FN Thomson Reuters Web of Science™ VR 1.0 PT J AU DOWN, JD MAUCH, P WARHOL, M NEBEN, S FERRARA, JLM AF DOWN, JD MAUCH, P WARHOL, M NEBEN, S FERRARA, JLM TI THE EFFECT OF DONOR LYMPHOCYTES-T AND TOTAL-BODY IRRADIATION ON HEMATOPOIETIC ENGRAFTMENT AND PULMONARY TOXICITY FOLLOWING EXPERIMENTAL ALLOGENEIC BONE-MARROW TRANSPLANTATION SO TRANSPLANTATION LA English DT Article ID VERSUS-HOST DISEASE; MINOR HISTOCOMPATIBILITY BARRIERS; SINGLE-DOSE IRRADIATION; KILLER CELL-ACTIVITY; MOUSE LUNG; INTERSTITIAL PNEUMONITIS; ACUTE GRAFT; 1ST REMISSION; LETHAL GRAFT; X-RAYS AB To study the effects of donor T lymphocytes on engraftment and graft-versus-host disease in relation to recipient total-body irradiation, we have returned small numbers of T cells to T-cell-depleted bone marrow transplanted across a minor histocompatibility barrier in mice (B10.BR --> CBA). T-cell-depleted B10.BR marrow (10(7) cells) was transplanted into CBA recipients prepared with TBI doses ranging from 4 to 14 Gy. Selected animals also received 10(4) (0.1%) and 10(5) (1.0%) measured B10.BR T lymphocytes. The extent of donor marrow engraftment was determined from hemoglobin and carbonic anhydrase phenotyping of peripheral blood at 3 months posttransplant. Toxicity was assessed from breathing-rate measurements, histopathology, and animal survival. Addition of T cells had a profound effect on survival related to radiation dose. The TBI doses resulting in an LD50 at 12 weeks were 6.9 Gy, 9.3 Gy, and 13.0 Gy for animals receiving 10(5), 10(4), and no T cells, respectively. Mortality was associated with pulmonary dysfunction as measured by an elevation of breathing rates. Autopsy and histological analysis revealed extensive damage to the lung parenchyma. In contrast to the toxicity data, addition of T cells to the donor marrow had no effect on the TBI dose required for equivalent erythroid engraftment. These results demonstrate that in combination with TBI small numbers of T cells in the transplanted marrow do not aid engraftment but do significantly increase the risk of pulmonary toxicity. C1 HARVARD UNIV,SCH MED,JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. CHILDRENS HOSP MED CTR,BOSTON,MA 02115. PENN HOSP,DEPT PATHOL,PHILADELPHIA,PA 19107. RP DOWN, JD (reprint author), UNIV GRONINGEN,DEPT RADIOBIOL,BLOEMSINGEL 1,9713 BZ GRONINGEN,NETHERLANDS. FU NCI NIH HHS [R01-CA-10941] NR 49 TC 45 Z9 46 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 NOV PY 1992 VL 54 IS 5 BP 802 EP 808 DI 10.1097/00007890-199211000-00007 PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA JY228 UT WOS:A1992JY22800007 PM 1359684 ER PT J AU SUNDT, TM ARN, JS SACHS, DH AF SUNDT, TM ARN, JS SACHS, DH TI PATTERNS OF T-CELL ACCESSORY CELL-INTERACTION IN THE GENERATION OF PRIMARY ALLORESPONSES IN THE PIG SO TRANSPLANTATION LA English DT Article ID MONOCLONAL-ANTIBODIES; MINIATURE SWINE; CYCLOSPORINE-A; PATHWAYS; ALLOANTIGENS; ACTIVATION; REJECTION AB Partially inbred, MHC-homozygous miniature swine provide a unique model for the study of organ transplantation and the induction of tolerance in large animals. Models of both vascularized solid organ transplantation and bone marrow transplantation have previously been established. The availability of monoclonal antibodies reactive with porcine leukocyte subset antigens now makes possible studies of the cellular immunology in this species, affording the opportunity to examine mechanisms of transplant tolerance and graft rejection in increasing detail. Using such antibodies and peripheral blood leukocytes from pigs of recombinant MHC haplotypes, we have examined porcine T cell-accessory cell interactions in vitro with attention to T cell subsets and the class of MHC alloantigen stimulation. Primary allospecific MLR and CML cultures were studied after depletion of accessory cells from responder and/or stimulator populations. Although class II MHC antigens were expressed on the majority of porcine T cells before and after depletion, these cells were insufficient for antigen presentation, since there was an absolute requirement for ACs in the generation of primary alloresponses. Proliferative and CTL alloresponses could be generated provided that ACs of either stimulator or responder type were present. Selective depletion of CD4+ T cells from the responder population demonstrated: (a) that the interaction mediated by self ACs was CD4-dependent; (b) that two pathways exist for interaction involving allogeneic ACs; and (c) that the interaction involving allogeneic class II is CD4-dependent, while that with allogeneic class I is not. C1 MASSACHUSETTS GEN HOSP,TRANSPLANTAT BIOL RES CTR,MGH E,BLDG 149,13TH ST,BOSTON,MA 02129. NCI,IMMUNOL BRANCH,TRANSPLANTAT BIOL SECT,ROCKVILLE,MD 20892. FU NCI NIH HHS [1 R01 CA55553-01]; NIAID NIH HHS [1 R01 AI31046-01] NR 18 TC 14 Z9 14 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 NOV PY 1992 VL 54 IS 5 BP 911 EP 916 DI 10.1097/00007890-199211000-00027 PG 6 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA JY228 UT WOS:A1992JY22800027 PM 1440858 ER PT J AU WEINTRAUB, H ALROY, J DEGASPERI, R GOYAL, V SKUTELSKY, E PENTCHEV, PG WARREN, CD AF WEINTRAUB, H ALROY, J DEGASPERI, R GOYAL, V SKUTELSKY, E PENTCHEV, PG WARREN, CD TI STORAGE OF GLYCOPROTEIN IN NCTR-BALB/C MOUSE - LECTIN HISTOCHEMISTRY, AND BIOCHEMICAL-STUDIES SO VIRCHOWS ARCHIV B-CELL PATHOLOGY INCLUDING MOLECULAR PATHOLOGY LA English DT Article ID ENDO-BETA-GALACTOSIDASE; DISORDER; DISEASE; MICE; LACTOSAMINOGLYCAN; OLIGOSACCHARIDES; MANNOSIDOSIS; CHOLESTEROL; SPECIFICITY; ANIMALS AB A strain of Balb/C mice carrying a lysosomal storage disorder exhibits metabolic and phenotypic abnormalities similar to patients with sphingomelin-cholesterol lipidoses type II (i.e., Niemann-Pick C and D). Their foamy cells, which belong to the reticuloendothelial system, stained intensely by periodate-Schiff (PAS) reagent and were resistant to predigestion with diastase. To identify the chemical nature of the PAS-positive storage material, we applied lectin histochemistry and biochemical methods. Paraffin embedded sections, and delipidated frozen tissue sections., were treated with biotinylated lectins and localized with avidin-biotin-peroxidase complex. Araldite-embedded semithin sections were incubated with biotinylated lectins followed by avidin-gold and were enhanced with silver. By both histochemical methods the affected foamy cells stained positively as follows: Concanavalia ensiformis agglutinin, Datura stramonium agglutinin, Griffonia simplicifolia-I, Lens culinaris agglutinin, peanut agglutinin, Ricinus communis agglutinin-I, wheat germ agglutinin (WGA), and succinylated-WGA. Biochemical analysis of liver extracts complemented the histochemical data and demonstrated accumulation of glycoproteins containing polylactosaminoglycans in affected mice. Our findings indicate that the storage material in NCTR-Balb/C mice is heterogeneous. The lipids that are extracted by organic solvents during the histologic preparations mask the occurrence of polylactosaminoglycan containing glycoproteins in native frozen sections. C1 TUFTS UNIV,SCH MED,DEPT PATHOL,136 HARRISON AVE,BOSTON,MA 02111. TUFTS UNIV,DEPT PATHOL,BOSTON,MA 02111. TEL AVIV UNIV,SACKLER SCH MED,DEPT PATHOL,TEL AVIV,ISRAEL. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,LOVETT LABS,CARBOHYDRATE UNIT,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT BIOL CHEM,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. NINCDS,DEV & METAB BRANCH,BETHESDA,MD 20892. NR 27 TC 2 Z9 2 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-6075 J9 VIRCHOWS ARCH B JI Virchows Arch. B-Cell Molec. Pathol. PD NOV PY 1992 VL 62 IS 6 BP 347 EP 352 DI 10.1007/BF02899702 PG 6 WC Pathology SC Pathology GA JV181 UT WOS:A1992JV18100002 PM 1360721 ER PT J AU MCKEE, AC AF MCKEE, AC TI OSMOTIC SHIFTS, METABOLIC COMPROMISE, AND THE VULNERABILITY OF THE PONS SO WESTERN JOURNAL OF MEDICINE LA English DT Editorial Material ID CENTRAL PONTINE MYELINOLYSIS; LIVER-TRANSPLANTATION RP MCKEE, AC (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CHARLES S KUBIK LAB NEUROPATHOL,BOSTON,MA 02114, USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0093-0415 J9 WESTERN J MED JI West. J. Med. PD NOV PY 1992 VL 157 IS 5 BP 588 EP 590 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA JY240 UT WOS:A1992JY24000025 PM 1441515 ER PT J AU WANG, TC BRAND, SJ AF WANG, TC BRAND, SJ TI FUNCTION AND REGULATION OF GASTRIN IN TRANSGENIC MICE - A REVIEW SO YALE JOURNAL OF BIOLOGY AND MEDICINE LA English DT Article; Proceedings Paper CT CONF ON CURRENT CLINICAL AND SCIENTIFIC PERSPECTIVES IN GASTROENTEROLOGY CY APR 04-05, 1992 CL MONTAUK, NY ID GROWTH-FACTOR; TGF-ALPHA; PANCREAS; GENE; EXPRESSION; CELLS; LIVER; DIFFERENTIATION; OVEREXPRESSION; PROMOTER AB The gastrin gene is expressed in fetal pancreatic islet cells, but in the adult is expressed mainly in the gastric antrum. To study the regulation of the gastrin promoter, we created several transgenes containing the human and rat gastrin 5' flanking regions joined to the coding sequences of the human gastrin gene. The human gastrin transgene contained 1,300 bp of 5' flanking DNA, while the rat gastrin transgene contained 450 bp of 5' flanking DNA. The human gastrin transgene was expressed in fetal islets, but was not expressed in adult gastric antrum. In contrast, the rat gastrin transgene was expressed in adult antral G cells, but no expression was observed in fetal islets. To study the possible role of gastrin as an islet growth factor, a chimeric insulin-gastrin (INS-GAS) transgene was created, in which the expression of the human gastrin gene is driven from the rat insulin I promoter. These INS-GAS mice were mated with mice overexpressing TGFalpha, transcribed from a mouse metallothionein-transforming growth factor alpha (MT-TGFalpha) transgene. While overexpression of gastrin or TGFalpha alone had no effect on islet mass, overexpression of both transgenes resulted in a twofold increase in islet mass. In conclusion, these data indicate that (1) gastrin can interact synergistically with TGFalpha to stimulate islet growth; (2) the human gastrin transgene contains the islet specific enhancer; (3) the rat gastrin transgene contains the antral specific enhancer. RP WANG, TC (reprint author), MASSACHUSETTS GEN HOSP,DEPT MED,GASTROINTESTINAL UNIT,FRUIT ST,BOSTON,MA 02114, USA. FU NIDDK NIH HHS [DK01937, DK42127-03] NR 23 TC 12 Z9 12 U1 0 U2 0 PU YALE J BIOL MED INC PI NEW HAVEN PA 333 CEDAR ST, NEW HAVEN, CT 06510 SN 0044-0086 J9 YALE J BIOL MED JI Yale J. Biol. Med. PD NOV-DEC PY 1992 VL 65 IS 6 BP 705 EP 713 PG 9 WC Biology; Medicine, General & Internal; Medicine, Research & Experimental SC Life Sciences & Biomedicine - Other Topics; General & Internal Medicine; Research & Experimental Medicine GA LX445 UT WOS:A1992LX44500015 PM 1341073 ER PT J AU VITKIN, IA WILSON, BC KAPLAN, RS ANDERSON, RR AF VITKIN, IA WILSON, BC KAPLAN, RS ANDERSON, RR TI THE FEASIBILITY OF MONITORING EXOGENOUS DYE UPTAKE IN TISSUE INVIVO USING PULSED PHOTOTHERMAL RADIOMETRY SO JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY LA English DT Note DE OPTICAL PROPERTIES; PHOTOTHERMAL EFFECTS; PHOTOSENSITIZER ID MAMMALIAN-TISSUES; MEDIA C1 MCMASTER UNIV,HAMILTON REG CANC CTR,699 CONCESS ST,HAMILTON L8V 5C2,ONTARIO,CANADA. MASSACHUSETTS GEN HOSP,WELLMAN RES LABS PHOTOMED,BOSTON,MA 02114. FU NIADDK NIH HHS [AM25395] NR 13 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE SA LAUSANNE PI LAUSANNE 1 PA PO BOX 564, 1001 LAUSANNE 1, SWITZERLAND SN 1011-1344 J9 J PHOTOCH PHOTOBIO B JI J. Photochem. Photobiol. B-Biol. PD OCT 30 PY 1992 VL 16 IS 2 BP 235 EP 239 DI 10.1016/1011-1344(92)80010-S PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA KA457 UT WOS:A1992KA45700009 PM 1474428 ER PT J AU GEORGOPOULOS, K MOORE, DD DERFLER, B AF GEORGOPOULOS, K MOORE, DD DERFLER, B TI IKAROS, AN EARLY LYMPHOID-SPECIFIC TRANSCRIPTION FACTOR AND A PUTATIVE MEDIATOR FOR T-CELL COMMITMENT SO SCIENCE LA English DT Article ID HEMATOPOIETIC STEM-CELLS; CD3-DELTA GENE; YOLK-SAC; EXPRESSION; PRECURSORS; ONTOGENY; MOUSE AB In a screen for transcriptional regulators that control differentiation into the T cell lineage, a complementary DNA was isolated encoding a zinc finger protein (Ikaros) related to the Drosophila gap protein Hunchback. The Ikaros protein binds to and activates the enhancer of a gene encoding an early T cell differentiation antigen, CD3delta. During development, Ikaros messenger RNA was first detected in the mouse fetal liver and the embryonic thymus when hematopoietic and lymphoid progenitors initially colonize these organs; no expression was observed in the spleen or the bone marrow. The pattern of Ikaros gene expression and its ability to stimulate CD3delta transcription support the model that Ikaros functions in the specification and maturation of the T lymphocyte. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MOLEC BIOL,BOSTON,MA 02114. RP GEORGOPOULOS, K (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CUTANEOUS BIOL RES CTR,BOSTON,MA 02114, USA. NR 26 TC 319 Z9 324 U1 0 U2 4 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD OCT 30 PY 1992 VL 258 IS 5083 BP 808 EP 812 DI 10.1126/science.1439790 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JV692 UT WOS:A1992JV69200041 PM 1439790 ER PT J AU RICHARDSON, EP KUBIK, CS AF RICHARDSON, EP KUBIK, CS TI ALZHEIMERS-DISEASE SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Note RP RICHARDSON, EP (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 OCT 29 PY 1992 VL 327 IS 18 BP 1289 EP 1289 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA JV259 UT WOS:A1992JV25900007 ER PT J AU GROWDON, JH AF GROWDON, JH TI TREATMENT FOR ALZHEIMERS-DISEASE SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID DEGENERATION; ADULT; BRAIN RP GROWDON, JH (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 11 TC 41 Z9 41 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 OCT 29 PY 1992 VL 327 IS 18 BP 1306 EP 1308 DI 10.1056/NEJM199210293271810 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA JV259 UT WOS:A1992JV25900010 PM 1357552 ER PT J AU MEYEROVITCH, J BACKER, JM CSERMELY, P SHOELSON, SE KAHN, CR AF MEYEROVITCH, J BACKER, JM CSERMELY, P SHOELSON, SE KAHN, CR TI INSULIN DIFFERENTIALLY REGULATES PROTEIN PHOSPHOTYROSINE PHOSPHATASE-ACTIVITY IN RAT HEPATOMA-CELLS SO BIOCHEMISTRY LA English DT Article ID LEUKOCYTE-COMMON ANTIGEN; TYROSINE-PHOSPHATASE; HUMAN-PLACENTA; BETA-SUBUNIT; SIGNAL TRANSDUCTION; MOLECULAR-CLONING; XENOPUS OOCYTES; GROWTH-FACTOR; RECEPTOR; PHOSPHORYLATION AB We have studied the effect of insulin stimulation on phosphotyrosine phosphatase (PTPase) activity in the well-differentiated rat hepatoma cell line Fao. PTPase activity was measured using a P-32-labeled peptide corresponding to the major site of insulin receptor autophosphorylation. Of the PTPase activity in Fao cells, 14% was in the cytosolic fraction, whereas 86% was in the particulate fraction; this latter fraction also had a 4-fold higher specific activity. Purification of the particulate fraction by lectin chromatography resulted in a 50% increase in specific activity, although this glycoprotein-rich fraction contained only 1.5% of the total activity. Both the cytosolic and particulate PTPase fractions were active toward the tyrosyl-phosphorylated insulin receptor in vitro. The activity of the particulate fraction but not the cytosolic fraction was inhibited by addition of a micromolar concentration of a phosphorylated peptide corresponding to residues 1142-1153 of the human insulin receptor sequence. By contrast, addition of the nonphosphorylated peptide even at millimolar concentration was without effect. Both PTPase fractions were inhibited by Zn+ at similar concentrations, whereas the cytosolic PTPase activity was 10-fold more sensitive to vanadate inhibition. Treatment of cells with 100 nM insulin increased PTPase activity in the particulate fraction by 40% and decreased activity in the cytosolic fraction by 35%. These effects occurred within 15 min and were half-maximal at 3-4 nM insulin. When assessed as total activity, the magnitude of the changes in PTPase activity in the particulate and cytosolic fractions could not be explained on the basis of a translocation of PTPases between the two pools. We conclude that hepatoma cells possess discrete membrane and cytosolic PTPases with activity toward the tyrosyl-phosphorylated insulin receptor which can be regulated by physiological concentrations of insulin. PTPases may therefore modulate the tyrosyl phosphorylation of the insulin receptor and its substrates, and may be involved in the regulation of insulin-stimulated metabolic and growth-related effects. C1 JOSLIN DIABET CTR,DIV RES,ONE JOSLIN PL,BOSTON,MA 02215. BRIGHAM & WOMENS HOSP,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. FU FIC NIH HHS [1-FO5-TW04319-01]; NIDDK NIH HHS [DK 36836, DK 33201] NR 66 TC 29 Z9 29 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD OCT 27 PY 1992 VL 31 IS 42 BP 10338 EP 10344 DI 10.1021/bi00157a023 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JV258 UT WOS:A1992JV25800023 PM 1420153 ER PT J AU MILLER, JM MACGARVEY, U BEAL, MF AF MILLER, JM MACGARVEY, U BEAL, MF TI THE EFFECT OF PERIPHERAL LOADING WITH KYNURENINE AND PROBENECID ON EXTRACELLULAR STRIATAL KYNURENIC ACID CONCENTRATIONS SO NEUROSCIENCE LETTERS LA English DT Article DE KYNURENIC ACID; KYNURENINE; MICRODIALYSIS; PROBENECID; STRIATUM ID LIQUID-CHROMATOGRAPHY; QUINOLINIC ACID; MAMMALIAN BRAIN; RATS; ANTAGONIST; METABOLISM; RECEPTORS; INVIVO AB Kynurenic acid (KYA) is the only known endogenous excitatory amino acid antagonist in mammalian brain. In the present study we examined the effects of precursor loading with kynurenine (KYN) and blockade of organic acid transport with probenecid, either alone or in combination, on extracellular striatal KYA concentrations in unanesthetized rats. Baseline KYA concentrations were 1.61+/-0.29 pmol/ml. Following administration of KYN 150 mg/kg with increasing doses of probenecid a maximal increase in KYA to 946+/-210 pmol/ml was seen with probenecid 200 mg/kg. Probenecid 200 mg/kg alone increased KYA levels to 16.0+/-5.2 pmol/ml. The combination of probenecid 200 mg/kg with KYN 450 mg/kg produced a maximal increase of KYA to 2085+/-391 pmol/ml, a 1300-fold increase indicating marked potentiation. These results show that pharmacologic manipulation can markedly increase extracellular fluid concentrations of KYA into a range which may be useful in attempts to block NMDA receptor-mediated neurotoxicity. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,FRUIT ST,BOSTON,MA 02114. NR 20 TC 36 Z9 37 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD OCT 26 PY 1992 VL 146 IS 1 BP 115 EP 118 DI 10.1016/0304-3940(92)90186-B PG 4 WC Neurosciences SC Neurosciences & Neurology GA JW568 UT WOS:A1992JW56800030 PM 1475044 ER PT J AU STACEYCLEAR, A MCCARTHY, KA HALL, DA PILESPELLMAN, E WHITE, G HULKA, C WHITMAN, GJ MAHONEY, E KOPANS, DB AF STACEYCLEAR, A MCCARTHY, KA HALL, DA PILESPELLMAN, E WHITE, G HULKA, C WHITMAN, GJ MAHONEY, E KOPANS, DB TI BREAST-CANCER SURVIVAL AMONG WOMEN UNDER AGE 50 - IS MAMMOGRAPHY DETRIMENTAL SO LANCET LA English DT Article ID SCREENING TRIAL; MORTALITY; REDUCTION AB Great uncertainty exists about the benefit of detecting breast cancer by mammography in women under 50 years of age. We have reviewed the survival of patients aged 49 years or less whose cancers were detected by mammography alone. 117 women under the age of 50 years were diagnosed with breast cancer between 1978 and 1991 based only on an abnormal mammogram. Ductal carcinoma in-situ (DCIS) was found in 47 (40%) of these women, whilst 70 (60%) had infiltrating ductal or infiltrating lobular carcinomas. During the same interval, 928 women in this age group presented with palpable breast cancer. DCIS was diagnosed in 82 (9%) of these women, whilst 846 (91%) had infiltrating carcinoma. Among the infiltrating cancers detected by mammography alone, 50% were stage I, whilst only 30% of the women with palpable cancers were stage I. Five-year survival for all mammographically detected cancer patients was 95%, whereas for women with palpable cancers the survival was 74% (p < 0.00005). If DCIS is not included, the corresponding survivals are 91% for mammographically detected infiltrating cancers and 72% for palpable infiltrating cancers. Only 1 woman who died among those with palpable cancer had had a mammogram before diagnosis. Our data contradict the suggestion that women under 50 are put at a survival disadvantage by undergoing mammography. We believe that investigators who have reported negative results in this age group must examine other causes for their results. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CTR CANC,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DIV SURG ONCOL,BOSTON,MA 02114. HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,BOSTON,MA 02115. NR 21 TC 34 Z9 35 U1 1 U2 1 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD OCT 24 PY 1992 VL 340 IS 8826 BP 991 EP 994 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA JV014 UT WOS:A1992JV01400002 PM 1357448 ER PT J AU HASS, R BRACH, M GUNJI, H KHARBANDA, S KUFE, D AF HASS, R BRACH, M GUNJI, H KHARBANDA, S KUFE, D TI INHIBITION OF EGR-1 AND NF-KAPPA-B GENE-EXPRESSION BY DEXAMETHASONE DURING PHORBOL ESTER-INDUCED HUMAN MONOCYTIC DIFFERENTIATION SO BIOCHEMICAL PHARMACOLOGY LA English DT Article ID FINGER-ENCODING GENE; DNA-BINDING; GLUCOCORTICOID RECEPTOR; C-FOS; TRANSCRIPTION FACTOR; NUCLEAR FACTOR; REGULATORY SEQUENCE; ENHANCER SEQUENCES; PROTEIN; JUN AB The treatment of human myeloid leukemia cells (HL-60, U-937, THP-1) with 12-O-tetradecanoylphorbol-13-acetate (TPA) is associated with growth arrest and appearance of a differentiated monocytic phenotype. While previous studies have reported that the glucocorticoid dexamethasone blocks phenotypic characteristics of monocytic differentiation, we demonstrated in the present work that dexamethasone delays the effects of TPA on the loss of U-937 cell proliferation. We also demonstrated that this glucocortocoid inhibits TPA-induced increases in expression of the EGR-1 early response gene. The results of nuclear run-on assays and half-life experiments indicated that this effect of dexamethasone is regulated at the post-transcriptional level. Similar studies were performed for the NF-kappaB gene. While TPA treatment was associated with transient increases in NF-kappaB mRNA levels, this induction was blocked by dexamethasone. In contrast, dexamethasone had no significant effect on the activation of pre-existing NF-kappaB protein as determined in DNA-binding assays. Taken together, these findings suggest that the activated glucocorticoid receptor inhibits signaling pathways which include expression of the EGR-1 and NF-kappaB genes and that such effects may contribute to a block in TPA-induced monocytic differentiation. RP HASS, R (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,CLIN PHARMACOL LAB,44 BINNEY ST,BOSTON,MA 02115, USA. RI Hass, Ralf/F-3197-2012 OI Hass, Ralf/0000-0002-2481-7547 FU NCI NIH HHS [CA42802] NR 41 TC 27 Z9 27 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD OCT 20 PY 1992 VL 44 IS 8 BP 1569 EP 1576 DI 10.1016/0006-2952(92)90474-W PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA JW156 UT WOS:A1992JW15600014 PM 1417981 ER PT J AU DOMCHEK, SM AUGER, KR CHATTERJEE, S BURKE, TR SHOELSON, SE AF DOMCHEK, SM AUGER, KR CHATTERJEE, S BURKE, TR SHOELSON, SE TI INHIBITION OF SH2 DOMAIN PHOSPHOPROTEIN ASSOCIATION BY A NONHYDROLYZABLE PHOSPHONOPEPTIDE SO BIOCHEMISTRY LA English DT Article ID MIDDLE-T-ANTIGEN; PHOSPHATIDYLINOSITOL KINASE-ACTIVITY; SOLID-PHASE SYNTHESIS; SIGNAL TRANSDUCTION; AMINO-ACIDS; ORTHO-PHTHALDIALDEHYDE; POLYOMA-VIRUS; TYROSINE; TRANSFORMATION; RECEPTOR AB Using the association between the pp60c-src/polyoma virus middle T antigen (mT) complex and phosphatidylinositol 3'-kinase (PI 3-kinase) as a prototype for phosphoprotein-SH2 domain interactions, we tested whether a nonhydrolyzable phosphonopeptide would inhibit association. (Phosphonomethyl)-phenylalanine (Pmp) is a nonnatural analogue of phosphotyrosine in which the >C-O-PO3H2 moiety is replaced by >C-CH2-PO3H2. We synthesized a 13 amino acid phosphonopeptide (mT-Pmp315), a related phosphopeptide (mT-pY315), and an unmodified sequence (mT-Y315), all corresponding to the pp60c-src-phosphorylated site of the mT which is within a YMXM motif common to proteins that bind to and activate PI 3-kinase. Only the phosphonopeptide persistently blocked the in vitro association of the baculovirus-expressed pp60c-src/mT complex with cytosolic PI 3-kinase activity. Sustained inhibition of association by the phosphopeptide required the additional presence of vanadate, a potent protein tyrosine phosphatase (PTPase) inhibitor. The phosphopeptide and L-phosphonopeptide bound tightly (K(D) almost-qual-to 10-20 nM) and specifically to isolated SH2 domains of PI 3-kinase p85, demonstrating that the mechanism of inhibited association is competitive binding to PI 3-kinase SH2 domains. We conclude that the appropriate phosphonopeptide sequence inhibits the interaction between a tyrosine-phosphorylated protein and a cognate SH2 domain-containing protein and is resistant to the actions of PTPases. Proteolytically stable phosphonopeptide derivatives should be useful inhibitors of protein-protein interactions when introduced into cells and may provide a basis for the rational design of a new class of chemotherapeutic agent. C1 JOSLIN DIABET CTR,1 JOSLIN PL,BOSTON,MA 02215. BRIGHAM & WOMENS HOSP,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NCI,DEV THERAPEUT PROGRAM,MED CHEM LAB,BETHESDA,MD 20892. RI Burke, Terrence/N-2601-2014 FU NIDDK NIH HHS [DK08366] NR 42 TC 113 Z9 115 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD OCT 20 PY 1992 VL 31 IS 41 BP 9865 EP 9870 DI 10.1021/bi00156a002 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JU511 UT WOS:A1992JU51100002 PM 1382595 ER PT J AU CSERMELY, P KAHN, CR AF CSERMELY, P KAHN, CR TI INSULIN INDUCES THE PHOSPHORYLATION OF DNA-BINDING NUCLEAR PROTEINS INCLUDING LAMINS IN 3T3-F442A SO BIOCHEMISTRY LA English DT Article ID RAT-LIVER; KINASE-C; RESPONSE ELEMENT; IDENTIFICATION; SITES; GENE; ACTIVATION; RECEPTOR; DIFFERENTIATION; TRANSCRIPTION AB Insulin binding to its plasma membrane receptor stimulates a cascade of protein kinases and phosphatases which ultimately affects multiple processes in the membrane, cytosol, and nucleus of the cell, including transcription of specific genes. To gain insight into the relationship between the kinase cascade and the mechanism of insulin-induced nuclear events, we have studied the effect of insulin on the phosphorylation of DNA-binding nuclear proteins in differentiated NIH-3T3-F442A adipocytes. Insulin induced the phosphorylation of seven DNA-binding proteins: pp34, pp40, pp48, pp62, pp64, pp66, and pp72. The half-maximal response was observed at 10-30 min and reached its maximum at 60 min. The insulin-induced phosphorylation of each of these proteins was dose-dependent with ED50s of 2-10 nM. The phosphorylation of pp62, pp64, and pp72 took place on serine residues. On the basis of immunoprecipitation and immunoblotting experiments with anti-lamin antibodies, we found that the insulin-induced DNA-binding phosphoproteins pp62, pp64, pp66, and possibly pp48 were related to lamins A and C. The ED50 for insulin-stimulated lamin phosphorylation was approximately 10 nM, and phosphorylation was half-maximal at 30 min. The insulin-dependent phosphorylation of lamins and other DNA-binding proteins (pp34, pp40, and pp72) may play a mediatory role in the long-term effects of insulin. C1 JOSLIN DIABET CTR,1 JOSLIN PL,BOSTON,MA 02215. BRIGHAM & WOMENS HOSP,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. FU FIC NIH HHS [1F05 TW04319-01 B1-5]; NIDDK NIH HHS [DK 33201, DK 36836] NR 52 TC 16 Z9 16 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 OCT 20 PY 1992 VL 31 IS 41 BP 9940 EP 9946 DI 10.1021/bi00156a012 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JU511 UT WOS:A1992JU51100012 PM 1390777 ER PT J AU KAUFMAN, EN JAIN, RK AF KAUFMAN, EN JAIN, RK TI INVITRO MEASUREMENT AND SCREENING OF MONOCLONAL-ANTIBODY AFFINITY USING FLUORESCENCE PHOTOBLEACHING SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE ANTIBODY AFFINITY; BINDING CONSTANT; SCREENING; PHOTOBLEACHING; DIFFUSION; ANTIGEN EXPRESSION ID INTERNAL-REFLECTION-FLUORESCENCE; CELL-SURFACE; CORRELATION SPECTROSCOPY; IMMOBILIZED ANTIGEN; LATERAL TRANSPORT; RECOVERY; TUMORS; DIFFUSION; BINDING; MACROMOLECULES AB Antibody screening is a routine in vitro assay in monoclonal antibody development and production. We have recently adapted the fluorescence photobleaching method to quantify antibody mass transport and binding parameters in bulk solution (Kaufman and Jain, 1990, 1991 ). The present study uses this in vitro method to screen a series of monoclonal antibodies (IgG) developed against the rabbit VX2 carcinoma tumor line. These experiments indicate that the three antibodies recognize distinct epitopes on the tumor, with equilibrium binding constants of 1.3 +/- 0.5, 5.1 +/- 3.6 and 2.0 +/- 1.1 x 10(7) M-1 for the antibodies RVC-184, RVC-626 and RVC-779, respectively. The antibody diffusion coefficient revealed no dependence upon protein concentration or antigen bead volume fraction within the ranges investigated. It was demonstrated experimentally that the interactions conformed to a reaction limited binding model of fluorescence recovery, that the system was at equilibrium, and that non-specific binding due to the fluorescein probe was not significant. Once the non-reactive fraction of antibody is determined, this photobleaching technique does not require perturbation or physical separation of the unbound species. As such, it has many potential applications including in vivo investigation of binding parameters. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,EDWIN L STEELE LAB TUMOR BIOL,BOSTON,MA 02114. CARNEGIE MELLON UNIV,DEPT CHEM ENGN,PITTSBURGH,PA 15213. FU NCI NIH HHS [CA-49742, CA-36902] NR 71 TC 14 Z9 14 U1 0 U2 2 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 OCT 19 PY 1992 VL 155 IS 1 BP 1 EP 17 DI 10.1016/0022-1759(92)90265-U PG 17 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA JZ870 UT WOS:A1992JZ87000001 PM 1383343 ER PT J AU MARTIN, BC WARRAM, JH KROLEWSKI, AS BERGMAN, RN SOELDNER, JS KAHN, CR AF MARTIN, BC WARRAM, JH KROLEWSKI, AS BERGMAN, RN SOELDNER, JS KAHN, CR TI ROLE OF GLUCOSE AND INSULIN RESISTANCE IN DEVELOPMENT OF TYPE-2 DIABETES-MELLITUS - RESULTS OF A 25-YEAR FOLLOW-UP-STUDY SO LANCET LA English DT Article ID BETA-CELL; FAT DISTRIBUTION; PIMA-INDIANS; SENSITIVITY; MUSCLE; NIDDM; TRANSPORTERS; TOLERANCE; INVIVO; RISK AB Type 2 diabetes mellitus is characterised by resistance of peripheral tissues to insulin and a relative deficiency of insulin secretion. To find out which is the earliest or primary determinant of disease, we used a minimum model of glucose disposal and insulin secretion based on intravenous glucose tolerance tests to estimate insulin sensitivity (S(I)), glucose effectiveness (ie, insulin-independent glucose removal rate, S(G)), and first-phase and second-phase beta-cell responsiveness in normoglycaemic offspring of couples who both had type 2 diabetes. 155 subjects from 86 families were followed-up for 6-25 years. More than 10 years before the development of diabetes, subjects who developed the disease had lower values of both S(I) (mean 3.2 [SD 2.4] vs 8.1 [6.7] 10(-3) l min-1 pmol-1 insulin; p < 0.0001) and S(G) (1.6 [0.9] vs 2.3 [1.2] 10(-2) min-1, p < 0.0001) than did those who remained normoglycaemic). For the subjects with both S(I) and SG below the group median, the cumulative incidence of type 2 diabetes during the 25 years was 76% (95% confidence interval 54-99). By contrast, no subject with both S(I) and S(G) above the median developed the disease. Subjects with low S(I)/high S(G) or high S(I)/low S(G) had intermediate risks. Insulin secretion, especially first phase, tended to be increased rather than decreased in this prediabetic phase and was appropriate for the level of insulin resistance. The development of type 2 diabetes is preceded by and predicted by defects in both insulin-dependent and insulin- independent glucose uptake; the defects are detectable when the patients are normoglycaemic and in most cases more than a decade before diagnosis of disease. C1 HARVARD UNIV,SCH PUBL HLTH,JOSLIN DIABET CTR 1 JOSLIN PL,DEPT EPIDEMIOL,DIV RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. UNIV ZURICH,INST SOCIAL & PREVENT MED,CH-8006 ZURICH,SWITZERLAND. UNIV SO CALIF,SCH MED,DEPT PHYSIOL & BIOPHYS,LOS ANGELES,CA 90033. FU NIDDK NIH HHS [DK-29867, DK-33201, DK-36836] NR 31 TC 778 Z9 792 U1 3 U2 28 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD OCT 17 PY 1992 VL 340 IS 8825 BP 925 EP 929 DI 10.1016/0140-6736(92)92814-V PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA JT823 UT WOS:A1992JT82300001 PM 1357346 ER PT J AU MATSUSHIME, H EWEN, ME STROM, DK KATO, JY HANKS, SK ROUSSEL, MF SHERR, CJ AF MATSUSHIME, H EWEN, ME STROM, DK KATO, JY HANKS, SK ROUSSEL, MF SHERR, CJ TI IDENTIFICATION AND PROPERTIES OF AN ATYPICAL CATALYTIC SUBUNIT (P34(PSK-J3)/CDK4) FOR MAMMALIAN-D TYPE-G1 CYCLINS SO CELL LA English DT Article ID STIMULATING FACTOR-I; RETINOBLASTOMA SUSCEPTIBILITY GENE; CELL-CYCLE; SACCHAROMYCES-CEREVISIAE; PROTEIN-KINASE; G1 CYCLINS; M-PHASE; YEAST; EXPRESSION; FAMILY AB Murine D type cyclins associate with a catalytic subunit (p34PSK-J3 with properties distinct from known cyclin-dependent kinases (cdks). Mouse p34PSK-J3 shows less than 50% amino acid identity to p34cdc2, p33cdk2, and p36cdk3, lacks a PSTAIRE motif, and does not bind to p13suc1. Cyclin D1-p34PSK-J3 complexes accumulate in macrophages during G1 and decline in S phase, whereas complexes involving cyclins D2 and D3 form in proliferating T cells. Although histone H1 kinase activity is not detected in cyclin D or PSK-J3 immunoprecipitates, cyclin D-p34PSK-J3 complexes assembled in vitro stably bind and phosphorylate the retinoblastoma gene product (pRb) and an Rb-like protein (p107) but do not interact with pRb mutants that are functionally inactive. Thus, p34PSK-J3 is a cyclin D-regulated catalytic subunit that acts as an Rb (but not H1) kinase. C1 ST JUDE CHILDRENS RES HOSP, DEPT TUMOR CELL BIOL, MEMPHIS, TN 38105 USA. UNIV TENNESSEE, CTR HLTH SCI, COLL MED, DEPT BIOCHEM, MEMPHIS, TN 38163 USA. HARVARD UNIV, SCH MED, DANA FARBER CANC INST, BOSTON, MA 02115 USA. VANDERBILT UNIV, MED CTR, SCH MED, NASHVILLE, TN 37232 USA. RP MATSUSHIME, H (reprint author), ST JUDE CHILDRENS RES HOSP, HOWARD HUGHES MED INST, MEMPHIS, TN 38105 USA. FU NCI NIH HHS [P01-CA21765, R35-CA47064]; NIGMS NIH HHS [R29-GM38793] NR 61 TC 833 Z9 839 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD OCT 16 PY 1992 VL 71 IS 2 BP 323 EP 334 DI 10.1016/0092-8674(92)90360-O PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA JU395 UT WOS:A1992JU39500017 PM 1423597 ER PT J AU ENG, C FARRAYE, FA SHULMAN, LN PEPPERCORN, MA KRAUSS, CM CONNORS, JM STONE, RM AF ENG, C FARRAYE, FA SHULMAN, LN PEPPERCORN, MA KRAUSS, CM CONNORS, JM STONE, RM TI THE ASSOCIATION BETWEEN THE MYELODYSPLASTIC SYNDROMES AND CROHN DISEASE SO ANNALS OF INTERNAL MEDICINE LA English DT Note DE MYELODYSPLASTIC SYNDROMES; CROHN DISEASE; BONE MARROW CELLS; CHROMOSOME ABNORMALITIES; CHROMOSOMES, HUMAN, PAIR-20 ID INFLAMMATORY BOWEL-DISEASE AB The cases of four patients who had both a myelodysplastic syndrome and Crohn disease are reported. The association of these two disorders has not been reported previously. Bone marrow cells from three of the patients showed abnormalities in chromosome 20; in two cases, the abnormalities involved band 20q11. Potential relations between the myelodysplastic syndromes and Crohn disease are discussed. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV MED ONCOL,44 BINNEY ST,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DIV HEMATOL & ONCOL,BOSTON,MA 02115. BETH ISRAEL HOSP,DIV GASTROENTEROL,BOSTON,MA 02215. BETH ISRAEL HOSP,CTR INFLAMMATORY BOWEL DIS,DEPT MED,BOSTON,MA 02215. HARVARD COMMUNITY HLTH PLAN,DIV GASTROENTEROL,BOSTON,MA 02116. HARVARD COMMUNITY HLTH PLAN,DIV MED GENET,BOSTON,MA 02116. HARVARD UNIV,SCH MED,BOSTON,MA 02115. OI Eng, Charis/0000-0002-3693-5145 NR 11 TC 34 Z9 35 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 OCT 15 PY 1992 VL 117 IS 8 BP 661 EP 662 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA JR861 UT WOS:A1992JR86100006 PM 1530197 ER PT J AU WALKER, WA SANDERSON, IR AF WALKER, WA SANDERSON, IR TI EPITHELIAL BARRIER FUNCTION TO ANTIGENS - AN OVERVIEW SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID MILK-SENSITIVE ENTEROPATHY; CELIAC-DISEASE; INTESTINAL PERMEABILITY; VIRAL-ENTERITIS; CROHNS-DISEASE; ELEMENTAL DIET; SMALL BOWEL; HLA-DQ; ABSORPTION; MACROMOLECULES C1 HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,COMBINED PROGRAM PEDIAT GASTROENTEROL & NUTR,BOSTON,MA 02115. CHILDRENS HOSP MED CTR,BOSTON,MA 02115. RP WALKER, WA (reprint author), HARVARD UNIV,SCH MED,DEPT NUTR,BOSTON,MA 02115, USA. NR 40 TC 11 Z9 11 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD OCT 15 PY 1992 VL 664 BP 10 EP 17 DI 10.1111/j.1749-6632.1992.tb39744.x PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KC583 UT WOS:A1992KC58300002 PM 1456642 ER PT J AU MAHIDA, YR CIACCI, C PODOLSKY, DK AF MAHIDA, YR CIACCI, C PODOLSKY, DK TI PEPTIDE GROWTH-FACTORS - ROLE IN EPITHELIAL-LAMINA-PROPRIA CELL-INTERACTIONS SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID INFLAMMATORY BOWEL-DISEASE; HUMAN PEYERS PATCHES; SMOOTH-MUSCLE CELLS; RAT SMALL-INTESTINE; FACTOR-BETA; ANTIGEN PRESENTATION; SECRETORY COMPONENT; FACTOR-ALPHA; TGF-BETA; T-CELLS C1 MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CTR STUDY INFLAMMATORY BOWEL DIS,BOSTON,MA 02114. RP PODOLSKY, DK (reprint author), MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,BOSTON,MA 02114, USA. RI ciacci, carolina/A-2594-2012 OI ciacci, carolina/0000-0002-7426-1145 FU NIDDK NIH HHS [DK41557, P30 DK43351] NR 54 TC 3 Z9 3 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD OCT 15 PY 1992 VL 664 BP 148 EP 156 DI 10.1111/j.1749-6632.1992.tb39757.x PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KC583 UT WOS:A1992KC58300015 PM 1456646 ER PT J AU SHEPHERD, PR GOULD, GW COLVILLE, CA MCCOID, SC GIBBS, EM KAHN, BB AF SHEPHERD, PR GOULD, GW COLVILLE, CA MCCOID, SC GIBBS, EM KAHN, BB TI DISTRIBUTION OF GLUT3 GLUCOSE TRANSPORTER PROTEIN IN HUMAN TISSUES SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID SKELETAL-MUSCLE; BRAIN; EXPRESSION; SEQUENCE; ISOFORMS; FAMILY C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,330 BROOKLINE AVE,BOSTON,MA 02115. HARVARD UNIV,BETH ISRAEL HOSP,HARVARD THORNDIKE LAB,BOSTON,MA 02215. PFIZER INC,GROTON,CT. HARVARD UNIV,SCH MED,BOSTON,MA 02115. UNIV GLASGOW,DEPT BIOCHEM,GLASGOW G12 8QQ,SCOTLAND. FU NIDDK NIH HHS [DK43051] NR 18 TC 87 Z9 90 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD OCT 15 PY 1992 VL 188 IS 1 BP 149 EP 154 DI 10.1016/0006-291X(92)92362-2 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA JU247 UT WOS:A1992JU24700022 PM 1417839 ER PT J AU SALLES, G CHEN, CY REINHERZ, EL SHIPP, MA AF SALLES, G CHEN, CY REINHERZ, EL SHIPP, MA TI CD10/NEP IS EXPRESSED ON THY-1(LOW) B220+ MURINE B-CELL PROGENITORS AND FUNCTIONS TO REGULATE STROMAL CELL-DEPENDENT LYMPHOPOIESIS SO BLOOD LA English DT Article ID LYMPHOBLASTIC-LEUKEMIA ANTIGEN; NEUTRAL ENDOPEPTIDASE 24.11; AMINO-ACID SEQUENCE; TRANSFORMED PRE-B; FETAL BONE-MARROW; MOLECULAR-CLONING; MONOCLONAL-ANTIBODY; STEM-CELL; SUBSTANCE-P; VIRUS C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,IMMUNOBIOL LAB,44 BINNEY ST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. FU NCI NIH HHS [CA49232] NR 59 TC 53 Z9 53 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD OCT 15 PY 1992 VL 80 IS 8 BP 2021 EP 2029 PG 9 WC Hematology SC Hematology GA JT776 UT WOS:A1992JT77600021 PM 1382716 ER PT J AU KREISSMAN, SG GELBER, RD COHEN, HJ CLAVELL, LA LEAVITT, P SALLAN, SE AF KREISSMAN, SG GELBER, RD COHEN, HJ CLAVELL, LA LEAVITT, P SALLAN, SE TI INCIDENCE OF SECONDARY ACUTE MYELOGENOUS LEUKEMIA AFTER TREATMENT OF CHILDHOOD ACUTE LYMPHOBLASTIC-LEUKEMIA SO CANCER LA English DT Article DE ACUTE LYMPHOBLASTIC LEUKEMIA; SECONDARY ACUTE MYELOGENOUS LEUKEMIA; CHEMOTHERAPY; EPIPODOPHYLLOTOXIN ID ACUTE NONLYMPHOCYTIC LEUKEMIA; ACUTE MYELOID-LEUKEMIA; SMALL-CELL-CARCINOMA; HODGKINS-DISEASE; COMBINATION CHEMOTHERAPY; MYELODYSPLASTIC SYNDROME; INTENSIVE ASPARAGINASE; ALKYLATING-AGENTS; BONE-MARROW; THERAPY AB Background. Recent reports of secondary acute myelogenous leukemia (AML) occuring in children previously treated for acute lymphoblastic leukemia (ALL) prompted a review of patients with ALL treated at the Dana Farber Cancer Institute consortium (DFCI) between 1973 and 1987. Seven hundred fifty-two of 779 children treated for ALL entered complete remission. The mean follow-up time for the 752 patients was 4.4 years. Two children had AML develop 12 and 13 months after the diagnosis of ALL, respectively. Methods. The estimated overall risk of secondary AML was calculated for the patient population as instances per 1000 patient-years of follow-up. This was compared with recent reported cases from another institution. Results. The estimated overall risk of secondary AML was 0.61 instances per 1000 patient-years of follow-up (95% confidence interval: 0.15, 4.4). The difference between the risk of 0.61 among DFCI patients versus previously reported risk of 5.8 among a differently treated group of patients with ALL was statistically significant (P = 0.0008). No epipodophyllotoxin was used in the patients in the DFCI consortium. In contrast, an epipodophyllotoxin was used in 12 of 13 previously reported patients who had secondary AML develop. Conclusions. The authors concluded that the use of epipodophyllotoxins may be associated with an increased risk of having secondary AML develop in patients with ALL. