater-than-or-equal-to 1 proteinuria. In phase 2, the mean protein intake was 72.2 g/day in the negative/trace group and 65.3 g/day in the greater-than-or-equal-to 1 proteinuria group. In multivariate analysis, adjusting for age, sex, ethnicity, systolic blood pressure, and 2-h blood glucose, we were again unable to detect a significant correlation between dietary protein intake and clinical proteinuria. CONCLUSIONS - These data do not support the hypothesis that high-protein intake is a risk factor for clinical proteinuria in NIDDM subjects. Therefore, any recommendation for protein restriction in the diets of NIDDM subjects, before the development of NIDDM-related nephropathy, must be made with caution. C1 UNIV TEXAS,HLTH SCI CTR,DEPT CLIN EPIDEMIOL,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT GEN MED,SAN ANTONIO,TX 78284. RP JAMEEL, N (reprint author), AUDIE L MURPHY MEM VET ADM MED CTR,AMBULATORY CARE 11C,SAN ANTONIO,TX 78284, USA. OI Pugh, Jacqueline/0000-0003-4933-141X; Mitchell, Braxton/0000-0003-4920-4744 FU NHLBI NIH HHS [HL-36820, HL-24799]; NIDDK NIH HHS [DK-38392] NR 26 TC 22 Z9 22 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 FEB PY 1992 VL 15 IS 2 BP 178 EP 183 DI 10.2337/diacare.15.2.178 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA HA609 UT WOS:A1992HA60900004 PM 1547674 ER PT J AU WIDOM, B DIAMOND, MP SIMONSON, DC AF WIDOM, B DIAMOND, MP SIMONSON, DC TI ALTERATIONS IN GLUCOSE-METABOLISM DURING MENSTRUAL-CYCLE IN WOMEN WITH IDDM SO DIABETES CARE LA English DT Article ID ORAL-CONTRACEPTIVE AGENTS; CARBOHYDRATE-METABOLISM; INSULIN BINDING; FOLLICULAR-FLUID; INVITRO; HYPERANDROGENISM; HYPERGLYCEMIA; FERTILIZATION; GONADOTROPIN; PROGESTERONE AB OBJECTIVE - To examine the hormonal mechanisms underlying the variability in glycemic control during the different phases of the menstrual cycle in women with insulin-dependent diabetes mellitus (IDDM). RESEARCH DESIGN AND METHODS - Hyperglycemic (11.7 +/- 0.1 mM), hyperinsulinemic (24 +/- 3 mU/L) clamp studies were performed in 16 women with IDDM during the follicular (day 8 +/- 1) and luteal (day 23 +/- 1) phases of the menstrual cycle. Seven of the patients (group 1) experienced worsening glucose control during the luteal phase, whereas nine patients (group 2) did not. RESULTS - In group 1, glucose metabolism fell from 30.2 +/- 3.8-mu-mol . kg-1 . min-1 during the follicular phase to 24.5 +/- 2.0-mu-mol . kg-1 . min-1 during the luteal phase (P = 0.09), whereas in group 2 it increased from 18.5 +/- 1.2 to 23.2 +/- 2.3-mu-mol . kg-1 . min-1 (P = 0.03). The decrease in glucose metabolism during the luteal phase in patients in group 1 was associated with a significant rise in the serum estradiol levels from the follicular to luteal phase (164 +/- 39 vs. 352 +/- 59 pM, P = 0.006), whereas this rise was not observed in group 2 (334 +/- 156 vs. 423 +/- 74 pM, NS). Changes in other reproductive hormones (progesterone, testosterone, dihydrotestosterone, androstenedione, luteinizing hormone, follicular-stimulating hormone, or prolactin) were not related to die differences in glucose uptake in the two groups. CONCLUSIONS - 1) Marked heterogeneity in glucose metabolism is seen throughout the menstrual cycle in women with IDDM, 2) a subgroup of patients exhibits worsening premenstrual hyperglycemia and a decline in insulin sensitivity during the luteal phase, and 3) the deterioration in glucose uptake in this subgroup was associated with a greater increment in estradiol levels from the follicular to the luteal phase. C1 NEW ENGLAND DEACONESS HOSP,JOSLIN DIABET CTR,DEPT INTERNAL MED,BOSTON,MA 02215. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,BOSTON,MA 02115. YALE UNIV,SCH MED,DEPT OBSTET & GYNECOL,NEW HAVEN,CT 06510. OI Diamond, Michael/0000-0001-6353-4489 FU NIDDK NIH HHS [5-P30-DK-36386] NR 44 TC 49 Z9 52 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD FEB PY 1992 VL 15 IS 2 BP 213 EP 220 DI 10.2337/diacare.15.2.213 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA HA609 UT WOS:A1992HA60900008 PM 1547678 ER PT J AU NATHAN, DM SCHREIBER, E FOGEL, H MOJSOV, S HABENER, JF AF NATHAN, DM SCHREIBER, E FOGEL, H MOJSOV, S HABENER, JF TI INSULINOTROPIC ACTION OF GLUCAGON-LIKE PEPTIDE-I-(7-37) IN DIABETIC AND NONDIABETIC SUBJECTS SO DIABETES CARE LA English DT Note ID PRE-PROGLUCAGON; GENE-EXPRESSION; PANCREAS; PEPTIDE-1; SEQUENCE AB OBJECTIVE - Whether glucagonlike peptide-I-(7-37) (GLP-I-[7-37]), a naturally occurring intestinal peptide, is insulinotropic in nondiabetic and non-insulin-dependent (type II) diabetic subjects. RESEARCH DESIGN AND METHODS - GLP-I-(7-37) or saline placebo was infused (1- 5 ng . kg-1 . min-1 for 30 min) in 4 nondiabetic and 11 type II diabetic subjects in the fasting and prandial state. Glucose, insulin, and GLP-I-(7-37) levels were measured. RESULTS - GLP-I-(7-37) infusion resulted in a 3- to 10-fold increase in peak insulin levels and in insulin area under the curve in nondiabetic and diabetic subjects. In diabetic subjects, infusion concurrent with a standard meal eliminated the postprandial glucose excursion for 60 min after the meal. Insulin-releasing potency of GLP-I-(7-37) was attenuated at decreased glucose levels. CONCLUSIONS - GLP-I-(7-37) has potent insulinotropic effects in nondiabetic and diabetic subjects. Whether GLP-I-(7-37) is useful as a therapeutic medication in type II diabetes requires further investigation. C1 HARVARD UNIV,SCH MED,HOWARD HUGHES MED INST,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,MOLEC ENDOCRINOL LAB,BOSTON,MA 02114. RP NATHAN, DM (reprint author), MASSACHUSETTS GEN HOSP,DIABET UNIT,BULFINCH 4,BOSTON,MA 02114, USA. FU NIDDK NIH HHS [DK-30834] NR 14 TC 269 Z9 275 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD FEB PY 1992 VL 15 IS 2 BP 270 EP 276 DI 10.2337/diacare.15.2.270 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA HA609 UT WOS:A1992HA60900015 PM 1547685 ER PT J AU ZOPPINI, G KAHN, CR AF ZOPPINI, G KAHN, CR TI EFFECT OF PHOSPHOLIPASE TREATMENT ON INSULIN-RECEPTOR SIGNAL TRANSDUCTION SO DIABETOLOGIA LA English DT Article DE MEMBRANE LIPIDS; INSULIN RECEPTORS; INSULIN ACTION; TYROSINE PHOSPHORYLATION; PP-185 ID TYROSINE KINASE-ACTIVITY; CULTURED HEPATOMA-CELLS; MEMBRANE FLUIDITY; GLYCOSYL-PHOSPHATIDYLINOSITOL; PHOSPHORYLATION; LIPIDS; BINDING; PROTEIN; RESISTANCE; ACTIVATION AB To study the role of membrane lipids in signal transduction by the insulin receptor, we have studied the effect of phospholipase C (Clostridium perfringens) and a phosphatidylinositol-specific phospholipase (Staphylococcus aureus) on insulin binding, a function of the alpha-subunit, and tyrosine kinase activity, a function of the beta-subunit in IM-9 lymphocytes and NIH 3T3 fibroblasts transfected with the human insulin receptor. Treatment of the cells with phospholipase C at concentrations up to 3.4 U/ml did not affect specific insulin binding, but reduced insulin-stimulated receptor phosphorylation by 50%. This effect of phospholipase C was observed within 10 min of treatment and occurred with no change in the basal level of phosphorylation. Pre-treatment of cells with insulin for 5 min prior to enzyme addition prevented any change in kinase activity. Insulin-stimulated phosphorylation of pp 185, the presumed endogenous substrate for the insulin receptor kinase, was also reduced following phospholipase C treatment, with an almost complete loss of insulin stimulation after exposure of cells to enzyme at concentrations as low as 0.6 U/ml. In contrast to these effects of phospholipase C on intact cells, receptor autophosphorylation was not affected in insulin receptors purified on wheat germ agglutinin-agarose from phospholipase C treated cells. Likewise, the phospholipase C effect was reduced by the addition of phosphatidylcholine, but not by the addition of the protease inhibitors, aprotinin and phenylmethylsulfonyl fluoride, to the incubation indicating its dependence on phospholipid hydrolysis. Treatment of cells with the phosphatidylinositol-specific phospholipase C did not affect any of the parameters studied. These data suggest that the phospholipid environment in the plasma membrane is an important modulator of transmembrane signalling within the insulin receptor heterotetramer and at the level of substrate phosphorylation. C1 BRIGHAM & WOMENS HOSP,JOSLIN DIABET CTR,DEPT MED,DIV RES,ONE JOSLIN PL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. FU NIDDK NIH HHS [DK36836, DK31036] NR 51 TC 14 Z9 14 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 FEB PY 1992 VL 35 IS 2 BP 109 EP 115 DI 10.1007/BF00402541 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA HB850 UT WOS:A1992HB85000003 PM 1312492 ER PT J AU LEE, MM CATE, RL DONAHOE, PK WANECK, GL AF LEE, MM CATE, RL DONAHOE, PK WANECK, GL TI DEVELOPMENTALLY REGULATED POLYADENYLATION OF 2 DISCRETE MESSENGER RIBONUCLEIC-ACIDS FOR MULLERIAN INHIBITING SUBSTANCE SO ENDOCRINOLOGY LA English DT Article ID GRANULOSA-CELLS; RNA TRANSLATION; OOCYTE MEIOSIS; SERTOLI CELLS; POLY(A) TAIL; HORMONE; RAT; INVITRO; FETAL; MATURATION AB Mullerian inhibiting substance (MIS) is a 140-kilodalton homodimeric glycoprotein that causes regression of the Mullerian ducts in male embryos, and may also have a role in both males and females in the regulation of germ cell maturation. We examined the ontogeny of MIS messenger RNA (mRNA) in rat testes from midgestation through adulthood and found two discrete MIS mRNA species that are developmentally regulated. The larger 2.0-kilobase species is abundant at embryonic day 14, then decreases in late gestation, and is barely detectable after birth. The smaller 1.8-kilobase species is first noted at embryonic day 18 and is the major species detected postnatally. Both species are abundant just prior to birth, at embryonic day 21, then decrease markedly after birth. This variation in MIS mRNA levels correlates with the developmental expression of MIS protein. A series of oligonucleotide-directed ribonuclease H mapping experiments determined that the two mRNA species differ at their 3' ends in the extent of polyadenylation. Thus, differential polyadenylation of MIS mRNA may be an additional mechanism for regulating MIS expression during fetal and postnatal development. C1 MASSACHUSETTS GEN HOSP, MOLEC IMMUNOL RES LAB, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, SURG SERV, PEDIAT ENDOCRINE UNIT, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, CHILDRENS SERV, BOSTON, MA 02114 USA. BIOGEN INC, CAMBRIDGE, MA 02142 USA. RP LEE, MM (reprint author), MASSACHUSETTS GEN HOSP, PEDIAT SURG RES LAB, WARREN 10, BOSTON, MA 02114 USA. OI Lee, Mary/0000-0002-7204-4884 FU NCI NIH HHS [CA-17393] NR 40 TC 22 Z9 22 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD FEB PY 1992 VL 130 IS 2 BP 847 EP 853 DI 10.1210/en.130.2.847 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA HH371 UT WOS:A1992HH37100039 PM 1346380 ER PT J AU EPSTEIN, RJ AF EPSTEIN, RJ TI DOES THE BREAST-CANCER DOLLAR MAKE SENSE SO EUROPEAN JOURNAL OF CANCER LA English DT Article; Proceedings Paper CT BREAST CANCER WORKING CONF : BREAST CANCER - LOTS OF DATA, STEADY BUT SLOW CLINICAL PROGRESS CY SEP 03-06, 1991 CL PAUSCOLLEGE, LOUVAIN, BELGIUM SP EUROPEAN ORG RES & TREATMENT CANC HO PAUSCOLLEGE ID DOCTOR-PATIENT COMMUNICATION; RANDOMIZED COMPARATIVE TRIAL; FOLLOW-UP; CLINICAL-TRIAL; ADJUVANT THERAPY; RADIATION-THERAPY; DOSE-RESPONSE; CHEMOTHERAPY; MAMMOGRAPHY; MASTECTOMY AB The past decade has witnessed a transformation of breast cancer management. Innovative developments such as widespread mammographic screening, breast-conserving approaches to primary disease and adjuvant systemic therapy have improved the quality of breast cancer care in the community. These and other therapeutic developments have been accompanied by substantial increases in consumption of health care resources. With the exception of adjuvant systemic therapy for node-positive disease, the evidence that such increases have been associated with commensurate improvements in disease outcome is weak. Indefinite continuation of this trend may prove incompatible with socioeconomic realities. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. RP EPSTEIN, RJ (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. NR 92 TC 19 Z9 19 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD FEB-MAR PY 1992 VL 28A IS 2-3 BP 486 EP 491 DI 10.1016/S0959-8049(05)80084-X PG 6 WC Oncology SC Oncology GA HL783 UT WOS:A1992HL78300045 PM 1591070 ER PT J AU CALVO, V BIERER, BE VIK, TA AF CALVO, V BIERER, BE VIK, TA TI T-CELL RECEPTOR ACTIVATION OF A RIBOSOMAL S6 KINASE-ACTIVITY SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article ID CHICKEN-EMBRYO FIBROBLASTS; ANTIGEN RECEPTOR; PROTEIN-KINASE; TYROSINE PHOSPHORYLATION; MAP-2 KINASE; LYMPHOCYTES-T; INSULIN; IDENTIFICATION; PHOSPHATASE; ASSOCIATION AB Stimulation of the T cell receptor-CD3 complex activates multiple signal transduction pathways, including serine/threonine and tyrosine protein kinases. Stimulation of the human T cell line Jurkat via the T cell receptor-CD3 complex with anti-CD3 monoclonal antibody or incubation with the tumor promoter phorbol 12-myristate 13-acetate caused increases in S6 kinase and microtubule-associated protein 2 (MAP) kinase activities. An S6 kinase activity that was able to phosphorylate exogenous 40S ribosomal S6 protein was recovered in immunoprecipitates obtained using a 90-kDa ribosomal S6 kinase-specific antiserum and thus represents activation of a member of the 90-kDa ribosomal S6 kinase family. Stimulation of the S6 kinase activity correlated with an increase in a kinase activity able to phosphorylate exogenous 90-kDa ribosomal S6 kinase (rsk) attributed to a MAP kinase activity. These increases in S6 and MAP kinase activities further correlated with the appearance of a 42-kDa phosphoprotein detected by anti-phosphotyrosine immunoblotting. However, while the tyrosine phosphorylation of the 42-kDa protein and the MAP kinase activity are dependent on protein kinase C activity, residual S6 kinase activity can be detected following protein kinase C depletion and subsequent anti-CD3 stimulation. Thus, T cell activation through the T cell receptor-CD3 complex results in activation of a member of the 90-kDa S6 kinase family which correlates with, but can be independent of, MAP kinase activation. C1 BRIGHAM & WOMENS HOSP,DIV HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,CHILDRENS HOSP,SCH MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,DEPT CELLULAR & DEV BIOL,CAMBRIDGE,MA 02138. RP CALVO, V (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,ROOM D1610B,44 BINNEY ST,BOSTON,MA 02115, USA. RI Calvo, Victor/L-5024-2014 OI Calvo, Victor/0000-0002-5913-7058 NR 36 TC 20 Z9 20 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 FEB PY 1992 VL 22 IS 2 BP 457 EP 462 DI 10.1002/eji.1830220225 PG 6 WC Immunology SC Immunology GA HF952 UT WOS:A1992HF95200024 PM 1537381 ER PT J AU DURING, MJ FREESE, A DEUTCH, AY KIBAT, PG SABEL, BA LANGER, R ROTH, RH AF DURING, MJ FREESE, A DEUTCH, AY KIBAT, PG SABEL, BA LANGER, R ROTH, RH TI BIOCHEMICAL AND BEHAVIORAL RECOVERY IN A RODENT MODEL OF PARKINSONS-DISEASE FOLLOWING STEREOTAXIC IMPLANTATION OF DOPAMINE-CONTAINING LIPOSOMES SO EXPERIMENTAL NEUROLOGY LA English DT Article ID POLYMERIC BRAIN IMPLANT; CONTROLLED-RELEASE; LEVODOPA; RATS; TRANSPLANTATION; STRIATUM; DELIVERY; INVITRO; LESIONS; TISSUE C1 YALE UNIV,SCH MED,DEPT PHARMACOL,NEW HAVEN,CT 06510. YALE UNIV,SCH MED,DEPT PSYCHIAT,NEW HAVEN,CT 06510. MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. MIT,DEPT CHEM ENGN,CAMBRIDGE,MA 02139. MIT,DIV HLTH SCI & TECHNOL,CAMBRIDGE,MA 02139. UNIV MUNICH,SCH MED,INST MED PSYCHOL,W-8000 MUNICH 2,GERMANY. RI During, Matthew/E-3003-2011; Sabel, Bernhard/E-6579-2013 OI During, Matthew/0000-0002-3797-5026; FU NIGMS NIH HHS [GM-26698]; NIMH NIH HHS [MH-14092]; NINDS NIH HHS [NS-28227] NR 37 TC 25 Z9 27 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD FEB PY 1992 VL 115 IS 2 BP 193 EP 199 DI 10.1016/0014-4886(92)90053-S PG 7 WC Neurosciences SC Neurosciences & Neurology GA HB728 UT WOS:A1992HB72800001 PM 1735466 ER PT J AU GRAHAM, DY LEW, GM MALATY, HM EVANS, DG EVANS, DJ KLEIN, PD ALPERT, LC GENTA, RM AF GRAHAM, DY LEW, GM MALATY, HM EVANS, DG EVANS, DJ KLEIN, PD ALPERT, LC GENTA, RM TI FACTORS INFLUENCING THE ERADICATION OF HELICOBACTER-PYLORI WITH TRIPLE THERAPY SO GASTROENTEROLOGY LA English DT Article ID COLLOIDAL BISMUTH SUBCITRATE; ULCER; DISEASE C1 BAYLOR COLL MED,DEPT MED,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT PEDIAT,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT PATHOL,DIV MOLEC VIROL,HOUSTON,TX 77030. BAYLOR COLL MED,USDA ARS,CHILDRENS NUTR RES CTR,HOUSTON,TX 77030. RP GRAHAM, DY (reprint author), VET AFFAIRS MED CTR 111D,2002 HOLCOMBE BLVD,HOUSTON,TX 77030, USA. FU NIDDK NIH HHS [DK 39919] NR 18 TC 518 Z9 525 U1 1 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD FEB PY 1992 VL 102 IS 2 BP 493 EP 496 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA HA639 UT WOS:A1992HA63900015 PM 1732120 ER PT J AU KWIATKOWSKI, DJ HENSKE, EP WEIMER, K OZELIUS, L GUSELLA, JF HAINES, J AF KWIATKOWSKI, DJ HENSKE, EP WEIMER, K OZELIUS, L GUSELLA, JF HAINES, J TI CONSTRUCTION OF A GT POLYMORPHISM MAP OF HUMAN 9Q SO GENOMICS LA English DT Article ID GENETIC-LINKAGE MAP; HUMAN DNA; HUMAN GENOME; CYTOGENETIC ANALYSIS; HUMAN CHROMOSOME-9; SEQUENCE; LOCI; IDENTIFICATION; HYBRIDIZATION; ASSIGNMENTS C1 MASSACHUSETTS GEN HOSP,NEUROGENET LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. RP KWIATKOWSKI, DJ (reprint author), BRIGHAM & WOMENS HOSP,DIV EXPTL MED & HEMATOL ONCOL,BOSTON,MA 02115, USA. RI Haines, Jonathan/C-3374-2012 FU NHGRI NIH HHS [HG000598, HG00169]; NINDS NIH HHS [NS22031] NR 37 TC 170 Z9 171 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD FEB PY 1992 VL 12 IS 2 BP 229 EP 240 DI 10.1016/0888-7543(92)90370-8 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA GY879 UT WOS:A1992GY87900007 PM 1339384 ER PT J AU SCHER, HI KANTOFF, PW AF SCHER, HI KANTOFF, PW TI CHEMOTHERAPY FOR MUSCLE-INFILTRATING BLADDER-CANCER SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID TRANSITIONAL CELL-CARCINOMA; NEOADJUVANT CHEMOTHERAPY; CISPLATIN CHEMOTHERAPY; UROTHELIAL TUMORS; DOXORUBICIN; MANAGEMENT; CYCLOPHOSPHAMIDE; ADJUVANT; NODE; METHOTREXATE C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. CORNELL UNIV,MED CTR,COLL MED,DEPT MED,NEW YORK,NY 10021. RP SCHER, HI (reprint author), MEM SLOAN KETTERING CANC CTR,DEPT MED,DIV SOLID TUMOR ONCOL,GENITOURINARY ONCOL SERV,NEW YORK,NY 10021, USA. FU NCI NIH HHS [CA-05826, CA-09207-14] NR 42 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 FEB PY 1992 VL 6 IS 1 BP 169 EP 178 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA HE469 UT WOS:A1992HE46900010 PM 1556048 ER PT J AU KAUFMAN, DS SHIPLEY, WU ALTHAUSEN, AF AF KAUFMAN, DS SHIPLEY, WU ALTHAUSEN, AF TI RADIOTHERAPY AND CHEMOTHERAPY IN INVASIVE BLADDER-CANCER WITH POTENTIAL BLADDER SPARING SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID TRANSITIONAL CELL-CARCINOMA; CALIFORNIA-ONCOLOGY-GROUP; RADICAL CYSTECTOMY; CISPLATIN CHEMOTHERAPY; ADJUVANT CHEMOTHERAPY; RADIATION-THERAPY; URINARY-TRACT; METHOTREXATE; ADRIAMYCIN; EXPERIENCE C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT RADIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,CTR CANC,MED ONCOL SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CTR CANC,DEPT RADIAT ONCOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CTR CANC,UROL SERV,BOSTON,MA 02114. NR 39 TC 15 Z9 15 U1 1 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 FEB PY 1992 VL 6 IS 1 BP 179 EP 194 PG 16 WC Oncology; Hematology SC Oncology; Hematology GA HE469 UT WOS:A1992HE46900011 PM 1556049 ER PT J AU KANTOFF, PW SCHER, HI AF KANTOFF, PW SCHER, HI TI CHEMOTHERAPY FOR METASTATIC BLADDER-CANCER SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID TRANSITIONAL CELL-CARCINOMA; M-VAC METHOTREXATE; ADVANCED UROTHELIAL CANCER; PHASE-II; ONCOLOGY-GROUP; URINARY-TRACT; CISPLATIN; DOXORUBICIN; VINBLASTINE; CYCLOPHOSPHAMIDE C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. CORNELL UNIV,MED CTR,COLL MED,DEPT MED,NEW YORK,NY 10021. MEM SLOAN KETTERING CANC CTR,DEPT MED,DIV SOLID TUMOR ONCOL,GENITOURINARY ONCOL SERV,NEW YORK,NY 10021. RP KANTOFF, PW (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,44 BINNEY ST,BOSTON,MA 02115, USA. NR 32 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 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD FEB PY 1992 VL 6 IS 1 BP 195 EP 203 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA HE469 UT WOS:A1992HE46900012 PM 1556050 ER PT J AU KANTOFF, PW SCHER, HI AF KANTOFF, PW SCHER, HI TI BLADDER-CANCER SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Editorial Material C1 MEM SLOAN KETTERING CANC CTR,NEW YORK,NY 10021. RP KANTOFF, PW (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,44 BINEY ST,BOSTON,MA 02115, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD FEB PY 1992 VL 6 IS 1 BP U1 EP U1 PG 1 WC Oncology; Hematology SC Oncology; Hematology GA HE469 UT WOS:A1992HE46900013 ER PT J AU BUSH, RK RITTER, MW AF BUSH, RK RITTER, MW TI ALLERGEN IMMUNOTHERAPY FOR THE PATIENT WITH ALLERGIC RHINITIS SO IMMUNOLOGY AND ALLERGY CLINICS OF NORTH AMERICA LA English DT Article ID PLACEBO-CONTROLLED TRIAL; HAY-FEVER PATIENTS; DOUBLE-BLIND TRIAL; POLLEN EXTRACT; DERMATOPHAGOIDES-PTERONYSSINUS; RUSH IMMUNOTHERAPY; ANTIGEN CHALLENGE; NASAL SECRETIONS; RAGWEED-POLLEN; MUCOSA C1 UNIV WISCONSIN,DEPT MED,MADISON,WI 53706. RP BUSH, RK (reprint author), WILLIAM S MIDDLETON MEM VET ADM MED CTR,ALLERGY SECT,2500 OVERLOOK TERRACE,MADISON,WI 53705, USA. NR 70 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 0889-8561 J9 IMMUNOL ALLERGY CLIN JI Immunol. Allerg. Clin. North Am. PD FEB PY 1992 VL 12 IS 1 BP 107 EP 124 PG 18 WC Allergy; Immunology SC Allergy; Immunology GA HD054 UT WOS:A1992HD05400009 ER PT J AU FOX, JG PASTER, BJ DEWHIRST, FE TAYLOR, NS YAN, LL MACUCH, PJ CHMURA, LM AF FOX, JG PASTER, BJ DEWHIRST, FE TAYLOR, NS YAN, LL MACUCH, PJ CHMURA, LM TI HELICOBACTER-MUSTELAE ISOLATION FROM FECES OF FERRETS - EVIDENCE TO SUPPORT FECAL-ORAL TRANSMISSION OF A GASTRIC HELICOBACTER SO INFECTION AND IMMUNITY LA English DT Article ID CAMPYLOBACTER-PYLORI INFECTION; TO-PERSON TRANSMISSION; C-PYLORI; SUBSP-MUSTELAE; ANIMAL-MODEL; COLONIZATION; CARCINOMA; ORGANISMS; ANTIBODY; DISEASE AB Helicobacter mustelae has been isolated from stomachs of ferrets with chronic gastritis and ulcers. When H. mustelae is inoculated orally into H. mustelae-negative ferrets, the animals become colonized and develop gastritis, a significant immune response, and a transient hypochlorhydria. All of these features mimic Helicobacter pylori-induced gastric disease in humans. Because the epidemiology of H. pylori infection is poorly understood and its route of transmission is unknown, the feces of weanling and adult ferrets were cultured for the presence of H. mustelae. H. mustelae was isolated from the feces of 11 of 36 ferrets by using standard helicobacter isolation techniques. H. mustelae was identified by biochemical tests, ultrastructural morphology, reactivity with specific DNA probes, and 16S rRNA sequencing. H. mustelae was not recovered from 20-week-old ferrets which had been H. mustelae positive as weanlings, nor was H. mustelae recovered from 1-year-old ferrets. Isolation of H. mustelae from feces may correspond to periods of transient hypochlorhydria, or H. mustelae may be shed in feces intermittently. The H. mustelae-colonized ferret provides an ideal model for studying the pathogenesis and transmission of H. pylori-induced gastric disease. C1 FORSYTH DENT CTR,BOSTON,MA 02215. RP FOX, JG (reprint author), MIT,DIV COMPARAT MED,45-104,37 VASSAR ST,CAMBRIDGE,MA 02139, USA. FU NCI NIH HHS [P01-CA26731]; NCRR NIH HHS [RR01046, RR07036] NR 43 TC 67 Z9 67 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 FEB PY 1992 VL 60 IS 2 BP 606 EP 611 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA HA564 UT WOS:A1992HA56400042 PM 1370432 ER PT J AU SOUKIASIAN, SH RICE, B FOSTER, CS LEE, SJ AF SOUKIASIAN, SH RICE, B FOSTER, CS LEE, SJ TI THE T-CELL RECEPTOR IN NORMAL AND INFLAMED HUMAN CONJUNCTIVA SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE ATOPIC KERATOCONJUNCTIVITIS; AUTOIMMUNITY; CONJUNCTIVA; OCULAR CICATRICIAL PEMPHIGOID; T-CELL RECEPTOR (TCR) ID INTESTINAL INTRAEPITHELIAL LYMPHOCYTES; DENDRITIC EPIDERMAL-CELLS; DELTA-ANTIGEN RECEPTOR; GAMMA-DELTA; MONOCLONAL-ANTIBODIES; MYCOBACTERIUM-TUBERCULOSIS; CD3-GAMMA-DELTA COMPLEX; RHEUMATOID-ARTHRITIS; SYNOVIAL-FLUID; EXPRESSION AB The majority of human peripheral blood and lymphoid tissue T cells express the TCR alpha/beta-heterodimer, while the TCR gamma/delta is expressed on only a small subset of T lymphocytes. However, the majority of murine intraepithelial lymphocytes and most Thy-1+ murine dendritic epidermal cells express the TCR gamma/delta. Selective homing of avian TCR gamma/delta bearing lymphocytes to the intestinal epithelium also has been shown. These findings have suggested that these cells play a role against transformation and infection. More recently, a role in autoimmunity also has been proposed. We examined normal human conjunctiva and inflamed conjunctiva from patients with ocular cicatricial pemphigoid (OCP), an autoimmune disorder, and atopic keratoconjunctivitis (AKC). The majority of T cells in the epithelium and substantia propria of normal conjunctiva expressed the TCR alpha/beta. Tropism of TCR gamma/delta-expressing lymphocytes to normal human conjunctiva was not present. However, in OCP, there was a statistically significant increase in the absolute number of TCR gamma/delta cells/mm2 (epithelium, 33.9 +/- 10.5 [mean +/- standard error of the mean] vs. 159.9 +/- 51.5, P = < 0.0008; substantia propria, 4.1 +/- 0.9 vs. 240.1 +/- 191.3, P < 0.002) and TCR gamma/delta cells as a percentage of CD3+ cells (epithelium, 0.18 +/- 0.06 vs. 0.39 +/- 0.07, P = < 0.02; substantia propria, 0.10 +/- 0.05 vs. 0.33 +/- 0.08, P = < 0.03). This was not the case for AKC. These findings suggest that TCR gamma/delta lymphocytes play a specific but undefined role in certain conjunctival inflammatory conditions and may be important in autoimmunity. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,IMMUNOL SERV,243 CHARLES ST,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,HILLES IMMUNOL LAB,BOSTON,MA 02114. NR 44 TC 25 Z9 25 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 FEB PY 1992 VL 33 IS 2 BP 453 EP 459 PG 7 WC Ophthalmology SC Ophthalmology GA HE030 UT WOS:A1992HE03000028 PM 1531476 ER PT J AU CHOE, HR SODROSKI, J AF CHOE, HR SODROSKI, J TI CONTRIBUTION OF CHARGED AMINO-ACIDS IN THE CDR2 REGION OF CD4 TO HIV-1 GP120 BINDING SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE CD4; CHARGED AMINO ACIDS; GP120; HIV-1 ID HUMAN-IMMUNODEFICIENCY-VIRUS; IMMUNOGLOBULIN-LIKE DOMAIN; ENVELOPE GLYCOPROTEIN; RECEPTOR-BINDING; STRUCTURAL-ANALYSIS; T4 MOLECULE; SITE; TYPE-1; AIDS; IDENTIFICATION AB Several negatively charged amino acids of the human immunodeficiency virus type 1 (HIV-1) gp120 glycoprotein have been implicated in binding to the CD4 viral receptor. The CD4 region implicated in binding gp120 consists of a hydrophobic ridge protruding from a positively charged surface. To examine whether any of the surface charges on CD4 might contribute to gp120 binding, several amino acids near the CD4 regions previously implicated in gp120 binding were altered. Of the charged amino acids in the C" and D strands of the amino-terminal domain of CD4, alteration of only two, lysine 46 and arginine 59, dramatically disrupted ability to bind gp120. In the three-dimensional structure of CD4, these two basic amino acids are located proximal to phenylalanine 43, which we confirmed to be important for gp120 binding. By contrast, we could not confirm the observations that alteration of residues in the F strand (CDR3-like region) of CD4 significantly affected gp120-binding ability. These results support a model of the gp120-binding site that is dependent on discontinuous amino acids but spatially limited. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RP CHOE, HR (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HUMAN RETROVIROL,JF 623,44 BINNEY ST,BOSTON,MA 02115, USA. FU NIAID NIH HHS [RFA 90AI09] NR 33 TC 26 Z9 26 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD FEB PY 1992 VL 5 IS 2 BP 204 EP 210 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA GZ902 UT WOS:A1992GZ90200016 PM 1732513 ER PT J AU ANZUETO, A ANDRADE, FH MAXWELL, LC LEVINE, SM LAWRENCE, RA GIBBONS, WJ JENKINSON, SG AF ANZUETO, A ANDRADE, FH MAXWELL, LC LEVINE, SM LAWRENCE, RA GIBBONS, WJ JENKINSON, SG TI RESISTIVE BREATHING ACTIVATES THE GLUTATHIONE REDOX CYCLE AND IMPAIRS PERFORMANCE OF RAT DIAPHRAGM SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE RESPIRATORY MUSCLES; FREE RADICALS; MALONDIALDEHYDE; THIOBARBITURIC ACID-REACTIVE SUBSTANCES; ANTIOXIDANT; LIPID PEROXIDATION; INJURY; CONTRACTILE PROPERTIES ID LIPID-PEROXIDATION; BLOOD-FLOW; RESPIRATORY MUSCLES; SKELETAL-MUSCLE; EXERCISE; CONTRACTION; METABOLISM; FATIGUE; STRESS AB Free radical activation and lipid peroxidation have been described in skeletal muscle during strenuous exercise. We hypothesized that oxygen radicals could also be formed in the diaphragm muscle during strenuous resistive breathing and that these radicals might affect diaphragm function. Seven control and 12 experimental male Sprague-Dawley rats were studied. Six experimental animals were subjected to resistive breathing (RB) alone and six animals received 15 min of mechanical ventilatory support (MV) after the resistive breathing period. Inspiratory resistance was adjusted to maintain airway opening pressure at 70% maximum in both groups until exhaustion. Diaphragm samples were obtained for analysis of thiobarbituric acid-reactive substances (TBAR), reduced glutathione (GSH), and glutathione disulfide (GSSG). In vitro isometric contraction times, twitch (P(t)) tension and maximum tetanic (P(o)) tension, force-frequency curves, fatigue index, and recovery index were measured. In RB and MV compared with controls, there were significant decreases in P(t) and P(o). Diaphragm TBAR concentrations were increased in MV compared with controls or RB. GSSG-to-total glutathione ratio was increased in RB and MV compared with controls. Production of free radicals during RB and MV may represent an important mechanism of diaphragmatic injury that could contribute to the decline in contractility. C1 AUDIE L MURPHY VET AFFAIRS HOSP,SAN ANTONIO,TX 78284. RP ANZUETO, A (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV PULM DIS CRIT CARE,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. RI Andrade, Francisco/F-1258-2011 OI Andrade, Francisco/0000-0002-2460-5798 NR 33 TC 74 Z9 75 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 FEB PY 1992 VL 72 IS 2 BP 529 EP 534 PG 6 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA HE268 UT WOS:A1992HE26800019 PM 1559928 ER PT J AU HALES, CA MUSTO, SW JANSSENS, S JUNG, W QUINN, DA WITTEN, M AF HALES, CA MUSTO, SW JANSSENS, S JUNG, W QUINN, DA WITTEN, M TI SMOKE ALDEHYDE COMPONENT INFLUENCES PULMONARY-EDEMA SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE EICOSANOIDS; PULMONARY HEMODYNAMICS; SHEEP ID INHALATION INJURY; SYNTHETIC SMOKE; ACROLEIN; FORMALDEHYDE; MORTALITY; SHEEP AB The pulmonary edema of smoke inhalation is caused by the toxins of smoke and not the heat. We investigated the potential of smoke consisting of carbon in combination with either acrolein or formaldehyde (both common components of smoke) to cause pulmonary edema in anesthetized sheep. Seven animals received acrolein smoke, seven animals received a low-dose formaldehyde smoke, and five animals received a high-dose formaldehyde smoke. Pulmonary arterial pressure, pulmonary capillary wedge pressure, and cardiac output were not affected by smoke in any group. Peak airway pressure increased after acrolein (14 +/- 1 to 21 +/- 2 mmHg; P < 0.05) and after low- and high-dose formaldehyde (14 +/- 1 to 21 +/- 1 and 20 +/- 1 mmHg, respectively; both P < 0.05). The partial pressure of O2 in arterial blood fell sharply after acrolein [219 +/- 29 to 86 +/- 9 (SE) Torr; P < 0.05] but not after formaldehyde. Only acrolein resulted in a rise in lung lymph flow (6.5 +/- 2.2 to 17.9 +/- 2.6 ml/h; P < 0.05). Lung lymph-to-plasma protein ratio was unchanged for all three groups, but clearance of lymph protein was increased after acrolein. After acrolein, the blood-free extravascular lung water-to-lung dry weight ratio was elevated (P < 0.05) compared with both low- and high-dose formaldehyde groups (4.8 +/- 0.4 to 3.3 +/- 0.2 and 3.6 +/- 0.2, respectively). Lymph clearance (ng/h) of thromboxane B2, leukotriene B4, and the sulfidopeptide leukotrienes was elevated after acrolein but not formaldehyde. Histopathology disclosed moderate airway mucosal injury as well as juxtabronchial/juxtabronchiolar intra-alveolar edema after acrolein. Formaldehyde produced a similar tracheal injury but a lesser and variable degree of bronchial injury, with only sparce patchy intra-alveolar edema. Thus synthetic smoke containing acrolein but not formaldehyde produces non-cardiogenic pulmonary edema. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP HALES, CA (reprint author), MASSACHUSETTS GEN HOSP,SHRINERS BURN UNIT,DEPT MED,PULM CRIT CARE UNIT,BOSTON,MA 02114, USA. FU NHLBI NIH HHS [HL-36829] NR 19 TC 40 Z9 40 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 FEB PY 1992 VL 72 IS 2 BP 555 EP 561 PG 7 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA HE268 UT WOS:A1992HE26800023 PM 1559932 ER PT J AU HUALA, E STIGTER, J AUSUBEL, FM AF HUALA, E STIGTER, J AUSUBEL, FM TI THE CENTRAL DOMAIN OF RHIZOBIUM-LEGUMINOSARUM DCTD FUNCTIONS INDEPENDENTLY TO ACTIVATE TRANSCRIPTION SO JOURNAL OF BACTERIOLOGY LA English DT Article ID KLEBSIELLA-PNEUMONIAE; REGULATORY GENES; ENVIRONMENTAL STIMULI; CONSERVED DOMAINS; NIFH PROMOTER; NTRC; SEQUENCES; MUTAGENESIS; MUTATIONS; PROTEINS AB Sigma(54)-dependent transcriptional activators such as Escherichia coli NtrC, Rhizobium meliloti NifA, and Rhizobium leguminosarum DctD share similar central and carboxy-terminal domains but differ in the structure and function of their amino-terminal domains. We have deleted the amino-terminal and carboxy-terminal domains of R. leguminosarum DctD and have demonstrated that the central domain of DctD, like that of NifA, is transcriptionally competent. C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. RI Huala, Eva/B-1377-2009 NR 21 TC 81 Z9 82 U1 0 U2 2 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 FEB PY 1992 VL 174 IS 4 BP 1428 EP 1431 PG 4 WC Microbiology SC Microbiology GA HD467 UT WOS:A1992HD46700045 PM 1735730 ER PT J AU DEAHL, ST OBERLEY, LW OBERLEY, TD ELWELL, JH AF DEAHL, ST OBERLEY, LW OBERLEY, TD ELWELL, JH TI IMMUNOHISTOCHEMICAL IDENTIFICATION OF SUPEROXIDE DISMUTASES, CATALASE, AND GLUTATHIONE-S-TRANSFERASES IN RAT FEMORA SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID FREE-RADICALS; GROWTH PLATE; LOCALIZATION; TISSUES; EXPRESSION AB We used light microscopic immunohistochemistry to locate manganese superoxide dismutase, copper zinc superoxide dismutase, catalase, and glutathione-S-transferases in demineralized femora from rats of 4-14 weeks of age. Immunoblots confirmed the specificity of the polyclonal antibodies for the rat proteins of interest. Each of the enzymes exhibited a unique staining pattern. Copper-zinc superoxide dismutase was detected within some articular and epiphyseal chondrocytes of younger animals. Manganese superoxide dismutase was detected within some articular and epiphyseal chondrocytes, within some osteoprogenitor cells and osteoblasts, within many osteoclasts, and within some vascular smooth muscle cells. Catalase was identified within articular chondrocytes, epiphyseal chondrocytes, and osteocytes, whereas staining at the periphery of hypertrophic chondrocytes suggested extracellular and/or cell membrane-associted catalase. Glutathione-S-transferases were detected within and at the periphery of epiphyseal and articular chondrocytes and less prominently within cortical osteocytes. There were no major age-related changes in antioxidant enzyme distribution. C1 UNIV IOWA,RADIAT RES LAB,IOWA CITY,IA 52242. WILLIAM S MIDDLETON MEM VET ADM MED CTR,DEPT PATHOL,MADISON,WI 53705. FU NCI NIH HHS [CA41267]; NIDCR NIH HHS [1K16DE00176] NR 39 TC 23 Z9 23 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 1992 VL 7 IS 2 BP 187 EP 198 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA HD573 UT WOS:A1992HD57300009 PM 1570763 ER PT J AU BABA, H KARAPLIS, AC WIREN, KM KEUTMANN, HT KRONENBERG, HM AF BABA, H KARAPLIS, AC WIREN, KM KEUTMANN, HT KRONENBERG, HM TI INTERACTION OF NASCENT PREPROPARATHYROID HORMONE MOLECULES WITH MICROSOMAL-MEMBRANES SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID SIGNAL RECOGNITION PARTICLE; ENDOPLASMIC-RETICULUM MEMBRANE; SYNTHESIZING SECRETORY PROTEIN; ROUGH MICROSOMES; TRANSLOCATION; SEQUENCE; RECEPTOR; CLEAVAGE; BINDING; IDENTIFICATION AB To characterize the early steps in the interaction of nascent chains of preproparathyroid hormone (prepro-PTH) with the secretory apparatus, such truncated nascent chains still attached to ribosomes were tested for binding to microsomal membranes and cleavage by signal peptidase. Nascent chains of 114, 97, 88, 81, 70, and 59 residues were tested for their ability to bind tightly to membranes and to undergo signal sequence cleavage. Chains of 81 residues and longer bound tightly to the membranes and were cleaved by signal peptidase. The 88- and 81-residue precursors and their corresponding pro-proteins were less efficiently associated with the membranes than were the 114- and 97-residue precursors and their corresponding pro-proteins. The 70-residue chain bound to the membrane but was not cleaved. When this peptide was subsequently released from the ribosome with puromycin, it was cleaved by signal peptidase. The 59-residue chain bound only slightly to the microsomal membrane and was not cleaved by signal peptidase, even when the nascent peptide was released from the ribosome with puromycin. Thus the critical length for productive binding to microsomal membranes is between 59 and 70 residues; the length required for signal cleavage is between 70 and 81 residues. C1 MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. OI Wiren, Kristine/0000-0002-6159-4450 FU NIDDK NIH HHS [DK11794] NR 31 TC 5 Z9 5 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 1992 VL 7 IS 2 BP 199 EP 206 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA HD573 UT WOS:A1992HD57300010 PM 1570764 ER PT J AU TEICHER, BA HERMAN, TS HOPKINS, RE MENON, K AF TEICHER, BA HERMAN, TS HOPKINS, RE MENON, K TI EFFECT OF A BOVINE HEMOGLOBIN PREPARATION ON THE RESPONSE OF THE FSAIIC FIBROSARCOMA TO CHEMOTHERAPEUTIC ALKYLATING-AGENTS SO JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY LA English DT Article DE POLYMERIZED BOVINE HEMOGLOBIN SOLUTIONS; FSAIIC FIBROSARCOMA; CHEMOTHERAPEUTIC ALKYLATING AGENTS ID FLUOSOL-DA 20-PERCENT; MELPHALAN ANTITUMOR-ACTIVITY; SQUAMOUS-CELL CARCINOMA; PERFLUOROCHEMICAL EMULSION; RADIATION-THERAPY; CYTO-TOXICITY; CLINICAL-TRIAL; OXYGENATION CONDITIONS; MURINE FIBROSARCOMA; HYPERBARIC-OXYGEN AB Polymerized bovine hemoglobin solutions (PBHS) are being actively investigated as blood substitutes. In studies analogous to those we conducted with perfluorochemical emulsions/carbogen, we have examined the effect of PBHS +/- carbogen (95% O2, 5% CO2) breathing on the antitumor efficacy of melphalan, cyclophosphamide, N,N-bis(2-chloroethyl)-N-nitrosourea (BCNU) and cis-diamminedichloroplatinum(II) (cisplatin). The tumor growth delay of the FSaIIC fibrosarcoma treated with melphalan (10 mg/kg), cyclophosphamide (150 mg/kg), cisplatin (1 0 mg/kg) and BCNU (15 mg/kg) was increased about 2.2-fold, about 2.1-fold, about 1.2-fold and about 1.5-fold, respectively, when PBHS (12 mg/kg) was administered i.v. before each drug was injected i.p. The tumor growth delay produced by each drug was further increased when carbogen breathing for 6 h was allowed after administration of the drug and PBHS. In tumor cell survival experiments 24 h following drug treatment, the addition of PBHS increased the tumor cell killing of both melphalan and cyclophosphamide by about a factor of 10 at the lowest doses of each drug tested (10 mg/kg for melphalan and 100 mg/kg for cyclophosphamide) compared to the drug alone. However, at higher drug doses this effect was lost. The toxicity of each antitumor agent toward bone marrow (granulocyte/macrophage-colony-forming units) was increased 2- to 3-fold by the combined treatment. These results suggest that use of PBHS +/- carbogen breathing may add significantly to the efficacy of antitumor alkylating agents, however, the in vivo/in vitro data suggest that there will be increased bone marrow toxicity with this approach. This needs to be taken into account in the design of clinical trials. C1 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 PHS HHS [P01-19589] NR 61 TC 11 Z9 11 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 FEB PY 1992 VL 118 IS 2 BP 123 EP 128 DI 10.1007/BF01187500 PG 6 WC Oncology SC Oncology GA HC893 UT WOS:A1992HC89300004 PM 1735732 ER PT J AU DUNN, JCY TOMPKINS, RG YARMUSH, ML AF DUNN, JCY TOMPKINS, RG YARMUSH, ML TI HEPATOCYTES IN COLLAGEN SANDWICH - EVIDENCE FOR TRANSCRIPTIONAL AND TRANSLATIONAL REGULATION SO JOURNAL OF CELL BIOLOGY LA English DT Article ID RAT-HEPATOCYTES; GENE-EXPRESSION; PRIMARY CULTURE; MESSENGER-RNA; EXTRACELLULAR-MATRIX; BASEMENT-MEMBRANE; EPITHELIAL-CELLS; LIVER-CELLS; CONFIGURATION; DEPENDENCE AB The influence of extracellular matrix configuration on the tissue-specific function of cultured hepatocytes was investigated. Adult rat hepatocytes sandwiched between two layers of collagen gel were compared to cells cultured on a single layer of collagen gel for differences in the total RNA content, the level of albumin-specific mRNA, the rate of albumin gene transcription, and the rate of albumin mRNA translation. Adult hepatocytes in the sandwich system maintained the level of albumin mRNA similar to that found in the normal liver for at least six weeks, whereas the level of albumin mRNA declined rapidly in the single gel system. After one week of culture, hepatocytes in the single gel system could be induced to recover the high level of albumin mRNA and albumin production when a second layer of collagen gel was overlaid at that time. Furthermore, sandwiched hepatocytes maintained significantly higher transcriptional activity compared to cells in the single gel system. In addition to transcriptional control, the ultimate rate of albumin production was shown to depend on the rate of translation, which increased with culture time and reached a plateau in one to two weeks. This increase in translational activity over time in culture was observed in both the sandwich and the single gel systems and, thus, appeared to be independent of the configuration of extracellular matrix. C1 RUTGERS STATE UNIV,DEPT CHEM & BIOCHEM ENGN,PISCATAWAY,NJ 08854. RP DUNN, JCY (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,BOSTON,MA 02114, USA. FU NIDDK NIH HHS [DK-01746, R01 DK-41709] NR 54 TC 216 Z9 222 U1 1 U2 13 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD FEB PY 1992 VL 116 IS 4 BP 1043 EP 1053 DI 10.1083/jcb.116.4.1043 PG 11 WC Cell Biology SC Cell Biology GA HD550 UT WOS:A1992HD55000019 PM 1734019 ER PT J AU ALEXANDERBRIDGES, M ERCOLANI, L KONG, XF NASRIN, N AF ALEXANDERBRIDGES, M ERCOLANI, L KONG, XF NASRIN, N TI IDENTIFICATION OF A CORE MOTIF THAT IS RECOGNIZED BY 3 MEMBERS OF THE HMG CLASS OF TRANSCRIPTIONAL REGULATORS - IRE-ABP, SRY, AND TCF-1-ALPHA SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE INSULIN; GENE TRANSCRIPTION; GAPDH; HORMONE REGULATION; DIFFERENTIATION-DEPENDENT GENE EXPRESSION ID SEX-DETERMINING REGION; GROWTH-HORMONE GENE; DNA-BINDING MOTIF; SERTOLI CELLS; GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE; INSULIN REGULATION; PROTEIN-BINDING; RIBOSOMAL-RNA; AMYLASE GENE; EXPRESSION AB Insulin induces glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene transcription in part by regulating one or more proteins that bind a cis-acting element, IRE-A. We have recently cloned a protein, IRE-ABP, that binds the IRE-A element. IRE-ABP is a member of the HMG class of transcriptional regulators and is 67% identical within its HMG box domain to the candidate gene for the testis-determining factor, 5RY, IRE-ABP and SRY share binding specificity for the IRE-A motif. This sequence is also highly conserved with a core motif, 5'-Py- (a/t)-3', contained in T-cell specific genes that have affinity for TCF-1-alpha, another member of the HMG class of transcriptional regulators. Thus, diverse members of the HMG family interact with similar nucleotide sequences to regulate expression of genes that initiate and maintain the differentiated phenotype. We have found this core motif in the upstream region of many genes that are positively and negatively regulated by insulin. These observations suggest that IRE-ABP or a related family member may coordinate the expression of these genes. The HMG family of proteins has diverse functions ranging from the regulation of differentiation and mating type in yeast to the regulation of tissue-and species-specific gene expression in mammals. Insulin regulates GAPDH gene transcription in a tissue-specific manner. We propose that members of the IRE-ABP family play an important role in controlling tissue specificity of the insulin response. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,MED SERV,BOSTON,MA 02114. RP ALEXANDERBRIDGES, M (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,HOWARD HUGHES MED INST,DIABET UNIT,BOSTON,MA 02114, USA. NR 49 TC 36 Z9 36 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD FEB PY 1992 VL 48 IS 2 BP 129 EP 135 DI 10.1002/jcb.240480204 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA HB745 UT WOS:A1992HB74500003 PM 1618927 ER PT J AU BADEN, HP GOLDABER, ML KVEDAR, JC AF BADEN, HP GOLDABER, ML KVEDAR, JC TI KERATINOCYTES STIMULATE PROSTAGLANDIN-I2 SYNTHESIS BY 3T3-CELLS AND EXHIBIT ENHANCED CORNIFICATION WHEN EXPOSED TO PROSTAGLANDIN-I2 ANALOGS SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID ARACHIDONIC-ACID METABOLISM; CULTURED HUMAN KERATINOCYTES; TREATED 3T3 FIBROBLASTS; PROSTACYCLIN PRODUCTION; CORNIFIED ENVELOPE; ENDOTHELIAL-CELLS; MODULATION; MINOXIDIL; PROTEINS; LINE AB The predominant cyclooxygenase products of keratinocytes are prostaglandin (PG)E2 and PGF2-alpha with only trace amounts of PGl2 synthesis detected. When normal or immortal (NM1) keratinocytes were co-cultured with mitomycin C-treated 3T3 cells, increased synthesis of PGl2 was noted compared to mitomycin C-treated 3T3 cells alone. The PGl2 level in co-cultures was maximum within the first week and diminished rapidly thereafter. These results suggested keratinocytes enhance the production of PGl2 by 3T3 cells. Keratinocyte cultures incubated with lloprost and Piriprost, stable PGl2 analogues, showed evidence of increased cornification as demonstrated by staining with rhodanile blue, decreased shedding of cells into the culture medium, and more cornified material adhering to the culture surface. The cultures appeared to be responsive between the first and second weeks after plating and the inhibition of shedding could not be reversed by changing to drug-free medium. Control and treated cultures showed identical electrophoretic protein patterns. Immunoblots showed involucrin unchanged in extracts of control and treated cultures while the 22 kd pancornulin was absent in treated cultures. The findings that keratinocytes enhance the production of PGl2 by 3T3 cells and that PGl2 analogues enhance cornification of confluent keratinocytes raise the possibility that eicosanoids may serve as autoregulatory signals together with other factors. RP BADEN, HP (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT DERMATOL,BOSTON,MA 02114, USA. FU NIAMS NIH HHS [R01 AR06838-27, K08ARO1804-01] NR 35 TC 4 Z9 4 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD FEB PY 1992 VL 150 IS 2 BP 269 EP 275 DI 10.1002/jcp.1041500208 PG 7 WC Cell Biology; Physiology SC Cell Biology; Physiology GA HD553 UT WOS:A1992HD55300007 PM 1370840 ER PT J AU LLOYD, M MEVISSEN, G FISCHER, M OLSEN, W GOODSPEED, D GENINI, M BOLL, W SEMENZA, G MANTEI, N AF LLOYD, M MEVISSEN, G FISCHER, M OLSEN, W GOODSPEED, D GENINI, M BOLL, W SEMENZA, G MANTEI, N TI REGULATION OF INTESTINAL LACTASE IN ADULT HYPOLACTASIA SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE LACTASE; LACTASE DEFICIENCY; ADULT HYPOLACTASIA ID PHLORIZIN HYDROLASE; MESSENGER-RNA; ENZYME; DNA; BIOSYNTHESIS; EXPRESSION; DEFICIENCY; PROTEINS AB Relative deficiency of intestinal lactase activity during adulthood, adult hypolactasia, is a common condition worldwide. We studied the regulation of lactase-phlorizin hydrolase in normal and adult hypolactasic subjects by correlating transcript abundance in intestinal biopsies with relative synthetic rates for the protein in cultured intestinal explants. After metabolic labelling studies in six subjects, precursor lactase-phlorizin hydrolase was identified in amounts directly proportional to the enzyme-specific activity suggesting that levels of intestinal lactase are regulated by synthetic rate. Total intestinal RNA was extracted from biopsies of these subjects and three hypolactasic adults who had participated in previous biosynthesis studies. Transcript levels were markedly reduced in deficient subjects who demonstrated diminished lactase-phlorizin hydrolase synthesis. The sequence of 1 kb of 5'-flanking region of the lactase-phlorizin hydrolase gene was determined in two hypolactasic subjects and two controls. No sequence variability was identified to account for differences in mRNA levels or biosynthetic rates between the two groups. A single hypolactasic subject previously characterized as demonstrating delayed posttranslational processing, showed message levels intermediate between other deficients and controls. These results suggest that in the majority of our subjects, pretranslational mechanisms account for the predominate regulatory control of lactase-phlorizin hydrolase expression in the proximal intestine. C1 UNIV WISCONSIN,DEPT MED,MADISON,WI 53792. SWISS FED INST TECHNOL,DEPT BIOCHEM 2,CH-8092 ZURICH,SWITZERLAND. RP LLOYD, M (reprint author), WILLIAM S MIDDLETON MEM VET ADM MED CTR,GASTROENTEROL RES LAB,2500 OVERLOOK TERRACE,MADISON,WI 53705, USA. FU NCI NIH HHS [CA 22484-13]; NIADDK NIH HHS [AM-13927]; NIDDK NIH HHS [K08 DK01789] NR 22 TC 63 Z9 65 U1 0 U2 2 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 FEB PY 1992 VL 89 IS 2 BP 524 EP 529 DI 10.1172/JCI115616 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA HD270 UT WOS:A1992HD27000025 PM 1737843 ER PT J AU YOUKER, K SMITH, CW ANDERSON, DC MILLER, D MICHAEL, LH ROSSEN, RD ENTMAN, ML AF YOUKER, K SMITH, CW ANDERSON, DC MILLER, D MICHAEL, LH ROSSEN, RD ENTMAN, ML TI NEUTROPHIL ADHERENCE TO ISOLATED ADULT CARDIAC MYOCYTES - INDUCTION BY CARDIAC LYMPH COLLECTED DURING ISCHEMIA AND REPERFUSION SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE CARDIAC LYMPH; CYTOKINE INDUCTION; INTERCELLULAR ADHESION MOLECULE-1; INTERLEUKIN-6; ISCHEMIA-REPERFUSION INJURY ID INTERLEUKIN-1 RECEPTOR ANTAGONIST; ACUTE MYOCARDIAL ISCHEMIA; INFARCT SIZE; TRANSENDOTHELIAL MIGRATION; MONOCLONAL-ANTIBODY; INTERFERON-GAMMA; CANINE HEART; ACUTE PHASE; LEUKOCYTES; INJURY AB Canine neutrophils can be induced to adhere in vitro to isolated adult cardiac myocytes by stimulation of the neutrophils with chemotactic factors such as zymosan-activated serum (ZAS) only if the myocytes have been previously exposed to cytokines such as interleukin 1 (IL-1) or tumor necrosis factor-alpha. These cytokines induce synthesis and surface expression of intercellular adhesion molecule-1 (ICAM-1) on the myocyte, and neutrophil adhesion is almost entirely CD18 and ICAM-1 dependent. The present study examines cardiac-specific lymph collected from awake dogs during 1-h coronary occlusion and 3 d of reperfusion for its ability to induce both ICAM-1 expression in cardiac myocytes, and neutrophil-myocyte adherence. Reperfusion lymph induced ICAM-1 expression in isolated myocytes, and myocyte adherence to ZAS-stimulated neutrophils that was completely inhibited by anti-CD18 and anti-ICAM-1 monoclonal antibodies. This activity peaked at 90 min of reperfusion and persisted for up to 72 h. Preischemic lymph was not stimulatory. IL-1 appeared not to be a stimulating factor in lymph in that dilutions of lymph were found to inhibit the stimulatory effects of recombinant IL-1-beta. However, investigation of interleukin 6 (IL-6) revealed that recombinant IL-6 stimulated myocyte adhesiveness for ZAS-stimulated neutrophils (ED50 = 0.002 U/ml) and expression of ICAM-1 by isolated myocytes. IL-6 neutralizing antibody markedly reduced the ability of reperfusion lymph to stimulate adhesion and ICAM-1 expression, and estimates of levels of IL-6 in reperfusion lymph ranged from 0.035 to 0.14 U/ml. These results indicate that cytokines capable of promoting neutrophil-myocyte adhesion occur in extracellular fluid during reperfusion of ischemic myocardium, and that one of these cytokines is IL-6. Neutrophil-myocyte adhesion may be of pathogenic significance because it may enhance the cytotoxic activity of the neutrophil. C1 METHODIST HOSP,DEPT MED,CARDIOVASC SCI SECT,DALLAS,TX 75222. DEBAKEY HEART CTR,DALLAS,TX. TEXAS CHILDRENS HOSP,DEPT PEDIAT,SPEROS P MARTEL LAB LEUKOCYTE BIOL,HOUSTON,TX 77030. BAYLOR COLL MED,VET ADM HOSP,DEPT CELL BIOL,HOUSTON,TX 77030. BAYLOR COLL MED,VET ADM HOSP,DEPT MICROBIOL & IMMUNOL,HOUSTON,TX 77030. FU NHLBI NIH HHS [HL-23161, HL-42550, HL-41408] NR 53 TC 177 Z9 182 U1 0 U2 2 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 FEB PY 1992 VL 89 IS 2 BP 602 EP 609 DI 10.1172/JCI115626 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA HD270 UT WOS:A1992HD27000035 PM 1346618 ER PT J AU WEISS, GR MARGOLIN, KA ARONSON, FR SZNOL, M ATKINS, MB DUTCHER, JP GAYNOR, ER BOLDT, DH DOROSHOW, JH BAR, MH HAWKINS, MJ DEMCHAK, PA GUCALP, R FISHER, RI AF WEISS, GR MARGOLIN, KA ARONSON, FR SZNOL, M ATKINS, MB DUTCHER, JP GAYNOR, ER BOLDT, DH DOROSHOW, JH BAR, MH HAWKINS, MJ DEMCHAK, PA GUCALP, R FISHER, RI TI A RANDOMIZED PHASE-II TRIAL OF CONTINUOUS INFUSION INTERLEUKIN-2 OR BOLUS INJECTION INTERLEUKIN-2 PLUS LYMPHOKINE-ACTIVATED KILLER-CELLS FOR ADVANCED RENAL-CELL CARCINOMA SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID RECOMBINANT INTERLEUKIN-2; ADOPTIVE IMMUNOTHERAPY; ADVANCED CANCER; LYMPHOCYTES C1 NCI,DIV CANC THERAPY,INVEST DRUG BRANCH,CANC THERAPY EVALUAT PROGRAM,BETHESDA,MD 20892. CITY HOPE CANC RES CTR,DUARTE,CA. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. TUFTS UNIV,NEW ENGLAND MED CTR,BOSTON,MA 02111. ALBERT EINSTEIN CANC CTR,NEW YORK,NY. LOYOLA UNIV,MED CTR,MAYWOOD,IL 60153. RP WEISS, GR (reprint author), UNIV TEXAS,HLTH SCI CTR,AUDIE L MURPHY MEM VET ADM HOSP,DEPT MED & MED ONCOL,SAN ANTONIO,TX 78284, USA. FU NCI NIH HHS [N01-CM73702, N01-CM73703, N01-CM73707] NR 11 TC 125 Z9 124 U1 0 U2 1 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 FEB PY 1992 VL 10 IS 2 BP 275 EP 281 PG 7 WC Oncology SC Oncology GA HB270 UT WOS:A1992HB27000014 PM 1732429 ER PT J AU TALCOTT, JA SIEGEL, RD FINBERG, R GOLDMAN, L AF TALCOTT, JA SIEGEL, RD FINBERG, R GOLDMAN, L TI RISK ASSESSMENT IN CANCER-PATIENTS WITH FEVER AND NEUTROPENIA - A PROSPECTIVE, 2-CENTER VALIDATION OF A PREDICTION RULE SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID GRANULOCYTOPENIC PATIENTS; ANTIBIOTIC-THERAPY; RANDOMIZED TRIAL; FEBRILE EPISODES; TOBRAMYCIN; CARBENICILLIN; COMBINATION; MOXALACTAM C1 BRIGHAM & WOMENS HOSP, DEPT MED, DIV CLIN EPIDEMIOL, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02115 USA. MIRIAM HOSP, DEPT MED, PROVIDENCE, RI 02906 USA. BROWN UNIV, SCH MED, PROVIDENCE, RI 02912 USA. RP TALCOTT, JA (reprint author), HARVARD UNIV, SCH MED, DANA FARBER CANC INST, BOSTON, MA 02115 USA. RI Finberg, Robert/E-3323-2010 FU NCI NIH HHS [CA01418, CA08242] NR 19 TC 356 Z9 367 U1 1 U2 5 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB PY 1992 VL 10 IS 2 BP 316 EP 322 PG 7 WC Oncology SC Oncology GA HB270 UT WOS:A1992HB27000020 PM 1732432 ER PT J AU HAFFAJEE, AD SOCRANSKY, SS SMITH, C DIBART, S AF HAFFAJEE, AD SOCRANSKY, SS SMITH, C DIBART, S TI THE USE OF DNA PROBES TO EXAMINE THE DISTRIBUTION OF SUBGINGIVAL SPECIES IN SUBJECTS WITH DIFFERENT LEVELS OF PERIODONTAL DESTRUCTION SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE PERIODONTAL DISEASE; PERIODONTITIS; SUBGINGIVAL SPECIES; DNA PROBES AB The present investigation examined the distribution of 14 subgingival species at a total of 2299 sites in 90 subjects with different levels of periodontal destruction. Subgingival plaque samples taken from the mesial aspect of each tooth were anaerobically dispersed, diluted and plated on non selective media. After anaerobic incubation, colonies were lifted to nylon filters and specific species detected using digoxygenin-labeled whole chromosomal DNA probes. The mean total viable count for all sites in all subjects was 8.3 x 10(6). The probes accounted for an average of 27.8% of the total viable count. The % of subjects in which each species was detected was as follows; V. parvula, 98; B. intermedius I. 98: S. sanguis II, 96; B. intermedius II, 95; C. ochracea, 94; B. gingivalis, 91; S. sanguis I. 85; W. recta, 83; F. nucleatum ss. vincentii, 82; S. intermedius, 80; B. forsythus, 76; P. micros, 74; A. actinomycetemcomitans serotype a, 62 and A. actinomycetemcomitans serotype b, 52. The % of sites colonized by each of the 14 test species varied considerably within different subjects. The median number of sites colonized by different species ranged from 3.6% for A. actinomycetemcomitans serotype b to 43.5% for V. parvula. In half the subjects, the mean % of the total viable counts for each of the test species was < 4%. When subjects were divided on the basis of % of sites at baseline with > 3 mm attachment loss, the 14 probes accounted for 29.9% of the microbiota in the localized disease group and 25% in the widespread disease group. In general, suspected pathogens were slightly higher in the localized disease subjects, but suspected beneficial species were comparable in both groups. Cluster analysis was used to subset subjects on the basis of their mean percentages of the 14 test species. 5 groups were formed with > 60% similarity (Bray-Curtis coefficient) but 21 subjects failed to fit any of the groups. The latter subjects were characterized by low numbers of the test species and were older exhibiting widespread disease and recession. RP HAFFAJEE, AD (reprint author), FORSYTH DENT CTR,140 FENWAY,BOSTON,MA 02115, USA. FU NIDCR NIH HHS [DE-02847, DE-04881] NR 8 TC 38 Z9 40 U1 0 U2 3 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 FEB PY 1992 VL 19 IS 2 BP 84 EP 91 DI 10.1111/j.1600-051X.1992.tb00445.x PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA HD025 UT WOS:A1992HD02500003 PM 1318331 ER PT J AU AMES, D WIRSHING, WC SZUBA, MP AF AMES, D WIRSHING, WC SZUBA, MP TI ORGANIC MENTAL-DISORDERS ASSOCIATED WITH BUPROPION IN 3 PATIENTS SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID DELIRIUM AB Bupropion hydrochloride is a phenylaminoketone antidepressant whose clinical pharmacology is poorly understood. Part of bupropion's action may be attributed to inhibition of dopamine reuptake that may induce organic mental disorders in certain susceptible patients. We report three cases of organic mental disorders in patients receiving bupropion hydrochloride for treatment of the depressed phase of their bipolar-type mood instability. The organic mental disorders that occurred in these patients were characterized largely by visual disturbances-visual hallucinations and visual illusions-although one patient also experienced auditory hallucinations. The patients' use of concomitant medications and potential drug interactions are carefully evaluated and the literature on bupropion's ability to induce organic mental disorders is reviewed. We suggest a number of possible mediating mechanisms for these syndromes including dose-related dopaminergic augmentation, accumulation of toxic metabolics, predisposition to psychosis, and drug interactions. C1 W LOS ANGELES VET AFFAIRS MED CTR B-151H,11301 WILSHIRE BLVD,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,SCH MED,DEPT PSYCHIAT & BEHAV SCI,LOS ANGELES,CA 90024. FU NIMH NIH HHS [T32MH17140] NR 12 TC 27 Z9 27 U1 0 U2 2 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 FEB PY 1992 VL 53 IS 2 BP 53 EP 55 PG 3 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA HH967 UT WOS:A1992HH96700004 PM 1541606 ER PT J AU KRUSKALL, MS ALPER, CA AWDEH, Z YUNIS, EJ MARCUSBAGLEY, D AF KRUSKALL, MS ALPER, CA AWDEH, Z YUNIS, EJ MARCUSBAGLEY, D TI THE IMMUNE-RESPONSE TO HEPATITIS-B VACCINE IN HUMANS - INHERITANCE PATTERNS IN FAMILIES SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID SURFACE-ANTIGEN HBSAG; HISTOCOMPATIBILITY COMPLEX HAPLOTYPES; SUPPRESSOR T-CELLS; GENETIC-REGULATION; CONTROLS NONRESPONSIVENESS; DERMATITIS-HERPETIFORMIS; STRUCTURAL POLYMORPHISM; ANCESTRAL HAPLOTYPES; NON-RESPONSIVENESS; DIABETES-MELLITUS AB We have recently shown that the human antibody response to the hepatitis B virus surface antigen (HBsAg) vaccine is major histocompatibility complex (MHC) associated. In studies of nonresponders to the vaccine, we found an increased incidence of individuals homozygous for human histocompatibility leukocyte antigen (HLA) proteins associated with the extended (conserved) haplotype [HLA-B8,SC01,DR3]. In later prospective vaccination trials, we showed that none of five individuals homozygous for this haplotype developed more than 1,300 radioimmunoassay (RIA) units of antibody (mean, 467 RIA units), while all heterozygotes made at least 2,500 RIA units (mean antibody level, 15,608 units). Our results suggested that [HLA-B8,SC01,DR3] lacks an immune response gene for HBsAg, and that response is inherited in a dominant fashion. To provide further evidence for this hypothesis, we have now analyzed the results of HBsAg immunization in families. 43 members of 10 families were immunized with the hepatitis B vaccine, including seven families where at least one member bore the haplotype [HLA-B8,SC01,DR3], and three families where one member had already received, but failed to respond to, the vaccine. In two of these three families, the presence of [HLA-B8,SC01,DR3] was subsequently found. Of nine MHC-identical sibling pairs in the study, both members of eight pairs had similar antibody responses (five nonresponder and three responder pairs). In all families with such sibling pairs, including the discordant pair, rank-ordering members by antibody level demonstrated that no relative's value came between the sibling pair values. Furthermore, of nine [HLA-B8,SC01,DR3]-haplotype-homozygous individuals, six were nonresponders, and two others had only low-normal responses. [HLA-B8,SC01,DR3]-heterozygous family members always had higher levels of antibody than their homozygous relatives. Linkage analysis of nonresponse to HLA haplotypes revealed a maximum likelihood LOD (logarithm of the odds) score of 6.3 at a recombination fraction of 0.1. The MHC association with lack of antibody response to HBsAg was not seen with tetanus immunization, where 1 of 20 HBsAg responders and 1 of 21 poor or nonresponders had tetanus titers of < 1:512; both tetanus nonresponders were [HLA-B8,SC01,DR3] heterozygotes. Our results indicate that: (a) response to the HBsAg vaccine is MHC linked, and inherited in a dominant fashion; (b) an abnormal or missing immune response (Ir) gene for HBsAg is a characteristic of most examples of the extended haplotype [HLA-B8,SC01,DR3]; and (c) other haplotypes also have abnormal or missing Ir genes for HBsAg. C1 CHARLES A DANA RES INST,DEPT PATHOL,BOSTON,MA 02215. CHARLES A DANA RES INST,DEPT MED,BOSTON,MA 02215. BETH ISRAEL HOSP,HARVARD THORNDIKE LAB,BOSTON,MA 02215. CHILDRENS HOSP MED CTR,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT IMMUNOGENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP KRUSKALL, MS (reprint author), CTR BLOOD RES,BOSTON,MA 02115, USA. FU NHLBI NIH HHS [HL-29583]; NICHD NIH HHS [HD-17461]; NIDDK NIH HHS [DK-26844] NR 40 TC 119 Z9 122 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 FEB 1 PY 1992 VL 175 IS 2 BP 495 EP 502 DI 10.1084/jem.175.2.495 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA HB061 UT WOS:A1992HB06100021 PM 1531063 ER PT J AU FINCO, O LI, SL CUCCIA, M ROSEN, FS CARROLL, MC AF FINCO, O LI, SL CUCCIA, M ROSEN, FS CARROLL, MC TI STRUCTURAL DIFFERENCES BETWEEN THE 2 HUMAN-COMPLEMENT C4 ISOTYPES AFFECT THE HUMORAL IMMUNE-RESPONSE SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID STEROID 21-HYDROXYLASE GENES; 4TH COMPONENT; NULL ALLELES; ANTIBODY-RESPONSE; C-4; POLYMORPHISM; RECEPTOR; ALPHA-2-MACROGLOBULIN; SPECIFICITY; LYMPHOCYTES AB An animal model has been used to address the question of the biological importance of the known structural difference between the two isotypes of human C4, i.e., C4A and C4B Guinea pigs deficient in C4 were reconstituted transiently with either human C4A or C4B protein and immunized with the bacteriophage phi-X174. Results from this study showed that C4A-reconstituted animals made a secondary response, i.e., switch from IgM to IgG; whereas the C4B-reconstituted animals did not. C1 HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. UNIV PAVIA,DEPT GENET,I-27100 PAVIA,ITALY. CTR BLOOD RES,BOSTON,MA 02115. RP FINCO, O (reprint author), HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115, USA. FU NIAID NIH HHS [AI-22537] NR 35 TC 33 Z9 34 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 FEB 1 PY 1992 VL 175 IS 2 BP 537 EP 543 DI 10.1084/jem.175.2.537 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA HB061 UT WOS:A1992HB06100025 PM 1732415 ER PT J AU LI, YP STASHENKO, P AF LI, YP STASHENKO, P TI PROINFLAMMATORY CYTOKINES TUMOR-NECROSIS-FACTOR-ALPHA AND IL-6, BUT NOT IL-1, DOWN-REGULATE THE OSTEOCALCIN GENE PROMOTER SO JOURNAL OF IMMUNOLOGY LA English DT Article ID BONE-FORMATION INVITRO; TRANSCRIPTION FACTOR AP-1; OSTEOBLAST-LIKE CELLS; PARATHYROID-HORMONE; CHLORAMPHENICOL ACETYLTRANSFERASE; INTERLEUKIN-1; RESORPTION; PROTEIN; PROSTAGLANDIN-E2; ELEMENT AB A proinflammatory cytokine cascade, including IL-1-alpha, IL-1-beta, TNF-alpha, IL-6, and IL-8, is activated in response to infection or immunologic insult. Besides their immunologic effects, several of these mediators stimulate bone resorption and inhibit bone formation. Osteocalcin, the most abundant noncollagenous protein present in bone, is an osteoblast-specific product whose production closely correlates with bone formation, and which has also been implicated in control of bone resorption. IL-1 and TNF have previously been shown to down-regulate osteocalcin production in vitro and in vivo, although the mechanism of this inhibition is unknown. In the present studies, IL-1-beta and TNF-alpha both inhibited 1,25-dihydroxyvitamin D3-stimulated production of osteocalcin protein and mRNA by ROS 17/2.8 osteosarcoma cells, whereas IL-6 had no effect on protein and only weakly inhibited mRNA. To determine if down-regulation was exerted at the transcriptional level, an osteocalcin promoter-chloramphenicol acetyltransferase (CAT) fusion gene was constructed (PHOC-CAT). After transient transfection of PHOC-CAT into ROS 17/2.8 osteosarcoma cells, reporter CAT activity was up-regulated by vitamin D at concentrations above 10(-12) M. In screening studies, TNF-alpha (-57%) and IL-6 (-37%) inhibited vitamin D-stimulated osteocalcin transcription, whereas IL-1-alpha, IL-1-beta, and IL-8 had no effect. Other immune cytokines and growth factors, including IL-2, IL-3, IL-7, and M-CSF, also failed to regulate osteocalcin transcription. Despite their lack of promoter regulation, IL-1-alpha and IL-1-beta also stimulated PGE2 production by ROS 17/2.8, further confirming the ability of the host cell to respond to these mediators. In dose-response experiments, down-regulation by TNF-alpha was significant at concentrations as low as 0.14 pM (0.1 U/ml), whereas approximately 10(4)-fold higher concentration of IL-6 was required to exert a similar effect. TNF-alpha-mediated down-regulation was unaffected by indomethacin. These data demonstrate that of these cytokines, TNF-alpha alone potently down-regulates osteocalcin promoter function, whereas IL-1 acts posttranscriptionally, possibly by reducing mRNA stability. Heterogeneity therefore exists among the proinflammatory cytokines with respect to the level at which control of osteocalcin expression is exerted. C1 FORSYTH RES INST,140 THE FENWAY,BOSTON,MA 02115. FU NIDCR NIH HHS [DE-07378, DE-09018] NR 53 TC 70 Z9 72 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 FEB 1 PY 1992 VL 148 IS 3 BP 788 EP 794 PG 7 WC Immunology SC Immunology GA HB535 UT WOS:A1992HB53500019 PM 1309841 ER PT J AU HODGSON, J AF HODGSON, J TI THE STATUS OF METALINGUISTIC SKILLS IN READING DEVELOPMENT SO JOURNAL OF LEARNING DISABILITIES LA English DT Article ID PHONOLOGICAL AWARENESS; SPEECH; ACQUISITION; KINDERGARTEN; INFORMATION; DYSLEXIA; CHILDREN; LITERACY AB Diane Sawyer (this issue) presents an account of reading development and its disabilities that stresses the contribution of a hierarchy of metalinguistic skills in the segmentation and manipulation of speech. Two of her central claims are discussed: (1) Failure to master the productive relationship between spelling and sound may often originate in difficulty in the prerequisite ability to carry out phonemic segmentation; the population so affected may include both "true" and "apparent" types of dyslexia, with rather different prognoses; and (2) a range of hierarchically and temporally organized sublexical metalinguistic speech skills govern the timecourse of reading development. Evidence from cognitive neuropsychological case reports is reviewed for its bearing on these claims and for its implications for the strong metalinguistic hypothesis, which contends that explicit, conscious mastery of the relationship between phonology and orthography is a necessary (and perhaps sufficient) precondition for the development of fluent reading. C1 MASSACHUSETTS GEN HOSP,INST HLTH PROFESS,CTR READING & WRITING,BOSTON,MA 02114. RP HODGSON, J (reprint author), MASSACHUSETTS GEN HOSP,NEUROLINGUIST LAB,15 RIVER ST,BOSTON,MA 02108, USA. NR 31 TC 4 Z9 4 U1 0 U2 4 PU PRO-ED INC PI AUSTIN PA 8700 SHOAL CREEK BLVD, AUSTIN, TX 78757-6897 SN 0022-2194 J9 J LEARN DISABIL JI J. Learn. Disabil. PD FEB PY 1992 VL 25 IS 2 BP 96 EP 101 PG 6 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA HC687 UT WOS:A1992HC68700002 PM 1583421 ER PT J AU SWENSEN, CH FULLER, SR AF SWENSEN, CH FULLER, SR TI EXPRESSION OF LOVE, MARRIAGE PROBLEMS, COMMITMENT, AND ANTICIPATORY GRIEF IN THE MARRIAGES OF CANCER-PATIENTS SO JOURNAL OF MARRIAGE AND THE FAMILY LA English DT Article ID COUPLES; SPOUSE AB Married couples in which one of the spouses has terminal cancer reported their expression of love, marriage problems, and commitment to each other after the diagnosis of cancer and as they recall their relationship before the diagnosis of cancer. They were compared with a matched comparison group of healthy subjects. The cancer couples reported expressing more love to each other after the diagnosis of cancer and more love than the comparison group. There was no difference in marriage problems. The cancer couples were found to be less committed to each other after the diagnosis of cancer. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114. RP SWENSEN, CH (reprint author), PURDUE UNIV,DEPT PSYCHOL SCI,W LAFAYETTE,IN 47907, USA. NR 22 TC 14 Z9 14 U1 1 U2 5 PU NATL COUNCIL FAMILY RELATIONS PI MINNEAPOLIS PA 3989 CENTRAL AVE NE #550, MINNEAPOLIS, MN 55421 SN 0022-2445 J9 J MARRIAGE FAM JI J. Marriage Fam. PD FEB PY 1992 VL 54 IS 1 BP 191 EP 196 DI 10.2307/353286 PG 6 WC Family Studies; Sociology SC Family Studies; Sociology GA HG963 UT WOS:A1992HG96300016 ER PT J AU LABEIT, D BACK, W VONWEIZACKER, F HERMANN, P MELCHERT, F LEONARD, K LABEIT, S AF LABEIT, D BACK, W VONWEIZACKER, F HERMANN, P MELCHERT, F LEONARD, K LABEIT, S TI INCREASED DETECTION OF HPV-16 VIRUS IN INVASIVE, BUT NOT IN EARLY CERVICAL CANCERS SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE CERVICAL CANCER; HPV 16 E6/E7; PCR; FORMALDEHYDE-FIXED PARAFFIN-EMBEDDED (FFPE) BIOPSIES ID HUMAN PAPILLOMAVIRUS TYPE-16; POLYMERASE CHAIN-REACTION; DNA; SEQUENCES; CARCINOMA; FRAGMENTS; TISSUE AB Human papilloma virus type 16 (HPV 16) DNA is found in about 50% of cervical squamous cell carcinomas (SCCs), and this association has raised the possibility of a causal role for HPV 16 in cervical carcinogenesis. We have tested this hypothesis by assaying a series of biopsies (n = 119) ranging from normal mucosa to infiltrating SCC with the PCR-technique for the presence of HPV 16 DNA. While HPV 16 DNA was detected in 50% of our cases with invasive SCC, the incidence of HPV 16-positive samples was about 10% in all other biopsies ranging from normal mucosa to cases of carcinoma in situ. HPV 16 therefore appears to be involved in late tumor promotion but not in early tumor development. C1 EUROPEAN MOLEC BIOL LAB,MEYERHOFSTR 1,W-6900 HEIDELBERG,GERMANY. KLINIKUM MANNHEIM,FRAUENKLIN,MANNHEIM,GERMANY. KLINIKUM MANNHEIM,INST PATHOL,MANNHEIM,GERMANY. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,MOLEC HEPATOL LAB,BOSTON,MA 02114. NR 30 TC 8 Z9 8 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD FEB PY 1992 VL 36 IS 2 BP 131 EP 135 DI 10.1002/jmv.1890360210 PG 5 WC Virology SC Virology GA HB785 UT WOS:A1992HB78500009 PM 1316424 ER PT J AU WATERS, GS ROCHON, E CAPLAN, D AF WATERS, GS ROCHON, E CAPLAN, D TI THE ROLE OF HIGH-LEVEL SPEECH PLANNING IN REHEARSAL - EVIDENCE FROM PATIENTS WITH APRAXIA OF SPEECH SO JOURNAL OF MEMORY AND LANGUAGE LA English DT Article ID SHORT-TERM-MEMORY; SENTENCE COMPREHENSION; ARTICULATION; STORE C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP WATERS, GS (reprint author), MCGILL UNIV,SCH HUMAN COMMUN DISORDERS,1266 PINE AVE W,MONTREAL H3G 1A8,QUEBEC,CANADA. OI Rochon, Elizabeth/0000-0001-5521-0513 NR 37 TC 88 Z9 90 U1 1 U2 8 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0749-596X J9 J MEM LANG JI J. Mem. Lang. PD FEB PY 1992 VL 31 IS 1 BP 54 EP 73 DI 10.1016/0749-596X(92)90005-I PG 20 WC Linguistics; Psychology; Psychology, Experimental SC Linguistics; Psychology GA GZ680 UT WOS:A1992GZ68000004 ER PT J AU BASHIR, R COAKHAM, H HOCHBERG, F AF BASHIR, R COAKHAM, H HOCHBERG, F TI EXPRESSION OF LFA-1 ICAM-1 IN CNS LYMPHOMAS - POSSIBLE MECHANISM FOR LYMPHOMA HOMING INTO THE BRAIN SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE PRIMARY CNS LYMPHOMA; NON-HODGKIN LYMPHOMA; ADHESION MOLECULES ID EPSTEIN-BARR VIRUS; IMMUNE-DEFICIENCY SYNDROME; NERVOUS-SYSTEM LYMPHOMA; CELL-ADHESION; NUDE-MICE; TRANSFORMATION; TISSUES; LINES AB We examined a possible role for the adhesion molecules LFA-1 and ICAM-1 in localizing central nervous system non-Hodgkin's lymphomas (CNS-NHLs) to the brain. Fresh frozen sections from 12 monoclonal CNS NHLs (11 primary, one secondary) were stained with monoclonal antibodies to LFA-1 alpha-chain (CD11a), beta-chain (CD18) and, ICAM-1 (CD54). Additional staining made use of rat monoclonal antibodies to the human and mouse high endothelial venule antigens HECA 452 and MECA 79 and mouse ICAM-1. The expression of these same molecules was also studied in mice with severe combined immunodeficiency (SCID) mice, bearing intracranial human lymphoblastoid cells. Eleven of the CNS-NHL tumors expressed LFA-1-alpha (one strongly, one intermediate, nine weakly). Nine of the tumors weakly expressed LFA-1-beta.. Nine of twelve tumors weakly expressed ICAM-1. In six of seven tumors definite blood vessels stained for ICAM-1. Non-tumor brain from two patients and non-tumor cerebral blood vessels showed no staining with CD11a, CD18 or CD54 antibodies. Strong expression of LFA-alpha and LFA-beta as well as ICAM-1 was noted in human lymphoblastoid cells (LCLs)/SCID mouse CNS lymphomas. Tumor blood vessels in these mice stained for mouse ICAM-1. Normal SCID mouse brains showed no staining with CD11a, CD18, CD54 or mouse ICAM-1 antibodies. Human, human/mouse CNS lymphomas, normal human, and mouse brains showed no staining with either HECA 452 or MECA 79. Our data suggests that CNS lymphomas express LFA-1-alpha, LFA-1-beta and to a lesser degree ICAM-1 antigen, while tumor blood vessel endothelium expresses ICAM-1. LFA-1-alpha-LFA-1-beta/ICAM-1 interaction may play a role in large cell lymphoma homing and persistence in the brain. C1 UNIV NEBRASKA,MED CTR,DEPT INTERNAL MED,NEUROL SECT,OMAHA,NE 68105. FRENCHAY HOSP,DEPT NEUROSURG,BRISTOL BS16 1LE,AVON,ENGLAND. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. RP BASHIR, R (reprint author), UNIV NEBRASKA,COLL MED,NEUROL SECT,OMAHA,NE 68198, USA. NR 40 TC 36 Z9 36 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD FEB PY 1992 VL 12 IS 2 BP 103 EP 110 PG 8 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA GZ464 UT WOS:A1992GZ46400001 PM 1348529 ER PT J AU GLOWACKA, D GINTY, DD WAGNER, JA AF GLOWACKA, D GINTY, DD WAGNER, JA TI SYNERGISTIC EFFECTS OF NERVE GROWTH-FACTOR AND PHORBOL 12-MYRISTATE 13-ACETATE ON RAPID MOTILITY AND PROCESS FORMATION IN PC12 CELLS - THE ROLE OF LAMININ SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE NGF; PMA; PROTEIN KINASE-C; EGF; INTEGRIN; ACTIN ID PROTEIN KINASE-C; NEURITE OUTGROWTH; PHEOCHROMOCYTOMA CELLS; SURFACE GALACTOSYLTRANSFERASE; ADHESION; LINE; PHOSPHORYLATION; METABOLISM; CALCIUM AB A126-1B2 cells, a PKA (cAMP-dependent protein kinase)-deficient variant of PC12 cells, but not parental PC12 cells, form processes within 15-30 min of exposure to both nerve growth factor (NGF) and activators of protein kinase C when grown on tissue culture plastic (Glowacka and Wagner, J Neurosci Res 25:453-462, 1990). Time-lapse microscopy has demonstrated that these processes are formed by a novel mechanism, i.e., rapid movement of the cell body away from a point of attachment, which morphologically resembles a growth cone. These "fast" neurites are attached to the substratum at a number of points, which display membrane activity in the form of active ruffling and the extension of filopodia and membrane pleats. Thus, these processes are formed by a mechanism distinct from that used by PC12 and other neuronal cells to form processes in culture. Wild-type PC12 cells also migrate and form fast neurites in response to a combination of NGF and phorbol 12-myristate 13-acetate (PMA), when they are grown in conditioned media or plates, suggesting that a secreted factor that can bind to the substratum is essential for the rapid formation of these neurites. Similarly, wild-type PC12 cells grown on a laminincoated substratum also migrate and form "fast neurites" in response to a combination of NGF and PMA. This rapid migration is attenuated by an anti-alpha-1,beta-1-integrin antisera, implicating a laminin-integrin interaction; and it is inhibited by alpha-lactalbumin, suggesting an involvement of a beta-1,4 galactosyltransferase in the response. The formation of fast neurites is not dependent on concurrent protein synthesis, but it is inhibited by lithium, cytochalasin D, and methylthioadenosine or pretreatment of cells with NGF. Thus PC12 cells grown on the appropriate substrate have the ability to migrate rapidly and thereby form neuron-like processes within minutes of exposure to NGF and PMA. This morphological response to a combination of agents may provide an alternative means by which nerve cells form connections. Alternatively, it may reflect a mechanism that facilitates cellular migration during developmental processes. C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. FU NCI NIH HHS [CA40929] NR 29 TC 12 Z9 12 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 FEB PY 1992 VL 31 IS 2 BP 263 EP 272 DI 10.1002/jnr.490310207 PG 10 WC Neurosciences SC Neurosciences & Neurology GA HD578 UT WOS:A1992HD57800006 PM 1573676 ER PT J AU HOLMAN, BL JOHNSON, KA GERADA, B CARVALHO, PA SATLIN, A AF HOLMAN, BL JOHNSON, KA GERADA, B CARVALHO, PA SATLIN, A TI THE SCINTIGRAPHIC APPEARANCE OF ALZHEIMERS-DISEASE - A PROSPECTIVE-STUDY USING TECHNETIUM-99M-HMPAO SPECT SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article ID EMISSION COMPUTED-TOMOGRAPHY; CEREBRAL BLOOD-FLOW; TC-99M HM-PAO; PRESENILE DEMENTIA; INFARCT DEMENTIA; I-123 IMP; PERFUSION; DIAGNOSIS; SEVERITY AB Alzheimer's disease produces regional abnormalities in brain blood flow and metabolism that may result in recognizable scintigraphic patterns. We determined the predictive value of Tc-99m-HMPAO SPECT for the presence of Alzheimer's disease based on a prospective study of 132 consecutive patients coming to our nuclear medicine clinical unit for evaluation of their memory loss or cognitive abnormalities. During clinical follow-up averaging 10.1 mo, a final diagnosis was established in 113 patients, 52 of which had Alzheimer's disease. The probability of Alzheimer's disease was determined for seven scintigraphic patterns. The probability was 19% that patients with memory loss and normal perfusion had Alzheimer's disease. For abnormal perfusion patterns, the probability of Alzheimer's disease was 82% with bilateral temporoparietal defects, 77% with bilateral temporoparietal defects with additional defects, 57% with unilateral temporoparietal defects, 43% with frontal defects only, 18% with other large defects and 0% with multiple small cortical defects. We conclude that for Tc-99m-HMPAO SPECT the predictive value of bilateral temporoparietal defects for Alzheimer's disease is high, while the perfusion patterns of unilateral temporoparietal perfusion defects and frontal defects only, which occur in 20% of patients with Alzheimer's disease, are not predictive of that disease. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. MCLEAN HOSP,DEPT PSYCHIAT,BELMONT,MA 02178. HARVARD UNIV,SCH MED,DEPT RADIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. RP HOLMAN, BL (reprint author), BRIGHAM & WOMENS HOSP,DEPT RADIOL,75 FRANCIS ST,BOSTON,MA 02115, USA. NR 35 TC 221 Z9 225 U1 0 U2 7 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 FEB PY 1992 VL 33 IS 2 BP 181 EP 185 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA HB893 UT WOS:A1992HB89300003 PM 1732438 ER PT J AU PROVENZALE, J AF PROVENZALE, J TI THE CURRENT ROLE OF SPECT IN IMAGING SUBDURAL-HEMATOMA SO JOURNAL OF NUCLEAR MEDICINE LA English DT Editorial Material ID CEREBRAL BLOOD-FLOW RP PROVENZALE, J (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,DIV NEURORADIOL,BOSTON,MA 02129, USA. NR 5 TC 1 Z9 4 U1 0 U2 0 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 FEB PY 1992 VL 33 IS 2 BP 248 EP 250 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA HB893 UT WOS:A1992HB89300017 PM 1732448 ER PT J AU SHAMBERGER, RC WEINSTEIN, HJ AF SHAMBERGER, RC WEINSTEIN, HJ TI THE ROLE OF SURGERY IN ABDOMINAL BURKITTS-LYMPHOMA SO JOURNAL OF PEDIATRIC SURGERY LA English DT Article; Proceedings Paper CT 22ND ANNUAL MEETING OF THE AMERICAN PEDIATRIC SURGICAL ASSOC CY MAY 15-18, 1991 CL LAKE BUENA VISTA, FL SP AMER PEDIAT SURG ASSOC DE BURKITTS LYMPHOMA; CYTOREDUCTIVE SURGERY ID NON-HODGKINS-LYMPHOMA; CHILDHOOD; CLASSIFICATION; MANAGEMENT C1 CHILDRENS HOSP MED CTR,DANA FARBER CANC INST,DEPT PEDIAT HEMATOL ONCOL,BOSTON,MA 02115. RP SHAMBERGER, RC (reprint author), CHILDRENS HOSP MED CTR,DANA FARBER CANC INST,DEPT SURG,300 LONGWOOD AVE,BOSTON,MA 02115, USA. NR 19 TC 21 Z9 22 U1 1 U2 1 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 FEB PY 1992 VL 27 IS 2 BP 236 EP 240 DI 10.1016/0022-3468(92)90319-3 PG 5 WC Pediatrics; Surgery SC Pediatrics; Surgery GA HD566 UT WOS:A1992HD56600019 PM 1564624 ER PT J AU HABER, J KENT, RL AF HABER, J KENT, RL TI CIGARETTE-SMOKING IN A PERIODONTAL PRACTICE SO JOURNAL OF PERIODONTOLOGY LA English DT Article DE TOBACCO ADVERSE EFFECTS; PERIODONTITIS/ETIOLOGY ID CO-TWIN CONTROL; TOBACCO SMOKERS; DISEASE FACTORS; LUNG-CANCER; SUBSETS; HABITS AB THIS CASE-CONTROL STUDY COMPARES the prevalence of cigarette smoking among patients in a periodontal practice (cases) with that of patients in referring general dental practices (controls). Smoking histories of patients (age greater-than-or-equal-to 25 years) in a periodontal practice and five general dental practices were obtained by questionnaire. From the general practices, only patients reporting negative histories for periodontitis were studied. Periodontal status of the periodontal practice patients was based on bone loss from full mouth radiographic surveys and gingival pocket depths. Patients were stratified by age (25 to 40, 41 to 55, and > 55 years) and sex. The combined frequency of current or former cigarette smoking reported by 196 periodontal practice patients with moderate or advanced periodontitis (M-A perio group) was higher than that reported by 209 general dental practice patients (gen prac group) in all age and sex catagories. The age and sex adjusted summary odds ratio for a positive smoking history among M-A perio subjects relative to gen prac subjects was 2.6 (P < 0.001). Separate corresponding odds ratios (age and sex adjusted) for current smoking versus never smoking in the two groups were 3.3 (P < 0.001) and for former smoking versus never smoking 2.1 (P < 0.004). Among current smokers, patients in the M-A perio group reported heavy smoking (> 10 cigarettes/day) relatively more often than control subjects (adjusted R.O. = 5.7; P < 0.001). In the M-A perio group the frequency of current smoking increased with disease severity. These associations add to the accumulating evidence suggesting that both current and former smokers are at increased risk for periodontitis, and that cigarette smoking is a major risk factor for periodontitis. C1 FORSYTH DENT CTR,DEPT BIOSTAT,BOSTON,MA 02115. TUFTS UNIV,SCH DENT MED,DEPT ORAL PATHOL,BOSTON,MA 02111. RP HABER, J (reprint author), TUFTS UNIV,SCH MED,DEPT PATHOL,M&V BLDG,ROOM 312,136 HARRISON AVE,BOSTON,MA 02111, USA. FU NIDCR NIH HHS [DE04881, DE08463] NR 37 TC 140 Z9 144 U1 1 U2 11 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 FEB PY 1992 VL 63 IS 2 BP 100 EP 106 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA HD751 UT WOS:A1992HD75100006 PM 1552463 ER PT J AU CHUANG, TY HEINRICH, LA SCHULTZ, MD REIZNER, GT KUMM, RC CRIPPS, DJ AF CHUANG, TY HEINRICH, LA SCHULTZ, MD REIZNER, GT KUMM, RC CRIPPS, DJ TI PUVA AND SKIN-CANCER - A HISTORICAL COHORT STUDY ON 492 PATIENTS SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID LONG-TERM PHOTOCHEMOTHERAPY; 8-YEAR FOLLOW-UP; POPULATION-BASED INCIDENCE; SQUAMOUS-CELL CARCINOMA; CUTANEOUS CARCINOMA; ULTRAVIOLET-LIGHT; PSORIASIS; TUMORS; METHOXSALEN; PSORALENS AB Background: The safety of psoralen plus ultraviolet A (PUVA) light therapy has been an issue of debate. A few multiple-center cooperative studies have reported an increase of basal cell and squamous cell carcinomas among PUVA-treated patients. In our institute, more than 1000 patients have been treated with PUVA since 1975. Objective: We investigated the incidence of skin cancer among patients who received high doses of PUVA to see whether such incidence increased. Methods: This is a historical cohort study of two comparison groups of patients. Subjects under study were 492 psoriasis patients who received PUVA treatments between 1975 and 1989. One group of 103 patients; defined as the high-dose group, received an accumulated PUVA dose of 1000 joules/cm2 or more; another group of 389 patients, as the low-dose group, received 200 joules/cm2 or less. The occurrence of skin cancer in the two comparison groups is analyzed. Results: In the high-dose group we observed an increased number of patients with squamous cell carcinoma, keratoacanthoma, and actinic keratosis. We did not see any patients with genital cancer, melanoma, or an increased number of patients with basal cell carcinoma. Conclusion: The risk of squamous cell carcinoma developing in patients who received a high dose of PUVA is confirmed. We speculate a combination of factors, including PUVA, may contribute to this risk. C1 WILLIAM S MIDDLETON MEM VET ADM MED CTR,MED SERV,DERMATOL SECT,MADISON,WI. UNIV WISCONSIN,DEPT MED,DIV DERMATOL,MADISON,WI 53706. FU NIADDK NIH HHS [AM09995] NR 29 TC 64 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 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD FEB PY 1992 VL 26 IS 2 BP 173 EP 177 DI 10.1016/0190-9622(92)70021-7 PN 1 PG 5 WC Dermatology SC Dermatology GA HB885 UT WOS:A1992HB88500003 PM 1552048 ER PT J AU BARNHILL, RL ROUSH, GC ERNSTOFF, MS KIRKWOOD, JM AF BARNHILL, RL ROUSH, GC ERNSTOFF, MS KIRKWOOD, JM TI INTERCLINICIAN AGREEMENT ON THE RECOGNITION OF SELECTED GROSS MORPHOLOGICAL FEATURES OF PIGMENTED LESIONS - STUDIES OF MELANOCYTIC NEVI-V SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID MELANOMA; DIAGNOSIS; NAEVI AB Background: Since the late 1970s clinical criteria for dysplastic melanocytic nevi (DMN) have been proposed and discussed. However, to our knowledge, no rigorous quantitative evaluation of the ability of examiners to agree on the gross morphologic features ascribed to DMN or atypical melanocytic lesions in general has been conducted. Objective: The purpose of the study was to determine rates of interclinician agreement for recognizing seven clinical features associated with melanocytic lesions. Methods: The gross morphologic features of 156 pigmented lesions, judged to be the clinically most atypical, from 156 consecutively examined patients with cutaneous melanoma were analyzed. Independent of the other clinicians' examinations, four physicians (two medical oncologists, one internist-epidemiologist, and one dermatologist-dermatopathologist) recorded seven gross morphologic features of the most atypical pigmented lesion on each patient. For up to 122 patients, the rates of interobserver agreement on recognizing these clinical features were measured by intraclass correlation. Results: Among the clinical features assessed, the examiners noted macular components in 85.7% to 96.3% of lesions, asymmetry in 47.2% to 79.5%, irregular borders in 55.1% to 80.2%, ill-defined borders in 40.1% to 83.9%, and haphazard color in 40.8% to 73.9% of lesions. Despite this range of variance among examiners, there were statistically significant rates of interclinician agreement for the recognition of the latter features. There was less agreement in assessing individual colors within lesions. Conclusion: These findings substantiate that certain gross morphologic features routinely used in the clinical evaluation of melanocytic lesions can be recognized with a significant degree of reliability. C1 CANC PREVENT RES INST,NEW YORK,NY. MASSACHUSETTS GEN HOSP,DERMATOL SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. UNIV PITTSBURGH,SCH MED,DEPT MED,DIV MED ONCOL,PITTSBURGH,PA 15261. RP BARNHILL, RL (reprint author), MASSACHUSETTS GEN HOSP,DIV DERMATOPATHOL,DERMATOPATHOL UNIT,WARREN 827,FRUIT ST,BOSTON,MA 02114, USA. NR 12 TC 21 Z9 21 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD FEB PY 1992 VL 26 IS 2 BP 185 EP 190 DI 10.1016/0190-9622(92)70023-9 PN 1 PG 6 WC Dermatology SC Dermatology GA HB885 UT WOS:A1992HB88500005 PM 1552050 ER PT J AU DRAKE, LA CEILLEY, RI CORNELISON, RL DOBES, WL DORNER, W GOLTZ, RW LEWIS, CW SALASCHE, SJ TURNER, MLC COSKEY, RJ DRAKE, LA HORDINSKY, MK ROSENBERG, EW SOLOMON, AR AF DRAKE, LA CEILLEY, RI CORNELISON, RL DOBES, WL DORNER, W GOLTZ, RW LEWIS, CW SALASCHE, SJ TURNER, MLC COSKEY, RJ DRAKE, LA HORDINSKY, MK ROSENBERG, EW SOLOMON, AR TI GUIDELINES OF CARE FOR ALOPECIA-AREATA SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID SQUARIC ACID DIBUTYLESTER; TOPICAL MINOXIDIL; THERAPEUTIC TOOL; CONTACT ALLERGY; PUVA TREATMENT; DINITROCHLOROBENZENE; DERMATITIS; INOSIPLEX; IRRITANT; TOTALIS RP DRAKE, LA (reprint author), MASSACHUSETTS GEN HOSP,DEPT DERMATOL,BOSTON,MA 02114, USA. NR 34 TC 16 Z9 16 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 FEB PY 1992 VL 26 IS 2 BP 247 EP 250 DI 10.1016/S0190-9622(08)80299-X PN 1 PG 4 WC Dermatology SC Dermatology GA HB885 UT WOS:A1992HB88500020 PM 1552060 ER PT J AU HELD, JL DRUKER, BJ KOHN, SR BYRNES, W MARGOLIS, RJ AF HELD, JL DRUKER, BJ KOHN, SR BYRNES, W MARGOLIS, RJ TI ATYPICAL, NONFATAL, TRANSFUSION-ASSOCIATED, ACUTE GRAFT-VERSUS-HOST DISEASE IN A PATIENT WITH HODGKINS-DISEASE SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Note C1 NASHOBA COMMUNITY HOSP,DEPT MED,AYER,MA. NASHOBA COMMUNITY HOSP,DEPT FAMILY PRACTICE,AYER,MA. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. BOSTON UNIV,SCH MED,DEPT DERMATOL & DERMATOPATHOL,BOSTON,MA 02118. YALE UNIV,SCH MED,DEPT DERMATOL,NEW HAVEN,CT 06510. NR 2 TC 1 Z9 1 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 FEB PY 1992 VL 26 IS 2 BP 261 EP 262 DI 10.1016/S0190-9622(08)80305-2 PN 1 PG 2 WC Dermatology SC Dermatology GA HB885 UT WOS:A1992HB88500026 PM 1552066 ER PT J AU YOSHIKAWA, TT AF YOSHIKAWA, TT TI TUBERCULOSIS IN AGING ADULTS SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Review ID SHORT-COURSE CHEMOTHERAPY; PULMONARY TUBERCULOSIS; MILIARY TUBERCULOSIS; ELDERLY PATIENTS; RAPID DIAGNOSIS; EXTRAPULMONARY TUBERCULOSIS; MYCOBACTERIAL DISEASES; NURSING-HOME; DELAYED-HYPERSENSITIVITY; JOINT TUBERCULOSIS RP YOSHIKAWA, TT (reprint author), US DEPT VET AFFAIRS,OFF GERIATR & EXTENDED CARE 114,810 VERMONT AVE NW,WASHINGTON,DC 20420, USA. NR 153 TC 33 Z9 34 U1 0 U2 1 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 FEB PY 1992 VL 40 IS 2 BP 178 EP 187 PG 10 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA HC685 UT WOS:A1992HC68500014 PM 1740604 ER PT J AU KUSUMI, K CONWAY, B CUNNINGHAM, S BERSON, A EVANS, C IVERSEN, AKN COLVIN, D GALLO, MV COUTRE, S SHPAER, EG FAULKNER, DV DERONDE, A VOLKMAN, S WILLIAMS, C HIRSCH, MS MULLINS, JI AF KUSUMI, K CONWAY, B CUNNINGHAM, S BERSON, A EVANS, C IVERSEN, AKN COLVIN, D GALLO, MV COUTRE, S SHPAER, EG FAULKNER, DV DERONDE, A VOLKMAN, S WILLIAMS, C HIRSCH, MS MULLINS, JI TI HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ENVELOPE GENE STRUCTURE AND DIVERSITY INVIVO AND AFTER COCULTIVATION INVITRO SO JOURNAL OF VIROLOGY LA English DT Article ID FELINE LEUKEMIA-VIRUS; PERIPHERAL-BLOOD; VIRAL DETERMINANTS; MONONUCLEAR-CELLS; RECEPTOR-BINDING; CHAIN-REACTION; III INFECTION; HTLV-III/LAV; CD4 RECEPTOR; T-CELL AB Nested-primer polymerase chain reaction (PCR) has been applied to the molecular cloning of 4.6-kb half-genome fragments of human immunodeficiency virus type 1 (HIV-1) taken directly from the peripheral blood mononuclear cells (PBMC) of an individual with neurological symptoms of HIV-1 infection. In a similar manner, gp120-coding portions of the envelope gene were cloned after PBMC from the same blood sample were cocultivated with uninfected PBMC for 28 days. The complete 1.6-kb nucleotide sequence of the gp120 gene was determined from each of 35 clones examined. Two of 13 (15%) PBMC-derived gp120 genes and 3 of 22 (14%) coculture-derived gp120 genes were defective as a result of frameshifts and an in-frame stop codon(s). Mean diversity between individual gp120-coding sequences in PBMC was fivefold greater (3.24%) than after coculture (0.65%). A predominant sequence or "strain" was found after coculture that was distinct from the diverse viral genotypes detected in vivo and therefore was selectively amplified during in vitro propagation. Multiple distinct third variable (V3) regions encoding the principal neutralizing domain of the envelope protein were detected in PBMC-derived genes, suggesting the presence of immunologic diversity of HIV env genes in vivo not reflected in the cocultured virus sample. The large size of the HIV fragments generated in this study will permit analysis of the diversity of immunologic reactivity, gene function, and pathogenicity of HIV genomes present within infected individuals, including the functional significance of the loss of diversity that occurs upon coculture. C1 HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA 02114. STANFORD UNIV,MED CTR,SCH MED,DEPT MICROBIOL & IMMUNOL,STANFORD,CA 94305. RI Kusumi, Kenro/J-2626-2012 OI Kusumi, Kenro/0000-0002-1458-4540 FU NIAID NIH HHS [AI85007, AI27762] NR 82 TC 151 Z9 152 U1 1 U2 3 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 FEB PY 1992 VL 66 IS 2 BP 875 EP 885 PG 11 WC Virology SC Virology GA GY965 UT WOS:A1992GY96500030 PM 1731112 ER PT J AU PALLAS, DC WELLER, W JASPERS, S MILLER, TB LANE, WS ROBERTS, TM AF PALLAS, DC WELLER, W JASPERS, S MILLER, TB LANE, WS ROBERTS, TM TI THE 3RD SUBUNIT OF PROTEIN PHOSPHATASE-2A (PP2A), A 55-KILODALTON PROTEIN WHICH IS APPARENTLY SUBSTITUTED FOR BY T-ANTIGENS IN COMPLEXES WITH THE 36-KILODALTON AND 63-KILODALTON PP2A SUBUNITS, BEARS LITTLE RESEMBLANCE TO T-ANTIGENS SO JOURNAL OF VIROLOGY LA English DT Article ID MEDIUM TUMOR-ANTIGEN; POLYOMA-VIRUS; CELLULAR PROTEINS; CATALYTIC SUBUNIT; MOLECULAR-CLONING; INFECTED-CELLS; GENE-PRODUCTS; OKADAIC ACID; ASSOCIATION; SEQUENCE AB The small and middle T (tumor) antigens of polyomavirus have been shown previously to associate with the 36-kDa catalytic subunit and the 63-kDa regulatory subunit of protein phosphatase type 2A, apparently substituting for a normal third 55-kDa regulatory subunit (D. C. Pallas, L. K. Shahrik, B. L. Martin, S. Jaspers, T. B. Miller, D. L. Brautigan, and T. M. Roberts, Cell 60:167-176, 1990). To facilitate a comparison of the normal regulatory subunit and T antigens, we isolated a 2.14-kb cDNA clone encoding this 55-kDa subunit from a rat liver library. Using a probe from the coding region of this gene, we detected a major 2.4-kb mRNA transcript in liver and muscle RNAs. The 55-kDa protein phosphatase 2A subunit purified from rat skeletal muscle generates multiple species when analyzed on two-dimensional gels. Transcription and translation of the clone in vitro produced a full-length protein that comigrated precisely on two-dimensional gels with three of these species, indicating that the 55-kDa protein is apparently modified similarly in vivo and in reticulocyte lysates. Additional species in the purified preparation were not found in the translate, suggesting that there are probably two or more isoforms of this protein in rat muscle. Somewhat surprisingly, there was no clear homology with T-antigen amino acid sequences. C1 UNIV MASSACHUSETTS,MED CTR,DEPT BIOCHEM & MOLEC BIOL,WORCESTER,MA 01655. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,BIOL LABS,HARVARD MICROCHEM FACIL,CAMBRIDGE,MA 02138. RP PALLAS, DC (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELLULAR & MOLEC BIOL,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA45285, R01 CA057327, CA30002]; NIDDK NIH HHS [DK 18269] NR 47 TC 72 Z9 74 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 1992 VL 66 IS 2 BP 886 EP 893 PG 8 WC Virology SC Virology GA GY965 UT WOS:A1992GY96500031 PM 1370560 ER PT J AU FLEMINGTON, EK BORRAS, AM LYTLE, JP SPECK, SH AF FLEMINGTON, EK BORRAS, AM LYTLE, JP SPECK, SH TI CHARACTERIZATION OF THE EPSTEIN-BARR-VIRUS BZLF1 PROTEIN TRANSACTIVATION DOMAIN SO JOURNAL OF VIROLOGY LA English DT Article ID DNA-BINDING SPECIFICITY; SWITCH GENE BZLF1; TRANSCRIPTIONAL ACTIVATOR; INFECTED LYMPHOCYTES; ZTA TRANSACTIVATOR; C-FOS; PROMOTER; CELLS; EXPRESSION; INDUCTION AB Initiation of the Epstein-Barr virus (EBV) lytic cycle is dependent on expression of the viral transactivator Zta, which is encoded by the BZLF1 gene. Described here is an initial mapping of the regions of Zta involved in activating transcription. The data indicate that the amino-terminal 153 amino acids of Zta are important for activity, and in particular the region from residues 28 to 78 appears to be critical for Zta function. However, other features of Zta may be important for activity since a Gal4-Zta chimeric protein, generated by fusing the amino-terminal 167 residues of Zta to the DNA binding domain of the yeast transactivator Gal4, transactivated a minimal promoter containing one upstream Gal4 binding site but was unable to exhibit synergistic transactivation when assayed with a reporter containing five upstream Gal4 binding sites. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR VIROL,44 BINNEY ST,BOSTON,MA 02115. FU NCI NIH HHS [5R01 CA43143] NR 40 TC 75 Z9 76 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 FEB PY 1992 VL 66 IS 2 BP 922 EP 929 PG 8 WC Virology SC Virology GA GY965 UT WOS:A1992GY96500035 PM 1309920 ER PT J AU BLUM, HE ZHANG, ZS GALUN, E VONWEIZSACKER, F GARNER, B LIANG, TJ WANDS, JR AF BLUM, HE ZHANG, ZS GALUN, E VONWEIZSACKER, F GARNER, B LIANG, TJ WANDS, JR TI HEPATITIS-B VIRUS X-PROTEIN IS NOT CENTRAL TO THE VIRAL LIFE-CYCLE INVITRO SO JOURNAL OF VIROLOGY LA English DT Note ID COMPLETE NUCLEOTIDE-SEQUENCE; GENE PRODUCT; DNA; TRANSACTIVATOR; ACTIVATION; EXPRESSION; CELLS; PARTICLES; DUCK AB The hepatitis B x (HBx) gene is the smallest open reading frame of the hepatitis B virus (HBV) genome. It is conserved among all mammalian hepadnaviruses and is expressed during viral infection. While the HBx protein (pX) has been shown to trans-activate the transcription of a wide range of viral and cellular genes and to induce liver cancer in transgenic mice, the significance of pX for the life cycle of HBV itself has not been elucidated. To assess the function of pX in viral replication and virion export, we designed an X-minus mutant by introduction of a stop codon at the beginning of the HBx gene without affecting the viral polymerase gene product. Transient transfection analyses using different cell lines revealed that this X-minus mutant directs the synthesis of wild-type levels of viral proteins, replicative intermediates, and virion export. These data suggest that the expression of the highly conserved HBx gene is not central for the life cycle of HBV in vitro but may be involved in the pathogenicity of hepadnavirus infection, including liver cancer development. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CTR CANC,MOLEC HEPATOL LAB,BOSTON,MA 02129. NR 32 TC 121 Z9 124 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 FEB PY 1992 VL 66 IS 2 BP 1223 EP 1227 PG 5 WC Virology SC Virology GA GY965 UT WOS:A1992GY96500074 PM 1731101 ER PT J AU FRISCH, RE SNOW, R GERARD, EL JOHNSON, L KENNEDY, D BARBIERI, R ROSEN, BR AF FRISCH, RE SNOW, R GERARD, EL JOHNSON, L KENNEDY, D BARBIERI, R ROSEN, BR TI MAGNETIC-RESONANCE-IMAGING OF BODY-FAT OF ATHLETES COMPARED WITH CONTROLS, AND THE OXIDATIVE-METABOLISM OF ESTRADIOL SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID WEIGHT; CANCER C1 MASSACHUSETTS GEN HOSP E,NMR IMAGING CTR,BOSTON,MA. MASSACHUSETTS GEN HOSP E,CTR NEUROSCI,BOSTON,MA. BRIGHAM & WOMENS HOSP,DEPT OBSTET & GYNECOL,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT POPULAT SCI,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. RP FRISCH, RE (reprint author), HARVARD UNIV,CTR POPULAT STUDIES,9 BOW ST,CAMBRIDGE,MA 02138, USA. FU NICHD NIH HHS [HD23536] NR 10 TC 13 Z9 13 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD FEB PY 1992 VL 41 IS 2 BP 191 EP 193 DI 10.1016/0026-0495(92)90151-Y PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA HC642 UT WOS:A1992HC64200017 PM 1736042 ER PT J AU SCURFIELD, RM TICE, SN AF SCURFIELD, RM TICE, SN TI INTERVENTIONS WITH MEDICAL AND PSYCHIATRIC EVACUEES AND THEIR FAMILIES - FROM VIETNAM THROUGH THE GULF WAR SO MILITARY MEDICINE LA English DT Article AB Clinical, milieu, and patient management psycho-social interventions are identified and discussed concerning medical and psychiatric evacuees from a war zone. The acute psychological state of evacuees, specific areas of inquiry from the onset of becoming a casualty through initial hospitalization stateside, and interventions to address psychological aspects of being wounded or a psychiatric evacuee are highlighted. Issues and dynamics to address with the families, to include clinical experiences with families of Vietnam, Panama, and Gulf War military returnees are described, as well as specific risk factors for Operation Desert Storm families and personnel. Distinctive stressors faced by women, national guard and reserves, and ethnic minority personnel in Operation Desert Storm are identified. Finally, complications and recommendations concerning the appropriate diagnoses for psychiatric evacuees, and the stressors faced by the health care provider, are presented. Specific recommendations by veterans who themselves were evacuated from Vietnam are described in the veterans' own words. RP SCURFIELD, RM (reprint author), US DEPT VET AFFAIRS,PACIFIC CTR PTSD & OTHER WAR RELATED DISORDERS,300 ALA MOANA BLVD,HONOLULU,HI 96850, USA. NR 0 TC 7 Z9 7 U1 0 U2 0 PU ASSN MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0026-4075 J9 MIL MED JI Milit. Med. PD FEB PY 1992 VL 157 IS 2 BP 88 EP 97 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA HC531 UT WOS:A1992HC53100015 PM 1603393 ER PT J AU GARNER, DC AF GARNER, DC TI DEFENSE-HEALTH-AGENCY SO MILITARY MEDICINE LA English DT Letter RP GARNER, DC (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSN MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0026-4075 J9 MIL MED JI Milit. Med. PD FEB PY 1992 VL 157 IS 2 BP A6 EP A6 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA HC531 UT WOS:A1992HC53100001 PM 1603381 ER PT J AU GEORGOPOULOS, K MORGAN, BA MOORE, DD AF GEORGOPOULOS, K MORGAN, BA MOORE, DD TI FUNCTIONALLY DISTINCT ISOFORMS OF THE CRE-BP DNA-BINDING PROTEIN MEDIATE ACTIVITY OF A T-CELL-SPECIFIC ENHANCER SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID AMP RESPONSE ELEMENT; CYCLIC-AMP; CD3-DELTA GENE; C-JUN; TRANSCRIPTION FACTOR; LEUCINE ZIPPER; EXPRESSION; DOMAIN; RECOGNITION; ACTIVATION AB Expression of the CD3-delta gene of the T-cell receptor (TCR) complex is regulated by a T-cell-specific enhancer. A highly conserved 40-bp motif (element delta-A) within the CD3-delta enhancer is responsible for mediating its activity and specificity. Element delta-A exhibits sequence similarities to the cyclic AMP response element (CRE) but does not respond to changes in the level of cyclic AMP. Using the delta-A element as a probe, we have isolated three cDNA clones encoding three distinct protein isoforms, products of differential splicing and alternate promoter usage of the CRE-BP gene. These isoforms share the DNA binding and dimerization domains at the C terminus of the protein but differ at their N termini. In transfection assays, their activities as transcription regulators differ: CRE-BP2 is a potent activator, CRE-BP3 is a weak activator, and CRE-BP1 is transcriptionally inert. Mutations in the basic region of the CRE-BP1 protein which abrogate its ability to bind DNA render this protein a dominant repressor of the delta-A enhancer. Antibodies to the CRE-BP protein interact specifically with the ubiquitous and predominantly T-cell-restricted nuclear complexes that bind to the delta-A element and suggest the presence of this protein in homo- and heterodimeric complexes. Since the delta-A motif is also present in the enhancer and promoter of the TCR alpha and beta-genes, the CRE-BP isoforms may mediate expression of other members of the CD3/TCR complex during T-cell development. C1 MASSACHUSETTS GEN HOSP,CUTANEOUS BIOL RES CTR,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. RP GEORGOPOULOS, K (reprint author), MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114, USA. FU NICHD NIH HHS [HD07408-02] NR 36 TC 63 Z9 64 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 FEB PY 1992 VL 12 IS 2 BP 747 EP 757 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA HB066 UT WOS:A1992HB06600030 PM 1531087 ER PT J AU CHAN, PY SPRINGER, TA AF CHAN, PY SPRINGER, TA TI EFFECT OF LENGTHENING LYMPHOCYTE FUNCTION-ASSOCIATED ANTIGEN-3 ON ADHESION TO CD2 SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID MONOCLONAL-ANTIBODY; BINDING-SITES; RECEPTOR CD2; LFA-3; LIGAND; GLYCOPROTEIN; SURFACE; CELLS; RECOGNITION; PROTEINS AB The effect of lengthening the distance in an adhesion molecule between the receptor binding site and the membrane anchor was studied by inserting four Ig-like domains into the two Ig domain lymphocyte function-associated antigen 3 (LFA-3) molecule. The extended molecule expressed in Chinese hamster ovary (CHO) cells bound to CD2 on T lymphocytes 4- to 20-fold more efficiently than the wild-type molecule at 4-degrees-C. Treatment of the CHO clones with neuraminidase to remove sialic acid, or with deoxymannojirimycin to reduce the bulk of N-linked glycosylation, showed that adhesion to both the wild-type and the chimeric LFA-3 molecules was under the influence of cell-cell repulsive forces to a similar extent and that these treatments had less effect than lengthening LFA-3. At higher temperatures, such as 22 and 37-degrees-C, the efficiency of binding to the wild-type LFA-3 increased to levels comparable with binding to extended LFA-3. Our results suggest that more distal locations of the adhesive binding site from the cell membrane anchor increase the efficiency of cell-cell adhesion by enhancing the frequency of receptor encounter with ligand and that more proximal locations of the adhesive binding site can provide efficient cell-cell adhesion at physiological temperatures. C1 HARVARD UNIV,CTR BLOOD RES,BOSTON,MA 02115. RP CHAN, PY (reprint author), HARVARD UNIV,SCH MED,800 HUNTINGTON AVE,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA-31798] NR 37 TC 27 Z9 27 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 FEB PY 1992 VL 3 IS 2 BP 157 EP 166 PG 10 WC Cell Biology SC Cell Biology GA HD215 UT WOS:A1992HD21500003 PM 1348006 ER PT J AU KONZAK, KE MOORE, DD AF KONZAK, KE MOORE, DD TI FUNCTIONAL ISOFORMS OF PIT-1 GENERATED BY ALTERNATIVE MESSENGER-RNA SPLICING SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID GROWTH-HORMONE GENE; TRANSCRIPTION FACTOR; POU-DOMAIN; BINDING-SITES; EXPRESSION; PROTEIN; PROMOTER; GHF-1; REPRESSION; EXTINCTION AB Pit-1 is a pituitary-specific transcription factor that activates expression of the GH and PRL genes. We have isolated a cDNA encoding a variant isoform of Pit-1 that we term Pit-1-beta. Pit-1-beta contains an insertion of 26 amino acids in the transactivation domain as a consequence of the utilization of an alternative 3' splice acceptor at the end of the first intron. Like the previously described Pit-1-alpha, Pit-1-beta transactivates both the GH and PRL promoters. However, the larger isoform acts as a more potent inducer of GH. C1 MASSACHUSETTS GEN HOSP, DEPT MOLEC BIOL, BOSTON, MA 02114 USA. NR 30 TC 90 Z9 91 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 FEB PY 1992 VL 6 IS 2 BP 241 EP 247 DI 10.1210/me.6.2.241 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA HH583 UT WOS:A1992HH58300010 PM 1569967 ER PT J AU TORIMOTO, Y DANG, NH TANAKA, T PRADO, C SCHLOSSMAN, SF MORIMOTO, C AF TORIMOTO, Y DANG, NH TANAKA, T PRADO, C SCHLOSSMAN, SF MORIMOTO, C TI BIOCHEMICAL-CHARACTERIZATION OF CD26 (DIPEPTIDYL PEPTIDASE-IV) - FUNCTIONAL COMPARISON OF DISTINCT EPITOPES RECOGNIZED BY VARIOUS ANTI-CD26 MONOCLONAL-ANTIBODIES SO MOLECULAR IMMUNOLOGY LA English DT Article ID T-CELL ACTIVATION; HUMAN LYMPHOCYTE-T; PERIPHERAL-BLOOD; CD4 CELLS; ANTIGEN; SURFACE; TA1; INTERLEUKIN-2; INHIBITORS; MOLECULE AB In this paper, we performed further biochemical characterization of the CD26 antigen, as defined by the mAbs in anti-1F7 and anti-Ta1, in order to clarify the observed functional differences among these mAbs. For this purpose, we developed a mAb, anti-5F8, which recognizes yet another epitope on the CD26 antigen different from that recognized by anti-1F7 and anti-Ta1 and compared their respective effect on T cell activation as well as the structures recognized by these mAbs. Functionally, anti-5F8 did not exhibit a comitogenic effect on T cell activation via the CD3 and CD2 pathways. Peptide mapping studies suggested that the 110 kDa molecules precipitated by these mAbs are identical. We showed that the 110 kDa CD26 structure on human T cells is composed of a family of heterogeneous molecules, as determined by isoelectric focusing studies. In addition, we demonstrated that the CD26 antigen has a DPPIV enzyme activity and this enzyme activity is found only on the principal basic structure of CD26 but not on the additional acidic structures. Biochemical studies also revealed that these mAbs recognized distinct epitopes on the CD26 antigen. Pulse-chase studies showed the the 1F7 epitope was found on both the immature (100 kDa) and mature (110 kDa) forms of the CD26 antigen. On the other hand, the Ta1 and 5F8 epitopes were expressed mainly on the mature form of the CD26 antigen. Moreover, anti-1F7 consistently precipitated an additional 43 kDa molecule in association with the principal 110 kDa molecule. Taken together, these data suggested that the additional 43 kDa structure or the distinct epitope recognized by anti-IF7 may play a role in human T cell activation via the CD3 and CD2 pathways. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. FU NIAMS NIH HHS [AR-33713]; PHS HHS [A1-12069] NR 32 TC 66 Z9 68 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD FEB PY 1992 VL 29 IS 2 BP 183 EP 192 DI 10.1016/0161-5890(92)90099-J PG 10 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA HF032 UT WOS:A1992HF03200005 PM 1371820 ER PT J AU COULL, BM LEVINE, SR BREY, RL AF COULL, BM LEVINE, SR BREY, RL TI THE ROLE OF ANTIPHOSPHOLIPID ANTIBODIES IN STROKE SO NEUROLOGIC CLINICS LA English DT Review ID SYSTEMIC LUPUS-ERYTHEMATOSUS; ANTI-CARDIOLIPIN ANTIBODIES; ACQUIRED IMMUNODEFICIENCY SYNDROME; TRANSIENT ISCHEMIC ATTACKS; HEALTHY ELDERLY POPULATION; GUILLAIN-BARRE-SYNDROME; PROTEIN-C ACTIVATION; ANTICARDIOLIPIN ANTIBODIES; SNEDDONS SYNDROME; ENDOTHELIAL-CELLS C1 PORTLAND VET AFFAIRS MED CTR,PORTLAND,OR. HENRY FORD HOSP,DEPT NEUROL,CTR STROKE RES,CLIN STROKE SERV,DETROIT,MI 48202. HENRY FORD HOSP,DEPT NEUROL,CTR STROKE RES,ACUTE STROKE UNIT,DETROIT,MI 48202. UNIV MICHIGAN,SCH MED,DEPT NEUROL,ANN ARBOR,MI 48104. UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. RP COULL, BM (reprint author), OREGON HLTH SCI UNIV,DEPT NEUROL,L-226,3181 SW SAM JACKSON PK DR,PORTLAND,OR 97201, USA. FU NINDS NIH HHS [2P01 NS17493-08] NR 140 TC 43 Z9 45 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0733-8619 J9 NEUROL CLIN JI Neurol. Clin. PD FEB PY 1992 VL 10 IS 1 BP 125 EP 143 PG 19 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA HD662 UT WOS:A1992HD66200008 PM 1556999 ER PT J AU GORMAN, DG BENSON, DF VOGEL, DG VINTERS, HV AF GORMAN, DG BENSON, DF VOGEL, DG VINTERS, HV TI CREUTZFELDT-JAKOB DISEASE IN A PATHOLOGIST SO NEUROLOGY LA English DT Note C1 W LOS ANGELES VET AFFAIRS MED CTR,BEHAV NEUROSCI SECT,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,PSYCHIAT SERV,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT NEUROL,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT PATHOL,LOS ANGELES,CA 90024. NR 6 TC 27 Z9 27 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0028-3878 J9 NEUROLOGY JI Neurology PD FEB PY 1992 VL 42 IS 2 BP 463 EP 463 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA HD792 UT WOS:A1992HD79200046 PM 1736189 ER PT J AU VANDEKAR, LD BONADONNA, AM RITTENHOUSE, PA KERR, JE LEVY, AD IYER, L HERBERT, GB SANZ, MCA LENT, SJ CARNES, M AF VANDEKAR, LD BONADONNA, AM RITTENHOUSE, PA KERR, JE LEVY, AD IYER, L HERBERT, GB SANZ, MCA LENT, SJ CARNES, M TI PRIOR CHRONIC EXPOSURE TO COCAINE INHIBITS THE SEROTONERGIC STIMULATION OF ACTH AND SECRETION OF CORTICOSTERONE SO NEUROPHARMACOLOGY LA English DT Article DE COCAINE; ACTH; CORTICOSTERONE; 5-HT; PARA-CHLOROAMPHETAMINE; 5-HT RECEPTORS; 5-HT UPTAKE ID PARAVENTRICULAR NUCLEUS; RECEPTOR SUBTYPE; BRAIN-SEROTONIN; RAT; NEURONS; CORTICOTROPIN; ACTIVATION; AGONISTS; RENIN; MECHANISM AB The effect of long-term pretreatment with cocaine on serotonergic regulation of ACTH (adrenocorticotropic hormone; corticotropin) and secretion of corticosterone in rats was investigated. The following observations were made: (1) Pretreatment with cocaine had no significant effect on basal levels of ACTH and corticosterone in plasma. However, cocaine caused a reduction in the ability of the 5-HT (5-hydroxytryptamine, serotonin) releaser p-chloroamphetamine (PCA) to increase corticosterone in plasma, 42 hr after the last injection of cocaine. (2) Exposure to cocaine for 7 days was sufficient to produce a maximal inhibition of the PCA-induced increase in ACTH in plasma. (3) The inhibitory effect of cocaine on PCA-induced release of ACTH was more marked than on corticosterone. (4) Conversely, the dose-dependent stimulatory effect of two 5-HT1 agonists, RU 24969 (5-methoxy-3-(1,2,3,4-tetrahydro-4-pyridinyl)-1H-indole) and m-CPP (m-chlorophenylpiperazine), on ACTH and corticosterone was not reduced by 7 days of exposure to cocaine. Taken together, these findings indicate that pretreatment with cocaine reduced the function of serotonergic nerve-terminals but not postsynaptic receptors, that stimulate ACTH and secretion of corticosterone. C1 WILLIAM S MIDDLETON MEM VET ADM MED CTR,GERIATR SECT,MADISON,WI 53705. UNIV WISCONSIN,DEPT MED,MADISON,WI 53705. RP VANDEKAR, LD (reprint author), LOYOLA UNIV,STRITCH SCH MED,DEPT PHARMACOL,2160 S 1ST AVE,MAYWOOD,IL 60153, USA. FU NIDA NIH HHS [DA04865]; NIMH NIH HHS [MH45812] NR 40 TC 33 Z9 33 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD FEB PY 1992 VL 31 IS 2 BP 169 EP 175 DI 10.1016/0028-3908(92)90028-N PG 7 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA HD051 UT WOS:A1992HD05100011 PM 1313159 ER PT J AU HORNIG, GW ZERVAS, NT AF HORNIG, GW ZERVAS, NT TI SLIT DEFECT OF THE DIAPHRAGMA SELLAE WITH VALVE EFFECT - OBSERVATION OF A SLIT VALVE SO NEUROSURGERY LA English DT Article DE DIAPHRAGMA SELLAE DEFECT; INTRASELLAR ARACHNOID CYST AB Malformations of the diaphragma sellae may permit transdiaphragmatic cerebrospinal fluid pulsations that lead to expansion of the sella turcica. The purpose of this report is to describe an intrasellar arachnoid cyst observed during surgery being filled by the action of an apparent one-way valve. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,NEUROSURG SERV,BOSTON,MA 02114. NR 6 TC 25 Z9 25 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 FEB PY 1992 VL 30 IS 2 BP 265 EP 267 PG 3 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA HA454 UT WOS:A1992HA45400022 PM 1545899 ER PT J AU HABER, DA BUCKLER, AJ AF HABER, DA BUCKLER, AJ TI WT1 - A NOVEL TUMOR SUPPRESSOR GENE INACTIVATED IN WILMS-TUMOR SO NEW BIOLOGIST LA English DT Review DE WILMS TUMOR; TUMOR SUPPRESSOR GENES; KIDNEY DEVELOPMENT; ZINC FINGER GENE ID ZINC-FINGER GENE; WIEDEMANN-BECKWITH SYNDROME; EARLY GROWTH-RESPONSE; SOMATIC-CELL HYBRIDS; FACTOR-II GENE; HUMAN CHROMOSOME-11; WAGR REGION; RETINOBLASTOMA GENE; PHYSICAL MAP; BAND 11P13 C1 MIT,CAMBRIDGE,MA 02139. RP HABER, DA (reprint author), MASSACHUSETTS GEN HOSP,CTR CANC,BOSTON,MA 02125, USA. NR 91 TC 50 Z9 51 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 1043-4674 J9 NEW BIOL PD FEB PY 1992 VL 4 IS 2 BP 97 EP 106 PG 10 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA JR310 UT WOS:A1992JR31000003 PM 1313285 ER PT J AU LIVNI, E FISCHMAN, AJ RAY, S SINCLAIR, I ELMALEH, DR ALPERT, NM WEISS, S CORREIA, JA WEBB, D DAHL, R ROBESON, W MARGOULEFF, D LISS, R STRAUSS, HW RUBIN, RH AF LIVNI, E FISCHMAN, AJ RAY, S SINCLAIR, I ELMALEH, DR ALPERT, NM WEISS, S CORREIA, JA WEBB, D DAHL, R ROBESON, W MARGOULEFF, D LISS, R STRAUSS, HW RUBIN, RH TI SYNTHESIS OF F-18 LABELED FLUCONAZOLE AND POSITRON EMISSION TOMOGRAPHY STUDIES IN RABBITS SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article ID CEREBROSPINAL-FLUID; PENETRATION; HUMANS; HYPOTHESIS; TRIAZOLES; PROFILE; DRUG AB [4-F-18] 2-(2,4-difluorophenyl)-1,3-bis(1H-1,2,4-triazol-1-yl)-2-propanol ([4-F-18] fluconazole) was synthesized from its amino precursor. Fieldel-Crafts acylation of 3-fluoroacetanilide with chloroacetyl chloride produced 2'-fluoro-4'-acteamido-2-(1H-1,2,4-triazole-1-yl) acetophenone in 12% yield. Sequential reaction with (1) dimethylsulphoxonium methylide and (2) 1,2,4-triazole followed by in situ hydrolysis resulted in 2-(2-fluoro-4-aminophenyl)-1,3-bis(1H-1,2,4-triazol-1-yl)-2-propanol in 19% yield. A modified Schiemann reaction on this product resulted in [4-F-18]fluconazole with a radiochemical yield of 1.0-2.0% (EOS) within 2 h. [4-F-18]Fluconazole was used to measure the pharmacokinetics of fluconazole in rats by measurement of radioactivity in excised tissues and in rabbits by PET. In both species, there was rapid equilibration of [4-F-18]fluconazole to a relatively uniform distribution of radioactivity in most organs. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,DIV NUCL MED,32 FRUIT ST,BOSTON,MA 02114. HARVARD UNIV,SCH MED,MED SERV,CLIN INVEST PROGRAM,DEPT RADIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,MED SERV,CLIN INVEST PROGRAM,DEPT MED,BOSTON,MA 02115. PFIZER LTD,SANDWICH CT13 9NJ,KENT,ENGLAND. PFIZER INC,ROERIG MED DEPT,NEW YORK,NY 10017. N SHORE UNIV HOSP,MANHASSET,NY 11030. HARVARD UNIV,SCH MED,BRIGHAM & WOMENS HOSP,DEPT SURG,BOSTON,MA 02115. NR 23 TC 11 Z9 11 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0883-2897 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD FEB PY 1992 VL 19 IS 2 BP 191 EP 199 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA GW472 UT WOS:A1992GW47200007 ER PT J AU GUYER, DR PULIAFITO, CA MONES, JM FRIEDMAN, E CHANG, W VERDOONER, SR AF GUYER, DR PULIAFITO, CA MONES, JM FRIEDMAN, E CHANG, W VERDOONER, SR TI DIGITAL INDOCYANINE-GREEN ANGIOGRAPHY IN CHORIORETINAL DISORDERS SO OPHTHALMOLOGY LA English DT Article ID INFRARED-ABSORPTION ANGIOGRAPHY; CHOROIDAL NEOVASCULARIZATION; CIRCULATION; FLOW AB The authors performed digital indocyanine-green angiography in 37 patients with chorioretinal disorders. Eighteen patients had choroidal neovascularization, 7 patients had atrophic age-related maculopathy, and 12 patients had uncommon choroidal and retinal disorders. A Topcon indocyanine-green camera was integrated with a digital (1024-line resolution) angiography system. Compared with conventional video or photographic indocyanine-green angiography, this technique offers enhanced image resolution, the possibility of direct qualitative comparison with fluorescein angiography, image archiving, hard-copy generation, and tracing capabilities to plan laser treatment strategies and monitor the adequacy of laser therapy after surgery. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,MORSE LASER RES LAB,BOSTON,MA 02114. OPHTHALM IMAGING SYST INC,SACRAMENTO,CA. FU NIGMS NIH HHS [5R01 GM35459-04]; PHS HHS [IRE 407471] NR 21 TC 116 Z9 118 U1 2 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD FEB PY 1992 VL 99 IS 2 BP 287 EP 291 PG 5 WC Ophthalmology SC Ophthalmology GA HC225 UT WOS:A1992HC22500027 PM 1553221 ER PT J AU MAIDEN, MFJ TANNER, A MOORE, WEC AF MAIDEN, MFJ TANNER, A MOORE, WEC TI IDENTIFICATION OF SELENOMONAS SPECIES BY WHOLE-GENOMIC DNA PROBES, SODIUM DODECYL SULFATE-POLYACRYLAMIDE GEL-ELECTROPHORESIS, BIOCHEMICAL TESTS AND CELLULAR FATTY-ACID ANALYSIS SO ORAL MICROBIOLOGY AND IMMUNOLOGY LA English DT Article DE WHOLE GENOMIC DNA PROBE; SDS-PAGE; CELLULAR FATTY ACID ANALYSIS; SELENOMONAS SPECIES AB Nonisotopic, whole-genomic DNA probes, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). biochemical tests in microtiter trays and cellular fatty acid (CFA) analysis were compared for the identification of 5 oral Selenomonas species. DNA probes were prepared by biotin-labeling DNA extracted from the type strains of Selenonionas noxia, Selenomonas flueggei, Selenomonas artemidis, Selenomonas infelix and Selenomonas sputigena. The probes were hybridized with DNA from 21 reference strains, 18 fresh isolates of Selenomonas species, and 21 strains of other oral gram-negative species. Target DNAs were obtained by in situ extraction of colonies blotted onto filter paper. Streptavidin-linked alkaline phosphatase was used to detect homologous reactions of probe and target DNA. Each Selenomonas species DNA probe reacted with reference strains of only that species. All Selenomonas strains that reacted with the DNA probe for a particular species gave similar biochemical test results. SDS-PAGE protein profiles, and CFA profiles to those of the type strain of the corresponding species. All the methods tested were useful for identifying the species. and all yielded similar identifications of the fresh isolates. The DNA probes. however, had the potential for identifying Selenomonas species directly from primary isolation plates or plaque samples. RP MAIDEN, MFJ (reprint author), FORSYTH DENT CTR,140 THE FENWAY,BOSTON,MA 02115, USA. FU NIDCR NIH HHS [DE03488] NR 0 TC 6 Z9 6 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0902-0055 J9 ORAL MICROBIOL IMMUN JI Oral Microbiol. Immunol. PD FEB PY 1992 VL 7 IS 1 BP 7 EP 13 DI 10.1111/j.1399-302X.1992.tb00012.x PG 7 WC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology SC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology GA HA532 UT WOS:A1992HA53200002 PM 1528628 ER PT J AU GUNARATNAM, M SMITH, GLF SOCRANSKY, SS SMITH, CM HAFFAJEE, AD AF GUNARATNAM, M SMITH, GLF SOCRANSKY, SS SMITH, CM HAFFAJEE, AD TI ENUMERATION OF SUBGINGIVAL SPECIES ON PRIMARY ISOLATION PLATES USING COLONY LIFTS SO ORAL MICROBIOLOGY AND IMMUNOLOGY LA English DT Article DE COLONY LIFT; SUBGINGIVAL MICROORGANISM; DIGOXIGENIN-LABELED DNA PROBE AB This study evaluated the feasibility of using a colony lift method and DNA probes to enumerate bacterial species cultured on primary isolation plates. Fourteen digoxigenin-labeled whole chromosomal DNA probes representing 12 subgingival species were validated by hybridization with colony lifts prepared from 249 reference strains of 51 species grown on Trypticase soy agar plates supplemented with 5% sheep blood. Colonies of reference strains were lifted onto Nytran filters from plates and treated to lyse cells, remove cellular proteins, denature and fix microbial DNA to the filters. Positive reactions were detected with an anti-digoxigenin antibody conjugated to alkaline phosphatase and revealed by bromo-chloro-indolyl phosphate and nitroblue tetrazolium. Cross-reactions were not observed for 13/14 probes, but 2 strains of Streptococcus mitis reacted with the probe to Streptococcus sanguis II. Subgingival plaque samples were taken by means of a sterile curette from mesiobuccal surfaces of teeth present in each of 26 subjects with differing periodontal disease states. Samples were dispersed, diluted, plated and incubated anaerobically for 7 d at 35-degrees-C. Colonies were lifted as described above. Filters were cut into sections and hybridized with the 14 digoxigenin-labeled DNA probes. The probes were used to enumerate the test species and the total number of isolates was determined in 711 plaque samples. The colony lift method and DNA probes provided a sensitive, economical and quantitative method for enumerating cultivable microbial species in subgingival plaque samples. In addition, the amplification provided by growing the organisms on agar plates facilitated determination of numbers of organisms in small plaque samples, such as those from healthy sites. RP GUNARATNAM, M (reprint author), FORSYTH DENT CTR,140 THE FENWAY,BOSTON,MA 02115, USA. FU NIDCR NIH HHS [DE02487, DE04881] NR 0 TC 46 Z9 48 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0902-0055 J9 ORAL MICROBIOL IMMUN JI Oral Microbiol. Immunol. PD FEB PY 1992 VL 7 IS 1 BP 14 EP 18 DI 10.1111/j.1399-302X.1992.tb00013.x PG 5 WC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology SC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology GA HA532 UT WOS:A1992HA53200003 PM 1528619 ER PT J AU HAFFAJEE, AD SOCRANSKY, SS AF HAFFAJEE, AD SOCRANSKY, SS TI EFFECT OF SAMPLING STRATEGY ON THE FALSE-NEGATIVE RATE FOR DETECTION OF SELECTED SUBGINGIVAL SPECIES SO ORAL MICROBIOLOGY AND IMMUNOLOGY LA English DT Note DE SAMPLING; SUBGINGIVAL SPECIES; PLAQUE; FALSE-NEGATIVE RATE AB Subgingival plaque samples were obtained from the mesial surface of each tooth (maximum 28 samples per subject) in 62 subjects with prior evidence of destructive periodontal disease. The resulting 1596 samples were evaluated for their content of 14 selected taxa using a colony lift method and DNA probes. The present investigation compared the ability of 6 sampling strategies to detect a species known to be present in a subject as determined by the 28-site sampling procedure. On average, a species was not detected in 68% of the positive subjects if only the upper right first molar was sampled; 55% of subjects if both upper first molars were sampled; 36% of subjects if the 4 first molars were sampled; 28% of subjects if the 6 Ramfjord teeth were sampled; 60% of subjects if the deepest pocket was sampled and 25% of subjects if the 4 deepest pockets were sampled. The error rate was greatest for species that were infrequently detected in plaque samples such as Actinobacillus actinomycetemcomitans serotype b. This species was not detected in 49% of positive subjects, when the 6 Ramfjord teeth were sampled and 38% of subjects when the 4 deepest pockets were sampled. The data indicated that multiple plaque samples are needed to minimize false-negative rates. RP HAFFAJEE, AD (reprint author), FORSYTH DENT CTR,140 THE FENWAY,BOSTON,MA 02115, USA. FU NIDCR NIH HHS [DE-02847, DE-04881] NR 0 TC 54 Z9 56 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0902-0055 J9 ORAL MICROBIOL IMMUN JI Oral Microbiol. Immunol. PD FEB PY 1992 VL 7 IS 1 BP 57 EP 59 DI 10.1111/j.1399-302X.1992.tb00022.x PG 3 WC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology SC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology GA HA532 UT WOS:A1992HA53200012 PM 1528626 ER PT J AU TAKAHASHI, LK HAGLIN, C KALIN, NH AF TAKAHASHI, LK HAGLIN, C KALIN, NH TI PRENATAL STRESS POTENTIATES STRESS-INDUCED BEHAVIOR AND REDUCES THE PROPENSITY TO PLAY IN JUVENILE RATS SO PHYSIOLOGY & BEHAVIOR LA English DT Article DE PRENATAL STRESS; JUVENILE RATS; SOCIAL PLAY; FREEZING; STRESS; PITUITARY-ADRENAL HORMONES; DEFENSIVE BEHAVIOR ID CORTICOSTERONE LEVELS; PLASMA TESTOSTERONE; FEMALE RATS; CORTICOTROPIN; MALES AB We examined the hypothesis that prenatal stress potentiates defensive responsiveness which may interfere with the expression of appetitive behavioral activities. Sibling pairs of prenatally stressed and control juvenile rats were placed in an unfamiliar environment. The latency and frequency of social play, a sought-after activity of juvenile rats, were measured on 4 successive days beginning at 25 days of age. However, on Day 27, electric foot shock was administered in order to assess directly whether exposure to threat facilitates the occurrence of defensive behavior in prenatally stressed rats. In addition, to determine whether previous exposure to threat produces long-term suppressive effects on play, rats were retested on Day 28 in the absence of shock. Throughout the testing period, the latency to play, as indicated by one rat pouncing on the opponent, was significantly higher in prenatally stressed than control rats. The frequency of play, however, did not differ reliably between groups. These data suggest that prenatally stressed rats take longer to adapt to the test situation before initiating play than control rats. In both groups, exposure to shock on Day 27 significantly increased the latency to play. More importantly, prenatally stressed rats exhibited significantly higher durations of defensive freezing than control animals. When retested on Day 28, however, the duration of freezing declined significantly and no longer differed between groups. Data appear to support the hypothesis that prenatally stressed juvenile rats are responsive to stress which may modulate the inclination to exhibit social behavior. C1 WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI 53705. RP TAKAHASHI, LK (reprint author), UNIV WISCONSIN,SCH MED,DEPT PSYCHIAT,600 HIGHLAND AVE,MADISON,WI 53792, USA. FU NIMH NIH HHS [MH-43986] NR 29 TC 83 Z9 84 U1 2 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0031-9384 J9 PHYSIOL BEHAV JI Physiol. Behav. PD FEB PY 1992 VL 51 IS 2 BP 319 EP 323 DI 10.1016/0031-9384(92)90147-T PG 5 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA HA082 UT WOS:A1992HA08200015 PM 1313590 ER PT J AU SUN, TP GOODMAN, HM AUSUBEL, FM AF SUN, TP GOODMAN, HM AUSUBEL, FM TI CLONING THE ARABIDOPSIS GA1 LOCUS BY GENOMIC SUBTRACTION SO PLANT CELL LA English DT Article ID THALIANA L HEYNH; ENDOGENOUS GIBBERELLINS; LINKAGE MAP; DNA; HYBRIDIZATION; ELEMENT; TOBACCO; GENE; TRANSFORMATION; BIOSYNTHESIS AB Arabidopsis thaliana ga1 mutants are gibberellin-responsive dwarfs. We used the genomic subtraction technique to clone DNA sequences that are present in wild-type Arabidopsis (ecotype Landsberg erecta, Ler) but are missing in a presumptive ga1 deletion mutant, ga1-3. The cloned sequences correspond to a 5.0-kb deletion in the ga1-3 genome. Three lines of evidence indicated that the 5.0-kb deletion in the ga1-3 mutant is located at the GA1 locus. First, restriction fragment length polymorphism mapping showed that DNA sequences within the 5.0-kb deletion map to the GA1 locus. Second, cosmid clones that contain wild-type DNA inserts spanning the deletion in ga1-3 complemented the dwarf phenotype when integrated into the ga1-3 genome by Agrobacterium tumefaciens-mediated transformation. Third, we identified molecular lesions in four additional ga1 alleles within the 5.0-kb region deleted in mutant ga1-3. One of these lesions is a large insertion or inversion located within the most distal intron encoded by the GA1 locus. The three other lesions are all single base changes located within the two most distal exons. RNA gel blot analysis indicated that the GA1 locus encodes a 2.8-kb mRNA. We calculated a recombination rate of 10(-5) cM per nucleotide for the GA1 region of the Arabidopsis genome. C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. NR 39 TC 215 Z9 237 U1 1 U2 12 PU AMER SOC PLANT PHYSIOLOGISTS PI ROCKVILLE PA 15501 MONONA DRIVE, ROCKVILLE, MD 20855 SN 1040-4651 J9 PLANT CELL JI Plant Cell PD FEB PY 1992 VL 4 IS 2 BP 119 EP 128 PG 10 WC Biochemistry & Molecular Biology; Plant Sciences; Cell Biology SC Biochemistry & Molecular Biology; Plant Sciences; Cell Biology GA HG524 UT WOS:A1992HG52400004 ER PT J AU MAY, JW LARGIS, JK KATZ, AR AF MAY, JW LARGIS, JK KATZ, AR TI AN ABSORBABLE CATHETER SYSTEM FOR USE IN MICROVASCULAR AND PERIPHERAL VASCULAR-SURGERY - AN EXPERIMENTAL-STUDY IN THE CANINE SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID TISSUE PLASMINOGEN-ACTIVATOR; THERAPY; HEPARIN; STREPTOKINASE; THROMBOSIS; SALVAGE; FLAP AB An absorbable catheter for use in regional anticoagulation in microvascular and peripheral vascular surgery was studied in 20 sites in 10 adult beagle dogs to answer three questions: (1) Could the polyglycolic acid and trimethylene carbonate catheter withstand intraarterial pressures of infusion and completely absorb over a predictable time interval? (2) Could the catheter be filled with heparin and maintain patency for reuse after a 24-hour interval? (3) Could the catheter be placed in a side branch of a major artery and, after catheter dissolution, maintain long-term patency of the primary feeding artery? The catheters were completely absorbed from 24 to 34 weeks following implantation. The catheters were able to withstand intraarterial pressures, and no evidence of significant thrombosis of the primary feeding artery was seen in any animal studied. No complications of catheter leak, hematoma formation within the catheter placement sites, or sepsis were noted in any of the 20 catheter sites studied. C1 MASSACHUSETTS GEN HOSP,DEPT GEN SURG,HAND SURG SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. AMER CYANAMID CO,DIV MED DEVICE RES,WAYNE,NJ 07470. RP MAY, JW (reprint author), MASSACHUSETTS GEN HOSP,DIV PLAST & RECONSTRUCT SURG,BOSTON,MA 02114, USA. NR 21 TC 2 Z9 2 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD FEB PY 1992 VL 89 IS 2 BP 299 EP 305 DI 10.1097/00006534-199202000-00016 PG 7 WC Surgery SC Surgery GA HB648 UT WOS:A1992HB64800016 PM 1732899 ER PT J AU HU, H AF HU, H TI TOXIC WEAPONS, EPIDEMIOLOGY, AND HUMAN-RIGHTS SO POLITICS AND THE LIFE SCIENCES LA English DT Article C1 BRIGHAM & WOMENS HOSP, BOSTON, MA 02115 USA. RP HARVARD UNIV, SCH MED, DANA FARBER CANC INST, SCH PUBL HLTH, 180 LONGWOOD AVE, BOSTON, MA 02115 USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU BEECH TREE PUBLISHING PI GUILDFORD PA 10 WATFORD CLOSE,, GUILDFORD GU1 2EP, SURREY, ENGLAND SN 0730-9384 J9 POLIT LIFE SCI JI Polit. Life Sci. PD FEB PY 1992 VL 11 IS 1 BP 24 EP 26 PG 3 WC Biology; History & Philosophy Of Science; Social Issues SC Life Sciences & Biomedicine - Other Topics; History & Philosophy of Science; Social Issues GA HQ764 UT WOS:A1992HQ76400004 ER PT J AU KAHN, RS DAVIDSON, M HIRSCHOWITZ, J STERN, RG DAVIS, BM GABRIEL, S MOORE, C DAVIS, KL AF KAHN, RS DAVIDSON, M HIRSCHOWITZ, J STERN, RG DAVIS, BM GABRIEL, S MOORE, C DAVIS, KL TI NOCTURNAL GROWTH-HORMONE SECRETION IN SCHIZOPHRENIC-PATIENTS AND HEALTHY-SUBJECTS SO PSYCHIATRY RESEARCH LA English DT Article DE PSYCHOENDOCRINOLOGY; HORMONES; DOPAMINE; SEROTONIN ID SLOW-WAVE SLEEP; GH RELEASE; SOMATOSTATIN; SEROTONIN; DOPAMINE; HUMANS AB Plasma growth hormone concentrations were measured at hourly intervals between 10 p.m. and 8 a.m. the next morning in 15 drug-free chronic schizophrenic male inpatients and 14 healthy males. Growth hormone secretion was significantly lower in the patients as compared with the controls. Growth hormone release peaked around 1 a.m. in the controls, but a growth hormone peak was absent in the patient group. Increased dopamine activity, increased serotonin activity, or both could explain the absence of a nocturnal growth hormone surge in the schizophrenic patients. C1 BRONX VET ADM MED CTR,SERV PSYCHIAT,BRONX,NY 10468. CUNY MT SINAI SCH MED,NEUROENDOCRINOL LAB,NEW YORK,NY 10029. RP KAHN, RS (reprint author), BRONX VET ADM MED CTR,MT SINAI SCH MED,DEPT PSYCHIAT,CLIN RES UNIT,140 W KINGSBRIDGE RD,BRONX,NY 10468, USA. FU NIMH NIH HHS [R01 MH-37922-07] NR 27 TC 12 Z9 12 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD FEB PY 1992 VL 41 IS 2 BP 155 EP 161 DI 10.1016/0165-1781(92)90107-E PG 7 WC Psychiatry SC Psychiatry GA HJ675 UT WOS:A1992HJ67500007 PM 1574542 ER PT J AU FUTTERMAN, AD KEMENY, ME SHAPIRO, D POLONSKY, W FAHEY, JL AF FUTTERMAN, AD KEMENY, ME SHAPIRO, D POLONSKY, W FAHEY, JL TI IMMUNOLOGICAL VARIABILITY ASSOCIATED WITH EXPERIMENTALLY-INDUCED POSITIVE AND NEGATIVE AFFECTIVE STATES SO PSYCHOLOGICAL MEDICINE LA English DT Note ID MAJOR DEPRESSIVE DISORDER; LYMPHOCYTE FUNCTION; IMMUNE FUNCTION; MOOD; RESPONSIVENESS; IMAGERY; SYSTEM; EVENTS AB Functional and phenotypic immunological parameters were examined immediately before, after, and 30 minutes after experimentally-induced short-term positive (happiness) and negative (anxiety, depression) affective states and a neutral state, in five healthy subjects. Results indicated that all affective states induced more immune fluctuations (regardless of the direction) than the neutral state. Furthermore, among the affective states, anxiety induced the most immunological variability and depression the least. C1 HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,BOSTON,MA 02115. UNIV CALIF LOS ANGELES,SCH MED,DEPT PSYCHOL MICROBIOL & IMMUNOL,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT PSYCHIAT & BEHAV SCI,LOS ANGELES,CA 90024. OI Collier, Ann/0000-0001-7627-5447 FU NIAID NIH HHS [AI15332] NR 25 TC 27 Z9 27 U1 2 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD FEB PY 1992 VL 22 IS 1 BP 231 EP 238 PG 8 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA HK687 UT WOS:A1992HK68700025 PM 1574560 ER PT J AU WATERS, GS CAPLAN, D LEONARD, C AF WATERS, GS CAPLAN, D LEONARD, C TI THE ROLE OF PHONOLOGY IN READING-COMPREHENSION - IMPLICATIONS OF THE EFFECTS OF HOMOPHONES ON PROCESSING SENTENCES WITH REFERENTIALLY DEPENDENT CATEGORIES SO QUARTERLY JOURNAL OF EXPERIMENTAL PSYCHOLOGY SECTION A-HUMAN EXPERIMENTAL PSYCHOLOGY LA English DT Article ID SHORT-TERM-MEMORY; SPEECH; ANAPHORA; STORAGE; APHASIA; TASKS AB Two experiments investigated whether phonological representations are activated in the processing of anaphors in reading, and if they are, whether they play a role in the initial (first-pass) processing of the sentence or in review (second-pass) processes. Subjects made sentence acceptability judgements for sentences that contained either verb-gaps or indefinite and personal pronouns (overt anaphors). All sentences contained homophones. Half of the semantically unacceptable sentences were phonologically plausible if the homophones were inserted in the gap (e.g. The children sleighed in the winter, and the murderer in cold blood) or used as the referent of the pronoun (e.g. There is a sale on at the store and I have one at the boat). The other half of the semantically unacceptable sentences were phonologically implausible. In both experiments, half of the subjects saw the sentences under normal viewing conditions (whole sentence condition); for the other half of the subjects the words of each sentence were presented sequentially in the centre of the video screen at the rate of 250 msec/word (RSVP condition). A large proportion of the phonologically implausible sentences in the first experiment contained phrases in the second clause which resulted in semantic "oddities" (e.g. The children sleighed in the winter, and the murderer in the jar); the sentences in Experiment 2 did not contain such oddities. In Experiment 1 subjects made more errors on the phonologically plausible than implausible unacceptable sentences with both verb-gaps and pronouns in the whole sentence but not in the RSVP condition. There was no effect of phonological plausibility in Experiment 2. As the effect of phonological plausibility was only seen in the whole sentence condition, and only when the sentences contained semantic oddities, these data suggest that phonological information was not used in the first-pass analysis of the sentence, but rather when the subject re-read the sentence to find the referent. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. RP WATERS, GS (reprint author), MCGILL UNIV,SCH HUMAN COMMUN DISORDERS,1266 PINE AVE W,MONTREAL H3G 1A8,QUEBEC,CANADA. NR 46 TC 6 Z9 6 U1 0 U2 2 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE, EAST SUSSEX, ENGLAND BN3 2FA SN 0272-4987 J9 Q J EXP PSYCHOL-A JI Q. J. Exp. Psychol. Sect A-Hum. Exp. Psychol. PD FEB PY 1992 VL 44 IS 2 BP 343 EP 372 PG 30 WC Psychology; Psychology, Experimental SC Psychology GA HF609 UT WOS:A1992HF60900007 ER PT J AU MCLOUD, TC BOURGOUIN, PM GREENBERG, RW KOSIUK, JP TEMPLETON, PA SHEPARD, JAO MOORE, EH WAIN, JC MATHISEN, DJ GRILLO, HC AF MCLOUD, TC BOURGOUIN, PM GREENBERG, RW KOSIUK, JP TEMPLETON, PA SHEPARD, JAO MOORE, EH WAIN, JC MATHISEN, DJ GRILLO, HC TI BRONCHOGENIC-CARCINOMA - ANALYSIS OF STAGING IN THE MEDIASTINUM WITH CT BY CORRELATIVE LYMPH-NODE MAPPING AND SAMPLING SO RADIOLOGY LA English DT Article DE LYMPHATIC SYSTEM, NEOPLASMS; MEDIASTINUM; MEDIASTINUM, NEOPLASMS ID CELL LUNG-CANCER; COMPUTED-TOMOGRAPHY; PREOPERATIVE EVALUATION; RADIOGRAPHY; METASTASES AB One hundred forty-three patients with bronchogenic carcinoma were studied prospectively with computed tomography (CT) to determine the accuracy of CT in the evaluation of mediastinal nodal metastases. Mediastinal lymph nodes were localized according to the lymph node mapping scheme of the American Thoracic Society and were considered abnormal if they exceeded 1 cm in short-axis diameter. All patients underwent surgical staging, which consisted of either mediastinoscopy alone or mediastinoscopy and thoracotomy. At the time of surgical staging, all accessible nodes were either removed or sampled. The sensitivity of CT for mediastinal nodes on a per-patient basis was 64%, with a specificity of 62%. The sensitivity of CT for individual nodal stations involved with tumor was only 44%. The presence of obstructive pneumonitis did not appreciably alter the sensitivity of CT, but the specificity was lower (43%). The likelihood of metastases increased with lymph node size; however, seven of 19 (37%) lymph nodes that measured 2-4 cm in short-axis diameter were hyperplastic and did not contain metastases. The relative insensitivity of CT makes formal nodal sampling at the time of mediastinoscopy or thoractomy essential to detect lymph node metastases. C1 MASSACHUSETTS GEN HOSP, DEPT THORAC SURG, BOSTON, MA 02114 USA. RP MASSACHUSETTS GEN HOSP, DEPT RADIOL, BOSTON, MA 02114 USA. NR 26 TC 370 Z9 387 U1 0 U2 3 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD FEB PY 1992 VL 182 IS 2 BP 319 EP 323 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA HA586 UT WOS:A1992HA58600007 PM 1732943 ER PT J AU WEISSLEDER, R LEE, AS KHAW, BA SHEN, T BRADY, TJ AF WEISSLEDER, R LEE, AS KHAW, BA SHEN, T BRADY, TJ TI ANTIMYOSIN-LABELED MONOCRYSTALLINE IRON-OXIDE ALLOWS DETECTION OF MYOCARDIAL INFARCT - MR ANTIBODY IMAGING SO RADIOLOGY LA English DT Article DE HEART, MR; IRON; MAGNETIC RESONANCE (MR), ANTIBODY IMAGING; MYOCARDIUM, INFARCTION; MYOCARDIUM, MR ID MONOCLONAL-ANTIBODY; CONTRAST AGENTS; CELLS; SEPARATION; PARTICLES AB The synthesis and in vivo antigen targeting of a novel iron oxide compound were studied. A monocrystalline iron oxide nanoparticle (MION) was synthesized that contains a small (mean diameter, 2.9 nm +/- 0.9) single crystal core, passes through capillary membranes, and exhibits superpara-magnetism. The MION was attached to antimyosin Fab (R11D10) and used for immunospecific magnetic resonance (MR) imaging of cardiac infarcts. One hour after intravenous administration of MION-R11D10 in rats (100-mu-mol/kg), a marked decrease in the signal intensity of infarcted myocardium was observed. Immunohistochemical correlation confirmed the specific binding of the immunoconjugate to infarcted, but not to normal, myocardium. No decrease in cardiac signal intensity was observed when unconjugated MION was administered intravenously. The results indicate the feasibility of immunospecific MR imaging in living organisms. C1 HARVARD UNIV,MED SCH,BOSTON,MA 02129. RP WEISSLEDER, R (reprint author), MASSACHUSETTS GEN HOSP,CTR MGH NMR,DEPT RADIOL,13TH ST,BLDG 149,BOSTON,MA 02129, USA. NR 19 TC 128 Z9 131 U1 0 U2 8 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD FEB PY 1992 VL 182 IS 2 BP 381 EP 385 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA HA586 UT WOS:A1992HA58600018 PM 1732953 ER PT J AU JOHNSON, LA HOPPEL, BE GERARD, EL MILLER, SPF DOPPELT, SH ZIRZOW, GC ROSENTHAL, DI DAMBROSIA, JM HILL, SC BRADY, RO ROSEN, BR BARTON, NW AF JOHNSON, LA HOPPEL, BE GERARD, EL MILLER, SPF DOPPELT, SH ZIRZOW, GC ROSENTHAL, DI DAMBROSIA, JM HILL, SC BRADY, RO ROSEN, BR BARTON, NW TI QUANTITATIVE CHEMICAL-SHIFT IMAGING OF VERTEBRAL BONE-MARROW IN PATIENTS WITH GAUCHER DISEASE SO RADIOLOGY LA English DT Article DE BONES, PRIMARY METABOLIC ABNORMALITIES; BONE MARROW, MR; GAUCHER DISEASE; MAGNETIC RESONANCE (MR), CHEMICAL SHIFT ID MAGNETIC-RESONANCE; PROTON; INVOLVEMENT; DISORDERS; CT AB To evaluate extent of bone marrow involvement and disease severity in Gaucher patients, results of modified Dixon quantitative chemical shift imaging (QCSI) of the lumbar spine were correlated with quantitative analysis of marrow triglycerides and glucocerebrosides and with quantitative determination of splenic volume at magnetic resonance (MR) imaging. High-field-strength MR spectra of surgical marrow specimens were dominated by a single fat and a water peak, validating use of QCSI. QCSI showed average vertebral marrow fat fractions of 10% +/- 8 in Gaucher patients (normal adult averages, 29% +/- 6). Relaxation times for lipid was water approximated normal averages; bulk T1 values were significantly longer, reflecting decreased marrow fat. Glucocerebroside concentrations were higher in Gaucher marrow and inversely correlated with triglyceride concentrations. Extent of marrow infiltration determined by fat fraction measurements correlated with disease severity measured by splenic enlargement. These results show that as Gaucher cells infiltrate bone marrow and displace normal marrow adipocytes, bulk T1 increases due to the higher T1 of water compared with that of fat. QCSI provides a sensitive, noninvasive technique for evaluating bone marrow involvement in Gaucher disease. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,CTR MGH NMR,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,DEPT ORTHOPED SURG,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CTR AMBULATORY CARE,BOSTON,MA 02114. MIT,CAMBRIDGE,MA 02139. NINCDS,BETHESDA,MD 20892. NIH,DEPT DIAGNOST RADIOL,BETHESDA,MD 20892. FU NCI NIH HHS [R01-CA-40303] NR 39 TC 75 Z9 75 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD FEB PY 1992 VL 182 IS 2 BP 451 EP 455 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA HA586 UT WOS:A1992HA58600030 PM 1732964 ER PT J AU REIMER, P WEISSLEDER, R WITTENBERG, J BRADY, TJ AF REIMER, P WEISSLEDER, R WITTENBERG, J BRADY, TJ TI RECEPTOR-DIRECTED CONTRAST AGENTS FOR MR IMAGING - PRECLINICAL EVALUATION WITH AFFINITY ASSAYS SO RADIOLOGY LA English DT Article DE LIVER, MR; LIVER NEOPLASMS, MR; MAGNETIC RESONANCE (MR), CONTRAST ENHANCEMENT ID SUPERPARAMAGNETIC IRON-OXIDE; ASIALOGLYCOPROTEIN RECEPTORS; CARCINOMA AB In this study, the target-specific behavior of magnetic resonance (MR) imaging contrast agents directed at human hepatic asialoglycoprotein (ASG) receptors was evaluated in vitro with use of two novel assays: relaxation time measurements of incubated human cell membrane solutions and iron staining of biopsy samples. Specific uptake of ASG receptor-directed agents was demonstrated in human samples of normal liver tissue, areas of hepatitis, regenerating nodules, areas of focal nodular hyperplasia, and hepatic adenomas. A conventional iron oxide preparation not directed at ASG receptors failed to demonstrate specific uptake in these tissues. Attachment of the ASG receptor-directed agents was competitively blocked with a receptor agonist (D(+)-galactose) in these tissues. No attachment of conventional or receptor agents was seen in areas of hepatocellular carcinoma, cholangiocarcinoma, or liver metastases. The studies indicate that in vitro receptor assays are useful in predicting the affinity of new receptor-directed MR imaging contrast agents in human tissue prior to clinical trials. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,CTR MGH NMR,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02129. FU NCI NIH HHS [CA 48279] NR 12 TC 33 Z9 35 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 FEB PY 1992 VL 182 IS 2 BP 565 EP 569 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA HA586 UT WOS:A1992HA58600049 PM 1732982 ER PT J AU RAHMAN, MU HUDSON, AP SCHUMACHER, HR AF RAHMAN, MU HUDSON, AP SCHUMACHER, HR TI CHLAMYDIA AND REITERS-SYNDROME (REACTIVE ARTHRITIS) SO RHEUMATIC DISEASE CLINICS OF NORTH AMERICA LA English DT Article ID UROGENITAL INVOLVEMENTS; TRACHOMATIS INFECTIONS; BORRELIA-BURGDORFERI; SEXUAL PARTNERS; DISEASE; EPIDEMIOLOGY; CELLS; MICE; HYBRIDIZATION; PATHOGENESIS C1 MED COLL PENN,DEPT MICROBIOL & IMMUNOL,PHILADELPHIA,PA 19129. UNIV PENN,SCH MED,PHILADELPHIA,PA 19104. DEPT VET AFFAIRS MED CTR,CTR ARTHRITIS IMMUNOL,PHILADELPHIA,PA. DEPT VET AFFAIRS MED CTR,RES SERV,PHILADELPHIA,PA. NR 88 TC 36 Z9 38 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-857X J9 RHEUM DIS CLIN N AM JI Rheum. Dis. Clin. North Am. PD FEB PY 1992 VL 18 IS 1 BP 67 EP 79 PG 13 WC Rheumatology SC Rheumatology GA LA276 UT WOS:A1992LA27600007 PM 1561410 ER PT J AU RAHMAN, MU SCHUMACHER, HR HUDSON, AP AF RAHMAN, MU SCHUMACHER, HR HUDSON, AP TI RECURRENT ARTHRITIS IN REITERS-SYNDROME - A FUNCTION OF INAPPARENT CHLAMYDIAL INFECTION OF THE SYNOVIUM SO SEMINARS IN ARTHRITIS AND RHEUMATISM LA English DT Article DE INAPPARENT INFECTION; CHLAMYDIA; SYNOVIUM; REITERS SYNDROME ID REACTIVE ARTHRITIS; UROGENITAL INVOLVEMENTS; SEXUAL PARTNERS; TRACHOMATIS; DISEASE; EPIDEMIOLOGY; PATHOGENESIS; PERSISTENT; DISORDERS; FEATURES C1 UNIV PENN,SCH MED,UNIV & WOODLAND AVE,PHILADELPHIA,PA 19104. DEPT VET AFFAIRS MED CTR 151K,CTR ARTHRITIS IMMUNOL,PHILADELPHIA,PA 19104. MED COLL PENN,DEPT MICROBIOL & IMMUNOL,PHILADELPHIA,PA 19129. DEPT VET AFFAIRS MED CTR,RES SERV,PHILADELPHIA,PA 19104. FU NCRR NIH HHS [RR00040] NR 70 TC 24 Z9 24 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0049-0172 J9 SEMIN ARTHRITIS RHEU JI Semin. Arthritis Rheum. PD FEB PY 1992 VL 21 IS 4 BP 259 EP 266 DI 10.1016/0049-0172(92)90057-K PG 8 WC Rheumatology SC Rheumatology GA HE979 UT WOS:A1992HE97900008 PM 1570519 ER PT J AU HALEY, EC KASSELL, NF TORNER, JC WEIR, B TUCKER, WS PEERLESS, SJ WISOFF, H CARTER, LP RATCHESON, R SPETZLER, R FRIEDMAN, A CAMPBELL, R SMITH, R HEROS, R TEW, J FLAMM, E MILLER, C SIMEONE, F MARSHALL, LF PITTS, L DAY, A CHOU, SN HOFF, J YONAS, H GINNOTTA, S RAY, M SAMSON, D MEACHAM, W GRUBB, R AF HALEY, EC KASSELL, NF TORNER, JC WEIR, B TUCKER, WS PEERLESS, SJ WISOFF, H CARTER, LP RATCHESON, R SPETZLER, R FRIEDMAN, A CAMPBELL, R SMITH, R HEROS, R TEW, J FLAMM, E MILLER, C SIMEONE, F MARSHALL, LF PITTS, L DAY, A CHOU, SN HOFF, J YONAS, H GINNOTTA, S RAY, M SAMSON, D MEACHAM, W GRUBB, R TI THE INTERNATIONAL COOPERATIVE STUDY ON THE TIMING OF ANEURYSM SURGERY - THE NORTH-AMERICAN EXPERIENCE SO STROKE LA English DT Article DE CEREBRAL ANEURYSM; SUBARACHNOID HEMORRHAGE; CLINICAL TRIALS ID SUBARACHNOID HEMORRHAGE; MANAGEMENT; VASOSPASM AB Background and Purpose: The timing of aneurysm surgery after subarachnoid hemorrhage is a major neurosurgical controversy addressed by the International Cooperative Study on the Timing of Aneurysm Surgery (1980-1983). The present report examines the results of this trial in the subgroup of patients admitted to North American centers. Methods: The method of study was a large, multicenter, prospective, epidemiological survey. Neurosurgeons were required to indicate prospectively the interval to planned aneurysm surgery at the time of patient admission. Outcome at 6 months was determined by a blinded evaluator, and overall management results were analyzed by the planned surgical interval. Results: Seven hundred seventy-two (21.9% of the total study population) patients admitted from days 0 to 3 after subarachnoid hemorrhage were accrued in North American centers. Overall outcome in patients planned for surgery in days 0-3 was equivalent in terms of mortality (after adjustment for prognostic variables) to patients planned for days 11-32, but the early patients had significantly improved rates of good recovery (70.9% versus 61.7%, p < 0.01). Patients planned for surgery during the days 7-10 interval had nearly twice the mortality of patients in the other intervals. Conclusions: In contrast to the results from the overall trial, which found no difference between early and delayed surgery, results were best in North American centers when surgery was planned between days 0 and 3 after subarachnoid hemorrhage. These findings argue strongly for early diagnosis and referral for surgical intervention of North American patients suspected of having a ruptured cerebral aneurysm. C1 UNIV VIRGINIA,MED CTR,SCH MED,DEPT NEUROL,CHARLOTTESVILLE,VA 22901. UNIV VIRGINIA,MED CTR,SCH MED,DEPT NEUROL SURG,CHARLOTTESVILLE,VA 22901. UNIV ALBERTA,EDMONTON T6G 2E1,ALBERTA,CANADA. UNIV TORONTO,TORONTO M5S 1A1,ONTARIO,CANADA. UNIV WESTERN ONTARIO,LONDON N6A 3K7,ONTARIO,CANADA. YESHIVA UNIV ALBERT EINSTEIN COLL MED,BRONX,NY 10461. BARROW NEUROL INST,PHOENIX,AZ. CASE WESTERN INST,CLEVELAND,OH. DUKE UNIV,DURHAM,NC 27706. INDIANA UNIV,INDIANAPOLIS,IN 46204. LOUISIANA STATE UNIV,NEW ORLEANS,LA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. MAYFIELD NEUROSURG INST,CINCINNATI,OH. NYU MED CTR,NEW YORK,NY 10016. OHIO STATE UNIV,COLUMBUS,OH 43210. PENN HOSP,PHILADELPHIA,PA 19107. UNIV CALIF SAN DIEGO,MED CTR,SAN DIEGO,CA 92103. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. UNIV FLORIDA,GAINESVILLE,FL 32611. UNIV IOWA,IOWA CITY,IA 52242. UNIV MINNESOTA,MINNEAPOLIS,MN 55455. UNIV MICHIGAN,ANN ARBOR,MI 48109. UNIV MISSISSIPPI,JACKSON,MS 39216. UNIV PITTSBURGH,PITTSBURGH,PA 15260. UNIV SO CALIF,LOS ANGELES,CA 90089. UNIV TENNESSEE CTR HLTH SCI,MEMPHIS,TN 38163. UNIV TEXAS,HLTH SCI CTR,DALLAS,TX 75235. VANDERBILT UNIV,NASHVILLE,TN 37240. WASHINGTON UNIV,SCH MED,ST LOUIS,MO 63110. FU NINDS NIH HHS [NS-15940] NR 19 TC 181 Z9 190 U1 0 U2 5 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 1992 VL 23 IS 2 BP 205 EP 214 PG 10 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA HE880 UT WOS:A1992HE88000008 PM 1561649 ER PT J AU OGILVY, CS CHAPMAN, PH MCGRAIL, K AF OGILVY, CS CHAPMAN, PH MCGRAIL, K TI SUBDURAL EMPYEMA COMPLICATING BACTERIAL-MENINGITIS IN A CHILD - ENHANCEMENT OF MEMBRANES WITH GADOLINIUM ON MAGNETIC-RESONANCE-IMAGING IN A PATIENT WITHOUT ENHANCEMENT ON COMPUTED-TOMOGRAPHY SO SURGICAL NEUROLOGY LA English DT Article DE MENINGITIS; SUBDURAL EMPYEMA; SUBDURAL EFFUSION; MAGNETIC RESONANCE IMAGING ID BRAIN-ABSCESS; DIAGNOSIS; CT AB Subdural empyema is a known yet infrequent complication of bacterial meningitis. Subdural effusions occur frequently with meningitis in children and usually resolve spontaneously or with subdural raps. Subdural empyema should be suspected when a patient fails to respond to antibiotic therapy or worsens neurologically. Computed tomography (CT) scans with contrast often show enhancement of subdural collections when an empyema exists. However, this is not true all of the time. We present a case of subdural empyema complicating bacterial meningitis in a 4 month old in which CT enhancement was not present yet magnetic resonance imaging (MRI) scans with gadolinium demonstrated intense enhancement. For comparison, we present a second case of a child with sterile subdural effusions due to meningitis that demonstrates an absence of contrast enhancement on MRI studies. MRI scans with contrast may offer a more sensitive means of making an early diagnosis of subdural empyema. RP OGILVY, CS (reprint author), MASSACHUSETTS GEN HOSP,NEUROSURG SERV,FRUIT ST,BOSTON,MA 02114, USA. NR 10 TC 9 Z9 9 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0090-3019 J9 SURG NEUROL JI Surg. Neurol. PD FEB PY 1992 VL 37 IS 2 BP 138 EP 141 DI 10.1016/0090-3019(92)90190-X PG 4 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA HB604 UT WOS:A1992HB60400010 PM 1347665 ER PT J AU AWDEH, ZL ALPER, CA FICI, D EYNON, E BISHARA, A YUNIS, EJ AF AWDEH, ZL ALPER, CA FICI, D EYNON, E BISHARA, A YUNIS, EJ TI PREDICTABILITY OF ALLOREACTIVITY AMONG UNRELATED INDIVIDUALS SO TISSUE ANTIGENS LA English DT Article DE PRIMARY MIXED LYMPHOCYTE REACTION; ALLOREACTIVITY AMONG UNRELATED INDIVIDUALS; HLA-DR MATCHING; EXTENDED HAPLOTYPE MATCHING ID MAJOR HISTOCOMPATIBILITY COMPLEX; INHERITED STRUCTURAL POLYMORPHISM; MIXED-LYMPHOCYTE CULTURE; HLA-IDENTICAL SIBLINGS; MARROW TRANSPLANTATION; EXTENDED HAPLOTYPES; ELECTROPHORESIS; DISEQUILIBRIUM; ASSIGNMENT; RESPONSES AB Extended haplotypes are specific HLA-B, BF, C2, C4A, C4B and DR allelic combinations that occur at high frequencies and show positive linkage disequilibrium among these highly polymorphic MHC markers. About 30% of all normal caucasian haplotypes are extended, and the matching of two extended haplotypes in unrelated individuals has been shown to match for the determinants of primary mixed lymphocyte reactivity (MLR-I). In this work we report that the matching of one extended haplotype and a serologically defined HLA-DR generic type on the second chromosome in unrelated individuals is associated with the absence of mixed lymphocyte reactivity in 15 to 30% of the cases studied. Our results suggest that, for those individuals who carry either one or two extended haplotypes, it is relatively easy to identify an unrelated MRI-I-matched subject. However, for individuals lacking at least one extended haplotype, it should be difficult to find an MLR-I-matched unrelated subject. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. AMER RED CROSS,BLOOD SERV,DEDHAM,MA. HADASSAH MED CTR,TISSUE TYPING UNIT,JERUSALEM,ISRAEL. RP AWDEH, ZL (reprint author), CTR BLOOD RES,800 HUNTINGTON AVE,BOSTON,MA 02115, USA. FU NHLBI NIH HHS [HL29583]; NIAID NIH HHS [AI14157]; NICHD NIH HHS [HD17461] NR 35 TC 10 Z9 10 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PD FEB PY 1992 VL 39 IS 2 BP 51 EP 57 DI 10.1111/j.1399-0039.1992.tb01907.x PG 7 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA HH641 UT WOS:A1992HH64100001 PM 1574798 ER PT J AU HAUG, CE JENKINS, RL ROHRER, RJ AUCHINCLOSS, H DELMONICO, FL FREEMAN, RB LEWIS, WD COSIMI, AB AF HAUG, CE JENKINS, RL ROHRER, RJ AUCHINCLOSS, H DELMONICO, FL FREEMAN, RB LEWIS, WD COSIMI, AB TI LIVER-TRANSPLANTATION FOR PRIMARY HEPATIC CANCER SO TRANSPLANTATION LA English DT Article; Proceedings Paper CT 17TH ANNUAL MEETING OF THE AMERICAN SOC OF TRANSPLANT SURGEONS CY MAY 29-31, 1991 CL CHICAGO, IL SP AMER SOC TRANSPLANT SURGEONS ID MALIGNANCY; EXPERIENCE; SURVIVAL; THERAPY AB Although early survival following transplantation for primary hepatic cancer is excellent, previously reported high recurrence rates have generally discouraged liver replacement for this indication. Since the inception of the Boston Center for Liver Transplantation (BCLT) in 1983, 33 of 383 (8.6%) liver allograft recipients have undergone orthotopic transplantation as definitive treatment for otherwise unresectable cancer. Diagnoses included hepatocellular carcinoma (HCCA) in 24 patients (73%), and cholangiocarcinoma (CHCA) in 9 patients (27%). Actuarial survival rates for patients with hepatocellular carcinoma were 71%, 56%, and 42% at 1, 2, and 3 years, respectively. The actuarial survival rates for patients with cholangiocarcinoma were 89% at 6 months, and 56% at 1, 2, and 3 years. Of the nine patients with cholangiocarcinoma, 56% (5/9) developed recurrent disease. Although this recurrence rate is disheartening, because of the lack of other morbidity, long-term survival in these patients is comparable to patients with HCCA. In contrast, recurrent hepatocellular carcinoma developed in 25% of recipients (5/20) who survived longer than 3 months posttransplantation. Other causes of death in patients with hepatocellular carcinoma included perioperative complications, 16.6% (4/24); sepsis, 8.3% (2/24); coronary artery disease, 4.2% (1/24); and lymphoma, 4.2% (1/24). Favorable prognostic factors included: primary tumor < 3 cm in size and absence of associated cirrhosis. These results emphasize that orthotopic liver transplantation can provide a long-term cure for approximately 50% of patients whose primary hepatic malignancy is unresectable by conventional procedures. C1 NEW ENGLAND MED CTR HOSP,DEPT SURG,BOSTON,MA 02111. NEW ENGLAND DEACONESS HOSP,DEPT SURG,BOSTON,MA 02215. RP HAUG, CE (reprint author), MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114, USA. NR 23 TC 108 Z9 109 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD FEB PY 1992 VL 53 IS 2 BP 376 EP 382 DI 10.1097/00007890-199202010-00021 PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA HD765 UT WOS:A1992HD76500021 PM 1310823 ER PT J AU SMITH, CV NAKAJIMA, K MIXON, A GUZZETTA, PC ROSENGARD, BR FISHBEIN, JM SACHS, DH AF SMITH, CV NAKAJIMA, K MIXON, A GUZZETTA, PC ROSENGARD, BR FISHBEIN, JM SACHS, DH TI SUCCESSFUL INDUCTION OF LONG-TERM SPECIFIC TOLERANCE TO FULLY ALLOGENEIC RENAL-ALLOGRAFTS IN MINIATURE SWINE SO TRANSPLANTATION LA English DT Article; Proceedings Paper CT 17TH ANNUAL MEETING OF THE AMERICAN SOC OF TRANSPLANT SURGEONS CY MAY 29-31, 1991 CL CHICAGO, IL SP AMER SOC TRANSPLANT SURGEONS ID BONE-MARROW TRANSPLANTATION; CLASS-II GENES; MAJOR HISTOCOMPATIBILITY COMPLEX; POSTTRANSPLANT ANTITHYMOCYTE GLOBULIN; RHESUS-MONKEYS; IMMUNOLOGICAL-UNRESPONSIVENESS; SKIN ALLOGRAFTS; INJECTED MICE; MHC ANTIGENS; SURVIVAL AB Major histocompatibility complex class II matching is of overwhelming importance for achieving tolerance to kidney transplants (KTX) in miniature swine. When class II antigens are matched, long-term specific tolerance across complete MHC class I antigen barriers can uniformly be induced by a 12-day perioperative course of cyclosporine. This same regimen is ineffective in fully MHC-mismatched combinations. We hypothesized that initial induction of tolerance to kidney donor class II antigens by bone marrow transplantation might allow tolerance to be induced to a subsequent fully allogeneic KTX in combination with CsA therapy. We report here the results of such fully allogeneic KTX performed in 4 recipients of prior single-haplotype class II-mismatched BMT. All animals received KTX from donors class II matched to the BMT donor and received a 12-day course of intravenous CsA (10 mg/kg/day). All four animals have maintained normal serum creatinine values (less than 2.0 mg/dl) for greater than 200 days posttransplant. Specific hyporesponsiveness to both BMT and KTX donor-type MHC antigens was found in mixed lymphocyte culture and cell-mediated lympholysis assays. Compared with third-party grafts, significantly prolonged survival of BMT donor-specific (P = 0.031) and KTX donor-specific (P = 0.031) skin grafts was observed. These results demonstrate that induction of tolerance to class II antigens by BMT allows a short course of CsA to induce specific tolerance to fully allogeneic renal allografts. C1 NCI,IMMUNOL BRANCH,TRANSPLANTAT BIOL SECT,BETHESDA,MD 20892. RP SMITH, CV (reprint author), MASSACHUSETTS GEN HOSP,TRANSPLANTAT BIOL RES CTR,MGH E,BLDG 149,13TH ST,BOSTON,MA 02114, USA. NR 51 TC 33 Z9 33 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD FEB PY 1992 VL 53 IS 2 BP 438 EP 444 PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA HD765 UT WOS:A1992HD76500033 PM 1531395 ER PT J AU SUCHER, NJ LIPTON, SA AF SUCHER, NJ LIPTON, SA TI A SLOWLY INACTIVATING K+ CURRENT IN RETINAL GANGLION-CELLS FROM POSTNATAL RAT SO VISUAL NEUROSCIENCE LA English DT Note DE RETINA; GANGLION CELLS; PATCH CLAMP; CELL CULTURE; RAT ID HIPPOCAMPAL-NEURONS; SYMPATHETIC NEURON; POTASSIUM CURRENTS; VOLTAGE-CLAMP; CHANNELS; CULTURE; ACETYLCHOLINE; CONDUCTANCES; RESPONSES; DIVERSITY AB The whole-cell configuration of the patch-clamp technique was used to study voltage-gated K+ conductances in retinal ganglion cells from postnatal rat. Retinal ganglion cells were fluorescently labeled in situ, dissociated from the retina, and maintained in culture. With physiological solutions in the bath and the pipette, depolarizing voltage steps from physiological holding potentials activated Na+-(I(Na)), Ca2+ (I(Ca)), and K+-currents studied previously in retinal ganglion cells. Here we report on a slowly decaying K+ current, not heretofore reported in rat. With 4-AP, TEA, and Co2+ in the bath, to block I(A), I(K), and I(K(Ca)), respectively, a slowly decaying outward current was activated from -80 mV by steps positive to -40 mV. This current was present in 92% of all ganglion cells tested (n = 83). It activated within 10 ms and inactivated with a voltage-independent time constant of about 70 ms at 35-degrees-C. Inactivation was voltage-dependent, half-maximal at -55 mV, and almost complete at 0 mV. The current was blocked by internal Cs+ and TEA, or by external application of 1 mM Ba2+, but not by 3 mM extracellular Co2+. The biophysical and pharmacological properties of this current are distinctly different from those of slowly inactivating K+ currents studied in other rat neurons. It was very similar, however, to a slowly inactivating K+ current previously reported in ganglion cells of tiger salamander retina. This last finding indicates conservation of a defined K+ channel type in functionally related cells in both lower vertebrates and mammals. C1 CHILDRENS HOSP MED CTR,DEPT NEUROL,CELLULAR & MOLEC NEUROSCI LAB,ENDERS BLDG,SUITE 361,BOSTON,MA 02115. BETH ISRAEL HOSP,BOSTON,MA 02215. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02115. OI Sucher, Nikolaus/0000-0001-6233-1612 FU NEI NIH HHS [R01 EY05477]; NICHD NIH HHS [HD06276] NR 28 TC 17 Z9 17 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0952-5238 J9 VISUAL NEUROSCI JI Visual Neurosci. PD FEB PY 1992 VL 8 IS 2 BP 171 EP 176 PG 6 WC Neurosciences; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA HB669 UT WOS:A1992HB66900010 PM 1558829 ER PT J AU FUSTER, V BADIMON, L BADIMON, JJ CHESEBRO, JH AF FUSTER, V BADIMON, L BADIMON, JJ CHESEBRO, JH TI MECHANISMS OF DISEASE - THE PATHOGENESIS OF CORONARY-ARTERY DISEASE AND THE ACUTE CORONARY SYNDROMES .2. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID ACUTE MYOCARDIAL-INFARCTION; PLASMINOGEN-ACTIVATOR INHIBITOR; MIDDLE-AGED MEN; VASCULAR ENDOTHELIAL-CELLS; GENERAL-POPULATION SAMPLE; CARDIOVASCULAR-DISEASE; HEART-DISEASE; PRIMARY-PREVENTION; RISK-FACTORS; FAMILIAL HYPERCHOLESTEROLEMIA C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. MAYO CLIN & MAYO GRAD SCH MED,ROCHESTER,MN 55901. MAYO CLIN & MAYO FDN,ROCHESTER,MN 55905. RP FUSTER, V (reprint author), MASSACHUSETTS GEN HOSP,CARDIAC UNIT,32 FRUIT ST,BOSTON,MA 02114, USA. RI BADIMON, LINA/O-4711-2014; Fuster, Valentin/H-4319-2015 OI BADIMON, LINA/0000-0002-9162-2459; Fuster, Valentin/0000-0002-9043-9986 NR 101 TC 1426 Z9 1466 U1 4 U2 27 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 JAN 30 PY 1992 VL 326 IS 5 BP 310 EP 318 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA HA991 UT WOS:A1992HA99100006 PM 1728735 ER PT J AU TEIXIDO, J PARKER, CM KASSNER, PD HEMLER, ME AF TEIXIDO, J PARKER, CM KASSNER, PD HEMLER, ME TI FUNCTIONAL AND STRUCTURAL-ANALYSIS OF VLA-4 INTEGRIN ALPHA-4-SUBUNIT CLEAVAGE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MONOCLONAL-ANTIBODY; ADHESION MECHANISM; CELL ATTACHMENT; PLATELET GPIIB; FIBRONECTIN; FAMILY; RECEPTORS; PROTEINS; LYMPHOCYTES; SUPERFAMILY AB The cell surface heterodimer VLA-4 (alpha-4-beta-1), a member of the integrin family of adhesion receptors, is involved in both cell-extracellular matrix and cell-cell adhesion. Unlike any other integrin alpha-subunit, the intact (150 kDa) alpha-4 subunit of VLA-4 can sometimes be cleaved into two noncovalently associated fragments (80 and 70 kDa). Using biosynthetic and mixing experiments, we found that human alpha-4 cleavage is a regulated, compartmentalized event, occurring soon after maturation of the beta-1-associated alpha-4 subunit. Cleavage of alpha-4, which is increased following T cell activation, has been suggested to correlate with altered VLA-4 functions. To address directly the functional importance of alpha-4 cleavage, we have studied VLA-4-mediated adhesion functions in cells expressing intact alpha-4 in comparison with cells expressing cleaved alpha-4. For this purpose, we first sequenced the N terminus of the endogenously produced 70-kDa alpha-4 fragment and identified the alpha-4 cleavage site between Lys557-Arg558 and Ser559. To abolish cleavage, we converted Arg558 to Leu or Lys557 to Gln by site-directed mutagenesis of the alpha-4 cDNA and then transfected both mutant and wild type alpha-4 cDNAs into VLA-4-negative K562 cells. Whereas transfection with wild type alpha-4 cDNA yielded predominantly cleaved alpha-4 subunit, the Leu558-alpha-4 yielded only intact alpha-4 subunit, and Gln557-alpha-4 yielded mostly intact alpha-4 subunit. Transfectants with the intact or the cleaved alpha-4 were equally capable of engaging in VLA-4-dependent adhesion to vascular cell adhesion molecule-1 and to the Hep II fragment of fibronectin (40 kDa) and aggregated equally well in response to anti-alpha-4 antibodies. Thus, cleavage of the alpha-4 subunit in these transfectants did not alter any of the known VLA-4-mediated adhesion functions. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR VIROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV IMMUNOCHEM,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT RHEUMATOL & IMMUNOL,BOSTON,MA 02115. RI Teixido, Joaquin/J-8543-2014 OI Teixido, Joaquin/0000-0002-3177-4151 FU NCI NIH HHS [CA42368]; NIAID NIH HHS [K11 AI00903] NR 48 TC 65 Z9 67 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 25 PY 1992 VL 267 IS 3 BP 1786 EP 1791 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HA485 UT WOS:A1992HA48500060 PM 1730718 ER PT J AU MCCAFFREY, PG JAIN, J JAMIESON, C SEN, R RAO, A AF MCCAFFREY, PG JAIN, J JAMIESON, C SEN, R RAO, A TI A T-CELL NUCLEAR FACTOR RESEMBLING NF-AT BINDS TO AN NF-KAPPA-B SITE AND TO THE CONSERVED LYMPHOKINE PROMOTER SEQUENCE CYTOKINE-1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LYMPHOCYTE-SPECIFIC FACTORS; STIMULATING FACTOR GENE; LONG TERMINAL REPEAT; RECEPTOR-ALPHA-GENE; DNA-BINDING; INTERLEUKIN-2 GENE; CYCLOSPORINE-A; REL ONCOGENE; TRANSCRIPTIONAL ACTIVATOR; MONOCLONAL-ANTIBODY AB Nuclear extracts from a nontransformed murine T lymphocyte clone contained two inducible factors that bound to a nuclear factor kappa-B (NF-kappa-B) site. One factor was NF-kappa-B, and the other was differentiated from NF-kappa-B by its mobility in the electrophoretic mobility shift assay and its lack of sensitivity to protein kinase C depletion. Competition and methylation interference assays showed that the binding site for the novel factor was limited to nucleotides in the 3' half of the kappa-B site. This part of the kappa-B site resembled sequences in the binding site for a second inducible nuclear factor of T cells, NF-AT, as well as a conserved sequence found in several lymphokine genes, termed "cytokine-1" (CK-1). Competition and methylation interference analysis showed that both NF-AT and CK-1 sequences bound a factor similar to the novel kappa-B-binding factor and that binding involved a four-nucleotide sequence (TTCC) that the kappa-B, CK-1, and NF-AT sites have in common. The complexes that form with each site have characteristics of NF-AT: they are induced upon T cell receptor stimulation, are sensitive to protein synthesis inhibitors and cyclosporin A, and are not sensitive to protein kinase C depletion. Thus, a factor or factors similar to NF-AT can bind to three distinct promoter sequences which occur commonly in several T cell activation genes. These results raise the possibility that related factors binding to kappa-B, CK-1, and NF-AT sequences could play a role in the coordinate induction of T cell activation genes. In addition, our results suggest that kappa-B and CK-1 sites represent potential cyclosporin-sensitive promoter elements by virtue of their ability to bind an NF-AT-like factor. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. BRANDEIS UNIV,ROSENSTIEL BASIC MED SCI RES CTR,DEPT BIOL,WALTHAM,MA 02254. RP MCCAFFREY, PG (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR VIROL,MAYER BLDG,ROOM 613,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA42471]; NIGMS NIH HHS [GM38925] NR 45 TC 89 Z9 89 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 25 PY 1992 VL 267 IS 3 BP 1864 EP 1871 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HA485 UT WOS:A1992HA48500073 PM 1730723 ER PT J AU BARSKY, AJ AF BARSKY, AJ TI PALPITATIONS, CARDIAC AWARENESS, AND PANIC DISORDER SO AMERICAN JOURNAL OF MEDICINE LA English DT Article; Proceedings Paper CT SYMP ON PANIC DISORDER : SOMATIZATION, MEDICAL UTILIZATION, AND TREATMENT CY MAY 31, 1991 CL SEATTLE, WA SP UPJOHN ID CORONARY-ARTERY DISEASE; SILENT MYOCARDIAL ISCHEMIA; HEART-RATE CONTROL; ANGINA-PECTORIS; CHEST PAIN; PERCEPTION; DEPRESSION; ANXIETY; SOMATIZATION; COMPLAINTS AB This article reviews and appraises a variety of studies on panic disorder, visceral sensitivity, and cardiac disease. The literature reviewed includes descriptive surveys, small-scale experimental manipulations, and clinical interventions. Instruments have included structured diagnostic interviews, clinical observation, self-report inventories, direct measures of perceptual sensitivity, and cognitive tests. The subjects in these studies have ranged from community residents to carefully defined samples of designated patients with psychiatric or cardiac disease. We then outline a prospective investigation to examine the prominence of palpitations in panic anxiety and speculate on the importance of sensitivity to cardiac sensation in several other clinical conditions characterized by marked discrepancies between cardiac activity and cardiac symptoms. C1 MASSACHUSETTS GEN HOSP,PRIMARY CARE PROGRAM,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. RP BARSKY, AJ (reprint author), MASSACHUSETTS GEN HOSP,PSYCHIAT SERV,WANG BLDG,ROOM 805,FRUIT ST,BOSTON,MA 02114, USA. FU NHLBI NIH HHS [HL43216] NR 35 TC 6 Z9 6 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 JAN 24 PY 1992 VL 92 SU 1A BP S31 EP S34 DI 10.1016/0002-9343(92)90134-W PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA HB549 UT WOS:A1992HB54900007 PM 1734732 ER PT J AU WALSH, C CEPKO, CL AF WALSH, C CEPKO, CL TI WIDESPREAD DISPERSION OF NEURONAL CLONES ACROSS FUNCTIONAL REGIONS OF THE CEREBRAL-CORTEX SO SCIENCE LA English DT Article ID MEDIATED GENE-TRANSFER; CELL LINEAGE; SOMATOSENSORY CORTEX; MIGRATION PATTERNS; CORTICAL BARRELS; NERVOUS-SYSTEM; RAT; RETROVIRUS; HINDBRAIN; NEOCORTEX AB The cerebral cortex of the mammalian brain has expanded rapidly during the course of evolution and acquired structurally distinguishable areas devoted to separate functions. In some brain regions, topographic restrictions to cell intermixing occur during embryonic development. As a means of examining experimentally whether such restrictions occur during formation of functional subdivisions in the rat neocortex, clonally related neocortical cells were marked by retroviral-mediated transfer of a histochemical marker gene. Clonal boundaries were determined by infection of the developing brain with a library of genetically distinct viruses and amplification of single viral genomes by the polymerase chain reaction. Many clonally related neurons in the cerebral cortex became widely dispersed across functional areas of the cortex. Specification of cortical areas therefore occurs after neurogenesis. C1 HARVARD UNIV,SCH MED,DEPT GENET,25 SHATTUCK ST,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. FU NINDS NIH HHS [NS 23021] NR 53 TC 397 Z9 401 U1 0 U2 5 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JAN 24 PY 1992 VL 255 IS 5043 BP 434 EP 440 DI 10.1126/science.1734520 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA HA590 UT WOS:A1992HA59000031 PM 1734520 ER PT J AU FUSTER, V BADIMON, L BADIMON, JJ CHESEBRO, JH AF FUSTER, V BADIMON, L BADIMON, JJ CHESEBRO, JH TI MECHANISMS OF DISEASE - THE PATHOGENESIS OF CORONARY-ARTERY DISEASE AND THE ACUTE CORONARY SYNDROMES .1. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID ACUTE MYOCARDIAL-INFARCTION; UNSTABLE ANGINA-PECTORIS; SMOOTH-MUSCLE CELLS; HUMAN ATHEROSCLEROTIC PLAQUES; LOW-DENSITY LIPOPROTEIN; CHEMOTACTIC FACTOR; ANGIOGRAPHIC MORPHOLOGY; VASCULAR INJURY; CAROTID-ARTERY; TISSUE FACTOR C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. MAYO CLIN & MAYO FDN,ROCHESTER,MN 55905. RP FUSTER, V (reprint author), MASSACHUSETTS GEN HOSP,CARDIAC UNIT,32 FRUIT ST,BOSTON,MA 02114, USA. RI BADIMON, LINA/O-4711-2014; Fuster, Valentin/H-4319-2015 OI BADIMON, LINA/0000-0002-9162-2459; Fuster, Valentin/0000-0002-9043-9986 NR 100 TC 2450 Z9 2530 U1 6 U2 71 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 JAN 23 PY 1992 VL 326 IS 4 BP 242 EP 250 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA HA431 UT WOS:A1992HA43100006 PM 1727977 ER PT J AU HIRSCH, MS AF HIRSCH, MS TI THE TREATMENT OF CYTOMEGALOVIRUS IN AIDS - MORE THAN MEETS THE EYE SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID IMMUNODEFICIENCY VIRUS TYPE-1; REPLICATION INVITRO; FOSCARNET; PHOSPHONOFORMATE RP HIRSCH, MS (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114, USA. NR 10 TC 16 Z9 16 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 JAN 23 PY 1992 VL 326 IS 4 BP 264 EP 266 DI 10.1056/NEJM199201233260409 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA HA431 UT WOS:A1992HA43100009 PM 1309391 ER PT J AU ANTONIADES, HN GALANOPOULOS, T NEVILLEGOLDEN, J MAXWELL, M AF ANTONIADES, HN GALANOPOULOS, T NEVILLEGOLDEN, J MAXWELL, M TI EXPRESSION OF INSULIN-LIKE GROWTH FACTOR-I AND FACTOR-II AND THEIR RECEPTOR MESSENGER-RNAS IN PRIMARY HUMAN ASTROCYTOMAS AND MENINGIOMAS - INVIVO STUDIES USING INSITU HYBRIDIZATION AND IMMUNOCYTOCHEMISTRY SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID HUMAN-MALIGNANT GLIOMA; CENTRAL NERVOUS-SYSTEM; FACTOR-II GENE; FACTOR PDGF; SOMATOMEDIN-C; BRAIN-TUMORS; COEXPRESSION; BINDING; PROTEIN; MICE AB These studies demonstrate the expression of IGF-I, IGF-II, and their respective receptor mRNAs in primary human astrocytomas and meningiomas. In situ hybridization and immunocytochemistry have localized a strong expression of both IGF-I and IGF-II mRNAs and of their protein products in the tumor cells of astrocytomas and meningiomas. The expression of IGF-I and IGF-II mRNAs in the tumor cells was accompanied by the co-expression of their respective type-I and type-II IGF receptor mRNAs. Control, non-malignant human brain expressed IGF-I mRNA and IGF-I and IGF-II receptor mRNAs. There was no significant expression of IGF-II mRNA in the control brain specimens. Control pachymeninges (dura mater) expressed low levels of IGF-I mRNA and IGF-I receptor mRNA. There was no significant expression of IGF-II and IGF-II receptor mRNAs in pachymeninges. The co-expression of IGFs and their receptors in brain tumors may contribute in their development and maintenance. The strong inappropriate expression of IGF-II mRNA and its protein product in the tumor cells of astrocytomas and meningiomas, but not in normal brain specimens, may serve as molecular markers for the early detection of these tumors. C1 HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT NUTR,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,NEUROSURG SERV,BOSTON,MA 02114. RP ANTONIADES, HN (reprint author), HARVARD UNIV,SCH PUBL HLTH,CTR BLOOD RES,800 HUNTINGTON AVE,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA30101]; NHLBI NIH HHS [HL29583] NR 34 TC 122 Z9 122 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JAN 21 PY 1992 VL 50 IS 2 BP 215 EP 222 DI 10.1002/ijc.2910500210 PG 8 WC Oncology SC Oncology GA GZ852 UT WOS:A1992GZ85200009 PM 1370435 ER PT J AU CUNNINGHAM, CC GORLIN, JB KWIATKOWSKI, DJ HARTWIG, JH JANMEY, PA BYERS, HR STOSSEL, TP AF CUNNINGHAM, CC GORLIN, JB KWIATKOWSKI, DJ HARTWIG, JH JANMEY, PA BYERS, HR STOSSEL, TP TI ACTIN-BINDING PROTEIN REQUIREMENT FOR CORTICAL STABILITY AND EFFICIENT LOCOMOTION SO SCIENCE LA English DT Article ID DICTYOSTELIUM MUTANT; HUMAN-PLATELETS; ALPHA-ACTININ; MEMBRANE; ASSOCIATION; MACROPHAGES; HEPATOCYTES; GELATION; LINKING; FILAMIN AB Three unrelated tumor cell lines derived from human malignant melanomas lack actin-binding protein (ABP), which cross-links actin filaments in vitro and connects these filaments to plasma membrane glycoproteins. The ABP-deficient cells have impaired locomotion and display circumferential blebbing of the plasma membrane. Expression of A.BP in one of the lines after transfection restored translocational motility and reduced membrane blebbing. These findings establish that ABP functions to stabilize cortical actin in vivo and is required for efficient cell locomotion. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT MED,DIV HEMATOL ONCOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,CHILDRENS HOSP,DEPT HEMATOL ONCOL,DIV PEDIAT ONCOL,BOSTON,MA 02115. RP CUNNINGHAM, CC (reprint author), HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT MED,DIV EXPTL MED,BOSTON,MA 02115, USA. FU NHLBI NIH HHS [HL 19429]; NIAID NIH HHS [AI 08051]; NIAMS NIH HHS [AR 38910] NR 30 TC 443 Z9 448 U1 2 U2 12 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JAN 17 PY 1992 VL 255 IS 5042 BP 325 EP 327 DI 10.1126/science.1549777 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GZ695 UT WOS:A1992GZ69500040 PM 1549777 ER PT J AU WEISS, J AXELROD, L WHITCOMB, RW HARRIS, PE CROWLEY, WF JAMESON, JL AF WEISS, J AXELROD, L WHITCOMB, RW HARRIS, PE CROWLEY, WF JAMESON, JL TI HYPOGONADISM CAUSED BY A SINGLE AMINO-ACID SUBSTITUTION IN THE BETA SUBUNIT OF LUTEINIZING-HORMONE SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Note ID HUMAN CHORIONIC-GONADOTROPIN; MOLECULAR-BIOLOGY; DNA; CELLS; INFERTILITY; GENE C1 MASSACHUSETTS GEN HOSP,DEPT MED,THYROID UNIT,JACKSON 1021,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MED,DIABET UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MED,REPROD ENDOCRINOL UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,NATL CTR INFERTIL RES,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. OI Jameson, James/0000-0001-9538-4059 FU NICHD NIH HHS [HD 23519, HD 29164, R01 HD015788, U01 HD044417, U54 HD028138] NR 21 TC 250 Z9 260 U1 0 U2 4 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 16 PY 1992 VL 326 IS 3 BP 179 EP 183 DI 10.1056/NEJM199201163260306 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA GZ213 UT WOS:A1992GZ21300006 PM 1727547 ER PT J AU ROSENBERGER, PB AF ROSENBERGER, PB TI DYSLEXIA - IS IT A DISEASE SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material RP ROSENBERGER, PB (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 6 TC 4 Z9 4 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 JAN 16 PY 1992 VL 326 IS 3 BP 192 EP 193 DI 10.1056/NEJM199201163260308 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA GZ213 UT WOS:A1992GZ21300008 PM 1727548 ER PT J AU ANDERSON, RR AF ANDERSON, RR TI TATTOOING SHOULD BE REGULATED SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP ANDERSON, RR (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 5 TC 29 Z9 30 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 JAN 16 PY 1992 VL 326 IS 3 BP 207 EP 207 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA GZ213 UT WOS:A1992GZ21300033 PM 1727564 ER PT J AU YARCHOAN, R TSIATIS, AA BRODER, S AF YARCHOAN, R TSIATIS, AA BRODER, S TI CD4 COUNTS AND HIV-RELATED DEATHS - REPLY SO ANNALS OF INTERNAL MEDICINE LA English DT Letter C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. RP YARCHOAN, R (reprint author), NCI,BETHESDA,MD 20892, USA. NR 5 TC 4 Z9 4 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JAN 15 PY 1992 VL 116 IS 2 BP 169 EP 170 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA GZ356 UT WOS:A1992GZ35600015 ER PT J AU HABER, DA AF HABER, DA TI MULTIDRUG RESISTANCE (MDR-1) IN LEUKEMIA - IS IT TIME TO TEST SO BLOOD LA English DT Editorial Material ID CLASS-II REGION; P-GLYCOPROTEIN; DRUG-RESISTANCE; MYELOGENOUS LEUKEMIA; COMPLEMENTARY-DNA; HAMSTER-CELLS; HUMAN-TUMORS; GENE FAMILY; EXPRESSION; MYELOMA RP HABER, DA (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,CTR CANC,BOSTON,MA 02129, USA. NR 45 TC 58 Z9 58 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 JAN 15 PY 1992 VL 79 IS 2 BP 295 EP 298 PG 4 WC Hematology SC Hematology GA GZ357 UT WOS:A1992GZ35700001 PM 1346094 ER PT J AU TYCKO, B RITZ, J SALLAN, S SKLAR, J AF TYCKO, B RITZ, J SALLAN, S SKLAR, J TI CHANGING ANTIGEN RECEPTOR GENE REARRANGEMENTS IN A CASE OF EARLY PRE-B-CELL LEUKEMIA - EVIDENCE FOR A TUMOR PROGENITOR-CELL WITH STEM-CELL FEATURES AND IMPLICATIONS FOR MONITORING RESIDUAL DISEASE SO BLOOD LA English DT Article ID IMMUNOGLOBULIN; LYMPHOMA; LOCUS; SUBGROUPS C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT PATHOL,DIV DIAGNOST MOLEC BIOL,BOSTON,MA 02115. RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NCI NIH HHS [1P01-CA-34183, R01-CA-38621] NR 25 TC 37 Z9 37 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 JAN 15 PY 1992 VL 79 IS 2 BP 481 EP 488 PG 8 WC Hematology SC Hematology GA GZ357 UT WOS:A1992GZ35700027 PM 1309670 ER PT J AU FREEMAN, GJ DISTECHE, CM GRIBBEN, JG ADLER, DA FREEDMAN, AS DOUGERY, J NADLER, LM AF FREEMAN, GJ DISTECHE, CM GRIBBEN, JG ADLER, DA FREEDMAN, AS DOUGERY, J NADLER, LM TI THE GENE FOR B7, A COSTIMULATORY SIGNAL FOR T-CELL ACTIVATION, MAPS TO CHROMOSOMAL REGION 3Q13.3-3Q21 SO BLOOD LA English DT Article ID ACUTE NONLYMPHOCYTIC LEUKEMIA; INSITU HYBRIDIZATION; LOCALIZATION; ANTIGEN; MEGAKARYOCYTES; ABNORMALITIES; POLYMORPHISMS; ASSIGNMENTS; EXPRESSION C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. UNIV WASHINGTON,DEPT PATHOL,SEATTLE,WA 98195. RP FREEMAN, GJ (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,MAYER 726,44 BINNEY ST,BOSTON,MA 02115, USA. FU FIC NIH HHS [1FO5 TWO4469]; NCI NIH HHS [CA-40216]; NIA NIH HHS [AG0057] NR 42 TC 30 Z9 31 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 JAN 15 PY 1992 VL 79 IS 2 BP 489 EP 494 PG 6 WC Hematology SC Hematology GA GZ357 UT WOS:A1992GZ35700028 PM 1370389 ER PT J AU SOIFFER, RJ MURRAY, C COCHRAN, K CAMERON, C WANG, E SCHOW, PW DALEY, JF RITZ, J AF SOIFFER, RJ MURRAY, C COCHRAN, K CAMERON, C WANG, E SCHOW, PW DALEY, JF RITZ, J TI CLINICAL AND IMMUNOLOGICAL EFFECTS OF PROLONGED INFUSION OF LOW-DOSE RECOMBINANT INTERLEUKIN-2 AFTER AUTOLOGOUS AND T-CELL DEPLETED ALLOGENEIC BONE-MARROW TRANSPLANTATION SO BLOOD LA English DT Article ID VERSUS-HOST DISEASE; ACUTE LYMPHOBLASTIC-LEUKEMIA; NATURAL-KILLER-CELLS; CHRONIC MYELOGENOUS LEUKEMIA; HEMATOLOGICAL MALIGNANCY; ADOPTIVE IMMUNOTHERAPY; CHEMO-RADIOTHERAPY; CANCER-PATIENTS; GRAFT; CHEMOTHERAPY C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. RP SOIFFER, RJ (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,44 BINNEY ST,BOSTON,MA 02115, USA. RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NCI NIH HHS [CA 34183]; NCRR NIH HHS [RR05526]; NIAID NIH HHS [AI 29530] NR 47 TC 200 Z9 200 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 JAN 15 PY 1992 VL 79 IS 2 BP 517 EP 526 PG 10 WC Hematology SC Hematology GA GZ357 UT WOS:A1992GZ35700032 PM 1730094 ER PT J AU SHOCKLEY, TR LIN, K SUNG, C NAGY, JA TOMPKINS, RG DEDRICK, RL DVORAK, HF YARMUSH, ML AF SHOCKLEY, TR LIN, K SUNG, C NAGY, JA TOMPKINS, RG DEDRICK, RL DVORAK, HF YARMUSH, ML TI A QUANTITATIVE-ANALYSIS OF TUMOR SPECIFIC MONOCLONAL-ANTIBODY UPTAKE BY HUMAN-MELANOMA XENOGRAFTS - EFFECTS OF ANTIBODY IMMUNOLOGICAL PROPERTIES AND TUMOR-ANTIGEN EXPRESSION LEVELS SO CANCER RESEARCH LA English DT Article ID SOLID TUMORS; RADIOLABELED ANTIBODIES; CARCINOMA XENOGRAFTS; IMMUNOGLOBULIN-G; COLON-CARCINOMA; BLOOD-FLOW; LOCALIZATION; CELLS; BIODISTRIBUTION; KINETICS AB The time-dependent (5 min-72 h) localization of 3 radiolabeled antimelanoma monoclonal antibodies (MAbs 436, IND1, and 9.2.27) was studied in paired label experiments in small (4-12 mg) s.c. human melanoma xenografts (SK-MEL-2 and M21) in athymic nude mice. MAb 436 recognizes a M(r) 125,000 cell surface melanoma-associated glycoprotein antigen (125 kDa-MAA); MAbs IND1 and 9.2.27 recognize a high molecular weight melanoma-associated antigen, but with equilibrium association constants differing by 2 orders of magnitude (10(8)-10(10) M-1). The two tumors were found to differ in their antigen expression levels and in both interstitial and vascular volumes. Accumulation of MAbs in both tumors was determined primarily by antigen expression levels and also by physiological factors such as vascular permeability and vascular volume; at the dose administered (20-mu-g/mouse), differences in MAb affinity among specific MAbs had minimal effect on accumulation. Quantitative flow cytometry measurements showed that antigen expression in vivo differed from that of cultured tumor cells. In vivo, expression of the M(r) 125,000 MAA decreased by a factor of about 2.5 in both tumors. In contrast, the in vivo expression of the high molecular weight MAA decreased in M21 tumors but increased by 2.0-3.5-fold in SK-MEL-2 tumors. Data were analyzed using a three-compartment pharmacokinetic model (C. Sung et al., Cancer Res., 52:377-384,1992) to provide plasma-to-tissue transport constants (k), the interstitial fluid flow rate (L), and estimates of the in vivo interstitial MAb binding site concentration (B(o)). For all MAbs, the plasma-to-tissue transport constants were consistently greater for M21 tumors (0.44-0.85-mu-l/min/g) than for SK-MEL-2 tumors (0.28-0.66-mu-l/min/g), and values of k for both tumors were approximately 1 order of magnitude greater than those for skeletal muscle (0.06-0.08-mu-l/min/g). The model-estimated binding site concentration of melanoma-specific antibodies was 15-70 times lower than that predicted by experimental measurements of tumor antigen concentrations. Factors that may contribute to this discrepancy include inaccessibility of tumor cell binding sites to MAb and MAb catabolism. In summary, these results indicate that, for the MAb dose used in this study, variables pertaining to the tumor target (ie., antigen expression levels, vascular volume, and vascular permeability) are the most important for determining MAb accumulation in tumors. C1 RUTGERS STATE UNIV,DEPT CHEM & BIOCHEM ENGN,PISCATAWAY,NJ 08854. RUTGERS STATE UNIV,CTR ADV BIOTECHNOL & MED,PISCATAWAY,NJ 08854. MIT,DEPT CHEM ENGN,CAMBRIDGE,MA 02139. BETH ISRAEL HOSP,DEPT PATHOL,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. BETH ISRAEL HOSP,CHARLES A DANA RES INST,BOSTON,MA 02215. NIH,BIOMED ENGN & INSTRUMENTAT BRANCH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. MASSACHUSETTS GEN HOSP,SURG SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. FU NCI NIH HHS [CA-50453, CA-28471] NR 59 TC 70 Z9 70 U1 2 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 1992 VL 52 IS 2 BP 357 EP 366 PG 10 WC Oncology SC Oncology GA GZ693 UT WOS:A1992GZ69300019 PM 1728407 ER PT J AU SUNG, C SHOCKLEY, TR MORRISON, PF DVORAK, HF YARMUSH, ML DEDRICK, RL AF SUNG, C SHOCKLEY, TR MORRISON, PF DVORAK, HF YARMUSH, ML DEDRICK, RL TI PREDICTED AND OBSERVED EFFECTS OF ANTIBODY-AFFINITY AND ANTIGEN DENSITY ON MONOCLONAL-ANTIBODY UPTAKE IN SOLID TUMORS SO CANCER RESEARCH LA English DT Article ID BINDING; PROTEIN; MICE; BIODISTRIBUTION; XENOGRAFTS; KINETICS; MELANOMA; TISSUE; LOCALIZATION; DEGRADATION AB The uptake and binding of monoclonal antibodies (MAbs) in solid tumors after a bolus i.v. injection are described using a compartmental pharmacokinetic model. The model assumes that MAb permeates into tumor unidirectionally from plasma across capillaries and clears from tumor by interstitial fluid flow and that interstitial antibody-antigen interactions are characterized by the Langmuir isotherm for reversible, saturable binding. Typical values for plasma clearance and tumor capillary permeability of a MAb and for interstitial fluid flow and interstitial volume fraction of a solid tumor were used to simulate the uptake of MAbs at various values of the binding affinity or antigen density for a range of MAb doses. The model indicates that at low doses, an increase in binding affinity may lead to an increase in MAb uptake. On the other hand, at doses approaching saturation of antigen or when uptake is permeation limited, an increase in the binding affinity from moderate to high affinity will have only a small effect on increasing MAb uptake. The model also predicts that an increase in antigen density will greatly increase MAb uptake when uptake is not permeation limited. Our experiments on MAb uptake in melanoma tumors in athymic mice after injection of 20-mu-g MAb (initial plasma concentration, about 120 nm) are consistent with these model-based conclusions. Two MAbs differing in affinity by more than 2 orders of magnitude (3.8 x 10(8) M-1 and 5 x 10(10) M-1) but with similar in vivo antigen densities in M21 melanoma attained similar concentrations in the tumor. Two MAbs of similar affinity but having a 3-fold difference in in vivo antigen density in SK-MEL-2 melanoma showed that the MAb targeted to the more highly expressed antigen attained a higher MAb concentration. We also discuss the model predictions in relation to other experiments reported in the literature. The theoretical and experimental findings suggest that, for high dose applications, efforts to increase MAb uptake in a tumor should emphasize the identification of an abundantly expressed antigen on tumor cells more than the selection of a very high affinity MAb. C1 MIT,DEPT CHEM ENGN,CAMBRIDGE,MA 02139. BETH ISRAEL HOSP,DEPT PATHOL,BOSTON,MA 02215. BETH ISRAEL HOSP,CHARLES A DANA RES INST,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RUTGERS STATE UNIV,DEPT CHEM & BIOCHEM ENGN,PISCATAWAY,NJ 08854. RUTGERS STATE UNIV,CTR ADV BIOTECHNOL & MED,PISCATAWAY,NJ 08854. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP SUNG, C (reprint author), NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892, USA. NR 28 TC 79 Z9 79 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 JAN 15 PY 1992 VL 52 IS 2 BP 377 EP 384 PG 8 WC Oncology SC Oncology GA GZ693 UT WOS:A1992GZ69300021 PM 1728409 ER PT J AU LEUNIG, M GOETZ, AE DELLIAN, M ZETTERER, G GAMARRA, F JAIN, RK MESSMER, K AF LEUNIG, M GOETZ, AE DELLIAN, M ZETTERER, G GAMARRA, F JAIN, RK MESSMER, K TI INTERSTITIAL FLUID PRESSURE IN SOLID TUMORS FOLLOWING HYPERTHERMIA - POSSIBLE CORRELATION WITH THERAPEUTIC RESPONSE SO CANCER RESEARCH LA English DT Note ID MACROMOLECULES; TRANSPORT; DELIVERY; TISSUES AB Elevated interstitial fluid pressure (IFP) of tumors may be a physiological barrier to the delivery of certain therapeutic agents. The objective of this study was to rind out if IFP could be lowered using localized hyperthermia and if the reduction in IFP could predict the tumor response to treatment. Amelanotic melanoma (A-Mel-3) implanted into the dorsal skin of Syrian golden hamsters was exposed to hyperthermic treatment after 7 days of tumor growth at tumor volumes of about 100-150 mm3. Hyperthermia was induced by immersing the tumor in a water bath at 43-degrees-C for 30 or 60 min. Forty-eight h later the IFP of control and treated tumors was determined by using the wick-in-needle technique. The mean IFP in control tumors was 12.6 mmHg. Hyperthermic treatment for 30 min induced a significant decrease to 2.8 mmHg (P < 0.001 versus controls), whereas a 60-min immersion of the tumors induced a further decrease to 0.8 mmHg (P < 0.05 versus 43-degrees-C for 30 min). Separate experiments on tumor growth in corresponding groups of animals revealed a significant growth delay of 2.7 days after hyperthermia for 30 min. Enhanced growth delay and partial tumor response in 66% of the tumors were found following 60 min of hyperthermia at 43-degrees-C. The thermal dose-dependent decrease in IFP presumably results from the dose-dependent damage to the tumor vasculature. In addition, the association of an enhanced biological effect with a more pronounced reduction of interstitial fluid pressure suggests that the IFP might serve as a quantitative parameter to predict the response of tumors to hyperthermic therapy. C1 UNIV MUNICH,KLINIKUM GROSSHADERN,INST SURG RES,MARCHIONINISTR 15,W-8000 MUNICH 70,GERMANY. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,STEELE LAB,BOSTON,MA 02114. RI Leunig, Michael/E-7951-2017 OI Leunig, Michael/0000-0002-2036-5416 FU NCI NIH HHS [CA37239, CA49792] NR 21 TC 83 Z9 87 U1 0 U2 4 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 JAN 15 PY 1992 VL 52 IS 2 BP 487 EP 490 PG 4 WC Oncology SC Oncology GA GZ693 UT WOS:A1992GZ69300040 PM 1728421 ER PT J AU SWEADNER, KJ MCGRAIL, KM KHAW, BA AF SWEADNER, KJ MCGRAIL, KM KHAW, BA TI DISCOORDINATE REGULATION OF ISOFORMS OF NA,K-ATPASE AND MYOSIN HEAVY-CHAIN IN THE HYPOTHYROID POSTNATAL RAT-HEART AND SKELETAL-MUSCLE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NA+-K+-ATPASE; THYROID-HORMONE; NEONATAL RAT; BETA-SUBUNIT; ALPHA-MYOSIN; CATALYTIC SUBUNIT; MESSENGER-RNAS; ANTIMYOSIN FAB; EXPRESSION; ISOZYME AB During postnatal life, many contractile and electrophysiological properties of the rat heart undergo changes. Among the changes is a switch in the expression of Na,K-ATPase catalytic subunit isoforms. Thyroid hormone has been postulated to play an important role in the postnatal transformation of the heart, and its effect on myosin heavy chain isoform gene transcription is well documented. To test whether it controls Na,K-ATPase gene switching in vivo, we made neonatal rats hypothyroid by maternal treatment with methimazole. The expression of Na,K-ATPase catalytic subunit isoforms in cardiac and skeletal muscle membranes was measured with specific antibodies at time points from birth to 4 weeks of age. Postnatal changes in Na,K-ATPase isoform expression in cardiac ventricle and hind limb skeletal muscle were similar in control and hypothyroid animals. In the same hypothyroid animals, the postnatal switch from the V3 (beta) isoform of myosin heavy chain to the V1 (alpha) isoform was blocked. The conclusion is that thyroid hormone may have a modulatory role in Na,K-ATPase gene expression, but it is not the developmental signal that dominates gene switching. C1 MASSACHUSETTS GEN HOSP,DEPT NUCL MED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT CELLULAR & MOLEC PHYSIOL,BOSTON,MA 02115. RP SWEADNER, KJ (reprint author), MASSACHUSETTS GEN HOSP,DEPT NEUROSURG RES,WELLMAN 4,FRUIT ST,BOSTON,MA 02114, USA. FU NHLBI NIH HHS [HL 36271] NR 46 TC 36 Z9 36 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 15 PY 1992 VL 267 IS 2 BP 769 EP 773 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GY960 UT WOS:A1992GY96000017 PM 1309775 ER PT J AU DORFMAN, DM WILSON, DB BRUNS, GAP ORKIN, SH AF DORFMAN, DM WILSON, DB BRUNS, GAP ORKIN, SH TI HUMAN TRANSCRIPTION FACTOR GATA-2 - EVIDENCE FOR REGULATION OF PREPROENDOTHELIN-1 GENE-EXPRESSION IN ENDOTHELIAL-CELLS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PUTATIVE ZINC FINGER; DNA-BINDING FACTOR; SEQUENCE; ACTIVATION; PROTEINS; LOCALIZATION; COMPLEXES; NUMBER; COMMON; FAMILY AB Previously, we showed that the promoter of the gene encoding preproendothelin-1 (PPET-1) contains a GATA motif that is essential for activity and interacts with a nuclear factor similar in size and binding specificity to the erythroid transcription factor GATA-1. To identify this endothelial GATA-binding protein, a human endothelial cell cDNA library was screened with oligonucleotide probes for a portion of the zinc finger domain of GATA-1. A 2.6-kilobase cDNA encoding a 470 amino acid protein was obtained. Sequence analysis revealed a predicted protein which is the human counterpart of a related chicken protein, designated GATA-2. Human GATA-2 is expressed by a variety of cells, including erythroid, HeLa, and endothelial cells. A complex of a GATA-containing probe and recombinant GATA-2 expressed in COS cells comigrates with that present in gel shift experiments with nuclear extract derived from endothelial cells. In addition, expressed human GATA-2 protein transactivates reporter gene constructs containing either minimal GATA promoter elements or the native PPET-1 promoter in a cotransfection assay. Retinoic acid treatment of endothelial cells results in down-regulation of GATA-2 expression as well as down-regulation of PPET-1 gene expression. Human homologs of other known GATA-binding transcription factors are either absent from endothelial cells (in the case of GATA-1) or made in small quantities and not significantly affected by retinoic acid in these cells (in the case of GATA-3), making it unlikely that they regulate the PPET-1 gene. We propose that GATA-2 is the GATA-binding protein required for PPET-1 gene expression in endothelial cells. C1 HOWARD HUGHES MED INST,BOSTON,MA 02115. HARVARD UNIV,CHILDRENS HOSP,SCH MED,DIV GENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. RP DORFMAN, DM (reprint author), HARVARD UNIV,CHILDRENS HOSP,SCH MED,DIV HEMATOL ONCOL,BOSTON,MA 02115, USA. RI Wilson, David/K-7433-2014 OI Wilson, David/0000-0002-1826-7745 FU NHLBI NIH HHS [5P32HL07574] NR 36 TC 262 Z9 265 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 15 PY 1992 VL 267 IS 2 BP 1279 EP 1285 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GY960 UT WOS:A1992GY96000093 PM 1370462 ER PT J AU BACKER, JM SCHROEDER, GG KAHN, CR MYERS, MG WILDEN, PA CAHILL, DA WHITE, MF AF BACKER, JM SCHROEDER, GG KAHN, CR MYERS, MG WILDEN, PA CAHILL, DA WHITE, MF TI INSULIN STIMULATION OF PHOSPHATIDYLINOSITOL 3-KINASE ACTIVITY MAPS TO INSULIN-RECEPTOR REGIONS REQUIRED FOR ENDOGENOUS SUBSTRATE PHOSPHORYLATION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FACTOR-I RECEPTOR; TYROSINE KINASE-ACTIVITY; COOH-TERMINAL TRUNCATION; GROWTH-FACTOR RECEPTORS; PDGF RECEPTOR; MIDDLE-T; INTACT-CELLS; BETA-SUBUNIT; BINDING SITE; PROTEIN AB We have studied the phosphatidylinositol 3-kinase (PtdIns 3-kinase) in insulin-stimulated Chinese hamster ovary (CHO) cells expressing normal (CHO/IR) and mutant human insulin receptors. Insulin stimulation of CHO/IR cells results in an increase in PtdIns 3-kinase activity associated with anti-phosphotyrosine (alpha-PY) immunoprecipitates, which has been previously shown to correlate with the in vivo production of PtdIns(3,4)P2, and PtdIns(3,4,5)P3 (Ruderman, N., Kapeller, R., White, M. F., and Cantley, L. C. (1990) Proc. Natl. Acad. Sci. U. S. A. 87, 1411-1415). Stimulation was maximal within 1 min and showed a dose response identical to that of insulin receptor autophosphorylation. The PtdIns 3-kinase also associated with the insulin receptor in an insulin-stimulated manner, as approximately 50% of the total alpha-PY-precipitable activity could be specifically immunoprecipitated with anti-insulin receptor antibody. Mutant insulin receptors displayed variable ability to stimulate the PtdIns 3-kinase, but in all cases the presence of PtdIns 3-kinase in alpha-PY immunoprecipitates correlated closely with the tyrosyl phosphorylation of the endogenous substrate pp185. In CHO cells expressing a kinase-deficient mutant (IR(A1018)), there was no observable insulin stimulation of PtdIns 3-kinase activity in alpha-PY immunoprecipitates and no tyrosyl phosphorylation of pp185. Substitution of Tyr1146 in the insulin receptor regulatory region with phenylalanine partially impaired receptor autophosphorylation, pp185 phosphorylation, and insulin-stimulated increases in alpha-PY-precipitable PtdIns 3-kinase activity. In contrast, a deletion mutant lacking 12 amino acids from the juxtamembrane region (IR(DELTA-960)) displayed normal in vivo autophosphorylation but failed to stimulate the PtdIns 3-kinase or phosphorylate pp185. Finally, a mutant receptor from which the C-terminal 43 amino acids had been deleted (IR(DELTA-CT)) exhibited normal insulin-stimulated autophosphorylation, pp185 phosphorylation, and stimulation of the PtdIns 3-kinase activity in alpha-PY immunoprecipitates. These data suggest that the PtdIns 3-kinase is itself a substrate of the insulin receptor kinase or associates preferentially with a substrate. A comparison of the biological activities of the mutant receptors with their activation of the PtdIns 3-kinase furthermore suggests that the PtdIns 3-kinase may be linked to insulin's ability to regulate DNA synthesis and cell growth. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP BACKER, JM (reprint author), BRIGHAM & WOMENS HOSP,JOSLIN DIABET CTR,DEPT MED,DIV RES,1 JOSLIN PL,BOSTON,MA 02115, USA. FU NIDDK NIH HHS [DK38712, DK33201, DK36836] NR 60 TC 138 Z9 138 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 JAN 15 PY 1992 VL 267 IS 2 BP 1367 EP 1374 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GY960 UT WOS:A1992GY96000107 PM 1309768 ER PT J AU TORIMOTO, Y ROTHSTEIN, DM DANG, NH SCHLOSSMAN, SF MORIMOTO, C AF TORIMOTO, Y ROTHSTEIN, DM DANG, NH SCHLOSSMAN, SF MORIMOTO, C TI CD31, A NOVEL CELL-SURFACE MARKER FOR CD4 CELLS OF SUPPRESSOR LINEAGE, UNALTERED BY STATE OF ACTIVATION SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LEUKOCYTE-COMMON ANTIGEN; MEMORY T-CELLS; HUMAN LYMPHOCYTES-T; HELPER-INDUCER; MONOCLONAL-ANTIBODIES; DIFFERENTIAL EXPRESSION; 2H4 MOLECULE; SUBSETS; SUBPOPULATIONS; UCHL1 AB In this study, we examined the role of CD31 as a cell surface marker for subsets of human CD4 cells. CD31, as defined by a newly developed mAb termed anti-1F11, can divide activated as well as resting CD4 cells into distinct functional subpopulations, based on its surface expression. Among CD4 cells freshly isolated from peripheral blood, anti-1F11 preferentially reacts with the CD45RA+ subset. The majority of helper activity for B cell IgG synthesis and memory function to recall Ag such as tetanus toxoid or mumps was found within the CD31- CD4 cell population, whereas CD31+ CD4 cells provided poor helper function for B cell IgG synthesis and were more responsive to Con A and autologous MHC (autologous MLR). The expression of CD31 on CD45RA+ CD4 cells did not change after activation, despite the loss of CD45RA from the cell surface. Conversely, CD31 was not acquired after activation of CD45RO+ CD45RA- CD4 cells. Furthermore, activated CD4 cells expressing CD31 can induce suppressor function for B cell IgG synthesis, whereas the reciprocal population of activated CD4 cells (CD31-) provide strong helper function for B cell IgG production. Finally, IL-4 production could only be induced by stimulation with PMA and ionomycin in either resting or activated CD31- CD4 cells. Thus, CD31 may prove useful in defining CD4 populations with reciprocal functional programs. Moreover, unlike other markers used for this purpose, the expression of CD31 does not change after activation and may serve as a more useful marker for identification of cells of suppressor or helper lineage. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,DIV TUMOR IMMUNOL,44 BINNEY ST,BOSTON,MA 02115. FU NIAID NIH HHS [AI-12069, AI-29530]; NIAMS NIH HHS [AR-33713] NR 47 TC 72 Z9 73 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 JAN 15 PY 1992 VL 148 IS 2 BP 388 EP 396 PG 9 WC Immunology SC Immunology GA GZ965 UT WOS:A1992GZ96500012 PM 1345920 ER PT J AU BLUMENTHAL, M MARCUSBAGLEY, D AWDEH, Z JOHNSON, B YUNIS, EJ ALPER, CA AF BLUMENTHAL, M MARCUSBAGLEY, D AWDEH, Z JOHNSON, B YUNIS, EJ ALPER, CA TI HLA-DR2, [HLA-B7, SC31, DR2], AND [HLA-B8, SC01, DR3] HAPLOTYPES DISTINGUISH SUBJECTS WITH ASTHMA FROM THOSE WITH RHINITIS ONLY IN RAGWEED POLLEN ALLERGY SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INHERITED STRUCTURAL POLYMORPHISM; MAJOR HISTOCOMPATIBILITY COMPLEX; HUMAN IMMUNE-RESPONSE; HEPATITIS-B VACCINE; RADIOALLERGOSORBENT TEST; GENETIC-POLYMORPHISM; IGE ANTIBODIES; ASSOCIATION; RA5; NOMENCLATURE AB MHC haplotypes were determined for 52 patients with ragweed pollen allergy, with and without asthma, and 27 non-atopic controls. Total IgE levels were unimodally distributed in all study groups and were higher in atopic patients in general compared with non-atopics. There was no difference in total IgE levels in patients with rhinitis only compared with those with rhinitis and asthma. IgE anti-Amb a V was detected (after subtraction of values representing the means + 2 SD of the non-atopics) in 9 of 20 asthmatics but only 3 of 32 patients with only rhinitis and was thus associated with asthma. Mean anti-Amb a V was much higher in the antibody-positive asthmatics (1710 U/ml) than in the positive patients with rhinitis only (469 U/ml). The extended MHC haplotype [HLA-B7, SC31, DR2] and its possible DR-containing fragment (SC31, DR2), were found almost exclusively among the patients with IgE anti-Amb a V and were significantly elevated in patients with asthma. DR2 in general, but not DR2 without SC31, was significantly increased in frequency in patients with anti-Amb a V. In contrast, the extended haplotype [HLA-B8, SC01, DR3] and DR3 in general were increased among patients with rhinitis only and patients without IgE anti-Amb a V compared with general controls. Thus, [HLA-B8, SC01, DR3] and DR3 appear to be "protective" for the production of this antibody and the occurrence of asthma. The findings are consistent with an MHC-linked gene or genes on [HLA-B7, SC31, DR2] (but not necessarily DR2, Dw2, or DQw6 in general) controlling the IgE immune response to Amb a V and associated with asthma in ragweed pollen-sensitive subjects. In patients with rhinitis alone and generally undetectable levels of IgE anti-Amb a V, the increase in [HLA-B8, SC01, DR3] and DR3 may mark a response to an as yet unidentified Ag associated with ragweed allergy and rhinitis only. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. RP BLUMENTHAL, M (reprint author), UNIV MINNESOTA,DEPT MED,420 DELAWARE ST SE,MINNEAPOLIS,MN 55455, USA. FU NHLBI NIH HHS [HL 29583]; NICHD NIH HHS [HD 17461]; NIDDK NIH HHS [DK 26844] NR 46 TC 75 Z9 75 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 15 PY 1992 VL 148 IS 2 BP 411 EP 416 PG 6 WC Immunology SC Immunology GA GZ965 UT WOS:A1992GZ96500015 PM 1729361 ER PT J AU CHENG, LZ WORKMAN, JL KINGSTON, RE KELLY, TJ AF CHENG, LZ WORKMAN, JL KINGSTON, RE KELLY, TJ TI REGULATION OF DNA-REPLICATION INVITRO BY THE TRANSCRIPTIONAL ACTIVATION DOMAIN OF GAL4-VP16 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE CHROMATIN; DNA-BINDING PROTEIN; CHIMERIC TRANSCRIPTION FACTOR ID SIMIAN-VIRUS 40; FUNCTIONAL-ORGANIZATION; GAL4 DERIVATIVES; ORIGIN; ELEMENTS; PROTEINS; INITIATION; BINDING AB Studies of DNA viruses have provided evidence that eukaryotic transcriptional activator proteins can enhance the efficiency of DNA replication as well as transcription. The mechanism of this effect was studied in vitro using the chimeric transcription factor GAL4-VP16 and a DNA template containing GAL4 binding sites adjacent to the simian virus 40 origin of DNA replication. The binding of GAL4-VP16 prevented the repression of DNA replication which otherwise occurred when the template was assembled into chromatin. Relief of repression by GAL4-VP16 required both its DNA-binding and transcriptional activation domains but did not require RNA synthesis. The results are consistent with a general model in which transcriptional activators stimulate eukaryotic DNA replication by modifying the outcome of the competition between initiation factors and histones for occupancy of the origin. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT MOLEC BIOL & GENET,BALTIMORE,MD 21205. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. NR 28 TC 81 Z9 81 U1 0 U2 0 PU NATL ACAD PRESS 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 JAN 15 PY 1992 VL 89 IS 2 BP 589 EP 593 DI 10.1073/pnas.89.2.589 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GZ696 UT WOS:A1992GZ69600029 PM 1309949 ER PT J AU SCHMID, K HEDIGER, MA BROSSMER, R COLLINS, JH HAUPT, H MARTI, T OFFNER, GD SCHALLER, J TAKAGAKI, K WALSH, MT SCHWICK, HG ROSEN, FS REMOLDODONNELL, E AF SCHMID, K HEDIGER, MA BROSSMER, R COLLINS, JH HAUPT, H MARTI, T OFFNER, GD SCHALLER, J TAKAGAKI, K WALSH, MT SCHWICK, HG ROSEN, FS REMOLDODONNELL, E TI AMINO-ACID-SEQUENCE OF HUMAN PLASMA GALACTOGLYCOPROTEIN - IDENTITY WITH THE EXTRACELLULAR REGION OF CD43 (SIALOPHORIN) SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE GLYCANS ID WISKOTT-ALDRICH SYNDROME; LYMPHOCYTE SURFACE SIALOGLYCOPROTEIN; OVINE SUBMAXILLARY MUCIN; O-LINKED GLYCOPROTEINS; MONOCLONAL-ANTIBODY; MOLECULE; IDENTIFICATION; GLYCOSYLATION; LEUKOSIALIN; ACTIVATION AB The amino acid sequence of galactoglycoprotein purified from human plasma was elucidated to 75% completeness by using chemical degradation of peptides and glycopeptides derived from digests of the protein with seven specific proteases. This sequence represents a polypeptide chain of approximately 220 amino acid residues including a high content of serine, threonine, alanine, and proline with one N-linked and multiple O-linked glycans. Comparison of peptide sequences from the native galactoglycoprotein and the deglycosylated derivative demonstrated the locations of 25 sites of O-glycosylation and three serine sites that are not glycosylated. The homogeneous N terminus was established as serine. C-terminal analysis revealed multiple C-terminal residues, suggesting that galactoglycoprotein molecules are of varying lengths. A search of a protein data base revealed that the galactoglycoprotein polypeptide is identical to the N-terminal (extracellular) polypeptide region of the blood-cell surface molecule CD43 (sialophorin, leukosialin). Further support of the relatedness of these molecules was obtained by immunoprecipitation of I-125 labeled galactoglycoprotein by monoclonal anti-CD43 antibodies. The composition and properties of the molecules together with the known structure of the gene encoding CD43 suggest that galactoprotein is derived by proteolytic cleavage from transmembrane "hexasaccharide CD43," known to be expressed on neutrophils, activated T lymphocytes, and platelets. C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. UNIV MARYLAND,SCH MED,DEPT BIOL CHEM,BALTIMORE,MD 21201. BOSTON UNIV,SCH MED,DEPT BIOCHEM,BOSTON,MA 02118. HARVARD UNIV,BRIGHAM & WOMENS HOSP,DIV RENAL,BOSTON,MA 02115. UNIV HEIDELBERG,FAC MED,DEPT BIOCHEM,W-6900 HEIDELBERG,GERMANY. UNIV MARYLAND,MARYLAND BIOTECHNOL INST,CTR MED BIOTECHNOL,BALTIMORE,MD 21201. BOSTON UNIV,SCH MED,DEPT BIOPHYS,BOSTON,MA 02118. UNIV BERN,INST BIOCHEM,CH-3000 BERN,SWITZERLAND. BEHRINGWERKE AG,W-3550 MARBURG,GERMANY. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. FU NIAID NIH HHS [AI29880]; NIDDK NIH HHS [DK-43171]; NIGMS NIH HHS [GM-10374] NR 38 TC 40 Z9 41 U1 0 U2 2 PU NATL ACAD PRESS 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 JAN 15 PY 1992 VL 89 IS 2 BP 663 EP 667 DI 10.1073/pnas.89.2.663 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GZ696 UT WOS:A1992GZ69600044 PM 1731338 ER PT J AU FIELDSBERRY, SC HALLIDAY, AL CEPKO, CL AF FIELDSBERRY, SC HALLIDAY, AL CEPKO, CL TI A RECOMBINANT RETROVIRUS ENCODING ALKALINE-PHOSPHATASE CONFIRMS CLONAL BOUNDARY ASSIGNMENT IN LINEAGE ANALYSIS OF MURINE RETINA SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CHICKEN OPTIC TECTUM; CELL LINEAGE; MIGRATION PATTERNS; COMMON PROGENITOR; CEREBRAL-CORTEX; GENE-EXPRESSION; SEQUENCE; CONSTRUCTION; ARRANGEMENT; EVOLUTION AB Recombinant retroviruses encoding the histochemically detectable enzyme beta-galactosidase have been used to investigate lineage in the vertebrate nervous system. Identification of the descendants of individual progenitors is straightforward when progeny cells are arranged in a reproducible, clustered pattern, but difficulties in interpretation arise when progeny migrate extensively and/or in an irregular pattern. To better resolve clonal boundaries, additional histochemical marker viruses that engender distinctive reaction products can be used in combination with lacZ-bearing viruses. To this end, we have created a retrovirus vector, DAP, encoding an easily assayable enzyme, human placental alkaline phosphatase. DAP was found to be at least as useful as a lacZ-encoding retrovirus (e.g., BAG) with respect to high viral titer, stability of expression, and in identification of infected cells in vivo. Moreover, it was found to be neutral with respect to postnatal rodent retinal development and offered superior staining characteristics relative to lacZ. Coinfection of rodent retina with DAP and BAG allowed an examination of the clonal nature of radial arrays of labeled retinal cells that previously had been described as products of a single infected progenitor. Of 1100 radial arrays examined for the presence of both DAP- and BAG-infected cells, only 1.2% were the result of infection with more than one virus. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROSURG,BOSTON,MA 02114. RP FIELDSBERRY, SC (reprint author), HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115, USA. FU NINDS NIH HHS [NS 23021] NR 43 TC 238 Z9 239 U1 0 U2 0 PU NATL ACAD PRESS 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 JAN 15 PY 1992 VL 89 IS 2 BP 693 EP 697 DI 10.1073/pnas.89.2.693 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GZ696 UT WOS:A1992GZ69600050 PM 1731342 ER PT J AU STASZEWSKI, R AF STASZEWSKI, R TI MURPHY LAW OF LIMITING DILUTION CLONING REVISITED - SUBCLONING SO STATISTICS IN MEDICINE LA English DT Letter RP STASZEWSKI, R (reprint author), MASSACHUSETTS GEN HOSP,DEPT DERMATOL,BOSTON,MA 02114, USA. NR 3 TC 0 Z9 0 U1 0 U2 2 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 JAN 15 PY 1992 VL 11 IS 1 BP 132 EP 133 PG 2 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 HC732 UT WOS:A1992HC73200012 PM 1557571 ER PT J AU KVEDAR, JC PION, IA BILODEAU, EB BADEN, HP GRECO, MA AF KVEDAR, JC PION, IA BILODEAU, EB BADEN, HP GRECO, MA TI DETECTION OF SUBSTRATES OF KERATINOCYTE TRANSGLUTAMINASE INVITRO AND INVIVO USING A MONOCLONAL-ANTIBODY TO DANSYLCADAVERINE SO BIOCHEMISTRY LA English DT Article ID CROSS-LINKED ENVELOPE; HUMAN EPIDERMAL-CELLS; TERMINAL DIFFERENTIATION; MICROGRAM QUANTITIES; CORNIFIED ENVELOPE; HUMAN-ERYTHROCYTES; PROTEIN; IDENTIFICATION; LINKING; LOCALIZATION AB A method providing more sensitive detection of transglutaminase substrates was developed to localize transglutaminase activity in tissue and to identify in vivo substrates in epidermal extracts. The enhanced sensitivity of this method was achieved via the generation of a monoclonal antibody (designated E7) made to dansylcadaverine. Transglutaminase substrates were visualized by western blot after a 1-min incubation with dansylcadaverine in contrast to the 2 h required when [C-14]putrescine incorporation was measured by autoradiography of SDS-polyacrylamide gels. In addition, putative substrates not apparent using conventional methods were readily detected by western analysis. An ELISA assay to measure transglutaminase activity showed similar sensitivity to the traditional radiometric assay (Lorand et al., 1972). The correlation between the ELISA procedure and the radiometric assay was high (r2 = 0.924). Strips of neonatal human and mouse skin incubated in dansylcadaverine-supplemented culture medium were used to localize enzyme activity and to detect substrates in vivo. Transglutaminase activity was demonstrated at the cellular periphery in the upper spinous and granular cell layers of the epidermis. Substrates detected in epidermal extracts were similar to those detected using the in vitro assay. This technique allows for highly sensitive and nonradiometric analysis of both enzymatic activity and the substrates involved. The extension of this methodology to an in vivo system is the first demonstration of a system in which the dynamics of cornified envelope assembly may be further studied. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT DERMATOL,BOSTON,MA 02129. FU NIAMS NIH HHS [AR01804-02] NR 42 TC 11 Z9 11 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 JAN 14 PY 1992 VL 31 IS 1 BP 49 EP 56 DI 10.1021/bi00116a009 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GZ438 UT WOS:A1992GZ43800009 PM 1370626 ER PT J AU CHO, HJ RAMER, SE ITOH, M KITAS, E BANNWARTH, W BURN, P SAITO, H WALSH, CT AF CHO, HJ RAMER, SE ITOH, M KITAS, E BANNWARTH, W BURN, P SAITO, H WALSH, CT TI CATALYTIC DOMAINS OF THE LAR AND CD45 PROTEIN TYROSINE PHOSPHATASES FROM ESCHERICHIA-COLI EXPRESSION SYSTEMS - PURIFICATION AND CHARACTERIZATION FOR SPECIFICITY AND MECHANISM SO BIOCHEMISTRY LA English DT Article ID LEUKOCYTE COMMON ANTIGEN; INORGANIC-PHOSPHATE; O-18 EXCHANGE; FAMILY AB The cytoplasmic domains of two human transmembrane protein tyrosine phosphatases (PTPases), LAR and CD45, have been expressed in Escherichia coli, purified to near-homogeneity, and compared for catalytic efficiency toward several phosphotyrosine-containing peptide substrates. A 615-residue LAR fragment (LAR-D1D2) containing both tandemly repeated PTPase domains shows almost identical specific activity and high catalytic efficiency as the 40-kDa single-domain LAR-D1 fragment, consistent with a single functional active site in the 70-kDa LAR-D1D2 enzyme. A 90-kDa fragment of the human leukocyte CD45 PTPase, containing two similar tandemly repeated PTPase domains, shows parallel specificity to LAR-D1 and LAR-D1D2 with a high k(cat)/K(m) value for a phosphotyrosyl undecapeptide. Sufficient purified LAR-D1 and LAR-D1D2 PTPases were available to demonstrate enzymatic exchange of O-18 from O-18(4) inorganic phosphate into (H2O)-O-16 at rates of approximately 1 X 10(-2) s-1. The oxygen-18 exchange probably proceeds via a phosphoenzyme intermediate. Brief incubation of all three PTPase fragments with a [P-32]phosphotyrosyl peptide substrate prior to quench with SDS sample buffer and gel electrophoresis led to autoradiographic detection of P-32-labeled enzymes. Pulse/chase studies on the LAR P-32-enzyme showed turnover of the labeled phosphoryl group. C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HOFFMANN LA ROCHE AG,CENT RES DEPT,BASEL,SWITZERLAND. FU NCI NIH HHS [CA51132]; NIGMS NIH HHS [GM20011] NR 25 TC 67 Z9 68 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 JAN 14 PY 1992 VL 31 IS 1 BP 133 EP 138 DI 10.1021/bi00116a019 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GZ438 UT WOS:A1992GZ43800019 PM 1370625 ER PT J AU REENSTRA, WW SABOLIC, I BAE, HR VERKMAN, AS AF REENSTRA, WW SABOLIC, I BAE, HR VERKMAN, AS TI PROTEIN KINASE-A DEPENDENT MEMBRANE-PROTEIN PHOSPHORYLATION AND CHLORIDE CONDUCTANCE IN ENDOSOMAL VESICLES FROM KIDNEY CORTEX SO BIOCHEMISTRY LA English DT Article ID CYSTIC-FIBROSIS; PROXIMAL TUBULE; CHANNELS; ACIDIFICATION; RECONSTITUTION; NA+,K+-ATPASE; TRANSPORT; EPITHELIA; LYSOSOMES; CELLS AB Regulation of Cl conductance by protein kinase A may play a role in control of endosomal acidification [Bae, H.-R., & Verkman, A. S. (1990) Nature, 348, 637-6391. To investigate the mechanism of kinase A action, cell-free measurements of Cl transport and membrane protein phosphorylation were carried out in apical endocytic vesicles from rabbit kidney proximal tubule. Cl transport was measured by a stopped-flow quenching assay in endosomes labeled in vivo with the fluorescent Cl indicator 6-methoxy-N-(3-sulfopropyl)quinolinium. Phosphorylation was studied in a purified endosomal preparation by SDS-PAGE and autoradiography of membrane proteins labeled by [gamma-P-32]ATP. Endosomes had a permeability (P(Cl)) for conductive Cl transport of 3.1 x 10(-8) cm/s at 23-degrees-C which was stilbene inhibitable. P(Cl) was increased by 90 +/- 20% by a 10-min preincubation with the catalytic subunit of kinase A (PKA, 10 units/mL) and MgATP (0.5 mM) with anion selectivity Cl > I > Br. The increase in P(Cl) was blocked by 100-mu-M N-[2-(methylamino)ethyl]-5-isoquinolinesulfonamide (H-8) and was reversed by addition of alkaline phosphatase (AP, 40 units/mL) after incubation with PKA and MgATP; the increase in P(Cl) was not blocked by pretreatment with AP. Incubation of endosomes with 1-mu-M [gamma-P-32]ATP gave phosphoproteins at 35 and 48 kDa in the absence of PKA and an additional prominent phosphoprotein at 67 kDa in the presence of PKA; the 67-kDa band was nearly absent when excess unlabeled ATP or H-8 was present at the time of PKA addition or when AP was added after incubation; PKA-dependent phosphorylation of the 67-kDa band was enhanced (2.3 +/- 0.2)-fold by pretreatment with AP. P-32 incorporation in excised bands showed about one 67-kDa phosphoprotein per endosome. These results suggest that, in a cell-free system, protein kinase A increases Cl conductance in endosomes from kidney proximal tubule by a phosphorylation mechanism. The labeled protein has a size similar to that of the 64-kDa putative kidney Cl channel reported by Landry et al. [(1990) Science 244, 1469-1472] but is much smaller than the approximately 170-kDa cystic fibrosis transmembrane conductance regulatory protein. C1 UNIV CALIF SAN FRANCISCO,CARDIOVASC RES INST,DEPT PHYSIOL,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,CTR CYST FIBROSIS,SAN FRANCISCO,CA 94143. CHILDRENS HOSP,RES INST,OAKLAND,CA 94609. MASSACHUSETTS GEN HOSP,RENAL UNIT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP REENSTRA, WW (reprint author), UNIV CALIF SAN FRANCISCO,DEPT MED,1065 HLTH SCI & TOWER,SAN FRANCISCO,CA 94143, USA. FU NHLBI NIH HHS [HL42368]; NIDDK NIH HHS [DK35124, DK39354] NR 35 TC 23 Z9 23 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 JAN 14 PY 1992 VL 31 IS 1 BP 175 EP 181 DI 10.1021/bi00116a026 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GZ438 UT WOS:A1992GZ43800026 PM 1310027 ER PT J AU ABE, O ABE, R ASAISHI, K ENOMOTO, K HATTORI, T INO, Y KIKUCHI, K KOYAMA, H SAWA, K UCHINO, J YOSHIDA, M HAYBITTLE, JL VANDEVELDE, T VERMORKEN, JB HARVEY, VJ HOLDAWAY, TM KAY, RG MASON, BH FORBES, JF BASTERT, G SAUERBREI, W SCHEURLEN, H SCHUMACHER, M FOCAN, C LOBELLE, JP PEEK, U OATES, GD POWELL, J DURAND, M MAURIAC, L GELMAN, RS HENDERSON, IC SHAPIRO, CL HANCOCK, AK JACKSON, S RAGAZ, J HENDERSON, IC KORZUN, A WOOD, WC YOSHIMOTO, M BAUM, M HOUGHTON, J HORGAN, K HUGHES, L STEWART, HJ GORDON, NH DAVIS, HL DELOZIER, T MACELESECH, J RAMBERT, P ANDRYSEK, O BARKMANOVA, J OWEN, JR HOWELL, A RIBEIRO, GC SWINDELL, R DEOLIVEIRA, CF CARSTENSEN, B PALSHOF, T JOHANSEN, H KORZENIOWSKI, S SKOLYSZEWSKI, J ANDERSEN, KW DOMBERNOWSKY, P MOURIDSEN, HT ROSE, C CORCORAN, N TRAMPISCH, HJ ABELOFF, MD CARBONE, PC GLICK, J GRAY, R TORMEY, DC BUYSE, M MIGNOLET, F PARIDAENS, R VANDRIEL, OJR SYLVESTER, RJ VANDEVELDE, CJH VANDONGEN, JA WELVAART, K SCANLON, EF SCHURMAN, S CATALANO, R CREECH, RH DESCHRYVER, A MCGREGOR, K YOSEF, HMA MCARDLE, CS SMITH, DC LARA, PC DENT, DM GUDGEON, CA HACKING, A BOCCARDO, F IZUO, M BENTLEY, A DORAN, Z FENTIMAN, IS HAYWARD, JL RUBENS, RD KAUFMANN, M JONAT, W SCHEURLEN, H VONFOURNIER, D KAUFMANN, M KLEFSTROM, P CUZICK, J MARGREITER, R ASSELAIN, B POUILLARD, P BAHI, J MILLA, A SANCHIZ, F CASTIGLIONE, M CAVALLI, F COLLINS, J GELBER, RD GOLDHIRSCH, A ISLEY, MR LINDTNER, J PRICE, KN RUDENSTAM, CM SENN, HJ BLISS, JM CHILVERS, CED COOMBES, RC MARTY, M BOROVIK, R BRUFMAN, G ROBINSON, E PANNUTI, F TAKASHIMA, S YASUTOMI, T HOLM, LE SONOO, H YAMASHITA, J BONTE, J BUZDAR, AU SMITH, T MARTIN, P ROMAIN, S AHMANN, D SCHAID, DJ HAKES, T NORTON, L WITTES, R FOROGLOU, P LISSAIOS, B BONADONNA, G DELVECCHIO, M VALAGUSSA, P VERONESI, U DUBOIS, JB BRUFMAN, G HAYAT, H BIANCO, AR LIPPMAN, ME PIERCE, LJ SIMON, R STEINBERG, SM NOMURA, Y DELAHUERTA, R SAINZ, MG BROWN, A FISHER, B REDMOND, C WOLMARK, N BAUM, M JACKSON, IM PALMER, MK INGLE, JN SCHAID, DJ BENGTSSON, NO LARSSON, LG LYTHGOE, JP SWINDELL, R KISSIN, M BLAMEY, RW MITCHELL, AK ROBERTSON, JFR CASTIGLIONE, M FLUCKIGER, H SENN, HJ NAKAMURA, Y MATHE, G MISSET, JL DESHPANDE, N DIMARTINO, L CLARKE, EA MCLAUGHLIN, JR CLARK, RM LEVINE, M MORIMOTO, K GUNDERSEN, S HAUERJENSEN, M HOST, H CROSSLEY, E DURRANT, K HARRIS, A CLARKE, M COLLINS, R GODWIN, J GRAY, R GREAVES, E HARWOOD, C MEAD, G PETO, R WHEATLEY, K HILL, C LACOUR, J LAPLANCHE, A LE, M SARRAZIN, D SEMIGLAZOV, V BROCKSCHMIDT, J COOPER, MR MEAKIN, JW PANZARELLA, T PRITCHARD, KI TREURNIETDONKER, AD VANPUTTEN, WLJ EASTON, D POWLES, TJ GAZET, JC DOUGLAS, P HACKING, A HOST, H LINDTNER, A NOTTER, G BRYANT, AJS EWING, GH KRUSHEN, JL NISSENMEYER, R FORREST, APM MCDONALD, C STEWART, HJ MOLLER, TR RYDEN, S CARSTENSEN, J HATSCHEK, T SODERBERG, M CARPENTER, JT CRAWLEY, J GREEN, S OSBORNE, CK RUTQVIST, LE WALLGREN, A BRENNER, H HERCBERGS, A DEBOER, G PATERSON, AHG PRITCHARD, KI NAJA, A REID, M SPITTLE, M SENANAYAKE, F MEIER, P TENGRUP, I TENNVALLNITTBY, L CAFFIER, H BEZWODA, WR HOLMBERG, L SEVELDA, P ZIELINSKY, CC JAKESZ, R BUCHANAN, RB CROSS, M DUNN, JA GILLESPIE KELLY, K MORRISON, JM LITTON, A CHLEBOWSKI, RT AF ABE, O ABE, R ASAISHI, K ENOMOTO, K HATTORI, T INO, Y KIKUCHI, K KOYAMA, H SAWA, K UCHINO, J YOSHIDA, M HAYBITTLE, JL VANDEVELDE, T VERMORKEN, JB HARVEY, VJ HOLDAWAY, TM KAY, RG MASON, BH FORBES, JF BASTERT, G SAUERBREI, W SCHEURLEN, H SCHUMACHER, M FOCAN, C LOBELLE, JP PEEK, U OATES, GD POWELL, J DURAND, M MAURIAC, L GELMAN, RS HENDERSON, IC SHAPIRO, CL HANCOCK, AK JACKSON, S RAGAZ, J HENDERSON, IC KORZUN, A WOOD, WC YOSHIMOTO, M BAUM, M HOUGHTON, J HORGAN, K HUGHES, L STEWART, HJ GORDON, NH DAVIS, HL DELOZIER, T MACELESECH, J RAMBERT, P ANDRYSEK, O BARKMANOVA, J OWEN, JR HOWELL, A RIBEIRO, GC SWINDELL, R DEOLIVEIRA, CF CARSTENSEN, B PALSHOF, T JOHANSEN, H KORZENIOWSKI, S SKOLYSZEWSKI, J ANDERSEN, KW DOMBERNOWSKY, P MOURIDSEN, HT ROSE, C CORCORAN, N TRAMPISCH, HJ ABELOFF, MD CARBONE, PC GLICK, J GRAY, R TORMEY, DC BUYSE, M MIGNOLET, F PARIDAENS, R VANDRIEL, OJR SYLVESTER, RJ VANDEVELDE, CJH VANDONGEN, JA WELVAART, K SCANLON, EF SCHURMAN, S CATALANO, R CREECH, RH DESCHRYVER, A MCGREGOR, K YOSEF, HMA MCARDLE, CS SMITH, DC LARA, PC DENT, DM GUDGEON, CA HACKING, A BOCCARDO, F IZUO, M BENTLEY, A DORAN, Z FENTIMAN, IS HAYWARD, JL RUBENS, RD KAUFMANN, M JONAT, W SCHEURLEN, H VONFOURNIER, D KAUFMANN, M KLEFSTROM, P CUZICK, J MARGREITER, R ASSELAIN, B POUILLARD, P BAHI, J MILLA, A SANCHIZ, F CASTIGLIONE, M CAVALLI, F COLLINS, J GELBER, RD GOLDHIRSCH, A ISLEY, MR LINDTNER, J PRICE, KN RUDENSTAM, CM SENN, HJ BLISS, JM CHILVERS, CED COOMBES, RC MARTY, M BOROVIK, R BRUFMAN, G ROBINSON, E PANNUTI, F TAKASHIMA, S YASUTOMI, T HOLM, LE SONOO, H YAMASHITA, J BONTE, J BUZDAR, AU SMITH, T MARTIN, P ROMAIN, S AHMANN, D SCHAID, DJ HAKES, T NORTON, L WITTES, R FOROGLOU, P LISSAIOS, B BONADONNA, G DELVECCHIO, M VALAGUSSA, P VERONESI, U DUBOIS, JB BRUFMAN, G HAYAT, H BIANCO, AR LIPPMAN, ME PIERCE, LJ SIMON, R STEINBERG, SM NOMURA, Y DELAHUERTA, R SAINZ, MG BROWN, A FISHER, B REDMOND, C WOLMARK, N BAUM, M JACKSON, IM PALMER, MK INGLE, JN SCHAID, DJ BENGTSSON, NO LARSSON, LG LYTHGOE, JP SWINDELL, R KISSIN, M BLAMEY, RW MITCHELL, AK ROBERTSON, JFR CASTIGLIONE, M FLUCKIGER, H SENN, HJ NAKAMURA, Y MATHE, G MISSET, JL DESHPANDE, N DIMARTINO, L CLARKE, EA MCLAUGHLIN, JR CLARK, RM LEVINE, M MORIMOTO, K GUNDERSEN, S HAUERJENSEN, M HOST, H CROSSLEY, E DURRANT, K HARRIS, A CLARKE, M COLLINS, R GODWIN, J GRAY, R GREAVES, E HARWOOD, C MEAD, G PETO, R WHEATLEY, K HILL, C LACOUR, J LAPLANCHE, A LE, M SARRAZIN, D SEMIGLAZOV, V BROCKSCHMIDT, J COOPER, MR MEAKIN, JW PANZARELLA, T PRITCHARD, KI TREURNIETDONKER, AD VANPUTTEN, WLJ EASTON, D POWLES, TJ GAZET, JC DOUGLAS, P HACKING, A HOST, H LINDTNER, A NOTTER, G BRYANT, AJS EWING, GH KRUSHEN, JL NISSENMEYER, R FORREST, APM MCDONALD, C STEWART, HJ MOLLER, TR RYDEN, S CARSTENSEN, J HATSCHEK, T SODERBERG, M CARPENTER, JT CRAWLEY, J GREEN, S OSBORNE, CK RUTQVIST, LE WALLGREN, A BRENNER, H HERCBERGS, A DEBOER, G PATERSON, AHG PRITCHARD, KI NAJA, A REID, M SPITTLE, M SENANAYAKE, F MEIER, P TENGRUP, I TENNVALLNITTBY, L CAFFIER, H BEZWODA, WR HOLMBERG, L SEVELDA, P ZIELINSKY, CC JAKESZ, R BUCHANAN, RB CROSS, M DUNN, JA GILLESPIE KELLY, K MORRISON, JM LITTON, A CHLEBOWSKI, RT TI SYSTEMIC TREATMENT OF EARLY BREAST-CANCER BY HORMONAL, CYTOTOXIC, OR IMMUNE THERAPY - 133 RANDOMIZED TRIALS INVOLVING 31000 RECURRENCES AND 24000 DEATHS AMONG 75000 WOMEN .2. SO LANCET LA English DT Review ID REQUIRING PROLONGED OBSERVATION; SURGICAL ADJUVANT BREAST; TAMOXIFEN THERAPY; CHEMOTHERAPY; IRRADIATION; PATIENT; DESIGN; TUMORS C1 INTEGRAAL KANKERCTR, AMSTERDAM, NETHERLANDS. AUCKLAND BREAST CANC STUDY GRP, AUCKLAND, NETHERLANDS. AKAD WISSENSCH DDR, O-1086 BERLIN, GERMANY. BIRMINGHAM GEN HOSP, BIRMINGHAM, ENGLAND. FDN BERGONIE, F-33076 BORDEAUX, FRANCE. HARVARD UNIV, SCH MED, DANA FARBER CANC INST, BOSTON, MA 02115 USA. BRADFORD ROYAL INFIRM, BRADFORD, ENGLAND. BRITISH COLUMBIA CANC FDN, VANCOUVER V5Z 3J3, BC, CANADA. CANC INST HOSP, TOKYO, JAPAN. CANC RES CAMPAIGN, LONDON, ENGLAND. CARDIFF SURG TRIALISTS, CARDIFF, WALES. CASE WESTERN RESERVE UNIV, CLEVELAND, OH 44106 USA. CTR REG FRANCOIS BACLESSE, CAEN, FRANCE. CTR RENE HUGUENIN, ST CLOUD, FRANCE. CHARLES UNIV, CS-11636 PRAGUE 1, CZECHOSLOVAKIA. CHELTENHAM GEN HOSP, CHELTENHAM, ENGLAND. CHRISTIE HOSP & HOLT RADIUM INST, MANCHESTER M20 9BX, LANCS, ENGLAND. COIMBRA INST ONCOL, COIMBRA, PORTUGAL. DANISH CANC REGISTRY, COPENHAGEN, DENMARK. COPENHAGEN RADIUM CTR, COPENHAGEN, DENMARK. CRACOW INST ONCOL, KRAKOW, POLAND. ST LUKES HOSP, DUBLIN, IRELAND. UNIV DUSSELDORF, W-4000 DUSSELDORF 1, GERMANY. EUROPEAN ORG RES TREATMENT CANC, BRUSSELS, BELGIUM. EASTERN COOPERAT ONCOL GRP, BOSTON, MA USA. DANISH BREAST CANC COOPERAT GRP, COPENHAGEN, DENMARK. CANC & LEUKEMIA GRP B, BROOKLINE, MA USA. EVANSTON HOSP CORP, EVANSTON, IL 60201 USA. FOX CHASE CANC INST, PHILADELPHIA, PA 19111 USA. STATE UNIV GHENT HOSP, B-9000 GHENT, BELGIUM. GLASCOW BEATSON ONCOL CTR, GLASGOW, SCOTLAND. VICTORIA INFIRM, GLASGOW G42 9TY, SCOTLAND. GRANADA UNIV HOSP, GRANADA, SPAIN. GROOTE SCHUUR HOSP, CAPE TOWN 7925, SOUTH AFRICA. GUNMA UNIV, MAEBASHI, GUNMA 371, JAPAN. GUYS HOSP, LONDON SE1 9RT, ENGLAND. UNIV HEIDELBERG, W-6900 HEIDELBERG, GERMANY. UNIV HEIDELBERG 2, HEIDELBERG, GERMANY. UNIV HEIDELBERG 1, HEIDELBERG, GERMANY. DEACONESS MED CTR, HELSINKI, FINLAND. IMPERIAL CANC RES FUND, LONDON WC2A 3PX, ENGLAND. UNIV INNSBRUCK, A-6020 INNSBRUCK, AUSTRIA. INST CURIE, F-75231 PARIS 05, FRANCE. INST SALAH AZAIZ, TUNIS, TUNISIA. INST POLICLIN, BARCELONA, SPAIN. INT LUDWIG BREAST CANC STUDY GRP, LONDON, ENGLAND. CHARING CROSS HOSP, INT COLLABORAT CANC GRP, LONDON W6 8RP, ENGLAND. TECHNION ISRAEL INST TECHNOL, RAMBAM MED CTR, HAIFA, ISRAEL. KAROLINSKA HOSP, S-10401 STOCKHOLM 60, SWEDEN. KAWASAKI MED UNIV, KURASHIKI, OKAYAMA 70101, JAPAN. KUMAMOTO UNIV GRP, KUMAMOTO, JAPAN. ACAD HOSP ST RAFAEL, B-3000 LOUVAIN, BELGIUM. MD ANDERSON CANC CTR, HOUSTON, TX USA. LAB CANEROL BIOL APM, MARSEILLE, FRANCE. MAYO CLIN & MAYO FDN, ROCHESTER, MN 55905 USA. MEM SLOAN KETTERING CANC CTR, NEW YORK, NY 10021 USA. METAXAS MEM CANC HOSP, ATHENS, GREECE. IST NAZL STUDIO & CURA TUMORI, I-20133 MILAN, ITALY. CTR PAUL LAMARQUE, F-34033 MONTPELLIER, FRANCE. NAPLES UNIV, I-80138 NAPLES, ITALY. NCI, BETHESDA, MD 20892 USA. NATL KYUSHU CANC CTR HOSP, KYUSHU, JAPAN. NATL MED CTR, MEXICO CITY, DF, MEXICO. NATL SURG ADJUVANT PROJECT BREAST & BOWEL CANC, PITTSBURGH, PA USA. N CENT CANC TREATMENT GRP, ROCHESTER, MN USA. NORTHWICK PK HOSP & CLIN RES CTR, HARROW HA1 3UJ, MIDDX, ENGLAND. NOTTINGHAM CITY HOSP, NOTTINGHAM NG5 1PB, ENGLAND. OITA PREFECTURAL HOSP, OITA, JAPAN. ONCOL HOSP A BUSINICO, SARDINIA, FRANCE. ONTARIO CANC TREATMENT & RES FDN, TORONTO, ONTARIO, CANADA. ONTARIO CLIN ONCOL GRP, TORONTO, ONTARIO, CANADA. OSAKA CITY MED SCH, OSAKA, JAPAN. OSLO RADIUM HOSP, OSLO, NORWAY. CHURCHILL HOSP, OXFORD OX3 7LJ, ENGLAND. IMPERIAL CANC RES FUND, MRC, CLIN TRIAL SERV UNIT, OXFORD, ENGLAND. INST GUSTAVE ROUSSY, F-94805 VILLEJUIF, FRANCE. NN PETROV ONCOL RES INST, LENINGRAD 188646, USSR. PIEDMONT ONCOL ASSOC, ATLANTA, GA USA. PRINCESS MARGARET HOSP, TORONTO M4X 1K9, ONTARIO, CANADA. ROTTERDAM RADIOTHERAPEUT INST, ROTTERDAM, NETHERLANDS. ROYAL MARSDEN HOSP, INST CANC RES, LONDON, ENGLAND. ST GEORGE HOSP, LONDON, ENGLAND. SASKATCHEWAN CANC FDN, SASKATOON, SASKATCHEWAN, CANADA. SW ONCOL GRP, KANSAS CITY, KS 66103 USA. STOCKHOLM BREAST CANC STUDY GRP, STOCKHOLM, SWEDEN. TEL AVIV UNIV, IL-69978 TEL AVIV, ISRAEL. TORONTO EDMONTON BREAST CANC STUDY GRP, TORONTO, ONTARIO, CANADA. TOULOUSE CTR CLAUDIUS REGAUD, TOULOUSE, FRANCE. UNIV CHICAGO, CHICAGO, IL 60637 USA. UNIV LUND, S-22101 LUND, SWEDEN. UNIV WURZBURG, W-8700 WURZBURG, GERMANY. UNIV WITWATERSRAND, JOHANNESBURG 2001, SOUTH AFRICA. UPPSALA OREBRO CANC STUDY GRP, UPPSALA, SWEDEN. VIENNA UNIV HOSP, DEPT GYNAECOL 1, VIENNA, AUSTRIA. VIENNA UNIV HOSP, DEPT SURG 1, VIENNA, AUSTRIA. WESSEX RADIOTHERAPY CTR, WESSEX, ENGLAND. ADDENBROOKES HOSP, CAMBRIDGE CB2 2QQ, ENGLAND. RP ABE, O (reprint author), RADCLIFFE INFIRM, NUFFIELD DEPT CLIN MED, ICRF MRC CLIN TRIAL SERV UNIT, OXFORD OX2 6HE, ENGLAND. RI Jonat, Walter/E-3024-2010; McLaughlin, John/E-4577-2013; Barkmanova, Jaroslava/A-1411-2017; Brenner, Hermann/B-4627-2017 OI Barkmanova, Jaroslava/0000-0003-1406-7292; Brenner, Hermann/0000-0002-6129-1572 NR 39 TC 871 Z9 875 U1 2 U2 29 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 EI 1474-547X J9 LANCET JI Lancet PD JAN 11 PY 1992 VL 339 IS 8785 BP 71 EP 85 PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA GZ156 UT WOS:A1992GZ15600001 ER PT J AU SABOLIC, I SHI, LB BROWN, D AUSIELLO, DA VERKMAN, AS AF SABOLIC, I SHI, LB BROWN, D AUSIELLO, DA VERKMAN, AS TI PROTEINASES INHIBIT H+-ATPASE AND NA+/H+ EXCHANGE BUT NOT WATER TRANSPORT IN APICAL AND ENDOSOMAL MEMBRANES FROM RAT PROXIMAL TUBULE SO BIOCHIMICA ET BIOPHYSICA ACTA LA English DT Article DE ATPASE, H+; WATER TRANSPORT; SODIUM ION-PROTON EXCHANGE; PROTEINASE; MERCURIAL; ENZYME INHIBITION; SODIUM ION PROTON ANTIPORT; (RAT) ID RENAL BRUSH-BORDER; RED-CELL WATER; UREA TRANSPORT; PLASMA-MEMBRANE; KIDNEY CORTEX; PROTON PUMPS; ECTO-ATPASE; VESICLES; CHANNELS; PERMEABILITIES AB A marked increase in water permeability can be induced in Xenopus oocytes by injection of mRNA from tissues that express water channels, suggesting that the water channel is a protein. In view of this and previous reports which showed that proteinases may interfere with mercurial inhibition of water transport in red blood cells (RBC), we examined the influence of trypsin, chymotrypsin, papain, pronase, subtilisin and thermolysin on water permeability as well as on ATPase activity, H+-pump, passive H+ conductance, and Na+/H+ exchange in apical brush-border vesicles (BBMV) and endosomal (EV) vesicles from rat renal cortex. H+ transport was measured by Acridine orange fluorescence quenching and water transport by stopped-flow light scattering. As measured by potential-driven H+ accumulation in BBMV and EV, proteinase treatment had little effect on vesicle integrity. In BBMV, ecto-ATPase activity was inhibited by 15-30%, Na+/H+ exchange by 20-55%, and H+ conductance was unchanged. Osmotic water permeability (P(f)) was 570-mu-m/s and was inhibited 85-90% by 0.6 mM HgCl2; proteinase treatment did not effect P(f) or the HgCl2 inhibition. In EV, NEM-sensitive H+ accumulation and ATPase activity were inhibited by > 95%. P(f) (140-mu-m/s) and HgCl2 inhibition (75-85%) were not influenced by proteinase treatment. SDS-PAGE showed selective digestion of multiple polypeptides by proteinases. These results confirm the presence of water channels in BBMV and EV and demonstrate selective inhibition of ATPase function and Na+/H+ exchange by proteinase digestion. The lack of effect of proteinases on water transport contrasts with previous data in RBC which showed that proteinases prevent the inhibition of water transport by mercurials. We conclude that the water channel may be a small integral membrane protein which, unlike the H+-ATPase and Na+/H+ exchanger, has no functionally important membrane domains that are sensitive to proteolysis. C1 UNIV CALIF SAN FRANCISCO,CARDIOVASC RES INST,DEPT PHYSIOL,SAN FRANCISCO,CA 94143. MASSACHUSETTS GEN HOSP,MED SERV,RENAL UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. UNIV CALIF SAN FRANCISCO,CARDIOVASC RES INST,DEPT MED,SAN FRANCISCO,CA 94143. NR 34 TC 11 Z9 11 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-3002 J9 BIOCHIM BIOPHYS ACTA PD JAN 10 PY 1992 VL 1103 IS 1 BP 137 EP 147 DI 10.1016/0005-2736(92)90067-V PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA HC617 UT WOS:A1992HC61700018 PM 1309658 ER PT J AU OCKENHOUSE, CF BETAGERI, R SPRINGER, TA STAUNTON, DE AF OCKENHOUSE, CF BETAGERI, R SPRINGER, TA STAUNTON, DE TI PLASMODIUM FALCIPARUM-INFECTED ERYTHROCYTES BIND ICAM-1 AT A SITE DISTINCT FROM LFA-1, MAC-1, AND HUMAN RHINOVIRUS SO CELL LA English DT Article ID INTERCELLULAR-ADHESION MOLECULE-1; MEMBRANE GLYCOPROTEIN; ENDOTHELIAL-CELLS; RECEPTOR; LIGAND; IDENTIFICATION; IMMUNOGLOBULIN; INTERFERON; ACTIVATION; ADHERENCE AB The attachment of erythrocytes infected with P. falciparum to human venular endothelium is the primary step leading to complications from severe and cerebral malaria. Intercellular adhesion molecule-1 (ICAM-1, CD54) has been implicated as a cytoadhesion receptor for P. falciparum-infected erythrocytes. Characterization of domain deletion, human/murine chimeric ICAM-1 molecules, and amino acid substitution mutants localized the primary binding site for parasitized erythrocytes to the first amino-terminal immunoglobulin-like domain of ICAM-1. The ICAM-1 binding site is distinct f rom those recognized by LFA-1, Mac-1, and the human major-type rhinoviruses. Synthetic peptides encompassing the binding site on ICAM-1 inhibited malaria-infected erythrocyte adhesion to ICAM-1-coated surfaces with a K(i) of 0.1-0.3 mM, whereas the K(i) for soluble ICAM-1 is 0.15-mu-M. These findings have implications for the therapeutic reversal of malaria-infected erythrocyte sequestration in the host microvasculature. C1 WALTER REED ARMY MED CTR,DEPT MED,WASHINGTON,DC 20307. BOEHRINGER INGELHEIM PHARMACEUT INC,RIDGEFIELD,CT 06877. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. RP OCKENHOUSE, CF (reprint author), WALTER REED ARMY MED CTR,INST RES,WASHINGTON,DC 20307, USA. FU NCI NIH HHS [CA31798] NR 29 TC 130 Z9 131 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD JAN 10 PY 1992 VL 68 IS 1 BP 63 EP 69 DI 10.1016/0092-8674(92)90206-R PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA GZ583 UT WOS:A1992GZ58300009 PM 1346257 ER PT J AU SHIRODKAR, S EWEN, M DECAPRIO, JA MORGAN, J LIVINGSTON, DM CHITTENDEN, T AF SHIRODKAR, S EWEN, M DECAPRIO, JA MORGAN, J LIVINGSTON, DM CHITTENDEN, T TI THE TRANSCRIPTION FACTOR E2F INTERACTS WITH THE RETINOBLASTOMA PRODUCT AND A P107-CYCLIN-A COMPLEX IN A CELL CYCLE-REGULATED MANNER SO CELL LA English DT Article ID ADENOVIRUS E1A PROTEINS; SV40 LARGE-T; GENE-PRODUCT; SUSCEPTIBILITY GENE; TRANS-ACTIVATION; DNA-REPLICATION; RB GENE; TRANSACTIVATION; PROMOTER; BINDING AB E2F is a transcription factor believed to play a role in the activation of genes required for cellular proliferation. Its regulation is likely important for maintenance of G0 and for the initiation of cell growth. The retinoblastoma product (RB) forms a complex with E2F in G1 in primary and established human cells. As these cells enter S, a second E2F-containing complex appears. It contains p107, a nuclear "pocket" protein with similarities in structure and protein-binding properties to RB, and cyclin A, a cyclin believed to play a role in facilitating DNA replication. Hence, the regulation of E2F is carried out differently in G1 or S. The presence of cyclin A and a pocket protein, a possible cell growth regulator, in the same S phase-associated complex suggests a link between the function of E2F and the regulation of the DNA replication process. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP SHIRODKAR, S (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115, USA. NR 50 TC 573 Z9 576 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD JAN 10 PY 1992 VL 68 IS 1 BP 157 EP 166 DI 10.1016/0092-8674(92)90214-W PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA GZ583 UT WOS:A1992GZ58300017 PM 1531040 ER PT J AU CAO, L FAHA, B DEMBSKI, M TSAI, LH HARLOW, E DYSON, N AF CAO, L FAHA, B DEMBSKI, M TSAI, LH HARLOW, E DYSON, N TI INDEPENDENT BINDING OF THE RETINOBLASTOMA PROTEIN AND P107 TO THE TRANSCRIPTION FACTOR E2F SO NATURE LA English DT Article ID LARGE T-ANTIGEN; ADENOVIRUS E1A PROTEINS; GENE-PRODUCT; POLYACRYLAMIDE GELS; SV40; TRANSFORMATION; REGIONS; CELLS AB THE cellular protein p107 and the retinoblastoma protein (pRB) have many features in common. Most strikingly, they contain homologous protein domains that mediate interaction with the oncoproteins of several small DNA tumour viruses, including adenovirus E1A and SV40 large-T antigen 1-9. In cells that do not contain these viral oncoproteins, pRB interacts with the cellular transcription factor E2F (refs 10-12) or a related protein termed DRTF1 (ref. 13). E2F associates with a form of pRB that is found primarily in G1 cells 10. It seems that the E2F-pRB complex dissociates near the G1-S boundary before the initiation of S phase, releasing free E2F and apparently, stimulating the ability of E2F to activate transcription 14. Cells that express E1A have no or little pRB-E2F complex, presumably because of the association of E1A with pRB 10,15. During S phase, E2F forms a second complex that contains cyclin A but apparently lacks pRB 1-5. Here, we report that p107 is found in the cyclin A/E2F complex and that this complex also contains p33cdk2. These observations suggest that p107 and pRB cooperate in the regulation of E2F activity, each affecting different stages of the cell cycle. Thus, by binding to pRB and p107, E1A and large-T antigen target two distinct aspects of E2F regulation. C1 MASSACHUSETTS GEN HOSP CANC CTR, BLDG 149, 13TH ST, BOSTON, MA 02129 USA. NR 35 TC 379 Z9 383 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD JAN 9 PY 1992 VL 355 IS 6356 BP 176 EP 179 DI 10.1038/355176a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GY629 UT WOS:A1992GY62900063 PM 1530885 ER PT J AU SAAG, MS POWDERLY, WG CLOUD, GA ROBINSON, P GRIECO, MH SHARKEY, PK THOMPSON, SE SUGAR, AM TUAZON, CU FISHER, JF HYSLOP, N JACOBSON, JM HAFNER, R DISMUKES, WE AF SAAG, MS POWDERLY, WG CLOUD, GA ROBINSON, P GRIECO, MH SHARKEY, PK THOMPSON, SE SUGAR, AM TUAZON, CU FISHER, JF HYSLOP, N JACOBSON, JM HAFNER, R DISMUKES, WE TI COMPARISON OF AMPHOTERICIN-B WITH FLUCONAZOLE IN THE TREATMENT OF ACUTE AIDS-ASSOCIATED CRYPTOCOCCAL MENINGITIS SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ACQUIRED IMMUNODEFICIENCY SYNDROME; FLUCYTOSINE; NEOFORMANS; EXPERIENCE AB Background. Intravenous amphotericin B, with or without flucytosine, is usually standard therapy for cryptococcal meningitis in patients with the acquired immunodeficiency syndrome (AIDS): Fluconazole, an oral triazole agent, represents a promising new approach to the treatment of cryptococcal disease. Methods. In a randomized multicenter trial, we compared intravenous amphotericin B with oral fluconazole as primary therapy for AIDS-associated acute cryptococcal meningitis. Eligible patents, in all of whom the diagnosis had been confirmed by culture, were randomly assigned in a 2:1 ratio to receive either fluconazole (200 mg per day) or amphotericin B. Treatment was considered successful if the patient had had two consecutive negative cerebrospinal fluid cultures by the end of the 10-week treatment period. Results. Of the 194 eligible patients, 131 received fluconazole and 63 received amphotericin B (mean daily dose, 0.4 mg per kilogram of body weight in patients with successful treatment and 0.5 mg per kilogram in patients with treatment failure; P = 0.34). Treatment was successful in 25 of the 63 amphotericin B recipients (40 percent; 95 percent confidence interval, 26 percent to 53 percent) and in 44 of the 131 fluconazole recipients (34 percent; 95 percent confidence interval, 25 percent to 42 percent) (P = 0.40). There was no significant difference between the groups in overall mortality due to cryptococcosis (amphotericin vs. fluconazole, 9 of 63 [14 percent] vs. 24 of 131 [18 percent]; P = 0.48); however, mortality during the first two weeks of therapy was higher in the fluconazole group (15 percent vs. 8 percent; P = 0.25). The median length of time to the first negative cerebrospinal fluid culture was 42 days (95 percent confidence interval, 28 to 71) in the amphotericin B group and 64 days (95 percent confidence interval, 53 to 67) in the fluconazole group (P = 0.25). Multivariate analyses identified abnormal mental status (lethargy, somnolence, or obtundation) as the most important predictive factor of a high risk of death during therapy (P < 0.0001). Conclusions. Fluconazole is an effective alternative to amphotericin B as primary treatment of cryptococcal meningitis in patients with AIDS. Single-drug therapy with either drug is most effective in patients who are at low risk for treatment failure. The optimal therapy for patients at high risk remains to be determined. C1 UNIV ALABAMA, SCH MED, DEPT MED, DIV INFECT DIS, BIRMINGHAM, AL 35233 USA. UNIV ALABAMA, SCH MED, CTR COMPREHENS CANC, DIV BIOSTAT, BIRMINGHAM, AL 35233 USA. WASHINGTON UNIV, SCH MED, DIV INFECT DIS, ST LOUIS, MO 63110 USA. ST LOUIS VET AFFAIRS MED CTR, ST LOUIS, MO USA. COLUMBIA UNIV, ST LUKES ROOSEVELT HOSP, SCH MED, NEW YORK, NY 10027 USA. UNIV TEXAS SAN ANTONIO, SAN ANTONIO, TX 78285 USA. AUDIE L MURPHY VET AFFAIRS HOSP, SAN ANTONIO, TX USA. EMORY UNIV, GRADY MEM HOSP, ATLANTA, GA 30322 USA. BOSTON CITY HOSP, DEPT MED, BOSTON, MA 02118 USA. BOSTON UNIV, UNIV HOSP, DEPT MED, BOSTON, MA 02215 USA. GEORGE WASHINGTON UNIV, DEPT MED, WASHINGTON, DC 20052 USA. MED COLL GEORGIA, DEPT MED, AUGUSTA, GA 30912 USA. TULANE UNIV, DEPT MED, NEW ORLEANS, LA 70118 USA. MT SINAI MED CTR, DEPT MED, DIV INFECT DIS, NEW YORK, NY 10029 USA. BRONX VET AFFAIRS MED CTR, BRONX, NY USA. NIAID, DIV AIDS, BETHESDA, MD 20892 USA. NIAID, DIV MICROBIOL & INFECT DIS, BETHESDA, MD 20892 USA. PFIZER INC, CENT RES, GROTON, CT 06340 USA. RP SAAG, MS (reprint author), UNIV ALABAMA, BIRMINGHAM VET AFFAIRS MED CTR, 700 19TH ST S, RM 2B-108, BIRMINGHAM, AL 35233 USA. FU NCRR NIH HHS [RR-00032]; NIAID NIH HHS [N01-AI-15082, NIH-NIAID-DMID-91-04] NR 25 TC 476 Z9 492 U1 1 U2 4 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 9 PY 1992 VL 326 IS 2 BP 83 EP 89 DI 10.1056/NEJM199201093260202 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA GY045 UT WOS:A1992GY04500002 PM 1727236 ER PT J AU FERRUCCI, JT AF FERRUCCI, JT TI SCREENING FOR COLORECTAL-CANCER SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP FERRUCCI, JT (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 1 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 JAN 9 PY 1992 VL 326 IS 2 BP 136 EP 136 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA GY045 UT WOS:A1992GY04500018 PM 1727227 ER PT J AU WEEKS, JC TIERNEY, MR WEINSTEIN, MC AF WEEKS, JC TIERNEY, MR WEINSTEIN, MC TI PROPHYLACTIC IMMUNE GLOBULIN IN CHRONIC LYMPHOCYTIC-LEUKEMIA - REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. RP WEEKS, JC (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU 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 JAN 9 PY 1992 VL 326 IS 2 BP 139 EP 139 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA GY045 UT WOS:A1992GY04500027 ER PT J AU SURMAN, OS AF SURMAN, OS TI QUEUING IN CANADA SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter RP SURMAN, OS (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 8 PY 1992 VL 267 IS 2 BP 234 EP 234 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA GY046 UT WOS:A1992GY04600019 PM 1550613 ER PT J AU SAIKI, H CHAN, ET WONG, E YAMAMURO, W OOKHTENS, M KAPLOWITZ, N AF SAIKI, H CHAN, ET WONG, E YAMAMURO, W OOKHTENS, M KAPLOWITZ, N TI ZONAL DISTRIBUTION OF CYSTEINE UPTAKE IN THE PERFUSED-RAT-LIVER SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GLUTATHIONE; HETEROGENEITY; HEPATOCYTES; TRANSPORT AB When in situ perfused rat livers were administered tracer or physiologic concentrations of [S-35]cysteine, a zone III (perivenous) predominance of uptake was observed in either antegrade or retrograde single-pass perfusion, as determined by quantitative densitometry of autoradiographs of liver section. This pattern remained unchanged from 30 s to 5 min observed. At higher supraphysiologic doses a more uniform acinar distribution of cysteine uptake was observed. Uptake rates of cysteine in antegrade perfusion indicated an apparent saturable component at low but physiologic cysteine concentrations. That uptake rather than metabolic trapping accounts for this perivenular pattern was supported by finding identical zonal distribution under conditions in which GSH and protein synthesis were markedly inhibited. Furthermore, increasing or decreasing hepatic cysteine pool sizes did not affect the extraction or zonation. These results suggest that a low K(m) transport system for cysteine is localized in zone III of the hepatic acinus. C1 UNIV SO CALIF,SCH MED,DEPT MED,DIV GASTROINTESTINAL & LIVER DIS,LOS ANGELES,CA 90033. US DEPT VET AFFAIRS,OUTPATIENT CLIN,LOS ANGELES,CA 90013. FU NIDDK NIH HHS [DK30312] NR 16 TC 18 Z9 18 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 JAN 5 PY 1992 VL 267 IS 1 BP 192 EP 196 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GY439 UT WOS:A1992GY43900035 PM 1730587 ER PT J AU LALLEMANTLECOEUR, S LALLEMANT, M AF LALLEMANTLECOEUR, S LALLEMANT, M TI TWINNING AMONG HIV-INFECTED MOTHERS SO LANCET LA English DT Letter ID HUMAN IMMUNODEFICIENCY VIRUS; TRANSMISSION; INFANTS; TYPE-1; WOMEN C1 ORSTOM,PARIS,FRANCE. RP LALLEMANTLECOEUR, S (reprint author), HARVARD UNIV,SCH MED,SIDNEY FARBER CANC INST,BOSTON,MA 02115, USA. NR 10 TC 1 Z9 1 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD JAN 4 PY 1992 VL 339 IS 8784 BP 66 EP 67 DI 10.1016/0140-6736(92)90199-D PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA GY043 UT WOS:A1992GY04300060 PM 1345997 ER PT J AU EWEN, ME FAHA, B HARLOW, E LIVINGSTON, DM AF EWEN, ME FAHA, B HARLOW, E LIVINGSTON, DM TI INTERACTION OF P107 WITH CYCLIN-A INDEPENDENT OF COMPLEX-FORMATION WITH VIRAL ONCOPROTEINS SO SCIENCE LA English DT Article ID RETINOBLASTOMA GENE-PRODUCT; LARGE T-ANTIGEN; SV40 LARGE-T; CELL-CYCLE; SUSCEPTIBILITY GENE; BINDING; PROTEIN; PHOSPHORYLATION; ADENOVIRUS-E1A; REGIONS AB The p107 protein and the retinoblastoma protein (R-B) both bind specifically to two viral oncoproteins, the SV40 T antigen (T) and adenoviral protein E1A (E1A). Like RB, p107 contains a segment (the pocket) that, alone, can bind specifically to T, EIA, and multiple cellular proteins. Cyclin A bound to the p107 pocket, but not the R-B pocket. Although both pockets contain two, related collinear subsegments (A and B), the unique sequence in the p107 pocket that occupies the space between A and B is required for the interaction with cyclin A. C1 MASSACHUSETTS GEN HOSP,CTR CANC,BOSTON,MA 02129. RP EWEN, ME (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115, USA. NR 33 TC 220 Z9 221 U1 0 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 JAN 3 PY 1992 VL 255 IS 5040 BP 85 EP 87 DI 10.1126/science.1532457 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GX791 UT WOS:A1992GX79100043 PM 1532457 ER PT J AU FAHA, B EWEN, ME TSAI, LH LIVINGSTON, DM HARLOW, E AF FAHA, B EWEN, ME TSAI, LH LIVINGSTON, DM HARLOW, E TI INTERACTION BETWEEN HUMAN CYCLIN-A AND ADENOVIRUS E1A-ASSOCIATED P107 PROTEIN SO SCIENCE LA English DT Article ID LARGE T-ANTIGEN; CELL-CYCLE; RETINOBLASTOMA PROTEIN; E1A PROTEINS; BINDING; COMPLEXES; REGIONS; PRODUCT; GENE AB The products of the adenovirus early region IA (EIA) gene are potent oncoproteins when tested in standard transformation and immortalization assays. Many of the changes induced by EIA may be due to its interaction with cellular proteins. Four of these cellular proteins are the retinoblastoma protein (pRB), p107, cyclin A, and p33cdk2. The pRB and p107 proteins are structurally related and have several characteristics in common, including that they both bind to the SV40 large T oncoprotein as well as to E1A. Cyclin A and p33cdk2 are thought to function in the control of the cell cycle. They bind to one another, forming a kinase that closely resembles the cell cycle-regulating complexes containing p34cdc2. Cyclin A is now shown to bind to p107 in the absence of E1A. The association of p107 with cyclin A suggests a direct link between cell cycle control and the function of p107. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. RP FAHA, B (reprint author), MASSACHUSETTS GEN HOSP,CTR CANC,BOSTON,MA 02129, USA. FU NCI NIH HHS [CA 13106, CA 55339] NR 30 TC 214 Z9 215 U1 0 U2 2 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JAN 3 PY 1992 VL 255 IS 5040 BP 87 EP 90 DI 10.1126/science.1532458 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GX791 UT WOS:A1992GX79100044 PM 1532458 ER PT J AU TAYLOR, SL NORDLEE, JA BUSH, RK AF TAYLOR, SL NORDLEE, JA BUSH, RK TI FOOD ALLERGIES SO ACS SYMPOSIUM SERIES LA English DT Review ID BREAST-FED INFANTS; NATURAL-HISTORY; HYPERSENSITIVITY REACTIONS; ATOPIC-DERMATITIS; ADVERSE REACTIONS; COWS MILK; IMMEDIATE HYPERSENSITIVITY; SENSITIVE INDIVIDUALS; ASTHMATIC-PATIENTS; CHILDREN C1 WILLIAM S MIDDLETON MEM VET ADM MED CTR, MADISON, WI 53705 USA. UNIV WISCONSIN, DEPT MED, MADISON, WI 53792 USA. RP UNIV NEBRASKA, DEPT FOOD SCI & TECHNOL, LINCOLN, NE 68583 USA. NR 82 TC 6 Z9 6 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0097-6156 J9 ACS SYM SER JI ACS Symp. Ser. PY 1992 VL 484 BP 316 EP 329 PG 14 WC Chemistry, Multidisciplinary SC Chemistry GA HN997 UT WOS:A1992HN99700028 ER PT J AU FINI, ME GIRARD, MT MATSUBARA, M AF FINI, ME GIRARD, MT MATSUBARA, M TI COLLAGENOLYTIC GELATINOLYTIC ENZYMES IN CORNEAL WOUND-HEALING SO ACTA OPHTHALMOLOGICA LA English DT Article; Proceedings Paper CT 8TH INTERNATIONAL MEDICAL SYMP ON WOUND HEALING OF THE OCULAR SURFACE / 30TH CONGRESS OF NORDIC OPHTHALMOLOGISTS CY AUG, 1991 CL HELSINKI, FINLAND SP PAULO FDN, NORD OPHTHALMOLOGISTS DE COLLAGENASE; GELATINASE; CORNEA; STROMA; BASEMENT MEMBRANE; COLLAGEN; EXTRACELLULAR MATRIX; WOUND HEALING; CORNEAL ULCERATION ID BASEMENT-MEMBRANE; EXPRESSION; FIBRILS; INVITRO; TISSUE; CELLS AB We have documented changes in expression of collagenolytic/gelatinolytic enzymes of the matrix metalloproteinase family (MMP) in healing or ulcerating corneal wounds of rat or rabbit. Correlation of our findings with specific changes in the extracellular matrix of the repair tissue suggests two different roles for the enzymes, MMP-2 and MMP-9. MMP-2 is expressed in undamaged corneal stroma where it may degrade the occasional collagen molecule that becomes damaged. After corneal wounding, expression of this enzyme is increased and much of it appears in the active form. These changes persist for at least seven months, suggesting that MMP-2 is involved in the prolonged process of collagen remodelling in the stromal repair tissue. MMP-9 is expressed in the epithelial layer of repair tissue with a timing suggesting it might participate in controlling resynthesis of the basement membrane. MMP-9 also appears to be involved in degradation of the epithelial basement membrane that precedes corneal ulceration. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,HARVARD CUTANEOUS BIOL RES CTR,BOSTON,MA 02114. HARVARD UNIV,SCH MED,CHANNING LAB,DEPT DERMATOL,BOSTON,MA 02115. NR 34 TC 36 Z9 38 U1 0 U2 0 PU ARHUS UNIV HOSPITAL PI AARHUS PA DEPT OHPTHALMOLOGY, DK-8000 AARHUS, DENMARK SN 0001-639X J9 ACTA OPHTHALMOL PY 1992 VL 70 SU 202 BP 26 EP 33 PG 8 WC Ophthalmology SC Ophthalmology GA JC385 UT WOS:A1992JC38500007 ER PT J AU WEAVER, LT ROSENTHAL, SR GLADSTONE, W WINTER, HS AF WEAVER, LT ROSENTHAL, SR GLADSTONE, W WINTER, HS TI CARNITINE DEFICIENCY - A POSSIBLE CAUSE OF GASTROINTESTINAL DYSMOTILITY SO ACTA PAEDIATRICA LA English DT Article ID NEWBORN-INFANTS; METABOLISM AB An infant with delayed development and peripheral myopathy, nourished on a soy-based liquid diet deficient in carnitine, had gastrointestinal dysmotility manifested by postprandial vomiting, oral drooling, delayed gastric emptying and infrequent bowel movements. Oesophageal manometry showed a reduced lower oesophageal sphincter pressure for age with abnormal distal motility. Serum carnitine concentration was 9.9-mu-mol l-1. After dietary supplementation of carnitine the gastrointestinal symptoms resolved, oesophageal manometry returned to normal, and serum carnitine increased to 37.2-mu-mol l-1. Dietary carnitine deficiency in infancy may be a cause of smooth muscle dysmotility of the gastrointestinal tract. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PEDIAT,COMBINED PROGRAM GASTROENTEROL & NUTR,BOSTON,MA 02114. HARVARD UNIV,CHILDRENS HOSP,SCH MED,DEPT PEDIAT,COMBINED PROGRAM GASTROENTEROL & NUTR,BOSTON,MA 02115. NR 11 TC 10 Z9 11 U1 1 U2 1 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0803-5253 J9 ACTA PAEDIATR JI Acta Paediatr. PD JAN PY 1992 VL 81 IS 1 BP 79 EP 81 DI 10.1111/j.1651-2227.1992.tb12085.x PG 3 WC Pediatrics SC Pediatrics GA HG253 UT WOS:A1992HG25300018 PM 1376181 ER PT J AU HABER, DA HOUSMAN, DE AF HABER, DA HOUSMAN, DE TI THE GENETICS OF WILMS-TUMOR SO ADVANCES IN CANCER RESEARCH LA English DT Review ID BECKWITH-WIEDEMANN SYNDROME; FACTOR-II-GENE; RETINOBLASTOMA SUSCEPTIBILITY GENE; ZINC-FINGER GENE; NORMAL HUMAN CHROMOSOME-11; EARLY GROWTH-RESPONSE; SOMATIC-CELL HYBRIDS; WAGR REGION; PHYSICAL MAP; BAND 11P13 C1 MASSACHUSETTS GEN HOSP,CTR CANC,BOSTON,MA 02129. RP HABER, DA (reprint author), MIT,CTR CANC RES,CAMBRIDGE,MA 02139, USA. NR 143 TC 74 Z9 74 U1 1 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0065-230X J9 ADV CANCER RES JI Adv. Cancer Res. PY 1992 VL 59 BP 41 EP 68 DI 10.1016/S0065-230X(08)60302-4 PG 28 WC Oncology SC Oncology GA MD693 UT WOS:A1992MD69300002 PM 1325734 ER PT J AU ROGERS, RP STROMINGER, JL SPECK, SH AF ROGERS, RP STROMINGER, JL SPECK, SH TI EPSTEIN-BARR-VIRUS IN B-LYMPHOCYTES - VIRAL GENE-EXPRESSION AND FUNCTION IN LATENCY SO ADVANCES IN CANCER RESEARCH LA English DT Review ID LINKED LYMPHOPROLIFERATIVE SYNDROME; BURKITTS-LYMPHOMA CELLS; INFECTIOUS-MONONUCLEOSIS PATIENTS; HEALTHY SEROPOSITIVE INDIVIDUALS; GROWTH-TRANSFORMED LYMPHOCYTES; TERMINAL PROTEIN GENE; RNA EBER GENES; MEMBRANE-PROTEIN; NUCLEAR ANTIGEN-2; NASOPHARYNGEAL CARCINOMA C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR VIROL,BOSTON,MA 02115. RP ROGERS, RP (reprint author), UNIV N CAROLINA,SCH DENT,DEPT DIAGNOST,CHAPEL HILL,NC 27514, USA. NR 160 TC 29 Z9 29 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 0065-230X J9 ADV CANCER RES JI Adv. Cancer Res. PY 1992 VL 58 BP 1 EP 26 DI 10.1016/S0065-230X(08)60288-2 PG 26 WC Oncology SC Oncology GA MC969 UT WOS:A1992MC96900001 PM 1312289 ER PT J AU ALEXANDERBRIDGES, M DUGAST, I ERCOLANI, L KONG, XF GIERE, L NASRIN, N AF ALEXANDERBRIDGES, M DUGAST, I ERCOLANI, L KONG, XF GIERE, L NASRIN, N TI MULTIPLE INSULIN-RESPONSIVE ELEMENTS REGULATE TRANSCRIPTION OF THE GAPDH GENE SO ADVANCES IN ENZYME REGULATION LA English DT Review ID GROWTH-FACTOR; AMYLASE GENE; EXPRESSION; CELLS; PROTEIN; CAMP; MICE RP HARVARD UNIV, MASSACHUSETTS GEN HOSP,SCH MED, HOWARD HUGHES MED INST,DEPT MED, DIABET UNIT, BOSTON, MA 02114 USA. NR 19 TC 2 Z9 2 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0065-2571 J9 ADV ENZYME REGUL JI Adv. Enzym. Regul. PY 1992 VL 32 BP 149 EP 159 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HU553 UT WOS:A1992HU55300011 ER PT B AU ALEXANDERBRIDGES, M DUGAST, I ERCOLANI, L KONG, XF GIERE, L NASRIN, N AF ALEXANDERBRIDGES, M DUGAST, I ERCOLANI, L KONG, XF GIERE, L NASRIN, N BE WEBER, G TI MULTIPLE INSULIN-RESPONSIVE ELEMENTS REGULATE TRANSCRIPTION OF THE GAPDH GENE SO ADVANCES IN ENZYME REGULATION, VOL 32 SE ADVANCES IN ENZYME REGULATION LA English DT Proceedings Paper CT 32ND SYMP ON REGULATION OF ENZYME ACTIVITY AND SYNTHESIS IN NORMAL AND NEOPLASTIC TISSUES CY SEP 30-OCT 01, 1991 CL INDIANA UNIV SCH MED, INDIANAPOLIS, IN SP INDIANA UNIV SCH MED, AMER CYANAMID, BURROUGHS WELLCOME, ELI LILLY, HOFFMANN LA ROCHE, PFIZER, SCHERING, WARNER LAMBERT HO INDIANA UNIV SCH MED ID GROWTH-FACTOR; AMYLASE GENE; EXPRESSION; CELLS; PROTEIN; CAMP; MICE RP ALEXANDERBRIDGES, M (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,HOWARD HUGHES MED INST,DEPT MED,DIABET UNIT,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON PRESS LTD PI OXFORD PA OXFORD BN 0-08-041862-7 J9 ADV ENZYME REGUL PY 1992 VL 32 BP 149 EP 159 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BV62B UT WOS:A1992BV62B00011 ER PT J AU SCHRIEVER, F NADLER, LM AF SCHRIEVER, F NADLER, LM TI THE CENTRAL ROLE OF FOLLICULAR DENDRITIC CELLS IN LYMPHOID-TISSUES SO ADVANCES IN IMMUNOLOGY LA English DT Review ID HUMAN-B-CELLS; INTERCELLULAR-ADHESION MOLECULE-1; ANTIGEN-DRIVEN SELECTION; RETICULUM CELLS; GERMINAL CENTER; IMMUNE-COMPLEXES; HUMAN TONSILS; MONOCLONAL-ANTIBODIES; HIV-1 INFECTION; MEMORY CELLS C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT MED,BOSTON,MA 02115. FU NCI NIH HHS [CA40216] NR 126 TC 71 Z9 71 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 0065-2776 J9 ADV IMMUNOL JI Adv. Immunol. PY 1992 VL 51 BP 243 EP 284 DI 10.1016/S0065-2776(08)60489-7 PG 42 WC Immunology SC Immunology GA MC108 UT WOS:A1992MC10800004 PM 1502976 ER PT S AU HEYDARI, AR RICHARDSON, A AF HEYDARI, AR RICHARDSON, A BE Franceschi, C Crepaldi, G Cristofalo, VJ Vijg, J TI DOES GENE-EXPRESSION PLAY ANY ROLE IN THE MECHANISM OF THE ANTIAGING EFFECT OF DIETARY RESTRICTION SO AGING AND CELLULAR DEFENSE MECHANISMS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Proceedings Paper CT CONF ON AGING AND CELLULAR DEFENSE MECHANISMS CY SEP 22-26, 1991 CL MODENA, ITALY SP NEW YORK ACAD SCI, NIA, SIGMA TAU, EURAGE RP HEYDARI, AR (reprint author), AUDIE L MURPHY MEM VET ADM MED CTR,CTR GERIATR RES EDUC & CLIN,SAN ANTONIO,TX 78284, USA. NR 0 TC 17 Z9 17 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA NEW YORK SN 0077-8923 BN 0-89766-729-8 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1992 VL 663 BP 384 EP 395 DI 10.1111/j.1749-6632.1992.tb38682.x PG 12 WC Geriatrics & Gerontology; Immunology; Physiology SC Geriatrics & Gerontology; Immunology; Physiology GA BX33J UT WOS:A1992BX33J00041 PM 1482068 ER PT J AU WILLIAMS, AB MCNELLY, EA WILLIAMS, AE DAQUILA, RT AF WILLIAMS, AB MCNELLY, EA WILLIAMS, AE DAQUILA, RT TI METHADONE-MAINTENANCE TREATMENT AND HIV TYPE-1 SEROCONVERSION AMONG INJECTING DRUG-USERS SO AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV LA English DT Article ID HUMAN IMMUNODEFICIENCY VIRUS; SAN-FRANCISCO; RISK-FACTORS; INFECTION; AIDS; AMSTERDAM; PROGRAMS AB This study examined whether methadone maintenance treatment decreases drug injection enough to significantly limit HIV-1 transmission among injection drug users (IDU). When HIV-1 seroconversion status among prospectively followed methadone maintenance clients was analyzed by treatment retention, 1/56 (2%) of those who remained continuously in treatment seroconverted while 8/42 (19%) of those whose methadone treatment was interrupted seroconverted. When controlled for length of follow up, the difference in seroconversion rate was not statistically significant. Subjects in continuous treatment had a seroconversion rate of 0.7 per 100 person years (95% Confidence Interval [CI] = 0.1, 5.3) and those with interrupted treatment a rate of 4.3 per 100 person years (95% CI = 2.2, 8.6). Subjects in continuous treatment reported less needle sharing (p < 0.0002), fewer needle sharing partners (p < 0.002), fewer sexual partners (p < 0.03), and were more likely to be women (p < 0.01). These data indicate the need for larger studies to evaluate both client and drug treatment program characteristics which might concomitantly increase treatment retention and decrease HIV-1 risk. C1 AMER RED CROSS,JEROME HOLLAND LABS,BETHESDA,MD 20814. APT FDN,NEW HAVEN,CT. HARVARD UNIV,SCH MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA 02114. RP WILLIAMS, AB (reprint author), YALE UNIV,SCH NURSING,DIV ADULT HLTH,POB 9740,NEW HAVEN,CT 06536, USA. FU NIDA NIH HHS [DAO 330-02] NR 20 TC 48 Z9 50 U1 0 U2 0 PU CARFAX PUBL CO PI ABINGDON PA PO BOX 25, ABINGDON, OXFORDSHIRE, ENGLAND OX14 3UE SN 0954-0121 J9 AIDS CARE JI Aids Care-Psychol. Socio-Med. Asp. Aids/Hiv PY 1992 VL 4 IS 1 BP 35 EP 41 DI 10.1080/09540129208251618 PG 7 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Respiratory System; Social Sciences, Biomedical SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychology; Respiratory System; Biomedical Social Sciences GA HM187 UT WOS:A1992HM18700004 PM 1314099 ER PT J AU BOUCHER, CA WACKERS, FJT ZARET, BL MENA, IG BOUCHER, C BECKER, L TAILLEFER, R POHOST, G DUPRAS, G BERMAN, D VERANI, M MOORE, W KIRCHNER, P SAMUELS, L WACKERS, F HOLMAN, BL BELLER, G BROWN, M PARKERN, D BOUDREAU, R MENA, I BOUCHER, C JONES, R WACKERS, F VERANI, M AF BOUCHER, CA WACKERS, FJT ZARET, BL MENA, IG BOUCHER, C BECKER, L TAILLEFER, R POHOST, G DUPRAS, G BERMAN, D VERANI, M MOORE, W KIRCHNER, P SAMUELS, L WACKERS, F HOLMAN, BL BELLER, G BROWN, M PARKERN, D BOUDREAU, R MENA, I BOUCHER, C JONES, R WACKERS, F VERANI, M TI TC-99M SESTAMIBI MYOCARDIAL IMAGING AT REST FOR ASSESSMENT OF MYOCARDIAL-INFARCTION AND 1ST-PASS EJECTION FRACTION SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CORONARY-ARTERY DISEASE; METHOXYISOBUTYL ISONITRILE; TL-201; PERFUSION; REPERFUSION; ISCHEMIA; QUANTIFICATION; SCINTIGRAPHY; OCCLUSION; HYPEREMIA AB The ability of technetium (Tc)-99m sestamibi myocardial perfusion imaging at rest to evaluate myocardial infarction and first-pass ejection fraction was studied in a trial involving 18 institutions. Protocol I compared regional perfusion with occurrence of infarction by Q wave or by gated blood pool scan wall motion abnormality in 146 patients. Protocol II assessed first-pass right and left ventricular ejection fraction in 85 patients. In protocol I, Tc-99m sestamibi images were abnormal in 104 of 111 patients (94%) with both a Q wave and a gated scan wall motion abnormality and was normal in 23 of 25 patients (92%) in whom both were normal. Therefore, concordance existed in 105 (94%) patients. Of 115 patients with a Q wave, 107 (93%) had an abnormal Tc-99m sestamibi study. Of 115 patients with a gated scan wall motion abnormality, 108 (94%) had an abnormal Tc-99m sestamibi study. Tc-99m sestamibi imaging showed corresponding perfusion abnormalities in 81% of 69 anterior Q-wave infarcts, 73% of 55 inferior Q-wave infarcts and 88% of 8 posterior infarcts. Specificity in normal regions on electrocardiography and wall motion was 91, 100 and 100%, respectively, for anterior, inferior and posterior regions, respectively, between wall motion and perfusion. Of 17 myocardial segments per patient, there was concordance in 74% of patients. First pass Tc-99m sestamibi imaging of ejection fraction agreed well with conventional first-pass imaging for the right and left ventricle. It is concluded that Tc-99m sestamibi myocardial imaging at rest reliably diagnoses and localizes infarction and assesses ejection fraction by first-pass imaging. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. JOHNS HOPKINS UNIV HOSP,BALTIMORE,MD 21205. HOP HOTEL DIEU,MONTREAL H2W 1T8,QUEBEC,CANADA. UNIV ALABAMA HOSP & CLIN,BIRMINGHAM,AL 35233. MONTREAL HEART INST,MONTREAL H1T 1C8,QUEBEC,CANADA. CEDARS SINAI MED CTR,LOS ANGELES,CA 90048. METHODIST HOSP,HOUSTON,TX 77030. ST LUKES EPISCOPAL HOSP,HOUSTON,TX 77030. UNIV IOWA HOSP & CLIN,IOWA CITY,IA 52242. ST LOUIS UNIV,MED CTR,ST LOUIS,MO 63103. YALE UNIV,SCH MED,NEW HAVEN,CT 06510. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. UNIV VIRGINIA HOSP,CHARLOTTESVILLE,VA 22908. MAYO CLIN & MAYO FDN,ROCHESTER,MN 55905. HENRY FORD HOSP,DETROIT,MI 48202. UNIV MINNESOTA HOSP & CLIN,MINNEAPOLIS,MN 55455. UNIV CALIF LOS ANGELES,HARBOR MED CTR,LOS ANGELES,CA 90024. DUKE UNIV,MED CTR,DURHAM,NC 27710. RP BOUCHER, CA (reprint author), MASSACHUSETTS GEN HOSP,CARDIAC UNIT,BOSTON,MA 02114, USA. NR 29 TC 24 Z9 24 U1 0 U2 1 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 JAN 1 PY 1992 VL 69 IS 1 BP 22 EP 27 DI 10.1016/0002-9149(92)90670-T PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA GY225 UT WOS:A1992GY22500004 PM 1530901 ER PT J AU RUOCCO, NA RING, ME HOLUBKOV, R JACOBS, AK DETRE, KM FAXON, DP FAXON, DP KELLETT, MA SANBORN, T JACOBS, AK ERARIO, M KING, SB DOUGLAS, J SUTOR, C KENT, KM EWELS, C KEHOE, K BLOCK, PC BLOCK, E HOLMES, DR VLIETSTRA, RE REEDER, GS BRESNAHAN, JF BRESNAHAN, DR BOVE, AA VONHAMMES, L BREVIG, S ALBASSEM, M LANCE, D BENTIVOGLIO, LG SHAPPELL, E COWLEY, MJ VETROVEC, GW LEWIS, SA DISCIASCIO, G KELLY, K GOSSELIN, AJ SWAYE, PS VIGNOLA, PA YON, H BOURASSA, MG DAVID, PR LABBE, M FAILLE, C CANNON, RO LEON, M MINCEMOYER, R MYLER, RK STERTZER, SH CLARK, DA MURPHY, M WILLIAMS, DO EMIN, S GALICHIA, JP MEIRES, J LEATHERMAN, LL SPRINGER, AJ MATTIES, J DORROS, G JANKEMATHIAK, L ENGEL, M DETRE, KM KELSEY, SF WILSON, J HOLUBKOV, R STEENKISTE, AR AMOROSO, W ELLIOTT, H NEIDERMEYER, V SWANSON, P ZONA, J GIBBONS, D WOLK, R ROBERTSON, T AF RUOCCO, NA RING, ME HOLUBKOV, R JACOBS, AK DETRE, KM FAXON, DP FAXON, DP KELLETT, MA SANBORN, T JACOBS, AK ERARIO, M KING, SB DOUGLAS, J SUTOR, C KENT, KM EWELS, C KEHOE, K BLOCK, PC BLOCK, E HOLMES, DR VLIETSTRA, RE REEDER, GS BRESNAHAN, JF BRESNAHAN, DR BOVE, AA VONHAMMES, L BREVIG, S ALBASSEM, M LANCE, D BENTIVOGLIO, LG SHAPPELL, E COWLEY, MJ VETROVEC, GW LEWIS, SA DISCIASCIO, G KELLY, K GOSSELIN, AJ SWAYE, PS VIGNOLA, PA YON, H BOURASSA, MG DAVID, PR LABBE, M FAILLE, C CANNON, RO LEON, M MINCEMOYER, R MYLER, RK STERTZER, SH CLARK, DA MURPHY, M WILLIAMS, DO EMIN, S GALICHIA, JP MEIRES, J LEATHERMAN, LL SPRINGER, AJ MATTIES, J DORROS, G JANKEMATHIAK, L ENGEL, M DETRE, KM KELSEY, SF WILSON, J HOLUBKOV, R STEENKISTE, AR AMOROSO, W ELLIOTT, H NEIDERMEYER, V SWANSON, P ZONA, J GIBBONS, D WOLK, R ROBERTSON, T TI RESULTS OF CORONARY ANGIOPLASTY OF CHRONIC TOTAL OCCLUSIONS (THE NATIONAL-HEART,-LUNG,-AND-BLOOD-INSTITUTE 1985-1986 PERCUTANEOUS TRANSLUMINAL ANGIOPLASTY REGISTRY) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID BLOOD-INSTITUTE REGISTRY; ARTERY OCCLUSION; TERM AB There has been increasing application of coronary angioplasty to patients with chronic total occlusions. The acute and long-term outcome in 271 patients after coronary angioplasty (142 single and 129 multiple stenoses) of a total occlusion was compared with 1,429 patients undergoing angioplasty of subtotal (less-than-or-equal-to 99% stenosis) occlusions (885 single and 544 multilesion) participating in the 1985-1986 National Heart, Lung, and Blood Institute Percutaneous Transluminal Coronary Angioplasty Registry. Baseline characteristics were similar for each lesion group except for a higher incidence of prior myocardial infarction and left ventricular dysfunction (ejection fraction < 50%) in patients with total occlusion. Major complications (death, myocardial infarction or emergency bypass surgery) were similar (p = not significant) between patients with total and subtotal occlusions for single (6 vs 7%) and multilesion angioplasty (9 vs 6%). At 2 years, after making adjustments for baseline variables, patients with a total occlusion had a significantly increased risk of death compared with those with subtotal occlusion. There were no significant differences in cumulative event rates for myocardial infarction or bypass surgery. Approximately three-fourths of patients in each group were free of angina at 2 years. In conclusion, angioplasty of chronic total occlusions is associated with a similar acute complication rate. Despite similar relief of anginal symptoms, patients in the total occlusion group have a higher 2-year mortality. C1 BOSTON UNIV HOSP,MED CTR,BOSTON,MA 02218. EMORY UNIV HOSP,ATLANTA,GA 30322. GEORGETOWN UNIV HOSP,WASHINGTON,DC 20007. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. MAYO CLIN & MAYO FDN,ROCHESTER,MN 55905. MED CTR HOSP,HOUSTON,TX. MED COLL PENN,PHILADELPHIA,PA 19129. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,RICHMOND,VA 23298. MIAMI HEART INST,MIAMI BEACH,FL 33140. MONTREAL HEART INST,MONTREAL H1T 1C8,QUEBEC,CANADA. NHLBI,BETHESDA,MD 20892. SETON MED CTR,DALY CITY,CA. BROWN UNIV,RHODE ISL HOSP,PROVIDENCE,RI 02903. ST FRANCIS REG MED CTR,WICHITA,KS 67214. ST LUKES EPISCOPAL HOSP,HOUSTON,TX 77030. ST LUKES HOSP,MILWAUKEE,WI 53215. UNIV PITTSBURGH,PITTSBURGH,PA 15260. UNIV PITTSBURGH,GRAD SCH PUBL HLTH,DEPT EPIDEMIOL,PITTSBURGH,PA 15260. BOSTON UNIV HOSP,DEPT MED,BOSTON,MA. RP RUOCCO, NA (reprint author), BOSTON UNIV HOSP,MED CTR,EVAND MEM DEPT CLIN RES,CARDIOL SECT,88 E NEWTON ST,BOSTON,MA 02118, USA. FU NHLBI NIH HHS [HL-33292] NR 16 TC 70 Z9 76 U1 0 U2 3 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 JAN 1 PY 1992 VL 69 IS 1 BP 69 EP 76 DI 10.1016/0002-9149(92)90678-R PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA GY225 UT WOS:A1992GY22500012 PM 1729870 ER PT J AU COLLINS, FA MURPHY, DL REISS, AL SIMS, KB LEWIS, JG FREUND, L KAROUM, F ZHU, DP MAUMENEE, IH ANTONARAKIS, SE AF COLLINS, FA MURPHY, DL REISS, AL SIMS, KB LEWIS, JG FREUND, L KAROUM, F ZHU, DP MAUMENEE, IH ANTONARAKIS, SE TI CLINICAL, BIOCHEMICAL, AND NEUROPSYCHIATRIC EVALUATION OF A PATIENT WITH A CONTIGUOUS GENE SYNDROME DUE TO A MICRODELETION XP11.3 INCLUDING THE NORRIE DISEASE LOCUS AND MONOAMINE-OXIDASE (MAOA AND MAOB) GENES SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE NORRIE DISEASE; MONOAMINE-OXIDASE; X-CHROMOSOME; CONTIGUOUS GENE SYNDROME ID CLONED DNA-SEQUENCE; PROXIMAL SHORT ARM; X-CHROMOSOME; DIAGNOSTIC-INTERVIEW; PRESSOR SENSITIVITY; PRENATAL-DIAGNOSIS; CLOSE LINKAGE; DELETION; PLASMA; INACTIVATION AB Norrie disease is a rare X-linked recessive disorder characterized by blindness from infancy. The gene for Norrie disease has been localized to Xp11.3. More recently, the genes for monoamine oxidase (MAOA, MAOB) have been mapped to the same region. This study evaluates the clinical, biochemical, and neuropsychiatric data in an affected male and 2 obligate heterozygote females from a single family with a submicroscopic deletion involving Norrie disease and MAO genes. The propositus was a profoundly retarded, blind male; he also had neurologic abnormalities including myoclonus and stereotopy-habit disorder. Both obligate carrier females had a normal IQ. The propositus' mother met diagnostic criteria for "chronic hypomania and schizotypal features." The propositus' MAO activity was undetectable and the female heterozygotes had reduced levels comparable to patients receiving MAO inhibiting antidepressants. MAO substrate and metabolite abnormalities were found in the propositus' plasma and CSF. This study indicates that subtle biochemical and possibly neuropsychiatric abnormalities may be detected in some heterozygotes with the microdeletion in Xp11.3 due to loss of the gene product for the MAO genes; this deletion can also explain some of the complex phenotype of this contiguous gene syndrome in the propositus. C1 JOHNS HOPKINS UNIV HOSP,SCH MED,CTR MED GENET,CMSC 1003,600 N WOLFE ST,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV HOSP,SCH MED,DEPT PEDIAT,BALTIMORE,MD 21205. NIMH,CLIN SCI LAB,CLIN CTR 10-3D41,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,DEPT PSYCHIAT,DIV CHILD PSYCHIAT,BEHAV GENET RES CTR,BALTIMORE,MD 21205. KENNEDY INST,BALTIMORE,MD. MASSACHUSETTS GEN HOSP,CTR NEUROSCI,MOLEC NEUROGENET LAB,BOSTON,MA 02114. JOHNS HOPKINS UNIV,SCH MED,WILMER EYE INST,JOHNS HOPKINS CTR HEREDITARY EYE DIS,BALTIMORE,MD 21205. RI Antonarakis, Stylianos/N-8866-2014 OI Antonarakis, Stylianos/0000-0001-8907-5823 FU NHGRI NIH HHS [HG00373] NR 50 TC 61 Z9 61 U1 0 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD JAN 1 PY 1992 VL 42 IS 1 BP 127 EP 134 DI 10.1002/ajmg.1320420126 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA GW607 UT WOS:A1992GW60700025 PM 1308352 ER PT J AU SZERLIP, HM HEEGER, P FELDMAN, GM AF SZERLIP, HM HEEGER, P FELDMAN, GM TI COMPARISON BETWEEN ACETATE AND BICARBONATE DIALYSIS FOR THE TREATMENT OF LITHIUM INTOXICATION SO AMERICAN JOURNAL OF NEPHROLOGY LA English DT Article DE LITHIUM INTOXICATION; HEMODIALYSIS; ACETATE; BICARBONATE ID DATA-COLLECTION-SYSTEM AB Lithium is used to treat manic-depressive disorders, but toxic side effects commonly occur. The preferred treatment of severe lithium intoxication is hemodialysis. No data, however, exist comparing the effectiveness of acetate to bicarbonate dialysis for the removal of lithium. We present a case of lithium intoxication treated with both. During acetate dialysis, lithium removal occurred exclusively from the extracellular fluid space, while during bicarbonate dialysis. lithium removal occurred equally from both the extracellular and intracellular fluid spaces. We hypothesize that acetate but not bicarbonate activates the sodium-hydrogen antiporter on cell membranes, and that lithium, substituting for sodium, is driven into cells. This may explain the rebound in lithium levels commonly noted after conventional dialysis. We recommend bicarbonate hemodialysis as the therapy of choice for severe lithium intoxication. C1 UNIV PENN,SCH MED,PHILADELPHIA,PA 19104. PHILADELPHIA VET AFFAIRS MED CTR,PHILADELPHIA,PA. NR 16 TC 11 Z9 11 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-8095 J9 AM J NEPHROL JI Am. J. Nephrol. PD JAN-APR PY 1992 VL 12 IS 1-2 BP 116 EP 120 DI 10.1159/000168430 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA JJ236 UT WOS:A1992JJ23600021 PM 1415356 ER PT J AU MIKULIS, DJ OGILVY, CS MCKEE, A DAVIS, KR OJEMAN, RG AF MIKULIS, DJ OGILVY, CS MCKEE, A DAVIS, KR OJEMAN, RG TI SPINAL-CORD INFARCTION AND FIBROCARTILAGENOUS EMBOLI SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Note DE SPINAL CORD, INFARCTION; SPINAL CORD, MAGNETIC RESONANCE; COMMENTARIES C1 MASSACHUSETTS GEN HOSP,DEPT NEUROSURG,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT NEUROPATHOL,BOSTON,MA 02114. NR 18 TC 27 Z9 28 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 JAN-FEB PY 1992 VL 13 IS 1 BP 155 EP 160 PG 6 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA HA037 UT WOS:A1992HA03700023 PM 1595434 ER PT J AU WASSERMAN, BA MIKULIS, DJ MANZIONE, JV AF WASSERMAN, BA MIKULIS, DJ MANZIONE, JV TI ORIGIN OF THE RIGHT VERTEBRAL ARTERY FROM THE LEFT SIDE OF THE AORTIC-ARCH PROXIMAL TO THE ORIGIN OF THE LEFT SUBCLAVIAN ARTERY SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article DE ARTERIES, ABNORMALITIES AND ANOMALIES; ARTERIES, VERTEBRAL; CEREBRAL ANGIOGRAPHY AB The authors describe a patient in whom there was an anomalous origin of the right vertebral artery from the aortic arch, proximal to the origin of the left subclavian artery-another potential vertebral origin anomaly that one may encounter when performing cerebral angiography. C1 UNIV ROCHESTER,SCH MED & DENT,DEPT RADIOL & SURG,ROCHESTER,NY 14642. MASSACHUSETTS GEN HOSP,DEPT RADIOL,NEURORADIOL SECT,BOSTON,MA 02114. NR 14 TC 18 Z9 18 U1 0 U2 0 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD JAN-FEB PY 1992 VL 13 IS 1 BP 355 EP 358 PG 4 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA HA037 UT WOS:A1992HA03700068 PM 1595475 ER PT J AU SILVERMAN, PR WORDEN, JW AF SILVERMAN, PR WORDEN, JW TI CHILDRENS REACTIONS IN THE EARLY MONTHS AFTER THE DEATH OF A PARENT SO AMERICAN JOURNAL OF ORTHOPSYCHIATRY LA English DT Article ID CHILDHOOD BEREAVEMENT; STRESS AB The reactions of a nonclinical group of 125 dependent children aged 6-17 years were examined within four months of the death of a parent. Focus was on normative behavior in the domains of the children's reactions to the death itself, their affective experience, their efforts at remaining connected to the deceased, their social network and support system, and changes in their families resulting from the death. C1 MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. FU NIMH NIH HHS [MH 41791] NR 41 TC 98 Z9 98 U1 5 U2 17 PU AMER ORTHOPSYCHIATRIC ASSN PI NEW YORK PA 19 W 44TH ST, NEW YORK, NY 10036 SN 0002-9432 J9 AM J ORTHOPSYCHIAT JI Am. J. Orthopsychiatr. PD JAN PY 1992 VL 62 IS 1 BP 93 EP 104 DI 10.1037/h0079304 PG 12 WC Psychiatry; Social Work SC Psychiatry; Social Work GA GZ736 UT WOS:A1992GZ73600011 PM 1546765 ER PT J AU GRAVES, DT BARNHILL, R GALANOPOULOS, T ANTONIADES, HN AF GRAVES, DT BARNHILL, R GALANOPOULOS, T ANTONIADES, HN TI EXPRESSION OF MONOCYTE CHEMOTACTIC PROTEIN-1 IN HUMAN-MELANOMA INVIVO SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Note ID HUMAN ENDOTHELIAL-CELLS; MACROPHAGE CONTENT; TUMOR PROGRESSION; SOLID TUMORS; IDENTIFICATION; INFILTRATION; PHENOTYPE; PRODUCTS; NECROSIS; CYTOKINE AB A common feature of human melanoma is infiltration by monocytes at early stages of tumorigenesis. This infiltration may be highly significant since macrophages have the capacity to alter the behavior of tumor cells. The authors previously demonstrated that the predominant monocyte chemoattractant produced by tumor cells in vitro was monocyte chemotactic protein-1 (MCP-1). The authors identify the expression of MCP-1 in pathologic specimens of both primary and metastatic human melanoma but not in normal skin. The finding that MCP-1 is produced by malignant melanoma suggests that specific genes are expressed in tumor cells that can induce the recruitment of monocytes in vivo. C1 CTR BLOOD RES,BOSTON,MA. HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,CAMBRIDGE,MA 02138. HARVARD UNIV,SCH PUBL HLTH,DEPT NUTR,CAMBRIDGE,MA 02138. BOSTON UNIV,MED CTR,DEPT BIOCHEM,BOSTON,MA 02118. MASSACHUSETTS GEN HOSP,DIV DERMATOPATHOL,BOSTON,MA 02114. RP GRAVES, DT (reprint author), BOSTON UNIV,MED CTR,DEPT ORAL BIOL,G10,100 E NEWTON ST,BOSTON,MA 02118, USA. FU NCI NIH HHS [CA30101]; NHLBI NIH HHS [HL29583]; NIDCR NIH HHS [DE07559] NR 27 TC 98 Z9 99 U1 1 U2 2 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JAN PY 1992 VL 140 IS 1 BP 9 EP 14 PG 6 WC Pathology SC Pathology GA GZ636 UT WOS:A1992GZ63600003 PM 1731532 ER PT J AU JAMESON, JL WEISS, J POLAK, JM CHILDS, GV BLOOM, SR STEEL, JH CAPEN, CC PRENTICE, DE FETTER, AW LANGLOSS, JM AF JAMESON, JL WEISS, J POLAK, JM CHILDS, GV BLOOM, SR STEEL, JH CAPEN, CC PRENTICE, DE FETTER, AW LANGLOSS, JM TI GLYCOPROTEIN HORMONE ALPHA-SUBUNIT PRODUCING PITUITARY-ADENOMAS IN RATS TREATED FOR ONE YEAR WITH CALCITONIN SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID TRANSGENIC MICE; GROWTH-HORMONE; BINDING-SITES; MESSENGER-RNA; CELL ADENOMAS; SECRETION; HYPERPLASIA; PEPTIDE; TUMORS; GENE AB Calcitonin, a calcium-lowering hormone, has been associated with an increased incidence of nonfunctioning pituitary tumors in rats. In this study, rats were treated with calcitonin (80 IU/kg/d) for 52 weeks. After treatment with calcitonin, immunohistochemistry and in situ hybridization analyses demonstrated that most pituitary tumors expressed the glycoprotein hormone alpha-subunit. Expression of the alpha-subunit was identified rarely in hyperplastic lesions of control animals. Serum levels of GH, PRL, ACTH, LH, and FSH were unchanged in calcitonin-treated rats relative to controls. However, TSH levels were increased 2.1 fold after chronic treatment with calcitonin in both male and female rats (P < 0.001). The level of glycoprotein hormone alpha-subunit was markedly increased (20-fold) in male rats with smaller elevations in female rats. Time course studies demonstrated that increases in serum alpha-subunit levels could be detected by 24 weeks of treatment and that elevations in alpha-subunit were present in the majority of animals by 40 weeks of treatment with calcitonin. The authors conclude that high doses of calcitonin, administered to rats for 6 months or longer, increases the incidence of alpha-subunit-producing pituitary tumors. C1 SANDOZ PHARMA,DEPT PATHOL,BASEL,SWITZERLAND. UNIV TEXAS,MED BRANCH,DEPT ANAT & NEUROSCI,GALVESTON,TX 77550. HAMMERSMITH HOSP,ROYAL POSTGRAD MED SCH,DEPT HISTOCHEM,LONDON W12 0HS,ENGLAND. HAMMERSMITH HOSP,ROYAL POSTGRAD MED SCH,DEPT ENDOCRINOL,LONDON W12 0HS,ENGLAND. OHIO STATE UNIV,DEPT PATHOBIOL,COLUMBUS,OH 43210. RHONE POULENC RORER CENT RES,HORSHAM,PA. RP JAMESON, JL (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,THYROID UNIT,JACKSON 1021,FRUIT ST,BOSTON,MA 02114, USA. RI Steel, Jennifer/B-4737-2013; OI Steel, Jennifer/0000-0003-4439-0090; Jameson, James/0000-0001-9538-4059 FU NICHD NIH HHS [HD23262] NR 34 TC 8 Z9 8 U1 0 U2 5 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JAN PY 1992 VL 140 IS 1 BP 75 EP 84 PG 10 WC Pathology SC Pathology GA GZ636 UT WOS:A1992GZ63600009 PM 1370597 ER PT J AU SELLMAYER, A KRANE, SM OUELLETTE, AJ BONVENTRE, JV AF SELLMAYER, A KRANE, SM OUELLETTE, AJ BONVENTRE, JV TI 1-ALPHA,25-(OH)2 VITAMIN-D3 ENHANCES EXPRESSION OF THE GENES ENCODING CA-2+-BINDING PROTEIN-MRP-8 AND PROTEIN-MRP-14 SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE MIGRATION INHIBITORY FACTOR; MACROPHAGE; DIFFERENTIATION; U-937 CELLS; CYSTIC FIBROSIS ANTIGEN; L1-PROTEIN; S-100-PROTEINS; MACROPHAGES ID CALCIUM-BINDING PROTEINS; CYSTIC-FIBROSIS ANTIGEN; OSTEOCALCIN GENE; DEOXYRIBONUCLEIC-ACID; RIBONUCLEIC-ACID; ACTIVITY INVITRO; POLYMERASE-I; CELLS; 1,25-DIHYDROXYVITAMIN-D3; PHOSPHORYLATION AB Two closely related Ca2+-binding proteins, migration inhibitory factor-related protein (MRP)-8 and MRP-14, are synthesized under specific conditions of myeloid cell differentiation. Because 1-alpha,25-dihydroxyvitamin D3 [1,25-(OH)2D3] induces myeloid cell differentiation and expression of other S-100 class calcium-binding proteins, we examined the effects of 1,25-(OH)2D3 on MRP mRNA levels in human U-937 histiocytic lymphoma cells. 1,25-(OH)2D3 increased MRP-8 and MRP-14 mRNA levels in a time- and dose-dependent manner. MRP mRNA levels were maximal at 24 h and remained elevated for at least 96 h after exposure of the cells to 1,25-(OH)2D3. MRP-8 mRNA accumulation required 100- to 1,000-fold higher concentrations of 25-(OH)D3, which binds to the 1,25-(OH)2D3 intracellular receptor with 100- to 1,000-fold lower affinity. Other differentiating agents, dimethyl sulfoxide, retinoic acid, and dexamethasone, also increased levels of MRP-8 and MRP-14 mRNA. Phorbol myristate acetate enhanced MRP-14 mRNA levels to a greater extent than MRP-8 mRNA levels, suggesting differential regulation of MRP gene expression by protein kinase C. The 1,25-(OH)2D3-induced relative increase in MRP mRNA levels was not changed by a 1,000-fold reduction in extracellular [Ca2+]. Thus 1,25-(OH)2D3 is potentially a physiological modulator of MRP gene expression. Expression of the MRP-8 and MRP-14 genes may be important for differentiation of myeloid cells. C1 MASSACHUSETTS GEN HOSP,RENAL UNIT,JACKSON 8,32 FRUIT ST,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,MED SERV,ARTHRITIS UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,SURG SERV,BOSTON,MA 02114. SHRINES BURNS INST,CELL BIOL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02114. FU NIDDK NIH HHS [DK-38453, DK-39773, DK-38165] NR 36 TC 15 Z9 17 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 JAN PY 1992 VL 262 IS 1 BP C235 EP C242 PN 1 PG 8 WC Physiology SC Physiology GA HA742 UT WOS:A1992HA74200031 PM 1733233 ER PT J AU FREYALDENHOVEN, AM GUTIERREZ, GE LIFSCHITZ, MD KATZ, MS AF FREYALDENHOVEN, AM GUTIERREZ, GE LIFSCHITZ, MD KATZ, MS TI PROTEIN-KINASE-C DIFFERENTIALLY MODULATES PTH-SENSITIVE AND PGE2-SENSITIVE ADENYLATE-CYCLASE IN OSTEOBLAST-LIKE CELLS SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE PHORBOL ESTER; G PROTEINS; PERTUSSIS TOXIN ID S49 LYMPHOMA-CELLS; NUCLEOTIDE REGULATORY PROTEIN; BETA-ADRENERGIC-RECEPTOR; EPIDERMAL GROWTH-FACTOR; PARATHYROID-HORMONE; PHORBOL-ESTER; SARCOMA CELLS; SIGNALING PATHWAYS; PERTUSSIS TOXIN; CYCLIC-AMP AB The effects of phorbol 12-myristate 13-acetate (PMA), a known activator of protein kinase C, on receptor-mediated stimulation of adenylate cyclase were evaluated in a rat osteosarcoma cell line (UMR-106) with the osteoblast phenotype. Pretreatment of UMR-106 cells with PMA increased parathyroid hormone (PTH)-stimulated adenylate cyclase activity and inhibited prostaglandin E2 (PGE2)-responsive enzyme activity. In addition, PMA enhanced enzyme activation by forskolin, which is thought to exert a direct stimulatory action on the catalytic subunit of adenylate cyclase. The regulatory effects of PMA were concentration dependent and of rapid onset (less-than-or-equal-to 1 min). Treatment with PMA also resulted in translocation of protein kinase C activity from the cytosol to the particulate cell fraction. Pertussis toxin, which attenuates inhibition of adenylate cyclase mediated by the inhibitory guanine nucleotide-binding regulatory protein (G(i)), augmented PTH-sensitive adenylate cyclase activity and reduced the incremental increase in PTH response produced by PMA. The results suggest that activation of protein kinase C increases PTH-stimulated adenylate cyclase activity by actions on G(i) and/or the catalytic subunit and decreases PGE2 responsiveness by a mechanism involving the PGE2 receptor. C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT PHYSIOL,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,CTR GERIATR RES EDUC & CLIN CTR,SAN ANTONIO,TX 78284. NR 41 TC 20 Z9 20 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 JAN PY 1992 VL 262 IS 1 BP E87 EP E95 PN 1 PG 9 WC Physiology SC Physiology GA HA742 UT WOS:A1992HA74200046 PM 1733255 ER PT J AU FREEMAN, GL WIDMAN, LE CAMPBELL, JM COLSTON, JT AF FREEMAN, GL WIDMAN, LE CAMPBELL, JM COLSTON, JT TI AN EVALUATION OF PULSUS ALTERNANS IN CLOSED-CHEST DOGS SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE CONTRACTILITY; ISOVOLUMIC RELAXATION; STARLINGS LAW ID CONSCIOUS DOGS; HEART; PERFORMANCE; VENTRICLE AB Pulsus alternans is a condition in which the arterial pressure generated by the heart oscillates between two levels on a beat-to-beat basis. We evaluated the onset of pulsus alternans in chronically instrumented dogs subjected to tachycardia and inferior vena caval occlusion. During pulsus alternans, the left ventricular (LV) end-diastolic volume (EDV) was larger before the strong beats (28.7 +/- 5.3 vs. 25.9 +/- 4.5 ml, P < 0.001 by paired t test), suggesting that the Frank-Starling mechanism participates in the alternating difference in end-systolic pressure. In addition, however, the ratio of pressure to volume at end systole was greater in the strong beats (2.01 +/- 0.36 vs. 1.46 +/- 0.45, P < 0.005 by paired t test), a difference that cannot be explained by the Frank-Starling mechanism alone. This indicates that there is also a difference in end-systolic inotropic states between strong and weak beats. These changes occurred without significant alterations in beat-to-beat levels of coronary flow. The time constant of isovolumic pressure fall (T) was faster for the strong beats (37.5 +/- 4.2 vs. 61.1 +/- 12.7 ms, P < 0.002 by paired t test). The onset of oscillation in T preceded the onset of changes in LVEDV and LV systolic pressure in every case by an average of seven beats (range 3-11), suggesting that abnormalities of intracellular calcium handling led to the occurrence of pulsus alternans. The data could be simulated using a three-compartment model of intracellular calcium in which calcium uptake from the contractile elements and rerelease to them occurs separately, with each following a monoexponential time course. Our results suggest that abnormalities of LV relaxation precede pulsus alternans, establishing the conditions for both oscillations in end-diastolic volume (Frank-Starling effect) and in beat-to-beat contractile state. C1 AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. RP FREEMAN, GL (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284, USA. NR 28 TC 19 Z9 19 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 JAN PY 1992 VL 262 IS 1 BP H278 EP H284 PN 2 PG 7 WC Physiology SC Physiology GA HA743 UT WOS:A1992HA74300038 PM 1733317 ER PT J AU FREEMAN, GL COLSTON, JT AF FREEMAN, GL COLSTON, JT TI MYOCARDIAL DEPRESSION PRODUCED BY SUSTAINED TACHYCARDIA IN RABBITS SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE HEART FAILURE; CONTRACTILITY; POSTREST CONTRACTION ID CONGESTIVE HEART-FAILURE; CHRONIC SUPRAVENTRICULAR TACHYCARDIA; CLOSED-CHEST DOGS; SARCOPLASMIC-RETICULUM; EXPERIMENTAL-MODEL; MUSCLE AB Much recent attention has been focused on the tachycardia-induced heart failure model. We hypothesized that sustained tachycardia would lead to myocardial depression in rabbits, as it does in dogs and swine. We evaluated the passive and active length-tension relations and postrest contraction behavior in right ventricular papillary muscles from 22 New Zealand White rabbits, 11 controls, and 11 subjected to ventricular pacing at a rate of 400 beats/min for 29.4 +/- 10.6 days. Studies were performed in oxygenated buffer at 22-degrees-C. Active tension was significantly reduced at muscle lengths of 0.95.L(max) and above; at L(max) it was 4.7 +/- 0.2 g/mm2 for the control group and 3.3 +/- 0.2 g/mm2 for the paced group (P < 0.005). Both groups showed increased force development when the concentration of calcium in the buffer was increased. There were no differences between the groups in the passive length-tension relations. Of note, postrest contraction data showed that the second postrest beat was smaller for the paced animals for rest intervals up to 2 min, suggesting that beat-to-beat transarcolemmal calcium handling may differ from normal in this model. We conclude that sustained tachycardia will lead to myocardial depression in rabbits; the extension of this model to a small animal species may offer new ways to explore its causative mechanisms. C1 AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. RP FREEMAN, GL (reprint author), UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX 78284, USA. NR 23 TC 14 Z9 14 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 JAN PY 1992 VL 262 IS 1 BP H63 EP H67 PN 2 PG 5 WC Physiology SC Physiology GA HA743 UT WOS:A1992HA74300009 PM 1733323 ER PT J AU GARZATREVINO, ES OVERALL, JE HOLLISTER, LE AF GARZATREVINO, ES OVERALL, JE HOLLISTER, LE TI VERAPAMIL VERSUS LITHIUM IN ACUTE MANIA SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID SCALE AB Twenty acutely manic patients were studied in a double-blind randomized trial comparing verapamil with lithium. The Petterson Mania Scale, the Brief Psychiatric Rating Scale (BPRS), and the Clinical Global Impression (CGI) were administered before treatment and weekly during 4 weeks of treatment to evaluate response to verapamil and lithium. Both treatment groups improved significantly, and there were no significant overall differences between treatments. C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,HOUSTON,TX 77225. RP GARZATREVINO, ES (reprint author), AUDIE L MURPHY MEM VET ADM MED CTR,PSYCHIAT SERV,7400 MERTON MINTER BLVD,SAN ANTONIO,TX 78284, USA. NR 10 TC 68 Z9 68 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JAN PY 1992 VL 149 IS 1 BP 121 EP 122 PG 2 WC Psychiatry SC Psychiatry GA GX040 UT WOS:A1992GX04000019 PM 1728160 ER PT J AU SALMAN, SD AF SALMAN, SD TI THE ABNORMAL OSTIOMEATAL COMPLEX AND SINUSITIS SO AMERICAN JOURNAL OF RHINOLOGY LA English DT Article AB Abnormalities in the ostiomeatal complex (OMC) constitute a major factor in the pathogenesis of sinusitis. They may be appreciated by the classical anterior rhinoscopy, the endoscopic examination, and/or the coronal computed tomographic (CT) scan. Cases are seen, however, with clinical and radiological evidence of blockage of the OMC with no clinical sinusitis. Conversely, cases with definite sinusitis may have negative clinical examination and CT scans. Some patients continue lo have sinusitis despite anatomically successful endoscopic surgery. It should be remembered that sinusitis may be caused by or facilitated by factors other than obstructions of the OMC. The decision to surgically treat sinusitis remains a clinical one based on a comprehensive evaluation. RP SALMAN, SD (reprint author), HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BOSTON,MA 02114, USA. NR 0 TC 4 Z9 5 U1 0 U2 1 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 SN 1050-6586 J9 AM J RHINOL JI Am. J. Rhinol. PD JAN-FEB PY 1992 VL 6 IS 1 BP 29 EP 32 DI 10.2500/105065892781976763 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA HK064 UT WOS:A1992HK06400006 ER PT J AU MORRISON, MC MUELLER, PR LEE, MJ SAINI, S BRINK, JA DAWSON, SL CORTELL, ED HAHN, PF AF MORRISON, MC MUELLER, PR LEE, MJ SAINI, S BRINK, JA DAWSON, SL CORTELL, ED HAHN, PF TI SCLEROTHERAPY OF MALIGNANT PLEURAL EFFUSION THROUGH SONOGRAPHICALLY PLACED SMALL-BORE CATHETERS SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID DRAINAGE; PNEUMOTHORAX; TETRACYCLINE; MANAGEMENT; EMPYEMA AB Pleural sclerosis after drainage with a small-bore catheter was performed in 21 patients with malignant pleural effusions. Intrapleural catheters 7- to 24-French in size were placed by using sonographic guidance. Tetracycline (18 patients) and bleomycin (four patients) were used as sclerosing agents (one patient had both). Clinical and radiologic follow-up was available on all patients until they died (range, 2 weeks to 25 months; mean, 3.6 months). Pleural sclerosis was successful in 15 (71%) of 21 patients. Two patients in whom pleurodesis failed had pleural sclerosis repeated, with one success and one failure. All of the failures were in patients in whom the amount of chest-tube drainage was more than 100 ml/day. Pleurodesis with tetracycline was painful in six patients; no pain was associated with use of bleomycin. Small pneumothoraces developed in four patients at the time of chest-tube placement, without consequence. A superimposed infection that developed in a patient having continuous drainage of pleural fluid was successfully treated with antibiotics. Pleural sclerotherapy can be performed through sonographically placed small-bore catheters with results comparable to those seen with large-bore, surgically placed catheters. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,FRUIT ST,BOSTON,MA 02114. NR 18 TC 65 Z9 65 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 JAN PY 1992 VL 158 IS 1 BP 41 EP 43 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA GW608 UT WOS:A1992GW60800006 PM 1370073 ER PT J AU PALMER, WE BLOCH, SM CHEW, FS AF PALMER, WE BLOCH, SM CHEW, FS TI MENETRIER DISEASE SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,32 FRUIT ST,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 1 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 JAN PY 1992 VL 158 IS 1 BP 62 EP 62 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA GW608 UT WOS:A1992GW60800011 PM 1727360 ER PT J AU CLEVELAND, RH CONSTANTINOU, C BLICKMAN, JG JARAMILLO, D WEBSTER, E AF CLEVELAND, RH CONSTANTINOU, C BLICKMAN, JG JARAMILLO, D WEBSTER, E TI VOIDING CYSTOURETHROGRAPHY IN CHILDREN - VALUE OF DIGITAL FLUOROSCOPY IN REDUCING RADIATION-DOSE SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID VESICOURETERAL REFLUX; RADIOGRAPHY; REDUCTION; SCOLIOSIS; EXPOSURE AB Voiding cystourethrography is a commonly used fluoroscopic procedure in children that can directly irradiate the gonads. As a consequence, much attention has been given to reducing the dose of radiation received during the procedure. A digital fluoroscope, especially adapted for use in children, was evaluated for potential reduction of the dose of radiation during the procedure. Entrance and midplane doses were calculated on child-sized phantoms by using the digital fluoroscope, digital spot films, and 105-mm spot films. Subsequently, data were collected on 47 children, grouped by ages (neonate to 1 year, 1-5 years, and 5-7 years), in whom voiding cystourethrography was performed by using the same exposure factors as those for the phantoms. On the basis of the exposure doses for the phantoms and recorded clinical peak kilovoltages, milliamperes, milliseconds, and fluoroscopic time, average skin and ovarian doses were calculated for each group of children. These doses were compared with previously reported doses for fluoroscopic and radionuclide voiding cystourethrography. Results of line-pair resolution studies for the digital spot films and 105-mm spot films were similar. Images from the digital device and 105-mm images obtained on a conventional fluoroscope were considered equally adequate for clinical decision making. The average midplane and skin doses with digital spot films for children less than 5 years old were equal to or less than 0.66 and 2.37 mGy, respectively, as opposed to 1.37 and 5.32 mGy with the 105-mm spot films. Previously reported ovarian doses range from 2.52 to 10.0 mGy for fluoroscopic voiding cystourethrography and from 0.04 to 0.05 mGy for radionuclide voiding cystourethrography. The use of digital spot films reduced dose approximately 50% compared with 105-mm spot films; the ovarian dose was 0.62 mGy greater than that for radionuclide voiding cystourethrography. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. BROCKTON HOSP,DEPT RADIAT ONCOL,BROCKTON,MA 02402. NR 13 TC 47 Z9 49 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 JAN PY 1992 VL 158 IS 1 BP 137 EP 142 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA GW608 UT WOS:A1992GW60800029 PM 1727340 ER PT J AU MOORE, B VANSONNENBERG, E CASOLA, G NOVELLINE, RA AF MOORE, B VANSONNENBERG, E CASOLA, G NOVELLINE, RA TI THE RELATIONSHIP BETWEEN BACK PAIN AND LEAD APRON USE IN RADIOLOGISTS SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID HISTORY AB Anecdotal experience has suggested that back pain in radiologists may result from extensive wearing of lead aprons. To investigate this possibility, we sent questionnaires to 688 radiologists in various subspecialties whose use of lead aprons varied from none to moderate to extensive. The questionnaire included both objective items that quantitated apron use and back pain and subjective items that asked, for example, if the respondent believed that lead aprons were responsible for his or her back pain. We received 236 responses (34% response rate). Objective data from those radiologists who had experienced no back pain before wearing a lead apron (179 radiologists, 26% of those surveyed) were tabulated; respondents were grouped according to age, time spent wearing a lead apron, and degree of back pain. Odds ratios were calculated. Answers to subjective questions for all respondents were tabulated. Back pain was reported by 52% of those who estimated their lead apron use at greater than or equal to 10 hr per week, the mean response, as opposed to 46% of those who wore lead aprons fewer than 10 hr a week. These and related results were not statistically significant. Our study does not prove that wearing a lead apron is a significant risk factor for the development of back pain. C1 UNIV CALIF SAN DIEGO,MED CTR,DEPT RADIOL,225 DICKINSON ST,SAN DIEGO,CA 92103. UNIV CALIF SAN DIEGO,MED CTR,DEPT MED,SAN DIEGO,CA 92103. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIOL,BOSTON,MA 02114. NR 12 TC 46 Z9 47 U1 1 U2 3 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JAN PY 1992 VL 158 IS 1 BP 191 EP 193 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA GW608 UT WOS:A1992GW60800038 PM 1530763 ER PT J AU RATTNER, DW LEGERMATE, DA LEE, MJ MUELLER, PR WARSHAW, AL AF RATTNER, DW LEGERMATE, DA LEE, MJ MUELLER, PR WARSHAW, AL TI EARLY SURGICAL DEBRIDEMENT OF SYMPTOMATIC PANCREATIC NECROSIS IS BENEFICIAL IRRESPECTIVE OF INFECTION SO AMERICAN JOURNAL OF SURGERY LA English DT Article; Proceedings Paper CT 32ND ANNUAL MEETING OF THE SOC FOR SURGERY OF THE ALIMENTARY TRACT CY MAY 20-22, 1991 CL NEW ORLEANS, LA SP SOC SURG ALIMENTARY TRACT ID NECROTIZING PANCREATITIS; APACHE-II; ABSCESS; MANAGEMENT AB In order lo assess the recent trend of nonoperative management of pancreatic necrosis, we reviewed 82 variables in 73 consecutive patients with symptomatic necrotizing pancreatitis. The mortality rate for the series was 25% (18 of 73). The only preintervention variables that correlated with mortality were APACHE II score greater than 15 (p = 0.01), preintervention blood transfusion (p < 0.001), respiratory failure (p < 0.001), and shock (p < 0.01). Patients who developed recurrent sepsis following the initial intervention had a significantly higher mortality rate (17 of 34) than those who did not (1 of 39) (p < 0.001). The rate of recurrent sepsis varied widely among individual surgeons and correlated with APACHE II score. The presence of infected versus noninfected necrosis did not correlate significantly with outcome. When percutaneous radiologically guided drainage was the initial therapeutic modality (n = 6), recurrent sepsis requiring surgical drainage inevitably occurred. Patients treated with percutaneous drainage (often in combination with surgical drainage) had a longer hospital stay (82 versus 42 days, p < 0.001), spent more days in the intensive care unit (31 versus 6 days, p < 0.001), and required more days of total parenteral nutrition (57 versus 27 days, p < 0.001) than those treated solely by surgical means. We conclude that aggressive initial surgical debridement should be the first step in managing symptomatic pancreatic necrosis and that the presence of infection should not be the sole determinant of intervention. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP RATTNER, DW (reprint author), MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114, USA. NR 14 TC 176 Z9 181 U1 0 U2 2 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD JAN PY 1992 VL 163 IS 1 BP 105 EP 110 DI 10.1016/0002-9610(92)90261-O PG 6 WC Surgery SC Surgery GA HA423 UT WOS:A1992HA42300019 PM 1733356 ER PT J AU CLEMENT, PB YOUNG, RH SCULLY, RE AF CLEMENT, PB YOUNG, RH SCULLY, RE TI DIFFUSE, PERINODULAR, AND OTHER PATTERNS OF HYDROPIC DEGENERATION WITHIN AND ADJACENT TO UTERINE LEIOMYOMAS - PROBLEMS IN DIFFERENTIAL-DIAGNOSIS SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE UTERUS; LEIOMYOMA; HYDROPIC DEGENERATION; MYXOID CHANGE; INTRAVENOUS LEIOMYOMATOSIS; MYXOID LEIOMYOSARCOMA ID INTRAVENOUS LEIOMYOMATOSIS; UTERUS AB We describe 10 uterine leiomyomas with hydropic changes that created problems in differential diagnosis. The patients ranged in age from 41 to 51 years (mean, 45 years). Their presenting symptoms did not differ from those of patients with typical uterine leiomyomas. The follow-up, available for eight patients, was uneventful. Gross and microscopic examination revealed otherwise typical or cellular leiomyomas with focal accumulations of edema fluid (hydropic degeneration), typically associated with variable amounts of collagen ("hyaline degeneration"). Significant accumulations of acid mucins (myxoid degeneration) were present in only one case. These changes resulted in one or more of the following; (a) a characteristic perinodular hydropic change that mimicked intravenous leiomyomatosis on both gross and microscopic examination; (b) hydropic changes extending beyond the confines of the leiomyomas that raised the suspicion of myxoid leiomyosarcoma; and (c) extensive or subtotal obliteration of the usual architecture of the leiomyoma, often accompanied by numerous thick-walled blood vessels, that tended to obscure its smooth-muscle nature. Awareness of these changes combined with mucin stains and immunohistochemical stains for endothelial antigens should facilitate the diagnosis. Hydropic leiomyomas are clinically similar to typical leiomyomas; it is obviously important that they not be confused with intravenous leiomyomatosis or myxoid leiomyosarcoma. C1 UNIV BRITISH COLUMBIA,DEPT PSYCHOL,VANCOUVER V6T 1W5,BC,CANADA. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,JAMES HOMER WRIGHT PATHOL LABS,BOSTON,MA 02114. RP CLEMENT, PB (reprint author), VANCOUVER GEN HOSP,DEPT PSYCHOL,VANCOUVER V5Z 1M9,BC,CANADA. NR 11 TC 57 Z9 62 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 JAN PY 1992 VL 16 IS 1 BP 26 EP 32 DI 10.1097/00000478-199201000-00004 PG 7 WC Pathology; Surgery SC Pathology; Surgery GA HC702 UT WOS:A1992HC70200004 PM 1309411 ER PT J AU KAPLAN, MA PETTIT, CL ZUKERBERG, LR HARRIS, NL AF KAPLAN, MA PETTIT, CL ZUKERBERG, LR HARRIS, NL TI PRIMARY LYMPHOMA OF THE TRACHEA WITH MORPHOLOGICAL AND IMMUNOPHENOTYPIC CHARACTERISTICS OF LOW-GRADE B-CELL LYMPHOMA OF MUCOSA-ASSOCIATED LYMPHOID-TISSUE SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE MUCOSA-ASSOCIATED LYMPHOID TISSUE; TRACHEA; EXTRANODAL LYMPHOMA; LOW-GRADE B-CELL LYMPHOMA; MALT ID PRIMARY MALIGNANT-LYMPHOMA; MYOEPITHELIAL SIALADENITIS; CONJUNCTIVA; DIAGNOSIS; ORBIT AB A patient with primary extranodal lymphoma arising in the trachea presented with severe upper airway obstruction. The tumor was localized at presentation. The patient has remained disease-free for 12 months following surgical resection and local radiation treatment. The tumor had distinctive morphologic features characteristic of low-grade lymphomas of mucosa-associated lymphoid tissue (MALT), including a diffuse infiltrate of small lymphocytes and centrocyte-like cells surrounding reactive follicles, with plasmacytoid differentiation, and lympho-epithelial lesions. The tumor cells expressed monotypic immunoglobulin but not CD5 or CD10. This case provides evidence that primary lymphomas of the trachea in some cases are tumors of mucosa-associated lymphoid tissue. C1 MASSACHUSETTS GEN HOSP,JAMES HOMER WRIGHT PATHOL LABS,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. NR 19 TC 27 Z9 28 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 JAN PY 1992 VL 16 IS 1 BP 71 EP 75 DI 10.1097/00000478-199201000-00011 PG 5 WC Pathology; Surgery SC Pathology; Surgery GA HC702 UT WOS:A1992HC70200011 PM 1728197 ER PT J AU TASHKIN, DP KHALSA, ME GORELICK, D CHANG, P SIMMONS, MS COULSON, AH GONG, H AF TASHKIN, DP KHALSA, ME GORELICK, D CHANG, P SIMMONS, MS COULSON, AH GONG, H TI PULMONARY STATUS OF HABITUAL COCAINE SMOKERS SO AMERICAN REVIEW OF RESPIRATORY DISEASE LA English DT Article ID DIFFUSING-CAPACITY; LUNG-FUNCTION; SMOKING; ABUSE; PNEUMOMEDIASTINUM; TOBACCO; COMPLICATIONS; DYSFUNCTION; DERIVATION; MARIJUANA AB We determined the prevalence of respiratory symptoms and lung dysfunction in a large sample of habitual smokers of freebase cocaine ("crack") alone and in combination with tobacco and/or marijuana. In addition, we compared these findings with those in an age- and race-matched sample of nonusers of crack who did or did not smoke tobacco and/or marijuana. A detailed respiratory and drug use questionnaire and a battery of lung function tests were administered to (1) a convenience sample of 202 habitual smokers of cocaine (cases) who denied intravenous drug abuse and (2) a reference sample of 99 nonusers of cocaine (control subjects). The cocaine smokers (85% black) included the following: 68 never-smokers of marijuana, ot whom 43 currently smoked tobacco and 25 did not, and 134 ever-smokers of marijuana (42 current and 92 former), of whom 92 currently smoked tobacco and 42 did not. The control subjects (96% black) included the following: 69 never-smokers of marijuana, of whom 26 currently smoked tobacco and 43 did not, and 30 ever-smokers of marijuana (18 current and 12 former), of whom 21 currently smoked tobacco and 9 did not. Cases smoked an average of 6.5 g cocaine per week for a mean of 53 months. The median time of the most recent use of crack prior to study was 19 days (range < 1 to 180 days). After controlling for the use of other smoked substances, frequent crack use was associated with: (1) a high prevalence of at least occasional occurrences of acute cardiorespiratory symptoms within 1 to 12 h after smoking cocaine (cough productive of black sputum [43.7%], hemoptysis [5.7%], chest pain [38.5%], usually worse with deep breathing, and cardiac palpitations [52.6%]) and (2) a mild but significant impairment in the diffusing capacity of the lung. We conclude that heavy, habitual cocaine smoking produces evidence of respiratory tract injury manifested by a high prevalence of acute respiratory symptoms temporally related to freebase use, and an abnormality in gas transfer (diffusion) in the lung, which is evident weeks to months after most recent use. The mechanism of the defect in gas transfer is unknown, but it could reflect damage to the alveolar capillary membrane or an abnormality involving the precapillary pulmonary vasculature. C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT PSYCHIAT,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT BIOSTAT,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT EPIDEMIOL,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH PUBL HLTH,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,BRENTWOOD DIV,LOS ANGELES,CA. RP TASHKIN, DP (reprint author), UNIV CALIF LOS ANGELES,SCH MED,DEPT MED,LOS ANGELES,CA 90024, USA. FU NIDA NIH HHS [R01 DA-03018] NR 54 TC 67 Z9 69 U1 1 U2 2 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 0003-0805 J9 AM REV RESPIR DIS JI Am. Rev. Respir. Dis. PD JAN PY 1992 VL 145 IS 1 BP 92 EP 100 PG 9 WC Respiratory System SC Respiratory System GA GZ104 UT WOS:A1992GZ10400018 PM 1731605 ER PT J AU HASSOUN, PM THOMPSON, BT HALES, CA AF HASSOUN, PM THOMPSON, BT HALES, CA TI PARTIAL REVERSAL OF HYPOXIC PULMONARY-HYPERTENSION BY HEPARIN SO AMERICAN REVIEW OF RESPIRATORY DISEASE LA English DT Article ID MUSCLE CELL-PROLIFERATION; RAT; INHIBITION; CIRCULATION; PREVENTION; RECOVERY; ARTERIES; DISEASE; GROWTH; WALL AB Chronic hypoxia produces pulmonary hypertension and an increase in medial thickness of pulmonary arteries that reach maximal values after 10 days of hypoxia. We previously showed that heparin given during the first 10 days of hypoxia reduced the development of both pulmonary hypertension and vascular remodeling in the guinea pig. To determine if heparin could reverse established hypoxic pulmonary hypertension and vascular remodeling, we administered heparin by continuous subcutaneous infusion (20 U/kg/h) for the last 7 days of a 21-day exposure to hypoxia (10% O2, balance N2) and compared these animals with normal saline-infused hypoxic control and room air-exposed animals. Hypoxia increased pulmonary artery pressure from 11 +/- 1 mm Hg (mean +/- SEM) in room air animals to 20 +/- 2 mm Hg (p < 0.05) in saline-treated hypoxic control animals. Heparin reduced pulmonary artery pressure to 16 +/- 1 mm Hg (p < 0.05 versus hypoxic control and room air control animals). Total pulmonary resistance (TPR) increased with hypoxia from 0.043 +/- 0.003 mm Hg x min x kg-1 x ml-1 in room air to 0.090 +/- 0.004 in hypoxia (p < 0.05), and in the rise in TPR was also partially reversed by heparin to 0.068 +/- 0.0003 (p < 0.05). The percentage of medial thickness of alveolar duct arteries increased from 5.8 +/- 0.6% in room air to 9.5 +/- 0.1% (p < 0.05) after 3 wk of hypoxia, and heparin therapy partially reversed the increase in medial thickness to 7.2 +/- 0.7% (p < 0.05 versus both hypoxia control and room air). Hematocrit increased with hypoxia and was not significantly different in hypoxic control or heparin-treated groups (56 +/- 3 versus 50 +/- 4, respectively, p < 0.05). We conclude that heparin, at doses that previously have been shown to impair the development of hypoxic pulmonary hypertension and vascular remodeling, may also partially reverse these changes once fully established. C1 MASSACHUSETTS GEN HOSP,DEPT MED,PULM CRIT CARE UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. FU NHLBI NIH HHS [HL-07354, HL-39150] NR 28 TC 26 Z9 26 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 0003-0805 J9 AM REV RESPIR DIS JI Am. Rev. Respir. Dis. PD JAN PY 1992 VL 145 IS 1 BP 193 EP 196 PG 4 WC Respiratory System SC Respiratory System GA GZ104 UT WOS:A1992GZ10400034 PM 1731584 ER PT J AU ALBIN, MS RITTER, RR REINHART, R ERICKSON, D ROCKWOOD, A AF ALBIN, MS RITTER, RR REINHART, R ERICKSON, D ROCKWOOD, A TI VENOUS AIR-EMBOLISM DURING RADICAL RETROPUBIC PROSTATECTOMY SO ANESTHESIA AND ANALGESIA LA English DT Article ID COMPLICATION; MANAGEMENT; SURGERY C1 UNIV TEXAS,HLTH SCI CTR,AUDIE MURPHY MEM VET HOSP,DEPT SURG UROL,SAN ANTONIO,TX 78284. RP ALBIN, MS (reprint author), UNIV TEXAS,HLTH SCI CTR,AUDIE MURPHY MEM VET HOSP,DEPT ANESTHESIOL,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. NR 17 TC 16 Z9 16 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 JAN PY 1992 VL 74 IS 1 BP 151 EP 153 PG 3 WC Anesthesiology SC Anesthesiology GA GX025 UT WOS:A1992GX02500026 PM 1734780 ER PT J AU GOUDSOUZIAN, NG FERRARI, L AF GOUDSOUZIAN, NG FERRARI, L TI HEART-RATE AND THE OCULOCARDIAC REFLEX SO ANESTHESIA AND ANALGESIA LA English DT Letter ID CHILDREN C1 MASSACHUSETTS EYE & EAR HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. RP GOUDSOUZIAN, NG (reprint author), MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114, USA. NR 3 TC 0 Z9 0 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 JAN PY 1992 VL 74 IS 1 BP 166 EP 167 PG 2 WC Anesthesiology SC Anesthesiology GA GX025 UT WOS:A1992GX02500034 PM 1531171 ER PT J AU ALLEN, PD LOPEZ, JR SANCHEZ, V RYAN, JF SRETER, FA AF ALLEN, PD LOPEZ, JR SANCHEZ, V RYAN, JF SRETER, FA TI EU-4093 DECREASES INTRACELLULAR [CA2+] IN SKELETAL-MUSCLE FIBERS FROM CONTROL AND MALIGNANT HYPERTHERMIA SUSCEPTIBLE SWINE SO ANESTHESIOLOGY LA English DT Article DE IONS, CALCIUM, INTRACELLULAR; MALIGNANT HYPERTHERMIA, TREATMENT, DANTROLENE; EU-4093; MEASUREMENT TECHNIQUE, ION-SELECTIVE MICROELECTRODE; SKELETAL MUSCLE ID SARCOPLASMIC-RETICULUM; CALCIUM-CONCENTRATION; RYANODINE RECEPTOR; DANTROLENE SODIUM; AZUMOLENE; RELEASE; HUMANS; CA-2+; PIGS AB The mechanisms causing the malignant hyperthermia (MH) syndrome are related to a malfunction of intracellular Ca2+ homeostasis and can be prevented or reversed by dantrolene. EU 4093 (Azumolene(R), 1-[[[5-(4-bromophenyl)-2-oxyzolyl] methylene]amino]-2-4-imidazolidinedione) is a 30-fold more water-soluble analogue of dantrolene that is believed to have the same effects as dantrolene on the intracellular free Ca2+ concentration ([Ca2+]i) in skeletal muscle and that should have similar efficacy in treating and preventing the clinical manifestations of MH in response to a halothane/succinylcholine challenge. To test this hypothesis, experiments were carried out in four controls (Yorkshire) and eight MH-susceptible crossbreed swine (Poland China X Pietrain). The resting [Ca2+]i in normal muscle fibers measured by Ca2+-selective microelectrodes was 111 +/- 12 nM (mean +/- standard deviation, n = 30), whereas in the MH muscles the resting [Ca2+]i was 395 +/- 36 nM, (n = 28) (P = 0.0001). EU 4093 decreased [Ca2+]i in MH-susceptible skeletal muscle in a dose-related fashion from 207 to 38 nM after 0.5 to 2.0 mg/kg, respectively, and had a similar effect in control skeletal muscle (58 to 30 nM) after the same doses. In MH-susceptible swine, a dose of 2.0 mg/kg was successful in preventing any clinical signs of the MH syndrome during a subsequent halothane/succinylcholine challenge. A dose of 0.5 mg/kg was able to attenuate but not reverse the clinical signs of the MH syndrome after a halothane challenge, whereas a dose of 1.0 mg/kg was completely successful in reversing this effect in all subjects. These results indicate that EU 4093 is able to decrease the resting [Ca2+]i in normal and MH-susceptible skeletal muscle and prevent and treat the clinical MH syndrome. These data suggest that it has a mechanism of action similar to that of dantrolene. C1 INST VENEZOLANO INVEST CIENT,CTR BIOFIS & BIOQUIM,CARACAS 1010A,VENEZUELA. MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. BOSTON BIOMED RES INST,DEPT MUSCLE RES,BOSTON,MA 02114. RP ALLEN, PD (reprint author), BRIGHAM & WOMENS HOSP,DEPT ANESTHESIA,75 FRANCIS ST,BOSTON,MA 02115, USA. FU NIGMS NIH HHS [GM 15904-19] NR 23 TC 13 Z9 14 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD JAN PY 1992 VL 76 IS 1 BP 132 EP 138 DI 10.1097/00000542-199201000-00019 PG 7 WC Anesthesiology SC Anesthesiology GA GY980 UT WOS:A1992GY98000019 PM 1729917 ER PT J AU SMALL, S ALI, HH LENNON, VA BROWN, RH CARR, DB DEARMENDI, A AF SMALL, S ALI, HH LENNON, VA BROWN, RH CARR, DB DEARMENDI, A TI ANESTHESIA FOR AN UNSUSPECTED LAMBERT-EATON MYASTHENIC SYNDROME WITH AUTOANTIBODIES AND OCCULT SMALL-CELL LUNG-CARCINOMA SO ANESTHESIOLOGY LA English DT Article DE NEUROMUSCULAR BLOCKADE, PROLONGED RESPONSE; NEUROMUSCULAR RELAXANTS, D-TUBOCURARINE; SUCCINYLCHOLINE; NEUROMUSCULAR DISEASES, LAMBERT-EATON MYASTHENIC SYNDROME; MYASTHENIA GRAVIS; SEROLOGY, OMEGA CONOTOXIN ID CALCIUM CHANNELS C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. MAYO CLIN & MAYO GRAD SCH MED,ROCHESTER,MN 55901. NR 21 TC 10 Z9 10 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 JAN PY 1992 VL 76 IS 1 BP 142 EP 145 DI 10.1097/00000542-199201000-00022 PG 4 WC Anesthesiology SC Anesthesiology GA GY980 UT WOS:A1992GY98000022 PM 1309626 ER PT J AU THOMAS, JD WEYMAN, AE AF THOMAS, JD WEYMAN, AE TI NUMERICAL MODELING OF VENTRICULAR FILLING SO ANNALS OF BIOMEDICAL ENGINEERING LA English DT Article DE DIASTOLE; DIASTOLIC FUNCTION; ECHOCARDIOGRAPHY; DOPPLER; MITRAL VALVE; RELAXATION; COMPLIANCE; MATHEMATICAL MODELING ID 3-DIMENSIONAL COMPUTATIONAL METHOD; CONGESTIVE HEART-FAILURE; COMPUTER-ASSISTED DESIGN; PRESSURE-VOLUME RELATION; CORONARY-ARTERY DISEASE; CANINE LEFT-VENTRICLE; DIASTOLIC FUNCTION; DOPPLER ECHOCARDIOGRAPHY; MITRAL-VALVE; BLOOD-FLOW AB The fluid dynamical and physiological assumptions underlying general mathematical modeling of ventricular filling are outlined. We then describe the use of a lumped parameter model and computer simulation to study how the early transmitral velocity profile is affected by isolated changes in ventricular compliance and relaxation, atrial pressure and compliance, and valvular morphology. We show that the transmitral velocity is fundamentally affected by two physical determinants: the transmitral pressure difference and the net compliance of the atrium and the ventricle. These physical determinants in turn are specified by the various physiologic parameters of interest. This approach has shown that peak velocity is most strongly affected by initial left atrial pressure, lowered somewhat by prolonged relaxation, low atrial and ventricular compliance, and systolic dysfunction. Peak acceleration is directly affected by atrial pressure and inversely affected by the time constant of isovolumic relaxation, with little influence of compliance, whereas the deceleration rate is almost purely given by mitral valve area divided by instantaneous atrioventricular compliance at the end of the rapid filling wave. RP THOMAS, JD (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,NONINVAS CARDIAC LAB,ZERO EMERSON PL,SUITE 2F,BOSTON,MA 02114, USA. NR 63 TC 25 Z9 25 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0090-6964 J9 ANN BIOMED ENG JI Ann. Biomed. Eng. PY 1992 VL 20 IS 1 BP 19 EP 39 DI 10.1007/BF02368504 PG 21 WC Engineering, Biomedical SC Engineering GA HH550 UT WOS:A1992HH55000003 PM 1562102 ER PT J AU WHITE, A AF WHITE, A TI OUTPATIENT MANAGEMENT OF PYELONEPHRITIS SO ANNALS OF EMERGENCY MEDICINE LA English DT Letter RP WHITE, A (reprint author), MASSACHUSETTS GEN HOSP,DEPT EMERGENCY SERV,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD JAN PY 1992 VL 21 IS 1 BP 111 EP 111 DI 10.1016/S0196-0644(05)82272-3 PG 1 WC Emergency Medicine SC Emergency Medicine GA GX195 UT WOS:A1992GX19500027 PM 1599559 ER PT J AU ANDERSON, DC ASINGER, RW NEWBURG, SM FARMER, CC WANG, K BUNDLIE, SR KOLLER, RL JAGIELLA, WM KREHER, S JORGENSEN, CR SHARKEY, SW FLAKER, GC WEBEL, R NOLTE, B STEVENSON, P BYER, J WRIGHT, W CHESEBRO, JH WIEBERS, DO HOLLAND, AE MILLER, DM BARDSLEY, WT LITIN, SC MEISSNER, I ZERBE, DM MCANULTY, JH MARCHANT, C COULL, BM FELDMAN, G HAYWARD, A GANDARA, E MACMILLAN, K BLANK, N LEONARD, AD KANTER, MC ISENSEE, LM QUIROGA, ES PRESTI, CH TEGELER, CH LOGAN, WR HAMILTON, WP GREEN, BJ BACON, RS REDD, RM CADELL, DJ GOMEZ, CR JANOSIK, DL LABOVITZ, AJ KELLEY, RE CHAHINE, R CRISTO, L PALERMO, M PEREZ, O FEINBERG, WM VOLD, BK KERN, KB APPLETON, C MILLER, VT HOCKERSMITH, CJ COHEN, BA MARTIN, GJ PAWLOW, AJ HALPERIN, JL ROTHLAUF, EB WEINBERGER, JM GOLDMAN, ME FUSTER, V DITTRICH, HC ROTHROCK, JF HAGENHOFF, C HELGASON, CM KONDOS, GT HOFF, J KAUFMANN, L RABJOHNS, RR MCRAE, RP GHALI, J ADAMS, HP THEILEN, EO BILLER, J BROWN, DD MARSH, EE SIRNA, SJ MITCHELL, VL ROTHBART, RM BAILEY, GH BURKHARDT, C BLACKSHEAR, JL WEAVER, L LEE, G LANE, G RUBINO, F SAFFORD, R KRONMAL, RA MCBRIDE, R ATHEARN, MW PEARCE, LA NASCO, E HART, RG SHERMAN, CP SHERMAN, DG TALBERT, RL DACY, TL HEBERLING, PA AF ANDERSON, DC ASINGER, RW NEWBURG, SM FARMER, CC WANG, K BUNDLIE, SR KOLLER, RL JAGIELLA, WM KREHER, S JORGENSEN, CR SHARKEY, SW FLAKER, GC WEBEL, R NOLTE, B STEVENSON, P BYER, J WRIGHT, W CHESEBRO, JH WIEBERS, DO HOLLAND, AE MILLER, DM BARDSLEY, WT LITIN, SC MEISSNER, I ZERBE, DM MCANULTY, JH MARCHANT, C COULL, BM FELDMAN, G HAYWARD, A GANDARA, E MACMILLAN, K BLANK, N LEONARD, AD KANTER, MC ISENSEE, LM QUIROGA, ES PRESTI, CH TEGELER, CH LOGAN, WR HAMILTON, WP GREEN, BJ BACON, RS REDD, RM CADELL, DJ GOMEZ, CR JANOSIK, DL LABOVITZ, AJ KELLEY, RE CHAHINE, R CRISTO, L PALERMO, M PEREZ, O FEINBERG, WM VOLD, BK KERN, KB APPLETON, C MILLER, VT HOCKERSMITH, CJ COHEN, BA MARTIN, GJ PAWLOW, AJ HALPERIN, JL ROTHLAUF, EB WEINBERGER, JM GOLDMAN, ME FUSTER, V DITTRICH, HC ROTHROCK, JF HAGENHOFF, C HELGASON, CM KONDOS, GT HOFF, J KAUFMANN, L RABJOHNS, RR MCRAE, RP GHALI, J ADAMS, HP THEILEN, EO BILLER, J BROWN, DD MARSH, EE SIRNA, SJ MITCHELL, VL ROTHBART, RM BAILEY, GH BURKHARDT, C BLACKSHEAR, JL WEAVER, L LEE, G LANE, G RUBINO, F SAFFORD, R KRONMAL, RA MCBRIDE, R ATHEARN, MW PEARCE, LA NASCO, E HART, RG SHERMAN, CP SHERMAN, DG TALBERT, RL DACY, TL HEBERLING, PA TI PREDICTORS OF THROMBOEMBOLISM IN ATRIAL-FIBRILLATION .1. CLINICAL-FEATURES OF PATIENTS AT RISK SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE ATRIAL FIBRILLATION; CEREBROVASCULAR DISORDERS; HEART FAILURE, CONGESTIVE; HYPERTENSION; THROMBOEMBOLISM ID SYSTEMIC EMBOLIZATION; STROKE; FRAMINGHAM; COMPLICATIONS; TRIAL AB Objective: To identify those patients with nonrheumatic atrial fibrillation who are at high risk and those at low risk for arterial thromboembolism. Design: Cohort study of patients assigned to placebo in a randomized clinical trial. Setting: Five hundred sixty-eight inpatients and outpatients with nonrheumatic atrial fibrillation assigned to placebo therapy at 15 U.S. medical centers from 1987 to 1989 in the Stroke Prevention in Atrial Fibrillation study. Patients were followed for a mean of 1.3 years. Measurements: Clinical variables were assessed at study entry and correlated with subsequent ischemic stroke and systemic embolism by multivariate analysis. Main Results: Recent (within 3 months) congestive heart failure, a history of hypertension, and previous arterial thromboembolism were each significantly and independently associated with a substantial risk for thromboembolism (> 7% per year; P less-than-or-equal-to 0.05). The presence of these three independent clinical predictors (recent congestive heart failure, history of hypertension, previous thromboembolism) defined patients with rates of thromboembolism of 2.5% per year (no risk factors), 7.2% per year (one risk factor), and 17.6% per year (two or three risk factors). Nondiabetic patients without these risk factors, comprising 38% of the cohort, had a low risk for thromboembolism (1.4% per year; 95% Cl, 0.05% to 3.7%). Patients without clinical risk factors who were under 60 years of age had no thromboembolic events. Conclusion: Patients with atrial fibrillation at high risk (> 7% per year) and low risk (< 3% per year) for thromboembolism can be identified by readily available clinical variables. C1 STAT & EPIDEMIOL RES CORP,SPAF STAT COORDINAT CTR,1107 NE 45TH ST,SUITE 520,SEATTLE,WA 98105. HENNEPIN CTY MED CTR,MINNEAPOLIS,MN 55415. ABBOTT NW HOSP,MINNEAPOLIS,MN. UNIV MISSOURI,COLUMBIA,MO 65201. MAYO CLIN & MAYO FDN,ROCHESTER,MN 55905. OREGON HLTH SCI UNIV,PORTLAND,OR 97201. KAISER PERMANENTE,PORTLAND,OR. UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. ST JOHNS MERCY MED CTR,ST LOUIS,MO 63141. ST LOUIS UNIV,MED CTR,ST LOUIS,MO 63103. UNIV MIAMI,SCH MED,MIAMI,FL 33152. UNIV ARIZONA,COLL MED,TUCSON,AZ 85721. NORTHWESTERN UNIV,SCH MED,CHICAGO,IL 60611. MT SINAI MED CTR,NEW YORK,NY 10029. UNIV CALIF SAN DIEGO,MED CTR,LA JOLLA,CA 92093. UNIV ILLINOIS,COLL MED,CHICAGO,IL 60680. UNIV ILLINOIS,COLL MED,PEORIA,IL 61656. UNIV IOWA,COLL MED,IOWA CITY,IA 52242. UNIV COLORADO,COLL MED,BOULDER,CO 80309. MAYO CLIN,JACKSONVILLE,FL. UNIV WASHINGTON,SEATTLE,WA 98195. UNIV TEXAS,HLTH SCI CTR,CTR CLIN COORDINAT,SAN ANTONIO,TX 78284. RI Fuster, Valentin/H-4319-2015 OI Fuster, Valentin/0000-0002-9043-9986 NR 24 TC 299 Z9 304 U1 0 U2 3 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JAN 1 PY 1992 VL 116 IS 1 BP 1 EP 5 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA GX157 UT WOS:A1992GX15700001 ER PT J AU ANDERSON, DC ASINGER, RW NEWBURG, SM FARMER, CC WANG, K BUNDLIE, SR KOLLER, RL JAGIELLA, WM KREHER, S JORGENSEN, CR SHARKEY, SW FLAKER, GC WEBEL, R NOLTE, B STEVENSON, P BYER, J WRIGHT, W CHESEBRO, JH WIEBERS, DO HOLLAND, AE MILLER, DM BARDSLEY, WT LITIN, SC MEISSNER, I ZERBE, DM MCANULTY, JH MARCHANT, C COULL, BM FELDMAN, G HAYWARD, A GANDARA, E MACMILLAN, K BLANK, N LEONARD, AD KANTER, MC ISENSEE, LM QUIROGA, ES PRESTI, CH TEGELER, CH LOGAN, WR HAMILTON, WP GREEN, BJ BACON, RS REDD, RM CADELL, DJ GOMEZ, CR JANOSIK, DL LABOVITZ, AJ KELLEY, RE CHAHINE, R CRISTO, L PALERMO, M PEREZ, O FEINBERG, WM VOLD, BK KERN, KB APPLETON, C MILLER, VT HOCKERSMITH, CJ COHEN, BA MARTIN, GJ PAWLOW, AJ HALPERIN, JL ROTHLAUF, EB WEINBERGER, JM GOLDMAN, ME FUSTER, V DITTRICH, HC ROTHROCK, JF HAGENHOFF, C HELGASON, CM KONDOS, GT HOFF, J KAUFMANN, L RABJOHNS, RR MCRAE, RP GHALI, J ADAMS, HP THEILEN, EO BILLER, J BROWN, DD MARSH, EE SIRNA, SJ MITCHELL, VL ROTHBART, RM BAILEY, GH BURKHARDT, C BLACKSHEAR, JL WEAVER, L LEE, G LANE, G RUBINO, F SAFFORD, R KRONMAL, RA MCBRIDE, R PEARCE, LA NASCO, E HART, RG SHERMAN, CP SHERMAN, DG TALBERT, RL DACY, TL HEBERLING, PA AF ANDERSON, DC ASINGER, RW NEWBURG, SM FARMER, CC WANG, K BUNDLIE, SR KOLLER, RL JAGIELLA, WM KREHER, S JORGENSEN, CR SHARKEY, SW FLAKER, GC WEBEL, R NOLTE, B STEVENSON, P BYER, J WRIGHT, W CHESEBRO, JH WIEBERS, DO HOLLAND, AE MILLER, DM BARDSLEY, WT LITIN, SC MEISSNER, I ZERBE, DM MCANULTY, JH MARCHANT, C COULL, BM FELDMAN, G HAYWARD, A GANDARA, E MACMILLAN, K BLANK, N LEONARD, AD KANTER, MC ISENSEE, LM QUIROGA, ES PRESTI, CH TEGELER, CH LOGAN, WR HAMILTON, WP GREEN, BJ BACON, RS REDD, RM CADELL, DJ GOMEZ, CR JANOSIK, DL LABOVITZ, AJ KELLEY, RE CHAHINE, R CRISTO, L PALERMO, M PEREZ, O FEINBERG, WM VOLD, BK KERN, KB APPLETON, C MILLER, VT HOCKERSMITH, CJ COHEN, BA MARTIN, GJ PAWLOW, AJ HALPERIN, JL ROTHLAUF, EB WEINBERGER, JM GOLDMAN, ME FUSTER, V DITTRICH, HC ROTHROCK, JF HAGENHOFF, C HELGASON, CM KONDOS, GT HOFF, J KAUFMANN, L RABJOHNS, RR MCRAE, RP GHALI, J ADAMS, HP THEILEN, EO BILLER, J BROWN, DD MARSH, EE SIRNA, SJ MITCHELL, VL ROTHBART, RM BAILEY, GH BURKHARDT, C BLACKSHEAR, JL WEAVER, L LEE, G LANE, G RUBINO, F SAFFORD, R KRONMAL, RA MCBRIDE, R PEARCE, LA NASCO, E HART, RG SHERMAN, CP SHERMAN, DG TALBERT, RL DACY, TL HEBERLING, PA TI PREDICTORS OF THROMBOEMBOLISM IN ATRIAL-FIBRILLATION .2. ECHOCARDIOGRAPHIC FEATURES OF PATIENTS AT RISK SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE THROMBOEMBOLISM; ATRIAL FIBRILLATION; CEREBROVASCULAR DISORDERS; HYPERTENSION; HEART FAILURE, CONGESTIVE ID LEFT-VENTRICULAR MASS; SYSTEMIC EMBOLIZATION; STROKE; COMPLICATIONS AB Objective: To identify echocardiographic predictors of arterial thromboembolism in patients with nonrheumatic atrial fibrillation and to determine whether these add to clinical variables for risk stratification. Design: Cohort study of patients assigned to placebo in a randomized clinical trial. Setting: Five hundred sixty-eight inpatients and outpatients with nonrheumatic atrial fibrillation assigned to placebo therapy at 15 U.S. medical centers from 1987 to 1989 in the Stroke Prevention in Atrial Fibrillation study. Patients were followed for a mean of 1.3 years. Measurements: M-mode and two-dimensional (2-D) echocardiograms performed at study entry and interpreted by local cardiologists. The predictive value of 14 echocardiographic variables for later ischemic stroke or systemic embolism was assessed by multivariate analysis. Main Results: Left ventricular dysfunction from 2-D echocardiograms (P = 0.003) and the size of the left atrium from M-mode echocardiograms (P = 0.02) were the strongest independent predictors of later thromboembolism. Multivariate analysis of these two independent echocardiographic predictors with the three independent clinical predictors of thromboembolism (history of hypertension, recent congestive heart failure, previous thromboembolism) identified 26% of the cohort with a low risk for thromboembolism (1.0% per year; 95% Cl, 0.2% to 4.0%). Compared with risk stratification using clinical variables alone, echocardiographic results altered thromboembolic risk stratification in 18% of the entire cohort and in 38% of those without clinical risk factors. Conclusions: Both left ventricular and left atrial variables are significant predictors of thromboembolism in patients with nonvalvular atrial fibrillation. Our results challenge traditional views of the pathogenesis of ischemic stroke in patients with atrial fibrillation and suggest that standard echocardiography contributes to risk stratification, differentiating the one third of patients without clinical risk factors who are at increased risk for stroke from the remainder who may not need antithrombotic prophylaxis. C1 STAT & EPIDEMIOL RES CORP,SPAF STAT COORDINAT CTR,1107 NE 45TH ST,SUITE 520,SEATTLE,WA 98105. HENNEPIN CTY MED CTR,MINNEAPOLIS,MN 55415. ABBOTT NW HOSP,MINNEAPOLIS,MN. UNIV MISSOURI,COLUMBIA,MO 65201. MAYO CLIN & MAYO FDN,ROCHESTER,MN 55905. OREGON HLTH SCI UNIV,PORTLAND,OR 97201. KAISER PERMANENTE,PORTLAND,OR. UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. ST JOHNS MERCY MED CTR,ST LOUIS,MO 63141. ST LOUIS UNIV,MED CTR,ST LOUIS,MO 63103. UNIV MIAMI,SCH MED,MIAMI,FL 33152. UNIV ARIZONA,COLL MED,TUCSON,AZ 85721. NORTHWESTERN UNIV,SCH MED,CHICAGO,IL 60611. MT SINAI MED CTR,NEW YORK,NY 10029. UNIV CALIF SAN DIEGO,MED CTR,LA JOLLA,CA 92093. UNIV ILLINOIS,COLL MED,CHICAGO,IL 60680. UNIV ILLINOIS,COLL MED,PEORIA,IL 61656. UNIV IOWA,COLL MED,IOWA CITY,IA 52242. UNIV COLORADO,COLL MED,BOULDER,CO 80309. MAYO CLIN,JACKSONVILLE,FL. UNIV WASHINGTON,SEATTLE,WA 98195. UNIV TEXAS,HLTH SCI CTR,CTR CLIN COORDINAT,SAN ANTONIO,TX 78284. RI Fuster, Valentin/H-4319-2015 OI Fuster, Valentin/0000-0002-9043-9986 NR 25 TC 332 Z9 337 U1 0 U2 3 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JAN 1 PY 1992 VL 116 IS 1 BP 6 EP 12 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA GX157 UT WOS:A1992GX15700002 ER PT J AU SAYERS, MH ANDERSON, KC GOODNOUGH, LT KURTZ, SR LANE, TA PISCIOTTO, P SILBERSTEIN, LE AF SAYERS, MH ANDERSON, KC GOODNOUGH, LT KURTZ, SR LANE, TA PISCIOTTO, P SILBERSTEIN, LE TI REDUCING THE RISK FOR TRANSFUSION-TRANSMITTED CYTOMEGALOVIRUS-INFECTION SO ANNALS OF INTERNAL MEDICINE LA English DT Review ID BONE-MARROW TRANSPLANTATION; RED-BLOOD-CELLS; VIRUS CMV INFECTION; RENAL-TRANSPLANTATION; IMMUNE GLOBULIN; NEWBORN-INFANTS; ACUTE-LEUKEMIA; PREVENTION; DISEASE; DONORS AB Objective: To define the groups of patients at risk for transfusion-transmitted cytomegalovirus infection and to define the methods to reduce this risk. Data Sources: English-language publications on transfusion medicine. Study Selection and Data Extraction: Studies were selected that described cytomegalovirus infection in transfusion-dependent patients. Special attention was paid to reports that included observations about the prevalence and clinical manifestations of cytomegalovirus infection and recommendations for the prevention of infection. Data Synthesis. Some patients with impaired immune responses who have never been exposed to cytomegalovirus are at risk for transfusion-transmitted cytomegalovirus infection. This infection, which is associated with substantial morbidity and mortality, can be avoided by additional screening of blood donors or by special processing of components for transfusion. Conclusions. Transfusion products that are unlikely to transmit cytomegalovirus infection can be prepared by filtration to remove leukocytes or can be obtained by selecting donors who are seronegative for antibodies to cytomegalovirus. These products are indicated for certain groups of immunosuppressed patients, including pregnant women who are cytomegalovirus seronegative, premature infants of low birth weight who are born to cytomegalovirus-seronegative mothers, cytomegalovirus-seronegative recipients of allogeneic bone marrow transplants from cytomegalovirus-seronegative donors, and cytomegalovirus-seronegative patients with the acquired immunodeficiency syndrome (AIDS). C1 UNIV WASHINGTON,SEATTLE,WA 98195. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. UNIV HOSP CLEVELAND,CLEVELAND,OH 44106. IRELAND CANC CTR,CLEVELAND,OH. LAHEY CLIN FDN,MED CTR,BURLINGTON,MA. UNIV CALIF SAN DIEGO,LA JOLLA,CA 92093. UNIV CONNECTICUT,CTR HLTH,FARMINGTON,CT 06032. UNIV PENN,BLOOD BANK,PHILADELPHIA,PA 19104. RP SAYERS, MH (reprint author), PUGET SOUND BLOOD CTR,921 TERRY AVE,SEATTLE,WA 98104, USA. NR 68 TC 84 Z9 85 U1 2 U2 2 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JAN 1 PY 1992 VL 116 IS 1 BP 55 EP 62 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA GX157 UT WOS:A1992GX15700010 PM 1309201 ER PT J AU NIHEI, K KOWALL, NW AF NIHEI, K KOWALL, NW TI NEUROFILAMENT AND NEURAL CELL-ADHESION MOLECULE IMMUNOCYTOCHEMISTRY OF HUNTINGTONS-DISEASE STRIATUM SO ANNALS OF NEUROLOGY LA English DT Article ID ALZHEIMERS-DISEASE; MONOCLONAL-ANTIBODY; PYRAMIDAL NEURONS; CORTICAL-NEURONS; LOCALIZATION; NEOSTRIATUM; CORTEX; GOLGI AB We examined normal and Huntington's disease (HD) human striatum with specific monoclonal antibodies to nonphosphorylated (SMI 32) and phosphorylated (SMI 31) neurofilament and neural cell adhesion molecule (NCAM). SMI 32 identifies medium-sized neuronal perikarya and dendrites in normal striatum. Axons are not immunoreactive. In high-grade HD striatum (grades 3 and 4) SMI 32 neurons are morphologically abnormal and significantly depleted. Dendritic arbors are intensely immunoreactive, tortuous, and fragmented, especially in the subependymal zone. Proliferative SMI 32-positive sprout-like structures and axon-like processes are seen. SMI 31 normally stains a fine meshwork of axon-like processes that become intensely immunoreactive, condensed, convoluted, and fragmented in HD. NCAM staining is minimal in normal straitum, but, in HD striatum, many dot- and thread-like structures are found, especially in the subependymal region. The abnormalities revealed by SMI 31, SMI 32, and NCAM suggest that neurofilament phosphorylation is altered and growth related proteins are reexpressed in HD. Dephosphorylation and destabilization of the cytoskeleton may contribute to neuronal injury and death in HD. C1 MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,EXPTL NEUROPATHOL LAB,BOSTON,MA 02114. RI Kowall, Neil/G-6364-2012 OI Kowall, Neil/0000-0002-6624-0213 FU NINDS NIH HHS [NS 25588] NR 26 TC 21 Z9 21 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 JAN PY 1992 VL 31 IS 1 BP 59 EP 63 DI 10.1002/ana.410310111 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA GY489 UT WOS:A1992GY48900009 PM 1531909 ER PT J AU BORODIC, GE FERRANTE, R WIEGNER, AW YOUNG, RR AF BORODIC, GE FERRANTE, R WIEGNER, AW YOUNG, RR TI TREATMENT OF SPASTICITY WITH BOTULINUM TOXIN SO ANNALS OF NEUROLOGY LA English DT Letter C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. VET ADM MED CTR W ROXBURY,SPINAL CORD INJURY SERV,BOSTON,MA 02132. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP BORODIC, GE (reprint author), MASSACHUSETTS EYE & EAR HOSP,DEPT OPHTHALMOL,BOSTON,MA 02114, USA. NR 6 TC 7 Z9 7 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 JAN PY 1992 VL 31 IS 1 BP 113 EP 113 DI 10.1002/ana.410310122 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA GY489 UT WOS:A1992GY48900020 PM 1543342 ER PT J AU DAMSTRUP, L ANDERSEN, J KUFE, DW HAYES, DF POULSEN, HS AF DAMSTRUP, L ANDERSEN, J KUFE, DW HAYES, DF POULSEN, HS TI IMMUNOCYTOCHEMICAL DETERMINATION OF THE ESTROGEN-REGULATED PROTEINS MR 24,000, MR 52,000 AND DF3 BREAST-CANCER ASSOCIATED ANTIGEN - CLINICAL-VALUE IN ADVANCED BREAST-CANCER AND CORRELATION WITH ESTROGEN-RECEPTOR SO ANNALS OF ONCOLOGY LA English DT Article DE BREAST CANCER; DF3 ANTIGEN; MR 24,000 PROTEIN; MR 52,000 PROTEIN; RESPONSE TO ENDOCRINE THERAPY ID MONOCLONAL-ANTIBODIES; CATHEPSIN-D; CARCINOEMBRYONIC ANTIGEN; PROGESTERONE RECEPTORS; CELLS; ASSAY; THERAPY; TUMORS; CA15-3; TISSUE AB The M(r) 24,000 and M(r) 52,000 estrogen-regulated cytosol proteins, and the breast cancer-associated antigen DF3 have been studied in an immunocytochemical assay. Primary tumor specimens from 119 patients with advanced breast cancer who received endocrine therapy have been studied. Monoclonal antibodies were used for the detection of the proteins in formalin-fixed paraffin-embedded blocks. No correlation between M(r) 52,000-positive specimens and the presence of estrogen receptor (ER) could be established (p = 0.87, chi-square test) whereas a statistically significant association between M(r) 24,000 (p = 0.0002), DF3 antigen (p = 0.044) and ER was demonstrated. No intercorrelation was found between M(r) 24,000 and M(r) 52,000 or DF3 (p = 0.63, 0.98 and 0.12 respectively). Clinical response was evaluated for immunocytochemical findings, M(r) 24,000 (p = 0.37), M(r) 52,000 (p = 0.61) and DF3 (p = 0.68) showed no association whereas ER was statistically correlated (p = 0.00005). Neither overall survival nor disease-free survival correlated to M(r) 24,000 (p = 0.18 and 0.75 respectively, logrank test), M(r) 52,000 (p = 0.095 and 0.38), or DF3 (p = 0.22 and 0.13) staining, whereas ER-positive tumors did (p = 0.00005). Discrimination between ER-positive responders and ER-positive non-responders was not possible using either M(r) 52,000, M(r) 24,000 or DF3 staining. Based on our findings we conclude that immunocytochemical staining for M(r) 52,000, M(r) 24,000 or DF3 cannot be used as a marker to predict response to endocrine therapy in patients with advanced or recurrent breast cancer. C1 RIGSHOSP,DEPT ONCOL 5074,BLEGDAMSVEJ 9,DK-2100 COPENHAGEN,DENMARK. RADIUMSTATIONEN,DANISH CANC SOC,DEPT EXPTL CLIN ONCOL,RECEPTOR LAB,AARHUS,DENMARK. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. UNIV COPENHAGEN,INST PATHOL ANAT,DK-1168 COPENHAGEN,DENMARK. RADIUMSTATIONEN,DEPT ONCOL,AARHUS,DENMARK. FU NCI NIH HHS [CA 11378] NR 29 TC 13 Z9 14 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD JAN PY 1992 VL 3 IS 1 BP 71 EP 77 PG 7 WC Oncology SC Oncology GA HC082 UT WOS:A1992HC08200017 PM 1606073 ER PT J AU SCHMIDT, J RATTNER, DW LEWANDROWSKI, K COMPTON, CC MANDAVILLI, U KNOEFEL, WT WARSHAW, AL AF SCHMIDT, J RATTNER, DW LEWANDROWSKI, K COMPTON, CC MANDAVILLI, U KNOEFEL, WT WARSHAW, AL TI A BETTER MODEL OF ACUTE-PANCREATITIS FOR EVALUATING THERAPY SO ANNALS OF SURGERY LA English DT Article ID ACUTE HEMORRHAGIC-PANCREATITIS; NECROTIZING PANCREATITIS; RAT; SCORPION; MICE AB Existing models of acute pancreatitis have limitations to studying novel therapy. Whereas some produce mild self-limited pancreatitis, others result in sudden necrotizing injury. The authors developed an improved model providing homogeneous moderately severe injury by superimposing secretory hyperstimulation on minimal intraductal bile acid exposure. Sprague-Dawley rats (n = 231) received low-pressure intraductal glycodeoxycholic acid (GDOC) at very low (5 or 10 mmol/L) concentrations followed by intravenous cerulein. Cerulein or GDOC alone caused only very mild inflammation. However, GDOC combined with cerulein was uniformly associated with more edema (p < 0.0005), acinar necrosis (p < 0.01), inflammation (p < 0.006), and hemorrhage (p < 0.01). Pancreatic injury was further increased and death was potentiated by increasing volume and duration of intraductal low-dose GDOC infusion. There was significant morphologic progression between 6 and 24 hours. The authors conclude that (1) combining minimal intraductal bile acid exposure intravenous hyperstimulation produces homogeneous pancreatitis of intermediate severity that can be modulated at will; (2) the injury is progressive over at least 24 hours with finite mortality rate; (3) the model provides superior opportunity to study innovative therapy. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,WACC 336,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02114. NR 32 TC 445 Z9 552 U1 1 U2 11 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD JAN PY 1992 VL 215 IS 1 BP 44 EP 56 PG 13 WC Surgery SC Surgery GA GY757 UT WOS:A1992GY75700008 PM 1731649 ER PT J AU GRILLO, HC MATHISEN, DJ WAIN, JC AF GRILLO, HC MATHISEN, DJ WAIN, JC TI LARYNGOTRACHEAL RESECTION AND RECONSTRUCTION FOR SUBGLOTTIC STENOSIS SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 27TH ANNUAL MEETING OF THE SOC OF THORACIC SURGEONS CY FEB 18-20, 1991 CL SAN FRANCISCO, CA SP SOC THORAC SURGEONS ID TRACHEAL ANASTOMOSIS; CRICOID RESECTION; LARYNGEAL; MANAGEMENT; AIRWAY AB Eighty patients with inflammatory stenoses of the subglottic larynx and upper trachea were treated by single-stage laryngotracheal resection and reconstruction. Fifty stenoses originated from postintubation lesions (endotracheal tubes, tracheostomy, cricothyroidostomy), 7 originated from trauma, 19 were idiopathic, and 4 were miscellaneous. Repair consisted of resection of the anterolateral cricoid arch in all patients, plus resection of posterior laryngeal stenosis where present, with salvage of the posterior cricoid plate, appropriate resection and tailoring of the trachea, and primary anastomosis using a posterior membranous tracheal wall flap to resurface the bared cricoid cartilage in 31 patients. One postoperative death resulted from acute myocardial infarction. Long-term results were excellent in 18 patients, good in 48, satisfactory in 8, and failure in 2. Three additional patients had good results at discharge but were followed up for less than 6 months. 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 93 Z9 106 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 JAN PY 1992 VL 53 IS 1 BP 54 EP 63 PG 10 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA GY488 UT WOS:A1992GY48800009 PM 1728242 ER PT J AU SCHATZ, DG OETTINGER, MA SCHLISSEL, MS AF SCHATZ, DG OETTINGER, MA SCHLISSEL, MS TI V (D) J RECOMBINATION - MOLECULAR-BIOLOGY AND REGULATION SO ANNUAL REVIEW OF IMMUNOLOGY LA English DT Review DE V (D) J RECOMBINATION; LYMPHOID DEVELOPMENT; RECOMBINATION ACTIVATING GENE; RAG-1; RAG-2 ID T-CELL-RECEPTOR; PRE-B-CELLS; HEAVY-CHAIN GENE; COMBINED IMMUNE-DEFICIENCY; LYMPHOID V(D)J RECOMBINATION; GAMMA-DELTA-GENES; IMMUNOGLOBULIN GENES; TRANSGENIC MICE; SIGNAL SEQUENCES; ANTIBODY DIVERSITY C1 YALE UNIV,SCH MED,IMMUNOBIOL SECT,NEW HAVEN,CT 06510. MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. JOHNS HOPKINS UNIV,SCH MED,DEPT MOLEC BIOL & GENET,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21205. RP SCHATZ, DG (reprint author), YALE UNIV,SCH MED,HOWARD HUGHES MED INST,NEW HAVEN,CT 06510, USA. RI Schatz, David/A-6748-2013 OI Schatz, David/0000-0002-5669-1176 NR 110 TC 390 Z9 391 U1 0 U2 5 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 SN 0732-0582 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 1992 VL 10 BP 359 EP 383 DI 10.1146/annurev.immunol.10.1.359 PG 25 WC Immunology SC Immunology GA HN012 UT WOS:A1992HN01200014 PM 1590991 ER PT J AU COLTEN, HR ROSEN, FS AF COLTEN, HR ROSEN, FS TI COMPLEMENT DEFICIENCIES SO ANNUAL REVIEW OF IMMUNOLOGY LA English DT Review DE COMPLEMENT; GENETICS; GENETIC DEFICIENCIES; MOLECULAR GENETICS ID PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA; SYSTEMIC LUPUS-ERYTHEMATOSUS; FRAGMENT LENGTH POLYMORPHISM; AMINO-ACID-SEQUENCE; MAJOR HISTOCOMPATIBILITY COMPLEX; HEREDITARY ANGIONEUROTIC-EDEMA; LEUKOCYTE ADHESION DEFICIENCY; DECAY-ACCELERATING FACTOR; HOMOZYGOUS C3-DEFICIENT HUMANS; STEROID 21-HYDROXYLASE GENES AB The complement system consists of about two dozen plasma and cell membrane proteins which function as cofactors in defense against pathogenic microbes and in the generation of many immunopathogenic disorders. The complexity of this system and its role in other biological functions has been appreciated within the last two decades. Recognition of genetic deficiencies of the complement proteins and their phenotypic expression has provided additional insights into the physiological role of the complement system. Complementary DNA (cDNA) clones for most of the complement components are now available, and the gene structures for many have been elucidated. Application of molecular biological methods to studies of the complement system and its deficiencies has permitted both the determination of primary structure and chromosomal localization of complement genes (Figure 1) and the capacity to elucidate the molecular basis of complement deficiency disorders. C1 CTR BLOOD RES,BOSTON,MA 02115. RP COLTEN, HR (reprint author), WASHINGTON UNIV,SCH MED,DEPT PEDIAT,ST LOUIS,MO 63110, USA. NR 186 TC 91 Z9 95 U1 0 U2 1 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 SN 0732-0582 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 1992 VL 10 BP 809 EP 834 DI 10.1146/annurev.immunol.10.1.809 PG 26 WC Immunology SC Immunology GA HN012 UT WOS:A1992HN01200029 PM 1591004 ER PT J AU RUSTGI, AK PODOLSKY, DK AF RUSTGI, AK PODOLSKY, DK TI THE MOLECULAR-BASIS OF COLON CANCER SO ANNUAL REVIEW OF MEDICINE LA English DT Review DE DOMINANT ONCOGENE; TUMOR SUPPRESSOR GENE; HEREDITARY POLYPOSIS SYNDROMES; CHROMOSOMAL ALLELIC DELETION ID COLORECTAL CANCERS; GENE AB There are approximately 160,000 new cases of colon cancer every year in the United States. Colon carcinoma results from the aggregate effects of multiple genetic alterations. Some genetic alterations may be inherited, while others reflect somatic mutations. The latter may themselves be the indirect result of environmental factors such as diet. It is the total accumulation of these genetic changes, combining the activation of oncogenes with the inactivation of tumor suppressor genes, that is responsible for determining the biologic properties of colon cancer. RP RUSTGI, AK (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,GASTROENTEROL UNIT,BOSTON,MA 02114, USA. NR 13 TC 16 Z9 16 U1 2 U2 2 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 SN 0066-4219 J9 ANNU REV MED JI Annu. Rev. Med. PY 1992 VL 43 BP 61 EP 68 DI 10.1146/annurev.med.43.1.61 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA HL709 UT WOS:A1992HL70900006 PM 1580606 ER PT J AU DINAUER, MC ORKIN, SH AF DINAUER, MC ORKIN, SH TI CHRONIC GRANULOMATOUS-DISEASE SO ANNUAL REVIEW OF MEDICINE LA English DT Review DE INTERFERON-GAMMA; RESPIRATORY BURST; SUPEROXIDE; NADPH-OXIDASE; CYTOCHROME-B; PHAGOCYTE; NEUTROPHIL; MACROPHAGE ID RESPIRATORY BURST OXIDASE; 2 CYTOSOLIC COMPONENTS; CYTOCHROME-B; CHROMOSOMAL LOCATION; HUMAN-NEUTROPHILS; INTERFERON-GAMMA; NADPH OXIDASE; CLONING; GENE; EXPRESSION AB Chronic granulomatous disease (CGD) encompasses a group of rare inherited disorders characterized by defects in a phagocyte-specific NADPH-oxidase complex that forms the superoxide radical during the respiratory burst. In this chapter, the protein components and cellular biochemistry of the oxidase are reviewed in light of recent genetic and biochemical studies of CGD. The classification and molecular genetic analysis of CGD is discussed. Finally, the use of recombinant human interferon-gamma as a new therapeutic agent for management of the disorder is reviewed. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PEDIAT,BOSTON,MA 02115. HOWARD HUGHES MED INST,BOSTON,MA 02115. RP DINAUER, MC (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,CHILDRENS HOSP,DIV HEMATOL ONCOL,BOSTON,MA 02115, USA. FU NHLBI NIH HHS [HL45635, HL02253]; NICHD NIH HHS [HD18661] NR 23 TC 75 Z9 79 U1 0 U2 0 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 SN 0066-4219 J9 ANNU REV MED JI Annu. Rev. Med. PY 1992 VL 43 BP 117 EP 124 DI 10.1146/annurev.med.43.1.117 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA HL709 UT WOS:A1992HL70900011 PM 1316094 ER PT J AU BONVENTRE, JV WEINBERG, JM AF BONVENTRE, JV WEINBERG, JM TI KIDNEY-PRESERVATION EXVIVO FOR TRANSPLANTATION SO ANNUAL REVIEW OF MEDICINE LA English DT Review DE ACUTE RENAL FAILURE; ORGAN PRESERVATION; ISCHEMIA; CRYOPROTECTION ID ACUTE-RENAL-FAILURE; PERFUSED RAT-KIDNEY; TUBULE CELL INJURY; EXOGENOUS ADENINE-NUCLEOTIDES; SOLID-ORGAN PRESERVATION; DELAYED GRAFT FUNCTION; EURO-COLLINS SOLUTIONS; COLD-STORAGE SOLUTION; HUMAN-LIVER GRAFTS; UW-SOLUTION AB Ischemic injury to the renal allograft, prior to implantation, is an important cause of delayed graft function. With improved understanding of the pathophysiological mechanisms involved, strategies have been devised to minimize ischemic injury during preservation ex vivo. It is clear that reducing the warm ischemic time, flushing the kidney with hypothermic solution containing cell-impermeant compounds, and maintaining the organ at low temperature ex vivo have increased the duration that the kidney can be preserved. The effectiveness of a number of other components of preservation solutions, as well as the relative merits of continuous perfusion of the organ ex vivo, is more controversial. In this chapter, we review the mechanistic features of ischemic acute renal failure and discuss various preservation strategies and their success in the context of these basic principles of ischemic pathophysiology. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02114. UNIV MICHIGAN,DEPT MED,ANN ARBOR,MI 48109. VET ADM MED CTR,ANN ARBOR,MI 48109. RP BONVENTRE, JV (reprint author), MASSACHUSETTS GEN HOSP,MED SERV,BOSTON,MA 02114, USA. NR 267 TC 58 Z9 58 U1 0 U2 1 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 SN 0066-4219 J9 ANNU REV MED JI Annu. Rev. Med. PY 1992 VL 43 BP 523 EP 553 PG 31 WC Medicine, General & Internal SC General & Internal Medicine GA HL709 UT WOS:A1992HL70900040 PM 1580605 ER PT J AU ALLENDOERFER, R YATES, RR MARQUIS, AJ LOEBENBERG, D RINALDI, MG GRAYBILL, JR AF ALLENDOERFER, R YATES, RR MARQUIS, AJ LOEBENBERG, D RINALDI, MG GRAYBILL, JR TI COMPARISON OF SCH-39304 AND ITS ISOMERS, RR-42427 AND SS-42426, FOR TREATMENT OF MURINE CRYPTOCOCCAL AND COCCIDIOIDAL MENINGITIS SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Note ID INVIVO EFFICACY; AMPHOTERICIN-B; FLUCONAZOLE; SCH39304; TRIAZOLE AB SCH 39304 (304) and its isomers, SCH 42426 (426) and SCH 42427 (427), are new orally administered antifungal azole derivatives. In this study, we compared the efficacy of 304 with that of 426 and 427 in murine models of cryptococcal and coccidioidal meningitis. On day 18 postinfection with Cryptococcus neoformans, controls showed 80% mortality. The 50% protective doses calculated at this day were 0.56 mg of 304 per kg of body weight, 23.5 mg of 426 per kg, and 0.11 mg of 427 per kg. Controls with coccidioidal meningitis all succumbed, and treated mice at the same time point showed 50% protective doses of 10.8 mg/kg for 304, 200 mg/kg for 426, and 2.1 mg/kg for 427. We conclude that isomer 427 is five times as potent, whereas 426 is 1/50th as potent as 304 in these experimental mycoses. C1 UNIV TEXAS,HLTH SCI CTR,DEPT PATHOL,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. SCHERING PLOUGH RES CORP,BLOOMFIELD,NJ 07003. RP ALLENDOERFER, R (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284, USA. NR 17 TC 9 Z9 9 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JAN PY 1992 VL 36 IS 1 BP 217 EP 219 PG 3 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA GY477 UT WOS:A1992GY47700044 PM 1590692 ER PT J AU ZWEIG, AD DEUTSCH, TF AF ZWEIG, AD DEUTSCH, TF TI SHOCK-WAVES GENERATED BY CONFINED XECL EXCIMER LASER ABLATION OF POLYIMIDE SO APPLIED PHYSICS B-PHOTOPHYSICS AND LASER CHEMISTRY LA English DT Article ID POLYMERS; PLASMA; NM; TISSUE; WATER; FILMS AB We investigate shock waves generated by excimer laser ablation of sheet polyimide confined in water. The velocities of the ablation-induced pressure waves in the water are determined by an optical probe system. We measure supersonic velocities up to a few hundred microns away from the irradiated surface, indicating the formation of shock waves. We use these velocities to calculate the corresponding pressures. They are already in the kbar range at fluences comparable to the threshold of ablation. The shock pressure varies as the square root of the incident laser fluence, a behavior that is explained by the rapid heating of the confined gaseous products of ablation. The initially planar shock waves propagate, become spherical, and decay within a few hundred microns in the surrounding water to acoustic waves. During spherical expansion the shock pressure drops as the inverse of the square of the propagation distance. The shock waves generated may be relevant in explaining photoacoustic damage observed in biological tissue after excimer-ablation at corresponding irradiances. They may also be important in material processing applications of excimer laser ablation of polymers as they can lead to plastic deformation. RP ZWEIG, AD (reprint author), MASSACHUSETTS GEN HOSP,WELLMAN LABS PHOTOMED,BOSTON,MA 02114, USA. NR 27 TC 40 Z9 41 U1 1 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0721-7269 J9 APPL PHYS B-PHOTO PD JAN PY 1992 VL 54 IS 1 BP 76 EP 82 DI 10.1007/BF00331737 PG 7 WC Physics, Applied SC Physics GA HB490 UT WOS:A1992HB49000010 ER PT J AU LIPSITZ, SR LAIRD, NM HARRINGTON, DP AF LIPSITZ, SR LAIRD, NM HARRINGTON, DP TI A 3-STAGE ESTIMATOR FOR STUDIES WITH REPEATED AND POSSIBLY MISSING BINARY OUTCOMES SO APPLIED STATISTICS-JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES C LA English DT Article DE GENERALIZED LEAST SQUARES ESTIMATOR; REPEATED MEASURES; UNBALANCED DATA; WITHIN-SUBJECTS COVARIANCE MATRIX ID LOGISTIC-REGRESSION DIAGNOSTICS; LINEAR-MODELS AB This paper describes methods for analysing repeated measures data when the outcome is binary at each occasion. The models relate the expected value of the binary response at each occasion to covariates via the logistic link function. The method of estimation is a three-stage, generalized least squares method and is similar to the methods described by Ware and Jennrich and Schluchter for repeated continuous outcomes. The estimates are asymptotically equivalent to the estimates obtained from Liang and Zeger's 'generalized estimating equations' but have the advantage that they exist in some situations (i.e. small sample sizes, unbalanced data) when the Liang and Zeger estimates do not and can be computed using a newly available statistical package (BMDP 5V) designed for analysing unbalanced repeated continuous responses. Residual diagnostics are also briefly discussed. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. RP LIPSITZ, SR (reprint author), HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,677 HUNTINGTON AVE,BOSTON,MA 02115, USA. NR 17 TC 12 Z9 12 U1 0 U2 0 PU BLACKWELL PUBL LTD PI OXFORD PA 108 COWLEY RD, OXFORD, OXON, ENGLAND OX4 1JF SN 0035-9254 J9 APPL STAT-J ROY ST C JI Appl. Stat.-J. R. Stat. Soc. PY 1992 VL 41 IS 1 BP 203 EP 213 DI 10.2307/2347629 PG 11 WC Statistics & Probability SC Mathematics GA GW303 UT WOS:A1992GW30300018 ER PT J AU GREEN, HA BUA, D ANDERSON, RR NISHIOKA, NS AF GREEN, HA BUA, D ANDERSON, RR NISHIOKA, NS TI BURN DEPTH ESTIMATION USING INDOCYANINE GREEN FLUORESCENCE SO ARCHIVES OF DERMATOLOGY LA English DT Article ID INJURY; SKIN; ANGIOGRAPHY; ULTRASOUND; EXCISION AB Expedient primary excision of deep dermal and full-thickness burn wounds with subsequent skin grafting is the standard of care in most burn institutions, but differentiating full-thickness from partial-thickness burns is often difficult. Because accurate early assessment of burn depth may improve care, a variety of technical methods have attempted to measure burn depth but these methods have had limited success. We describe a new technique to determine burn depth that uses infrared (840- to 850-nm) fluorescence emission from intravenously administered indocyanine green following excitation with infrared (780 nm) and UV light (369 nm). Full-thickness and partial-thickness burns in hairless rat skin were distinguished based on the infrared-induced and UV-induced fluorescence intensity ratios relative to normal, unburned skin immediately after the burn and on postburn days 1 through 3 and 7. Dual-wavelength excitation of indocyanine green infrared fluorescence can delineate full-thickness from partial-thickness burns at an early date, allowing prognosis, surgical planning, and early primary excision and grafting. C1 MASSACHUSETTS GEN HOSP,WELLMAN LAB PHOTOMED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP GREEN, HA (reprint author), MASSACHUSETTS GEN HOSP,DEPT DERMATOL,WELLMAN 2,BOSTON,MA 02114, USA. NR 75 TC 33 Z9 33 U1 2 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD JAN PY 1992 VL 128 IS 1 BP 43 EP 49 DI 10.1001/archderm.128.1.43 PG 7 WC Dermatology SC Dermatology GA GZ894 UT WOS:A1992GZ89400004 PM 1739286 ER PT J AU RIZZO, JF CRONINGOLOMB, A GROWDON, JH CORKIN, S ROSEN, TJ SANDBERG, MA CHIAPPA, KH LESSELL, S AF RIZZO, JF CRONINGOLOMB, A GROWDON, JH CORKIN, S ROSEN, TJ SANDBERG, MA CHIAPPA, KH LESSELL, S TI RETINOCALCARINE FUNCTION IN ALZHEIMERS-DISEASE - A CLINICAL AND ELECTROPHYSIOLOGICAL STUDY SO ARCHIVES OF NEUROLOGY LA English DT Article ID OPTIC-NERVE; ELECTRORETINOGRAPHIC RESPONSES; VISUAL DISTURBANCES; PATTERN ERG; DEGENERATION; SECTION; VISION; COLOR; PERCEPTION; DIAGNOSIS AB Impaired visual function in Alzheimer's disease (AD) could result from either precortical or cortical lesions, or both. In a parallel psychophysical study of visual function in AD, we found that contrast sensitivity function, color vision, stereoacuity, and backward masking were impaired relative to the performance of age-matched control subjects, whereas performance on a critical flicker fusion test was normal. The intent of the present study was to determine whether abnormalities of the retinocalcarine pathway contribute to visual dysfunction. We performed neuro-ophthalmological examinations on 38 patients with AD; from this group, 25 received additional psychophysical testing and 13 underwent electrophysiological testing. Clinical neuro-ophthalmological examinations, full-field electroretinograms, focal electroretinograms, and pattern visual evoked potentials were normal in all patients tested. There was no evidence of retinocalcarine abnormality specific to AD. We conclude that the visual impairment experienced by some patients with AD primarily results from involvement of the visual association cortices rather than from precortical damage, at least before the end stage of the disease. C1 MIT,DEPT BRAIN & COGNIT SCI,CAMBRIDGE,MA 02139. HARVARD UNIV,SCH MED,DEPT OPHTHALMOL,BOSTON,MA 02115. BOSTON UNIV,DEPT PSYCHOL,BOSTON,MA 02215. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. BOSTON UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02118. MIT,CLIN RES CTR,CAMBRIDGE,MA 02139. RP RIZZO, JF (reprint author), MASSACHUSETTS EYE & EAR HOSP,243 CHARLES ST,BOSTON,MA 02114, USA. FU NEI NIH HHS [EY08398] NR 45 TC 64 Z9 64 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD JAN PY 1992 VL 49 IS 1 BP 93 EP 101 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA GY793 UT WOS:A1992GY79300018 PM 1728270 ER PT J AU SCHOLL, GB SONG, HS WINKLER, DE WRAY, SH AF SCHOLL, GB SONG, HS WINKLER, DE WRAY, SH TI THE PATTERN VISUAL EVOKED-POTENTIAL AND PATTERN ELECTRORETINOGRAM IN DRUSEN-ASSOCIATED OPTIC NEUROPATHY SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID CLINICAL ANALYSIS; DISK DRUSEN; PSEUDO-PAPILLEDEMA; STIMULUS FIELD; GLAUCOMA; DISEASE; PSEUDOPAPILLOEDEMA; NEURITIS; DEFECTS; VISION AB Sixteen patients (29 eyes) with optic disc drusen were studied prospectively for clinical and electrophysiologic evidence of impaired optic nerve conduction. Abnormalities were detected in the following areas: visual acuity, eight (28%) of 29 eyes; kinetic visual field, 22 (76%) of 29 eyes; results of Farnsworth-Munsell 100-Hue test, 12 (41%) of 29 eyes; and flash visual evoked potential, 13 (54%) of 24 eyes. Simultaneous pattern visual evoked potentials and results of pattern electroretinograms were recorded. The P100 latency of the pattern visual evoked potential was prolonged in 41% of eyes. The P50 and N95 components of the pattern electroretinogram were also analyzed. The P50 amplitude was reduced in only four (17%) of 24 eyes. The most common abnormality was a reduction in amplitude or the absence of the N95 component in 19 (79%) of 24 eyes, reflecting ganglion cell dysfunction. The data support mounting evidence that the P50 and N95 components of the pattern electroretinogram have different retinal origins. RP SCHOLL, GB (reprint author), MASSACHUSETTS GEN HOSP,DEPT NEUROL,NEUROVISUAL DISORDERS UNIT,ACC 837,15 PARKMAN ST,BOSTON,MA 02114, USA. NR 43 TC 18 Z9 20 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 JAN PY 1992 VL 110 IS 1 BP 75 EP 81 PG 7 WC Ophthalmology SC Ophthalmology GA GZ621 UT WOS:A1992GZ62100026 PM 1731726 ER PT J AU SCHEIN, OD HIBBERD, PL STARCK, T BAKER, AS KENYON, KR AF SCHEIN, OD HIBBERD, PL STARCK, T BAKER, AS KENYON, KR TI MICROBIAL-CONTAMINATION OF IN-USE OCULAR MEDICATIONS SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID LENS CARE SYSTEMS; CORNEAL ULCERS; PSEUDOMONAS-AERUGINOSA; CONTACT-LENSES; KERATITIS; WEAR AB Two hundred twenty in-use medications from 101 patients with nonmicrobial ocular surface disease were studied by culturing the bottle caps, a drop produced by simple inversion, and the interior contents removed sterilely. Conjunctival cultures were taken from these patients and 50 age-matched controls. Pathogenic organisms were harvested from conjunctivae significantly more frequently (P < .01) from cases (34 of 101) than from controls (five of 50). Sixty-four medications (29%) had microorganisms cultured from at least one medication site. Gram-negative organisms were significantly more likely (P < .00001) to be isolated from all medication sites than gram-positive organisms. Additionally, when isolated from medication sites, the gram-negative organisms were highly likely to be cultured from the conjunctiva as well. This was not true for pathogenic gram-negative organisms. We conclude that a cycle of contamination between in-use medications and conjunctivae may represent an important risk factor for microbial keratitis in patients with ocular surface disease. C1 JOHNS HOPKINS UNIV,WILMER INST,DANA CTR PREVENT OPHTHALMOL,BALTIMORE,MD 21218. MASSACHUSETTS EYE & EAR HOSP,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT INFECT DIS,BOSTON,MA 02114. NR 17 TC 49 Z9 52 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 JAN PY 1992 VL 110 IS 1 BP 82 EP 85 PG 4 WC Ophthalmology SC Ophthalmology GA GZ621 UT WOS:A1992GZ62100027 PM 1731727 ER PT J AU LIANG, LL EPSTEIN, DL DEKATER, AW SHAHSAFAEI, A ERICKSONLAMY, KA AF LIANG, LL EPSTEIN, DL DEKATER, AW SHAHSAFAEI, A ERICKSONLAMY, KA TI ETHACRYNIC-ACID INCREASES FACILITY OF OUTFLOW IN THE HUMAN EYE INVITRO SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID CYNOMOLGUS MONKEY; TRABECULAR CELL; CYTOCHALASIN-B; CYTOSKELETON; NA2EDTA; ROUTES AB Anterior segments of human donor eyes were perfused with culture medium at a perfusion pressure of 15 mm Hg in a 5% carbon dioxide environment at 37-degrees-C. After determination of a baseline facility of outflow, the perfusion chamber contents were exchanged with either drug vehicle or ethacrynic acid, at concentrations ranging from 0.01 to 0.25 mmol/L, after which postdrug facility was measured in the continuous presence of drug vehicle or ethacrynic acid. Ethacrynic acid increased facility of outflow from 28% to 105% at ethacrynic acid concentrations of 0.01 to 0.25 mmol/L, respectively. No morphologic correlate of the facility increase was observed with 0.01-mmol/L ethacrynic acid, nor were there any signs of cellular toxic effects. At 0.1 mmol/L, separations between trabecular meshwork cells and breaks between inner-wall cells were observed. At 0.25 mmol/L, focal areas of cell swelling and necrosis were noted. This study demonstrated that ethacrynic acid increases outflow facility in the aged human eye at concentrations that produce no apparent toxic effects. Therefore, ethacrynic acid may potentially prove useful in the treatment of glaucoma. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,HOWE LAB,243 CHARLES ST,BOSTON,MA 02114. FU NEI NIH HHS [EY001894, EY07321] NR 17 TC 55 Z9 57 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 JAN PY 1992 VL 110 IS 1 BP 106 EP 109 PG 4 WC Ophthalmology SC Ophthalmology GA GZ621 UT WOS:A1992GZ62100032 PM 1731701 ER PT J AU MACDONELL, RAL RICH, JM CROS, D SHAHANI, BT ALI, HH AF MACDONELL, RAL RICH, JM CROS, D SHAHANI, BT ALI, HH TI THE LAMBERT-EATON MYASTHENIC SYNDROME - A CAUSE OF DELAYED RECOVERY FROM GENERAL-ANESTHESIA SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE ANESTHESIA; MYASTHENIC SYNDROME; NEUROPHYSIOLOGY AB A 70-year-old man required prolonged ventilation after surgery to remove a rectal neoplasm. The cause of the slow recovery from the effects of neuromuscular blocking agents used during his anesthetic was the Lambert-Eaton myasthenic syndrome (LEMS). Before surgery, he had no neuromuscular symptoms, even in retrospect. LEMS should be considered in the diagnosis of prolonged recovery from neuromuscular blockade, even in previously asymptomatic patients. C1 MASSACHUSETTS GEN HOSP,CLIN NEUROPHYSIOL LAB,BOSTON,MA 02114. NR 9 TC 3 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD JAN PY 1992 VL 73 IS 1 BP 98 EP 100 PG 3 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA GZ554 UT WOS:A1992GZ55400020 PM 1729983 ER PT J AU CONWAY, B BASKAR, P BECHTEL, LJ KAPLAN, JC HIRSCH, MS SCHOOLEY, RT PINCUS, SH AF CONWAY, B BASKAR, P BECHTEL, LJ KAPLAN, JC HIRSCH, MS SCHOOLEY, RT PINCUS, SH TI EOSINOPHILS AS HOST-CELLS FOR HIV-1 SO ARCHIVES OF VIROLOGY LA English DT Note ID ZIDOVUDINE; INFECTION; AIDS AB Transient expression of HIV-1 p24 antigen was observed in eosinophils acutely infected with the HTLV-IIIB strain of HIV-1. PCR analysis of eosinophils isolated from 18 seropositive individuals showed HIV-1 sequences to be present in 2 subjects. These data suggest that eosinophils may act as host cells for HIV-1. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA 02114. SUNY BUFFALO,DEPT DERMATOL,BUFFALO,NY 14260. UNIV COLORADO,DIV INFECT DIS,DENVER,CO 80202. RP CONWAY, B (reprint author), OTTAWA GEN HOSP,DIV INFECT DIS,ROOM LM-15,501 SMYTH RD,OTTAWA K1H 8L6,ONTARIO,CANADA. FU NCI NIH HHS [CA12464]; NIAID NIH HHS [AI16432, AI24847] NR 9 TC 12 Z9 12 U1 2 U2 2 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 VIENNA, AUSTRIA SN 0304-8608 J9 ARCH VIROL JI Arch. Virol. PY 1992 VL 127 IS 1-4 BP 373 EP 377 DI 10.1007/BF01309600 PG 5 WC Virology SC Virology GA JZ763 UT WOS:A1992JZ76300031 PM 1456897 ER PT J AU HAJJAR, RJ GROSSMAN, W GWATHMEY, JK AF HAJJAR, RJ GROSSMAN, W GWATHMEY, JK TI RESPONSIVENESS OF THE MYOFILAMENTS TO CA-2+ IN HUMAN HEART-FAILURE - IMPLICATIONS FOR CA-2+ AND FORCE REGULATION SO BASIC RESEARCH IN CARDIOLOGY LA English DT Article; Proceedings Paper CT MEETING ON CELLULAR AND MOLECULAR ALTERATIONS IN HUMAN FAILING MYOCARDIUM CY JUN, 1991 CL GARGELLEN, AUSTRIA DE MYOFILAMENTS; CALCIUM; HUMAN; PROTEIN KINASE-C; CARDIOMYOPATHY ID RECENT CLINICAL DEVELOPMENTS; POSITIVE INOTROPIC AGENTS; CONTRACTILE PROTEINS; DPI 201-106; CARDIOTONIC AGENT; HUMAN MYOCARDIUM; TROPONIN-T; ADULT-RAT; CALCIUM; RABBIT AB Myofilament calcium sensitivity and maximal calcium-activated force are fundamental properties of the contractile proteins in the heart. We examined these properties in normal human right-ventricular trabeculae carneae obtained from hearts of brain-dead patients with no known cardiac disease, and from patients with end-stage heart failure undergoing cardiac transplantation. There were no differences in calcium-activation of the control and myopathic muscles from chemically-skinned trabeculae or from intact tetanized preparations. We then tested the effect of DPI 201-106 (4-[3-(4-diphenylimethyl-1-piperazinyl)-2-hydroxypropoxy]-1H-indole-carbonitrile), a new inotropic agent, in both preparations. In myopathic muscles, 1-mu-M DPI sensitized the myofilaments to Ca2+, as evidenced by a significant shift of the [Ca2+]-force relationship towards lower [Ca2+], in both skinned and intact preparations. On the other hand, the same concentration of DPI did not affect the calcium-activation in control muscles in both preparations. We also found that the twitch [Ca2+]-force relationship. which has been used as an indication of myofilament sensitivity, was dissociated from the steady-state [Ca2+]-force relationship, and was shifted along the [Ca2+] axis by modulation in the time-course of the twitch and [Ca2+]i, and not by the sensitivity of the myofilaments to Ca2+. Protein kinase C stimulation differentially altered the responsiveness of the myofilaments to Ca2+ in normal and myopathic muscle fibers. We propose that even though calcium activation and maximal calcium-activated force are unaltered in myopathic hearts there are changes in thin filament regulation in myopathic hearts that result in altered responses to agents that directly act on the thin filaments, and that the potential for force development is similar in normal and myopathic human hearts. C1 BETH ISRAEL HOSP,CHARLES A DANA RES INST,330 BROOKLINE AVE,BOSTON,MA 02215. BETH ISRAEL HOSP,DEPT MED,DIV CARDIOVASC,BOSTON,MA 02215. HARVARD UNIV,BETH ISRAEL HOSP,THORNDIKE LAB,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,MED SERV,DEPT CELLULAR & MOLEC PHYSIOL,BOSTON,MA 02114. FU NHLBI NIH HHS [HL 36797, HL 39091, HL 38189] NR 43 TC 14 Z9 14 U1 0 U2 1 PU DR DIETRICH STEINKOPFF VERLAG PI BERLIN 33 PA C/O SPRINGER-VERLAG, HEIDELBERGER PLATZ 3, 1000 BERLIN 33, GERMANY SN 0300-8428 J9 BASIC RES CARDIOL JI Basic Res. Cardiol. PY 1992 VL 87 SU 1 BP 143 EP 159 PG 17 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA JA178 UT WOS:A1992JA17800013 PM 1497567 ER PT J AU ROSS, NS HANSEN, TPB AF ROSS, NS HANSEN, TPB TI RIBOFLAVIN DEFICIENCY IS ASSOCIATED WITH SELECTIVE PRESERVATION OF CRITICAL FLAVOENZYME-DEPENDENT METABOLIC PATHWAYS SO BIOFACTORS LA English DT Review ID RAT-LIVER MITOCHONDRIA; COENZYME-A DEHYDROGENASE; ACIDURIA TYPE-II; GLUTATHIONE-REDUCTASE; SHORT-CHAIN; IRON; PURIFICATION; ADULT; STIMULATION; PYRIDOXINE AB Riboflavin is a water soluble vitamin that serves as a precursor of flavin mononucleotide and flavin adenine dinucleotide. These two compounds are coenzymes in a variety of electron transfer reactions that occur in energy producing, biosynthetic, detoxifying and electron scavenging pathways. When an organism is confronted with inadequate dietary riboflavin, characteristic changes occur in the cellular distribution of the various flavin fractions as well as in the activities of flavin-dependent enzymes. These changes suggest a specific hierarchic response to riboflavin deficiency, e.g. the core electron transfer chain required for ATP synthesis is preserved while the enzymes required for the first step of fatty acid beta-oxidation are diminished. The mechanisms by which the specific changes in enzyme activity are mediated have not been completely identified, but appear to result from a combination of diminished access of normal or near normal levels of apoenzyme to coenzyme and diminished abundance of apoenzyme. The changes in apoenzyme content potentially result from alterations in either protein stability or gene expression. The response to riboflavin deficiency of several kev enzyme systems and the pathways affected will be discussed and a hierarchic order by which specific enzyme activities are preserved while others are decreased will be proposed. The current understanding of the molecular mechanisms by which these changes are mediated will be discussed. RP ROSS, NS (reprint author), W LOS ANGELES DEPT VET AFFAIRS MED CTR,ENDOCRINE SECT W111D,WILSHIRE & SAWTELLE BLVD,LOS ANGELES,CA 90073, USA. FU NICHD NIH HHS [HD25299] NR 49 TC 28 Z9 28 U1 0 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0951-6433 J9 BIOFACTORS JI Biofactors PD JAN PY 1992 VL 3 IS 3 BP 185 EP 190 PG 6 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA HA918 UT WOS:A1992HA91800004 PM 1599612 ER PT B AU STARK, DD AF STARK, DD BE MAGIN, RL LIBURDY, RP PERSSON, B TI CLINICAL INDICATIONS FOR MRI SO BIOLOGICAL EFFECTS AND SAFETY ASPECTS OF NUCLEAR MAGNETIC RESONANCE IMAGING AND SPECTROSCOPY SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Proceedings Paper CT CONF ON BIOLOGICAL EFFECTS AND SAFETY ASPECTS OF NUCLEAR MAGNETIC RESONANCE IMAGING AND SPECTROSCOPY CY MAY 15-17, 1991 CL BETHESDA, MD SP NEW YORK ACAD SCI, NCI, FDA, BERLEX LABS, BRISTOL MYERS SQUIBB PHARM RES INST, SOC MAGNET RESONANCE IMAGING RP STARK, DD (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA NEW YORK BN 0-89766-698-4 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1992 VL 649 BP 332 EP 334 DI 10.1111/j.1749-6632.1992.tb49621.x PG 3 WC Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy SC Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy GA BW41Q UT WOS:A1992BW41Q00026 PM 1580504 ER PT J AU PONGOR, P BETTS, J MUCKLE, DS BENTLEY, G AF PONGOR, P BETTS, J MUCKLE, DS BENTLEY, G TI WOVEN CARBON SURFACE REPLACEMENT IN THE KNEE - INDEPENDENT CLINICAL REVIEW SO BIOMATERIALS LA English DT Article DE CARBON FIBERS; JOINT RESURFACING; KNEE ID CARTILAGE AB An independent assessment was performed of the results of woven carbon implants of mesh or rods into articular cartilage defects performed by two surgeons in the knees of 96 patients. Eight had symptomatic osteochondritis, 31 had chondromalacia patellae and 57 had early osteoarthritis. They were reviewed up to 5 yr after operation. Seventy-six patients (79%) experienced an improvement in analogue pain score and similar improvements occurred in a range of functional activities (P = 0.002). No evidence of inflammatory change or deterioration in joint damage was found. It is concluded that this relatively minor procedure is valuable in younger patients with troublesome symptoms due to early articular cartilage damage and does not prejudice further operative treatment. C1 MIDDLESBROUGH GEN HOSP,AYRESOME GREEN LANE,MIDDLESBROUGH,CLEVELAND,ENGLAND. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. QUEEN ELIZABETH HOSP,GATESHEAD,TYNE & WEAR,ENGLAND. ROYAL NATL ORTHOPAED HOSP,STANMORE,MIDDX,ENGLAND. RP BENTLEY, G (reprint author), MIDDLESBROUGH GEN HOSP,AYRESOME GREEN LANE,MIDDLESBROUGH,CLEVELAND,ENGLAND. NR 12 TC 15 Z9 15 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PY 1992 VL 13 IS 15 BP 1070 EP 1076 DI 10.1016/0142-9612(92)90139-F PG 7 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA KD007 UT WOS:A1992KD00700003 PM 1493190 ER PT J AU TEICHER, BA HOLDEN, SA ARA, G HERMAN, TS HOPKINS, RE MENON, K AF TEICHER, BA HOLDEN, SA ARA, G HERMAN, TS HOPKINS, RE MENON, K TI EFFECT OF A BOVINE HEMOGLOBIN PREPARATION (SBHS) ON THE RESPONSE OF 2 MURINE SOLID TUMORS TO RADIATION-THERAPY OR CHEMOTHERAPEUTIC ALKYLATING-AGENTS SO BIOMATERIALS ARTIFICIAL CELLS AND IMMOBILIZATION BIOTECHNOLOGY LA English DT Article ID CLASSIFICATION; OXYGENATION; BINDING AB When tested in mice bearing the Lewis lung tumor with 2, 3. or 4 Gy daily for 5 days, SBHS produced a dose-modifying factor of 1.6 that was increased to 2.1 with carbogen. The addition of SBHS (1.32 gm protein/kg) to treatment with melphalan (MEL) resulted in a 2.2-fold increase in the tumor growth delay (TGD). The combination of SBHS with carbogen (6 h) produced a 3.6-fold increase in TGD compared with MEL alone. The addition of SBHS to treatment with cyclophosphamide (CTX) resulted in a 2-fold increase in the TGD. However, the combination of SBHS and carbogen was much more effective resulting in a 4.6-fold increase in TGD. There was a 1.3-fold increase in TGD with SBHS and CDDP compared with CDDP alone. The combination of SBHS and carbogen was a more effective addition to CDDP resulting in a 1.9-fold increase in TGD. The addition of SBHS to treatment with BCNU increased the TGD produced by BCNU by 1.5-fold. The combination of SBHS/BCNU and carbogen resulted in a 2.3-fold increase in TGD over that obtained with BCNU alone. C1 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. NR 15 TC 19 Z9 19 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 1055-7172 J9 BIOMAT ARTIF CELL IM JI Biomater. Artif. Cells Immobil. Biotechnol. PY 1992 VL 20 IS 2-4 BP 657 EP 660 PG 4 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA JM745 UT WOS:A1992JM74500064 PM 1391491 ER PT J AU HODAKOWSKI, GT PAGE, RD HARRINGER, W JACOBS, EE LARAIA, PJ SVIZZERO, T GUERRERO, JL AUSTEN, WG VLAHAKES, GJ AF HODAKOWSKI, GT PAGE, RD HARRINGER, W JACOBS, EE LARAIA, PJ SVIZZERO, T GUERRERO, JL AUSTEN, WG VLAHAKES, GJ TI ULTRA-PURE POLYMERIZED BOVINE HEMOGLOBIN BLOOD SUBSTITUTE - EFFECTS ON THE CORONARY CIRCULATION SO BIOMATERIALS ARTIFICIAL CELLS AND IMMOBILIZATION BIOTECHNOLOGY LA English DT Article AB The effects of stroma-free hemoglobin (SFHgb) on the coronary circulation remain unclear. An intact canine model utilizing intracoronary adenosine to abolish the confounding effect of autoregulation was used to study maximal myocardial oxygen delivery during progressive hemodilution with polymerized bovine SFHgb. The circumflex coronary artery was instrumented with a flow probe, hydraulic constrictor, and proximal and distal catheters for adenosine infusion and distal pressure measurement, respectively. This preparation was used to generate diastolic coronary pressure-flow relations during maximal vasodilation. Maximal coronary conductance and maximal myocardial oxygen delivery were determined in two groups of 7 dogs each following hemodilution, first with 6% hetastarch (Control), followed by further hemodilution with ultra-pure, polymerized, bovine SFHgb. After hemodilution with SFHgb, maximal coronary flow increased slightly without evidence of coronary vasoconstriction. Since hemodilution with this material increases oxygen carrying capacity, maximal oxygen delivery is greater than Control, despite the very low canine hematocrit. These findings suggest: 1) SFHgb can provide adequate oxygen delivery to the myocardium despite extreme degrees of hemodilution, and 2) in this intact model, there is no evidence of adverse coronary vasomotion. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP HODAKOWSKI, GT (reprint author), MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114, USA. RI Guerrero, Jorge/I-3666-2015 OI Guerrero, Jorge/0000-0003-4315-7318 NR 6 TC 16 Z9 16 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 1055-7172 J9 BIOMAT ARTIF CELL IM JI Biomater. Artif. Cells Immobil. Biotechnol. PY 1992 VL 20 IS 2-4 BP 669 EP 672 PG 4 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA JM745 UT WOS:A1992JM74500066 PM 1391493 ER PT J AU TEICHER, BA AF TEICHER, BA TI USE OF PERFLUOROCHEMICAL EMULSIONS IN CANCER-THERAPY SO BIOMATERIALS ARTIFICIAL CELLS AND IMMOBILIZATION BIOTECHNOLOGY LA English DT Article ID FLUOSOL-DA 20-PERCENT; SQUAMOUS-CELL CARCINOMA; MELPHALAN ANTITUMOR-ACTIVITY; FSAIIC MURINE FIBROSARCOMA; RADIATION-THERAPY; CLINICAL-TRIAL; CYTO-TOXICITY; BLOOD-FLOW; HYPERBARIC-OXYGEN; TUMOR-CELL AB Over the past 10 years, the use of perfluorochemical emulsions (PFCE) and carbogen or oxygen breathing has been explored as an adjuvant to radiation therapy and/or chemotherapy in the treatment of solid tumors. The rationale for the use of PFCE and oxygen breathing in this therapeutic setting is that solid tumor masses contain areas of hypoxia which are therapeutically resistant. Since x-rays and many chemotherapeutic agents require oxygen to be maximally cytotoxic and most normal tissues are well-oxygenated, the additional oxygen put in circulation by the PFCE should not increase die normal tissue toxicities produced by the various therapies. The largest body of preclinical work and all of the clinical studies in cancer conducted with PFCE, thus far, have been done with Fluosol-DA, 20%. Oxygen microelectrode studies have confirmed increased oxygenation in previously hypoxic tumor regions after the administration of Fluosol-DA and carbogen breathing. The preclinical studies have shown very positive effects with single dose and fractionated radiation in several rodent solid tumor models. Many widely used anticancer drugs including antitumor alkylating agents and adriamycin are enhanced by PFCE and carbogen breathing for longer time periods (6 h). More recently, several experimental concentrated PFCE preparations have become available and work with these is actively under way in several laboratories. Clinical studies with radiation and four or five chemotherapeutic drugs as single agents have indicated that Fluosol-DA followed by oxygen breathing can be administered safely in a variety of cancer therapeutic settings. Further clinical studies with Fluosol-DA are planned. C1 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. NR 89 TC 10 Z9 11 U1 0 U2 2 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 1055-7172 J9 BIOMAT ARTIF CELL IM JI Biomater. Artif. Cells Immobil. Biotechnol. PY 1992 VL 20 IS 2-4 BP 875 EP 882 PG 8 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA JM745 UT WOS:A1992JM74500101 PM 1391527 ER PT J AU HOLDEN, SA TEICHER, BA HA, C ARA, G HERMAN, TS AF HOLDEN, SA TEICHER, BA HA, C ARA, G HERMAN, TS TI ENHANCEMENT BY PERFLUSION EMULSION (OXYGENT(R)) AND CARBOGEN BREATHING OF THE TUMOR-GROWTH DELAY OF THE FSAIIC FIBROSARCOMA AFTER TREATMENT WITH ANTITUMOR ALKYLATING-AGENTS SO BIOMATERIALS ARTIFICIAL CELLS AND IMMOBILIZATION BIOTECHNOLOGY LA English DT Article ID FLUOSOL-DA; CYTO-TOXICITY; CLASSIFICATION; CELL AB Many anticancer drugs require oxygen to be cytotoxic, or are selectively cytotoxic toward cells under oxygenated conditions. The effects of the dilute perfluorochemical emulsion Fluosol-DA with a wide variety of chemotherapeutic agents have been explored; however, It has not been possible to determine the optimal level of circulating perfluorochemical emulsion with anticancer drugs because the volume of Fluosol that my be administered in limited. Using a concentrated 90% Perflubron emulsion, Oxygent(R), a wide range of perfluorochemical emulsion doses have been examined in combination with melphalan, cyclophosphamide and BCNU in a murine solid tumor model. When Oxygent was administered by injection i.v. just prior to the injection of melphalan (10 mg/kg), the greatest tumor growth delays were obtained with Oxygent levels between 4 and 12 g PFC/kg. With each of these drugs the greatest tumor growth delays were obtained when the drug was prepared in the emulsion and the combination injected i.v. In each case, each dose of drug was followed by 6 h. of breathing carbogen. C1 JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. RP HOLDEN, SA (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. NR 19 TC 9 Z9 9 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 1055-7172 J9 BIOMAT ARTIF CELL IM JI Biomater. Artif. Cells Immobil. Biotechnol. PY 1992 VL 20 IS 2-4 BP 895 EP 898 PG 4 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA JM745 UT WOS:A1992JM74500103 PM 1391529 ER PT J AU TEICHER, BA HERMAN, TS MENON, K AF TEICHER, BA HERMAN, TS MENON, K TI ENHANCEMENT OF FRACTIONATED RADIATION-THERAPY BY AN EXPERIMENTAL CONCENTRATED PERFLUBRON EMULSION (OXYGENT(R)) IN THE LEWIS LUNG-CARCINOMA SO BIOMATERIALS ARTIFICIAL CELLS AND IMMOBILIZATION BIOTECHNOLOGY LA English DT Article ID FLUOSOL-DA 20-PERCENT; SQUAMOUS-CELL CARCINOMA; PERFLUOROCHEMICAL EMULSION; CANCER-THERAPY; TUMORS; RADIOSENSITIVITY; INCREASE; CARBOGEN; MICE; PO2 AB The concentrated Perflubron emulsion, Oxygent(R), in combination with breathing a 95% oxygen atmosphere, significantly enhanced the response of the murine Lewis lung carcinoma to fractionated radiation therapy. Administration of 4 to 12 g PFC/kg was most effective if administered prior to each x-ray fraction, however, alternated day and even once weekly administration of 8 or 12 PFC/kg and 95% oxygen breathing with each x-ray fraction resulted in significant improvements in tumor growth delay. C1 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. NR 24 TC 11 Z9 11 U1 0 U2 2 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 1055-7172 J9 BIOMAT ARTIF CELL IM JI Biomater. Artif. Cells Immobil. Biotechnol. PY 1992 VL 20 IS 2-4 BP 899 EP 902 PG 4 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA JM745 UT WOS:A1992JM74500104 PM 1391530 ER PT J AU NEAR, RI AF NEAR, RI TI GENE CONVERSION OF IMMUNOGLOBULIN VARIABLE REGIONS IN MUTAGENESIS CASSETTES BY REPLACEMENT PCR MUTAGENESIS SO BIOTECHNIQUES LA English DT Article ID ANTI-DIGOXIN ANTIBODIES; ESCHERICHIA-COLI; GENERATION; BINDING; HEAVY; EXPRESSION; REPERTOIRE; AFFINITY; CLONING; LIBRARY AB A technique, Replacement PCR Mutagenesis, was developed to replace one immunoglobulin variable region (V) in a M13 phage cassette with a different, homologous V. This allows the use of the same mutagenesis and subsequent expression vectors for many V regions or V segments. The method combines PCR of V fragments and in vitro mutagenesis. Primers homologous to 3' and 5' ends of both V regions initiate PCR synthesis of the V DNA fragment (donor) that will replace the V region (recipient) in M13. Donor V PCR DNA may originate from mRNA, cloned V genes or genomic templates. The donor V PCR DNA is denatured and annealed to the M13 cassette containing the recipient V to be supplanted. The second strand is synthesized, transfected into bacteria and mutant plaques selected by hybridization. Since restriction sites in primers are not required, altered primer-encoded amino acids are avoided. Further, the PCR donor piece can be of any length if it shares homology with the recipient gene. This allows construction and expression of complete gene replacements and chimeras. This method is also applicable to V "humanization" and studying sets of homologous genes containing polymorphic or evolutionary disparities. The potential uses of the technique are discussed. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP NEAR, RI (reprint author), MASSACHUSETTS GEN HOSP,CELLULAR & MOLEC RES LAB,BOSTON,MA 02144, USA. FU NHLBI NIH HHS [HL-19259] NR 36 TC 7 Z9 7 U1 1 U2 1 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD JAN PY 1992 VL 12 IS 1 BP 88 EP & PG 0 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GZ184 UT WOS:A1992GZ18400023 PM 1734930 ER PT J AU RAKESTRAW, SL FORD, WE TOMPKINS, RG RODGERS, MAJ THORPE, WP YARMUSH, ML AF RAKESTRAW, SL FORD, WE TOMPKINS, RG RODGERS, MAJ THORPE, WP YARMUSH, ML TI ANTIBODY-TARGETED PHOTOLYSIS - INVITRO IMMUNOLOGICAL, PHOTOPHYSICAL, AND CYTOTOXIC PROPERTIES OF MONOCLONAL-ANTIBODY DEXTRAN SN(IV) CHLORIN-E6 IMMUNOCONJUGATES SO BIOTECHNOLOGY PROGRESS LA English DT Article ID SINGLET OXYGEN; SENSITIZED PHOTOOXIDATION; LUMINESCENCE MEASUREMENTS; MALIGNANT-TUMORS; FLASH-PHOTOLYSIS; TRIPLET-STATES; HEMATOPORPHYRIN; CELLS; KINETICS; MODEL AB A set of anti-melanoma immunoconjugates were prepared which contained chlorin e6: antibody molar ratios of 18.9:1, 11.2:1, 6.8:1, and 1.7:1. All immunoconjugates retained antigen binding activity regardless of the chromophore:antibody substitution ratio that was attained. In contrast, the ground-state absorption spectra of the immunoconjugates showed features which appeared to be dependent on the chromophore:antibody molar ratio. In addition, the quantum yield of singlet oxygen generated by the conjugated chromophores was observed to be significantly less than that observed with the unbound dye. Time-resolved absorbance spectroscopy of the chromophore excited triplet state indicated that the loss of singlet oxygen quantum yield resulted from diminished chromophore triplet yield. Analysis of data obtained from in vitro photolysis of target melanoma cells, in combination with that obtained from the immunochemical and photochemical studies, indicates that the observed immunoconjugate phototoxicity can be reasonably quantitatively represented by (1) the ability of the immunoconjugate to bind SK-MEL-2 cell surface antigen, (2) the amount of chromophore localized at the target cells by immunoconjugate binding, (3) the delivered dose of light at 634 nm, and (4) the singlet oxygen quantum yield of the antibody-bound photosensitizer. Though these data argue strongly for photolysis by the cumulative dosage of singlet oxygen at the cell membrane, nonetheless, the concurrent photoinduced release of other cytotoxic agents should not be ruled out. C1 RUTGERS STATE UNIV,DEPT CHEM & BIOCHEM ENGN,PISCATAWAY,NJ 08855. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,SURG SERV,BOSTON,MA 02114. RUTGERS STATE UNIV,CTR ADV BIOTECHNOL & MED,PISCATAWAY,NJ 08855. BOWLING GREEN STATE UNIV,CTR PHOTOCHEM SCI,BOWLING GREEN,OH 43403. FU NIGMS NIH HHS [GM 24235] NR 62 TC 29 Z9 31 U1 0 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 8756-7938 J9 BIOTECHNOL PROGR JI Biotechnol. Prog. PD JAN-FEB PY 1992 VL 8 IS 1 BP 30 EP 39 DI 10.1021/bp00013a006 PG 10 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA HC775 UT WOS:A1992HC77500006 PM 1371392 ER PT J AU FREEDMAN, AS MUNRO, JM MORIMOTO, C MCINTYRE, BW RHYNHART, K LEE, N NADLER, LM AF FREEDMAN, AS MUNRO, JM MORIMOTO, C MCINTYRE, BW RHYNHART, K LEE, N NADLER, LM TI FOLLICULAR NON-HODGKINS-LYMPHOMA CELL-ADHESION TO NORMAL GERMINAL-CENTERS AND NEOPLASTIC FOLLICLES INVOLVES VERY LATE ANTIGEN-4 AND VASCULAR CELL-ADHESION MOLECULE-1 SO BLOOD LA English DT Article ID T-CELLS; B-CELLS; DIFFERENTIAL EXPRESSION; MONOCLONAL-ANTIBODIES; DENDRITIC CELLS; LYMPHOCYTES-B; VLA-4; RECEPTORS; LEUKEMIA; TISSUE C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. UNIV TEXAS,MD ANDERSON CANCER CTR,DEPT IMMUNOL,HOUSTON,TX 77030. RP FREEDMAN, AS (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA40216, CA55207] NR 58 TC 74 Z9 75 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 JAN 1 PY 1992 VL 79 IS 1 BP 206 EP 212 PG 7 WC Hematology SC Hematology GA GX614 UT WOS:A1992GX61400026 PM 1370204 ER PT J AU SYKES, M AF SYKES, M TI DISSOCIATING GRAFT-VS-HOST DISEASE FROM THE GRAFT-VS-LEUKEMIA EFFECT OF ALLOGENEIC T-CELLS - THE POTENTIAL ROLE OF IL-2 SO BONE MARROW TRANSPLANTATION LA English DT Article; Proceedings Paper CT SYMP ON BONE MARROW TRANSPLANTATION CY JAN 13-26, 1992 CL KEYSTONE, CO SP SANDOZ PHARM ID BONE-MARROW TRANSPLANTATION; HISTOCOMPATIBILITY BARRIERS; LYMPHOCYTES-T; CHIMERAS; INTERLEUKIN-2; DEPLETION; INVIVO; MICE; REACTIVITY; PROTECTION RP SYKES, M (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CTR TRANSPLANTAT RES BIOL,SURG SERV,MGH E BLDG 149,BOSTON,MA 02129, USA. FU NCI NIH HHS [R01CA55290]; NIAID NIH HHS [R01AI31158] NR 51 TC 8 Z9 9 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. PY 1992 VL 10 SU 1 BP 1 EP 4 PG 4 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA JK414 UT WOS:A1992JK41400002 PM 1521080 ER PT J AU FERRARA, JLM AF FERRARA, JLM TI ADVANCES IN GVHD - NOVEL LYMPHOCYTE SUBSETS AND CYTOKINE DYSREGULATION SO BONE MARROW TRANSPLANTATION LA English DT Article; Proceedings Paper CT SYMP ON BONE MARROW TRANSPLANTATION CY JAN 13-26, 1992 CL KEYSTONE, CO SP SANDOZ PHARM ID INTERLEUKIN-1 RECEPTOR ANTAGONIST; VERSUS-HOST DISEASE; BONE-MARROW TRANSPLANTATION; GRAFT; IL-1; PREVENTION; INVIVO; CELLS; PHASE C1 HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. RP FERRARA, JLM (reprint author), CHILDRENS HOSP MED CTR,DANA FARBER CANC INST,DIV PEDIAT HEMATOL ONCOL,BOSTON,MA 02115, USA. NR 17 TC 13 Z9 13 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. PY 1992 VL 10 SU 1 BP 10 EP 12 PG 3 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA JK414 UT WOS:A1992JK41400004 PM 1387830 ER PT J AU TEPPER, RI AF TEPPER, RI TI THE TUMOR-CYTOKINE TRANSPLANTATION ASSAY AND THE ANTITUMOR-ACTIVITY OF INTERLEUKIN-4 SO BONE MARROW TRANSPLANTATION LA English DT Article; Proceedings Paper CT SYMP ON FOETAL AND NEONATAL CELL TRANSPLANTATION AND RETROVIRAL GENE THERAPY CY JAN 05-08, 1992 CL ANNECY, FRANCE SP MERIEUX FDN ANNECY ID CELL STIMULATORY FACTOR; GENE-TRANSFER; IMMUNITY; TUMORIGENICITY; GENERATION; POTENT; INVIVO RP TEPPER, RI (reprint author), MASSACHUSETTS GEN HOSP,CTR CANC,BLDG 149 13TH ST,BOSTON,MA 02129, USA. NR 18 TC 13 Z9 13 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. PY 1992 VL 9 SU 1 BP 177 EP 181 PG 5 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA JD064 UT WOS:A1992JD06400045 PM 1504664 ER PT J AU FOSS, MC VONOEYEN, P VLACHOKOSTA, FV AOKI, TT AF FOSS, MC VONOEYEN, P VLACHOKOSTA, FV AOKI, TT TI FUEL OXIDATION BY INSULIN-DEPENDENT DIABETICS DURING LATE PREGNANCY IN RESPONSE TO AN ORAL GLUCOSE-LOAD SO BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH LA English DT Article DE CARBOHYDRATE AND LIPID OXIDATION; GLUCOSE METABOLISM; BLOOD SUBSTRATES AND C-PEPTIDE; DIABETES-MELLITUS; LATE PREGNANCY AB 1. To determine the oxidative response to a 50-g oral glucose challenge by diabetic women during late pregnancy under a more intensive therapeutic regimen than is conventionally employed, six normal pregnant women and ten insulin-dependent pregnant diabetic women were studied during the third trimester. Fuel (carbohydrate and lipid) oxidation rates were determined by indirect calorimetry, blood levels of substrates and C-peptide were measured directly, and glucose metabolism data (oxidation and nonoxidative metabolism) were estimated for both groups at the postabsorptive state and for the 2-h period following glucose ingestion. 2. The increases in the non-protein respiratory quotient (npRQ) and carbohydrate oxidation rates in response to glucose ingestion in the diabetic pregnant group were significantly smaller than in the normal pregnant individuals. The total amount of glucose oxidized by the diabetic pregnant group during the 2-h tests (6.1 +/- 0.6 g/m2) was significantly smaller than that oxidized by the normal pregnant group (8.3 +/- 0.4 g/m2), whereas there was more but not statistically significant lipid oxidation in the diabetic group (3.0 +/- 0.3 vs 2.6 +/- 0.1 g/m2). 3. The diabetic pregnant group not only oxidized less glucose (10.9 +/- 1.1 vs 14.1 +/- 0.8 g, P < 0.05) but more of this hexose remained in their glucose space (9.1 +/- 1.6 vs 3.2 +/- 1.1, P < 0.05) and they excreted 2.8 +/- 1.0 g into the urine. 4. The diabetic pregnant subjects had significantly lower blood levels of lactate, pyruvate and C-peptide than the normal pregnant subjects, but significantly higher blood levels of glucose, beta-hydroxybutyrate and acetoacetate. 5. The present data show that an intensive conventional therapeutic regimen during late pregnancy was not sufficient to completely normalize the glucose-processing capability of insulin-dependent diabetic patients. C1 HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,BOSTON,MA 02115. UNIV CALIF DAVIS,SACRAMENTO MED CTR,DEPT INTERNAL MED,SACRAMENTO,CA 95817. RP FOSS, MC (reprint author), UNIV SAO PAULO,FAC MED RIBEIRAO PRETO,DEPT CLIN MED,BR-14049 RIBEIRAO PRETO,SP,BRAZIL. FU NIADDK NIH HHS [AM15191, AM20530] NR 26 TC 0 Z9 0 U1 0 U2 0 PU ASSOC BRAS DIVULG CIENTIFICA PI SAO PAULO PA FACULDADE MEDICINA, SALA 21, 14049 RIBEIRAO PRETO, SAO PAULO, BRAZIL SN 0100-879X J9 BRAZ J MED BIOL RES JI Brazilian J. Med. Biol. Res. PY 1992 VL 25 IS 2 BP 135 EP 144 PG 10 WC Biology; Medicine, Research & Experimental SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine GA HK884 UT WOS:A1992HK88400006 PM 1339509 ER PT J AU LIND, SE KOPANS, D GOOD, MJD AF LIND, SE KOPANS, D GOOD, MJD TI PATIENTS PREFERENCES FOR LEARNING THE RESULTS OF MAMMOGRAPHIC EXAMINATIONS SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE MAMMOGRAPHY; PATIENT PREFERENCES; DOCTOR-PATIENT COMMUNICATION; TEST RESULTS ID RADIOLOGY; RIGHTS; ROLES AB The communication of diagnostic test results is an important aspect of the interaction between doctors and patients. Communication of mammogram results is of particular interest because the test is used to detect a common and potentially dangerous malignancy and because patients in the United States are able in some locations to obtain mammography at their own request, rather than being referred by a physician. We conducted a survey to learn about the preferences of a group of women at a traditional mammography center for learning the results of this commonly performed test. We asked women undergoing mammography to respond to questionnaires designed to learn: 1) How they felt about different methods of telling patients the results of mammograms; 2) How they were informed of the results of previous mammograms; 3) How they were told the results of the current mammograms. Patients indicated that if no abnormality is detected, they prefer to have their doctor call with the result, but if the study is 'abnormal' they wish to be told by their own physician in the office. Failing to notify the patient if the study is normal was the least preferred outcome. This group of patients did not express an interest in the most immediate form of notification (i.e. learning the result from the radiologist performing the test). Analysis of how patients felt about ways in which they were previously informed of the results of mammograms suggests that their reactions are influenced to a large extent by their clinical status. Patients undergoing mammography for diagnostic purposes, for example, were less pleased by a 'preferred' method (i.e. being told by their physician) than were those undergoing screening mammography. While patients have opinions about how they would prefer to be told their mammogram results, they are accepting of a variety of methods of telling, if they are receiving good news. If abnormalities are found, patients prefer to be told in person by their own physician. Interpretations of surveys of patient satisfaction should be tempered by the finding that the clinical status of the patient alters their perceptions of satisfaction with this aspect of their physician's behavior. Patient preferences may change if increasing numbers of women are told their results by the radiologist. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BREAST IMAGING UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT RADIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT SOCIAL MED,BOSTON,MA 02115. RP LIND, SE (reprint author), BRIGHAM & WOMENS HOSP,221 LONGWOOD AVE,BOSTON,MA 02115, USA. NR 8 TC 30 Z9 30 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 1992 VL 23 IS 3 BP 223 EP 232 DI 10.1007/BF01833519 PG 10 WC Oncology SC Oncology GA JZ666 UT WOS:A1992JZ66600005 PM 1463862 ER PT J AU THOR, AD KOERNER, FC EDGERTON, SM WOOD, WC STRACHER, MA SCHWARTZ, LH AF THOR, AD KOERNER, FC EDGERTON, SM WOOD, WC STRACHER, MA SCHWARTZ, LH TI PS2 EXPRESSION IN PRIMARY BREAST CARCINOMAS - RELATIONSHIP TO CLINICAL AND HISTOLOGICAL FEATURES AND SURVIVAL SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE BREAST CANCER; ESTROGEN RECEPTOR; PROGNOSIS; PROGNOSTIC FACTORS; PS2 ID CANCER CELL-LINE; 5' FLANKING REGION; PROGESTERONE RECEPTORS; HEAT-SHOCK; MULTIVARIATE-ANALYSIS; PROGNOSTIC VALUE; CATHEPSIN-D; ESTROGEN; PROTEIN; GENE AB pS2 protein expression has been reported to have prognostic significance in human breast carcinomas and to correlate with estrogen receptor positivity, although these findings have not been confirmed by all investigators. pS2 positivity was compared to various clinical and histologic parameters in a retrospective study of 290 patients (median follow-up 7.2 years) and significantly correlated with tumor grade and estrogen receptor content (p = 0.001 and p = 0.0007, respectively). Significant associations between pS2 positivity and lymph node metastases, T stage, histologic tumor type, and patient age were not observed. Univariate and multivariate analyses (controlling for estrogen receptor content, T and N stage) of the patient population at large showed that pS2 positivity was not predictive of disease-free or overall survival. Univariate analysis of lymph node negative patients demonstrated that both pS2 and estrogen receptor positivity were significantly associated with a better outcome. Multivariate analysis of these patients, however, showed that only estrogen receptor data had independent prognostic significance. This study suggests that immunohistochemical analysis for pS2 protein expression will not contribute additional prognostic information if the estrogen receptor content is known. C1 MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,ORTHOPAED BIOMECH LAB,BOSTON,MA 02114. RP THOR, AD (reprint author), MASSACHUSETTS GEN HOSP,DEPT PATHOL,COX 5,FRUIT ST,BOSTON,MA 02114, USA. FU NCI NIH HHS [P01 CA44768] NR 35 TC 44 Z9 45 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 1992 VL 21 IS 2 BP 111 EP 119 DI 10.1007/BF01836957 PG 9 WC Oncology SC Oncology GA HZ936 UT WOS:A1992HZ93600004 PM 1627814 ER PT J AU LEES, S HANSON, DB AF LEES, S HANSON, DB TI EFFECT OF FLUORIDE DOSAGE ON BONE-DENSITY, SONIC VELOCITY, AND LONGITUDINAL MODULUS OF RABBIT FEMURS SO CALCIFIED TISSUE INTERNATIONAL LA English DT Article DE FLUORIDE DOSAGE; COMPACT BONE; DENSITY; SONIC VELOCITY; ELASTIC MODULUS; STATIC LOAD STRESS AB Relationships between the fluoride dosage administered to weanling New Zealand white male rabbits and some mechanical properties of the compact bone were investigated for a wide range of dosages. The measured quantities were density, longitudinal sonic velocity in the radial direction, and fluoride ion concentration in compact bone. The longitudinal elastic modulus was estimated from the product of the density and the square of the sonic velocity. The relative static load stress was estimated from the ratio of the final body weight to the cross-sectional area of the femur. These measurements and derived quantities provide quantitative measures of bone quality. A slight peak (2% greater than reference) was determined for the density and a slightly larger peak (5% above reference) for the longitudinal sonic velocity at a dosage of approximately 20 mg/kg/day. The longitudinal elastic modulus exhibited a substantial peak, 14% greater than reference. The relative static load stress showed a very slight peak as a function of dosage and also as a function of fluoride concentration in the bone. When plotted against the elastic modulus, a nonlinear monotonic increase was observed with modulus, showing that the cross-sectional area of the bone is responsive to the stiffness of the tissue. Stiffer tissue produces a smaller cross section, whereas a more compliant tissue requires a marked increase in the area. There appears to be an improvement of bone quality for low fluoride dosage which tends to be masked by biological variability. The derived quantities, longitudinal elastic modulus, and relative static load stress provide the clearest demonstration of the improvement. There is marked deterioration for higher dosage. The conclusions are limited by a need to relate the properties of rabbit to human bone, and young growing bone to older osteoporotic bone. RP LEES, S (reprint author), FORSYTH DENT CTR,DEPT BIOENGN,140 FENWAY,BOSTON,MA 02115, USA. FU NIA NIH HHS [AG02325] NR 12 TC 20 Z9 20 U1 0 U2 2 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 JAN PY 1992 VL 50 IS 1 BP 88 EP 92 DI 10.1007/BF00297303 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA GV959 UT WOS:A1992GV95900017 PM 1739876 ER PT J AU DANIELS, AL COTE, CJ POLANER, DM AF DANIELS, AL COTE, CJ POLANER, DM TI CONTINUOUS OXYGEN-SATURATION MONITORING FOLLOWING RECTAL METHOHEXITONE INDUCTION IN PEDIATRIC-PATIENTS SO CANADIAN JOURNAL OF ANAESTHESIA-JOURNAL CANADIEN D ANESTHESIE LA English DT Article DE ANESTHESIA, PEDIATRIC; ANESTHETICS, RECTAL, METHOHEXITONE; PREMEDICATION, METHOHEXITONE; MEASUREMENT TECHNIQUES, PULSE OXIMETRY; MONITORING, OXYGEN ID CHILDREN; ANESTHESIA AB Rectal methohexitone has been used to induce anaesthesia in paediatric patients for a number of years. This study was conducted in order to confirm the safety of this method of induction for uncomplicated routine paediatric patients. Children between the ages of six months and six years were considered candidates for induction with methohexitone (10%, 25-30 mg.kg-1). Patients were monitored with a continuous oxygen saturation recording. Forty-nine patients participated in this study and anaesthesia was induced successfully in 44. The mean age of the patients was 2.7 +/- 1.6 yr. The mean weight was 13.8 +/- 4.3 kg and the mean dose of methohexitone for successful induction was 27.0 +/- 3.0 mg.kg-1. Continuous oximeter recordings were available in 31 of the 42 patients who allowed oximeter placement prior to administration of methohexitone. No major desaturation events were noted in any patient. Two brief episodes of desaturation occurred. One with a nadir of 90% which lasted for 45 sec and another with a nadir of 86% which lasted for 26 sec. Both children had their heads flexed over their parents' shoulders at the time of the event resulting in partial airway obstruction. Both of these episodes were the result of upper airway obstruction which was clinically diagnosed by the anesthetist and readily corrected by repositioning the head. This study confirms the efficacy and safety of rectal methohexitone for induction of general anaesthesia in children. Mechanical obstruction of the airway following induction seems to be the most likely cause for oxygen desaturation. Monitoring of pulse oximetry does not appear necessary provided the child is carefully observed for adequacy of air exchange. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ANAESTHESIA,BOSTON,MA 02114. NR 11 TC 8 Z9 8 U1 0 U2 0 PU CANADIAN ANAESTHETISTS SOC INC PI TORONTO PA 1 EGLINTON AVE EAST, SUITE 208, TORONTO ON M4P 3A1, CANADA SN 0832-610X J9 CAN J ANAESTH JI Can. J. Anaesth.-J. Can. Anesth. PD JAN PY 1992 VL 39 IS 1 BP 27 EP 30 PG 4 WC Anesthesiology SC Anesthesiology GA GX666 UT WOS:A1992GX66600006 PM 1733529 ER PT J AU AMES, A AF AMES, A TI ENERGY-REQUIREMENTS OF CNS CELLS AS RELATED TO THEIR FUNCTION AND TO THEIR VULNERABILITY TO ISCHEMIA - A COMMENTARY BASED ON STUDIES ON RETINA SO CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY LA English DT Article; Proceedings Paper CT SYMP ON THE PHYSIOLOGY, PHARMACOLOGY, AND BIOPHYSICS OF GANGLIONIC TRANSMISSION CY AUG 12-14, 1991 CL UNIV ALBERTA, EDMONTON, CANADA SP INT BRAIN RES ORG HO UNIV ALBERTA DE ENERGY METABOLISM; OXYGEN CONSUMPTION; GLYCOLYSIS; NEUROPHYSIOLOGICAL FUNCTION; SODIUM TRANSPORT; ISCHEMIA ID NONOXIDATIVE GLUCOSE CONSUMPTION; PHYSIOLOGIC NEURAL ACTIVITY; CENTRAL NERVOUS-SYSTEM; RAT-BRAIN; CYTOCHROME-OXIDASE; SMOOTH-MUSCLE; VISUAL-CORTEX; METABOLISM; GLYCOLYSIS; HYPOXIA AB CNS tissue is well known to have large energy requirements. However, because of the difficulty of measuring rates of energy usage, relatively little is known about which cell types and which neurophysiological functions are the principal energy users. In experiments performed on rabbit retina in vitro, it was possible to measure O2 consumption and lactate production with the retinas under resting conditions and in different states of physiological activity. Resting energy consumption was large, as has been previously reported, and there were increases of up to 2.3 times with activity. Under some circumstances, the demands appeared to exceed the energy available. It was calculated that less than 5% of the energy generated by the retina was used for ''vegetative metabolism'' (i.e., for the anabolic reactions essential for viability), so that even in the resting state, the great majority of the energy usage appeared to be for function-related processes. This conclusion received further support from the finding that 50% of the energy generated was used for Na+ transport. The data obtained on retina are compared with published data on brain, which also suggest that a large fraction of the energy generated is used for function-related processes. It seems reasonable to conclude that by reversibly blocking the energy-demanding processes responsible for neurophysiological functioning, it would be possible to eliminate most of the energy requirements of CNS tissue and to reduce markedly its vulnerability to hypoperfusion. RP AMES, A (reprint author), MASSACHUSETTS GEN HOSP,NEUROSURG SERV,414 EDWARDS BLDG,BOSTON,MA 02114, USA. FU NINDS NIH HHS [NS 25753] NR 73 TC 69 Z9 70 U1 3 U2 4 PU NATL RESEARCH COUNCIL CANADA PI OTTAWA PA RESEARCH JOURNALS, MONTREAL RD, OTTAWA ON K1A 0R6, CANADA SN 0008-4212 J9 CAN J PHYSIOL PHARM JI Can. J. Physiol. Pharmacol. PY 1992 VL 70 SU S BP S158 EP S164 PG 7 WC Pharmacology & Pharmacy; Physiology SC Pharmacology & Pharmacy; Physiology GA KL246 UT WOS:A1992KL24600022 PM 1295666 ER PT J AU SWEADNER, KJ AF SWEADNER, KJ TI OVERLAPPING AND DIVERSE DISTRIBUTION OF NA-K ATPASE ISOZYMES IN NEURONS AND GLIA SO CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY LA English DT Article DE NA-K ATPASE; MONOCLONAL ANTIBODY; IMMUNOFLUORESCENCE; CENTRAL NERVOUS SYSTEM; RETINA; INSITU HYBRIDIZATION ID CENTRAL-NERVOUS-SYSTEM; NA+,K+-ATPASE ALPHA-SUBUNIT; 2 DIFFERENT NA,K-ATPASES; RAT-BRAIN; CATALYTIC SUBUNIT; MESSENGER-RNA; BETA-SUBUNIT; IMMUNOFLUORESCENT LOCALIZATION; ENZYMATIC-PROPERTIES; ADHESION MOLECULE AB The Na-K ATPase is the plasma membrane enzyme that catalyzes the active uptake of K+ and extrusion of Na+, thereby establishing ion concentration gradients between the inside and outside of the cell. It consumes a large fraction of the energy used in the brain. The enzyme is present in both neurons and glia. Studies of ion flux and of the properties of membrane-associated ATPase activity have suggested that there is more than one functional type of Na - K ATPase in the central nervous system. Molecular cloning has demonstrated that there are three different genes encoding catalytic (alpha) subunits and at least two genes encoding glycoprotein (beta) subunits; all are expressed in the brain. This brief review summarizes the current understanding of Na-K ATPase isozyme distribution and properties. Both neurons and glia can express different isoforms in a cell-specific manner. C1 HARVARD UNIV, SCH MED, DEPT CELLULAR & MOLEC PHYSIOL, BOSTON, MA 02115 USA. RP SWEADNER, KJ (reprint author), MASSACHUSETTS GEN HOSP, WELLMAN 4, FRUIT ST, BOSTON, MA 02114 USA. NR 45 TC 53 Z9 55 U1 0 U2 1 PU CANADIAN SCIENCE PUBLISHING, NRC RESEARCH PRESS PI OTTAWA PA 1200 MONTREAL ROAD, BUILDING M-55, OTTAWA, ON K1A 0R6, CANADA SN 0008-4212 J9 CAN J PHYSIOL PHARM JI Can. J. Physiol. Pharmacol. PY 1992 VL 70 SU S BP S255 EP S259 PG 5 WC Pharmacology & Pharmacy; Physiology SC Pharmacology & Pharmacy; Physiology GA KL246 UT WOS:A1992KL24600034 PM 1338295 ER PT J AU SCHWARTZ, JL TANAKA, J KHANDEKAR, V HERMAN, TS TEICHER, BA AF SCHWARTZ, JL TANAKA, J KHANDEKAR, V HERMAN, TS TEICHER, BA TI BETA-CAROTENE AND OR VITAMIN-E AS MODULATORS OF ALKYLATING-AGENTS IN SCC-25 HUMAN SQUAMOUS CARCINOMA-CELLS SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE BETA-CAROTENE; VITAMIN-E; ALKYLATING AGENTS; HUMAN SQUAMOUS CARCINOMA CELLS ID TUMOR NECROSIS FACTOR; ORAL-CANCER; ALPHA-TOCOPHEROL; LUNG-CANCER; REGRESSION; INHIBITION; RISK; CANTHAXANTHIN; PREVENTION; INDUCTION AB Dietary levels of beta-carotene and vitamin E have been associated with cancer prevention and to a lesser extent, with therapeutic enhancement of cancer treatment. We report on the cytotoxicity of beta-carotene, vitamin E, and the combination of beta-carotene and vitamin E in human SCC-25 squamous carcinoma cells under various environmental conditions found in solid tumor masses. Beta-Carotene was selectively cytotoxic toward normally oxygenated cells and was generally more cytotoxic at normal pH than at acidic pH (6.45). Vitamin E was selectively cytotoxic toward normally oxygenated cells following 6 h exposure at normal pH and was generally equally cytotoxic toward normally oxygenated and hypoxic cells under the other conditions tested. Beta-Carotene was an effective modulator of cisplatin (CDDP) cytotoxicity toward SCC-25 cells, whereas vitamin E was not. Both beta-carotene and vitamin E were effective modulators of melphalan cytotoxicity toward SCC-25 cells. Treatment of SCC-25 cells with beta-carotene (70-mu-M, 2 h) resulted in a reduction in superoxide dismutase activity, in glutathione-S-transferase activity, and in nonprotein sulfhydryl levels in the cells. Exposure to vitamin E or to a combination of beta-carotene and vitamin E increased the glutathione-S-transferase activity in SCC-25 cells by 40%-45% over the control value. Treatment with beta-carotene, vitamin E, or canthaxanthin reduced the incorporation of [H-3]-thymidine into SCC-25 cells but not that into normal human karotinocytes. The most marked reduction in [H-3]-thymidine incorporation into SCC-25 cells occurred following treatment with the combination of beta-carotene and melphalan. We hope to continue to explore the mechanisms of this effect and to study these combinations in vivo. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. HARVARD UNIV,SCH DENT MED,DEPT ORAL PATHOL,BOSTON,MA 02215. FU PHS HHS [P01-38493] NR 51 TC 33 Z9 33 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 JAN PY 1992 VL 29 IS 3 BP 207 EP 213 DI 10.1007/BF00686254 PG 7 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA HB107 UT WOS:A1992HB10700007 PM 1733553 ER PT J AU WIERNIK, PH YEAP, B VOGL, SE KAPLAN, BH COMIS, RL FALKSON, G DAVIS, TE FAZZINI, E CHEUVART, B HORTON, J AF WIERNIK, PH YEAP, B VOGL, SE KAPLAN, BH COMIS, RL FALKSON, G DAVIS, TE FAZZINI, E CHEUVART, B HORTON, J TI HEXAMETHYLMELAMINE AND LOW OR MODERATE DOSE CISPLATIN WITH OR WITHOUT PYRIDOXINE FOR TREATMENT OF ADVANCED OVARIAN-CARCINOMA - A STUDY OF THE EASTERN COOPERATIVE ONCOLOGY GROUP SO CANCER INVESTIGATION LA English DT Article ID STAGE-III; CANCER; CHEMOTHERAPY; FAILURE; DOXORUBICIN; SURVIVAL; TABLES AB A total of 248 analyzable patients with Stages III-IV ovarian epithelial cancer (114 with and 134 without prior chemotherapy) were randomized to one of four cisplatin (DDP)-hexamethylmelamine (HMM) regimens. In each, HMM, 200 mg/m2 was given orally daily on days 8-21 of each 21-day cycle. DDP was given i.v. on Day 1 at a dose of 37.5 mg/m2 (regimens A and B) or 75 mg/m2 (regimens C and D). In addition, since pyridoxine administration has been reported to reduce the neurotoxicity of HMM, that agent was given at a dose of 300 mg/m2 orally on Days 1-21 in regimens B and D. Randomization was stratified for performance status (0-1, 2-3) and largest tumor diameter at entry (> 2- less-than-or-equal-to 10 cm, > 10 cm) for previously untreated patients, and for performance status and time from initial diagnosis to entry on study (less-than-or-equal-to 1 year, > 1 year) for previously treated patients. The overall response rate (PR + CR) was 54%, with 25% of patients achieving a complete response. The 61% response rate with the higher dose DDP regimens was significantly greater than the 47% response rate with the lower dose regimens (p = 0.031). Multivariate analysis identified higher DDP dose, age < 60 years, no prior chemotherapy, small tumor bulk and favorable tumor grade as significant prognosticators for response. The overall median response duration was 8.3 months (range 1-70 months). Prior chemotherapy, pyridoxine administration, recent diagnosis, and large tumor size were identified by multivariate analysis as factors adversely affecting response duration. Patients treated with the higher dose DDP regimens had more severe nausea, vomiting, and neurotoxicity. This study demonstrates that the combination of DDP + HMM is an effective regimen for advanced ovarian carcinoma that yields response rates comparable to other more complex regimens, and that there is a dose-response relationship for DDP in ovarian cancer. Although pyridoxine administration significantly reduced neurotoxicity, its adverse effect on response duration suggests that the agent should not be administered with DDP or HMM. The mechanism by which pyridoxine may unfavorably affect response duration deserves further investigation. C1 HARVARD UNIV,SCH PUBL HLTH,DANA FARBER CANC INST,BOSTON,MA 02115. FOX CHASE CANC INST,PHILADELPHIA,PA 19111. UNIV PRETORIA,PRETORIA,SOUTH AFRICA. UNIV WISCONSIN,CTR CLIN CANC,MADISON,WI 53706. NYU MED CTR,NEW YORK,NY 10016. UNION UNIV,ALBANY,NY 12208. RP WIERNIK, PH (reprint author), ALBERT EINSTEIN CANC CTR,111 E 210TH ST,NEW YORK,NY 10467, USA. FU NCI NIH HHS [CA 23318, CA 18281, CA 14958] NR 24 TC 34 Z9 34 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 0735-7907 J9 CANCER INVEST JI Cancer Invest. PY 1992 VL 10 IS 1 BP 1 EP 9 DI 10.3109/07357909209032783 PG 9 WC Oncology SC Oncology GA HE712 UT WOS:A1992HE71200001 PM 1735009 ER PT J AU CASE, DC COLEMAN, M GOTTLIEB, A MCCARROLL, K AF CASE, DC COLEMAN, M GOTTLIEB, A MCCARROLL, K TI PHASE-I-II TRIAL OF HIGH-DOSE MELPHALAN IN PREVIOUSLY UNTREATED STAGE-III MULTIPLE-MYELOMA - CANCER AND LEUKEMIA GROUP-B STUDY 8512 SO CANCER INVESTIGATION LA English DT Article ID SOUTHWEST-ONCOLOGY-GROUP; PLASMA-CELL MYELOMA; COMBINATION CHEMOTHERAPY; IMPROVED SURVIVAL; INTRAVENOUS MELPHALAN; M-2 PROTOCOL; RISK MYELOMA; THERAPY; VINCRISTINE; CYCLOPHOSPHAMIDE AB To study the efficiency of high-dose melphalan in previously untreated patients with advanced myeloma, we performed a Phase I-II trial. Twenty-eight patients were treated at dose level of 60-140 mg/m2. Each patient was first treated with a priming dose of cyclophosphamide (300 mg) followed by high-dose melphalen 1 week later. One course of therapy was given. Patients were then followed without further therapy until relapse. Clinical and laboratory features of the 28 patients in this study included: median age 63, performance status 0-2, hypercalcemia 21%, bone pain 82%, paraprotein types: IgG 76%, Iga 20%, and paraproteinuria 71%. Because none of the patients acheived complete remission (CR) at 60 mg/m2, despite life-threatening toxicity in all patients, the dose level was rapidly increased to 140 mg/m2, a dose previously reported to induce a high percentage of CR. At this dose, CR was achieved in only 1 of 11 patients (9%). This patient had multiple plasmacytomas without generalized bone marrow involvement. One additional patient at 100 mg/m2 achieved CR. Of the whole group, 12 achieved PR. Durations of remissions were generally short: CR 6.3 and 18+ months and PR 2.3-18 month, median 6.9 months. Life-threatening myelosuppression was universal with prolonged pancytopenia. Treatment-related deaths from sepsis were observed in 29% of patients. The median survival of the entire group was 15.6 months. Older patients in this trial did not tolerate high-dose melphalen therapy well; this resulted in a high proportion of toxic deaths and poor overall survival. C1 MAINE MED CTR,DEPT MED,DIV ONCOL,PORTLAND,ME 04102. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,WINSTON SALEM,NC 27103. DARTMOUTH COLL,HITCHCOCK MED CTR,DARTMOUTH MED SCH,HANOVER,NH 03756. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. CORNELL UNIV,MED CTR,NEW YORK HOSP,DEPT MED,DIV HEMATOL ONCOL,NEW YORK,NY 10021. RHODE ISL HOSP,PROVIDENCE,RI 02902. SUNY HLTH SCI CTR,DEPT MED,SYRACUSE,NY. HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,BOSTON,MA 02115. RP CASE, DC (reprint author), MAINE MED CTR,DEPT MED,DIV HEMATOL,PORTLAND,ME 04102, USA. FU NCI NIH HHS [CA 31946, CA 04326, CA 03927] NR 36 TC 2 Z9 2 U1 0 U2 1 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 0735-7907 J9 CANCER INVEST JI Cancer Invest. PY 1992 VL 10 IS 1 BP 11 EP 17 DI 10.3109/07357909209032784 PG 7 WC Oncology SC Oncology GA HE712 UT WOS:A1992HE71200002 PM 1735010 ER EF