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PEDIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT BIOSTAT,BOSTON,MA 02115. UNIV PUERTO RICO,DEPT PEDIAT ONCOL,SAN JUAN,PR 00936. CHILDRENS HOSP MED CTR,DIV HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,BOSTON,MA 02115. UNIV ROCHESTER,DEPT PEDIAT,ROCHESTER,NY 14627. UNIV ROCHESTER,CTR CANC,ROCHESTER,NY 14627. FU NCI NIH HHS [CA 06516, CA 34183] NR 41 TC 37 Z9 37 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD OCT 15 PY 1992 VL 70 IS 8 BP 2208 EP 2213 DI 10.1002/1097-0142(19921015)70:8<2208::AID-CNCR2820700832>3.0.CO;2-P PG 6 WC Oncology SC Oncology GA JT859 UT WOS:A1992JT85900031 PM 1394053 ER PT J AU KORNBLITH, AB ANDERSON, J CELLA, DF TROSS, S ZUCKERMAN, E CHERIN, E HENDERSON, E WEISS, RB COOPER, MR SILVER, RT LEONE, L CANELLOS, GP GOTTLIEB, A HOLLAND, JC AF KORNBLITH, AB ANDERSON, J CELLA, DF TROSS, S ZUCKERMAN, E CHERIN, E HENDERSON, E WEISS, RB COOPER, MR SILVER, RT LEONE, L CANELLOS, GP GOTTLIEB, A HOLLAND, JC TI HODGKIN DISEASE SURVIVORS AT INCREASED RISK FOR PROBLEMS IN PSYCHOSOCIAL ADAPTATION SO CANCER LA English DT Article DE HODGKIN DISEASE; CANCER SURVIVORS; PSYCHOSOCIAL ADAPTATION ID CANCER SURVIVORS; ILLNESS; CHEMOTHERAPY; CHILDHOOD; QUALITY; SCALE AB Background. The long-term psychosocial adaptations of 273 survivors of advanced Hodgkin disease were assessed to determine the nature and extent of problems experienced and to identify those at high risk for maladaptation. Methods. Hodgkin disease survivors were identified who initially had been treated in clinical trials within the Cancer and Leukemia Group B from 1966 to 1986, were currently disease free, and had completed treatment for a minimum of 1 year. All survivors had advanced Hodgkin disease (with disease diagnosed at a mean age of 28 years). Survivors were at a mean age of 37 years at the time of interview (6.3 years after treatment completion), and 60% were male. Survivors were interviewed over the telephone 7-10 days after questionnaires were mailed to them concerning their psychological, social, vocational, and sexual functioning. Results. Psychological distress was found to be elevated by one standard deviation (SD) above that of healthy subjects on the Brief Symptom Inventory, and 22% met the criterion suggested for a psychiatric diagnosis. In addition, the following problems were reported by survivors to be a consequence of having had Hodgkin disease: denial of life (31%) and health (22%) insurance, sexual problems (37%), conditioned nausea in response to reminders of chemotherapy (39%), and a negative socioeconomic effect (36%). Survivors found to be at high risk for maladaptation were: men earning less than $15,000 per year or who were currently unemployed; unmarried individuals; those with serious illnesses since treatment completion; and those who were less educated. Conclusions. These findings suggest that including a routine assessment of these factors would help to target survivors in need of additional evaluation and treatment. C1 UNIV NEBRASKA,MED CTR,CTR BIOSTAT,CANC & LEUKEMIA GRP B,OMAHA,NE 68105. RUSH PRESBYTERIAN ST LUKES MED CTR,CHICAGO,IL 60612. UNIV MED & DENT NEW JERSEY,NEWARK,NJ 07103. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,WINSTON SALEM,NC 27103. NEW YORK HOSP,NEW YORK,NY 10021. RHODE ISL HOSP,PROVIDENCE,RI 02902. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NEW YORK STATE DEPT HLTH,ROSWELL PK MEM INST,BUFFALO,NY 14263. WALTER REED ARMY MED CTR,WASHINGTON,DC 20307. SUNY HLTH SCI CTR,SYRACUSE,NY. RP KORNBLITH, AB (reprint author), MEM SLOAN KETTERING CANC CTR,PSYCHIAT SERV,1275 YORK AVE,NEW YORK,NY 10021, USA. FU NCI NIH HHS [CA 32291, CA 03927, CA31946] NR 41 TC 108 Z9 108 U1 3 U2 4 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 OCT 15 PY 1992 VL 70 IS 8 BP 2214 EP 2224 DI 10.1002/1097-0142(19921015)70:8<2214::AID-CNCR2820700833>3.0.CO;2-X PG 11 WC Oncology SC Oncology GA JT859 UT WOS:A1992JT85900032 PM 1394054 ER PT J AU WAXMAN, DJ SUNDSETH, SS SRIVASTAVA, PK LAPENSON, DP AF WAXMAN, DJ SUNDSETH, SS SRIVASTAVA, PK LAPENSON, DP TI GENE-SPECIFIC OLIGONUCLEOTIDE PROBES FOR ALPHA, MU, PI, AND MICROSOMAL RAT GLUTATHIONE S-TRANSFERASES - ANALYSIS OF LIVER TRANSFERASE EXPRESSION AND ITS MODULATION BY HEPATIC ENZYME INDUCERS AND PLATINUM ANTICANCER DRUGS SO CANCER RESEARCH LA English DT Article ID SENSITIVE CELL-LINES; AMINO-ACID SEQUENCE; NUCLEOTIDE-SEQUENCE; MESSENGER-RNAS; CDNA CLONE; ALKYLATING-AGENTS; MULTIGENE FAMILY; TUMOR-CELLS; RESISTANCE; SUBUNIT AB Glutathione S-transferases (GSTs) play an important role in the detoxification of diverse electrophilic chemicals, including anticancer drugs. Gene-specific oligonucleotide probes were developed to monitor the expression of individual GST mRNAs in livers of adult male rats treated with drugs and other chemical modulators of GST expression. Northern blot analysis of total liver RNA using probes specific for individual GSTs belonging to classes alpha (GSTs Ya1, Ya2, Yc), mu (GSTs Yb1, Yb2, Yb3), pi (GST Yp), and GST(ms) demonstrated the expression in liver of all but Yp mRNA. Kidney GST expression was at least as high as that in liver for GSTs Ya1, Yc, and Yp, while it was substantially lower but still detectable for GSTs Ya2, Yb2, and GST(ms). Several of the liver GST class alpha mRNAs, in particular Ya2, were inducible by pretreatment of rats with phenobarbital or isosafrole. In contrast, dexamethasone preferentially induced Yb1, Yb2, and Ya2, while two other inducers of liver drug metabolism, isoniazid and clofibrate, were less effective with respect to GST induction. GST(ms) mRNA was induced to a small extent or not at all by the agents tested. Treatment of adult male rats with the anticancer drug cisplatin increased liver expression of GST Yc mRNA and suppressed Ya1 mRNA levels with little or no major effect on several other GST mRNAs. Western blot analysis of liver cytosols prepared from the cisplatin-treated rats revealed corresponding changes in GST Yc and Ya protein levels. Comparable changes in liver GST Ya1 and Yc expression were effected by the cisplatin analogue iproplatin but not by carboplatin or transplatin. This pattern of response to these platinum drugs is comparable to that seen with respect to platinum drug-induced gonadal toxicity and modulation of liver cytochrome P450 expression, suggesting a common mechanistic basis for these diverse effects of platinum anticancer drugs on hepatic enzymes of drug metabolism. Together, these studies demonstrate the utility of oligonucleotide probes for phenotyping liver tissue for the expression of GST enzymes that can contribute to anticancer drug metabolism and resistance. They also raise the possibility of drug-drug interactions involving cisplatin and alkylating agent anticancer drugs that can be metabolized in liver by alpha-class GSTs. C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM & 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. NR 51 TC 42 Z9 43 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 15 PY 1992 VL 52 IS 20 BP 5797 EP 5802 PG 6 WC Oncology SC Oncology GA JU458 UT WOS:A1992JU45800035 PM 1394205 ER PT J AU BAXTER, LT FAN, Y JAIN, RK AF BAXTER, LT FAN, Y JAIN, RK TI PHARMACOKINETIC ANALYSIS OF THE PERIVASCULAR DISTRIBUTION OF BIFUNCTIONAL ANTIBODIES AND HAPTENS - COMPARISON WITH EXPERIMENTAL-DATA SO CANCER RESEARCH LA English DT Note ID NEOPLASTIC TISSUES; TRANSPORT; TUMORS; MACROMOLECULES; FLUID; MODEL AB A mathematical model is developed to describe the concentration profiles around individual tumor blood vessels for two-step approaches to cancer treatment. The model incorporates plasma pharmacokinetics, interstitial diffusion, reversible binding between antibody and hapten and between antibody and tumor-associated antigens, and physiological parameters to evaluate present experimental approaches and to suggest new guidelines for the effective use of two-step approaches. Results show considerable interaction between the binding kinetics, initial drug doses, and antigen density, with optimal parameter ranges depending on the desired goal: treatment or detection. The hapten concentration in tumors was found to be nonuniform because of specific binding to antibodies. While binding of the hapten to the bifunctional antibody is necessary for improved retention, too large a binding affinity may lead to very poor penetration of the hapten into regions far away from blood vessels. The time delay between antibody and hapten injection was found to be an important parameter. Longer time delays were found to be advantageous, subject to constraints such as internalization of the antibody and tumor growth during treatment. A proper combination of initial doses for the two species was also seen to be crucial for maximum effectiveness. Comparison of the model with the experimental data of Le Doussal et al. (Cancer Res., 51: 6650-6655, 1991) and Stickney et al. (Cancer Res., 50: 3445-3452, 1990) suggests two novel, yet testable, hypotheses: (a) the early pharmacokinetics of low molecular weight agents can have an important effect on later concentrations using two-step approaches; and (b) metabolism may play an important role in reducing concentrations in the tumor and tumor:plasma concentration ratios. These results should help in the effective design of two-step strategies. RP BAXTER, LT (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,EDWIN L STEELE LAB,BOSTON,MA 02114, USA. RI Yuan, Fan/A-1287-2011 FU NCI NIH HHS [CA-49792, CA-36902] NR 22 TC 60 Z9 61 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 OCT 15 PY 1992 VL 52 IS 20 BP 5838 EP 5844 PG 7 WC Oncology SC Oncology GA JU458 UT WOS:A1992JU45800044 PM 1394212 ER PT J AU PAN, YT KAMITANI, T BHUVANESWARAN, C HALLAQ, Y WARREN, CD YEH, ETH ELBEIN, AD AF PAN, YT KAMITANI, T BHUVANESWARAN, C HALLAQ, Y WARREN, CD YEH, ETH ELBEIN, AD TI INHIBITION OF GLYCOSYLPHOSPHATIDYLINOSITOL ANCHOR FORMATION BY MANNOSAMINE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PHOSPHATIDYLINOSITOL MEMBRANE ANCHOR; VARIANT SURFACE GLYCOPROTEIN; T-CELL RECEPTOR; GLYCOSYL-PHOSPHATIDYLINOSITOL; TRYPANOSOMA-BRUCEI; TAP TRANSCRIPTION; LINKAGE MUTANTS; BIOSYNTHESIS; THY-1; ACTIVATION AB Many eucaryotic cell surface proteins are anchored to the plasma membrane via a glycosylphosphatidylinositol (GPI), of which the core region is highly conserved from protozoa to mammalian cells. Previous studies (Lisanti, M. P., Field, M. C., Caras, I. W., Menon, A. K., and Rodiguez-Boulan, E. (1991) EMBO J. 10, 1969-1977) showed that mannosamine blocked the expression of a recombinant GPI-anchored protein in Madin-Darby canine kidney cells and converted this protein to an unpolarized secretory product. In the present study, we examined the effect of mannosamine on the formation of the glycan portion of the GPI anchor precursors. This amino sugar inhibited the incorporation of mannose into the glycan portion, and the inhibition was dose-dependent. Mannosamine was shown to be incorporated into the glycan as mannosamine, probably mostly in the second mannose position and thereby to block the further addition of mannose and other anchor components. The products formed in the presence of this drug were characterized by gel filtration and high resolution TLC both before and after deamination with nitrous acid and dephosphorylation by HF. Galactosamine and trehalosamine were inactive in this system, whereas glucosamine also inhibited mannose incorporation into GPI intermediates. C1 UNIV ARKANSAS MED SCI HOSP,DEPT BIOCHEM & MOLEC BIOL,LITTLE ROCK,AR 72205. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,BOSTON,MA 02114. FU NHLBI NIH HHS [HL-45851]; NIDDK NIH HHS [DK-21800, DK-40930] NR 25 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 OCT 15 PY 1992 VL 267 IS 29 BP 21250 EP 21255 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JT978 UT WOS:A1992JT97800114 PM 1400435 ER PT J AU REPKE, H BARBER, E ULBRICHT, S BUCHNER, K HUCHO, F KOPP, R SCHOLZ, H RUDD, CE HASELTINE, WA AF REPKE, H BARBER, E ULBRICHT, S BUCHNER, K HUCHO, F KOPP, R SCHOLZ, H RUDD, CE HASELTINE, WA TI GANGLIOSIDE-INDUCED CD4 ENDOCYTOSIS OCCURS INDEPENDENT OF SERINE PHOSPHORYLATION AND IS ACCOMPANIED BY DISSOCIATION OF P56(LCK) SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PROTEIN-TYROSINE KINASE; HUMAN LYMPHOCYTES-T; SELECTIVE MODULATION; SIGNAL TRANSDUCTION; P56LCK; RECEPTOR; COMPLEX; CELLS; ASSOCIATION; ACTIVATION AB Gangliosides induce a selective and complete modulation of CD4 from the surface of T cells. CD4 down-modulation occurs by CD4 endocytosis. This process is independent of serine phosphorylation of the cytoplasmic tail of CD4 and does not require the association between the tyrosine protein kinase p56lck and the cytoplasmic tail of CD4. Ganglioside-induced CD4 endocytosis is accompanied by the loss of p56lck activity associated with CD4. Sequential immunoprecipitation analysis using an anti-CD4 antibody and an anti-p56lck antiserum showed that this is caused by the dissociation of the enzyme from the cytoplasmic tail of CD4. The kinetics of p56lck dissociation after ganglioside treatment is identical to that of CD4 endocytosis, suggesting that p56lck is displaced in the process of endosome formation. The results indicate that CD4 endocytosis alone can cause the dissociation of the p56lck complex without the requirement for CD4 phosphorylation. C1 HARVARD UNIV, SCH MED, DANA FARBER CANC INST, DIV TUMOR IMMUNOL, BOSTON, MA 02115 USA. FREE UNIV BERLIN, INST BIOCHEM, W-1000 BERLIN 33, GERMANY. CENT INST MOLEC BIOL, O-1040 BERLIN, GERMANY. HUMBOLDT UNIV, BEREICH MED CHARITE, SCH MED, INST VIROL, O-1040 BERLIN, GERMANY. RP REPKE, H (reprint author), HARVARD UNIV, SCH MED, DANA FARBER CANC INST, DIV HUMAN RETROVIROL, 44 BINNEY ST, BOSTON, MA 02115 USA. FU NCI NIH HHS [P30 CA 06516]; NIAID NIH HHS [AI24845] NR 31 TC 38 Z9 38 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 15 PY 1992 VL 149 IS 8 BP 2585 EP 2591 PG 7 WC Immunology SC Immunology GA JT982 UT WOS:A1992JT98200007 PM 1401895 ER PT J AU HONG, X TONG, IL DEFOUGEROLLES, AR SPRINGER, TA AF HONG, X TONG, IL DEFOUGEROLLES, AR SPRINGER, TA TI ISOLATION, CHARACTERIZATION, AND EXPRESSION OF MOUSE ICAM-2 COMPLEMENTARY AND GENOMIC DNA SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INTERCELLULAR-ADHESION MOLECULE-1; PHORBOL ESTER; CHROMOSOMAL LOCATION; SUPERGENE FAMILIES; COUNTER-RECEPTOR; GENE-EXPRESSION; IMMUNE-SYSTEM; LFA-1; CLONING; IMMUNOGLOBULIN AB Intercellular adhesion molecule-2 (ICAM-2), a cell surface glycoprotein, is a second counter-receptor for lymphocyte function-associated Ag-1 (LFA-1). We report here the isolation and characterization of the cDNA and the gene that encode murine ICAM-2 (Accession numbers X65493 and X65490, respectively). The deduced sequence of the cDNA has 60% amino acid identity with its human counterpart and has the same expression pattern in cells and tissues. Furthermore, COS cells transfected with mouse ICAM-2 complementary and genomic DNA bind to purified human LFA-1, demonstrating the conservation of the function of ICAM-2 as a ligand for LFA-1 and conservation across species of sequences that are critical for binding to human LFA-1. COS cells transfected with the ICAM-2 cDNA do not react with mAb PA3, previously suggested to define ICAM-2 in the mouse. The mouse ICAM-2 gene was isolated and its structural organization determined. The gene is present in a single copy in the mouse genome and contains four exons spanning about 5.0 kb of DNA. The exon/intron architecture correlates to the structural domains of the protein and resembles that of other Ig superfamily members. The gene for ICAM-2, which is constitutively expressed in endothelial cells, has several conserved sequence motifs in its promoter region, including a direct repeat, and lacks transcription factor-binding sites present in the ICAM-1 gene, which is inducible in endothelial cells. C1 CTR BLOOD RES,800 HUNTINGTON AVE,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. NR 43 TC 0 Z9 0 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 OCT 15 PY 1992 VL 149 IS 8 BP 2650 EP 2655 PG 6 WC Immunology SC Immunology GA JT982 UT WOS:A1992JT98200016 ER PT J AU BLUMENTHAL, D EPSTEIN, AM AF BLUMENTHAL, D EPSTEIN, AM TI THE UNFINISHED BUSINESS OF PHYSICIAN-PAYMENT REFORM - REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. RP BLUMENTHAL, D (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 OCT 15 PY 1992 VL 327 IS 16 BP 1177 EP 1178 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA JT153 UT WOS:A1992JT15300032 ER PT J AU WEST, AB ROBERTS, TM KOLODNER, RD AF WEST, AB ROBERTS, TM KOLODNER, RD TI REGULATION OF THE REVERSE-TRANSCRIPTASE OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 BY DNTPS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE DNA POLYMERASE; NONCOMPETITIVE INHIBITION; SUBSTRATE INHIBITION; ALLOSTERIC REGULATION; AIDS ID LYMPHADENOPATHY-ASSOCIATED VIRUS; AIDS VIRUS; RNASE-H; DNA; 3'-AZIDO-3'-DEOXYTHYMIDINE; EXPRESSION; INHIBITOR; HIV; IDENTIFICATION; PROCESSIVITY AB Reverse transcriptase (RNA-directed DNA polymerase, EC 2.7.7.49) of human immunodeficiency virus type 1 has been examined with respect to the steady-state kinetics of polymerization of dNTPs into product DNA. With dNTPs as variable substrate, the kinetics of polymerization deviated from standard Michaelis-Menten kinetics. Substrate inhibition was observed at high substrate concentrations and negative cooperativity was seen at lower substrate concentrations. Examination of incorporation of substrate dNMPs in the presence of nucleotides not complementing the template demonstrated that dNTPs may act as noncompetitive inhibitors, as well as substrate. The K(i) of the enzyme for dNTPs was 104 muM. A working model is presented that accounts for the substrate inhibition. In this model, the reverse transcriptase is a multisubunit holoenzyme, where noncompetitive inhibition is mediated by one subunit binding nucleotide and down-regulating the enzymatically active 64-kDa subunit. With additional assumptions, this model can accommodate the negative cooperativity observed. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. RP WEST, AB (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELLULAR & MOLEC BIOL,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA06516]; NIAID NIH HHS [AI28691, AI27336] NR 40 TC 9 Z9 9 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 OCT 15 PY 1992 VL 89 IS 20 BP 9720 EP 9724 DI 10.1073/pnas.89.20.9720 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JT977 UT WOS:A1992JT97700073 PM 1384060 ER PT J AU VANDERSTRAETEN, D RODRIGUESPOUSADA, RA VILLARROEL, R HANLEY, S GOODMAN, HM VANMONTAGU, M AF VANDERSTRAETEN, D RODRIGUESPOUSADA, RA VILLARROEL, R HANLEY, S GOODMAN, HM VANMONTAGU, M TI CLONING, GENETIC-MAPPING, AND EXPRESSION ANALYSIS OF AN ARABIDOPSIS-THALIANA GENE THAT ENCODES 1-AMINOCYCLOPROPANE-1-CARBOXYLATE SYNTHASE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE DEVELOPMENT; ETHYLENE; GENE REGULATION; RESTRICTION FRAGMENT LENGTH POLYMORPHISM MAPPING; STRESS ID POLYMERASE CHAIN-REACTION; PLANT GENES; SEQUENCE; PROTEIN; TRANSCRIPTS; CUCURBITA; BINDING; INVIVO; POTATO AB A genomic clone of one member of the Arabidopsis thaliana (L.) Heynh. 1-aminocyclopropane-1-carboxylate (ACC) synthase (S-adenosyl-L-methionine methylthioadenosine-lyase, EC 4.4.1.14) gene family (AT-ACC1) was isolated and sequenced. A region of homology was found in the 5'-untranslated region with the promoter of a zucchini and a tomato ACC synthase gene. Comparison of its primary structure with other ACC synthases revealed conservation of seven peptide regions as well as similarity with 11 amino acids of the catalytic site of aminotransferases. Genomic DNA gel blotting suggested the existence of an ACC synthase multigene family in Arabidopsis, possibly with three other members, none of which is very closely related to AT-ACC1. The existence of at least one other gene was confirmed by the isolation of a cDNA (AT-ACC2) from a flower-specific cDNA library. The AT-ACC1 gene was mapped on the Arabidopsis restriction fragment length polymorphism map and is located on the top of chromosome 1. This position does not correspond to any known mutation on the genetic map. Expression of the AT-ACC1 gene was studied by reverse transcription-PCR on total RNA. Messenger accumulation was strong in young leaves and flowers. The gene was not induced by wounding of young leaves or in seedlings in the presence of auxin. Ethylene exposure of mature plants led to an induction of AT-ACC1 gene expression. It is suggested that AT-ACC1 protein has a role in developmental control of ethylene synthesis. C1 STATE UNIV GHENT,GENET LAB,KL LEDEGANCKSTR 35,B-9000 GENT,BELGIUM. MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. RI Van Der Straeten, Dominique/E-7385-2016 OI Van Der Straeten, Dominique/0000-0002-7755-1420 NR 34 TC 77 Z9 80 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 OCT 15 PY 1992 VL 89 IS 20 BP 9969 EP 9973 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JT977 UT WOS:A1992JT97700124 PM 1357670 ER PT J AU APITZCASTRO, R BADIMON, JJ BADIMON, L AF APITZCASTRO, R BADIMON, JJ BADIMON, L TI EFFECT OF AJOENE, THE MAJOR ANTIPLATELET COMPOUND FROM GARLIC, ON PLATELET THROMBUS FORMATION SO THROMBOSIS RESEARCH LA English DT Article DE AJOENE; THROMBUS FORMATION; VESSEL WALL; PLATELETS ID VIII-VONWILLEBRAND FACTOR; ARTERY SUBENDOTHELIUM; VESSEL WALL; SHEAR RATE; AGGREGATION; DEPOSITION; BLOOD; COLLAGEN; ADHESION; FIBRINOGEN AB Ajoene, (E,Z)-4,5,9-trithiadodeca-1,6,11-triene 9-oxide, is a potent antiplatelet compound isolated from alcoholic extracts of garlic (Allium sativum). Ajoene reversibly inhibits in vitro platelet aggregation as well as release reaction induced by all known agonists. We used a well characterized cylindrical perfusion chamber to study the effect of ajoene on platelet deposition onto physiological substrates such as pig aortic subendothelium and tunica media as a model of mildly and severely damaged vessel wall respectively. Experiments were performed under flow conditions of high and low shear rate that mimic laminar blood flow in small and medium size arteries (1690 sec-1 and 212 sec-1) . Our results indicate that ajoene prevents thrombus formation both at low and high shear rate in citrated whole blood. The inhibitory effect of ajoene on platelet-thrombus formation seems to be dependent on its inhibition of fibrinogen binding, since significantly higher concentrations of ajoene are needed to affect von Willebrand factor binding to GPIIb/IIIa receptors. Further, ajoene does not impair Ristocetin-induced platelet agglutination, mediated by GPIb. Our results suggest that ajoene may be useful for the acute prevention of thrombus formation induced by vascular damage. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114. IVIC,TROMBOSIS EXPTL LAB,CARACAS 1020A,VENEZUELA. RI BADIMON, LINA/O-4711-2014 OI BADIMON, LINA/0000-0002-9162-2459 FU NHLBI NIH HHS [HL-38933, HL-38393, HL-39840] NR 21 TC 51 Z9 52 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0049-3848 J9 THROMB RES JI Thromb. Res. PD OCT 15 PY 1992 VL 68 IS 2 BP 145 EP 155 DI 10.1016/0049-3848(92)90030-E PG 11 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA JY934 UT WOS:A1992JY93400005 PM 1475777 ER PT J AU SURMAN, OS AF SURMAN, OS TI DIAGNOSIS OF BRAIN-DEATH AND ORGAN DONATION 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 2 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 OCT 14 PY 1992 VL 268 IS 14 BP 1859 EP 1859 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA JR439 UT WOS:A1992JR43900028 PM 1404709 ER PT J AU YARMUSH, ML TONER, M DUNN, JCY ROTEM, A HUBEL, A TOMPKINS, RG AF YARMUSH, ML TONER, M DUNN, JCY ROTEM, A HUBEL, A TOMPKINS, RG TI HEPATIC TISSUE ENGINEERING - DEVELOPMENT OF CRITICAL TECHNOLOGIES SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID INTRACELLULAR ICE FORMATION; ISOLATED RAT HEPATOCYTES; SANDWICH CONFIGURATION; CRYOPRESERVATION; CULTURE; SYSTEM; LIVER; CELLS; RECOVERY C1 MASSACHUSETTS GEN HOSP,GASTROENTEROL SERV,BOSTON,MA 02114. RP YARMUSH, ML (reprint author), RUTGERS STATE UNIV,DEPT CHEM & BIOCHEM ENGN,PISCATAWAY,NJ 08854, USA. NR 35 TC 100 Z9 100 U1 0 U2 3 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD OCT 13 PY 1992 VL 665 BP 238 EP 252 DI 10.1111/j.1749-6632.1992.tb42588.x PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JV459 UT WOS:A1992JV45900020 PM 1416606 ER PT J AU NITSCH, RM SLACK, BE WURTMAN, RJ GROWDON, JH AF NITSCH, RM SLACK, BE WURTMAN, RJ GROWDON, JH TI RELEASE OF ALZHEIMER AMYLOID PRECURSOR DERIVATIVES STIMULATED BY ACTIVATION OF MUSCARINIC ACETYLCHOLINE-RECEPTORS SO SCIENCE LA English DT Article ID PROTEIN KINASE-C; DISEASE; DOMAIN; PHOSPHORYLATION; LOCALIZATION; CLEAVAGE; SUBTYPES; PEPTIDE AB Altered processing of the amyloid precursor protein (APP) is a central event in the formation of amyloid deposits in the brains of individuals with Alzheimer's disease. To investigate whether cellular APP processing is controlled by cell-surface neurotransmitter receptors, human embryonic kidney (293) cell lines were transfected with the genes for human brain muscarinic acetylcholine receptors. Stimulation of m1 and m3 receptor subtypes with carbachol increased the basal release of APP derivatives within minutes of treatment, indicating that preexisting APP is released in response to receptor activation. Receptor-activated APP release was blocked by staurosporine, suggesting that protein kinases mediate neurotransmitter receptor-controlled APP processing. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP NITSCH, RM (reprint author), MIT,DEPT BRAIN & COGNIT SCI,E25-604,CAMBRIDGE,MA 02139, USA. NR 33 TC 771 Z9 787 U1 1 U2 11 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD OCT 9 PY 1992 VL 258 IS 5080 BP 304 EP 307 DI 10.1126/science.1411529 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JR860 UT WOS:A1992JR86000036 PM 1411529 ER PT J AU WALSH, C CEPKO, CL RYDER, EF CHURCH, GM TABIN, C AF WALSH, C CEPKO, CL RYDER, EF CHURCH, GM TABIN, C TI THE DISPERSION OF NEURONAL CLONES ACROSS THE CEREBRAL-CORTEX - RESPONSE SO SCIENCE LA English DT Article C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. HOWARD HUGHES MED INST,BOSTON,MA. RP WALSH, C (reprint author), HARVARD UNIV,SCH MED,DEPT GENET,200 LONGWOOD AVE,BOSTON,MA 02115, USA. NR 5 TC 19 Z9 19 U1 1 U2 3 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD OCT 9 PY 1992 VL 258 IS 5080 BP 317 EP 320 DI 10.1126/science.258.5080.317-a PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JR860 UT WOS:A1992JR86000041 ER PT J AU QUINN, DA THOMPSON, BT TERRIN, ML THRALL, JH ATHANASOULIS, CA MCKUSICK, KA STEIN, PD HALES, CA AF QUINN, DA THOMPSON, BT TERRIN, ML THRALL, JH ATHANASOULIS, CA MCKUSICK, KA STEIN, PD HALES, CA TI A PROSPECTIVE INVESTIGATION OF PULMONARY-EMBOLISM IN WOMEN AND MEN SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ORAL-CONTRACEPTIVES; VENOUS THROMBOEMBOLISM; DISEASE; SAFETY AB Objective.-The aim of this study was to compare, in women and men suspected of pulmonary embolism, the frequency, risk factor's, diagnosis, and presentation of pulmonary embolism as well as the accuracy of the ventilation/perfusion scan (V/Q scan) as a diagnostic tool. Design.-Data were collected during a prospective study (the Prospective Investigation of Pulmonary Embolism Diagnosis) to establish the accuracy of the V/Q scan compared with pulmonary angiograms. Setting.-Six tertiary medical centers in Massachusetts, Michigan, Connecticut, Pennsylvania, and North Carolina. Participants.-Patients suspected of pulmonary embolism for whom a request was made for a V/Q scan or pulmonary angiogram (496 women and 406 men). Results.-Women 50 years old and under had a decreased frequency of pulmonary embolism compared with men of that age (16% vs 32%), but there was no difference in patients over 50 years old (Breslow-Day test, P<.01). Risk factors for pulmonary embolism, the usefulness of the V/Q scan, and 1-year mortality were not different for women and men. Estrogen use in women was not associated with an increased frequency of pulmonary embolism, except in women using oral contraceptives who had undergone surgery within 3 months; four of five (80%) had emboli compared with four of 28 (14%) age-matched surgical patients not using estrogens (P<.01). Conclusion.-Women 50 years old and under (even young women using oral contraceptives) who were suspected of having pulmonary emboli and were enrolled in the Prospective investigation of Pulmonary Embolism Diagnosis study had a smaller frequency of pulmonary embolism than men of that age, The risk factors for pulmonary embolism were the same for women and men, except that women using oral contraceptives had an increased risk of pulmonary embolism following surgery. Although the V/Q scan was a useful tool in the preliminary evaluation for pulmonary embolism in these women, a pulmonary angiogram was often needed for accurate diagnosis. C1 MASSACHUSETTS GEN HOSP,DEPT MED,PULM CRIT CARE UNIT,BULFINCH 1,FRUIT ST,BOSTON,MA 02114. HENRY FORD HEART & VASC INST,DETROIT,MI. MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. MARYLAND MED RES INST,BALTIMORE,MD. FU NHLBI NIH HHS [HR 34013, N01-HR 34008, HR 34009] NR 17 TC 85 Z9 85 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD OCT 7 PY 1992 VL 268 IS 13 BP 1689 EP 1696 DI 10.1001/jama.268.13.1689 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA JQ376 UT WOS:A1992JQ37600030 PM 1527878 ER PT J AU GLICK, JH GELBER, RD GOLDHIRSCH, A SENN, HJ AF GLICK, JH GELBER, RD GOLDHIRSCH, A SENN, HJ TI MEETING HIGHLIGHTS - ADJUVANT THERAPY FOR PRIMARY BREAST-CANCER SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material C1 OSPED CIVICO,LUGANO,SWITZERLAND. KANTONSSPITAL,CTR ONCOL,CH-9006 ST GALLEN,SWITZERLAND. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. RP GLICK, JH (reprint author), UNIV PENN,CTR CANC,6 PENN TOWER,3400 SPRUCE ST,PHILADELPHIA,PA 19104, USA. NR 25 TC 66 Z9 66 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 OCT 7 PY 1992 VL 84 IS 19 BP 1479 EP 1485 DI 10.1093/jnci/84.19.1479 PG 7 WC Oncology SC Oncology GA JQ627 UT WOS:A1992JQ62700014 PM 1433332 ER PT J AU ODA, A DRUKER, BJ SMITH, M SALZMAN, EW AF ODA, A DRUKER, BJ SMITH, M SALZMAN, EW TI ASSOCIATION OF PP60SRC WITH TRITON X-100-INSOLUBLE RESIDUE IN HUMAN BLOOD-PLATELETS REQUIRES PLATELET-AGGREGATION AND ACTIN POLYMERIZATION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GLYCOPROTEIN-IIB-IIIA; PROTEIN-TYROSINE PHOSPHORYLATION; COLONY-STIMULATING FACTOR; ROUS-SARCOMA VIRUS; SRC GENE-PRODUCT; MONOCLONAL-ANTIBODIES; FIBRINOGEN RECEPTOR; COMMON SET; THROMBIN; CYTOSKELETON AB Protein-tyrosine phosphorylation during platelet activation is inhibited under conditions that inhibit platelet binding of fibrinogen and aggregation. We suggested that pp60src, a major platelet tyrosine kinase, or its protein substrates might become associated with the cytoskeleton upon platelet stimulation, and that this might be related to aggregation. By Western blotting with an anti-Src monoclonal antibody, we found time-dependent association of pp60src with the cytoskeleton (10,000 x g Triton X-100-insoluble matrix) but not the "membrane" cytoskeleton (100,000 x g Triton X-100-insoluble matrix) in platelets activated by U46619 (PGH2 analog). Cytoskeletal association and platelet aggregation were inhibited by the peptide Arg-Gly-Asp-Ser (RGDS) (but not by Arg-Gly-Glu-Ser (RGES)), by 10E5 antibody against glycoprotein (Gp) IIb/IIIa, and by EGTA. U46619-induced association of pp60src with cytoskeleton but not secretion or aggregation was inhibited by cytochalasin D (2 muM). Both cytochalasin D and RGDS inhibited "slow" tyrosine phosphorylation of platelet proteins. Association of pp60src with cytoskeleton induced by U46619 or ADP was not blocked by aspirin. Aspirin blocked epinephrine-induced association of pp60src with the cytoskeleton during a second phase of aggregation when an initial phase had occurred without shape change or secretion. Association of GpIIb/IIIa with the cytoskeleton also accompanied platelet aggregation, shape change, and actin polymerization; this was shown with anti-GpIIb and anti-GpIIIa antibodies. Association of pp60src and GpIIb/IIIa with the cytoskeleton and slow tyrosine phosphorylation are related phenomena. C1 BETH ISRAEL HOSP,DEPT SURG,330 BROOKLINE AVE,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELLULAR MOLEC,BOSTON,MA 02115. FU NHLBI NIH HHS [HL-33014] NR 44 TC 93 Z9 93 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 OCT 5 PY 1992 VL 267 IS 28 BP 20075 EP 20081 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JR858 UT WOS:A1992JR85800053 PM 1400325 ER PT J AU RAISHER, BD GULICK, T ZHANG, ZF STRAUSS, AW MOORE, DD KELLY, DP AF RAISHER, BD GULICK, T ZHANG, ZF STRAUSS, AW MOORE, DD KELLY, DP TI IDENTIFICATION OF A NOVEL RETINOID-RESPONSIVE ELEMENT IN THE PROMOTER REGION OF THE MEDIUM CHAIN ACYL-COENZYME-A DEHYDROGENASE GENE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HORMONE RECEPTOR SUPERFAMILY; ACID RECEPTOR; COA DEHYDROGENASE; THYROID-HORMONE; MOLECULAR CHARACTERIZATION; MITOCHONDRIAL PROTEINS; BINDING PROTEIN; I GENE; EXPRESSION; DEFICIENCY AB To study the mechanisms involved in regulation of nuclear genes encoding mitochondrial enzymes in oxidative energy pathways, the promoter region of the medium-chain acyl-CoA dehydrogenase (MCAD) gene was analyzed. A series of hexamer sequences known to bind and confer responsiveness to a subset of members of the nuclear receptor superfamily of transcription factors was identified. Cotransfection of an MCAD promoter-chloramphenicol acetyltransferase (CAT) reporter plasmid with retinoic acid receptor (RAR)alpha, beta, or retinoid X receptor alpha (RXRalpha) resulted in 10-15-fold transcriptional activation in response to retinoic acid. The retinoic acid-induced activation was 3-4-fold higher with RXRalpha than with either RARalpha or RARbeta. Deletional analysis confirmed that a region between -341 and -308 base pairs upstream of the MCAD gene cap site conferred the RA-responsive transcriptional activation to homologous and heterologous promoters. Gel mobility shift assays demonstrated that the MCAD RARE interacted directly with overexpressed receptors. Mutational analysis of the RARE delineated three hexamer binding sequences with unique orientation and spacing compared to other reported retinoid responsive elements. These results indicate that the MCAD gene promoter region contains a novel regulatory element that interacts with members of the retinoid receptor family, with preferential activation by RXRalpha. This element likely plays a role in the transcriptional regulation of this gene and perhaps others involved in oxidative energy metabolism. C1 WASHINGTON UNIV,SCH MED,DEPT MED,DIV CARDIOVASC,660 S EUCLID AVE,BOX 8086,ST LOUIS,MO 63110. WASHINGTON UNIV,SCH MED,DEPT PEDIAT,ST LOUIS,MO 63110. WASHINGTON UNIV,SCH MED,DEPT BIOCHEM & MOLEC BIOPHYS,ST LOUIS,MO 63110. MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02114. NR 45 TC 62 Z9 62 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 OCT 5 PY 1992 VL 267 IS 28 BP 20264 EP 20269 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JR858 UT WOS:A1992JR85800081 PM 1328196 ER PT J AU MOTOKURA, T KEYOMARSI, K KRONENBERG, HM ARNOLD, A AF MOTOKURA, T KEYOMARSI, K KRONENBERG, HM ARNOLD, A TI CLONING AND CHARACTERIZATION OF HUMAN CYCLIN D3, A CDNA CLOSELY RELATED IN SEQUENCE TO THE PRAD1 CYCLIN-D1 PROTOONCOGENE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HISTONE MESSENGER-RNAS; CELL-CYCLE; SACCHAROMYCES-CEREVISIAE; CHROMOSOMAL-ABNORMALITIES; CANDIDATE ONCOGENE; GENE; G1; YEAST; TUMOR; RETINOBLASTOMAS AB Cyclins regulate cell cycle progression by complexing with and activating cdc2 or related kinases. PRAD1/cyclin D1 is a recently discovered putative oncogene in several types of human tumors and may regulate G1-S phase progression. We have cloned a related human cDNA, called cyclin D3, from a placental cDNA library by cross-hybridization with PRAD1. In synchronized HeLa cells, the mRNA levels of PRAD1 and cyclin D3 were regulated reciprocally through the cell cycle: cyclin D3 mRNA levels peaked in S phase, where PRAD1 mRNA was lowest in S. In normal human mammary epithelial (70N) cells synchronized by growth factor deprivation and subsequent growth factor stimulation, PRAD1 expression peaked in G1 and declined before S phase, while cyclin D3 expression rose later in G1 and remained elevated in S. Therefore, the close relationship (53.1% identity) between PRAD1 and cyclin D3 does not necessarily imply redundant functions of these candidate G1 cyclins; they may have distinct roles in progression from G1 through S phase. C1 MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,FRUIT ST,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELL GROWTH & REGULAT,BOSTON,MA 02115. FU NCI NIH HHS [CA08949, CA55909]; NIDDK NIH HHS [DK11794] NR 39 TC 152 Z9 156 U1 0 U2 4 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 OCT 5 PY 1992 VL 267 IS 28 BP 20412 EP 20415 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JR858 UT WOS:A1992JR85800103 PM 1383201 ER PT J AU ROBERTS, JD POLANER, DM LANG, P ZAPOL, WM AF ROBERTS, JD POLANER, DM LANG, P ZAPOL, WM TI INHALED NITRIC-OXIDE IN PERSISTENT PULMONARY-HYPERTENSION OF THE NEWBORN SO LANCET LA English DT Note ID RELAXING FACTOR AB Nitric oxide (NO) has vasodilatory effects on the pulmonary vasculature in adults and animals. We examined the effects on systemic oxygenation and blood pressure of inhaling up to 80 parts per million by volume of NO at F(i)O2 0.9 for up to 30 minutes by 6 infants with persistent pulmonary hypertension of the newborn (PPHN). In all infants this treatment rapidly and significantly increased preductal oxygen saturation (SpO2); in 5 infants postductal SpO2 and oxygen tensions also increased. Inhalation of NO did not cause systemic hypotension or raise methaemoglobin. These data suggest that low levels of inhaled NO have an important role in the reversal of hypoxaemia due to PPHN. C1 MASSACHUSETTS GEN HOSP,DEPT PEDIAT,BOSTON,MA 02114. RP ROBERTS, JD (reprint author), MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114, USA. OI Polaner, David/0000-0001-8716-6289 FU NHLBI NIH HHS [HL 42397] NR 8 TC 644 Z9 655 U1 0 U2 5 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD OCT 3 PY 1992 VL 340 IS 8823 BP 818 EP 819 DI 10.1016/0140-6736(92)92686-A PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA JR168 UT WOS:A1992JR16800005 PM 1357245 ER PT J AU CAMPBELL, A BALDESSARINI, RJ YEGHIAYAN, S AF CAMPBELL, A BALDESSARINI, RJ YEGHIAYAN, S TI ANTAGONISM OF LIMBIC AND EXTRAPYRAMIDAL ACTIONS OF INTRACEREBRALLY INJECTED DOPAMINE BY ERGOLINES WITH PARTIAL D2 AGONIST ACTIVITY IN THE RAT SO BRAIN RESEARCH LA English DT Article DE ANTIPSYCHOTIC; DOPAMINE; ERGOLINE; EXTRAPYRAMIDAL; INTRACRANIAL INJECTION; LIMBIC; STEREOTAXIC ID SYSTEM AB Bromocriptine and a series of experimental ergoline D2 partial agonists (SDZ-208-911, SDZ-212-327, SDZ-208-912) were evaluated for their interactions with exogenous dopamine (DA, at ED50 = 16 Ag) stereotaxically injected unilaterally into a limbic (superior-medial nucleus accumbens septi) or extrapyramidal (central corpus striatum) target site in rat brain. Behavioral measures to quantify responses were locomotor arousal induced by DA in accumbens and contralateral head turning with striatum. All agents, given systemically (i.p.), induced dose-dependent inhibition of behavioral responses to DA from both brain sites. In both accumbens and striatum, SDZ-212-327 was most potent and bromocriptine, least; however, bromocriptine was relatively much more potent in accumbens, and SDZ-208-912 somewhat more potent in striatum. These results add to the growing impression that agents with partial agonist actions at central DA receptors can show behaviorally inhibitory effects that may reflect paradoxical antidopaminergic actions against the full, natural agonist of DA receptors and that such effects can be regionally selective. C1 MASSACHUSETTS GEN HOSP,MAILMAN RES CTR,MCLEAN DIV,BELMONT,MA 02178. HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,NEUROSCI PROGRAM,BOSTON,MA 02115. FU NIMH NIH HHS [MH-34006, MH-31154, MH-47370] NR 18 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD OCT 2 PY 1992 VL 592 IS 1-2 BP 348 EP 352 DI 10.1016/0006-8993(92)91696-C PG 5 WC Neurosciences SC Neurosciences & Neurology GA JR759 UT WOS:A1992JR75900046 PM 1360315 ER PT J AU TONER, M TOMPKINS, RG CRAVALHO, EG YARMUSH, ML AF TONER, M TOMPKINS, RG CRAVALHO, EG YARMUSH, ML TI TRANSPORT PHENOMENA DURING FREEZING OF ISOLATED HEPATOCYTES SO AICHE JOURNAL LA English DT Article ID INTRACELLULAR ICE FORMATION; CRYOMICROSCOPIC ANALYSIS; SANDWICH CONFIGURATION; MOUSE OOCYTES; CELLS; RAT; CRYOPRESERVATION; GRANULOCYTES; BEHAVIOR; CULTURE AB The cellular response of isolated rat hepatocytes to freezing stress under various chemical and physical conditions was investigated using cryomicroscopic observations and a theoretical transport model. Cryomicroscopy was used to determine the cellular dehydration during freezing at different cooling rates. Using these results, water permeability parameters were also obtained. In addition, intracellular ice formation (IIF) parameters were obtained from rapid freezing experiments at a cooling rate of 400-degrees-C/min to decouple the effects of dehydration from IIF. The water permeability and IIF parameters were then used in a transport model to predict the probability of IIF under a wide range of chemical and physical conditions observed during cell freezing. In order to verify the model predictions, experiments were performed under similar conditions and compared to the theoretical predictions. The results suggest that slowly cooled cells ( < 80-degrees-C/min) dehydrate excessively and escape IIF. On the other hand rapidly cooled cells ( > 120-degrees-C/min) contain enough undercooled cellular water which undergoes IIF between -5 and -12-degrees-C. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,SURG SERV,BIGELOW 1302,BOSTON,MA 02114. MIT,DEPT MECH ENGN,CAMBRIDGE,MA 02139. RUTGERS STATE UNIV,DEPT CHEM & BIOCHEM ENGN,PISCATAWAY,NJ 08855. NR 45 TC 52 Z9 56 U1 1 U2 5 PU AMER INST CHEMICAL ENGINEERS PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 SN 0001-1541 J9 AICHE J JI AICHE J. PD OCT PY 1992 VL 38 IS 10 BP 1512 EP 1522 DI 10.1002/aic.690381004 PG 11 WC Engineering, Chemical SC Engineering GA JT337 UT WOS:A1992JT33700003 ER PT J AU BROWN, JH DELUCA, SA AF BROWN, JH DELUCA, SA TI GROWTH PLATE INJURIES - SALTER-HARRIS CLASSIFICATION SO AMERICAN FAMILY PHYSICIAN LA English DT Article AB Fracture of the growth plate is an injury unique to childhood. Most such fractures heal without permanent deformity. A small percentage, however, are complicated by growth arrest and subsequent deformity. The Salter-Harris classification of growth plate injuries aids in estimating both the prognosis and the potential for growth disturbance. The Salter-Harris system classifies growth plate fractures into five groups: type I, fracture through the growth plate; type II, fracture through the growth plate and metaphysis; type III, fracture through the growth plate and epiphysis; type IV, fracture through the growth plate, epiphysis and metaphysis, and type V, crush or compression injury of the growth plate. RP BROWN, JH (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 0 TC 14 Z9 14 U1 0 U2 8 PU AMER ACAD FAMILY PHYSICIANS PI KANSAS CITY PA 8880 WARD PARKWAY, KANSAS CITY, MO 64114-2797 SN 0002-838X J9 AM FAM PHYSICIAN JI Am. Fam. Physician PD OCT PY 1992 VL 46 IS 4 BP 1180 EP 1184 PG 5 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA JR198 UT WOS:A1992JR19800017 PM 1414883 ER PT J AU SCHWEITZER, P AF SCHWEITZER, P TI THE VALUES AND LIMITATIONS OF THE QT INTERVAL IN CLINICAL-PRACTICE SO AMERICAN HEART JOURNAL LA English DT Note ID ACUTE MYOCARDIAL-INFARCTION; ACTION-POTENTIAL DURATION; Q-T INTERVAL; DIABETIC AUTONOMIC NEUROPATHY; SUDDEN CARDIAC DEATH; HEART-RATE; VENTRICULAR-TACHYCARDIA; LONG QT; BAZETTS FORMULA; RATE DEPENDENCE C1 CUNY MT SINAI SCH MED,NEW YORK,NY 10029. RP SCHWEITZER, P (reprint author), BRONX VET AFFAIRS MED CTR,DEPT MED,DIV CARDIOL,BRONX,NY 10468, USA. NR 74 TC 23 Z9 24 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD OCT PY 1992 VL 124 IS 4 BP 1121 EP 1125 DI 10.1016/0002-8703(92)91013-Q PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA JQ688 UT WOS:A1992JQ68800052 PM 1529898 ER PT J AU WILLETT, CG TEPPER, JE KAUFMAN, DS SHELLITO, PC ELISEO, R CONVERY, K WOOD, WC AF WILLETT, CG TEPPER, JE KAUFMAN, DS SHELLITO, PC ELISEO, R CONVERY, K WOOD, WC TI ADJUVANT POSTOPERATIVE RADIATION-THERAPY FOR RECTAL ADENOCARCINOMA SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS LA English DT Article DE RECTAL ADENOCARCINOMA; POSTOPERATIVE IRRADIATION ID CURATIVE SURGERY; CANCER; CARCINOMA; CHEMOTHERAPY; RECURRENCE; PATTERNS AB From October 1975 to August 1988, 261 patients at high risk for local recurrence after curative resection of rectal carcinoma underwent high-dose postoperative irradiation. Patients received 45 Gy by a 4-field box usually followed by a boost to 50.4 Gy or higher when small bowel could be excluded from the reduced field. Since January 1986, patients also received 5-fluorouracil (5-FU) for 3 consecutive days during the first and last week of radiotherapy. Five-year actuarial local control and disease-free survival decreased with increasing stage of disease; patients with Stage B2 and B3 disease had local control rates of 83% and 87% and disease-free survivals of 55% and 74%, respectively. In patients with Stage C1 through C3 tumors, local control rates ranged from 76% to 23%, and disease-free survivals ranged from 62% to 10%, respectively. For patients with Stage C disease, disease-free survival decreased progressively with increasing lymph node involvement, but local control was independent of the extent of lymph node involvement. For each stage of disease, local control and disease-free survival did not correlate with the dose of pelvic irradiation. Preliminary data from this study suggest a trend toward improved local control for patients with Stage B2, C1, and C2 tumors who receive 5-FU for 3 consecutive days during the first and last weeks of irradiation compared with patients who do not receive 5-FU. Current prospective randomized studies are addressing questions regarding the optimum administration of chemotherapy with pelvic irradiation for patients following resection of rectal carcinoma. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CTR CANC,DEPT RADIAT ONCOL,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CTR CANC,DEPT MED ONCOL,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CTR CANC,DEPT SURG,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CTR CANC,DIV SURG ONCOL,BOSTON,MA 02114. UNIV N CAROLINA,SCH MED,DEPT RADIAT ONCOL,CHAPEL HILL,NC 27514. NR 16 TC 32 Z9 32 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0277-3732 J9 AM J CLIN ONCOL-CANC JI Am. J. Clin. Oncol.-Cancer Clin. Trials PD OCT PY 1992 VL 15 IS 5 BP 371 EP 375 DI 10.1097/00000421-199210000-00001 PG 5 WC Oncology SC Oncology GA JP204 UT WOS:A1992JP20400001 PM 1524036 ER PT J AU FALKSON, G RYAN, LM HALLER, DG AF FALKSON, G RYAN, LM HALLER, DG TI PHASE-II TRIAL FOR THE EVALUATION OF TRIMETREXATE IN PATIENTS WITH INOPERABLE SQUAMOUS CARCINOMA OF THE ESOPHAGUS SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS LA English DT Article DE TRIMETREXATE; CARCINOMA OF THE ESOPHAGUS ID CELL CARCINOMA; FOLATE ANTAGONISTS; LEUKEMIA-CELLS; METHOTREXATE; TMQ AB EST 2287 was a Phase II clinical trial conducted by the Eastern Cooperative Oncology Group (ECOG) designed to evaluate trimetrexate in patients with advanced, measurable, inoperable squamous cell carcinoma of the esophagus. The drug was given at a dose of 12 mg/m2 daily for 5 days every 21 days to patients with carcinoma of the esophagus. The purpose of this study was to evaluate treatment efficacy in terms of tumor response and to assess the toxicity. According to a two-stage stopping rule, the study closed after 15 patients had entered. There were no responses to treatment, and median survival from study entry was 4.3 months. There was one treatment-related death caused by infection. One patient experienced life-threatening hematologic toxicity. Overall severe or worse toxicity occurred in more than half of the patients. It is concluded that additional trials of trimetrexate at this dose and schedule in patients with carcinoma of the esophagus are not warranted. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HOSP UNIV PENN,PHILADELPHIA,PA 19104. RP FALKSON, G (reprint author), UNIV PRETORIA,DEPT MED ONCOL,POB 667,PRETORIA 0001,SOUTH AFRICA. RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 FU NCI NIH HHS [CA 23318, CA 15488, CA 21692] NR 21 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0277-3732 J9 AM J CLIN ONCOL-CANC JI Am. J. Clin. Oncol.-Cancer Clin. Trials PD OCT PY 1992 VL 15 IS 5 BP 433 EP 435 DI 10.1097/00000421-199210000-00007 PG 3 WC Oncology SC Oncology GA JP204 UT WOS:A1992JP20400012 PM 1387999 ER PT J AU NATOWICZ, MR ALPER, JK ALPER, JS AF NATOWICZ, MR ALPER, JK ALPER, JS TI GENETIC DISCRIMINATION AND THE AMERICANS WITH DISABILITIES ACT SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Letter C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. UNIV MASSACHUSETTS,DISABIL LAW CTR,BOSTON,MA 02125. UNIV MASSACHUSETTS,DEPT CHEM,BOSTON,MA 02125. RP NATOWICZ, MR (reprint author), SHRIVER CTR MENTAL RETARDAT,DIV MED GENET,WALTHAM,MA, USA. NR 3 TC 7 Z9 7 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1992 VL 51 IS 4 BP 895 EP 897 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA JQ667 UT WOS:A1992JQ66700028 PM 1415233 ER PT J AU NATOWICZ, MR ALPER, JK ALPER, JS AF NATOWICZ, MR ALPER, JK ALPER, JS TI GENETIC DISCRIMINATION AND PUBLIC SAFETY SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Letter C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. UNIV MASSACHUSETTS,DEPT CHEM,BOSTON,MA 02125. UNIV MASSACHUSETTS,CTR DISABIL LAW,BOSTON,MA 02125. RP NATOWICZ, MR (reprint author), SHRIVER CTR MENTAL RETARDAT,DIV MED GENET,WALTHAM,MA, USA. NR 2 TC 4 Z9 4 U1 1 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1992 VL 51 IS 4 BP 898 EP 899 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA JQ667 UT WOS:A1992JQ66700031 PM 11643032 ER PT J AU WOLPERT, HA STEEN, SN ISTFAN, NW SIMONSON, DC AF WOLPERT, HA STEEN, SN ISTFAN, NW SIMONSON, DC TI DISPARATE EFFECTS OF WEIGHT-LOSS ON INSULIN SENSITIVITY AND ERYTHROCYTE SODIUM-LITHIUM COUNTERTRANSPORT ACTIVITY SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article DE SODIUM-LITHIUM COUNTERTRANSPORT; INSULIN RESISTANCE; HYPERINSULINEMIA; INSULIN CLAMP; OBESITY AB Previous investigations have demonstrated an association between impaired insulin sensitivity and elevated erythrocyte sodium-lithium countertransport (Na+-Li+ CT) activity. It has been speculated that insulin resistance and endogenous hyperinsulinemia are causally related to the development of elevated Na+-Li+ CT activity. To test this hypothesis, we measured insulin sensitivity (euglycemic insulin clamp technique) and Na+-Li+ CT activity in eight obese women before (weight = 102 +/- 5 kg) and after (weight = 88 +/- 5 kg; P < .001) a 10 week weight reduction program. Maximal velocity of Na+-Li+ CT activity did not change (0.50 +/- 0.09 v 0.49 +/- 0.10 mmol/L red blood cells/h; P = NS) despite the significant improvement in insulin sensitivity (73 +/- 12 v 110 +/- 7 mg/m2/min; P < .0025) and reduction in fasting insulin levels (17 +/- 2 v 10 +/- 2 muU/mL; P < .05) that accompanied weight loss. These results suggest that insulin resistance and hyperinsulinemia are not linked pathophysiologically to the development of elevated Na+-Li+ CT activity. RP WOLPERT, HA (reprint author), NEW ENGLAND DEACONESS HOSP,JOSLIN DIABET CTR,DEPT INTERNAL MED,1 JOSLIN PL,BOSTON,MA 02215, USA. FU NHLBI NIH HHS [HL39392]; NIDDK NIH HHS [DK36836, DK43505] NR 0 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 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD OCT PY 1992 VL 5 IS 10 BP 754 EP 757 PG 4 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JU219 UT WOS:A1992JU21900016 PM 1418840 ER PT J AU LEWANDROWSKI, K CHEEK, R NATHAN, DM GODINE, JE HURXTHAL, K ESCHENBACH, K LAPOSATA, M AF LEWANDROWSKI, K CHEEK, R NATHAN, DM GODINE, JE HURXTHAL, K ESCHENBACH, K LAPOSATA, M TI IMPLEMENTATION OF CAPILLARY BLOOD-GLUCOSE MONITORING IN A TEACHING HOSPITAL AND DETERMINATION OF PROGRAM REQUIREMENTS TO MAINTAIN QUALITY TESTING SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID PERFORMANCE AB PURPOSE: To study the implementation of bedside capillary glucose monitoring using a hospital-wide quality control (QC) program. METHODS: A prospective study of QC performance in 7 outpatient and 39 inpatient treatment units was performed in a large teaching hospital over a 2-year period. Approximately 800 nurses were trained to perform bedside capillary glucose monitoring (Accu-Chek II, Boehringer-Mannheim, Indianapolis, IN). An eight-point QC program was instituted including proficiency testing, instrument maintenance, performance of daily controls, storage of reagent strips and supplies, instrument calibration, and documentation procedures. RESULTS: Comparison of laboratory and bedside test results (split-sample proficiency testing) revealed Y = 1.004X + 7.26, r = 0.95, with a mean percent difference of -4.2% (p <0.001). Less than 7% of results fell outside +/- 20% of the laboratory results. QC scores (0 = worst to 4 = best), based on adherence to the QC program, improved from 0 on the first inspection to 3.7 0.17 by the 11th inspection. The most common QC deficiencies were failure to perform split-sample testing (41.4%) and failure to perform instrument maintenance (30.2%). Significant differences were noted in the QC performance of different types of medical services. During the 2-year study period, the total number of glucose assays performed in the clinical laboratories decreased by 22.2% concurrent with initiation of bedside testing. The number of instruments in the hospital increased from 10 to 46. CONCLUSIONS: Bedside capillary glucose assays can be widely implemented in large hospitals with an acceptable degree of accuracy. QC programs with frequent inspections are necessary to identify units that function inadequately, and a formal disciplinary policy is required to ensure compliance with the program. C1 MASSACHUSETTS GEN HOSP,DEPT MED,DIABET UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DIV CLIN LABS,BOSTON,MA 02114. RP LEWANDROWSKI, K (reprint author), MASSACHUSETTS GEN HOSP,DEPT PATHOL,GRAY 5,BOSTON,MA 02114, USA. NR 17 TC 30 Z9 31 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 OCT PY 1992 VL 93 IS 4 BP 419 EP 426 DI 10.1016/0002-9343(92)90172-8 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA JT161 UT WOS:A1992JT16100010 PM 1415305 ER PT J AU SILVERMAN, PR NICKMAN, S WORDEN, JW AF SILVERMAN, PR NICKMAN, S WORDEN, JW TI DETACHMENT REVISITED - THE CHILDS RECONSTRUCTION OF A DEAD PARENT SO AMERICAN JOURNAL OF ORTHOPSYCHIATRY LA English DT Article ID GRIEF AB During the year following a parent's death, children in a community-based sample were found to have developed an inner construction of the dead parent. This continued, though altered, relationship appeared to facilitate their coping with the loss and with accompanying changes in their lives. Implications for understanding the bereavement process and for interventions focusing on detachment are discussed. RP SILVERMAN, PR (reprint author), MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,CHILD BEREAVEMENT STUDY,BOSTON,MA 02114, USA. FU NIMH NIH HHS [MH41791] NR 37 TC 52 Z9 52 U1 2 U2 6 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 OCT PY 1992 VL 62 IS 4 BP 494 EP 503 DI 10.1037/h0079366 PG 10 WC Psychiatry; Social Work SC Psychiatry; Social Work GA JV271 UT WOS:A1992JV27100003 PM 1443058 ER PT J AU LOUIS, DN VONDEIMLING, A SEIZINGER, BR AF LOUIS, DN VONDEIMLING, A SEIZINGER, BR TI A (CA)N DINUCLEOTIDE REPEAT ASSAY FOR EVALUATING LOSS OF ALLELIC HETEROZYGOSITY IN SMALL AND ARCHIVAL HUMAN BRAIN-TUMOR SPECIMENS SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Note ID POLYMERASE CHAIN-REACTION; GENE; POLYMORPHISMS; P53 AB Southern blotting is a widely used method of determining loss of chromosomal alleles in tumors, but cannot be used to analyze small biopsies and most fixed, embedded tissues. These problems preclude analysis of many surgical neuropathology specimens. We have employed a polymerase chain reaction assay for loss of heterozygosity (LOH) based on the (CA)n dinucleotide repeat polymorphisms found in abundance throughout the human genome. We compared this method to conventional Southern blotting in detecting LOH on chromosome 10 in gliomas. From tissue sections of 14 paraffin-embedded, formalin-fixed gliomas, we amplified the (CA)n repeat D10S89 locus and compared (CA)n repeat patterns between tumor DNA and constitutional DNA. Loss of one chromosome 10 (CA)n repeat allele was seen in informative glioblastomas that showed allelic loss by Southern blotting but not in gliomas that bad maintained both alleles. The (CA)n repeat method can be applied to small and fixed, embedded specimens, is rapid and simple to perform, and uses highly polymorphic probes. We suggest that (CA)n repeats are a less exclusive and more rapid means of studying LOH in brain tumors than Southern blotting and will provide further mapping data for the identification of tumor suppressor genes integral to glial tumorigenesis. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,NEUROSURG SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,MOLEC NEUROONCOL LAB,BOSTON,MA 02114. RP LOUIS, DN (reprint author), MASSACHUSETTS GEN HOSP,DEPT PATHOL NEUROPATHOL,WARREN 3,BOSTON,MA 02114, USA. RI von Deimling, Andreas/F-7774-2013 OI von Deimling, Andreas/0000-0002-5863-540X FU NCI NIH HHS [CA 09144] NR 17 TC 119 Z9 119 U1 0 U2 1 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 OCT PY 1992 VL 141 IS 4 BP 777 EP 782 PG 6 WC Pathology SC Pathology GA JR554 UT WOS:A1992JR55400003 PM 1415476 ER PT J AU BOGEN, SA BALDWIN, HS WATKINS, SC ALBELDA, SM ABBAS, AK AF BOGEN, SA BALDWIN, HS WATKINS, SC ALBELDA, SM ABBAS, AK TI ASSOCIATION OF MURINE CD31 WITH TRANSMIGRATING LYMPHOCYTES FOLLOWING ANTIGENIC-STIMULATION SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID CELL-ADHESION MOLECULE; RECEPTOR; EXPRESSION; CLONING AB Human CD31 is a recently characterized molecule present on leukocytes, platelets, and endothelium Its function is not known. Because it is a member of the immunoglobulin superfamily and structurally homologous to carcinoembryonic antigen, a putative intercellular adhesion molecule, it is believed that CD31 may function also as an adhesion molecule. In this report, we characterize the cellular reactivity of a monoclonal antibody to a murine protein that is homologous to CD31. To delineate the cellular reactivity of the murine CD31 homologue recognized by our monoclonal antibody, we used immunoperoxidase and immunoelectron microscopic techniques. The most striking finding was that the putative murine homolog of CD31 is expressed in particularly high amounts on endothelium-adherent lymphocytes transmigrating across sinusoidal or venular vascular boundaries. Such a distribution was apparent in draining murine lymph nodes during the peak of an immune response after immunization with a protein antigen in adjuvant, a situation in which there are many transmigrating lymphocytes Immunoelectron microscopic analysis also shows that CD31 is predominantly distributed on portions of transmigrating lymphocytes that are in contact with or adjacent to areas of contact with endothelial cells. These findings suggest a previously undescribed role for CD31 in lymphocyte recruitment and transmigration. C1 BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PHYSIOL & BIOPHYS,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. CHILDRENS HOSP PHILADELPHIA,PHILADELPHIA,PA. HOSP UNIV PENN,PHILADELPHIA,PA 19104. FU NHLBI NIH HHS [HL02197, HL39023]; NIAID NIH HHS [R01 AI25022] NR 21 TC 60 Z9 61 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD OCT PY 1992 VL 141 IS 4 BP 843 EP 854 PG 12 WC Pathology SC Pathology GA JR554 UT WOS:A1992JR55400011 PM 1415479 ER PT J AU BROWN, D LUI, B GLUCK, S SABOLIC, I AF BROWN, D LUI, B GLUCK, S SABOLIC, I TI A PLASMA-MEMBRANE PROTON ATPASE IN SPECIALIZED CELLS OF RAT EPIDIDYMIS SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Note DE ADENOSINE-TRIPHOSPHATASE; SPERM MATURATION; APICAL PLASMA MEMBRANE ID INTERCALATED CELLS; CARBONIC-ANHYDRASE; EPITHELIAL-CELLS; CYTO-CHEMISTRY; H+-ATPASE; KIDNEY; BAND-3; PH; ACIDIFICATION; LOCALIZATION AB Acidification of the luminal fluid in the epididymis is believed to play an important role in sperm maturation. Previous studies have shown that specialized cells in the epithelium lining the epididymis contain high levels of carbonic anhydrase and that these cells have rod-shaped intramembraneous particles when examined by freeze fracture. Both of these features are characteristic of proton-transporting intercalated cells in the kidney collecting duct. We now show that apical cells in the head of the epididymis and clear cells in the body and tail of the epididymis express high levels of a vacuolar proton-pumping adenosinetriphosphatase on their apical plasma membranes and on intracellular vesicles. By analogy with kidney intercalated cells, these cell types may be specialized for acid secretion in the epididymis. C1 MASSACHUSETTS GEN HOSP,RENAL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. WASHINGTON UNIV,JEWISH HOSP ST LOUIS,DIV RENAL,ST LOUIS,MO 63110. FU NIDDK NIH HHS [DK-42956] NR 27 TC 78 Z9 79 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 OCT PY 1992 VL 263 IS 4 BP C913 EP C916 PN 1 PG 4 WC Physiology SC Physiology GA JU805 UT WOS:A1992JU80500026 PM 1415677 ER PT J AU KEMENDY, AE KLEYMAN, TR EATON, DC AF KEMENDY, AE KLEYMAN, TR EATON, DC TI ALDOSTERONE ALTERS THE OPEN PROBABILITY OF AMILORIDE-BLOCKABLE SODIUM-CHANNELS IN A6 EPITHELIA SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE SODIUM TRANSPORT; ION CHANNEL; PATCH CLAMP; RENAL CELLS ID TOAD URINARY-BLADDER; APICAL MEMBRANE; NA+ CHANNEL; TRANSPORT; DENSITY; LOCALIZATION; SELECTIVITY; MECHANISMS; CELLS; MODEL AB We used patch-clamp methods to examine the effects of depletion and readdition of aldosterone on single, highly selective, amiloride-blockable sodium channels in the A6 cell line. Single-channel characteristics changed little before 24 h of continuous aldosterone depletion, although there was some reduction in short-circuit current. Thereafter, apical sodium permeability, measured as product of channel number per patch and individual channel open probability (NP(o)), was reduced between five- and sevenfold, primarily due to a large decrease in channel mean open time. With about the same time course, short-circuit current also decreased approximately fivefold. Readdition of aldosterone to depleted cells produced an increase in NP(o) within 2 h, primarily through an increase in mean open time. After readdition, channel number per patch increased twofold compared with cells not hormone deprived, with a return to control levels between 24 and 48 h after continuous exposure. The increase in short-circuit current followed a similar time course. The primary effect of aldosterone appears to be modulation of the open time of channels continuously present in the apical membrane, rather than promotion of the appearance or disappearance of channels from the membrane. In particular, it cannot be demonstrated statistically that aldosterone removal reduces the number of channels per patch, and there may actually be up to a twofold increase after a long period of aldosterone depletion. C1 EMORY UNIV,SCH MED,DEPT PHYSIOL,ATLANTA,GA 30322. UNIV PENN,DEPT MED & PHYSIOL,PHILADELPHIA,PA 19104. VET AFFAIRS MED CTR,PHILADELPHIA,PA 19104. FU NIDDK NIH HHS [DK-37963] NR 33 TC 168 Z9 169 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 OCT PY 1992 VL 263 IS 4 BP C825 EP C837 PN 1 PG 13 WC Physiology SC Physiology GA JU805 UT WOS:A1992JU80500016 PM 1329547 ER PT J AU ALFREY, AC AF ALFREY, AC TI TOXICITY OF TUBULE FLUID IRON IN THE NEPHROTIC SYNDROME SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE GLOMERULONEPHRITIS; DEFEROXAMINE; TRANSFERRIN ID GLOMERULAR INJURY; SERUM NEPHRITIS; OXYGEN RADICALS; RAT; DESFERRIOXAMINE; TRANSFERRIN; SUPEROXIDE; SIZE AB This study was carried out in rats with nephrotoxic serum nephritis after autologous phase proteinuria was well established to determine the effect of tubule fluid iron chelation on the course of this disease. Deferoxamine administration caused a reduction in urinary iron potentially capable of catalyzing hydroxyl radical (.OH) formation and kidney iron uptake (224 +/- 60 vs. 398 +/- 152 mg/kg). This was associated with a decrease in rate of progression of renal failure over the 21-day study period (creatinine clearance -0.199 +/- 0.152 vs. -0.509 +/- 0.336 ml/min, P < 0.05) and improved survival (8/8 vs. 4/8, P < 0.05). In addition deferoxamine caused a reduction in urinary transferrin excretion (32 +/- 15 vs. 74 +/- 16 mg/day) and fractional excretion of transferrin (2.01 +/- 1 vs. 5.9 +/- 3.7%) and an increase in serum transferrin levels (229 +/- 36 vs. 139 +/- 45 mg/dl, all P < 0.05). It is suggested that iron presented to the tubule fluid as a result of the glomerular leak for transferrin is dissociated from transferrin. In tum the iron is available in a form capable of catalyzing .OH formation, resulting in lipid peroxidation of tubule cell membranes. Deferoxamine chelation of tubule fluid iron retards the development of both tubulointerstitial injury and superimposed glomerular sclerosis in this model of membranous nephropathy. RP ALFREY, AC (reprint author), UNIV COLORADO,DENVER VET AFFAIRS HOSP,MED CTR,1055 CLERMONT ST,DENVER,CO 80220, USA. NR 31 TC 42 Z9 42 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD OCT PY 1992 VL 263 IS 4 BP F637 EP F641 PN 2 PG 5 WC Physiology SC Physiology GA JU806 UT WOS:A1992JU80600091 PM 1384359 ER PT J AU COLSTON, JT FREEMAN, GL AF COLSTON, JT FREEMAN, GL TI BENEFICIAL INFLUENCE OF VASOACTIVE-INTESTINAL-PEPTIDE ON VENTRICULOVASCULAR COUPLING IN CLOSED-CHEST DOGS SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE ARTERIAL DYNAMICS; MYOCARDIAL MECHANICS ID ADENYLATE-CYCLASE; CONSCIOUS DOGS; PRESSURE; POLYPEPTIDE; HEART; VIP; CONTRACTILITY; RESPONSES; AFTERLOAD; SECRETIN AB The effect of vasoactive intestinal peptide (VIP) on ventriculovascular coupling in the intact cardiovascular system has not been defined. We studied seven dogs chronically instrumented with left ventricular (LV) pressure manometers and three sets of diameter gauges before and after infusions of 0.02, 0.05, and 0.10 mug.kg-1.min-1 VIP. The dogs were studied after autonomic blockade, anesthesia, and intubation, with a fixed heart rate of 160 beats/min. Contractility was assessed using LV elastance at end systole (E(es)) and the slope of the stroke work-end-diastolic volume relation. The vascular influence of VIP was quantified by determining effective arterial elastance (E(a)) under steady-state conditions. The overall effect on ventriculovascular coupling was assessed using the transfer of mechanical energy from LV to the arterial system (Trans(PVA)) quantified as the percentage of pressure-volume area (PVA) expressed as stroke work. LV relaxation was measured using the time constant of LV pressure decay. The results showed that VIP increased contractility (E(es) increased to 129, 156, and 181% of control; P < 0.01 for all vs. control) and decreased effective arterial elastance (E(a) fell to 84, 68, and 64% of control; P < 0.0155 vs. control for the two higher doses). VIP had no consistent effects on LV relaxation. Thus, in addition to its positive ventricular effects (increased contractility), VIP has beneficial vascular effects (reduced E(a)). These properties combine to improve ventriculovascular coupling, such that VIP enhances delivery of mechanical energy from the LV to the circulatory bed. C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX 78284. AUDIE MURPHY MEM VET HOSP,SAN ANTONIO,TX 78284. NR 30 TC 11 Z9 11 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 OCT PY 1992 VL 263 IS 4 BP H1300 EP H1305 PN 2 PG 6 WC Physiology SC Physiology GA JU806 UT WOS:A1992JU80600041 ER PT J AU HOLDEN, WE BURNHAM, EM LEE, MA BAGBY, SP AF HOLDEN, WE BURNHAM, EM LEE, MA BAGBY, SP TI INFLUENCE OF GROWTH OXYGEN LEVEL ON EICOSANOID RELEASE FROM LUNG ENDOTHELIAL-CELLS DURING HYPOXIA SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE ENDOTHELIUM; ENDOTHELIAL CELLS; HYPOXIA; VASOCONSTRICTION; PROSTAGLANDINS ID VASOCONSTRICTION; VARIABILITY; INVITRO AB Eicosanoid products of arachidonic acid are suspected modulators of hypoxic vasoconstriction in the pulmonary vasculature. Vascular endothelial cells (EC) release several eicosanoids, but there is disagreement regarding the effect of hypoxia on EC eicosanoid release. We postulated that the oxygen level of growth in culture might influence the release of eicosanoids during acute hypoxia. We studied EC cultured from the main pulmonary arteries of pigs and grown at either 5% or near 20% oxygen, representing the normal limits of oxygen exposure to endothelium in normal lungs. Although cultures grown in 5% oxygen grew slightly faster by 4 days, the confluent cell number, protein content, and baseline eicosanoid release were no different compared with paired cultures grown in 20% oxygen. However, with an acute decrease in oxygen level, cultures grown in 5% oxygen released less prostaglandin E2, F2alpha, and 6-ketoprostaglandin F1alpha compared with amounts released at the growth oxygen level. In contrast, cultures grown in 20% oxygen released increased amounts of these eicosanoids compared with release at the growth oxygen level. Release of thromboxane B2 was not significantly different during hypoxia between cultures grown at 5% vs. 20% oxygen. In other experiments, cyclooxygenase activity, stimulated arachidonic acid release by calcium ionophore A23187, and uptake of arachidonic acid were no different in cultures grown at 5% vs. 20% oxygen. However, arachidonic acid release during hypoxia was reduced in 5% cultures and increased in 20% cultures. These experiments show that both the growth oxygen level and an acute change in oxygen level influence release of eicosanoids from pulmonary vascular EC and suggest that in vivo release of eicosanoids during hypoxia may be influenced by the oxygen level to which the cells are chronically accustomed. C1 OREGON HLTH SCI UNIV,PORTLAND,OR 97201. RP HOLDEN, WE (reprint author), PORTLAND VET AFFAIRS MED CTR,MED SERV,3710 SW US VET HOSP RD,PORTLAND,OR 97207, USA. NR 20 TC 3 Z9 3 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 OCT PY 1992 VL 263 IS 4 BP L454 EP L459 PN 1 PG 6 WC Physiology SC Physiology GA JU805 UT WOS:A1992JU80500082 PM 1415723 ER PT J AU CHEW, FS BROWN, JH AF CHEW, FS BROWN, JH TI BRONCHIAL CARCINOID SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID LUNG C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP CHEW, FS (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,32 FRUIT ST,BOSTON,MA 02114, USA. NR 3 TC 3 Z9 3 U1 0 U2 4 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD OCT PY 1992 VL 159 IS 4 BP 756 EP 756 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA JQ079 UT WOS:A1992JQ07900013 PM 1326886 ER PT J AU EICHHORN, JH YOUNG, RH SCULLY, RE AF EICHHORN, JH YOUNG, RH SCULLY, RE TI PRIMARY OVARIAN SMALL-CELL CARCINOMA OF PULMONARY TYPE - A CLINICOPATHOLOGICAL, IMMUNOHISTOLOGIC, AND FLOW CYTOMETRIC ANALYSIS OF 11 CASES SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE OVARY; SMALL CELL CARCINOMA; OAT CELL CARCINOMA; ENDOMETRIOID CARCINOMA; BRENNER TUMOR ID IMMUNOHISTOCHEMICAL ANALYSIS; ARGYROPHIL CELLS; NEUROENDOCRINE CARCINOMA; MUCINOUS TUMORS; UTERINE CERVIX; DNA CONTENT; ENDOMETRIUM; HYPERCALCEMIA; CANCER; LIGHT AB Eleven primary ovarian tumors that resembled small cell carcinoma of the lung are reported. They occurred in women 28-85 (mean 59) years of age, most of whom presented with abdominal swelling. Six of the tumors were unilateral and five bilateral; seven had spread beyond the ovary. The tumors ranged from 4.5 to 26 (mean 13.5) cm in greatest dimension and were mostly solid, with a variable minor cystic component. Microscopic examination showed small to medium-sized round to spindle-shaped cells with scanty cytoplasm, hyperchromatic nuclei, and inconspicuous nucleoli growing in sheets, closely packed nests, and occasionally islands and trabeculae. A component of endometrioid carcinoma was present in four tumors, another tumor showed squamous differentiation, another contained a cyst lined by atypical mucinous cells, and two others were associated with a Brenner tumor. Argyrophil granules were present focally in two of six tumors appropriately stained. Immunohistochemical staining was performed in nine cases: in six there was staining of the small cell component for keratin, in five for epithelial membrane antigen, in seven for neuron-specific enolase, in two for chromogranin, and in one for Leu-7. Vimentin staining was not observed. Flow cytometry was performed on eight tumors: five were aneuploid and three diploid. Five of seven patients with long-term follow-up died of, or with, disease at 1-13 (mean 8) months, one died after an unknown interval, and one was alive at 7.5 years. Two other patients had recurrent or residual disease at 6 and 8 months. C1 MASSACHUSETTS GEN HOSP,JAMES HOMER WRIGHT PATHOL LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RP EICHHORN, JH (reprint author), MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114, USA. NR 58 TC 90 Z9 98 U1 1 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD OCT PY 1992 VL 16 IS 10 BP 926 EP 938 DI 10.1097/00000478-199210000-00002 PG 13 WC Pathology; Surgery SC Pathology; Surgery GA JP403 UT WOS:A1992JP40300002 PM 1384368 ER PT J AU MILLER, KB KYUNGMANN, K MORRISON, FS WINTER, JN BENNETT, JM NEIMAN, RS HEAD, DR CASSILETH, PA OCONNELL, MJ AF MILLER, KB KYUNGMANN, K MORRISON, FS WINTER, JN BENNETT, JM NEIMAN, RS HEAD, DR CASSILETH, PA OCONNELL, MJ TI THE EVALUATION OF LOW-DOSE CYTARABINE IN THE TREATMENT OF MYELODYSPLASTIC SYNDROMES - A PHASE-III INTERGROUP STUDY SO ANNALS OF HEMATOLOGY LA English DT Article DE LOW-DOSE CYTARABINE; MYELODYSPLASTIC SYNDROME ID COLONY-STIMULATING FACTOR; AGGRESSIVE CHEMOTHERAPY; CYTOSINE-ARABINOSIDE; LEUKEMIA; CLASSIFICATION AB One hundred and forty one patients were treated in a combined Eastern Cooperative Oncology Group and Southwest Oncology Group phase-III study evaluating low-dose cytarabine (LDAC) versus supportive therapy for the treatment of myelodysplastic syndrome (MDS). Patients were randomized to either cytarabine 10 mg/m2 subcutaneously BID or supportive therapy. Central pathology review was required. All patients were classified according to the FAB criteria for MDS. The overall concordance rate for the MDS subtype was 52%, and 25 patients were pathology exclusions, including 20 with AML. The overall response rate to a single cycle of LDAC was 32%, with 11% complete and 21% partial responses. The median duration of response was 5.9 months, with a range of 1.4-33.5 months. Responses were seen in all subtypes. Infections were more common in the LDAC arm. There was no difference in the time to progression or the overall survival for patients treated with LDAC or supportive therapy. The incidence of leukemic transformation was similar in both arms at 15%, but it differed according to the MDS subtype. Patients receiving LDAC had a decreased transfusion requirement after 3 months. There was a significant correlation between the degree of cytoreduction after receiving a single cycle of LDAC and survival. This survival difference was most marked in patients with the RAEB and RAEB-T subtypes. Although LDAC produced responses in all subtypes of the MDS, there was no effect on overall survival or transformation to AML. However, selected patients benefited from a single cycle of LDAC with durable responses. A cytoreductive effect appears to be required for a durable response. Future studies should include pathology review and must address the clinical and biological heterogeneity of MDS. C1 UNIV MISSISSIPPI, MED CTR, JACKSON, MS 39216 USA. HARVARD UNIV, SCH MED, DANA FARBER CANC INST, BOSTON, MA 02115 USA. NORTHWESTERN UNIV, MED CTR, CHICAGO, IL 60611 USA. UNIV ROCHESTER, CTR CANC, ROCHESTER, NY 14627 USA. INDIANA UNIV, CTR CANC, INDIANAPOLIS, IN 46204 USA. ST JUDE CHILDRENS RES HOSP, MEMPHIS, TN 38101 USA. UNIV PENN, CTR CANC, PHILADELPHIA, PA 19104 USA. MAYO CLIN & MAYO FDN, ROCHESTER, MN 55905 USA. RP MILLER, KB (reprint author), TUFTS UNIV, NEW ENGLAND MED CTR HOSP, 750 WASHINGTON ST, NEMC BOX 245, BOSTON, MA 02111 USA. NR 26 TC 102 Z9 105 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0939-5555 J9 ANN HEMATOL JI Ann. Hematol. PD OCT PY 1992 VL 65 IS 4 BP 162 EP 168 DI 10.1007/BF01703109 PG 7 WC Hematology SC Hematology GA JX619 UT WOS:A1992JX61900002 PM 1420504 ER PT J AU NILES, JL MCCLUSKEY, RT ARNAOUT, MA AF NILES, JL MCCLUSKEY, RT ARNAOUT, MA TI WEGENER GRANULOMATOSIS SO ANNALS OF INTERNAL MEDICINE LA English DT Letter ID AUTOANTIBODIES RP NILES, JL (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 4 TC 0 Z9 0 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 OCT 1 PY 1992 VL 117 IS 7 BP 620 EP 620 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA JQ226 UT WOS:A1992JQ22600028 PM 1482486 ER PT J AU STOREY, E KOWALL, NW FINN, SF MAZUREK, MF BEAL, MF AF STOREY, E KOWALL, NW FINN, SF MAZUREK, MF BEAL, MF TI THE CORTICAL LESION OF HUNTINGTONS-DISEASE - FURTHER NEUROCHEMICAL CHARACTERIZATION, AND REPRODUCTION OF SOME OF THE HISTOLOGICAL AND NEUROCHEMICAL FEATURES BY N-METHYL-D-ASPARTATE LESIONS OF RAT CORTEX SO ANNALS OF NEUROLOGY LA English DT Article ID PARVALBUMIN IMMUNOREACTIVE NEURONS; QUINOLINIC ACID LESIONS; GAMMA-AMINOBUTYRIC ACID; CEREBRAL-CORTEX; ALZHEIMERS-DISEASE; GLUTAMIC-ACID; BRAIN-TISSUE; KAINIC ACID; DEGENERATION; NEUROTRANSMITTERS AB Huntington's disease is a progressive neurodegenerative disease in which the basal ganglia are preferentially affected. Recent evidence, however, suggests involvement of the cerebral cortex as well, with sparing of neurochemically defined subsets of gamma-aminobutyric acid (GABA)-ergic interneurons. In the present study, we examined changes in concentrations of the amino acid neurotransmitters GABA, glutamate, and aspartate in nine cortical regions from 23 patients with advanced Huntington's disease and 12 control brains. GABA concentrations were significantly increased in eight of the nine regions, consistent with a sparing of GABAergic local circuit neurons in the context of progressive cortical atrophy. Small but significant increases in glutamate were found in six of the nine regions, while aspartate levels were generally unaffected. Striate cortex (Brodmann's area 17) showed the most profound increases in GABA and glutamate. We also investigated the effects of powdering the excitotoxins N-methyl-D-aspartate (NMDA) or kainic acid onto the dura of rats. The resulting lesions were examined at 1 week and 6 months. The NMDA-induced lesions showed striking sparing of parvalbumin-positive neurons (a subset of GABAergic interneurons), and this sparing was reflected in neurochemical measurements of GABA; kainic acid lesions failed to display this selectivity. Somatostatin, cholecystokinin, and vasoactive intestinal polypeptide concentrations were spared by the NMDA-induced lesions, and substance P levels were significantly increased. These results provide evidence that NMDA excitotoxic lesions of cerebral cortex can produce a selective pattern of neuronal damage similar to that which occurs in Huntington's disease. C1 MASSACHUSETTS GEN HOSP,NEUROCHEM LAB,FRUIT ST,BOSTON,MA 02114. MCMASTER UNIV,MED CTR,DEPT MED,HAMILTON L8S 4L8,ONTARIO,CANADA. HARVARD UNIV,SCH MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,EXPT NEUROPATHOL LAB,BOSTON,MA 02114. RI Kowall, Neil/G-6364-2012; Storey, Elsdon/A-9889-2013 OI Kowall, Neil/0000-0002-6624-0213; NR 40 TC 47 Z9 47 U1 0 U2 2 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD OCT PY 1992 VL 32 IS 4 BP 526 EP 534 DI 10.1002/ana.410320408 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA JR738 UT WOS:A1992JR73800007 PM 1280937 ER PT J AU ANTHONY, JP RITTER, E MOELLEKEN, BRW AF ANTHONY, JP RITTER, E MOELLEKEN, BRW TI UTILITY OF THE INFERIOR GLUTEAL VESSELS IN FREE FLAP COVERAGE OF SACRAL WOUNDS SO ANNALS OF PLASTIC SURGERY LA English DT Article AB An improved technique for gaining access to the inferior gluteal vessels is presented. This method allows rapid isolation of these vessels, preservation of greater pedicle length, and improved access for the performance of microsurgery. The innervation and function of the gluteus maximus is also preserved. We believe the use of this technique makes the inferior gluteal vessels the receptor vessels of choice for microsurgical procedures in the sacral area. An illustrative patient is presented in whom these vessels were used for a combined serratus anterior-latissimus dorsi free muscle flap for sacral wound coverage. C1 UNIV CALIF SAN FRANCISCO,DIV PLAST & RECONSTRUCT SURG,SAN FRANCISCO,CA 94143. SAN FRANCISCO VET ADM MED CTR,SAN FRANCISCO,CA. NR 15 TC 13 Z9 14 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0148-7043 J9 ANN PLAS SURG JI Ann. Plast. Surg. PD OCT PY 1992 VL 29 IS 4 BP 371 EP 375 DI 10.1097/00000637-199210000-00017 PG 5 WC Surgery SC Surgery GA JT338 UT WOS:A1992JT33800017 PM 1466537 ER PT J AU GRILLO, HC SHEPARD, JAO MATHISEN, DJ KANAREK, DJ AF GRILLO, HC SHEPARD, JAO MATHISEN, DJ KANAREK, DJ TI POSTPNEUMONECTOMY SYNDROME - DIAGNOSIS, MANAGEMENT, AND RESULTS SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 28TH ANNUAL MEETING OF THE SOC OF THORACIC SURGEONS CY FEB 03-05, 1992 CL ORLANDO, FL SP SOC THORAC SURGEONS ID RIGHT-PNEUMONECTOMY SYNDROME; INFANCY AB Airway obstruction may be caused by extreme mediastinal shift and rotation after right pneumonectomy or after left pneumonectomy in the presence of a right aortic arch. Eleven adults (aged 18 to 58 years) with severe symptoms were treated surgically between 5 months to 17 years after pneumonectomy (7 right, 4 left). An initial patient with only one functional lobe was treated unsuccessfully by aortic division and bypass graft. Ten underwent mediastinal repositioning. After two recurrences prostheses were used to maintain mediastinal position. Five patients who underwent such repositioning are doing well from 5 months to more than 5 years later. One died 1 month after operation probably of pulmonary embolism. One who showed residual airway collapse after operation has some recurrent obstruction. Three other patients who showed severe malacic obstruction of the airway after mediastinal repositioning variously underwent aortic division with bypass graft and tracheal and bronchial resection. One is well almost 6 years later. Two died postoperatively. Occurrence of the syndrome is unpredictable. Where malacic changes have not occurred, mediastinal repositioning may reasonably be expected to correct obstruction. Optimal treatment for concurrent severely malacic airways is unclear. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT MED,PULM UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT RADIOL,BOSTON,MA 02115. RP GRILLO, HC (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,GEN THORAC SURG UNIT,BOSTON,MA 02114, USA. NR 15 TC 72 Z9 75 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 OCT PY 1992 VL 54 IS 4 BP 638 EP 651 PG 14 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA JP898 UT WOS:A1992JP89800005 PM 1417220 ER PT J AU FISCHMAN, AJ LIVNI, E BABICH, J ALPERT, NM LIU, YY THOM, E CLEELAND, R PROSSER, BL CALLAHAN, RJ CORREIA, JA STRAUSS, HW RUBIN, RH AF FISCHMAN, AJ LIVNI, E BABICH, J ALPERT, NM LIU, YY THOM, E CLEELAND, R PROSSER, BL CALLAHAN, RJ CORREIA, JA STRAUSS, HW RUBIN, RH TI PHARMACOKINETICS OF F-18 LABELED FLEROXACIN IN RABBITS WITH ESCHERICHIA-COLI INFECTIONS, STUDIED WITH POSITRON EMISSION TOMOGRAPHY SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID LIQUID-CHROMATOGRAPHIC DETERMINATION; INVITRO ACTIVITY; TISSUE; METABOLITES; PENETRATION; RO-23-6240; QUINOLONE; AM-833; URINE AB F-18-labeled fleroxacin was used to measure the pharmacokinetics of fleroxacin in healthy and infected animals by positron emission tomography (PET) and tissue radioactivity measurements. In all experiments, a pharmacological dose of unlabeled drug (10 mg/kg) was coinjected with the tracer. The pharmacokinetics of [F-18]fleroxacin was measured in groups of healthy mice (n = six per group) at 10, 30, 60, and 120 min after injection and in groups of rats with Escherichia coli thigh infections (n = six per group) at 60 and 120 min after injection by radioactivity measurements in excised tissues. In healthy rabbits (n = 4) and in rabbits with E. coli thigh infections (n = 4), tissue concentrations of drug were determined by serial PET imaging over 2 h; after the final image was acquired, animals were sacrificed and concentrations measured by PET were compared with the results of tissue radioactivity measurements. In all three species, there was rapid equilibration of [F-18]fleroxacin to significant concentrations in most peripheral organs; low concentrations of drug were detected in the brain. Accumulations of radiolabeled drug in infected and healthy thigh muscles were similar. Peak concentrations of drug of more than three times the MIC for 90% of members of the family Enterobacteriaceae (>100-fold for most organisms) were achieved in all tissues except brain and remained above this level for more than 2 h. Especially high peak concentrations were achieved in the kidney (>75 mug/g), liver (>50 mug/g), blood (>25 mug/g), and bone and lung (>10 mug/g). Since the MICs for 90% of all Enterobacteriaceae are <2 mug/ml, fleroxacin should be particularly useful in treating gram-negative infections affecting these tissues. In contrast, the low concentration of drug delivered to the brain should limit the toxicity of the drug for the central nervous system. C1 HOFFMANN LA ROCHE INC,NUTLEY,NJ. HARVARD UNIV,SCH MED,DEPT RADIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,MED SERV,CLIN INVEST PROGRAM,BOSTON,MA 02114. RP FISCHMAN, AJ (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,DIV NUCL MED,BOSTON,MA 02114, USA. NR 27 TC 23 Z9 24 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD OCT PY 1992 VL 36 IS 10 BP 2286 EP 2292 PG 7 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA JQ679 UT WOS:A1992JQ67900035 PM 1444310 ER PT J AU JOHNSON, CC TAYLOR, S PITSAKIS, P MAY, P LEVISON, ME AF JOHNSON, CC TAYLOR, S PITSAKIS, P MAY, P LEVISON, ME TI BACTERICIDAL ACTIVITY OF RAMOPLANIN AGAINST ANTIBIOTIC-RESISTANT ENTEROCOCCI SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Note ID INVITRO ACTIVITY; STREPTOCOCCUS-FAECALIS; CLOSTRIDIUM-DIFFICILE; VANCOMYCIN; TEICOPLANIN; GENTAMICIN; INFECTIONS; AGENTS; A16686; RISK AB Ramoplanin, a new lipoglycodepsipeptide antibiotic, was uniformly active against 65 strains of enterococci, including strains highly resistant to vancomycin, penicillin, G, and gentamicin. MBCs were usually within a fourfold dilution of the MICs. In time-kill studies, ramoplanin alone demonstrated dose-dependent bactericidal activity against enterococcal strains that resisted killing by vancomycin or penicillin in combination with gentamicin. C1 DEPT VET AFFAIRS MED CTR,PHILADELPHIA,PA 19104. RP JOHNSON, CC (reprint author), MED COLL PENN,3300 HENRY AVE,PHILADELPHIA,PA 19129, USA. NR 24 TC 35 Z9 35 U1 0 U2 3 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 OCT PY 1992 VL 36 IS 10 BP 2342 EP 2345 PG 4 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA JQ679 UT WOS:A1992JQ67900045 PM 1444316 ER PT J AU JOHN, JF ATKINS, LT MAPLE, PAH BRATOEVA, M AF JOHN, JF ATKINS, LT MAPLE, PAH BRATOEVA, M TI ACTIVITIES OF NEWER FLUOROQUINOLONES AGAINST SHIGELLA-SONNEI SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Note ID QUINOLONES; RESISTANT; EPIDEMIC; MARKERS AB The activities of six fluoroquinolones were determined for 117 separate strains of Shigella sonnei. The order of increasing activity (MICs for 90% of strains tested) was enoxacin (0.25 mug/ml), temafloxacin (0.032 mug/ml), sparfloxacin (0.016 mug/ml), CI-960 (0.008 mug/ml), ciprofloxacin (0.008 mug/ml), and PD-131628-2 (0.008 mug/ml). These data, along with results of killing and mutational rate studies, showed that all six fluoroquinolones were highly inhibitory against S. sonnei and five fluoroquinolones were rapidly and persistently bactericidal. C1 MED UNIV S CAROLINA,DIV INFECT DIS,CHARLESTON,SC 29425. RALPH H JOHNSON DEPT VET AFFAIRS MED CTR,CHARLESTON,SC 29403. ROYAL FREE HOSP,LONDON NW3 2QG,ENGLAND. NR 19 TC 5 Z9 5 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 OCT PY 1992 VL 36 IS 10 BP 2346 EP 2348 PG 3 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA JQ679 UT WOS:A1992JQ67900046 PM 1444317 ER PT J AU KERY, V KREPINSKY, JJF WARREN, CD CAPEK, P STAHL, PD AF KERY, V KREPINSKY, JJF WARREN, CD CAPEK, P STAHL, PD TI LIGAND RECOGNITION BY PURIFIED HUMAN MANNOSE RECEPTOR SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID ALVEOLAR MACROPHAGE LECTIN; 175-KDA MEMBRANE-PROTEIN; BIOLOGICAL SIGNIFICANCE; MODEL OLIGOSACCHARIDES; FUCOSYLATED N,N'-DIACETYLCHITOBIOSIDE; BINDING; DOMAINS; CELLS; IDENTIFICATION; TRISACCHARIDE C1 UNIV TORONTO,DEPT MOLEC & MED GENET,TORONTO M5S 1A8,ONTARIO,CANADA. UNIV TORONTO,CARBOHYDRATE RES CTR,TORONTO M5S 1A8,ONTARIO,CANADA. SLOVAK ACAD SCI,CS-84238 BRATISLAVA,CZECHOSLOVAKIA. MASSACHUSETTS GEN HOSP,LOVETT LABS,CARBOHYDRATE UNIT,BOSTON,MA. RP KERY, V (reprint author), WASHINGTON UNIV,SCH MED,DEPT CELL BIOL & PHYSIOL,BOX 8228,660 S EUCLID AVE,ST LOUIS,MO 63110, USA. RI Stahl, Philip/D-6315-2012 NR 37 TC 55 Z9 55 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 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD OCT PY 1992 VL 298 IS 1 BP 49 EP 55 DI 10.1016/0003-9861(92)90092-B PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA JN143 UT WOS:A1992JN14300007 PM 1524442 ER PT J AU BADEN, HP KVEDAR, JC MAGRO, CM AF BADEN, HP KVEDAR, JC MAGRO, CM TI LOOSE ANAGEN HAIR AS A CAUSE OF HEREDITARY HAIR LOSS IN CHILDREN SO ARCHIVES OF DERMATOLOGY LA English DT Article ID ADHESION MOLECULES; CADHERIN AB Background and Design.-The loose anagen hair syndrome is a recently described disorder with enhanced hair loss in which anagen hairs can be painlessly pulled from the scalp. Results.-In three families, we have observed an autosomal dominant form of inheritance. We have confirmed that the extracted bulbs consist only of cortical cells and that the hair shafts have an abnormal shape. Using routine light and electron microscopy, we observed disadhesion between all layers of the follicle and within some layers and premature keratinization of the inner root sheath of the follicle. In addition, abnormal maturation of the various layers was observed at the electron microscopic level, including regions of the cortex that contained decreased numbers of filaments. The disorder appears to be cyclic, since relatively normal and markedly affected regions of the shaft can be observed within a single follicle. Conclusions.-Possible mechanisms responsible for the disease include abnormal intercellular signaling and disturbances of desmosomal components and/or cadherins. C1 UNIV MANITOBA,HLTH SCI CTR,DEPT PATHOL,WINNIPEG R3T 2N2,MANITOBA,CANADA. RP BADEN, HP (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT DERMATOL,CUTANEOUS BIOL RES CTR,13TH ST,BOSTON,MA 02139, USA. NR 22 TC 41 Z9 46 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 OCT PY 1992 VL 128 IS 10 BP 1349 EP 1353 DI 10.1001/archderm.128.10.1349 PG 5 WC Dermatology SC Dermatology GA JT343 UT WOS:A1992JT34300006 PM 1417022 ER PT J AU MINTZ, J MINTZ, LI ARRUDA, MJ HWANG, SS AF MINTZ, J MINTZ, LI ARRUDA, MJ HWANG, SS TI TREATMENTS OF DEPRESSION AND THE FUNCTIONAL-CAPACITY TO WORK SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID SOCIAL ADJUSTMENT; COGNITIVE THERAPY; SELF-REPORT; EFFICACY; DISORDER; PHARMACOTHERAPY; SCHIZOPHRENIA; OUTPATIENTS; PREDICTION; RECURRENCE AB This study evaluated the effects of antidepressants and psychotherapy on work impairment in depressed patients. Original databases from 10 published treatment studies were compiled and analyzed (N=827). Functional work impairment was common at baseline, manifested by unemployment (11%) or on-the-job performance problems (absenteeism, decreased productivity, interpersonal problems, 44%). Generally, work outcomes were good when treatment was symptomatically effective, but the trajectories of work restoration and symptom remission were different, with work recovery appearing to take considerably longer. Relapse was an important determinant of long-term occupational outcome, particularly for seriously ill patients for whom relapse meant rehospitalization or other profound social disruption. Affective impairment was distinguished from functional impairment, with the former characterizing milder depression and the latter characterizing moderate to severe depression. Some methodological recommendations are discussed. C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT PSYCHIAT & BIOBEHAV SCI,LOS ANGELES,CA 90024. RP MINTZ, J (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,691-B117,11301 WILSHIRE BLVD,LOS ANGELES,CA 90073, USA. NR 41 TC 464 Z9 469 U1 2 U2 23 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 OCT PY 1992 VL 49 IS 10 BP 761 EP 768 PG 8 WC Psychiatry SC Psychiatry GA JR569 UT WOS:A1992JR56900001 PM 1417427 ER PT J AU PROCHAZKA, AV PETTY, TL NETT, L SILVERS, GW SACHS, DPL RENNARD, SI DAUGHTON, DM GRIMM, RH HEIM, C AF PROCHAZKA, AV PETTY, TL NETT, L SILVERS, GW SACHS, DPL RENNARD, SI DAUGHTON, DM GRIMM, RH HEIM, C TI TRANSDERMAL CLONIDINE REDUCED SOME WITHDRAWAL SYMPTOMS BUT DID NOT INCREASE SMOKING CESSATION SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID RANDOMIZED TRIAL; DOUBLE-BLIND; PLACEBO AB Background.-Clonidine may be useful in controlling tobacco withdrawal and in facilitating smoking cessation. This study was developed to test the efficacy of transdermal clonidine in promoting smoking cessation. Methods.-We conducted a five-center, double-blind, placebo-controlled, randomized controlled trial of transdermal clonidine in conjunction with a minimal behavioral intervention for smoking cessation. The intervention was based on the American Lung Association's Freedom From Smoking program. Self report of not smoking was validated with exhaled air carbon monoxide of less than 8 ppm and salivary cotinine of less than 20 ng/mL. Transdermal clonidine therapy began 1 week before the target quit date: 0.1 mg/24 h for the first 4 days increasing to 0.2 mg/24 h for the next 3 days, if the lower dose was tolerated. The highest tolerated dose was then continued for 6 weeks after target quit day. Withdrawal symptoms were measured daily for the first 7 days after target quit day. Results.-A total of 213 patients were enrolled (106 active drug and 107 placebo). During the study, 15.5% of patients had drug therapy discontinued due to adverse effects, 24.5% (26/106) taking active drug vs 8.4% (9/107) receiving placebo. There was a significant reduction in anxiety score from 3.0 to 2.4 (placebo vs active) and irritability score from 2.2 to 1.7 (placebo vs active) during the first week after cessation. There was no reduction in other withdrawal symptoms. The overall 12-week abstinence rate was 33.0% (35/106) in the active drug group vs 34.5% (37/107) in the placebo group (not significant). Conclusion.-This study demonstrated some reduction in early withdrawal symptoms with the use of a clonidine transdermal patch, but no increase in cessation rate, 6 weeks after medication had been discontinued. C1 PRESBYTERIAN UNIV HOSP,ST LUKES CTR HLTH SCI EDUC,DENVER,CO. UNIV NEBRASKA,DEPT MED,PULM SECT,CTR PULM DIS PREVENT,OMAHA,NE 68182. UNIV MINNESOTA,SCH PUBL HLTH,MINNEAPOLIS,MN 55455. VANDERBILT UNIV,DEPT MED,GEN INTERNAL MED SECT,NASHVILLE,TN 37240. RP PROCHAZKA, AV (reprint author), DENVER VET AFFAIRS MED CTR,AMBULATORY CARE SECT,DENVER,CO, USA. FU NIDA NIH HHS [DA-04986] NR 26 TC 30 Z9 30 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD OCT PY 1992 VL 152 IS 10 BP 2065 EP 2069 DI 10.1001/archinte.152.10.2065 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA JT163 UT WOS:A1992JT16300015 PM 1417380 ER PT J AU HENSON, JW WALKER, RW STOVER, DE FELS, AOS JALAJ, JK AF HENSON, JW WALKER, RW STOVER, DE FELS, AOS JALAJ, JK TI PNEUMOCYSTIS-CARINII PNEUMONIA ASSOCIATED WITH SOLID ECTOPIC CORTICOTROPIN-PRODUCING TUMORS - REPLY SO ARCHIVES OF NEUROLOGY LA English DT Letter C1 MEM SLOAN KETTERING CANC CTR,DEPT NEUROL,NEW YORK,NY 10021. MEM SLOAN KETTERING CANC CTR,DIV PULM,NEW YORK,NY 10021. CORNELL UNIV,MED CTR,NEW YORK HOSP,DEPT PSYCHIAT,NEW YORK,NY 10021. RP HENSON, JW (reprint author), MASSACHUSETTS GEN HOSP,NEUROL SERV,MOLEC NEUROONCOL LAB,FRUIT ST,BOSTON,MA 02114, USA. NR 4 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1992 VL 49 IS 10 BP 1012 EP 1012 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA JR326 UT WOS:A1992JR32600005 ER PT J AU SCHMAHMANN, JD LEIFER, D AF SCHMAHMANN, JD LEIFER, D TI PARIETAL PSEUDOTHALAMIC PAIN SYNDROME - CLINICAL-FEATURES AND ANATOMIC CORRELATES SO ARCHIVES OF NEUROLOGY LA English DT Article ID HUMAN CEREBRAL-CORTEX; RHESUS-MONKEY; ELECTRICAL-STIMULATION; ASSOCIATION CORTEX; THALAMIC AFFERENTS; POSTERIOR; ORGANIZATION AB We studied six patients who developed spontaneous hemibody pain following lesions of the parietal lobe. The pain was characterized as burning or icelike, and was associated with impairment of pin and temperature appreciation. Computed tomographic scanning showed that the common area of involvement in all cases was the white matter deep to both the caudal insula and the opercular region of the posterior parietal cortex. We suggest that disruption of the interconnections between these cerebral cortical areas (including the second somatosensory representation, SII) and the thalamus, particularly the intralaminar and ventroposterior nuclei, may be responsible for producing a thalamocortical disconnection syndrome with spontaneous pain as its clinical manifestation. C1 HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. CHILDRENS HOSP MED CTR,BOSTON,MA 02115. EDITH NOURSE ROGERS MEM VET ADM HOSP,BEDFORD,MA 01730. RP SCHMAHMANN, JD (reprint author), MASSACHUSETTS GEN HOSP,DEPT NEUROL,KENNEDY 905B,14 FRUIT ST,BOSTON,MA 02114, USA. FU NICHD NIH HHS [HD00888] NR 46 TC 113 Z9 113 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 OCT PY 1992 VL 49 IS 10 BP 1032 EP 1037 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA JR326 UT WOS:A1992JR32600009 PM 1417510 ER PT J AU GUYER, DR ADAMIS, AP GRAGOUDAS, ES FOLKMAN, J SLAKTER, JS YANNUZZI, LA AF GUYER, DR ADAMIS, AP GRAGOUDAS, ES FOLKMAN, J SLAKTER, JS YANNUZZI, LA TI SYSTEMIC ANTIANGIOGENIC THERAPY FOR CHOROIDAL NEOVASCULARIZATION - WHAT IS THE ROLE OF INTERFERON ALFA SO ARCHIVES OF OPHTHALMOLOGY LA English DT Editorial Material ID ANGIOGENESIS; INHIBITION; GROWTH C1 MASSACHUSETTS EYE & EAR INFIRM,243 CHARLES ST,BOSTON,MA 02114. NR 29 TC 18 Z9 18 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 OCT PY 1992 VL 110 IS 10 BP 1383 EP 1384 PG 2 WC Ophthalmology SC Ophthalmology GA JT349 UT WOS:A1992JT34900013 PM 1384461 ER PT J AU LU, Y ANDERSON, S CORBLEY, MJ ZHOU, YC PROSS, H HALIOTIS, T AF LU, Y ANDERSON, S CORBLEY, MJ ZHOU, YC PROSS, H HALIOTIS, T TI RAS MODULATES COMMITMENT AND MATURATION OF 10T1/2 FIBROBLASTS TO ADIPOCYTES SO BIOCHEMISTRY AND CELL BIOLOGY-BIOCHIMIE ET BIOLOGIE CELLULAIRE LA English DT Article DE RAS PROTOONCOGENE; CELL DIFFERENTIATION; SIGNAL TRANSDUCTION; INSULIN; ADIPOCYTES ID PROTEIN-KINASE-C; MAMMARY EPITHELIAL-CELLS; MOUSE EMBRYO CELLS; GENE-EXPRESSION; 3T3-L1 FIBROBLASTS; ADIPOSE CONVERSION; DOWN-REGULATION; ONCOGENE LEADS; FOS EXPRESSION; HA-RAS AB The positive association of the ras oncogene with human cancer and the recognition that malignancy may, in part, represent the imbalance between cell proliferation and differentiation have generated intense interest in the potential role of ras in cell differentiation. We investigated this possibility utilizing as a model system the differentiation of the mesenchymal cell line C3H 10T1/2 (10T1/2) to adipocytes, and a series of transfectants of 10T1/2 cells in which the level of the ras gene product (p21ras; Ras) can be effectively up- or down-modulated. In agreement with previous reports, we found that 10T1/2 cultures, propagated in the resting state for several weeks, spontaneously convert to fat cells at a very low frequency. Downmodulation of endogenous p21ras levels, as a consequence of expression of antisense ras, markedly increased the rapidity and frequency of adipose conversion (6- to 10-fold), which was equivalent in magnitude to that effected by the potent differentiating agent 5-azacytidine. Conversely, overexpression of ras completely inhibited cell differentiation. In addition, adipocytes derived from antisense-ras expressing lines were characterized by a decrease in hormone responsiveness, as well as an apparent deficiency in attaining the terminally differentiated state. These findings suggest that Ras may be a negative regulator of the decision-making step of fibroblast differentiation to adipocytes. In addition, Ras may play an essential positive role in the transduction of hormonal signals necessary for full adipocytic maturation during later progression along the differentiation pathway. C1 QUEENS UNIV,DEPT PATHOL,CANC RES LABS,KINGSTON K7L 3N6,ONTARIO,CANADA. QUEENS UNIV,DEPT MICROBIOL & IMMUNOL,KINGSTON K7L 3N6,ONTARIO,CANADA. BIOTECHNOL RES INST,DEPT MOLEC IMMUNOL,MONTREAL H4P 2R2,PQ,CANADA. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NR 42 TC 18 Z9 18 U1 0 U2 0 PU NATL RESEARCH COUNCIL CANADA PI OTTAWA PA RESEARCH JOURNALS, MONTREAL RD, OTTAWA ON K1A 0R6, CANADA SN 0829-8211 J9 BIOCHEM CELL BIOL JI Biochem. Cell Biol. PD OCT-NOV PY 1992 VL 70 IS 10-11 BP 1249 EP 1257 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KQ352 UT WOS:A1992KQ35200043 PM 1297345 ER PT J AU BLAZERYOST, BL SHAH, N JARETT, L COX, M SMITH, RM AF BLAZERYOST, BL SHAH, N JARETT, L COX, M SMITH, RM TI INSULIN AND IGF1 RECEPTORS IN A MODEL RENAL EPITHELIUM - RECEPTOR LOCALIZATION AND CHARACTERIZATION SO BIOCHEMISTRY INTERNATIONAL LA English DT Article ID GROWTH-FACTOR-I; NA+-TRANSPORT; BASOLATERAL MEMBRANES; PLASMA-MEMBRANE; MESANGIAL CELLS; RAT; SOMATOMEDIN; ANTIBODIES; BINDING; I-125-INSULIN C1 UNIV PENN,SCH MED,DEPT PATHOL & LAB MED,PHILADELPHIA,PA 19104. RP BLAZERYOST, BL (reprint author), VET AFFAIRS MED CTR,DEPT MED,RENAL ELECTROLYTE SECT,PHILADELPHIA,PA 19104, USA. FU NIDDK NIH HHS [DK19525, DK 28143] NR 36 TC 25 Z9 25 U1 0 U2 1 PU ACADEMIC PRESS AUST PI MARRICKVILLE PA LOCKED BAG 16, MARRICKVILLE NSW 2204, AUSTRALIA SN 0158-5231 J9 BIOCHEM INT PD OCT PY 1992 VL 28 IS 1 BP 143 EP 153 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JU246 UT WOS:A1992JU24600017 PM 1445387 ER PT J AU TAO, NJ LINDSAY, SM LEES, S AF TAO, NJ LINDSAY, SM LEES, S TI MEASURING THE MICROELASTIC PROPERTIES OF BIOLOGICAL-MATERIAL SO BIOPHYSICAL JOURNAL LA English DT Note ID ATOMIC-FORCE MICROSCOPE; SURFACE FORCES; SCALE FRICTION; TUNGSTEN TIP; TISSUES; WATER AB We have used the atomic force microscope (AFM) to measure the local rigidity modulus at points on the surface of a section of hydrated cow tibia. These data are obtained either from contrast changes that occur as the contact force is altered, or from force versus distance curves obtained at fixed points. These two methods yield the same values for rigidity modulus (at a given point). At low resolution, the elastic morphology and topography mirror the features seen in optical and electron micrographs. At high resolution we see dramatic variations in elastic properties across distances as small as 50 nm. C1 FORSYTH DENT CTR,DEPT BIOENGN,BOSTON,MA 02115. RP TAO, NJ (reprint author), ARIZONA STATE UNIV,DEPT PHYS,TEMPE,AZ 85287, USA. RI Tao, NJ/B-1628-2008 FU NIA NIH HHS [AGO 2325] NR 22 TC 162 Z9 165 U1 1 U2 22 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD OCT PY 1992 VL 63 IS 4 BP 1165 EP 1169 PG 5 WC Biophysics SC Biophysics GA JU251 UT WOS:A1992JU25100029 PM 1420932 ER PT J AU HALLEK, M LEPISTO, EM SLATTERY, KE GRIFFIN, JD ERNST, TJ AF HALLEK, M LEPISTO, EM SLATTERY, KE GRIFFIN, JD ERNST, TJ TI INTERFERON-GAMMA INCREASES THE EXPRESSION OF THE GENE ENCODING THE BETA-SUBUNIT OF THE GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR RECEPTOR SO BLOOD LA English DT Article ID TUMOR-NECROSIS-FACTOR; GROWTH-FACTOR RECEPTORS; HUMAN MYELOID CELLS; GM-CSF RECEPTOR; IFN-GAMMA; HUMAN-MONOCYTES; BINDING; DIFFERENTIATION; MODULATION; ACTIVATION C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,44 BINNEY ST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. FU NCI NIH HHS [CA36167] NR 39 TC 26 Z9 26 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 OCT 1 PY 1992 VL 80 IS 7 BP 1736 EP 1742 PG 7 WC Hematology SC Hematology GA JQ374 UT WOS:A1992JQ37400013 PM 1382701 ER PT J AU FINE, HA ANTMAN, KH AF FINE, HA ANTMAN, KH TI HIGH-DOSE CHEMOTHERAPY WITH AUTOLOGOUS BONE-MARROW TRANSPLANTATION IN THE TREATMENT OF HIGH-GRADE ASTROCYTOMAS IN ADULTS - THERAPEUTIC RATIONALE AND CLINICAL-EXPERIENCE SO BONE MARROW TRANSPLANTATION LA English DT Review ID MALIGNANT BRAIN-TUMORS; CENTRAL-NERVOUS-SYSTEM; PHASE-II; GLIOMAS; RADIOTHERAPY; BCNU; TRIAL; CANCER; GLIOBLASTOMA; VINCRISTINE AB High-grade astrocytomas are the most common primary malignant brain tumors in adults and constitute a significant cancer problem in the USA accounting for nearly 11 000 deaths annually. Despite improvements in neurosurgical techniques and radiotherapy, the prognosis of these patients remains dismal with median survivals of less than 1 year. Recent data suggest that conventional chemotherapy may be more active in these tumors than previously appreciated but survival has not been substantially altered. Poor drug delivery secondary to the unique neuroanatomical and pathologic constraints of the blood-brain and blood-tumor barrier may contribute to the lack of a significant impact of conventional dose chemotherapy on the natural history of these tumors. In addition, the substantial intratumor cellular heterogeneity invariably found in these tumors undoubtedly contributes to the development of drug resistance. Based on trials of high-dose chemotherapy with autologous bone marrow transplantation (ABMT) in other tumor types, clinical investigators have begun to consider the potential for high-dose chemotherapy to overcome problems of poor drug delivery and cellular drug resistance in brain tumors. In this report, the rationale behind the use of high-dose chemotherapy with ABMT in the treatment of patients with high-grade astrocytomas, and relevant clinical trials conducted to date, are reviewed. Although these trials suggest that survival is not improved in patients treated at the time of relapse, early data suggest that high-dose chemotherapy with ABMT may hold promise as adjuvant treatment in this patient population. RP FINE, HA (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,DIV CLIN ONCOL,44 BINNEY ST,BOSTON,MA 02115, USA. NR 54 TC 27 Z9 28 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD OCT PY 1992 VL 10 IS 4 BP 315 EP 321 PG 7 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA JT181 UT WOS:A1992JT18100001 PM 1330152 ER PT J AU TRIGGS, WJ CROS, D GOMINAK, SC ZUNIGA, G BERIC, A SHAHANI, BT ROPPER, AH ROONGTA, SM AF TRIGGS, WJ CROS, D GOMINAK, SC ZUNIGA, G BERIC, A SHAHANI, BT ROPPER, AH ROONGTA, SM TI MOTOR-NERVE INEXCITABILITY IN GUILLAIN-BARRE-SYNDROME - THE SPECTRUM OF DISTAL CONDUCTION BLOCK AND AXONAL DEGENERATION SO BRAIN LA English DT Article ID ELECTRODIAGNOSTIC ABNORMALITIES; PROGNOSTIC VALUE; POLYNEUROPATHY AB We studied 34 patients with the Guillain-Barre syndrome (GBS) to clarify the clinical significance of inexcitable motor nerves and of low amplitude compound muscle action potentials (CMAPs). The patients were subdivided into two groups. Group 1 included eight patients who had electrically inexcitable motor nerves within 2 wks of the first symptom. (Two patients without extensive conduction studies had only one inexcitable motor nerve.) The outcome in this group at 1 yr varied from complete recovery (five patients) to severe motor sequelae (three patients). Group 2 included 26 patients who had two electrophysiological assessments, and in whom the serial changes in CMAP amplitudes were analysed and cor-related to outcome. Fourteen of these 26 sets of serial studies were performed within 1 mth. Twelve of 26 patients in Group 2 showed decrease in the amplitude of CMAPs between serial studies; only six of these had a good outcome at 1 yr. Nine of 26 patients showed increase in CMAP amplitude between serial studies, of these eight had a good clinical outcome. Low-amplitude CMAPs or inexcitable motor nerves in the initial stages of GBS are due to distal pathology of the motor axons, either distal conduction block or axonal degeneration. The nature of these changes cannot be predicted by the results of the initial electrophysiological evaluation, including the presence or absence of active denervation. However, improvement of CMAP amplitude on sequential studies suggests a good outcome at 1 yr. We believe that, in the absence of a biological marker for GBS, individualization of an 'axonal variant' of the syndrome is not warranted at the present time. C1 MASSACHUSETTS GEN HOSP,CLIN NEUROPHYSIOL LAB,BIGELOW 12,FRUIT ST,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. TEMPLE UNIV HOSP & MED SCH,DEPT NEUROL,PHILADELPHIA,PA 19140. UNIV TEXAS,HLTH SCI CTR,DEPT NEUROL,HOUSTON,TX 77225. NR 23 TC 75 Z9 76 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0006-8950 J9 BRAIN JI Brain PD OCT PY 1992 VL 115 BP 1291 EP 1302 DI 10.1093/brain/115.5.1291 PN 5 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA JY715 UT WOS:A1992JY71500003 PM 1422789 ER PT J AU LEUCHTER, AF NEWTON, TF COOK, IA WALTER, DO ROSENBERGTHOMPSON, S LACHENBRUCH, PA AF LEUCHTER, AF NEWTON, TF COOK, IA WALTER, DO ROSENBERGTHOMPSON, S LACHENBRUCH, PA TI CHANGES IN BRAIN FUNCTIONAL CONNECTIVITY IN ALZHEIMER-TYPE AND MULTIINFARCT DEMENTIA SO BRAIN LA English DT Article ID SOMATOSENSORY EVOKED-POTENTIALS; VASCULAR DEMENTIA; MULTIINFARCT DEMENTIA; CLINICAL-DIAGNOSIS; EEG COHERENCE; DIFFERENTIAL-DIAGNOSIS; LAMINAR DISTRIBUTIONS; COMPUTED-TOMOGRAPHY; SENILE DEMENTIA; LEUKO-ARAIOSIS AB Clinical and neuropathological evaluation of elderly subjects with dementia has traditionally concentrated upon the focal distribution of brain disease, ignoring changes in the complex connections that link brain areas and that are crucial for cognition. We examined subjects with the two most common forms of dementia in the elderly (dementia of the Alzheimer type or DAT, and multi-infarct dementia or MID); and used electroencephalographic (EEG) coherence to examine the effects of these illnesses on the functional connections between brain areas. We studied coherence between brain areas known to be linked by two different types of connections: (i) dense narrow bands of long corticocortical fibres; (ii) broad complex networks of corticocortical and corticosubcortical fibres. Areas that were linked by dense narrow bands of long corticocortical fibres showed greatly diminished coherence in subjects with DAT; among MID subjects, this coherence was not significantly affected. Areas that were linked by broad connective networks showed the largest decreases in coherence among MID subjects. These findings are consistent with neuropathological evidence that Alzheimer's disease is a neocortical 'disconnection syndrome' in which there is a loss of structural and functional integrity of long corticocortical tracts. The findings further suggest that the vascular disease of MID most prominently affects broad fibre networks that may be more vulnerable to diffuse subcortical vascular damage. A ratio of coherence from complex corticocortical-corticosubcortical networks divided by coherence from long corticocortical tracts correctly classified 76% of subjects into DAT and MID categories. Overall, these results indicate that EEG coherence detects basic pathophysiological differences between subjects with DAT and MID, and that these differences may be clinically useful. C1 UNIV CALIF LOS ANGELES, NEUROPSYCHIAT INST & HOSP, CLIN ELECTROPHYSIOL LAB, LOS ANGELES, CA 90024 USA. W LOS ANGELES VET AFFAIRS MED CTR, DEPT PSYCHIAT, LOS ANGELES, CA USA. UNIV CALIF LOS ANGELES, SCH PUBL HLTH, DEPT BIOSTAT, LOS ANGELES, CA 90024 USA. RP UNIV CALIF LOS ANGELES, SCH MED, DEPT PSYCHIAT & BIOBEHAV SCI, 760 WESTWOOD PL, LOS ANGELES, CA 90024 USA. OI newton, thomas/0000-0002-3198-5901 FU NIMH NIH HHS [MH 00665, MH 17140, MH 40705] NR 79 TC 169 Z9 173 U1 0 U2 11 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 EI 1460-2156 J9 BRAIN JI Brain PD OCT PY 1992 VL 115 BP 1543 EP 1561 DI 10.1093/brain/115.5.1543 PN 5 PG 19 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA JY715 UT WOS:A1992JY71500018 PM 1422803 ER PT J AU GASSER, T FAHN, S BREAKEFIELD, XO AF GASSER, T FAHN, S BREAKEFIELD, XO TI THE AUTOSOMAL DOMINANT DYSTONIAS SO BRAIN PATHOLOGY LA English DT Article ID IDIOPATHIC TORSION DYSTONIA; DOPA-RESPONSIVE DYSTONIA; MARKED DIURNAL FLUCTUATION; BETA-HYDROXYLASE ACTIVITY; MYOCLONIC DYSTONIA; SYMPTOMATIC HEMIDYSTONIA; MUSCULORUM DEFORMANS; SEGREGATION ANALYSIS; MOVEMENT-DISORDERS; ASHKENAZI JEWS AB Dystonia is a term used to describe a specific set of abnormal movements that can occur as a symptom of a variety of neurologic disorders, but also as a disease entity in its own right. This review focuses on the primary dystonias and delineates the genetic contribution to these disorders. Included is a description of the well recognized forms of primary dystonias which manifest autosomal dominant inheritance, especially the "classic" type of early onset, generalized torsion dystonia, but also other clinically distinct forms such as myoclonic dystonia, paroxysmal dystonia, and DOPA-responsive dystonia. Also, a summary of the molecular genetic studies pertinent to these disorders and a discussion of the implications of recent genetic research for delineating the wide spectrum of this phenotypically and genetically heterogeneous group of diseases are forthcoming. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,MOLEC NEUROGENET UNIT,BOSTON,MA 02129. COLUMBIA UNIV COLL PHYS & SURG,DYSTONIA CLIN RES CTR,DEPT NEUROL,NEW YORK,NY 10032. NR 107 TC 13 Z9 13 U1 1 U2 2 PU INT SOC NEUROPATHOLOGY PI ZURICH PA ISN JOURNAL PO BOX, CH-8033 ZURICH, SWITZERLAND SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD OCT PY 1992 VL 2 IS 4 BP 297 EP 308 DI 10.1111/j.1750-3639.1992.tb00707.x PG 12 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA JR602 UT WOS:A1992JR60200005 PM 1341964 ER PT J AU SAVAGE, AP MALT, RA AF SAVAGE, AP MALT, RA TI SURVIVAL AFTER HEPATIC RESECTION FOR MALIGNANT-TUMORS SO BRITISH JOURNAL OF SURGERY LA English DT Article ID COLORECTAL LIVER METASTASES; PRIMARY HEPATOCELLULAR-CARCINOMA; NATURAL-HISTORY; MULTIVARIATE-ANALYSIS; SURGICAL-MANAGEMENT; CANCER; SURGERY; EXPERIENCE; DETERMINANTS; RECURRENCE AB A retrospective analysis of 194 patients who underwent hepatic resection for primary or metastatic malignant disease from January 1962 to December 1988 was undertaken to determine variables that might aid the selection of patients for hepatic resection. Hepatic metastases were the indication.for resection in 126 patients. The 5-year survival rate was 17 per cent. For patients with resected metastases from colorectal cancer (n = 104), the survival rate at 5 years was 18 per cent. The 5-year survival rate was 27 per cent when the resection margin was > 5 mm compared with 9 per cent when the margin was less-than-or-equal-to 5 mm (P < 0.01). No patient with extrahepatic invasion, lymphatic spread, involvement of the resection margin or gross residual disease survived to 5 years, compared with a 23 per cent 5-year survival rate for patients undergoing curative resection (P < 0.02). The survival rate of patients with poorly differentiated primary tumours was nil at 3 years compared with a 20 per cent 5-year survival rate for patients with well or moderately differentiated tumours (P not significant). The site and Dukes' classification of the primary tumour, the sex and preoperative carcinoembryonic antigen level of the patient, and the number and size of hepatic metastases did not effect the prognosis. The 5-year survival rate for patients with hepatocellular carcinoma (n = 42) was 25 per cent. An improved survival rate was found for patients whose alpha-fetoprotein level was normal (37 per cent at 5 years) compared with those having a raised level (nil at 3 years) (P < 0.01). Involvement of the resection margin, extrahepatic spread and spread to regional lymph nodes were associated with an 8 per cent 5-year survival rate versus 44 per cent for curative resection (P < 0-005). The presence of cirrhosis, the presence of symptoms, and the multiplicity and size of the tumour did not affect the prognosis. The 5-year survival rate of 11 patients with hepatic sarcoma was 25 per cent. No patient with peripheral cholangiocarcinoma survived to 1 year in contrast to patients with hilar cholangiocarcinoma, all.four of whom survived for more than 14 months. C1 MASSACHUSETTS GEN HOSP,SURG SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. NR 63 TC 47 Z9 47 U1 0 U2 1 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 OCT PY 1992 VL 79 IS 10 BP 1095 EP 1101 DI 10.1002/bjs.1800791035 PG 7 WC Surgery SC Surgery GA JT976 UT WOS:A1992JT97600033 PM 1330197 ER PT J AU BASTILLE, JD AF BASTILLE, JD TI SALARIES AND PROFESSIONAL AUTHORITY SO BULLETIN OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Editorial Material RP BASTILLE, JD (reprint author), MASSACHUSETTS GEN HOSP,TREADWELL LIB,BOSTON,MA 02114, USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU MEDICAL LIBRARY ASSOC PI CHICAGO PA STE 300, 6 N MICHIGAN AVE, CHICAGO, IL 60602 SN 0025-7338 J9 B MED LIBR ASSOC JI Bull. Med. Libr. Assoc. PD OCT PY 1992 VL 80 IS 4 BP 386 EP 387 PG 2 WC Information Science & Library Science SC Information Science & Library Science GA JT353 UT WOS:A1992JT35300016 PM 1422515 ER PT J AU TROP, M ANDERSON, TD SCHIFFRIN, EJ CARTER, EA AF TROP, M ANDERSON, TD SCHIFFRIN, EJ CARTER, EA TI EFFECT OF CHRONIC INTERLEUKIN-2 TREATMENT ON RES PHAGOCYTIC-ACTIVITY IN THE RAT SO BURNS LA English DT Article AB The effect of chronic interleukin-2 (IL-2) injection upon reticuloendothelial system (RES) function in the rat has been determined. Seven-day treatments with two doses of human recombinant IL-2 resulted in a dramatic reduction in the phagocytic uptake of the liver and spleen, while increasing the weight of both organs. There were dramatic histological changes in the intestine, liver and spleen as well. These results suggest that the chronic use of IL-2 can result in hepatic dysfunction, which is associated with altered RES phagocytic function. C1 MASSACHUSETTS GEN HOSP,COMBINED PROGRAM PEDIAT GASTROENTEROL & NUTR,DEPT PEDIAT,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BUTTERWORTH-HEINEMANN LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0305-4179 J9 BURNS JI Burns PD OCT PY 1992 VL 18 IS 5 BP 388 EP 389 PG 2 WC Critical Care Medicine; Dermatology; Surgery SC General & Internal Medicine; Dermatology; Surgery GA JQ855 UT WOS:A1992JQ85500006 ER PT J AU SILVA, JA LEONG, GB WINE, DB SAAB, S AF SILVA, JA LEONG, GB WINE, DB SAAB, S TI EVOLVING MISIDENTIFICATION SYNDROMES AND FACIAL RECOGNITION DEFICITS SO CANADIAN JOURNAL OF PSYCHIATRY-REVUE CANADIENNE DE PSYCHIATRIE LA English DT Article ID CAPGRAS SYNDROME; ATROPHY AB In this paper, the authors report the case of a 33 year old man with several misidentification delusions involving the self. Evidence suggests that one type of misidentification delusion may evolve into another type. Neuropsychological testing further suggests that misidentification delusions may be associated with subtle abnormalities in facial recognition abilities and with non dominant cerebral compromise. C1 UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA. NR 19 TC 7 Z9 7 U1 0 U2 0 PU CANADIAN PSYCHIATRIC ASSOC PI OTTAWA PA SUITE 200, 237 ARGYLE AVE, OTTAWA ON K2P 1B8, CANADA SN 0706-7437 J9 CAN J PSYCHIAT JI Can. J. Psychiat.-Rev. Can. Psychiat. PD OCT PY 1992 VL 37 IS 8 BP 574 EP 576 PG 3 WC Psychiatry SC Psychiatry GA JW687 UT WOS:A1992JW68700010 PM 1423161 ER PT J AU LYNCH, TJ CLARK, JR KALISH, LA FALLON, BG ELIAS, AD SKARIN, A FREI, E AF LYNCH, TJ CLARK, JR KALISH, LA FALLON, BG ELIAS, AD SKARIN, A FREI, E TI CONTINUOUS-INFUSION CISPLATIN, 5-FLUOROURACIL, AND BOLUS METHOTREXATE IN THE TREATMENT OF ADVANCED NON-SMALL-CELL LUNG-CANCER SO CANCER LA English DT Article DE NON-SMALL-CELL LUNG CANCER; CISPLATIN; 5-FLUOROURACIL; COMBINATION CHEMOTHERAPY; PERIPHERAL NEUROPATHY ID PHASE-I TRIAL; RANDOMIZED TRIAL; COMBINATION CHEMOTHERAPY; NEUROTOXICITY; CARCINOMA; 5-FU AB Background. Cisplatin and 5-fluorouracil have noted synergy in preclinical systems. The authors combined methotrexate with infusional cisplatin and 5-fluorouracil in an attempt to produce a regimen with improved activity in advanced NSCLC. Methods. Twenty-six ambulatory patients with previously untreated non-small cell lung cancer were treated with continuous-infusion cisplatin (25 mg/m2/day for 5 days), 5-fluorouracil (800 mg/m2/day for 5 days), and intermediate-dose methotrexate (200 mg/m2 on days 15, 22), followed by leucovorin rescue (PFM regimen). Results. Patients received a median of four cycles of therapy. Two patients had a complete response, and 10 had a partial response (overall response rate, 46.2% or 12 of 26). The median time to treatment failure was 22.5 weeks; the median survival was 55 weeks from the start of chemotherapy. There were no toxic deaths attributed to chemotherapy. Thrombocytopenia was the only Grade 4 toxicity (27%). Grade 1/4 and 2/4 peripheral neuropathy occurred in 17 of 26 patients (66%) and was associated with a cumulative cisplatin dose of more than 300 mg/m2. Conclusions. PFM (using continuous-infusion cisplatin) produced a high response rate but resulted in an high incidence of low-grade peripheral neuropathy. C1 HARVARD UNIV, SCH MED, DANA FARBER CANC INST, DIV BIOSTAT, BOSTON, MA 02215 USA. RP HARVARD UNIV, SCH MED, DANA FARBER CANC INST, DIV CLIN ONCOL, 44 BINNEY ST, BOSTON, MA 02215 USA. FU NCI NIH HHS [CA-06516, CA-19589] NR 26 TC 9 Z9 9 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD OCT 1 PY 1992 VL 70 IS 7 BP 1880 EP 1885 DI 10.1002/1097-0142(19921001)70:7<1880::AID-CNCR2820700713>3.0.CO;2-3 PG 6 WC Oncology SC Oncology GA JP692 UT WOS:A1992JP69200012 PM 1326396 ER PT J AU LEIFER, D GRABOWSKI, T SIMONIAN, N DEMIRJIAN, ZN AF LEIFER, D GRABOWSKI, T SIMONIAN, N DEMIRJIAN, ZN TI LEPTOMENINGEAL MYELOMATOSIS PRESENTING WITH MENTAL STATUS CHANGES AND OTHER NEUROLOGIC FINDINGS SO CANCER LA English DT Article DE MYELOMA; LEPTOMENINGEAL METASTASES; NEUROLOGIC MANIFESTATIONS; INTRATHECAL CHEMOTHERAPY ID MULTIPLE-MYELOMA; MENINGEAL MYELOMA; SOLID TUMORS; INVOLVEMENT; INFILTRATION; METASTASES AB Background. Leptomeningeal myelomatosis is a rare complication of multiple myeloma. Methods. The authors identified and studied three patients with leptomeningeal myelomatosis and reviewed previous case reports of this condition. Results. The patients described here had intermittent abnormalities in mental status or cranial nerve and brain stem abnormalities. Two of the patients responded dramatically, though transiently, to treatment. In one patient, the clinical findings correlated with lesions visualized by gadolinium-enhanced magnetic resonance imaging. Conclusions. These patients are typical of those reported previously. Patients with leptomeningeal myelomatosis often have a good response to treatment initially, but long-term survival is rare. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. RP LEIFER, D (reprint author), CHILDRENS HOSP MED CTR,DEPT NEUROL,BOSTON,MA 02115, USA. NR 39 TC 33 Z9 34 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 OCT 1 PY 1992 VL 70 IS 7 BP 1899 EP 1904 DI 10.1002/1097-0142(19921001)70:7<1899::AID-CNCR2820700716>3.0.CO;2-3 PG 6 WC Oncology SC Oncology GA JP692 UT WOS:A1992JP69200015 PM 1525764 ER PT J AU KANG, S BARNHILL, RL MIHM, MC SOBER, AJ AF KANG, S BARNHILL, RL MIHM, MC SOBER, AJ TI MULTIPLE PRIMARY CUTANEOUS MELANOMAS SO CANCER LA English DT Article DE MULTIPLE MELANOMAS; PRIMARY MELANOMA; DYSPLASTIC NEVI ID DYSPLASTIC NEVUS SYNDROME; MALIGNANT-MELANOMA; ASSOCIATION AB Background. Development of multiple primary cutaneous melanomas is a well-recognized phenomenon. As with single primary melanoma, personal and family histories of melanoma and dysplastic nevi (DN) are considered important risk factors. The natural history and impact of regular follow-up evaluation of this entity were examined. Method. Through a search of the computerized data bank of the Pathology Department and the Melanoma Registry of the Pigmented Lesion Clinic at Massachusetts General Hospital, 41 patients with multiple cutaneous melanomas were identified. Results. Mean (+/- standard error) age at first diagnosis was 49 +/- 2 years (range, 21-75 years). The male to female ratio was 2:1. The median number of primary melanomas was two (88%). Three patients had three and one had five. Melanoma types included superficial spreading (70%), nodular (8%), lentigo maligna (2%), and unclassified (10%), and in 7% the type was unknown. Nineteen (46%) patients had histologic and/or clinical evidence of DN. For the group with DN, the mean age at first diagnosis (44 +/- 3 years) was significantly less than that of patients without DN (54 +/- 3 years) (P < 0.05). Family history of melanoma was found in 10 patients (24%). Multiple melanomas were diagnosed concurrently in 16 patients (39%), whereas in 25 (61%) diagnosis was sequential. For the latter group, the mean tumor thickness from the first (1.21 +/- 0.28 mm) to the second melanoma (0.51 +/- 0.08 mm) decreased significantly (P < 0.05); the median time interval was 36 months (range, 2-372 months). Conclusion. These data confirm the need for complete skin examination for patients with newly diagnosed melanoma; and, with subsequent melanomas appearing as long as 31 years after the first melanoma, continued follow-up with complete skin examinations seems prudent. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT DERMATOL,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02114. FU NIAMS NIH HHS [5T 32 AR 07098-16] NR 16 TC 80 Z9 80 U1 5 U2 5 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 OCT 1 PY 1992 VL 70 IS 7 BP 1911 EP 1916 DI 10.1002/1097-0142(19921001)70:7<1911::AID-CNCR2820700718>3.0.CO;2-Q PG 6 WC Oncology SC Oncology GA JP692 UT WOS:A1992JP69200017 PM 1525766 ER PT J AU DECKER, HJH WULLICH, B WHALEY, JM HERRERA, G KLAUCK, SM SANDBERG, AA YANDELL, DW SEIZINGER, BR AF DECKER, HJH WULLICH, B WHALEY, JM HERRERA, G KLAUCK, SM SANDBERG, AA YANDELL, DW SEIZINGER, BR TI CYTOGENETIC AND MOLECULAR STUDIES OF A FAMILIAL RENAL-CELL CARCINOMA SO CANCER GENETICS AND CYTOGENETICS LA English DT Article ID RETINOBLASTOMA SUSCEPTIBILITY GENE; VONHIPPEL-LINDAU SYNDROME; HUMAN PROSTATE CARCINOMA; ALPHA-SATELLITE DNA; HUMAN CHROMOSOMES; INSITU HYBRIDIZATION; ALTERED EXPRESSION; HUMAN SARCOMAS; OSTEO-SARCOMA; RB GENE AB In a previously studied family with inherited renal cell carcinoma (RCC), RCC was shown to segregate with a constitutional balanced t(3;8)(p14.2;q24.1). In addition, we recently showed that in a RCC tumor from this family the constitutional translocation became unbalanced, suggesting a genetic mechanism that may be associated with the primary genetic events of tumorigenesis. We now report that the RCC tumor cells from this case showed additional cytogenetic alterations, possibly related to tumor progression, which include an additional tumor-specific translocation involving band 14 of chromosome 13. Because this band contains the retinoblastoma (RB) gene, we examined the tumor for aberrations in the RB gene using DNA sequence polymorphism analysis and pulsed-field gel electrophoresis (PFGE), but did not detect alterations in the RB gene. C1 MASSACHUSETTS GEN HOSP,MOLEC NEUROONCOL LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. SW BIOMED RES INST,CTR CANC,SCOTTSDALE,AZ. MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,BOSTON,MA 02114. FU NCI NIH HHS [R01 CA 49455, CA 41183] NR 39 TC 6 Z9 6 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0165-4608 J9 CANCER GENET CYTOGEN JI Cancer Genet. Cytogenet. PD OCT 1 PY 1992 VL 63 IS 1 BP 25 EP 31 DI 10.1016/0165-4608(92)90059-H PG 7 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA JZ593 UT WOS:A1992JZ59300005 PM 1423222 ER PT J AU WILLIAMS, ME SWERDLOW, SH ROSENBERG, CL ARNOLD, A AF WILLIAMS, ME SWERDLOW, SH ROSENBERG, CL ARNOLD, A TI CHARACTERIZATION OF CHROMOSOME-11 TRANSLOCATION BREAKPOINTS AT THE BCL-1 AND PRAD1 LOCI IN CENTROCYTIC LYMPHOMA SO CANCER RESEARCH LA English DT Article; Proceedings Paper CT WORKSHOP ON THE EMERGING EPIDEMIC OF NON-HODGKINS LYMPHOMA : CURRENT KNOWLEDGE REGARDING ETIOLOGICAL FACTORS CY OCT 22-23, 1991 CL BETHESDA, MD SP NCI ID INTERMEDIATE LYMPHOCYTIC LYMPHOMA; NON-HODGKINS LYMPHOMA; B-CELL LYMPHOMAS; ATAXIA TELANGIECTASIA; SQUAMOUS-CELL; T(11-14)(Q13-Q32) TRANSLOCATION; FREQUENT AMPLIFICATION; CANDIDATE ONCOGENE; MOLECULAR-CLONING; BREAST-CANCER AB The chromosome 11q13 bcl-1 locus is rearranged in the majority of centrocytic lymphomas, a CD5-positive B-cell non-Hodgkins lymphoma, as a result of reciprocal translocation with the 14q32 immunoglobulin heavy chain genes. Although several 11q13 bcl-1 breakpoint sites have been characterized, a postulated bcl-1 oncogene was not identified. Recently, however, a gene encoding cyclin D1, designated PRAD1, was proposed as a candidate bcl-1 oncogene; accumulated evidence now indicates this gene is bcl-1. To further characterize 11q13 breakpoints in B-cell neoplasms, we analyzed 26 centrocytic lymphomas and 68 other B-cell cancers by Southern blot using a panel of breakpoint probes spanning 110 kilobases of the bcl-1 and PRAD1 loci. Nineteen centrocytic cases (73%) showed rearrangement, 15 at bcl-1 breakpoint sites and 5 at PRAD1 sites. One case was rearranged at both bcl-1 and PRAD1 loci. All but the latter case showed comigration of rearranged bcl-1 or PRAD1 bands and immunoglobulin heavy chain joining gene bands, consistent with the t(11;14). bcl-1 rearrangement was present in only one of 68 noncentrocytic B-cell neoplasms; none showed PRAD1 rearrangement. Thus, bcl-1 and PRAD1 rearrangement is strongly associated with centrocytic lymphoma, providing a useful molecular marker for classifying this subtype of lymphoma and suggesting an important role for PRAD1 cyclin D1 in the pathogenesis of this neoplasm. C1 UNIV VIRGINIA,SCH MED,DEPT INTERNAL MED,CHARLOTTESVILLE,VA 22908. UNIV VIRGINIA,SCH MED,DEPT PATHOL,CHARLOTTESVILLE,VA 22908. UNIV CINCINNATI,DEPT PATHOL & LAB MED,CINCINNATI,OH 45267. MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. FU NCI NIH HHS [CA 46723]; NIDDK NIH HHS [DK 11794] NR 53 TC 118 Z9 118 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 1 PY 1992 VL 52 IS 19 SU S BP S5541 EP S5544 PG 4 WC Oncology SC Oncology GA JR138 UT WOS:A1992JR13800028 PM 1394169 ER PT J AU SCHWARTZ, GG SCHAEFER, S TROCHA, SD GARCIA, J STEINMAN, S MASSIE, BM WEINER, MW AF SCHWARTZ, GG SCHAEFER, S TROCHA, SD GARCIA, J STEINMAN, S MASSIE, BM WEINER, MW TI EFFECT OF SUPRANORMAL CORONARY BLOOD-FLOW ON ENERGY-METABOLISM AND SYSTOLIC FUNCTION OF PORCINE LEFT-VENTRICLE SO CARDIOVASCULAR RESEARCH LA English DT Article ID MYOCARDIAL-CONTRACTILITY; CANINE MYOCARDIUM; HEART; SPECTROSCOPY; PERFUSION; ADENOSINE; PRESSURE; INVIVO; HETEROGENEITY; PIGS AB Objective: The goal was to determine if supranormal coronary blood flow increases myocardial oxygen consumption, high energy phosphate levels, and systolic function in the in situ autoperfused heart. Methods: Thirteen anaesthetised open chest pigs with an intact, autoperfused coronary circulation, weight 30-40 kg, were studied. Measurements were made under basal conditions and during regional hyperperfusion of the anterior left ventricle produced by intracoronary infusion of adenosine (mean dose 3.3 mumol.min-1). Doppler coronary blood flow velocity in the anterior descending coronary artery, arterial and anterior interventricular venous blood oxygen content, high energy phosphates (by transmurally localised P-31 NMR), and myocardial wall thickening (by sonomicrometry) were measured. Results: With adenosine, coronary flow was increased to 355(SEM 59)% of control. Supranormal coronary flow produced no significant changes in anterior left ventricular oxygen consumption [99(12)% of control]. P-31 NMR spectroscopy revealed no significant changes in the peak intensities of phosphocreatine or ATP in either the subendocardium or subepicardium (90-97% of control). Systolic anterior left ventricular wall thickening also did not change [107(13)% of control]. Conclusions: Supranormal coronary flow does not augment myocardial oxygen consumption, high energy phosphates, or systolic function in the in situ autoperfused heart. Myocardial oxygen delivery does not limit oxidative metabolism under normal conditions. C1 UNIV CALIF SAN FRANCISCO,DEPT MED,CARDIOL SECT,SAN FRANCISCO,CA 94121. UNIV CALIF SAN FRANCISCO,MAGNET RESONANCE UNIT,SAN FRANCISCO,CA 94121. RP SCHWARTZ, GG (reprint author), UNIV CALIF SAN FRANCISCO,SAN FRANCISCO VET AFFAIRS MED CTR,4150 CLEMENT ST,SAN FRANCISCO,CA 94121, USA. FU NHLBI NIH HHS [HL28547, K08-HL02131, K11-HL02155] NR 39 TC 11 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD OCT PY 1992 VL 26 IS 10 BP 1001 EP 1006 DI 10.1093/cvr/26.10.1001 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA JV960 UT WOS:A1992JV96000015 PM 1486583 ER PT J AU SCHECTER, A PAPKE, O BALL, M CAU, HD DAI, LC MING, NQ QUYNH, HT PHUONG, NNT PHIET, PH CHI, HK VO, DT CONSTABLE, JD SPENCER, J AF SCHECTER, A PAPKE, O BALL, M CAU, HD DAI, LC MING, NQ QUYNH, HT PHUONG, NNT PHIET, PH CHI, HK VO, DT CONSTABLE, JD SPENCER, J TI DIOXIN AND DIBENZOFURAN LEVELS IN BLOOD AND ADIPOSE-TISSUE OF VIETNAMESE FROM VARIOUS LOCATIONS IN VIETNAM IN PROXIMITY TO AGENT ORANGE SPRAYING SO CHEMOSPHERE LA English DT Article ID CANCER MORTALITY; WORKERS; HERBICIDES; VETERANS; LYMPHOMA; NORTH; SOUTH AB Polychlorinated dibenzodioxins (PCDDs) and dibenzofurans (PCDFs) are of concern in Vietnam because of contamination from Agent Orange and other dioxin-containing chemicals. To map out levels of dioxins in Vietnam, between 1987 and 1991 pooled samples were collected in hospitals from discarded blood of adults and analyzed for dioxin content. Locations represented include Hanoi in the north, and thirteen areas in southern and central Vietnam. Because humans are at the top of the food chain, human blood dioxin levels can be used to monitor the environment and to acquire data of public health concern. Vietnamese adults, usually over the age of 40, were selected to increase the probability that 2,3,7,8-TCDD from Agent Orange, sprayed from 1962-1970 over 10% of the south, would be detected. One special group was included, veterans of the North Vietnam Army who served in the jungles of the south where Agent Orange was used. In general, considerable variation in TCDD level was observed, with elevated levels from certain areas in the south and also in the soldiers from the north of Vietnam who had served in the south. Seven hundred and twenty-one Vietnamese tissue samples were collected and are reported from twenty dioxin analyses. C1 OBSTET & GYNECOL HOSP, HO CHI MINH CITY, VIETNAM. CHO RAY HOSP, THANH PHO HO CHI MINH, VIETNAM. ERGO FORSCH GESELLSCH MBH, HAMBURG, GERMANY. UNIV HANOI, COLL MED, HANOI, VIETNAM. CORNELL UNIV, SCH MED, NEW YORK, NY 10021 USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, BOSTON, MA 02114 USA. RP SCHECTER, A (reprint author), SUNY HLTH SCI CTR SYRACUSE, COLL MED, DEPT PREVENT MED, CLIN CAMPUS, 88 ALDRICH AVE, BINGHAMTON, NY 13903 USA. NR 18 TC 7 Z9 7 U1 1 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0045-6535 EI 1879-1298 J9 CHEMOSPHERE JI Chemosphere PD OCT-NOV PY 1992 VL 25 IS 7-10 BP 1123 EP 1128 DI 10.1016/0045-6535(92)90117-A PG 6 WC Environmental Sciences SC Environmental Sciences & Ecology GA KC160 UT WOS:A1992KC16000036 ER PT J AU CAIRNS, JA FUSTER, V KENNEDY, JW AF CAIRNS, JA FUSTER, V KENNEDY, JW TI CORONARY THROMBOLYSIS SO CHEST LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; TISSUE PLASMINOGEN-ACTIVATOR; UNSTABLE ANGINA-PECTORIS; LEFT-VENTRICULAR FUNCTION; PLACEBO-CONTROLLED TRIAL; INTRACORONARY FIBRINOLYTIC THERAPY; PROSPECTIVE RANDOMIZED TRIAL; 12-MONTH FOLLOW-UP; INTRAVENOUS STREPTOKINASE; DOUBLE-BLIND C1 MASSACHUSETTS GEN HOSP,CARDIAC UNIT,BOSTON,MA 02114. UNIV WASHINGTON,DEPT MED,CARDIOL SECT,SEATTLE,WA 98195. RP CAIRNS, JA (reprint author), MCMASTER UNIV,HAMILTON GEN HOSP,CLIN UNIT,HAMILTON L8S 4L8,ONTARIO,CANADA. RI Fuster, Valentin/H-4319-2015 OI Fuster, Valentin/0000-0002-9043-9986 NR 122 TC 12 Z9 12 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 OCT PY 1992 VL 102 IS 4 SU S BP S482 EP S507 DI 10.1378/chest.102.4_Supplement.482S PG 26 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA JT655 UT WOS:A1992JT65500016 PM 1395830 ER PT J AU HIRSH, J DALEN, JE FUSTER, V HARKER, LB SALZMAN, EW AF HIRSH, J DALEN, JE FUSTER, V HARKER, LB SALZMAN, EW TI ASPIRIN AND OTHER PLATELET-ACTIVE DRUGS - THE RELATIONSHIP BETWEEN DOSE, EFFECTIVENESS, AND SIDE-EFFECTS SO CHEST LA English DT Article ID TOTAL HIP-REPLACEMENT; VEIN-GRAFT PATENCY; RANDOMIZED CONTROLLED TRIAL; SUBSTITUTE HEART-VALVES; MYOCARDIAL-INFARCTION; UNSTABLE ANGINA; THROMBOEMBOLIC COMPLICATIONS; INTERMITTENT CLAUDICATION; VENOUS THROMBOEMBOLISM; CYCLOOXYGENASE INHIBITION C1 BETH ISRAEL HOSP, MED, BOSTON, MA 02215 USA. UNIV ARIZONA, COLL MED, TUCSON, AZ 85721 USA. MASSACHUSETTS GEN HOSP, CARDIAC UNIT, BOSTON, MA 02114 USA. EMORY UNIV, DEPT MED, DIV HEMATOL ONCOL, ATLANTA, GA 30322 USA. RP HIRSH, J (reprint author), HAMILTON CIV HOSP, RES CTR, HAMILTON, ONTARIO, CANADA. RI Fuster, Valentin/H-4319-2015 OI Fuster, Valentin/0000-0002-9043-9986 NR 117 TC 51 Z9 51 U1 0 U2 3 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 SN 0012-3692 J9 CHEST JI Chest PD OCT PY 1992 VL 102 IS 4 SU S BP S327 EP S336 DI 10.1378/chest.102.4_Supplement.327S PG 10 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA JT655 UT WOS:A1992JT65500004 PM 1395819 ER PT J AU OHTANI, H SOUTHERN, JF STRAUSS, HW ISOBE, M AF OHTANI, H SOUTHERN, JF STRAUSS, HW ISOBE, M TI IMAGING OF ICAM-1 INDUCTION IN REJECTING HEART - A NEW SCINTIGRAPHIC APPROACH TO DETECT EARLY ALLOGRAFT-REJECTION SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. UNIV TOKYO,TOKYO 113,JAPAN. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 37 EP 37 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66000176 ER PT J AU VILLARREALLEVY, G SMITH, AJC MULUK, VS ODONNELL, C NEWELL, J EAGLE, KA OGARA, PT AF VILLARREALLEVY, G SMITH, AJC MULUK, VS ODONNELL, C NEWELL, J EAGLE, KA OGARA, PT TI GENDER DIFFERENCES IN THE EVALUATION AND TREATMENT OF PATIENTS WITH MYOCARDIAL-INFARCTION SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 39 EP 39 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66000184 ER PT J AU MILANI, RV LAVIE, CJ AF MILANI, RV LAVIE, CJ TI BENEFITS OF VIGOROUS NONPHARMACOLOGIC THERAPY IN PATIENTS WITH ISOLATED LOW HIGH-DENSITY-LIPOPROTEIN CHOLESTEROL SO CIRCULATION LA English DT Meeting Abstract C1 ALTON OCHSNER MED FDN & OCHSNER CLIN,NEW ORLEANS,LA 70121. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RI Milani, Richard/A-6045-2011 NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 63 EP 63 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66000281 ER PT J AU JANSSENS, SP SHIMOUCHI, A QUERTERMOUS, T BLOCH, DB BLOCH, KD AF JANSSENS, SP SHIMOUCHI, A QUERTERMOUS, T BLOCH, DB BLOCH, KD TI CLONING AND EXPRESSION OF A CDNA-ENCODING HUMAN ENDOTHELIUM-DERIVED RELAXING FACTOR/NITRIC OXIDE SYNTHASE SO CIRCULATION 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 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 86 EP 86 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66000373 ER PT J AU PAUL, SD KEANEY, KM EAGLE, KA WEINSTEIN, MC AF PAUL, SD KEANEY, KM EAGLE, KA WEINSTEIN, MC TI THE COSTS AND THE EFFECTIVENESS OF ANGIOTENSIN CONVERTING ENZYME-INHIBITION IN PATIENTS WITH CONGESTIVE-HEART-FAILURE SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 101 EP 101 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66000431 ER PT J AU ROELKE, M GARAN, H MCGOVERN, BA RUSKIN, JN AF ROELKE, M GARAN, H MCGOVERN, BA RUSKIN, JN TI THE MODES OF INITIATION OF VENTRICULAR-TACHYCARDIA BY ANALYSIS OF STORED INTRACARDIAC ELECTROGRAMS SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 131 EP 131 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66000552 ER PT J AU COLES, NA ODONNELL, C MULUK, V FIELDS, T ZISFEIN, J BARSKY, A HOSCHSTRASSER, B LIPSON, R COTHERN, M BOUCHER, C EAGLE, K AF COLES, NA ODONNELL, C MULUK, V FIELDS, T ZISFEIN, J BARSKY, A HOSCHSTRASSER, B LIPSON, R COTHERN, M BOUCHER, C EAGLE, K TI COMPARATIVE USEFULNESS OF PREDISCHARGE HOLTER AND THALLIUM FOR POST-MI RISK STRATIFICATION SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 139 EP 139 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66000584 ER PT J AU HOLMVANG, G CHESLER, DA VEVEA, M BALLEN, B BRADY, TJ KANTOR, HL AF HOLMVANG, G CHESLER, DA VEVEA, M BALLEN, B BRADY, TJ KANTOR, HL TI DETERMINATION OF PEAK JET VELOCITY FROM THE PROXIMAL ACCELERATION FIELD BY MAGNETIC-RESONANCE-IMAGING SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 163 EP 163 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66000678 ER PT J AU THEDENS, DR FLEAGLE, SR WEISSKOFF, RM HUNTER, GJ COHEN, MS KANTOR, HL SKORTON, DJ AF THEDENS, DR FLEAGLE, SR WEISSKOFF, RM HUNTER, GJ COHEN, MS KANTOR, HL SKORTON, DJ TI FEASIBILITY OF AUTOMATED DETECTION OF MYOCARDIAL BORDERS TO ASSESS CARDIAC ANATOMY FROM ECHO-PLANAR MAGNETIC-RESONANCE IMAGES SO CIRCULATION LA English DT Meeting Abstract C1 UNIV IOWA,IOWA CITY,IA 52242. MASSACHUSETTS GEN HOSP,CTR NUCL MAGNET RESONANCE,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 165 EP 165 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66000687 ER PT J AU TROUTON, TG ONUNAIN, SS KIM, YH GARAN, H RUSKIN, JN AF TROUTON, TG ONUNAIN, SS KIM, YH GARAN, H RUSKIN, JN TI ANATOMIC LOCATION OF SLOW AND FAST PATHWAYS IN PATIENTS WITH ATRIOVENTRICULAR NODAL REENTRY TACHYCARDIA SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 202 EP 202 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66000833 ER PT J AU PRABHU, SD MULLIGAN, LJ OROURKE, RA FREEMAN, GL AF PRABHU, SD MULLIGAN, LJ OROURKE, RA FREEMAN, GL TI EFFECT OF DOBUTAMINE ON VENTRICULAR ENERGETICS IN CLOSED-CHEST DOGS SO CIRCULATION 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 2 Z9 2 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 231 EP 231 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66000943 ER PT J AU MELE, D GUERRERO, JL VANDERVOORT, PM RIVERA, JM CAPE, EG YOGANATHAN, AP VLAHAKES, G THOMAS, JD WEYMAN, AE LEVINE, RA AF MELE, D GUERRERO, JL VANDERVOORT, PM RIVERA, JM CAPE, EG YOGANATHAN, AP VLAHAKES, G THOMAS, JD WEYMAN, AE LEVINE, RA TI DOPPLER-ECHOCARDIOGRAPHIC QUANTIFICATION OF TRICUSPID REGURGITATION BY THE MOMENTUM METHOD - INVIVO VALIDATION SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RI rivera, miguel/D-5026-2014 NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 258 EP 258 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66001049 ER PT J AU HIBBERD, MG SIU, SC HANDSCHUMACHER, MD JIANG, L NEWELL, JB LEVINE, RA AF HIBBERD, MG SIU, SC HANDSCHUMACHER, MD JIANG, L NEWELL, JB LEVINE, RA TI 3-DIMENSIONAL ECHOCARDIOGRAPHY - INCREASED ACCURACY FOR LEFT-VENTRICULAR VOLUME COMPARED WITH ANGIOGRAPHY SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 270 EP 270 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66001098 ER PT J AU SIU, SC RIVERA, JM HANDSHUMACHER, MD WEYMAN, AE PICARD, MH AF SIU, SC RIVERA, JM HANDSHUMACHER, MD WEYMAN, AE PICARD, MH TI LEFT-VENTRICULAR VOLUME QUANTITATION BY 3-DIMENSIONAL ECHOCARDIOGRAPHY - SIMPLIFICATION WITHOUT LOSS OF ACCURACY SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RI rivera, miguel/D-5026-2014 NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 270 EP 270 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66001097 ER PT J AU JIANG, L SIU, SC HANDSCHUMACHER, MD GUERRERO, JL DEPRADA, JV KING, ME PICARD, MH WEYMAN, AE LEVINE, RA AF JIANG, L SIU, SC HANDSCHUMACHER, MD GUERRERO, JL DEPRADA, JV KING, ME PICARD, MH WEYMAN, AE LEVINE, RA TI 3-DIMENSIONAL ECHOCARDIOGRAPHY - INVIVO VALIDATION FOR RIGHT VENTRICULAR VOLUME AND FUNCTION SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 272 EP 272 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66001106 ER PT J AU OLEARY, EL COLSTON, JT FREEMAN, GL AF OLEARY, EL COLSTON, JT FREEMAN, GL TI MAINTAINED LENGTH-DEPENDENT ACTIVATION OF SKINNED MYOCARDIAL FIBERS IN TACHYCARDIA HEART-FAILURE SO CIRCULATION 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 4 Z9 4 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 284 EP 284 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66001155 ER PT J AU YOSHIZUMI, M KOUREMBANAS, S QUERTERMOUS, T LEE, ME AF YOSHIZUMI, M KOUREMBANAS, S QUERTERMOUS, T LEE, ME TI TUMOR-NECROSIS-FACTOR INCREASES TRANSCRIPTION OF THE HEPARIN-BINDING EGF-LIKE GROWTH-FACTOR GENE IN VASCULAR ENDOTHELIAL-CELLS SO CIRCULATION 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 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 291 EP 291 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66001183 ER PT J AU VANDERVOORT, PM RIVERA, JM MELE, D WEYMAN, AE THOMAS, JD AF VANDERVOORT, PM RIVERA, JM MELE, D WEYMAN, AE THOMAS, JD TI VESSEL FLOW-RATES USING DIGITAL DOPPLER MAPS ARE UNDERESTIMATED IN TURBULENT-FLOW SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RI rivera, miguel/D-5026-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 317 EP 317 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66001288 ER PT J AU LUSCINSKAS, FW SCHLEIFFENBAUM, BE DING, H TEDDER, TF GIMBRONE, MA AF LUSCINSKAS, FW SCHLEIFFENBAUM, BE DING, H TEDDER, TF GIMBRONE, MA TI MONOCYTE ATTACHMENT TO INTERLEUKIN-4-ACTIVATED ENDOTHELIUM IS MEDIATED VIA L-SELECTIN AND VASCULAR ADHESION MOLECULE-1 UNDER NONSTATIC CONDITIONS SO CIRCULATION LA English DT Meeting Abstract C1 BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 333 EP 333 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66001349 ER PT J AU MUNOZ, J VIRELLA, G GALBRAITH, G LOPESVIRELLA, MF AF MUNOZ, J VIRELLA, G GALBRAITH, G LOPESVIRELLA, MF TI LDL-IMMUNE COMPLEXES ACTIVATE RESPIRATORY BURST AND CYTOKINE RELEASE IN HUMAN MONOCYTE-DERIVED MACROPHAGES SO CIRCULATION LA English DT Meeting Abstract C1 MED UNIV S CAROLINA,CHARLESTON,SC 29425. RALPH H JOHNSON VET ADM MED CTR,CHARLESTON,SC. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 335 EP 335 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66001359 ER PT J AU LEWANDOWSKI, ED AF LEWANDOWSKI, ED TI METABOLIC HETEROGENEITY OF INTRACELLULAR SUBSTRATE POOLS SO CIRCULATION 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 AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 340 EP 340 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66001378 ER PT J AU LIPSHULTZ, SE COLAN, SD GELBER, RD MONE, SM SANDERS, SP SALLAN, SE AF LIPSHULTZ, SE COLAN, SD GELBER, RD MONE, SM SANDERS, SP SALLAN, SE TI THE EFFECTS OF GENDER AND DOXORUBICIN DOSE-RATE ON LEFT-VENTRICULAR CONTRACTILITY IN LATE SURVIVORS OF CHILDHOOD LEUKEMIA SO CIRCULATION LA English DT Meeting Abstract C1 CHILDRENS HOSP MED CTR,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 363 EP 363 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66001468 ER PT J AU SEMIGRAN, MJ ARONEY, CN DEC, GW FIFER, MA AF SEMIGRAN, MJ ARONEY, CN DEC, GW FIFER, MA TI ABNORMALITIES IN DIASTOLIC FUNCTION PROGRESS OVER TIME IN CARDIAC TRANSPLANT RECIPIENTS SO CIRCULATION LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RI Aroney, Constantine/A-7672-2013 OI Aroney, Constantine/0000-0002-0908-7179 NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 378 EP 378 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66001529 ER PT J AU GOLD, HK TORRES, FW GARABEDIAN, HD WERNER, W JANG, IK KHAN, A HAGSTROM, JN YASUDA, T LEINBACH, RC NEWELL, JB BOVILL, EG STUMP, DC COLLEN, D AF GOLD, HK TORRES, FW GARABEDIAN, HD WERNER, W JANG, IK KHAN, A HAGSTROM, JN YASUDA, T LEINBACH, RC NEWELL, JB BOVILL, EG STUMP, DC COLLEN, D TI DOSE-RELATED REBOUND COAGULATION FOLLOWING A 4-HOUR INFUSION OF THE SPECIFIC THROMBIN INHIBITOR, ARGATROBAN, IN UNSTABLE ANGINA SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 386 EP 386 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66001562 ER PT J AU YASUDA, T GOLD, HK KOHMURA, C GUERRERO, L FALLON, JT LEINBACH, RC NAPIER, MA BUNTING, S COLLEN, D AF YASUDA, T GOLD, HK KOHMURA, C GUERRERO, L FALLON, JT LEINBACH, RC NAPIER, MA BUNTING, S COLLEN, D TI ENHANCEMENT OF CORONARY THROMBOLYSIS WITHOUT PROLONGATION OF THE BLEEDING-TIME BY ARG-GLY-ASP-CONTAINING PEPTIDE, 8X, AND RECOMBINANT TISSUE-TYPE PLASMINOGEN-ACTIVATOR (RT-PA) SO CIRCULATION LA English DT Meeting Abstract C1 GENENTECH INC,S SAN FRANCISCO,CA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 411 EP 411 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66001660 ER PT J AU GIBSON, CM CANNON, CP PIANA, RN MAHER, KA DAVIS, SF BREALL, JA DANIEL, VD AF GIBSON, CM CANNON, CP PIANA, RN MAHER, KA DAVIS, SF BREALL, JA DANIEL, VD TI RELATIONSHIP OF CORONARY FLOW TO MYOCARDIAL-INFARCTION SIZE - 2 SIMPLE NEW METHODS TO SUBCLASSIFY TIMI FLOW GRADES SO CIRCULATION LA English DT Meeting Abstract C1 TIMI 4 STUDY GRP,BOSTON,MA. NR 0 TC 11 Z9 11 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 453 EP 453 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66001826 ER PT J AU GIBSON, CM PIANA, RN DAVIS, SF MAHER, KA BREALL, JA DAVIS, V DIVER, DJ BAIM, DS AF GIBSON, CM PIANA, RN DAVIS, SF MAHER, KA BREALL, JA DAVIS, V DIVER, DJ BAIM, DS TI IMPROVEMENT IN MINIMUM LUMEN DIAMETER DURING THE 1ST DAY AFTER THROMBOLYSIS SO CIRCULATION LA English DT Meeting Abstract C1 TIMI 4 STUDY GRP,BOSTON,MA. NR 0 TC 11 Z9 11 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 453 EP 453 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66001825 ER PT J AU PONCELET, BP WEDEEN, VJ WEISSKOFF, RM COHEN, MS HOLMVANG, G BRADY, TJ KANTOR, HL AF PONCELET, BP WEDEEN, VJ WEISSKOFF, RM COHEN, MS HOLMVANG, G BRADY, TJ KANTOR, HL TI QUANTIFICATION OF THE LAD CORONARY FLOW WITH MAGNETIC-RESONANCE ECHO-PLANAR IMAGING SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,CTR NMR,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CARDIAC UNIT,BOSTON,MA 02114. RI Cohen, Mark/C-6610-2011 OI Cohen, Mark/0000-0001-6731-4053 NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 476 EP 476 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66001912 ER PT J AU DAMBRA, MN AKINS, CW BLACKSTONE, EH BONNEY, SL COHN, LE COSGROVE, DM LEVY, JM MADDI, RM KIRKLIN, JW AF DAMBRA, MN AKINS, CW BLACKSTONE, EH BONNEY, SL COHN, LE COSGROVE, DM LEVY, JM MADDI, RM KIRKLIN, JW TI APROTININ IN PRIMARY CARDIAC-VALVE REPLACEMENT REDUCES BLEEDING, INCREASES CREATININE SO CIRCULATION LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 495 EP 495 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66001990 ER PT J AU KIM, YH TROUTON, TG ONUNAIN, SS SOSASUAREZ, G MCGOVERN, BA RUSKIN, JN GARAN, H AF KIM, YH TROUTON, TG ONUNAIN, SS SOSASUAREZ, G MCGOVERN, BA RUSKIN, JN GARAN, H TI RESULTS OF TRANSCATHETER RADIOFREQUENCY ABLATION FOR TREATMENT OF VENTRICULAR-TACHYCARDIA SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 519 EP 519 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66002085 ER PT J AU ROELKE, M PALACIOS, IF AF ROELKE, M PALACIOS, IF TI A 10 YEAR EXPERIENCE OF 1,277 TRANSSEPTAL LEFT HEART CATHETERIZATIONS SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 593 EP 593 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66002381 ER PT J AU KHANDELWAL, M GARABEDIAN, HD GOLD, HK ARNOUT, J PALACIOS, IF AF KHANDELWAL, M GARABEDIAN, HD GOLD, HK ARNOUT, J PALACIOS, IF TI INTRACORONARY PLATELET ACTIVATION BY NONIONIC CONTRAST-MEDIA DURING ANGIOGRAPHY - A PROSPECTIVE, DOUBLE-BLIND RANDOMIZED STUDY SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. CTR THROMBOSIS & VASC RES,LOUVAIN,BELGIUM. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 650 EP 650 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66002606 ER PT J AU BROOKS, R GARAN, H VLAHAKES, GJ TORCHIANA, D MCGOVERN, B RUSKIN, JN AF BROOKS, R GARAN, H VLAHAKES, GJ TORCHIANA, D MCGOVERN, B RUSKIN, JN TI PREDICTORS OF SUCCESSFUL NONTHORACOTOMY CARDIOVERTER-DEFIBRILLATOR IMPLANTATION SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 657 EP 657 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66002633 ER PT J AU NIDORF, SM LEAVITT, M LEVINE, RA AF NIDORF, SM LEAVITT, M LEVINE, RA TI MITRAL-VALVE PROLAPSE - DECLINE OF THE EPIDEMIC SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 661 EP 661 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66002651 ER PT J AU NARULA, J DITLOW, C CHEN, F STRAUSS, HW KHAW, BA AF NARULA, J DITLOW, C CHEN, F STRAUSS, HW KHAW, BA TI NONINVASIVE LOCALIZATION OF EXPERIMENTAL ATHEROSCLEROTIC LESIONS WITH MURINE HUMAN CHIMERIC ANTIBODY Z2D3 F(AB)2 SO CIRCULATION LA English DT Meeting Abstract C1 NORTHEASTERN UNIV,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. VASOCOR,MENLO PK,CA. NR 0 TC 0 Z9 0 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 OCT PY 1992 VL 86 IS 4 SU S BP 709 EP 709 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66002839 ER PT J AU SEMIGRAN, MJ DEC, GW SOUTHERN, J FALLON, JT PALACIOS, IF AF SEMIGRAN, MJ DEC, GW SOUTHERN, J FALLON, JT PALACIOS, IF TI LEFT-VENTRICULAR ENDOMYOCARDIAL BIOPSY ADDS DIAGNOSTIC INFORMATION IN PATIENTS WITH DILATED CARDIOMYOPATHY SO CIRCULATION LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 795 EP 795 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66003181 ER PT J AU RIVERA, JM VANDERVOORT, PM MELE, D THOREAU, DH SIU, SC MORRIS, E WEYMAN, AE THOMAS, JD AF RIVERA, JM VANDERVOORT, PM MELE, D THOREAU, DH SIU, SC MORRIS, E WEYMAN, AE THOMAS, JD TI QUANTIFICATION OF TRICUSPID REGURGITATION BY THE PROXIMAL FLOW CONVERGENCE METHOD SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RI rivera, miguel/D-5026-2014 NR 0 TC 4 Z9 4 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 804 EP 804 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66003217 ER PT J AU CHEN, CG VANDERVOORT, PM HEIK, S WEYMAN, AE THOMAS, JD AF CHEN, CG VANDERVOORT, PM HEIK, S WEYMAN, AE THOMAS, JD TI IS THE PROXIMAL FLOW CONVERGENCE METHOD ACCURATE IN THE PRESENCE OF A 2ND OUTFLOW SO CIRCULATION LA English DT Meeting Abstract C1 UNIV HOSP HAMBURG,HAMBURG,GERMANY. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 5 Z9 5 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 805 EP 805 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66003221 ER PT J AU VATNER, DE KIUCHI, K SHANNON, RP HEMPEL, D VATNER, SF AF VATNER, DE KIUCHI, K SHANNON, RP HEMPEL, D VATNER, SF TI ABNORMAL SARCOPLASMIC-RETICULUM CALCIUM-CHANNEL BINDING OCCURS EARLY IN THE DEVELOPMENT OF HEART-FAILURE SO CIRCULATION LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. NEW ENGLAND REG PRIMATE RES CTR,SOUTHBOROUGH,MA 01772. MASSACHUSETTS GEN HOSP,CHILDRENS SERV,BOSTON,MA 02114. NR 0 TC 1 Z9 1 U1 0 U2 5 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 823 EP 823 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66003293 ER PT J AU KIUCHI, K SHEN, YT VATNER, SF VATNER, DE AF KIUCHI, K SHEN, YT VATNER, SF VATNER, DE TI IMPORTANCE OF AFFINITY STATE AS OPPOSED TO DENSITY OF BETA-ADRENERGIC RECEPTORS AND ADENYLYL CYCLASE ACTIVITY IN THE PHYSIOLOGICAL-RESPONSE TO BETA-STIMULATION AFTER CORONARY-ARTERY REPERFUSION IN CONSCIOUS DOGS SO CIRCULATION LA English DT Meeting Abstract C1 HARVARD UNIV,NEW ENGLAND REG PRIMATE RES CTR,SCH MED,SOUTHBOROUGH,MA 01772. MASSACHUSETTS GEN HOSP,CHILDRENS SERV,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 4 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 826 EP 826 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66003306 ER PT J AU LOPEZ, JJ TANG, SS DIAMANT, D INGELFINGER, JR WEINBERG, EO SCHUNKERT, H LORELL, BH AF LOPEZ, JJ TANG, SS DIAMANT, D INGELFINGER, JR WEINBERG, EO SCHUNKERT, H LORELL, BH TI DISTRIBUTION AND FUNCTION OF ANGIOTENSIN-AT(1) AND ANGIOTENSIN-AT(2) RECEPTOR SUBTYPES IN HYPERTROPHIED RAT HEARTS SO CIRCULATION LA English DT Meeting Abstract C1 BETH ISRAEL HOSP,BOSTON,MA 02215. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 3 Z9 3 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 OCT PY 1992 VL 86 IS 4 SU S BP 838 EP 838 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66003354 ER PT J AU IAKOVIDIS, P COHEN, DJ SWAIN, L CLEM, M GHIDONI, JJ EVERETT, MM BOYAN, BD AF IAKOVIDIS, P COHEN, DJ SWAIN, L CLEM, M GHIDONI, JJ EVERETT, MM BOYAN, BD TI ORAL MICROORGANISMS AND CALCIFIC AORTIC-STENOSIS SO CIRCULATION LA English DT Meeting Abstract C1 AUDIE MURPHY VET AFFAIRS MED CTR,SAN ANTONIO,TX. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 849 EP 849 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66003397 ER PT J AU NIDORF, SM HENNESSY, R NEWELL, JB WEYMAN, AE LEVINE, RA AF NIDORF, SM HENNESSY, R NEWELL, JB WEYMAN, AE LEVINE, RA TI MITRAL-VALVE PROLAPSE - THE RELATION BETWEEN MITRAL-VALVE MORPHOLOGY AND PROGNOSIS - A PROSPECTIVE ECHOCARDIOGRAPHIC STUDY SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 849 EP 849 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66003398 ER PT J AU COHEN, DJ IAKOVIDIS, P BROOKS, B SWAIN, L EVERETT, MM BOYAN, BD AF COHEN, DJ IAKOVIDIS, P BROOKS, B SWAIN, L EVERETT, MM BOYAN, BD TI ASSOCIATION OF A CALCIFIABLE PROTEOLIPID WITH HUMAN BICUSPID AORTIC-VALVE CALCIFICATION SO CIRCULATION LA English DT Meeting Abstract C1 AUDIE MURPHY VET AFFAIRS MED CTR,SAN ANTONIO,TX. UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX 78284. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 850 EP 850 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66003402 ER PT J AU HE, SQ HOPMEYER, J LEFEBVRE, X YOGANATHAN, AP LEVINE, RA AF HE, SQ HOPMEYER, J LEFEBVRE, X YOGANATHAN, AP LEVINE, RA TI IMPORTANCE OF LEAFLET ELONGATION IN CAUSING SYSTOLIC ANTERIOR MOTION OF THE MITRAL-VALVE SO CIRCULATION LA English DT Meeting Abstract C1 GEORGIA INST TECHNOL,ATLANTA,GA 30332. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 850 EP 850 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66003399 ER PT J AU COLLEN, D LU, HR STASSEN, JM VREYS, I YASUDA, T BUNTING, S GOLD, HK AF COLLEN, D LU, HR STASSEN, JM VREYS, I YASUDA, T BUNTING, S GOLD, HK TI ANTITHROMBOTIC AND HEMORRHAGENIC PROPERTIES OF SYNTHETIC PLATELET GPIIB/IIIA INHIBITORS IN PLATELET-MEDIATED THROMBOSIS IN THE DOG SO CIRCULATION LA English DT Meeting Abstract C1 CATHOLIC UNIV LEUVEN,B-3000 LOUVAIN,BELGIUM. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. GENENTECH INC,SAN FRANCISCO,CA 94080. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 867 EP 867 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66003467 ER PT J AU FORCE, T FREEMAN, M KEILSON, L MILANI, R CURTIS, K LEAF, A WEBER, P AF FORCE, T FREEMAN, M KEILSON, L MILANI, R CURTIS, K LEAF, A WEBER, P TI EFFECTS OF LIPID-LOWERING THERAPY ON PLATELET ACTIVATION INVIVO SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. MAINE MED CTR,PORTLAND,ME 04102. RI Milani, Richard/A-6045-2011 NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 868 EP 868 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66003472 ER PT J AU PARHAMISEREN, B KUSSIE, P REED, GL AF PARHAMISEREN, B KUSSIE, P REED, GL TI HUMAN-ANTIBODY RESPONSE TO STREPTOKINASE - A MOLECULAR ANALYSIS SO CIRCULATION 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 AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 868 EP 868 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66003474 ER PT J AU FISHER, CM AF FISHER, CM TI AMNESTIC SYNDROME ASSOCIATED WITH PROPRANOLOL TOXICITY - A CASE-REPORT SO CLINICAL NEUROPHARMACOLOGY LA English DT Note DE AMNESTIC SYNDROME; PROPRANOLOL; DRUG REACTION AB An elderly woman developed an Alzheimer-like subacute dementia as a result of propranolol toxicity. Analysis of the manifestations showed that severe impairment of memory accounted for virtually all of the abnormalities. There is evidence that cerebral reactions to drug toxicity can exhibit patterns that suggest highly selective involvement of functional subdivisions of the brain. RP FISHER, CM (reprint author), MASSACHUSETTS GEN HOSP,NEUROL SERV,FRUIT ST,BOSTON,MA 02114, USA. NR 5 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0362-5664 J9 CLIN NEUROPHARMACOL JI Clin. Neuropharmacol. PD OCT PY 1992 VL 15 IS 5 BP 397 EP 403 DI 10.1097/00002826-199210000-00008 PG 7 WC Clinical Neurology; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA JP421 UT WOS:A1992JP42100008 PM 1423339 ER PT J AU SQUIRES, LA NEUMEYER, AM BLOOMBERG, J KRISHNAMOORTHY, KS AF SQUIRES, LA NEUMEYER, AM BLOOMBERG, J KRISHNAMOORTHY, KS TI HYPERPYREXIA IN AN ADOLESCENT ON DESIPRAMINE TREATMENT SO CLINICAL PEDIATRICS LA English DT Note ID NEUROLEPTIC MALIGNANT SYNDROME; ANTIDEPRESSANT C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT CHILD PSYCHIAT,BOSTON,MA 02114. RP SQUIRES, LA (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT CHILD NEUROL,BOSTON,MA 02114, USA. NR 6 TC 1 Z9 1 U1 0 U2 0 PU WESTMINSTER PUBL INC PI GLEN HEAD PA 708 GLEN COVE AVE, GLEN HEAD, NY 11545 SN 0009-9228 J9 CLIN PEDIATR JI Clin. Pediatr. PD OCT PY 1992 VL 31 IS 10 BP 635 EP 636 DI 10.1177/000992289203101012 PG 2 WC Pediatrics SC Pediatrics GA JU455 UT WOS:A1992JU45500012 PM 1395373 ER PT J AU CHATZIPANTELI, K HEAD, CL AXELROD, L AF CHATZIPANTELI, K HEAD, CL AXELROD, L TI THE EFFECT OF INSULIN ON BLOOD-PRESSURE IN DIABETIC-KETOACIDOSIS AND DIABETES-MELLITUS IS MEDIATED BY REGULATION OF PROSTAGLANDIN PRODUCTION IN ADIPOSE-TISSUE SO CLINICAL RESEARCH LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DIABET UNIT,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 OCT PY 1992 VL 40 IS 3 BP A658 EP A658 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA JQ521 UT WOS:A1992JQ52100072 ER PT J AU DICKERSON, RN RAJTER, JJ MANZO, CB AF DICKERSON, RN RAJTER, JJ MANZO, CB TI TOTAL PARENTERAL-NUTRITION FACILITATES BACTERIAL TRANSLOCATION IN NORMAL AND ENDOTOXIN-STRESSED ANIMALS SO CLINICAL RESEARCH LA English DT Meeting Abstract C1 PHILADELPHIA COLL PHARM & SCI,PHILADELPHIA,PA 19104. VET AFFAIRS MED CTR,PHILADELPHIA,PA. RI Dickerson, Roland/C-5185-2008 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 OCT PY 1992 VL 40 IS 3 BP A672 EP A672 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA JQ521 UT WOS:A1992JQ52100146 ER PT J AU TAN, KC GRABBE, S HOSOI, J GRANSTEIN, RD AF TAN, KC GRABBE, S HOSOI, J GRANSTEIN, RD TI EPIDERMAL-CELL (EC) PRESENTATION OF TUMOR-ASSOCIATED ANTIGENS (TAA) FOR TOLERANCE SO CLINICAL RESEARCH LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,CUTANEOUS BIOL RES CTR,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 OCT PY 1992 VL 40 IS 3 BP A663 EP A663 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA JQ521 UT WOS:A1992JQ52100101 ER PT J AU CANNON, JG FRIEDBERG, JS GELFAND, JA TOMPKINS, RG BURKE, JF DINARELLO, CA AF CANNON, JG FRIEDBERG, JS GELFAND, JA TOMPKINS, RG BURKE, JF DINARELLO, CA TI CIRCULATING INTERLEUKIN-1-BETA AND TUMOR NECROSIS FACTOR-BETA CONCENTRATIONS AFTER BURN INJURY IN HUMANS SO CRITICAL CARE MEDICINE LA English DT Article DE BURN; TRAUMA; INTERLEUKIN-1; TUMOR NECROSIS FACTOR; FEVER; BODY TEMPERATURE; NEUTROPHIL; APACHE-II SCORE; CYTOKINE; AGE; SEPSIS; CRITICAL ILLNESS ID FACTOR-ALPHA; SEPTIC SHOCK; MONOCLONAL-ANTIBODIES; RECEPTOR ANTAGONIST; SERUM; CACHECTIN; EXPRESSION; INHIBITOR; SEPSIS; CELL AB Objectives: To measure plasma interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNFalpha) concentrations after burn injury and to determine if these concentrations relate to clinical status. Design: Prospective assessment. Setting: Hospital burn unit. Patients: Thirty-one patients with second- or third-degree burns, covering 10% to 95% of body surface area. Measurements and Main Results: Initial concentrations of IL-1beta were increased (mean 188 +/- 31 pg/mL), and the concentrations for each patient correlated with body temperature at the time of the blood sample (rho = 0.51,p <.015) (rho is a nonparametric statistical measure; a non-parametric analysis is mandatory for data that is categorical [Acute Physiology and Chronic Health Evaluation, APACHE, scores] and data that are not normally distributed [IL-1beta and tumor necrosis factor, TNF, data]). Mean TNFalpha concentrations were initially 264 +/- 132 pg(mL, and these concentrations were positively related to body temperature (rho = 0.4l,p <.05) and inversely related to the total WBC count (rho = -0.45, p <.025). Through the course of hospitalization, plasma cytokine levels fluctuated, but transient increases (sometimes into the nanogram/mL range) did not consistently correspond to changes in clinical signs or severity of illness, as determined by APACHE II scores. The maximum plasma cytokine levels in any patient were not related to age, but maximum IL-1beta concentrations were inversely related to burn size (rho = -0.46, p <.015). The final IL-1beta concentrations measured in the patients who died (n = 7) were significantly less than measurements in surviving patients matched for burn size and age taken at approximately the same time after admission. Conclusions: These results indicate that early after burn injury there is a correspondence of IL-1beta and TNFalpha with certain host responses, but these correlations disappear with the progression of illness. In general, IL-1beta and TNFalpha appear to be poor indicators of prognosis during burn injury; however, the association of mortality with low circulating IL-1beta values supports the concept of IL-1beta as being an essential mediator of host defenses. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,SURG SERV,BOSTON,MA 02114. TUFTS UNIV,NEW ENGLAND MED CTR,SCH MED,DEPT MED,BOSTON,MA 02111. FU NIAID NIH HHS [AI-15614]; NIGMS NIH HHS [GM-07035, GM21700] NR 40 TC 138 Z9 138 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD OCT PY 1992 VL 20 IS 10 BP 1414 EP 1419 DI 10.1097/00003246-199210000-00009 PG 6 WC Critical Care Medicine SC General & Internal Medicine GA JT937 UT WOS:A1992JT93700009 PM 1395662 ER PT J AU WECKER, H AUCHINCLOSS, H AF WECKER, H AUCHINCLOSS, H TI CELLULAR MECHANISMS OF REJECTION SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID SKIN ALLOGRAFT-REJECTION; T-CELLS; RECEPTOR; MICE; DEFICIENT; MONOCYTES; ANTIGENS; INVIVO; IL-10; MHC AB Studies by molecular biologists, protein chemists and cell biologists are rapidly providing new tools and information for those interested in the cellular mechanisms of graft rejection. Despite these contributions, a clear picture of the mechanisms involved in rejection has not yet evolved. However, whole new areas for research have developed, providing opportunities for new insights as well as therapeutic interventions. RP WECKER, H (reprint author), MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114, USA. NR 50 TC 22 Z9 22 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD OCT PY 1992 VL 4 IS 5 BP 561 EP 566 DI 10.1016/0952-7915(92)90026-B PG 6 WC Immunology SC Immunology GA KN238 UT WOS:A1992KN23800004 PM 1418719 ER PT J AU SHORE, JW AF SHORE, JW TI OCULOPLASTIC AND ORBITAL SURGERY SO CURRENT OPINION IN OPHTHALMOLOGY LA English DT Editorial Material RP SHORE, JW (reprint author), HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,50 STANIFORD ST,3RD FLOOR,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 1040-8738 J9 CURR OPIN OPHTHALMOL PD OCT PY 1992 VL 3 IS 5 BP 621 EP 622 DI 10.1097/00055735-199210000-00009 PG 2 WC Ophthalmology SC Ophthalmology GA JT388 UT WOS:A1992JT38800009 ER PT J AU LYONS, TJ AF LYONS, TJ TI LIPOPROTEIN GLYCATION AND ITS METABOLIC CONSEQUENCES SO DIABETES LA English DT Article; Proceedings Paper CT 14TH INTERNATIONAL DIABETES FEDERATION SATELLITE SYMP ON MACROVASCULAR COMPLICATIONS OF DIABETES MELLITUS CY JUN 20-22, 1991 CL CHARLESTON, SC SP AMER DIABETES ASSOC ID LOW-DENSITY LIPOPROTEIN; MONOCYTE-DERIVED MACROPHAGES; NON-ENZYMATIC GLYCOSYLATION; DEPENDENT DIABETIC-PATIENTS; CHOLESTERYL ESTER SYNTHESIS; CULTURED HUMAN-FIBROBLASTS; NONENZYMATIC GLYCOSYLATION; GLUCOSYLATION; DEGRADATION; IDENTIFICATION AB In people with diabetes, glycation of apolipoproteins correlates with other indices of recent glycemic control, including HbA1. For several reasons, increased glycation of apolipoproteins may play a role in the accelerated development of atherosclerosis in diabetic patients. Recognition of glycated LDL by the classical LDL receptor is impaired, whereas its uptake by human monocyte-macrophages is enhanced. These alterations may contribute to hyperlipidemia and accelerated foam-cell formation, respectively. Glycation of LDL also enhances its capacity to stimulate platelet aggregation. The uptake of VLDL from diabetic patients by human monocyte-macrophages is enhanced. This enhancement may be due, at least in part, to increased glycation of its lipoproteins. Glycation of HDL impairs its recognition by cells and reduces its effectiveness in reverse cholesterol transport. Glycation of apolipoproteins may also generate free radicals, increasing oxidative damage to the apolipoproteins themselves, the lipids in the particle core, and any neighboring macromolecules. This effect may be most significant in extravasated lipoproteins. In these, increased glycation promotes covalent binding to vascular structural proteins, and oxidative reactions may cause direct damage to the vessel wall. Glycoxidation, or browning, of sequestered lipoproteins may further enhance their atherogenicity. Finally, glycated or glycoxidized lipoproteins may be immunogenic, and lipoprotein-immune complexes are potent stimulators of foam-cell formation. C1 RALPH H JOHNSON DEPT VET AFFAIRS MED CTR,CHARLESTON,SC. RP LYONS, TJ (reprint author), MED UNIV S CAROLINA,DIV ENDOCRINOL METAB & NUTR,171 ASHLEY AVE,CHARLESTON,SC 29425, USA. NR 35 TC 145 Z9 149 U1 0 U2 7 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD OCT PY 1992 VL 41 SU 2 BP 67 EP 73 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JQ020 UT WOS:A1992JQ02000013 PM 1526339 ER PT J AU LOPESVIRELLA, MF VIRELLA, G AF LOPESVIRELLA, MF VIRELLA, G TI IMMUNE-MECHANISMS OF ATHEROSCLEROSIS IN DIABETES-MELLITUS SO DIABETES LA English DT Article; Proceedings Paper CT 14TH INTERNATIONAL DIABETES FEDERATION SATELLITE SYMP ON MACROVASCULAR COMPLICATIONS OF DIABETES MELLITUS CY JUN 20-22, 1991 CL CHARLESTON, SC SP AMER DIABETES ASSOC ID LOW-DENSITY-LIPOPROTEIN; SMOOTH-MUSCLE CELLS; MONOCYTE-DERIVED MACROPHAGES; HUMAN-ENDOTHELIAL-CELLS; CHOLESTERYL ESTER SYNTHESIS; FC RECEPTOR; HUMAN-BLOOD; RED-CELLS; COMPLEXES; INTERLEUKIN-1 AB It was recently proposed that the increased levels of modified lipoproteins in diabetic patients may be responsible for the accelerated development of macrovascular complications associated with the disease. Modified lipoproteins are believed to induce the transformation of macrophages into foam cells and, in some cases, to induce endothelial cell damage. In addition, modified lipoproteins trigger an immune response leading to the formation of antibodies and then to the formation of LDL-containing immune complexes. In this review, we summarize the evidence linking LDL glycation and oxidation with intracellular accumulation of cholesterol esters and foam-cell formation, and we discuss their potential for inducing an autoimmune response and the formation of lipoprotein-containing immune complexes. The formation of LDL-ICs seems particularly significant, because these ICs are avidly taken up by macrophages through their F(c) receptors and induce not only massive intracellular accumulation of CE but also a paradoxical increase in LDL-receptor expression. Our experimental data suggest that the uptake of LDL-IC is facilitated by RBC adsorption, in agreement with the role of RBC in the adsorption of circulating IC and their delivery to phagocytic cells. In addition, macrophages are activated when ingesting LDL-IC and release IL-1beta and TNF-alpha which can contribute to the initiation and progression of an atheromatous lesion by several mechanisms. Although it is difficult to envisage how LDL-IC could initiate an endothelial lesion, it is easy to speculate about their role as cofactors in the initiation and progression of the atherosclerotic process. C1 RALPH H JOHNSON DEPT VET AFFAIRS MED CTR,CHARLESTON,SC. MED UNIV S CAROLINA,DEPT MICROBIOL & IMMUNOL,CHARLESTON,SC 29425. RP LOPESVIRELLA, MF (reprint author), MED UNIV S CAROLINA,DEPT MED,DIV ENDOCRINOL METAB & NUTR,171 ASHLEY AVE,CHARLESTON,SC 29425, USA. NR 47 TC 76 Z9 77 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD OCT PY 1992 VL 41 SU 2 BP 86 EP 91 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JQ020 UT WOS:A1992JQ02000017 PM 1526343 ER PT J AU GISINGER, C LOPESVIRELLA, MF AF GISINGER, C LOPESVIRELLA, MF TI LIPOPROTEIN-IMMUNE COMPLEXES AND DIABETIC VASCULAR COMPLICATIONS SO DIABETES LA English DT Article; Proceedings Paper CT 14TH INTERNATIONAL DIABETES FEDERATION SATELLITE SYMP ON MACROVASCULAR COMPLICATIONS OF DIABETES MELLITUS CY JUN 20-22, 1991 CL CHARLESTON, SC SP AMER DIABETES ASSOC ID MONOCYTE-DERIVED MACROPHAGES; LOW-DENSITY LIPOPROTEINS; AUTOANTIBODIES; METABOLISM; ANTIBODIES; INVIVO AB In earlier studies, we showed that incubation of HMM with LDL IC led to cellular CE accumulation and to the transformation of macrophages into foam cells. This study demonstrates that the stimulation of macrophages with RBC-LDL-IC also increases the uptake of native LDL, most likely because of an increased LDL receptor number, as shown by Scatchard plot analysis (x-axis intercept 1267 vs. 352 ng LDL/mg protein in control cells). To determine whether the increase in LDL-receptor activity was secondary to a decrease in the macrophage free (nonassociated) cholesterol content, we measured the T-UC and the UC associated with intracellular intact LDL and demonstrated that 50% of the T-UC is associated with intact LDL. UC not associated with LDL (free cholesterol) was lower in LDL-IC-stimulated cells than in control cells. These results suggest that UC associated with nondegraded intracellular LDL is nonregulatory, a conclusion that was also supported by finding increased sterol synthesis (192.8 +/- 22.9 pmol/mg protein vs. 94.8 +/- 11.8) in RBC-LDL-IC-stimulated macrophages. In conclusion, the uptake of RBC-LDL-IC by macrophages led to increased intracellular accumulation of CE and UC, to a decrease in the cell regulatory pool of free cholesterol, and to an increase in LDL-receptor activity. C1 RALPH H JOHNSON DEPT VET AFFAIRS MED CTR,CHARLESTON,SC. MED UNIV S CAROLINA,CHARLESTON,SC 29425. RP GISINGER, C (reprint author), UNIV VIENNA,DEPT INTERNAL MED 3,WAHRINGER GURTEL 18-20,A-1090 VIENNA,AUSTRIA. NR 25 TC 5 Z9 6 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD OCT PY 1992 VL 41 SU 2 BP 92 EP 96 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JQ020 UT WOS:A1992JQ02000018 PM 1526344 ER PT J AU GOLDSTEIN, BJ DUDLEY, AL AF GOLDSTEIN, BJ DUDLEY, AL TI HETEROGENEITY OF MESSENGER-RNA THAT ENCODES THE RAT INSULIN-RECEPTOR IS LIMITED TO THE DOMAIN OF EXON 11 - ANALYSIS BY RNA HETERODUPLEX MAPPING, AMPLIFICATION OF CDNA, AND INVITRO TRANSLATION SO DIABETES LA English DT Article ID STRUCTURAL DIFFERENCES; EXPRESSION; PROMOTER; MUSCLE; BRAIN; PURIFICATION; TISSUES; LIVER; GENE; GELS AB Structural isoforms of the insulin receptor that occur in various tissues have been postulated to be involved in certain actions of insulin in target cells. To determine whether these insulin-receptor subtypes are caused by alterations in the receptor primary structure we used RNA heteroduplex mapping and amplification of cDNA to detect variation in the coding region of insulin-receptor mRNA from 5 rat tissues A complete series of overlapping antisense [P-32]RNA probes was prepared from plasmids containing segments of a full-length rat insulin-receptor cDNA, and probes were hybridized individually in solution with polyadenylated RNA from rat brain, kidney, liver, skeletal muscle. and spleen. After ribonuclease digestion, probe fragments were analyzed by denaturing gel electrophoresis Tissue-specific cleavage of the mRNA:RNA probe heteroduplex, attributable to sequence mismatch, was detected only for a single probe covering the distal alpha-subunit, as expected for the known alternative splicing of rat insulin-receptor mRNA in this region. No evidence for additional heterogeneity of the receptor mRNA coding region was observed in the 5 tissues studied either by RNA heteroduplex mapping or, in some areas, by regional amplification of insulin-receptor cDNA. Cell-free translation of size-fractionated polyadenylated RNA was used to further demonstrate that each of the major insulin-receptor mRNA size classes in rat contained both forms of the alternatively spliced mRNA transcripts and produced two insulin-proreceptor polypeptides. These results suggest that heterogeneity of the insulin-receptor mRNA coding region affecting the receptor primary structure is limited to the distal alpha-subunit near the subunit cleavage site. Many of the reported structural isoforms of the mature insulin receptor are therefore likely to occur by specific posttranslational processing events that may influence the transmission of the insulin signal in various tissues. C1 HARVARD UNIV, BRIGHAM & WOMENS HOSP, SCH MED, DEPT MED, BOSTON, MA 02115 USA. HARVARD UNIV, BRIGHAM & WOMENS HOSP,SCH MED,JOSLIN DIABETES CTR, DIV RES, BOSTON, MA 02115 USA. FU NIDDK NIH HHS [DK-31036, DK-36836] NR 39 TC 13 Z9 13 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD OCT PY 1992 VL 41 IS 10 BP 1293 EP 1300 DI 10.2337/diabetes.41.10.1293 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JP475 UT WOS:A1992JP47500010 PM 1397703 ER PT J AU KLEIN, RL WOHLTMANN, HJ LOPESVIRELLA, MF AF KLEIN, RL WOHLTMANN, HJ LOPESVIRELLA, MF TI INFLUENCE OF GLYCEMIC CONTROL ON INTERACTION OF VERY-LOW-DENSITY AND LOW-DENSITY LIPOPROTEINS ISOLATED FROM TYPE-I DIABETIC-PATIENTS WITH HUMAN MONOCYTE-DERIVED MACROPHAGES SO DIABETES LA English DT Article ID CHOLESTERYL ESTER SYNTHESIS; METABOLIC CONTROL; MELLITUS; PLASMA; GLYCOSYLATION; DEGRADATION; BINDING; SURFACE; THERAPY AB The VLDL and LDL tractions were isolated from 29 patients with type 1 diabetes at the time of admission to the hospital to restore glycemic control and again at discharge. These lipoprotein fractions were incubated with human monocyte-derived macrophages, and the rates of macrophage CE synthesis were determined. The rates of CE synthesis in human macrophages were significantly greater (P < 0.005) when incubated with VLDL isolated from type I diabetic patients before compared with after glycemic control was attained and averaged 1.84 +/- 0.52 and 1.09 +/- 0.27 nmol (1.20 +/- 0.34 and 0.71 +/- 0.18-mu-g) [C-14]cholesteryl oleate synthesized mg cell protein-1 . 20 h-1 respectively In contrast, when LDL isolated from the same patient during the same period was incubated with human macrophages, the rates of cellular cholesteryl ester synthesis did not differ significantly and averaged 4.23 +/- 1.26 and 3.91 +/- 0.96 nmol (2.75 +/- 0.82 and 2.55 +/- 0.63-mu-g) [C-14]cholesteryl oleate synthesized mg-1 cell protein . 20 h-1, respectively There was a significant increase in the total cholesterol content of VLDL isolated before glycemic control compared with that isolated after glycemic control was attained (P < 0.05) resulting from a significant increase in the FC and CE (P < 0.05) contents of these VLDL particles. There was a significant decrease in the ratio of FC to PL in VLDL, but not LDL, isolated after glycemic control (P < 0.05). The percentage of apoE in VLDL was significantly decreased (P < 0.05) after glycemic control was attained. In LDL isolated after glycemic control was achieved, a significant decrease (P < 0.005) in the percentage ot triglycerides was observed. In addition, there was a significant decrease (P < 0.0001) in the extent of glycation of LDL isolated after glycemic control. These studies suggest that during periods of poor glycemic control, the composition of VLDL isolated from type 1 diabetic patients is altered. These modified VLDLs stimulate CE synthesis rates in human macrophages and, thus, may contribute to the increased prevalence of atherosclerosis in diabetic patients. C1 MED UNIV S CAROLINA,DEPT MED,CHARLESTON,SC 29425. MED UNIV S CAROLINA,DEPT PEDIAT,CHARLESTON,SC 29425. RP KLEIN, RL (reprint author), RALPH H JOHNSON DEPT VET AFFAIRS MED CTR,RES SERV 151,109 BEE ST,CHARLESTON,SC 29401, USA. NR 40 TC 19 Z9 19 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD OCT PY 1992 VL 41 IS 10 BP 1301 EP 1307 DI 10.2337/diabetes.41.10.1301 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JP475 UT WOS:A1992JP47500011 PM 1397704 ER PT J AU CHEN, C THORENS, B BONNERWEIR, S WEIR, GC LEAHY, JL AF CHEN, C THORENS, B BONNERWEIR, S WEIR, GC LEAHY, JL TI RECOVERY OF GLUCOSE-INDUCED INSULIN-SECRETION IN A RAT MODEL OF NIDDM IS NOT ACCOMPANIED BY RETURN OF THE B-CELL GLUT2 GLUCOSE TRANSPORTER SO DIABETES LA English DT Article ID PANCREATIC BETA-CELLS; DIABETIC HYPERGLYCEMIA; GLUCAGON-SECRETION; DOWN-REGULATION; ISLETS; EXPRESSION; RESPONSES; RELEASE; LIVER; INSENSITIVITY AB The NSTZ rat model combines loss of glucose-induced insulin secretion with a reduced amount of the high K(m) B-cell glucose transporter, GLUT2. The purpose of this study was to determine whether the restoration of glucose-induced insulin secretion was paralleled by an increase of GLUT2. Rats injected at 2 days of age with 90 mg/kg STZ were studied al 8-13 wk of age. Insulin secretion was assessed in the isolated perfused pancreas with 16.7 mM glucose preceded by 40 min of 0 or 5.5 mM glucose. In control rats, 16.7 mM glucose caused the same large biphasic insulin response whether preceded by 0 or 5.5 mM glucose. In NSTZ rats, after 5.5 mM glucose 16.7 mM glucose elicited virtually no rise in insulin release. In contrast, after 0 mM glucose, a large insulin response to the glucose challenge occurred that was equal to that of the control groups when the differences in B-cell mass were taken into account. However, the dose-response curve for glucose-induced insulin secretion was shifted to the left, and no second phase of insulin secretion was observed. GLUT2 was assessed after the perfusions by indirect immunofluorescence with anti-GLUT2 antisera. Both control groups showed homogenous staining in all B-cells. NSTZ rats perfused with 5.5 mM glucose had a marked diminution in GLUT2 staining. We observed no increase in GLUT2 staining in the NSTZ rats perfused with 0 mM glucose. In summary, our results show: 1) the recovered glucose responsiveness in NSTZ rats after perfusion with 0 mM glucose appears in the presence of a reduced level of GLUT2; 2) the recovered glucose-induced insulin secretion is abnormal in that the glucose dose-response curve is shifted to lower glucose concentrations and a blunted second phase occurs. These results suggest that several steps are altered in the glucose signaling pathway of glucose unresponsive B-cells from NSTZ rats, and that a reduction of GLUT2 level may be only a partial cause of the secretory defects of diabetic B-cells. C1 JOSLIN DIABETES CTR,DIV RES,BOSTON,MA. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,NEW ENGLAND DEACONESS HOSP,SCH MED,DEPT MED,BOSTON,MA 02215. MIT,WHITEHEAD INST BIOMED RES,DEPT BIOL,CAMBRIDGE,MA 02139. FU NIDDK NIH HHS [DK-35449, DK-38543]; NIGMS NIH HHS [GM 40916] NR 50 TC 22 Z9 23 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD OCT PY 1992 VL 41 IS 10 BP 1320 EP 1327 DI 10.2337/diabetes.41.10.1320 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JP475 UT WOS:A1992JP47500013 PM 1397706 ER PT J AU GANDA, OP ARKIN, CF AF GANDA, OP ARKIN, CF TI HYPERFIBRINOGENEMIA - AN IMPORTANT RISK FACTOR FOR VASCULAR COMPLICATIONS IN DIABETES SO DIABETES CARE LA English DT Article ID PLASMA-FIBRINOGEN; MELLITUS; DISEASE; ATHEROSCLEROSIS; MORTALITY; EXERCISE; GLUCOSE AB OBJECTIVE - To evaluate the determinants of elevated fibrinogen levels and the impact of hyperfibrinogenemia on vascular complications in diabetes. RESEARCH DESIGN AND METHODS - Plasma fibrinogen, glucose, HbA1, and lipids were measured in 116 ambulatory type I and type II diabetic patients with (n = 59) or without (n = 57) clinical evidence of micro- or macrovascular complications. In 56 of these patients, factor VII activity and CRP also were measured. Univariate and multivariate data analyses were conducted. RESULTS - Overall mean +/- SE fibrinogen levels in patients (339 +/- 7.3 mg/dl) were elevated markedly compared with control subjects (248 +/- 9.1 mg/dl). Fibrinogen levels were elevated disproportionately in patients with type II diabetes (P < 0.0001), hypertension (P = 0.0001), obesity (P < 0.0001), and vascular complications (P < 0.0001). Fibrinogen was correlated significantly with age (P < 0.001), cholesterol (P = 0.002), CRP (P < 0.001), and factor VII activity (P = 0.032), but not with plasma glucose, triglycerides, HDL cholesterol, or disease duration. Stepwise multiple regression analyses revealed that type II diabetes and presence of vascular complications were major determinants of fibrinogen. For vascular complications, fibrinogen emerged as one of only three independent predictors, the other two being diabetes duration and hypertension. CONCLUSIONS - Fibrinogen frequently is elevated in diabetes and is an independent predictor of vascular complications. C1 NEW ENGLAND DEACONESS HOSP,DEPT MED,BOSTON,MA 02215. NEW ENGLAND DEACONESS HOSP,DEPT PATHOL,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP GANDA, OP (reprint author), JOSLIN DIABET CTR,1 JOSLIN PL,BOSTON,MA 02215, USA. NR 35 TC 143 Z9 144 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 OCT PY 1992 VL 15 IS 10 BP 1245 EP 1250 DI 10.2337/diacare.15.10.1245 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JP726 UT WOS:A1992JP72600001 PM 1425083 ER PT J AU LAIRSON, DR PUGH, JA KAPADIA, AS LORIMOR, RJ JACOBSON, J VELEZ, R AF LAIRSON, DR PUGH, JA KAPADIA, AS LORIMOR, RJ JACOBSON, J VELEZ, R TI COST-EFFECTIVENESS OF ALTERNATIVE METHODS FOR DIABETIC-RETINOPATHY SCREENING SO DIABETES CARE LA English DT Article AB OBJECTIVE - To assess from the perspectives of a government delivery system and patients, the cost-effectiveness of the 45-degree retinal camera compared to the standard ophthalmologists exam and an ophthalmic exam by a physician's assistant or nurse practitioner technician, for detecting nonproliferative and proliferative diabetic retinopathy. RESEARCH DESIGN AND METHODS - Comparison of 45-degree fundus photographs with and without pharmacological pupil dilation taken by technicians and interpreted by experts, direct and indirect ophthalmoscopy by ophthalmologists, and direct ophthalmoscopy by technicians with seven-field stereoscopic fundus photography (reference standard). Costs were estimated from market prices and actual resource use. The study included 352 patients attending outpatient diabetes and general-medicine clinics at VA and DOD facilities. RESULTS - Medical system costs per true positive were: 45-degree photos with dilation, $295; 45-degree photos without dilation, $378; ophthalmologist, $390; and technician, $794. Patient costs per true positive were: 45-degree photos with dilation, $139; 45-degree photos without dilation, $171; ophthalmologist, $306; and technician, $1009. Cost-effectiveness is sensitive to program size due to high fixed cost of the camera methods but not to prevalence. Cost-effectiveness of the technician exam is strongly affected by its sensitivity. CONCLUSIONS - Primary-care screening with retinal photographs through pharmacologically dilated pupils for diabetic retinopathy is an appropriate and cost-effective alternative to screening by an ophthalmologist in this setting. Ophthalmologists are scarce, primary-care physicians are extremely busy, and large clinics allow fixed equipment costs to be spread across many patients. C1 USAF,WILFORD HALL MED CTR,LACKLAND AFB,TX 78236. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. RP LAIRSON, DR (reprint author), UNIV TEXAS,HLTH SCI CTR,SCH PUBL HLTH,POB 20186,HOUSTON,TX 77225, USA. OI Pugh, Jacqueline/0000-0003-4933-141X NR 21 TC 54 Z9 55 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 OCT PY 1992 VL 15 IS 10 BP 1369 EP 1377 DI 10.2337/diacare.15.10.1369 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JP726 UT WOS:A1992JP72600021 PM 1425103 ER PT J AU NATHAN, DM HABENER, JF AF NATHAN, DM HABENER, JF TI DISCUSSING THE ROLE OF GLUCAGON-LIKE PEPTIDE-I - REPLY SO DIABETES CARE LA English DT Letter RP NATHAN, DM (reprint author), MASSACHUSETTS GEN HOSP,DIABET UNIT,BOSTON,MA 02114, USA. NR 5 TC 0 Z9 0 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 OCT PY 1992 VL 15 IS 10 BP 1441 EP 1441 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JP726 UT WOS:A1992JP72600043 ER PT J AU EGERTON, M ASHE, OR CHEN, D DRUKER, BJ BURGESS, WH SAMELSON, LE AF EGERTON, M ASHE, OR CHEN, D DRUKER, BJ BURGESS, WH SAMELSON, LE TI VCP, THE MAMMALIAN HOMOLOG OF CDC48, IS TYROSINE PHOSPHORYLATED IN RESPONSE TO T-CELL ANTIGEN RECEPTOR ACTIVATION SO EMBO JOURNAL LA English DT Article DE CELL CYCLE; PHOSPHORYLATION; SIGNAL TRANSDUCTION; LYMPHOCYTE-T ID PHOSPHOLIPASE C-GAMMA-1; SIGNAL TRANSDUCTION; PHOSPHATASE-ACTIVITY; PRECURSOR PROTEIN; GENE-EXPRESSION; ZETA-CHAIN; KINASE; YEAST; STIMULATION; CDNA AB Activation of T cells through the T cell antigen receptor (TCR) results in the rapid tyrosine phosphorylation of a number of cellular proteins, one of the earliest being a 100 kDa protein. We have sought to identify this 100 kDa substrate by partially purifying the protein by antiphosphotyrosine (APT) affinity purification, in order to obtain amino acid sequence data and, using this information, to isolate the cDNA clone encoding the molecule. We report here that the amino acid sequence data showed pp100 to be the murine equivalent of porcine valosin containing protein (VCP), a finding confirmed from the cloning and sequencing of the murine pp100 cDNA. Sequence analysis has shown VCP to be a member of a family of ATP binding, homo-oligomeric proteins, and the mammalian homolog of Saccharomyces cerevisiae cdc48p, a protein essential to the completion of mitosis in yeast. We also provide proof that both endogenous and expressed murine VCP are tyrosine phosphorylated in response to T cell activation. Thus we have identified a novel component of the TCR mediated tyrosine kinase activation pathway that may provide a link between TCR ligation and cell cycle control. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV MOLEC & CELLULAR BIOL,BOSTON,MA 02115. AMER RED CROSS,HOLLAND LAB,ROCKVILLE,MD 20850. RP EGERTON, M (reprint author), NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892, USA. FU NHLBI NIH HHS [HL-35762] NR 56 TC 120 Z9 122 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD OCT PY 1992 VL 11 IS 10 BP 3533 EP 3540 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA JN506 UT WOS:A1992JN50600006 PM 1382975 ER PT J AU FUKAYAMA, S TASHJIAN, AH BRINGHURST, FR AF FUKAYAMA, S TASHJIAN, AH BRINGHURST, FR TI MECHANISMS OF DESENSITIZATION TO PARATHYROID-HORMONE IN HUMAN OSTEOBLAST-LIKE SAOS-2 CELLS SO ENDOCRINOLOGY LA English DT Article ID PROTEIN KINASE-C; BETA-ADRENERGIC-RECEPTOR; OPOSSUM KIDNEY-CELLS; ADENYLATE-CYCLASE SYSTEM; CYCLIC-AMP PRODUCTION; CULTURED BONE-CELLS; ROS 17/2.8 CELLS; SARCOMA CELLS; PHORBOL-ESTER; HOMOLOGOUS DESENSITIZATION AB Signal transduction by the PTH receptor is now known to involve generation of multiple second messengers. Desensitization of the adenylate cyclase response to PTH is a common feature of bone- and kidney-derived target cells; however, no single mechanism appears to explain desensitization in the different cell types studied. To examine the role of protein kinase-A (PKA) in homologous desensitization to PTH, we employed human SaOS-2 osteoblast-like cells and a mutant subclone (Ca 4A), which expresses an inducible cAMP-resistant form of PKA. Pretreatment of SaOS-2 cells with PTH for 4 h reduced by 60-80% the cAMP response to subsequent rechallenge with the hormone. This homologous desensitization was significantly, but not completely, inhibited in Ca 4A cells. Desensitization was not mimicked by pretreatment of the cells with forskolin. PTH binding to its receptor was reduced 50% in both SaOS-2 and Ca 4A cells after 4-h incubation with PTH (homologous down-regulation), whereas forskolin did not cause receptor down-regulation. Pretreatment with the ionophore ionomycin for 4 24 h did not mimic desensitization to PTH. Both desensitization to PTH and receptor down-regulation were induced, however, by pretreatment with a phorbol ester (12-O-tetradecanoyl phorbol-13-acetate), and these effects were blocked completely by staurosporine. PTH-induced desensitization was not blocked by staurosporine, and receptor down-regulation was enhanced by the drug. Pertussis toxin did not prevent desensitization induced by either PTH or L2-0-tetradecanoyl phorbol-13-acetate. We conclude that homologous desensitization to PTH in SaOS-2 cells involves both cAMP-dependent and -independent mechanisms. Homologous PTH receptor down-regulation apparently is mediated by mechanisms independent of PKA activation. Neither pathway of homologous desensitization to PTH involves the action of pertussis toxin-sensitive G-proteins. C1 HARVARD UNIV, SCH MED, DEPT MED, BOSTON, MA 02114 USA. HARVARD UNIV, SCH PUBL HLTH, DEPT MOLEC & CELLULAR TOXICOL, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DEPT BIOL CHEM & MOLEC PHARMACOL, BOSTON, MA 02115 USA. RP FUKAYAMA, S (reprint author), MASSACHUSETTS GEN HOSP, ENDOCRINE UNIT, FRUIT ST, BOSTON, MA 02114 USA. FU NIADDK NIH HHS [AM-11794]; NIDDK NIH HHS [DK-10206] NR 60 TC 41 Z9 41 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD OCT PY 1992 VL 131 IS 4 BP 1757 EP 1769 DI 10.1210/en.131.4.1757 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JT904 UT WOS:A1992JT90400029 PM 1396321 ER PT J AU FUKAYAMA, S TASHJIAN, AH BRINGHURST, FR AF FUKAYAMA, S TASHJIAN, AH BRINGHURST, FR TI FORSKOLIN-INDUCED HOMOLOGOUS DESENSITIZATION VIA AN ADENOSINE 3',5'-MONOPHOSPHATE-DEPENDENT MECHANISM(S) IN HUMAN OSTEOBLAST-LIKE SAOS-2 CELLS SO ENDOCRINOLOGY LA English DT Article ID HUMAN-BONE CELLS; PARATHYROID-HORMONE PTH; ADENYLATE-CYCLASE; INHIBITORY-ACTION; DIRECT MODULATION; LEYDIG-CELLS; LINE SAOS-2; PROTEIN; EXPRESSION; DITERPENE AB We have reported that pretreatment of human SaOS-2 osteoblast-like cells with forskolin (Fsk; 10(-5) m) for 4 h strikingly inhibited subsequent cAMP responsiveness to a second challenge with Fsk (Fsk-induced homologous desensitization) without altering the responses to PTH or vasoactive intestinal peptide (VIP). Pretreatment with PTH acutely augmented Fsk responsiveness, despite desensitizing the cells to rechallenge with PTH. The present studies were performed to investigate the mechanism of this differential desensitization. Fsk-induced desensitization was not mimicked by 1,9-dideoxyforskolin, a Fsk analog that does not activate adenylate cyclase (AC) but does reproduce certain cAMP-independent effects of Fsk. Fsk-induced homologous desensitization was also completely blocked in a cAMP-resistant mutant SaOS-2 cell line (Ca 4A), in which protein kinase-A (PKA) is not activated by endogenous cAMP. However, pretreatment with PTH (or VIP), which induced a large increase in cAMP, did not attenuate, but, rather, increased, the subsequent cAMP response to Fsk. Potentiation by PTH was also observed in Ca 4A cells. Pretreatment of SaOS-2 cells with pertussis toxin (100 ng/ml) for 12 h strikingly inhibited the initial cAMP response to Fsk, although Fsk-induced homologous desensitization was still clearly observed. Pretreatment with cholera toxin (1 mug/ml) completely prevented Fsk-induced homologous desensitization. Combinations of maximal concentrations of Fsk plus hormones such as human PTH, human PTH-related peptide, or VIP elicited cAMP responses that were much more than additive, an effect not observed with combinations of hormones alone. We conclude that 1) Fsk-induced homologous desensitization of the AC response of SaOS-2 cells to a second challenge with Fsk is dependent upon activation of PKA; 2) one or more pertussis toxin-sensitive G-proteins contribute to full AC activation by Fsk, but are not involved in homologous desensitization; 3) augmentation by PTH (or VIP) pretreatment of Fsk-dependent AC activation involves an effector(s) other than PKA. These results provide further evidence that the regulation of AC responsiveness in SaOS-2 cells by PTH or VIP is complex and cannot be explained by activation of PKA alone. C1 HARVARD UNIV, SCH MED, DEPT MED, BOSTON, MA 02114 USA. HARVARD UNIV, SCH PUBL HLTH, DEPT MOLEC & CELLULAR TOXICOL, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DEPT BIOL CHEM & MOLEC PHARMACOL, BOSTON, MA 02115 USA. RP FUKAYAMA, S (reprint author), MASSACHUSETTS GEN HOSP, ENDOCRINE UNIT, FRUIT ST, BOSTON, MA 02114 USA. FU NIADDK NIH HHS [AM-11794]; NIDDK NIH HHS [DK-10206] NR 25 TC 12 Z9 12 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD OCT PY 1992 VL 131 IS 4 BP 1770 EP 1776 DI 10.1210/en.131.4.1770 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JT904 UT WOS:A1992JT90400030 PM 1327719 ER PT J AU WAEBER, G HABENER, JF AF WAEBER, G HABENER, JF TI NOVEL TESTIS GERM CELL-SPECIFIC TRANSCRIPT OF THE CREB GENE CONTAINS AN ALTERNATIVELY SPLICED EXON WITH MULTIPLE IN-FRAME STOP CODONS SO ENDOCRINOLOGY LA English DT Article ID BINDING PROTEIN CREB; EXPRESSION; DOMAIN AB The gene encoding the cAMP-responsive transcription factor CREB consists of multiple small exons some of which undergo alternative RNA splicing. We describe the finding of a novel transcript of the CREB gene expressed at high levels in the germ cells of the rat testis. The transcript contains an alternatively spliced exon inserted within the sequence encoding the transcriptional transactivation domain of CREB and this exon contains multiple in-frame stop codons. Furthermore, the exon is conserved in both rat and human genes (75% nucleotide identity). Although the function(s) of this RNA or the truncated CREB protein predicted to result from the translation of this unusual transcript is unknown, the high level of expression in the testicular germ cells and remarkable conservation of sequences in rat and human suggests that it may have a unique biological function in these cells. C1 HARVARD UNIV, MASSACHUSETTS GEN HOSP,SCH MED, HOWARD HUGHES MED INST,MOLEC ENDOCRINOL LAB, BOSTON, MA 02114 USA. FU NIDDK NIH HHS [DK-30457, DK-25532] NR 16 TC 39 Z9 39 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD OCT PY 1992 VL 131 IS 4 BP 2010 EP 2015 DI 10.1210/en.131.4.2010 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JT904 UT WOS:A1992JT90400067 PM 1396344 ER PT J AU FRUMAN, DA MATHER, PE BURAKOFF, SJ BIERER, BE AF FRUMAN, DA MATHER, PE BURAKOFF, SJ BIERER, BE TI CORRELATION OF CALCINEURIN PHOSPHATASE-ACTIVITY AND PROGRAMMED CELL-DEATH IN MURINE T-CELL HYBRIDOMAS SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article ID CD3/T-CELL RECEPTOR COMPLEX; DNA FRAGMENTATION; CYCLOSPORINE-A; PROTEIN PHOSPHATASES; IMMATURE THYMOCYTES; MACROLIDES FK-506; CALCIUM IONOPHORE; ACTIVATION; RAPAMYCIN; MECHANISMS AB Ligation of T cell receptor/CD3 complexes induces programmed cell death, or apoptosis, in immature thymocytes and many T cell hybridomas.While it has been demonstrated that T cell receptor-mediated apoptosis requires an increase in intracellular calcium concentration. the specific calcium-dependent signalling events leading to cell death are poorly defined. We have previously shown that T cell receptor/CD3-mediated induction of apoptosis in a murine T cell hybridoma is inhibited by the immunosuppressive drugs cyclosporin A (CsA) and FK506. Recently, it has been determined that these agents inhibit the activity of calcineurin, a calcium- and calmodulin-dependent serine/threonine phosphatase. Using an assay which measures calcineurin activity in cell lysates, we find that calcineurin-dependent dephosphorylation of a phosphopeptide substrate is potently inhibited in hybridomas treated with CsA or FK506. Drug dose-response analyses indicate that the level of cellular calcineurin activity correlates closely with the ability of these cells to undergo apoptosis. Thus, calcineurin appears to be a critical mediator of T cell receptor/CD3 signalling leading to programmed cell death in T cell hybridomas. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,44 BINNEY ST,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DIV HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DIV MED SCI,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. FU NCI NIH HHS [CA 39542] NR 39 TC 104 Z9 104 U1 0 U2 4 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 OCT PY 1992 VL 22 IS 10 BP 2513 EP 2517 DI 10.1002/eji.1830221008 PG 5 WC Immunology SC Immunology GA JV594 UT WOS:A1992JV59400007 PM 1382988 ER PT J AU KUTER, DJ GMINSKI, D ROSENBERG, RD AF KUTER, DJ GMINSKI, D ROSENBERG, RD TI BOTROCETIN AGGLUTINATION OF RAT MEGAKARYOCYTES - A RAPID METHOD FOR MEGAKARYOCYTE ISOLATION SO EXPERIMENTAL HEMATOLOGY LA English DT Article DE MEGAKARYOCYTE; BOTROCETIN; PURIFICATION ID VONWILLEBRAND-FACTOR; VENOM COAGGLUTININ; PLATELET; ELUTRIATION; RISTOCETIN; MATURATION; MEMBRANE; INVITRO; PLOIDY; DOMAIN AB Botrocetin isolated from the venom of Bothrops jaracara has been shown by others to induce binding of von Willebrand Factor to glycoprotein Ib and thereby produce platelet agglutination in a wide range of animal species. We have found that botrocetin also facilitates the agglutination of megakaryocytes and have, used this property to develop a method to isolate megakaryocytes from rat bone marrow. When botrocetin is added to a mixture of rat bone marrow, rat platelets, and rat plasma, coagglutination of megakaryocytes and platelets occurs. The agglutinated complexes, containing >95% of the megakaryocytes, may then be separated from the remaining marrow cells by filtration. Megakaryocytes account for 39% (range 30%-48%) of the isolated-cells and 83% (range 77%-88%) of the isolated cell mass. This method allows the virtually complete removal of megakaryocytes from bone marrow as well as their isolation to a high degree of purity. It should provide a useful, inexpensive, general method for the rapid isolation of megakaryocytes from multiple, small marrow samples from a wide range of species. C1 MASSACHUSETTS GEN HOSP,DEPT MED,HEMATOL ONCOL UNIT,BOSTON,MA 02114. BETH ISRAEL HOSP,DEPT MED,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP KUTER, DJ (reprint author), MIT,WHITAKER COLL,DEPT BIOL,77 MASSACHUSETTS AVE,CAMBRIDGE,MA 02139, USA. FU NHLBI NIH HHS [HL 39753] NR 18 TC 3 Z9 3 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD OCT PY 1992 VL 20 IS 9 BP 1085 EP 1089 PG 5 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA JP952 UT WOS:A1992JP95200009 PM 1468542 ER PT J AU SHIH, MC HEINRICH, P GOODMAN, HM AF SHIH, MC HEINRICH, P GOODMAN, HM TI CLONING AND CHROMOSOMAL MAPPING OF NUCLEAR GENES ENCODING CHLOROPLAST AND CYTOSOLIC GLYCERALDEHYDE-3-PHOSPHATE-DEHYDROGENASE FROM ARABIDOPSIS-THALIANA SO GENE LA English DT Article ID DEHYDROGENASE C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. NR 3 TC 10 Z9 10 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD OCT 1 PY 1992 VL 119 IS 2 BP 317 EP 319 DI 10.1016/0378-1119(92)90290-6 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA JQ153 UT WOS:A1992JQ15300024 PM 1398114 ER PT J AU SWISSHELM, K LEONARD, M SAGER, R AF SWISSHELM, K LEONARD, M SAGER, R TI PREFERENTIAL CHROMOSOME LOSS IN HUMAN PAPILLOMA-VIRUS DNA-IMMORTALIZED MAMMARY EPITHELIAL-CELLS SO GENES CHROMOSOMES & CANCER LA English DT Article ID BREAST-CANCER; INDEFINITE DIVISION; CELLULAR SENESCENCE; GENETIC-ANALYSIS; INTEGRATION; EXPRESSION; TYPE-16; P53; IDENTIFICATION; TRANSFORMATION AB Human papilloma virus (HPV) DNA-immortalized human mammary epithelial cells may provide a model system for studying the molecular basis of immortalization and its role in breast neoplasia. Cytogenetic analyses were performed on clones derived from HPV 16- and HPV 18-immortalized human mammary epithelial cells. The majority of the clones contained near-diploid karyotypes. The single most frequent whole-chromosome loss was that of chromosome 19. Regions that showed preference for deletion and/or translocation included 2pter, 11qter, and 15pter. Evidence of chromosome 19 loss was confirmed by polymerase chain reaction (PCR)-generated, chromosome 19-specific, dinucleotide microsatellite repeat polymorphism analysis. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC GENET,44 BINNEY ST,BOSTON,MA 02115. FU NCI NIH HHS [T32 CA09361-12, CA39814] NR 42 TC 6 Z9 6 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD OCT PY 1992 VL 5 IS 3 BP 219 EP 226 DI 10.1002/gcc.2870050308 PG 8 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA JV517 UT WOS:A1992JV51700006 PM 1384674 ER PT J AU FLETCHER, JA PINKUS, JL LAGE, JM MORTON, CC PINKUS, GS AF FLETCHER, JA PINKUS, JL LAGE, JM MORTON, CC PINKUS, GS TI CLONAL 6P21 REARRANGEMENT IS RESTRICTED TO THE MESENCHYMAL COMPONENT OF AN ENDOMETRIAL POLYP SO GENES CHROMOSOMES & CANCER LA English DT Note ID GROWTH; TUMORS; CELLS AB Previous cytogenetic analyses revealed t(6;20)(p21;q13) in two endometrial polyps. We karyotyped a large endometrial polyp in which 19 of 25 metaphase cells contained a t(1;6;4)(q21;p21;q13). Subsequent combined immunohistochemical/cytogenetic analysis showed all aberrant metaphase cells to be of mesenchymal derivation, whereas epithelial cells from the polyp were diploid. These studies indicate that rearrangement of chromosome band 6p21 is a characteristic cytogenetic aberration in the stromal component of endometrial polyps. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PEDIAT ONCOL,BOSTON,MA 02115. CHILDRENS HOSP MED CTR,DEPT HEMATOL ONCOL,BOSTON,MA 02115. CHILDRENS HOSP MED CTR,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. RP FLETCHER, JA (reprint author), BRIGHAM & WOMENS HOSP,DEPT PATHOL,75 FRANCIS ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [1K11CA01498-02] NR 13 TC 46 Z9 50 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 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD OCT PY 1992 VL 5 IS 3 BP 260 EP 263 DI 10.1002/gcc.2870050315 PG 4 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA JV517 UT WOS:A1992JV51700013 PM 1384681 ER PT J AU LEES, E FAHA, B DULIC, V REED, SI HARLOW, E AF LEES, E FAHA, B DULIC, V REED, SI HARLOW, E TI CYCLIN-E CDK2 AND CYCLIN-A CDK2 KINASES ASSOCIATE WITH P107 AND E2F IN A TEMPORALLY DISTINCT MANNER SO GENES & DEVELOPMENT LA English DT Article DE CELL CYCLE; CYCLIN-E; CDK2; E2F; P107 ID RETINOBLASTOMA GENE-PRODUCT; TRANSCRIPTION FACTOR E2F; CELL-CYCLE; SACCHAROMYCES-CEREVISIAE; PROTEIN-KINASE; G1 PHASE; G1-SPECIFIC CYCLINS; PROMOTING FACTOR; FISSION YEAST; MESSENGER-RNA AB Cyclin E is classified as a putative G1 cyclin on the basis of its cyclic pattern of mRNA expression, with maximal levels being detected near the G1/S boundary. We report here that cyclin E is found associated with the transcription factor E2F in a temporally regulated fashion. E2F is known to be a critical transcription factor for the expression of some S phase-specific proteins and is thought to be important for a series of others. Antisera specific for cyclin E were raised and used to demonstrate an association between cyclin E and E2F. This cyclin E/E2F complex was seen in a variety of human cell lines from various tissues, but its appearance was detected primarily during the G1 phase of the cell cycle. The cyclin E/E2F association decreased as cells entered S phase, just as the association of E2F with cyclin A became detectable. We characterized the cyclin E-E2F complex further to show that both the cyclin-dependent kinase-2 (cdk2) and p107 were present. Therefore, the p107/E2F complex is associated with two different cdk2 kinase complexes-one containing cyclin A and the other containing cyclin E-and the appearance of these complexes is temporally regulated during the cell cycle. The presence of cyclin E/E2F complexes in the G1 phase suggests a role for cyclin E in the control of genes required for the G1-to-S transition. C1 SCRIPPS RES INST, DEPT MOLEC BIOL, LA JOLLA, CA 92037 USA. RP LEES, E (reprint author), MASSACHUSETTS GEN HOSP, CTR CANC, BOSTON, MA 02129 USA. OI Dulic, Vjekoslav/0000-0003-1201-3901 FU NCI NIH HHS [CA55339]; NIGMS NIH HHS [GM 46006, GM38328] NR 70 TC 430 Z9 432 U1 1 U2 2 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0890-9369 J9 GENE DEV JI Genes Dev. PD OCT PY 1992 VL 6 IS 10 BP 1874 EP 1885 DI 10.1101/gad.6.10.1874 PG 12 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA JT979 UT WOS:A1992JT97900006 PM 1398067 ER PT J AU YOUNGMAN, S BATES, GP WILLIAMS, S MCCLATCHEY, AI BAXENDALE, S SEDLACEK, Z ALTHERR, M WASMUTH, JJ MACDONALD, ME GUSELLA, JF SHEER, D LEHRACH, H AF YOUNGMAN, S BATES, GP WILLIAMS, S MCCLATCHEY, AI BAXENDALE, S SEDLACEK, Z ALTHERR, M WASMUTH, JJ MACDONALD, ME GUSELLA, JF SHEER, D LEHRACH, H TI THE TELOMERIC 60 KB OF CHROMOSOME ARM 4P IS HOMOLOGOUS TO TELOMERIC REGIONS ON 13P, 15P, 21P, AND 22P SO GENOMICS LA English DT Article ID HUNTINGTON DISEASE GENE; LINKAGE DISEQUILIBRIUM; DNA SEGMENT; YEAST; LOCUS; CLONING; PROBES; RECOMBINATION; HYBRIDIZATION; SEQUENCE C1 IMPERIAL CANC RES FUND,HUMAN CYTOGENET LAB,LONDON WC2A 3PX,ENGLAND. MASSACHUSETTS GEN HOSP,NEUROGENET LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT BIOL CHEM,BOSTON,MA 02114. UNIV CALIF IRVINE,DEPT BIOL CHEM,IRVINE,CA 92717. GERMAN CANC RES CTR,W-6900 HEIDELBERG 1,GERMANY. RP YOUNGMAN, S (reprint author), IMPERIAL CANC RES FUND,GENOME ANAL LAB,LINCOLNS INN FIELDS,LONDON WC2A 3PX,ENGLAND. RI Sheer, Denise/C-6705-2011; Bates, Gillian/E-1146-2012 OI Sheer, Denise/0000-0001-9067-1796; Bates, Gillian/0000-0002-4041-6305 FU NHGRI NIH HHS [HG00317, HG00169]; NINDS NIH HHS [NS16367] NR 44 TC 37 Z9 37 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 OCT PY 1992 VL 14 IS 2 BP 350 EP 356 DI 10.1016/S0888-7543(05)80225-3 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA JR697 UT WOS:A1992JR69700018 PM 1427851 ER PT J AU LIN, MY MUNSHI, IA OUELLETTE, AJ AF LIN, MY MUNSHI, IA OUELLETTE, AJ TI THE DEFENSIN-RELATED MURINE CRS1C GENE - EXPRESSION IN PANETH CELLS AND LINKAGE TO DEFCR, THE CRYPTDIN LOCUS SO GENOMICS LA English DT Article ID RECOMBINANT INBRED STRAINS; MESSENGER-RNA; INSITU HYBRIDIZATION; SMALL-INTESTINE; LYSOZYME; LOCALIZATION; MICE; DUPLICATION; DIVERGENCE; EPITHELIUM C1 MASSACHUSETTS GEN HOSP,CELL BIOL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT BIOL CHEM,BOSTON,MA 02114. NR 31 TC 17 Z9 17 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD OCT PY 1992 VL 14 IS 2 BP 363 EP 368 DI 10.1016/S0888-7543(05)80227-7 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA JR697 UT WOS:A1992JR69700020 PM 1427853 ER PT J AU TANZI, RE ROMANO, DM BERGER, R BURACZYNSKA, MJ GASTON, SM KURNIT, DM PATTERSON, D GUSELLA, JF STEWART, GD AF TANZI, RE ROMANO, DM BERGER, R BURACZYNSKA, MJ GASTON, SM KURNIT, DM PATTERSON, D GUSELLA, JF STEWART, GD TI SEQUENCE-TAGGED SITES (STSS) FOR A SET OF MAPPED MARKERS ON CHROMOSOME-21 SO GENOMICS LA English DT Note ID GENETIC-LINKAGE MAP; LONG ARM; INTERFERON; PROTEINS; CLONING; HYBRIDS; CDNA C1 UNIV MICHIGAN, MED CTR, HOWARD HUGHES MED INST, DEPT PEDIAT, ANN ARBOR, MI 48109 USA. UNIV MICHIGAN, MED CTR, HOWARD HUGHES MED INST, DEPT HUMAN GENET, ANN ARBOR, MI 48109 USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROL, MOLEC NEUROGENET LAB, BOSTON, MA 02114 USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP,SCH MED,DEPT GENET, MOLEC NEUROGENET LAB, BOSTON, MA 02114 USA. ELEANOR ROOSEVELT INST CANC RES, DENVER, CO 80206 USA. FU NICHD NIH HHS [HD17449, N01-HD-9-2907]; NINDS NIH HHS [NS30428] NR 29 TC 13 Z9 13 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 EI 1089-8646 J9 GENOMICS JI Genomics PD OCT PY 1992 VL 14 IS 2 BP 498 EP 502 DI 10.1016/S0888-7543(05)80251-4 PG 5 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA JR697 UT WOS:A1992JR69700044 PM 1427866 ER PT J AU HAINES, JL AF HAINES, JL TI CHROMLOOK - AN INTERACTIVE PROGRAM FOR ERROR-DETECTION AND MAPPING IN REFERENCE LINKAGE DATA SO GENOMICS LA English DT Note ID MAP RP HAINES, JL (reprint author), MASSACHUSETTS GEN HOSP,MOLEC NEUROGENET UNIT,BLDG 149,6TH FLOOR,BOSTON,MA 02129, USA. RI Haines, Jonathan/C-3374-2012 FU NHGRI NIH HHS [R01-HG000324] NR 22 TC 15 Z9 15 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 0888-7543 J9 GENOMICS JI Genomics PD OCT PY 1992 VL 14 IS 2 BP 517 EP 519 DI 10.1016/S0888-7543(05)80257-5 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA JR697 UT WOS:A1992JR69700050 PM 1427871 ER PT J AU BUSCHMAN, E ARCECI, R CHE, M ARIAS, IM GROS, P AF BUSCHMAN, E ARCECI, R CHE, M ARIAS, IM GROS, P TI IDENTIFICATION AND FUNCTION OF MULTIDRUG RESISTANCE GENE-PRODUCTS IN THE BILE CANALICULUS SO HEPATOLOGY LA English DT Meeting Abstract C1 MCGILL UNIV,BIOCHEM,MONTREAL H3A 2T5,QUEBEC,CANADA. HARVARD UNIV,DANA FARBER CANC INST,BOSTON,MA 02115. TUFTS UNIV,PHYSIOL,BOSTON,MA 02111. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1992 VL 16 IS 4 BP A129 EP A129 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA JR380 UT WOS:A1992JR38000336 ER PT J AU CARTER, EA CHAPMAN, T AF CARTER, EA CHAPMAN, T TI DEMONSTRATION OF N-15 UREA PRODUCTION FROM N-15 AMMONIUM ACETATE BY RAT HEPATOCYTES USING GAS-CHROMATOGRAPHY MASS-SPECTROMETER (GC/MS) SO HEPATOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,COMBINED PROGRAM NUTR & GASTROENTEROL,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1992 VL 16 IS 4 BP A229 EP A229 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA JR380 UT WOS:A1992JR38000736 ER PT J AU CARTER, EA AF CARTER, EA TI ETHANOL INHIBITS THE HEPATIC ACUTE RESPONSE TO TERPENTINE, THERMAL-INJURY OR INTERLEUKIN-6 (IL-6) IN THE RAT SO HEPATOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,COMBINED PROGRAM NUTR & GASTROENTEROL,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1992 VL 16 IS 4 BP A229 EP A229 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA JR380 UT WOS:A1992JR38000734 ER PT J AU CARTER, EA ROSEN, B TENNANT, B AF CARTER, EA ROSEN, B TENNANT, B TI MR OF NORMAL AND TUMOR-BEARING WOODCHUCK HEPATITIS-VIRUS (WHV) INFECTED WOODCHUCK LIVER - CORRELATION WITH INSITU EXAMINATION SO HEPATOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,COMBINED PROGRAM NUTR & GASTROENTEROL,BOSTON,MA 02114. CORNELL UNIV,ITHACA,NY 14853. 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1992 VL 16 IS 4 BP A168 EP A168 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA JR380 UT WOS:A1992JR38000495 ER PT J AU CARTER, EA RYOO, J BUSHMANN, R CARRINGTON, PW AF CARTER, EA RYOO, J BUSHMANN, R CARRINGTON, PW TI DISTRIBUTION OF IGA IN NORMAL AND CIRRHOTIC HUMAN LIVERS SO HEPATOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,COMBINED PROGRAM NUTR & GASTROENTEROL,BOSTON,MA 02114. VET ADM W SIDE MED CTR,CHICAGO,IL 60680. 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1992 VL 16 IS 4 BP A163 EP A163 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA JR380 UT WOS:A1992JR38000472 ER PT J AU CHUNG, RT KAPLAN, LM AF CHUNG, RT KAPLAN, LM TI IDENTIFICATION AND CHARACTERIZATION OF A HEPATITIS-C VIRUS-SPECIFIC RNA-DEPENDENT RNA-POLYMERASE ACTIVITY FROM EXTRACTS OF INFECTED LIVER-TISSUE SO HEPATOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,BOSTON,MA 02114. 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1992 VL 16 IS 4 BP A132 EP A132 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA JR380 UT WOS:A1992JR38000350 ER PT J AU CHUNG, RT KAPLAN, LM AF CHUNG, RT KAPLAN, LM TI POSITIVE AND NEGATIVE STRAND HEPATITIS-C VIRUS (HCV) RNAS ARE PACKAGED WITHIN RIBONUCLEASE-PERMEABLE CAPSIDS OF CIRCULATING VIRIONS SO HEPATOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,GASTROENTEROL UNIT,BOSTON,MA 02114. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1992 VL 16 IS 4 BP A107 EP A107 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA JR380 UT WOS:A1992JR38000250 ER PT J AU DEVI, BG HENDERSON, GI SCHENKER, S AF DEVI, BG HENDERSON, GI SCHENKER, S TI EFFECT OF ETHANOL ON MITOCHONDRIAL MORPHOLOGIC AND BIOCHEMICAL INTEGRITY OF RAT FETAL HEPATOCYTES IN CULTURE SO HEPATOLOGY 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 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1992 VL 16 IS 4 BP A109 EP A109 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA JR380 UT WOS:A1992JR38000259 ER PT J AU DEVI, BG SCHENKER, S HENDERSON, GI AF DEVI, BG SCHENKER, S HENDERSON, GI TI PROTECTION OF RAT FETAL HEPATOCYTE MEMBRANES FROM ETHANOL-MEDIATED CELL INJURY AND GROWTH IMPAIRMENT SO HEPATOLOGY 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 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1992 VL 16 IS 4 BP A109 EP A109 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA JR380 UT WOS:A1992JR38000257 ER PT J AU HASEBE, C VANTHIEL, RC EYGENDAAL, D CHUNG, RT DIENSTAG, JL KAPLAN, LM AF HASEBE, C VANTHIEL, RC EYGENDAAL, D CHUNG, RT DIENSTAG, JL KAPLAN, LM TI PRIMARY SCREENING FOR VIRAL-RNA BY ITERATIVE PCR REVEALS A SIGNIFICANTLY INCREASED PREVALENCE OF HEPATITIS-C VIRUS (HCV) INFECTION IN HEALTH-WORKERS SO HEPATOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,BOSTON,MA 02114. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1992 VL 16 IS 4 BP A72 EP A72 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA JR380 UT WOS:A1992JR38000112 ER PT J AU LIANG, TJ JEFFERS, L CHEINGUER, H REDDY, R IDROVO, V PARKER, T RABASSA, A DEMEDINA, M AF LIANG, TJ JEFFERS, L CHEINGUER, H REDDY, R IDROVO, V PARKER, T RABASSA, A DEMEDINA, M TI VIRAL ETIOLOGY OF HEPATOCELLULAR-CARCINOMA IN UNITED-STATES SO HEPATOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,BOSTON,MA 02114. UNIV MIAMI,SCH MED,CTR LIVER DIS,MIAMI,FL 33152. VET ADM MED CTR,MIAMI,FL 33125. NR 0 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1992 VL 16 IS 4 BP A128 EP A128 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA JR380 UT WOS:A1992JR38000334 ER PT J AU LIANG, TJ HASEGAWA, K MUNOZ, SJ MARTIN, P FENG, CY DIENSTAG, JL AF LIANG, TJ HASEGAWA, K MUNOZ, SJ MARTIN, P FENG, CY DIENSTAG, JL TI HEPATITIS-B VIRUS PRECORE MUTATIONS AND FULMINANT-HEPATITIS IN USA - A PCR-BASED ASSAY FOR THE DETECTION OF SPECIFIC MUTATIONS SO HEPATOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,GASTROENTEROL UNIT,BOSTON,MA 02114. THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,PHILADELPHIA,PA 19107. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1992 VL 16 IS 4 BP A105 EP A105 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA JR380 UT WOS:A1992JR38000242 ER PT J AU NANJI, AA LAMB, RG SADRZADEH, SMH ZHAO, S DANNENBERG, AJ WAXMAN, DJ AF NANJI, AA LAMB, RG SADRZADEH, SMH ZHAO, S DANNENBERG, AJ WAXMAN, DJ TI LIVER MICROSOMAL PHOSPHOLIPASE-A AND PHOSPHOLIPASE-C IN EXPERIMENTAL ALCOHOLIC LIVER-INJURY - RELATIONSHIP TO ARACHIDONIC-ACID AND CYTOCHROME P450-2E1 SO HEPATOLOGY LA English DT Meeting Abstract C1 NEW ENGLAND DEACONESS HOSP,DEPT PATHOL,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA 02115. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT PHARMACOL,RICHMOND,VA 23298. CORNELL UNIV,MED CTR,NEW YORK HOSP,DEPT MED,NEW YORK,NY 10021. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT BIOL CHEM,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MOLEC PHARMACOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1992 VL 16 IS 4 BP A111 EP A111 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA JR380 UT WOS:A1992JR38000267 ER PT J AU NANJI, AA ZHAO, S SADRZADEH, SMH WAXMAN, DJ AF NANJI, AA ZHAO, S SADRZADEH, SMH WAXMAN, DJ TI SERIAL CHANGES IN CYTOCHROMES P450-2E1, P450-4A AND P450-2B1 IN EXPERIMENTAL ALCOHOLIC LIVER-INJURY SO HEPATOLOGY LA English DT Meeting Abstract C1 NEW ENGLAND DEACONESS HOSP,DEPT PATHOL,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MOLEC PHARMACOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT BIOL CHEM,BOSTON,MA 02115. NR 0 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1992 VL 16 IS 4 BP A112 EP A112 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA JR380 UT WOS:A1992JR38000268 ER PT J AU NICKELEIT, V CARTER, EA SANDERSON, I COLVIN, R AF NICKELEIT, V CARTER, EA SANDERSON, I COLVIN, R TI EFFECT OF THERMAL-INJURY ON HEPATIC FIBRONECTIN EXPRESSION IN THE RAT SO HEPATOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,COMBINED PROGRAM NUTR & GASTROENTEROL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1992 VL 16 IS 4 BP A186 EP A186 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA JR380 UT WOS:A1992JR38000564 ER PT J AU SASAKI, Y ZHANG, XF NISHIYAMA, M LAVAISSIERE, L AVRUCH, J WANDS, JR AF SASAKI, Y ZHANG, XF NISHIYAMA, M LAVAISSIERE, L AVRUCH, J WANDS, JR TI EXPRESSION AND PHOSPHORYLATION OF INSULIN-RECEPTOR SUBSTRATE-1 DURING LIVER-REGENERATION SO HEPATOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,CTR CANC,MOLEC HEPATOL LAB,BOSTON,MA. MASSACHUSETTS GEN HOSP,DIABET RES UNIT,BOSTON,MA. 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1992 VL 16 IS 4 BP A93 EP A93 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA JR380 UT WOS:A1992JR38000192 ER PT J AU SPEEG, KV MALDONADO, AL RABITO, FG SLAHETKA, MF AF SPEEG, KV MALDONADO, AL RABITO, FG SLAHETKA, MF TI ERYTHROMYCIN INHIBITS THE LIVER AND KIDNEY MULTIDRUG TRANSPORTERS IN THE RAT AND VARIABLY INHIBITS COLCHICINE CLEARANCE IN MAN SO HEPATOLOGY LA English DT Meeting Abstract C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1992 VL 16 IS 4 BP A162 EP A162 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA JR380 UT WOS:A1992JR38000470 ER PT J AU WEIZSAECKER, F BLUM, HE POYNARD, T WANDS, JR AF WEIZSAECKER, F BLUM, HE POYNARD, T WANDS, JR TI DETECTION OF LOW-LEVEL HEPATITIS-B AND HEPATITIS-C VIRUS GENOME IN ALCOHOLICS SO HEPATOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,CTR CANC,MOLEC HEPATOL LAB,BOSTON,MA 02114. UNIV HOSP ZURICH,DEPT INTERNAL MED,CH-8091 ZURICH,SWITZERLAND. HOP ANTOINE BECLERE,CLAMART,FRANCE. 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1992 VL 16 IS 4 BP A225 EP A225 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA JR380 UT WOS:A1992JR38000718 ER PT J AU WEIZSAECKER, F BLUM, HE WANDS, JR AF WEIZSAECKER, F BLUM, HE WANDS, JR TI RIBOZYME MEDIATED CLEAVAGE OF HEPATITIS-B AND DUCK HEPATITIS-B VIRUS-RNA SO HEPATOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,CTR CANC,MOLEC HEPATOL LAB,BOSTON,MA 02114. UNIV HOSP ZURICH,DEPT INTERNAL MED,CH-8091 ZURICH,SWITZERLAND. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1992 VL 16 IS 4 BP A88 EP A88 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA JR380 UT WOS:A1992JR38000174 ER PT J AU YAGER, J AF YAGER, J TI REFLECTIONS ON MODERN PSYCHIATRY - KUPFER,DJ SO HOSPITAL AND COMMUNITY PSYCHIATRY LA English DT Book Review C1 W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. RP YAGER, J (reprint author), UNIV CALIF LOS ANGELES,INST NEUROPSYCHIAT,LOS ANGELES,CA 90024, 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 0022-1597 J9 HOSP COMMUNITY PSYCH PD OCT PY 1992 VL 43 IS 10 BP 1048 EP 1048 PG 1 WC Public, Environmental & Occupational Health; Psychiatry SC Public, Environmental & Occupational Health; Psychiatry GA JR217 UT WOS:A1992JR21700034 ER PT J AU IGLESIAS, A DEULOFEUT, H DUBEY, DP SALAZAR, M EGEA, E YUNIS, EJ FRASER, PA AF IGLESIAS, A DEULOFEUT, H DUBEY, DP SALAZAR, M EGEA, E YUNIS, EJ FRASER, PA TI FUNCTIONAL DEFICIENCY OF ANTIGEN-PRESENTING CELLS IN THE SYNOVIAL-FLUID OF RHEUMATOID-ARTHRITIS SO HUMAN IMMUNOLOGY LA English DT Article ID CHRONIC INFLAMMATORY ARTHRITIS; LYMPHOCYTE-T SUBSETS; HLA-DR; INTERFERON-GAMMA; HUMAN-MONOCYTES; DEPRESSED PPD; EXPRESSION; PROLIFERATION; DQ; CYTOKINES AB In our study of rheumatoid arthritis (RA) patients, we observed a decrease of tetanus toxoid antigen-presenting capacity of synovial fluid (SF) adherent cells to autologous T cells of either SF or peripheral blood. Additionally, we found a higher capacity of adherent synovial cells to stimulate autologous T-lymphocytes. Our results suggest that antigen-presenting cells of the SF of RA patients have defects that may play a role in defective presentation of antigens in joints and may account for other abnormal functions important in the pathogenesis of RA. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV IMMUNOGENET,44 BINNEY ST,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT RHEUMATOL,BOSTON,MA 02115. FU NHLBI NIH HHS [HL-29583]; NIADDK NIH HHS [AM-16392]; NICHD NIH HHS [HD-17461] NR 22 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 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD OCT PY 1992 VL 35 IS 2 BP 109 EP 115 DI 10.1016/0198-8859(92)90018-I PG 7 WC Immunology SC Immunology GA KE205 UT WOS:A1992KE20500005 PM 1286976 ER PT J AU MCCLATCHEY, AI LIN, CS WANG, JZ HOFFMAN, EP ROJAS, C GUSELLA, JF AF MCCLATCHEY, AI LIN, CS WANG, JZ HOFFMAN, EP ROJAS, C GUSELLA, JF TI THE GENOMIC STRUCTURE OF THE HUMAN SKELETAL-MUSCLE SODIUM-CHANNEL GENE SO HUMAN MOLECULAR GENETICS LA English DT Article ID HYPERKALEMIC PERIODIC PARALYSIS; RAT-BRAIN; ALPHA-SUBUNIT; PARAMYOTONIA-CONGENITA; CLONED CDNA; EXPRESSION; SEQUENCE; LOCUS; DROSOPHILA; MUTATION AB Electrical excitability of neurons and muscle cells reflects the actions of a family of structurally related sodium channels. Mutations in the adult skeletal muscle sodium channel have been associated with the inherited neuromuscular disorders paramyotonia congenita (PMC) and hyperkalemic periodic paralysis (HPP). We have deciphered the entire genomic structure of the human skeletal muscle sodium channel gene and developed a restriction map of the locus. SCN4A consists of 24 exons spanning 35 kb of distance on chromosome 17q. We describe the sequence of all intron/exon boundaries, the presence of several polymorphisms in the coding sequence, and the locations within introns of two dinucleotide repeat polymorphisms. This is the first sodium channel for which the entire genomic structure has been resolved. The organization of the SCN4A exons relative to the proposed protein structure is presented and represents a foundation for functional and evolutionary comparisons of sodium channels. Knowledge of the exon structure and flanking intron sequences for SCN4A will permit a systematic search for mutations in PMC and HPP. C1 MASSACHUSETTS GEN HOSP, MOLEC NEUROGENET LAB, BOSTON, MA 02129 USA. UNIV PITTSBURGH, DEPT MOLEC GENET & BIOCHEM, PITTSBURGH, PA 15261 USA. UNIV PITTSBURGH, DEPT PEDIAT, PITTSBURGH, PA 15261 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02129 USA. UNIV PITTSBURGH, DEPT HUMAN GENET, PITTSBURGH, PA 15261 USA. FU NINDS NIH HHS [NS22224, NS24279] NR 36 TC 49 Z9 50 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD OCT PY 1992 VL 1 IS 7 BP 521 EP 527 PG 7 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA JV142 UT WOS:A1992JV14200011 PM 1339144 ER PT J AU ROSEN, DR SAPP, PC OREGAN, J HORVITZ, HR DONALDSON, DH NUSSBAUM, C GUSELLA, JF HAINES, JL PESTKA, S JUNG V PATTERSON, D BROWN, RH AF ROSEN, DR SAPP, PC OREGAN, J HORVITZ, HR DONALDSON, DH NUSSBAUM, C GUSELLA, JF HAINES, JL PESTKA, S JUNG, V PATTERSON, D BROWN, RH TI DINUCLEOTIDE REPEAT POLYMORPHISMS (D21S223 AND D21S224) AT 21Q22.1 SO HUMAN MOLECULAR GENETICS LA English DT Note C1 MASSACHUSETTS GEN HOSP, DAY NEUROMUSCULAR RES LAB, BOSTON, MA 02129 USA. MASSACHUSETTS GEN HOSP, MOLEC NEUROGENET LAB, BOSTON, MA 02129 USA. MIT, HOWARD HUGHES MED INST, CAMBRIDGE, MA 02139 USA. ELEANOR ROOSEVELT INST CANC RES, DENVER, CO USA. ROBERT WOOD JOHNSON MED SCH, DEPT MOLEC GENET & DENT NEW JERSEY, PISCATAWAY, NJ USA. RI Haines, Jonathan/C-3374-2012 FU NHGRI NIH HHS [HG00169, HG00324]; NIA NIH HHS [NIA AG00029] NR 1 TC 9 Z9 9 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD OCT PY 1992 VL 1 IS 7 BP 547 EP 547 DI 10.1093/hmg/1.7.547 PG 1 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA JV142 UT WOS:A1992JV14200017 PM 1307256 ER PT J AU LI, XP ABDI, K MENTZER, SJ AF LI, XP ABDI, K MENTZER, SJ TI CLONING HYBRIDOMAS IN A REVERSIBLE 3-DIMENSIONAL ALGINATE MATRIX SO HYBRIDOMA LA English DT Article ID MONOCLONAL-ANTIBODIES; CALCIUM ALGINATE; CELL IMMOBILIZATION; CULTURE; HEPATOCYTES; GROWTH; POLYSACCHARIDES; SECRETION; LINES; STATE AB Alginate is a transparent polymer of guluronic and mannuronic acids that provide a favorable microenvironment for cell growth. Alginate gelation is calcium dependent and temperature independent. To facilitate the isolation of stable and productive antibody-producing hybridomas, we have developed a technique of cloning hybridomas in the three-dimensional alginate matrix. To provide cavities for hybridoma growth, we encorporated 10-15% (v/v) gelatin into the alginate prior to gelation. We have cloned more than 90 monoclonal antibody-producing hybridomas using the alginate matrix. The alginate matrix is readily reversible with the addition of a calcium chelator. The alginate matrix permits efficient cloning in limited incubator space, without the use of a feeder layer, and with minimal amount of medium. The transparent matrix also permits easy screening for clonality and growth. C1 BRIGHAM & WOMENS HOSP,DIV THORAC SURG,75 FRANCIS ST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NR 30 TC 11 Z9 11 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0272-457X J9 HYBRIDOMA JI Hybridoma PD OCT PY 1992 VL 11 IS 5 BP 645 EP 652 DI 10.1089/hyb.1992.11.645 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Immunology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology GA JU871 UT WOS:A1992JU87100011 PM 1459587 ER PT J AU WODICKA, GR AGUIRRE, A DEFRAIN, PD SHANNON, DC AF WODICKA, GR AGUIRRE, A DEFRAIN, PD SHANNON, DC TI PHASE DELAY OF PULMONARY ACOUSTIC TRANSMISSION FROM TRACHEA TO CHEST-WALL SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article ID HUMAN RESPIRATORY SYSTEM; SOUND-TRANSMISSION; NORMAL MEN; PROPAGATION; PARENCHYMA; SPEED; LUNG AB The frequency-dependent propagation time, or phase delay tau (f), of sonic noise transmission from the trachea to the chest wall was estimated over the 100-600 Hz frequency range using a phase estimation technique from measurements performed on eight healthy subjects. Since tau (f) can be greater than one period of the input signal at frequencies greater than 100 Hz, the unambiguous phase estimate at 100 Hz was used as a starting-point to determine the phase less than with left parenthesis through H (f) and tau (f) at higher frequencies under the constraint that the spectra did not exhibit large point-to-point discontinuities. The resulting tau (f) range of 0.9-4.1 ms is consistent with sound propagation to the chest wall through both airways and surrounding parenchyma. The frequency and spatial dependence of tau (f) indicates that with increasing frequency more sonic energy travels further into the branching airway structure before coupling into the parenchyma. These results suggest that information concerning distinct regional lung structures may be obtained by probing the system acoustically over selected frequency bands. C1 PURDUE UNIV,HILLENBRAND BIOMED ENGN CTR,W LAFAYETTE,IN 47907. SIEMENS MED ELECTR CORP,DANVERS,MA 01923. MASSACHUSETTS GEN HOSP,CHILDRENS SERV,PEDIAT PULM UNIT,BOSTON,MA 02114. RP WODICKA, GR (reprint author), PURDUE UNIV,SCH ELECT ENGN,W LAFAYETTE,IN 47907, USA. NR 22 TC 23 Z9 24 U1 0 U2 1 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 SN 0018-9294 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD OCT PY 1992 VL 39 IS 10 BP 1053 EP 1059 DI 10.1109/10.161337 PG 7 WC Engineering, Biomedical SC Engineering GA JT791 UT WOS:A1992JT79100007 PM 1452171 ER PT J AU ENTINE, G SQUILLANTE, MR HAHN, R CIRIGNANO, LJ MCGANN, W BIGGS, PJ AF ENTINE, G SQUILLANTE, MR HAHN, R CIRIGNANO, LJ MCGANN, W BIGGS, PJ TI HIGH CONTRAST, CDTE PORTAL SCANNER FOR RADIATION-THERAPY SO IEEE TRANSACTIONS ON NUCLEAR SCIENCE LA English DT Article; Proceedings Paper CT 1991 NUCLEAR SCIENCE SYMP AND MEDICAL IMAGING CONF ( NSS / MIUC ) CY NOV 02-09, 1991 CL SANTA FE, NM SP IEEE, NUCL & PLASMA SCI SOC ID EXTERNAL BEAM RADIOTHERAPY; SYSTEM AB One of the most promising new technologies for improving the quality of radiation therapy is the use of real-time systems to produce portal images. In our approach, we are constructing a linear array of 256 CdTe photovoltaic detectors attached to a very compact linear scanner, all of which will be mounted in a cassette shaped package to be located under the patient table. The high stopping power of the CdTe allows a high contrast image to be made using only a single Linac pulse per line, resulting in a high contrast image in under 5 seconds. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP ENTINE, G (reprint author), RADIAT MONITORING DEVICES INC,WATERTOWN,MA, USA. NR 8 TC 5 Z9 5 U1 0 U2 0 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 SN 0018-9499 J9 IEEE T NUCL SCI JI IEEE Trans. Nucl. Sci. PD OCT PY 1992 VL 39 IS 5 BP 1480 EP 1484 DI 10.1109/23.173228 PN 1 PG 5 WC Engineering, Electrical & Electronic; Nuclear Science & Technology SC Engineering; Nuclear Science & Technology GA JZ684 UT WOS:A1992JZ68400053 ER PT J AU HENRICSON, BE PERERA, PY QURESHI, N TAKAYAMA, K VOGEL, SN AF HENRICSON, BE PERERA, PY QURESHI, N TAKAYAMA, K VOGEL, SN TI RHODOPSEUDOMONAS-SPHAEROIDES LIPID-A DERIVATIVES BLOCK INVITRO INDUCTION OF TUMOR-NECROSIS-FACTOR AND ENDOTOXIN TOLERANCE BY SMOOTH LIPOPOLYSACCHARIDE AND MONOPHOSPHORYL LIPID-A SO INFECTION AND IMMUNITY LA English DT Article ID FATTY-ACIDS; NONTOXIC LIPOPOLYSACCHARIDE; STRUCTURAL DETERMINATION; SALMONELLA-TYPHIMURIUM; ATCC-17023; PURIFICATION; MACROPHAGES AB Rhodopseudomonas (Rhodobacter) sphaeroides diphosphoryl lipid A is a relatively inert species of lipid A but has been shown to antagonize the effects of toxic lipopolysaccharide (LPS) both in vivo and in vitro. The antagonist and its monophosphoryl derivative were examined for the ability to block tumor necrosis factor synthesis and reverse tolerance induction in vitro in macrophage cultures stimulated with bioactive preparations of smooth LPS, rough LPS, diphosphoryl lipid A, and monophosphoryl lipid A. Inhibition of agonist activity and reversal of tolerance by these novel penta-acylated lipid A antagonists provides new insight into macrophage-LPS interactions. C1 UNIFORMED SERV UNIV HLTH SCI, DEPT MICROBIOL, 4301 JONES BRIDGE RD, BETHESDA, MD 20814 USA. WILLIAM S MIDDLETON MEM VET ADM MED CTR, MYCOBACTERIOL RES LAB, MADISON, WI 53705 USA. UNIV WISCONSIN, COLL AGR & LIFE SCI, DEPT BACTERIOL, MADISON, WI 53706 USA. FU NIGMS NIH HHS [GM-36054] NR 34 TC 30 Z9 30 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 EI 1098-5522 J9 INFECT IMMUN JI Infect. Immun. PD OCT PY 1992 VL 60 IS 10 BP 4285 EP 4290 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA JP779 UT WOS:A1992JP77900042 PM 1398939 ER PT J AU KLEIN, BS SONDEL, PM JONES, JM AF KLEIN, BS SONDEL, PM JONES, JM TI WI-1, A NOVEL 120-KILODALTON SURFACE PROTEIN ON BLASTOMYCES-DERMATITIDIS YEAST-CELLS, IS A TARGET ANTIGEN OF CELL-MEDIATED-IMMUNITY IN HUMAN BLASTOMYCOSIS SO INFECTION AND IMMUNITY LA English DT Article ID DELAYED-TYPE HYPERSENSITIVITY; TRANSFER PROTECTIVE IMMUNITY; LYMPHOCYTE-T CLONES; PULMONARY BLASTOMYCOSIS; LISTERIA-MONOCYTOGENES; INFECTION; MACROPHAGES; INVITRO; RECOGNITION; REACTIVITY AB A large body of experimental data has demonstrated the central role of T cells in acquired resistance to the dimorphic fungus Blastomyces dermatitidis. We examined the human T-cell response to WI-1, a 120-kDa B. dermatitidis yeast cell surface protein recently shown to be an immunodominant antigen of the B-cell response in infected humans. Peripheral blood lymphocytes from 10 blastomycosis patients studied proliferated in response to WI-1 (mean, 19,431 cpm) and to the standard, crude cell wall antigen, Blastomyces alkali- and water-soluble antigen (B-ASWS) (mean, 19,131 cpm); lymphocytes from 10 histoplasmosis patients and 10 normal control subjects did not respond to WI-1. WI-1 stimulation of patient lymphocytes and rechallenge with WI-1 or B-ASWS showed that the antigens share immunodominant epitopes. Of 100 WI-1-responsive T-cell clones derived from peripheral blood, 10 were studied in detail to assess the phenotype, function, and ligands recognized. The clones exhibit the CD3+ CD4+ phenotype of helper T cells; 2 of 10 clones (and 21% of antigen-stimulated peripheral blood lymphocytes) use the Vbeta8 T-cell receptor gene element to respond to WI-1. All the clones proliferate in response to both WI-1 and B-ASWS but not other fungal antigens, and some mediate potent cytolytic effects on WI-1- and B-ASWS-labeled targets. WI-1 recognition requires antigen processing and presentation of epitopes in association with HLA-DR (to noncytolytic clones) and HLA-DP (to cytolytic clones). From these findings, we conclude that CD4+ T cells with regulatory and cytolytic properties are involved in the development of acquired resistance to B. dermatitidis, that the cells are directed against WI-1, and that the manner of display of WI-1 peptide epitopes in conjunction with major histocompatibility complex class II may influence the profile of the immune response. C1 UNIV WISCONSIN,SCH MED,DEPT INTERNAL MED,MADISON,WI 53706. UNIV WISCONSIN,SCH MED,INFECT DIS SECT,MADISON,WI 53706. UNIV WISCONSIN,SCH MED,DEPT HUMAN ONCOL,MADISON,WI 53706. UNIV WISCONSIN,SCH MED,DEPT GENET,MADISON,WI 53706. UNIV WISCONSIN,SCH MED,HEMATOL & ONCOL SECT,MADISON,WI 53706. UNIV WISCONSIN HOSP & CLIN,MADISON,WI 53705. WILLIAM S MIDDLETON MEM VET ADM MED CTR,RES SERV,MADISON,WI 53705. RP KLEIN, BS (reprint author), UNIV WISCONSIN,SCH MED,DEPT PEDIAT,MADISON,WI 53706, USA. FU NCI NIH HHS [CA-32685]; NIAID NIH HHS [AI-00905] NR 53 TC 34 Z9 34 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 OCT PY 1992 VL 60 IS 10 BP 4291 EP 4300 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA JP779 UT WOS:A1992JP77900043 PM 1383148 ER PT J AU RANK, RG RAMSEY, KH PACK, EA WILLIAMS, DM AF RANK, RG RAMSEY, KH PACK, EA WILLIAMS, DM TI EFFECT OF GAMMA-INTERFERON ON RESOLUTION OF MURINE CHLAMYDIAL GENITAL-INFECTION SO INFECTION AND IMMUNITY LA English DT Note ID TUMOR NECROSIS FACTOR; FEMALE GUINEA-PIGS; ROLE INVIVO; TRACHOMATIS; IMMUNITY; MICE; INHIBITION AB Mice infected in the genital tract with the Chlamydia trachomatis agent of mouse pneumonitis were treated with monoclonal rat anti-gamma interferon (anti-IFN-gamma) antibody to determine whether IFN-gamma participated in the resolution of the infection. In two experiments, anti-IFN-gamma antibody treatment resulted in significantly prolonged infections. In support of these data, passive administration of recombinant IFN-gamma to chronically infected nu/nu mice was able to bring about resolution of the infection in some animals. C1 AUDIE L MURPHY MEM VET ADM MED CTR,DEPT MED,SAN ANTONIO,TX 78284. RP RANK, RG (reprint author), UNIV ARKANSAS MED SCI HOSP,DEPT MICROBIOL & IMMUNOL,LITTLE ROCK,AR 72205, USA. FU NIAID NIH HHS [AI26328, R15 AI037807, R15 AI037807-01A1] NR 15 TC 93 Z9 93 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 OCT PY 1992 VL 60 IS 10 BP 4427 EP 4429 PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA JP779 UT WOS:A1992JP77900062 PM 1398955 ER PT J AU AWAD, S HENDERSON, GB CERAMI, A HELD, KD AF AWAD, S HENDERSON, GB CERAMI, A HELD, KD TI EFFECTS OF TRYPANOTHIONE ON THE BIOLOGICAL-ACTIVITY OF IRRADIATED TRANSFORMING DNA SO INTERNATIONAL JOURNAL OF RADIATION BIOLOGY LA English DT Article ID SULFYDRYL-CONTAINING COMPOUNDS; CO-ION DEPLETION; COUNTERION CONDENSATION; RADIATION-DAMAGE; THIOLS; GLUTATHIONE; CYSTEAMINE; RADICALS; OXYGEN; RATES AB Held et al. (1984a,b) demonstrated previously that glutathione (GSH), a negatively charged thiol, is significantly less efficient in the hydrogen atom donation repair reaction with radicals induced by radiation in transforming DNA (t-DNA) than are other thiol compounds. Fahey et al. (1991a,b) postulated that the charge on thiols can influence their ability to radioprotect DNA. GSH, which is excluded from the vicinity of DNA due to its negative charge, is less protective than neutral or positively charged thiols. We have investigated this phenomenon further with trypanothione, the conjugate of glutathione and spermidine, N1,N8-bis (L-gamma-glutamyl-L-hemicystinyl-glycyl)-spermidine. Trypanothione exists in aerobic solution largely as the disulphide (T(S)2) but is maintained in the cell in the reduced form (T(SH)2) by means of an NADPH-dependent flavo-enzyme, trypanothione reductase (TR). Experimental data show that T(S)2 in the presence of TR radioprotects t-DNA in the absence of oxygen much better than GSH or spermidine alone or in combination. Little radio-protection by T(S)2 is seen when TR is not present. The results obtained with reduced trypanothione at low concentrations suggest that radioprotection of t-DNA in hypoxia occurs predominantly by H atom donation and slightly by .OH radical scavenging, and the protection is greater than that by GSH or spermidine because the polyamine moiety in trypanothione allows a greater concentration of GSH near the DNA molecule. C1 PICOWER INST MED RES,MANHASSET,NY 11030. ROCKEFELLER UNIV,MED BIOCHEM LAB,NEW YORK,NY 10021. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,BOSTON,MA 02114. FU NCI NIH HHS [CA18614, CA42167]; PHS HHS [AL 19428] NR 26 TC 17 Z9 18 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNDPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE SN 0955-3002 J9 INT J RADIAT BIOL JI Int. J. Radiat. Biol. PD OCT PY 1992 VL 62 IS 4 BP 401 EP 407 DI 10.1080/09553009214552281 PG 7 WC Biology; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA JR945 UT WOS:A1992JR94500003 PM 1357053 ER PT J AU CONLAY, LA SABOUNJIAN, LA WURTMAN, RJ AF CONLAY, LA SABOUNJIAN, LA WURTMAN, RJ TI EXERCISE AND NEUROMODULATORS - CHOLINE AND ACETYLCHOLINE IN MARATHON RUNNERS SO INTERNATIONAL JOURNAL OF SPORTS MEDICINE LA English DT Article; Proceedings Paper CT SESSION ON PHYSIOLOGY OF MOUNTAIN SPORTS, AT THE INTERNATIONAL CONGRESS ON MOUNTAIN SPORTS CY FEB 02-04, 1992 CL CHAMONIX, FRANCE DE CHOLINE; EXERCISE; ACETYLCHOLINE; LECITHIN; RUNNING AB Certain neurotransmitters (i.e., acetylcholine, catecholamines, and serotonin) are formed from dietary constituents (i.e., choline, tyrosine and tryptophan). Changing the consumption of these precursors alters release of their respective neurotransmitter products. The neurotransmitter acetylcholine is released from the neuromuscular junction and from brain. It is formed from choline, a common constituent in fish, liver, and eggs. Choline is also incorporated into cell membranes; membranes may likewise serve as an alternative choline source for acetylcholine synthesis. In trained athletes, running a 26 km marathon reduced plasma choline by approximately 40%, from 14.1 to 8.4 uM. Changes of similar magnitude have been shown to reduce acetylcholine release from the neuromuscular junction in vivo. Thus, the reductions in plasma choline associated with strenuous exercise may reduce acetylcholine release, and could thereby affect endurance or performance. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ANAESTHESIA,BOSTON,MA 02114. RP CONLAY, LA (reprint author), MIT,DEPT BRAIN & COGNIT SCI,NEUROENDOCRINE REGULAT LAB,E25-604,CAMBRIDGE,MA 02139, USA. NR 10 TC 23 Z9 26 U1 0 U2 2 PU GEORG THIEME VERLAG PI STUTTGART PA P O BOX 30 11 20, D-70451 STUTTGART, GERMANY SN 0172-4622 J9 INT J SPORTS MED JI Int. J. Sports Med. PD OCT PY 1992 VL 13 SU 1 BP S141 EP S142 DI 10.1055/s-2007-1024619 PG 2 WC Sport Sciences SC Sport Sciences GA JX592 UT WOS:A1992JX59200043 PM 1483754 ER PT J AU FAVA, M PEDRAZZI, F GUARALDI, GP ROMANO, G GENAZZANI, AR FACCHINETTI, F AF FAVA, M PEDRAZZI, F GUARALDI, GP ROMANO, G GENAZZANI, AR FACCHINETTI, F TI COMORBID ANXIETY AND DEPRESSION AMONG PATIENTS WITH LATE LUTEAL PHASE DYSPHORIC DISORDER SO JOURNAL OF ANXIETY DISORDERS LA English DT Article; Proceedings Paper CT 22ND CONGRESS OF THE INTERNATIONAL SOC OF PSYCHONEUROENDOCRINOLOGY CY JUN 17-20, 1991 CL SIENA, ITALY SP INT SOC PSYCHONEUROENDOCRINOL ID PREMENSTRUAL-SYNDROME; AXIS-I; PREVALENCE; INTERVIEW; WOMEN AB The presence of current anxiety and mood disorders was evaluated with the Structured Clinical Interview for the DSM-M-Revised (SCID) in three groups: (a) a group of 32 women with prospectively confirmed Late Luteal Phase Dysphoric Disorder (LLPDD), (b) a group of 35 women with secondary amenorrhea, and (c) a group of 38 female healthy volunteers. Both LLPDD and secondary amenorrhea patients had a greater percentage of comorbid anxiety or mood disorders compared to healthy volunteers. Although patients with amenorrhea displayed mood disorders more often than LLPDD patients, 59% of the 32 women with LLPDD had current anxiety disorders either alone or with comorbid mood disorders, and this percentage was.significantly higher (p < 0.005) than that of amenorrheic patients (23%). Generalized anxiety, panic disorder, and social phobia were the most common diagnoses among LLPDD women. In conclusion, patients with prospectively confirmed LLPDD appear more likely to suffer from current anxiety or mood disorders than healthy controls and to have current anxiety disorders more often than women with secondary amenorrhea. C1 UNIV MODENA,SCH MED,DEPT PSYCHIAT,I-41100 MODENA,ITALY. UNIV MODENA,SCH MED,DEPT OBSTET & GYNECOL,I-41100 MODENA,ITALY. RP FAVA, M (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PSYCHIAT,CLIN PSYCHOPHARMACOL UNIT,ACC 815,BOSTON,MA 02114, USA. RI Facchinetti, Fabio/K-9929-2014 OI Facchinetti, Fabio/0000-0003-4694-9564 NR 14 TC 44 Z9 45 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0887-6185 J9 J ANXIETY DISORD JI J. Anxiety Disord. PD OCT-DEC PY 1992 VL 6 IS 4 BP 325 EP 335 DI 10.1016/0887-6185(92)90004-Q PG 11 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA JP689 UT WOS:A1992JP68900004 ER PT J AU HELFET, DL JUPITER, JB GASSER, S AF HELFET, DL JUPITER, JB GASSER, S TI INDIRECT REDUCTION AND TENSION-BAND PLATING OF TIBIAL NONUNION WITH DEFORMITY SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID CONSTANT DIRECT-CURRENT; FRACTURES; NONUNIONS; MALUNIONS AB Thirty-three patients who had a malaligned non-union of the tibial diaphysis were treated by limited open exposure, indirect reduction with femoral distractor, tension-band plating, lag-screw fixation, and autogenous bone-grafting. The time from the injury to treatment of the non-union averaged twenty-nine months. Twenty-two of the fractures were originally open and sixteen fractures had had a previous infection before treatment of the non-union. The non-unions were classified as hypertrophic in eight patients, oligotrophic in eighteen, and atrophic in seven. All had severe deformity, or the nature or level of the non-union, or both, precluded intramedullary nailing as a treatment option. All thirty-three non-unions healed at an average of four months; the average length of follow-up was nineteen months. The deformity was corrected, within acceptable limits, in thirty-two of the patients. Full motion of the knee was achieved in twenty-nine patients and of the ankle, in eighteen. Complications included four instances of superficial skin breakdowns, one deep infection, and one fracture of the plate. For non-unions of the tibial diaphysis with deformity that are not amenable to intramedullary nailing, the techniques of limited exposure, indirect reduction, tension-band plating, and bone-grafting can yield excellent anatomical and functional results. C1 UNIV SO CALIF,DEPT ORTHOPAED,LOS ANGELES,CA 90089. TAMPA GEN HOSP,ORTHOPAED TRAUMA SERV,TAMPA,FL 33606. MASSACHUSETTS GEN HOSP,DEPT ORTHOPAED SURG,BOSTON,MA 02114. NR 66 TC 28 Z9 29 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 OCT PY 1992 VL 74A IS 9 BP 1286 EP 1297 PG 12 WC Orthopedics; Surgery SC Orthopedics; Surgery GA JZ289 UT WOS:A1992JZ28900002 PM 1429784 ER PT J AU HIPP, JA ROSENBERG, AE HAYES, WC AF HIPP, JA ROSENBERG, AE HAYES, WC TI MECHANICAL-PROPERTIES OF TRABECULAR BONE WITHIN AND ADJACENT TO OSSEOUS METASTASES SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID QUANTITATIVE COMPUTED-TOMOGRAPHY; LONG BONES; STRUCTURAL CONSEQUENCES; STRENGTH REDUCTIONS; DEPENDENCE; FRACTURE; LESIONS AB Despite radiographic and histologic evidence of trabecular bone density changes within and adjacent to osseous metastases, there currently exist no data to demonstrate whether these changes are important in predicting the risk of fracture. To determine if these density changes result in significant reductions in mechanical properties, trabecular bone specimens were prepared from lower thoracic and lumbar vertebrae from two cadavers with radiographic, gross, and histologic evidence of lytic and/or blastic osseous metastases. Each specimen was classified as normal, lytic, or blastic based on appearance in fine-grain radiographs of 8-9 mm thick coronal plane sections. Specimens were tested to failure in uniaxial compression, and tissue and apparent densities were measured. Mean tissue densities were within normal ranges. The mean apparent density for all specimens combined was within the normal range for human vertebrae, and the mean apparent density for radiographically normal (0.131 g/ml) and lytic (0.111 g/ml) specimens was less than the mean apparent density of blastic (0.182 g/ml) specimens (p < 0.02). The moduli of lytic and blastic specimens were less than for normal specimens (p < 0.025). The strength of lytic specimens was less than normal (p = 0.057), but the strength of blastic specimens was not (p > 0.1). Apparent density explained significant fractions of the variations in both modulus (p < 0.001) and strength (p < 0.001). The data suggest that blastic changes associated with osseous metastases to trabecular bone disrupt the normal dependence of trabecular mechanical properties on apparent density, but lytic changes do not. These data also suggest that fracture risk predictors that utilize bone density to estimate stiffness or strength should adjust for the effects of metastases. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,JAMES HOMER WRIGHT PATHOL LABS,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP HIPP, JA (reprint author), BETH ISRAEL HOSP,CHARLES A DANA RES INST,DEPT ORTHOPAED SURG,BOSTON,MA 02215, USA. FU NCI NIH HHS [CA40211-05] NR 30 TC 29 Z9 32 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 OCT PY 1992 VL 7 IS 10 BP 1165 EP 1171 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JT992 UT WOS:A1992JT99200007 PM 1456084 ER PT J AU SABOLIC, I WUARIN, F SHI, LB VERKMAN, AS AUSIELLO, DA GLUCK, S BROWN, D AF SABOLIC, I WUARIN, F SHI, LB VERKMAN, AS AUSIELLO, DA GLUCK, S BROWN, D TI APICAL ENDOSOMES ISOLATED FROM KIDNEY COLLECTING DUCT PRINCIPAL CELLS LACK SUBUNITS OF THE PROTON PUMPING ATPASE SO JOURNAL OF CELL BIOLOGY LA English DT Article ID INTEGRAL MEMBRANE-PROTEIN; SENSITIVE WATER CHANNEL; RAT-KIDNEY; ANTIDIURETIC-HORMONE; INTERCALATED CELLS; ENDOCYTIC VESICLES; URINARY-BLADDER; ADENOSINE-TRIPHOSPHATASE; PROXIMAL TUBULE; BRUSH-BORDER AB Endocytic vesicles that are involved in the vasopressin-stimulated recycling of water channels to and from the apical membrane of kidney collecting duct principal cells were isolated from rat renal papilla by differential and Percoll density gradient centrifugation. Fluorescence quenching measurements showed that the isolated vesicles maintained a high, HgCl2-sensitive water permeability, consistent with the presence of vasopressin-sensitive water channels. They did not, however, exhibit ATP-dependent luminal acidification, nor any N-ethylmaleimide-sensitive ATPase activity, properties that are characteristic of most acidic endosomal compartments. Western blotting with specific antibodies showed that the 31- and 70-kD cytoplasmically oriented subunits of the vacuolar proton pump were not detectable in these apical endosomes from the papilla, whereas they were present in endosomes prepared in parallel from the cortex. In contrast, the 56-kD subunit of the proton pump was abundant in papillary endosomes, and was localized at the apical pole of principal cells by immunocytochemistry. Finally, an antibody that recognizes the 16-kD transmembrane subunit of oat tonoplast ATPase cross-reacted with a distinct 16-kD band in cortical endosomes, but no 16-kD band was detectable in endosomes from the papilla. This antibody also recognized a 16-kD band in affinity-purified H+ ATPase preparations from bovine kidney medulla. Therefore, early endosomes derived from the apical plasma membrane of collecting duct principal cells fail to acidify because they lack functionally important subunits of a vacuolar-type proton pumping ATPase, including the 16-kD transmembrane domain that serves as the proton-conducting channel, and the 70-kD cytoplasmic subunit that contains the ATPase catalytic site. This specialized, non-acidic early endosomal compartment appears to be involved primarily in the hormonally induced recycling of water channels to and from the apical plasma membrane of vasopressin-sensitive cells in the kidney collecting duct. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02114. UNIV CALIF SAN FRANCISCO,DEPT MED,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,INST CARDIOVASC RES,SAN FRANCISCO,CA 94143. JEWISH HOSP ST LOUIS,DIV RENAL,ST LOUIS,MO 63110. RP SABOLIC, I (reprint author), MASSACHUSETTS GEN HOSP,RENAL UNIT,BOSTON,MA 02114, USA. FU NIDDK NIH HHS [DK 42956, DK 38452] NR 60 TC 42 Z9 42 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 OCT PY 1992 VL 119 IS 1 BP 111 EP 122 DI 10.1083/jcb.119.1.111 PG 12 WC Cell Biology SC Cell Biology GA JP865 UT WOS:A1992JP86500009 PM 1388176 ER PT J AU SCHLEIFFENBAUM, B SPERTINI, O TEDDER, TF AF SCHLEIFFENBAUM, B SPERTINI, O TEDDER, TF TI SOLUBLE L-SELECTIN IS PRESENT IN HUMAN PLASMA AT HIGH-LEVELS AND RETAINS FUNCTIONAL-ACTIVITY SO JOURNAL OF CELL BIOLOGY LA English DT Article ID LEUKOCYTE ADHESION MOLECULE-1; NODE HOMING RECEPTOR; COLONY-STIMULATING FACTOR; HIGH-ENDOTHELIAL VENULES; CELL-SURFACE MOLECULE; PROTEIN KINASE-C; NEUTROPHIL ADHESION; CD18-INDEPENDENT ADHESION; LYMPHOCYTE RECOGNITION; CHEMOTACTIC FACTORS AB L-selectin expressed by granulocytes, lymphocytes, and monocytes is responsible for initial leukocyte attachment to inflamed endothelium and high endothelial venules of peripheral lymph nodes. After leukocyte activation in vitro, L-selectin is rapidly shed from the cell surface. In this study, shed L-selectin (sL-selectin) from both lymphocytes and neutrophils was demonstrated to be present in high levels in human plasma by Western blot analysis and using a quantitative ELISA. In serum from normal human blood donors, a mean sL-selectin level of 1.6 +/- 0.8 mug/ml (n = 63) was found by ELISA. In addition, semi-purified sL-selectin from plasma inhibited L-selectin-specific attachment of lymphocytes to cytokine-activated endothelium in a dose-dependent manner. L-selectin-dependent leukocyte attachment was completely inhibited at sL-selectin concentrations of 8-15 mug/ml, while physiological concentrations of sL-selectin caused a small but consistent inhibition of lymphocyte attachment. sL-selectin in plasma also inhibited anti-L-selectin mAb (2-5 mug/ml) binding to the surface of leukocytes. Interestingly, one epitope present within the EGF-like domain of L-selectin was lost in sL-selectin, suggesting a conformational change in the structure of the receptor after shedding. The presence of serum sL-selectin with functional activity indicates a potential role for sL-selectin in the regulation of leukocyte attachment to endothelium. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. RP SCHLEIFFENBAUM, B (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA-34183, CA-54464]; NIAID NIH HHS [AI-26872] NR 58 TC 350 Z9 359 U1 0 U2 3 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 OCT PY 1992 VL 119 IS 1 BP 229 EP 238 DI 10.1083/jcb.119.1.229 PG 10 WC Cell Biology SC Cell Biology GA JP865 UT WOS:A1992JP86500019 PM 1382078 ER PT J AU HALLEK, M DRUKER, B LEPISTO, EM WOOD, KW ERNST, TJ GRIFFIN, JD AF HALLEK, M DRUKER, B LEPISTO, EM WOOD, KW ERNST, TJ GRIFFIN, JD TI GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR AND STEEL FACTOR INDUCE PHOSPHORYLATION OF BOTH UNIQUE AND OVERLAPPING SIGNAL TRANSDUCTION INTERMEDIATES IN A HUMAN FACTOR-DEPENDENT HEMATOPOIETIC-CELL LINE SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID RECEPTOR TYROSINE KINASE; C-KIT PROTOONCOGENE; GROWTH-FACTOR; PHOSPHOLIPASE-C; GM-CSF; PROGENITOR CELLS; PROTEIN; INTERLEUKIN-3; LIGAND; ACTIVATION AB Steel factor (SF), the ligand for the proto-oncogene c-kit, acts synergistically with GM-CSF or IL-3 to support the growth of normal human hematopoietic progenitor cells. We examined the effects of SF on GM-CSF or IL-3 induced proliferation of a human factor-dependent cell line, MO7. SF supported MO7 cell proliferation as well as IL-3 or GM-CSF alone, and its addition dramatically enhanced (three- to sixfold) maximal GM-CSF or IL-3 stimulated proliferation. SF did not increase the number or affinity of cell surface GM-CSF receptors. We examined several early events of signal transduction in an effort to elucidate the biochemical mechanisms of synergy of these factors. Since each of these three cytokines is believed to function in part through activation of a tyrosine kinase, we examined their effects on cellular phosphotyrosine containing proteins. Each cytokine induced rapid, transient, and concentration dependent tyrosine phosphorylation of a number of substrates. For GM-CSF and IL-3, these phosphoproteins were indistinguishable (150, 125, 106, 93, 80, 79, 73, 44, 42, and 36 kDa), while SF induced major or minor tyrosine phosphorylation of 205, 140-150, 116, 106, 94, 90, 80, 79, 73, 44, 42, 39, 36, 32 kDa phosphoproteins. Two other signal transduction intermediates known to be phosphorylated and activated by GM-CSF and IL-3, the 70-75 kDa Raf-1 kinase, and p42 mitogen-activated protein kinase-2 (MAPK), were also phosphorylated by SF. Combinations of GM-CSF or IL-3 with SF did not further increase the phosphorylation of Raf-1 or p42 MAPK when compared to any of the factors alone. In contrast SF, but not GM-CSF or IL-3, induced tyrosine phosphorylation of phospholipase C-gamma (PLC-gamma). These results indicate that SF and GM-CSF/IL-3 have partially overlapping effects on early signal transducing events, as well as striking differences, such as tyrosine phosphorylation of PLC-gamma. This cell line should provide a useful model system to investigate the complicated process of hematopoietic growth factor synergy. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. FU NCI NIH HHS [CA 36167, CA 34183] NR 60 TC 53 Z9 53 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD OCT PY 1992 VL 153 IS 1 BP 176 EP 186 DI 10.1002/jcp.1041530122 PG 11 WC Cell Biology; Physiology SC Cell Biology; Physiology GA JP455 UT WOS:A1992JP45500021 PM 1381714 ER PT J AU KATZ, MS GUTIERREZ, GE MUNDY, GR HYMER, TK CAULFIELD, MP MCKEE, RL AF KATZ, MS GUTIERREZ, GE MUNDY, GR HYMER, TK CAULFIELD, MP MCKEE, RL TI TUMOR-NECROSIS-FACTOR AND INTERLEUKIN-1 INHIBIT PARATHYROID HORMONE-RESPONSIVE ADENYLATE-CYCLASE IN CLONAL OSTEOBLAST-LIKE CELLS BY DOWN-REGULATING PARATHYROID-HORMONE RECEPTORS SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID HIGH-AFFINITY RECEPTORS; EPIDERMAL GROWTH-FACTOR; COLONY STIMULATING ACTIVITY; FACTOR-ALPHA; OSTEOSARCOMA CELLS; COLLAGEN-SYNTHESIS; BONE-RESORPTION; DEOXYRIBONUCLEIC-ACID; PLASMA-MEMBRANE; CAMP PRODUCTION AB The effects of the monokines tumor necrosis factor a (TNF) and interleukin 1 (IL 1) on parathyroid hormone (PTH)-responsive adenylate cyclase were examined in clonal rat osteosarcoma cells (UMR-106) with the osteoblast phenotype. Recombinant TNF and IL 1 incubated with UMR-106 cells for 48 hr each produced concentration-dependent inhibition of PTH-sensitive adenylate cyclase, with maximal inhibition of PTH response (40% for TNF, 24% for IL 1) occuring at 10(-8) M of either monokine. Both monokines also decreased adenylate cyclase stimulation by the tumor-derived PTH-related protein (PTHrP). In contrast, TNF and IL 1 had little or no inhibitory effect on receptor-mediated stimulation of adenylate cyclase by isoproterenol and nonreceptor-mediated enzyme activation by cholera toxin and forskolin; both monokines increased prostaglandin E2 stimulation of adenylate cyclase. Binding of the radioiodinated agonist mono-[I-125]-[Nle8,18, Tyr34]bPTH-(1-34)NH2 to UMR-106 cells in the presence of increasing concentrations of unlabeled [Nle8,18, Tyr34]bPTH-(1-34)NH2 revealed a decline in PTH receptor density (B(max)) without change in receptor binding affinity (dissociation constant, K(d)) after treatment with TNF or IL 1. Pertussis toxin increased PTH-sensitive adenylate cyclase activity but did not attenuate monokine-induced inhibition of PTH response. In time course studies, brief (1 hr) exposure of cells to TNF or IL 1 during early culture was sufficient to decrease PTH response but only after exposed cells were subsequently allowed to grow for prolonged periods. Inhibition of PTH response by monokines was blocked by cycloheximide. The results indicate that TNF and IL 1 impair responsiveness to PTH (and PTHrP) by a time- and protein synthesis-dependent down-regulation of PTH receptors linked to adenylate cyclase. C1 AUDIE L MURPHY MEM VET ADM MED CTR,CTR GERIATR RES EDUC & CLIN,SAN ANTONIO,TX 78284. MERCK SHARP & DOHME LTD,PARATHYROID HORMONE RES LAB,W POINT,PA 19486. RP KATZ, MS (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV GERIATR & GERONTOL,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. FU NIADDK NIH HHS [AM-28149] NR 39 TC 37 Z9 38 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD OCT PY 1992 VL 153 IS 1 BP 206 EP 213 DI 10.1002/jcp.1041530125 PG 8 WC Cell Biology; Physiology SC Cell Biology; Physiology GA JP455 UT WOS:A1992JP45500024 PM 1325978 ER PT J AU BICKEL, PE FREEMAN, MW AF BICKEL, PE FREEMAN, MW TI RABBIT AORTIC SMOOTH-MUSCLE CELLS EXPRESS INDUCIBLE MACROPHAGE SCAVENGER RECEPTOR MESSENGER-RNA THAT IS ABSENT FROM ENDOTHELIAL-CELLS SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE ACETYLATED LDL; ENDOTHELIAL CELLS; FOAM CELLS; OXIDIZED LDL; SCAVENGER RECEPTOR ID LOW-DENSITY-LIPOPROTEIN; NONRECIPROCAL CROSS COMPETITION; LIPID DROPLET ACCUMULATION; HAMSTER OVARY CELLS; ATHEROSCLEROTIC LESIONS; CHOLESTEROL DEPOSITION; GENE-EXPRESSION; BINDING-SITE; LIVER-CELLS; METABOLISM AB Scavenger receptors mediate uptake of modified low density lipoproteins by macrophages. The accumulation of lipids via this process is thought to lead to foam cell formation in developing atherosclerotic plaques. Smooth muscle cells, which can also be converted to foam cells in vivo, have not been shown to express the same scavenger receptor previously cloned in macrophages. We report the cloning of two cDNAs that encode type I and type II scavenger receptors isolated from rabbit smooth muscle cells. The deduced protein sequences of these isolates are highly homologous to the scavenger receptors previously isolated from macrophages. Treatment of smooth muscle cells with phorbol esters induced a marked increase in scavenger receptor mRNA and a fivefold increase in receptor degradation activity. Rabbit venous endothelial cells in primary culture and a bovine aortic endothelial cell line had no detectable scavenger receptor mRNA, despite having scavenger receptor degradation activity. The latter finding suggests that endothelial cells may possess a scavenger receptor which is structurally distinct from that found in macrophages and smooth muscle cells. The isolation of cDNAs encoding the rabbit scavenger receptor should prove useful for in vitro and in vivo studies that employ the rabbit as a model of human atherosclerosis. C1 MASSACHUSETTS GEN HOSP,DEPT MED,ENDOCRINE UNIT,BULFINCH BLDG,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. FU NHLBI NIH HHS [R01-HL-45098]; NIDDK NIH HHS [T32-DK07028-17] NR 37 TC 116 Z9 120 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 OCT PY 1992 VL 90 IS 4 BP 1450 EP 1457 DI 10.1172/JCI116012 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA JU681 UT WOS:A1992JU68100036 PM 1401078 ER PT J AU MARASCO, WA BAGLEY, J ZANI, C POSNER, M CAVACINI, L HASELTINE, WA SODROSKI, J AF MARASCO, WA BAGLEY, J ZANI, C POSNER, M CAVACINI, L HASELTINE, WA SODROSKI, J TI CHARACTERIZATION OF THE CDNA OF A BROADLY REACTIVE NEUTRALIZING HUMAN ANTI-GP 120 MONOCLONAL-ANTIBODY SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE ACQUIRED IMMUNODEFICIENCY SYNDROME; IMMUNOGLOBULINS; GENE REARRANGEMENT; AUTOANTIBODY; RESTRICTED IDIOTYPE ID HUMAN-IMMUNODEFICIENCY-VIRUS; IMMUNOGLOBULIN HEAVY-CHAIN; EXPERIMENTALLY INFECTED CHIMPANZEES; HUMAN RHEUMATOID FACTORS; B-CELL; MOLECULAR CHARACTERIZATION; NUCLEOTIDE-SEQUENCES; STRUCTURAL CHARACTERIZATION; CONSERVED DOMAINS; SOMATIC MUTATION AB The F105 mAb, identified in an HIV-1-infected individual, binds to a discontinuous epitope on the HIV-1 gp120 envelope glycoprotein, blocks the binding of gp120 to the CD4 viral receptor, and neutralizes a broad range of HIV-1 isolates. This study reports the primary nucleotide and deduced amino acid sequences of the rearranged heavy and light chains of the mAb F105. This IgG1k mAb uses a V(H) gene member of the V(H)4 gene family (V714) and is productively rearranged with a D-D fusion product of the dlr4 and da4 germline D(H) genes and the J(H5) gene. This rearranged heavy chain gene expresses the V(H)4-HV2a idiotope, which is seen in human monoclonal IgM cold agglutinins. The F105 V(k) appears to be derived from the Humvk325 germline gene and is rearranged with a J(k2) gene. For both chains, the mutational pattern in the rearranged V(H) and V(L) genes is indicative of an antigen-driven process. These studies show that production of a broadly neutralizing anti-HIV-1 antibody that recognizes determinants within the CD4 recognition site of the envelope glycoprotein is achieved by rearrangement of the V71-4 and Humvk325 germline variable region genes along with selected individual point mutations in the rearranged genes. C1 HARVARD UNIV,NEW ENGLAND DEACONESS HOSP,SCH MED,DEPT MED,BOSTON,MA 02215. RP MARASCO, WA (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HUMAN RETROVIROL,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [K08-CA01507]; NIAID NIH HHS [AI31783] NR 77 TC 48 Z9 48 U1 0 U2 3 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 OCT PY 1992 VL 90 IS 4 BP 1467 EP 1478 DI 10.1172/JCI116014 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA JU681 UT WOS:A1992JU68100038 PM 1401079 ER PT J AU SWENSON, JM FERRARO, MJ SAHM, DF CHARACHE, P TENOVER, FC HARDY, DJ MOELLERING, RC WILSON, WR AF SWENSON, JM FERRARO, MJ SAHM, DF CHARACHE, P TENOVER, FC HARDY, DJ MOELLERING, RC WILSON, WR TI NEW VANCOMYCIN DISK DIFFUSION BREAKPOINTS FOR ENTEROCOCCI SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID RESISTANT ENTEROCOCCI; TRANSFERABLE RESISTANCE; SUSCEPTIBILITY; TEICOPLANIN; FAECIUM AB Since 1988, when the first vancomycin-resistant enterococcus was described, several descriptions of failures of disk diffusion breakpoints to detect low-level vancomycin resistance (MICs, 8 to 32 mug/ml) have been published. A four-laboratory collaborative study was undertaken to establish more accurate breakpoints for the disk test. Mueller-Hinton agar was used to perform dilution testing (in three laboratories) and disk diffusion testing (in all laboratories). Results were determined at 18, 24, and 48 h, and zones of inhibition were read using both transmitted and reflected light. One hundred organisms (35 Enterococcus faecalis, 55 E. faecium, and 10 E. gallinarum or E. casseliflavus isolates) were selected to represent vancomycin-susceptible and -resistant phenotypes. Interlaboratory agreement of agar dilution MICs was better at 24 h (91 to 94% within +/-1 dilution) than at 18 h (76% within +/-1 dilution). Therefore, 24-h agar dilution MIC results were used as the reference. For disk diffusion, it was critical to note the presence of a haze or colonies inside the zone when interpreting the test, since this correlated better with the results of the agar dilution test. The presence of a haze or inner colonies was best detected by reading the zones with transmitted tight and incubating the plates for a full 24 h. When plotted against 24-h agar dilution MICs, breakpoints of less-than-or-equal-to 14 mm (resistant), 15 to 16 mm (intermediate), and greater-than-or-equal-to 17 mm (susceptible) resulted in 58 minor errors (14.5% of total values) and 5 very major errors (2.2% of resistant values or 1.3% of total values). No major errors were seen. Results of repeat testing using a common lot of Mueller-Hinton agar showed 52 minor errors (13.3%) and 4 major errors (4.2% of susceptible values or 1.0% of total values) but no very major errors. It is recommended that any haze or colonies within the zone be taken into account when determining zones of inhibition and that an MIC test be performed for strains with intermediate zones if vancomycin is being considered for treatment. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. UNIV CHICAGO,MED CTR,CLIN MICROBIOL LABS,CHICAGO,IL 60637. JOHNS HOPKINS MED INST,BALTIMORE,MD 21205. UNIV ROCHESTER,MED CTR,ROCHESTER,NY 14642. NEW ENGLAND DEACONESS HOSP,DEPT MED,BOSTON,MA 02215. MAYO CLIN & MAYO FDN,ROCHESTER,MN 55905. RP SWENSON, JM (reprint author), NATL CTR INFECT DIS,CTR DIS CONTROL,HOSP INFECT PROGRAM,NOSOCOMIAL PATHOGENS LAB BRANCH,ATLANTA,GA 30333, USA. NR 19 TC 40 Z9 41 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD OCT PY 1992 VL 30 IS 10 BP 2525 EP 2528 PG 4 WC Microbiology SC Microbiology GA JP653 UT WOS:A1992JP65300001 PM 1400949 ER PT J AU SEIDEN, M SKLAR, J AF SEIDEN, M SKLAR, J TI AIDS AND NON-HODGKINS-LYMPHOMA - A PRE-PRE-B-CELL MONOCLONAL LYMPHOMA VERSUS A NOVEL MECHANISM OF POLYCLONALITY SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter ID EPSTEIN-BARR VIRUS RP SEIDEN, M (reprint author), HARVARD UNIV,BRIGHAM & WOMENS HOSP,MASSACHUSETTS GEN HOSP,DANA FARBER CANC INST,BOSTON,MA 02115, USA. NR 6 TC 6 Z9 6 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 OCT PY 1992 VL 10 IS 10 BP 1650 EP 1650 PG 1 WC Oncology SC Oncology GA JQ719 UT WOS:A1992JQ71900021 PM 1403043 ER PT J AU PASTORFIDE, GC KIBBI, AG DEROA, AL BARNHILL, RL SOBER, AJ MIHM, MC BYERS, HR AF PASTORFIDE, GC KIBBI, AG DEROA, AL BARNHILL, RL SOBER, AJ MIHM, MC BYERS, HR TI IMAGE-ANALYSIS OF STAGE-1 MELANOMA (1.00-2.50 MM) - LYMPHOCYTIC INFILTRATES RELATED TO METASTASIS AND SURVIVAL SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Article ID CUTANEOUS MALIGNANT-MELANOMA; PROGNOSTIC FACTORS; MULTIFACTORIAL ANALYSIS; I MELANOMA; INTERLEUKIN-2; THICKNESS; FEATURES; CANCER; INDEX; CELLS AB Image analysis of histologic sections of 11 patients with clinical Stage 1 melanoma, 1.00 mm - 2.50 mm, who developed metastasis, was done to determine the significance of lymphocytic infiltrates relative to metastasis and survival. An age, sex, site, and thickness matched control group of non-metastasizing clinical Stage 1 melanoma revealed no significant difference in the lymphocytic infiltrate parameters from the metastasizing group with the exception of the ratio of lymphocyte infiltrate width to the tumor width (p = 0.003). Increased lymphocytic infiltrates within the tumor and subjacent to its base significantly correlated with delayed time to metastasis (p = 0.014 and p <0.001, respectively) and longer survival period (p = 0.045 and p <0.001, respectively). Lymphocytic infiltrate area at the tumor base in relation to tumor area was of prognostic value: the larger the ratio, the greater the time interval from metastasis to death (p = 0.008). C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT DERMATOL,BOSTON,MA 02114. AMER UNIV BEIRUT,MED CTR,BEIRUT,LEBANON. NR 31 TC 15 Z9 15 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD OCT PY 1992 VL 19 IS 5 BP 390 EP 397 DI 10.1111/j.1600-0560.1992.tb00611.x PG 8 WC Dermatology; Pathology SC Dermatology; Pathology GA JW080 UT WOS:A1992JW08000007 PM 1474192 ER PT J AU KURBAN, RS PREFFER, FI SOBER, AJ MIHM, MC BARNHILL, RL AF KURBAN, RS PREFFER, FI SOBER, AJ MIHM, MC BARNHILL, RL TI OCCURRENCE OF MELANOMA IN DYSPLASTIC NEVUS-SPILUS - REPORT OF CASE AND ANALYSIS BY FLOW-CYTOMETRY SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Article ID SPECKLED LENTIGINOUS NEVUS; MALIGNANT-MELANOMA; MELANOCYTIC NEVI; ANEUPLOIDY AB We report a case of melanoma arising in a large nevus spilus. On histologic examination, the nevus spilus had diagnostic features of melanocytic dysplasia. Further characterization by flow cytometry showed DNA-aneuploidy within the melanoma as well as in one of the darker pigmented papules within the nevus spilus. The significance of this finding and a review of melanomas originating in nevi spili are presented. C1 BRIGHAM & WOMENS HOSP,DEPT PATHOL,DIV DERMATOPATHOL,75 FRANCIS ST,BOSTON,MA 02115. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,DIV DERMATOPATHOL,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT DERMATOL,BOSTON,MA 02114. NR 24 TC 27 Z9 28 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD OCT PY 1992 VL 19 IS 5 BP 423 EP 428 DI 10.1111/j.1600-0560.1992.tb00615.x PG 6 WC Dermatology; Pathology SC Dermatology; Pathology GA JW080 UT WOS:A1992JW08000011 PM 1474193 ER PT J AU BENECH, PD SASTRY, K IYER, RR EICHBAUM, QG RAVEH, DP EZEKOWITZ, RAB AF BENECH, PD SASTRY, K IYER, RR EICHBAUM, QG RAVEH, DP EZEKOWITZ, RAB TI DEFINITION OF INTERFERON-GAMMA RESPONSE ELEMENTS IN A NOVEL HUMAN FC-GAMMA RECEPTOR GENE (FC-GAMMA-RIB) AND CHARACTERIZATION OF THE GENE STRUCTURE SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID TUMOR NECROSIS FACTOR; ALPHA-INTERFERON; MESSENGER-RNA; TRANSCRIPTION; MACROPHAGE; AFFINITY; INITIATOR; PROMOTER; SEQUENCE; SET AB The human FcgammaRI (CD64) is a high affinity receptor for the Fc portion of immunoglobulin (Ig), and its constitutively low expression on the cell surface of monocyte/macrophage and neutrophils is selectively upregulated by interferon gamma (IFN-gamma) treatment (Perussia, B., E. T. Dayton, R. Lazarus, V. Fanning, and G. Trinchieri. 1983. J. Exp. Med. 158:1092). Three distinct cDNAs have been cloned and code for proteins that predict three extracellular Ig-like domains (Allen, J. M., and B. Seed. 1989. Science [Wash. DC]. 243:378). Several differences in the coding region of these cDNAs suggest that in addition to polymorphic differences a second FcgammaRI gene could possibly exist. This alternative FcgammaRI gene (FcgammaRIb) was defined by the lack of a genomic HindIII restriction site (van der Winkel, J. G. J., L. U. Ernst, C. L. Anderson, and I. M. Chiu. 1991. J. Biol. Chem. 266:13449). We describe the characterization a second gene (FcgammaRIb) that has a termination codon in the third extracellular domain and therefore predicts a soluble form of the receptor. We also define two distinct IFN-gamma-responsive regions in the 5' flanking sequence of FcgammaRIb that resemble motifs that have been defined in the class II major histocompatibility complex promoter. The FcgammaRIb promoter does not possess canonical TATA or CCAAT boxes, but does possess a palindromic motif that closely resembles the initiator sequence identified in the terminal deoxynucleotidyl transferase/human leukocyte IFN/adeno-associated virus type II P5 gene promoters (Smale, S. T., and D. Baltimore. 1989. Cell. 57:103; Seto, E., Y. Shi, and T. Shenk. 1991. Nature [Lond.]. 354:241; Roy, A. L., M. Meisterernst, P. Pognonec, and R. C. Roeder. 1991. Nature [Lond.]. 354:245) virus type II P5 gene promoters raising interesting questions as to its role in the basal and myeloid-specific transcription of this gene. C1 CHILDRENS HOSP MED CTR,DIV HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,DANA FARBER CANC INST,BOSTON,MA 02115. NR 31 TC 22 Z9 24 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 OCT 1 PY 1992 VL 176 IS 4 BP 1115 EP 1123 DI 10.1084/jem.176.4.1115 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA JP862 UT WOS:A1992JP86200021 PM 1402657 ER PT J AU ADAMS, JC AF ADAMS, JC TI BIOTIN AMPLIFICATION OF BIOTIN AND HORSERADISH-PEROXIDASE SIGNALS IN HISTOCHEMICAL STAINS SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Note DE BIOTIN AMPLIFICATION; IMMUNOHISTOCHEMISTRY; LECTIN HISTOCHEMISTRY ID CATALYZED REPORTER DEPOSITION; IMMUNOASSAYS AB A procedure is described for intensifying histochemical reactions by amplification of biotinylated sites. This is achieved by deposition of biotinylated tyramine on the tissue through the enzymatic action of horseradish peroxidase (HRP). The amplified biotin sites are subsequently visualized by binding them to avidin, to which a marker is attached. This amplification greatly increases the sensitivity of staining procedures that employ HRP (and/or biotin) in tissue. For neuroanatomical pathway tracing methods, the procedure greatly increases the detectability of the injected tracer. For lectin histochemistry and immunohistochemistry, the amplification requires that the lectin or primary antibody be greatly diluted. This dilution results in less background staining and yet strong signals are produced even when very dilute reagents are used. Alternatively, the amplification permits much shorter incubations in primary antibodies when dilutions are used that would ordinarily be used with conventional bridge techniques. The procedure is also useful for amplifying very weak signals, such as those of immunoreactions in glutaraldehyde-fixed tissue. The amplification procedure, together with the availability of avidin probes labeled with fluorochromes, colloidal gold, or enzyme systems other than HRP, provides a means of greatly increasing the versatility of a variety of histochemical reactions, including those for detecting in situ hybridization probes, in addition to increasing the sensitivity of the reactions. RP ADAMS, JC (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,243 CHARLES ST,BOSTON,MA 02114, USA. FU NIDCD NIH HHS [DC 00269-08] NR 9 TC 511 Z9 514 U1 2 U2 14 PU HISTOCHEMICAL SOC INC PI NEW YORK PA MT SINAI MEDICAL CENTER 19 EAST 98TH ST SUTIE 9G, NEW YORK, NY 10029 SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD OCT PY 1992 VL 40 IS 10 BP 1457 EP 1463 PG 7 WC Cell Biology SC Cell Biology GA JP519 UT WOS:A1992JP51900002 PM 1527370 ER PT J AU NAGLERANDERSON, C MCNAIR, LA CRADOCK, A AF NAGLERANDERSON, C MCNAIR, LA CRADOCK, A TI SELF-REACTIVE, T-CELL RECEPTOR-GAMMA-DELTA+, LYMPHOCYTES FROM THE INTESTINAL EPITHELIUM OF WEANLING MICE SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; INTRAEPITHELIAL LYMPHOCYTES; MONOCLONAL-ANTIBODIES; GENE USAGE; EXPRESSION; ANTIGEN; BEARING; DIFFERENTIATION; SUBSET; SPECIFICITY AB Intraepithelial T lymphocytes (IEL) are dispersed throughout the intestinal epithelial lining but their role in cellular immune defense is unknown. Their location suggests that their highly activated state may be due to constant exposure to bacterial Ag. To study IEL specificity and function we have prepared a panel of IEL-T cell hybridomas from both adult and weanling C57B1/6 mice. Many of these expressed TCR-gamma-delta, a cell type rare in peripheral lymph nodes and spleen but predominant at epithelial surfaces. We have identified a subset of gamma-delta T cells from weanling mice which is self reactive, i.e., these hybrids secrete IL-2 spontaneously, without antigenic stimulation or a requirement for APC. Self-reactive TCR-gamma-delta+ hybrids and lines, all of which bear a particular TCR (V-gamma-1.1C-gamma-4V-delta-6), have previously been derived from neonatal thymus and the skin. Northern blot and immunoprecipitation analyses suggest that the self-reactive IEL hybrids also bear a C-gamma-4/V-delta-6 TCR. Antibody inhibition experiments showed that the self-reactivity of the IEL hybrids is TCR mediated. Spontaneous IL-2 production was blocked by soluble anti-CD3 and anti-TCR-gamma-delta antibodies but not by antibodies to the TCR-alpha-beta. The self-reactive IEL hybrids lack class II MHC and the class I-like proteins CD1 and TLA but express class I MHC. IEL hybrids may also require the vitronectin receptor as an accessory molecule for their activation because spontaneous IL-2 production is blocked by antibody to the vitronectin receptor as well as by the extracellular matrix protein active site peptide RGDS, but not the control peptide RGES. V-gamma-1.1C-gamma-4V-delta-6 T cells in the thymus, skin, and intestine may represent a small and unique subpopulation of lymphocytes with a potential for autoimmune reactivity at peripheral sites. C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP NAGLERANDERSON, C (reprint author), MASSACHUSETTS GEN HOSP,MUCOSAL IMMUNOL LAB,ROOM 3308,3 W,BLDG 149,13TH ST,BOSTON,MA 02129, USA. FU NIDDK NIH HHS [P30 DK43351] NR 63 TC 32 Z9 32 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 OCT 1 PY 1992 VL 149 IS 7 BP 2315 EP 2322 PG 8 WC Immunology SC Immunology GA JP189 UT WOS:A1992JP18900011 PM 1382095 ER PT J AU BRADY, HR SPERTINI, O JIMENEZ, W BRENNER, BM MARSDEN, PA TEDDER, TF AF BRADY, HR SPERTINI, O JIMENEZ, W BRENNER, BM MARSDEN, PA TEDDER, TF TI NEUTROPHILS, MONOCYTES, AND LYMPHOCYTES BIND TO CYTOKINE-ACTIVATED KIDNEY GLOMERULAR ENDOTHELIAL-CELLS THROUGH L-SELECTIN (LAM-1) INVITRO SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LEUKOCYTE ADHESION MOLECULE-1; NODE HOMING RECEPTOR; COLONY-STIMULATING FACTOR; EVOLUTIONARY CONSERVATION; VASCULAR ENDOTHELIUM; CD18-INDEPENDENT ADHESION; INTERACTION DOMAINS; SURFACE MOLECULE; MEL-14 ANTIGEN; HUMAN HOMOLOG AB The role of L-selectin (LAM-1) as a regulator of leukocyte adhesion to kidney microvascular glomerular endothelial cells was assessed in vitro by using L-selectin-directed mAb and an L-selectin cDNA-transfected cell line. The initial attachment of neutrophils, monocytes, and lymphocytes to TNF-activated bovine glomerular endothelial cells was significantly inhibited by the anti-LAM1-3 mAb. Under static conditions, anti-LAM1-3 mAb inhibited neutrophil adhesion by 15 +/- 5%, whereas the anti-LAM1-10 mAb, directed against a functionally silent epitope of L-selectin, was without effect. The binding of a CD18 mAb inhibited adhesion by 47 +/- 6%. In contrast, when the assays were carried out under nonstatic conditions or at 4-degrees-C, the anti-LAM1-3 mAb generated significantly greater inhibition (approximately 60%). CD18-dependent adhesion was minimal (approximately 10%) under these conditions. TNF-activated glomerular endothelial cells also supported adhesion of a mouse pre-B cell line transfected with L-selectin cDNA, but not wild-type cells. This process was also inhibited by the anti-LAM1-3 mAb. Leukocyte adhesion to unstimulated endothelial cells was independent of L-selectin, but, after TNF stimulation, L-selectin-mediated adhesion was observed at 4 h, with maximal induction persisting for 24 to 48 h. Leukocyte adhesion was not observed if glomerular endothelial cells were exposed to TNF in the presence of RNA or protein synthesis inhibitors. Leukocyte attachment to TNF-activated glomerular endothelial cells was also partially inhibited by treatment of the cells with mannose-6-phosphate or phosphomannan monoester, a soluble complex carbohydrate, or by prior treatment of glomerular endothelial cells with neuraminidase, suggesting that the glomerular endothelial cell ligand shares functional characteristics with those expressed by lymph node and large vessel endothelial cells. These data suggest that TNF activation induced the biosynthesis and surface expression of a ligand(s) for L-selectin on glomerular endothelial cells, which supports neutrophil, monocyte, and lymphocyte attachment under nonstatic conditions. C1 BRIGHAM & WOMENS HOSP,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,DANA FARBER CANC INST,CTR STUDY KIDNEY DIS,DIV TUMOR IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. UNIV TORONTO,ST MICHAELS HOSP,TORONTO M5B 1W8,ONTARIO,CANADA. RP BRADY, HR (reprint author), BRIGHAM & WOMENS HOSP,DIV RENAL,75 FRANCIS ST,BOSTON,MA 02115, USA. RI Marsden, Philip/B-1441-2012 FU NIDDK NIH HHS [DK-35930, DK-30410, DK-44380] NR 59 TC 94 Z9 94 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 OCT 1 PY 1992 VL 149 IS 7 BP 2437 EP 2444 PG 8 WC Immunology SC Immunology GA JP189 UT WOS:A1992JP18900028 PM 1382103 ER PT J AU RUBIN, D LAPOSATA, M AF RUBIN, D LAPOSATA, M TI CELLULAR INTERACTIONS BETWEEN N-6 AND N-3 FATTY-ACIDS - A MASS ANALYSIS OF FATTY-ACID ELONGATION/DESATURATION, DISTRIBUTION AMONG COMPLEX LIPIDS, AND CONVERSION TO EICOSANOIDS SO JOURNAL OF LIPID RESEARCH LA English DT Article DE PROSTAGLANDIN; PHOSPHOLIPID; DIHOMOGAMMALINOLENIC ACID; ARACHIDONIC ACID; EICOSAPENTAENOIC ACID; PROSTAGLANDIN-E1; PROSTAGLANDIN-E2; PROSTAGLANDIN-E3 ID HUMAN-ENDOTHELIAL CELLS; SMOOTH-MUSCLE CELLS; FISH OIL DIET; EICOSAPENTAENOIC ACID; ARACHIDONIC-ACID; HUMAN-PLATELETS; PROSTAGLANDIN-E1 TREATMENT; RHEUMATOID-ARTHRITIS; RAT-LIVER; METABOLISM AB The biologic effect of eicosanoids depends in large measure upon the relative masses in tissues of eicosanoids derived from the n-6 fatty acids, dihomogammalinolenic acid and arachidonic acid, and the n-3 fatty acid, eicosapentaenoic acid. Generation of this tissue balance is related to the relative cellular masses of these precursor fatty acids, the competition between them for entry into and release from cellular phospholipids, and their competition for the enzymes that catalyze their conversion to eicosanoids. In order to better understand these processes, we studied the cellular interactions of n-6 and n-3 fatty acids using an essential fatty acid-deficient, PGE-producing, mouse fibrosarcoma cell line, EFD-1. Unlike studies using cells with endogenous pools of n-6 and n-3 fatty acids, the use of EFD-1 cells enabled us to examine the metabolic fate of each family of fatty acids both in the presence and in the absence of the second family of fatty acids. Thus, the specific effects of one fatty acid family on the other could be directly assessed. In addition, we were able to replete the cells with dihomogammalinolenic acid (DHLA), arachidonic acid (AA), and eicosapentaenoic acid (EPA) of known specific activities; thus the masses of cellular DHLA, AA, and EPA, and their metabolites, PGE1, PGE2, and PGE3, respectively, could be accurately quantitated. The major findings of this study were: 1) n-6 fatty acids markedly stimulated the elongation of EPA to 22:5 whereas n-3 fatty acids inhibited the DELTA-5 desaturation of DHLA to AA and the elongation of AA to 22:4; 2) n-6 fatty acids caused a specific redistribution of cellular EPA from phospholipid to triacylglycerol; 3) n-3 fatty acids reduced the mass of DHLA and AA only in phosphatidylinositol whereas n-6 fatty acids reduced the mass of EPA to a similar extent in all cellular phospholipids; and 4) n-3 fatty acids caused an identical (33%) reduction in the bradykinin-induced release of PGE1 and PGE2, whereas n-6 fatty acids stimulated PGE3 release 2.3-fold. Together, these highly quantitative metabolic data increase our understanding of the regulation of both the cellular levels of DHLA, AA, and EPA, and their availability for eicosanoid synthesis. In addition, these findings provide a context for the effective use of these fatty acids in dietary therapies directed at modulation of eicosanoid production. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. FU NIDDK NIH HHS [DK 43159] NR 52 TC 41 Z9 42 U1 1 U2 3 PU LIPID RESEARCH INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD OCT PY 1992 VL 33 IS 10 BP 1431 EP 1440 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JN948 UT WOS:A1992JN94800003 PM 1472257 ER PT J AU PARKER, RM HAMBURG, P AF PARKER, RM HAMBURG, P TI COMPULSIVE EXERCISE AND THE EATING DISORDERS - TOWARD AN INTEGRATED THEORY OF ACTIVITY - YATES,A SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Book Review RP PARKER, RM (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD OCT PY 1992 VL 180 IS 10 BP 670 EP 671 DI 10.1097/00005053-199210000-00019 PG 2 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA JT350 UT WOS:A1992JT35000020 ER PT J AU LEE, JK SOBEL, RA CHIOCCA, EA KIM, TS MARTUZA, RL AF LEE, JK SOBEL, RA CHIOCCA, EA KIM, TS MARTUZA, RL TI GROWTH OF HUMAN ACOUSTIC NEUROMAS, NEUROFIBROMAS AND SCHWANNOMAS IN THE SUBRENAL CAPSULE AND SCIATIC-NERVE OF THE NUDE-MOUSE SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE ACOUSTIC NEUROMA; NEUROFIBROMA; NUDE MOUSE; SCHWANNOMA; SCIATIC NERVE; SUBRENAL CAPSULE; XENOGRAFT ID MODEL; EXPRESSION; SEQUENCES; SYSTEM; TUMORS; DNA AB To develop a reproducible in vivo model for the growth of human acoustic neuromas and neurofibromas, we implanted tumor specimens (6 acoustic neuromas; 4 neurofibromas; 3 schwannomas arising in skin and soft tissues) from 13 different patients into the subrenal capsules of 67 nude mice and sciatic nerves of 64 nude mide. The animals were anesthetized and the tumors were microscopically implanted. Serial tumor volumes were determined at intervals up to 2 months by reopening the incision and directly measuring the tumor size with a micrometer. The percentages of acoustic neuromas that survived or grew were 57.1% in the subrenal capsule and 88.9% in the sciatic nerves; the percentages of neurofibromas that survived and grew were 50% in the subrenal capsule and 70% in the sciatic nerves; and the percentages of schwannomas that survived and grew were 57.1% in the subrenal capsule and 94.1% in the sciatic nerve. Tumors in the sciatic nerve also survived and grew for a longer period than those in the subrenal capsules. Tumor enlargement and stability correlated with neovascularity. At 1 or 2 months after engraftment, the tumors showed histologic appearances similar to the original tumors and immunohistochemical analysis of cryostat sections demonstrated staining of the tumors, but not the host mouse tissues for human beta2-microglobulin, a species-specific marker. Furthermore, analysis of genomic DNA from implanted tumors revealed its human origin. We conclude that human acoustic neuromas, neurofibromas and schwannomas are readily grown in two sites in nude mice and that they retain their morphologic features and genomic identities. These tumors grow better and more consistently in the sciatic nerve than in the subrenal capsule. These are useful model systems for studying tumor growth and cellular modulation. C1 GEORGETOWN UNIV,MED CTR,DEPT NEUROSURG,3800 RESERVOIR RD,WASHINGTON,DC 20007. HARVARD UNIV,SCH MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT SURG,NEUROSURG SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. FU NINDS NIH HHS [NS26773, NS24279, NS20025] NR 20 TC 21 Z9 22 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 OCT PY 1992 VL 14 IS 2 BP 101 EP 112 PG 12 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA JP679 UT WOS:A1992JP67900002 PM 1432035 ER PT J AU RIVITZ, SM YASUDA, T AF RIVITZ, SM YASUDA, T TI PREDICTIVE VALUE OF DIPYRIDAMOLE THALLIUM IMAGING IN A PATIENT WITH MYOCARDIAL BRIDGING BUT WITHOUT FIXED OBSTRUCTIVE CORONARY-ARTERY DISEASE SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article ID EXERCISE TL-201 SCINTIGRAPHY; ANTERIOR DESCENDING ARTERY; PROGNOSTIC VALUE; CARDIAC RISK; CHEST PAIN; VASCULAR-SURGERY; PERFUSION SCINTIGRAPHY; WALL-MOTION; STENOSES; INFARCTION C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,DIV NUCL MED,TILTON 2,BOSTON,MA 02114. NR 40 TC 10 Z9 10 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 OCT PY 1992 VL 33 IS 10 BP 1905 EP 1913 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA JU520 UT WOS:A1992JU52000037 PM 1403164 ER PT J AU TODOROKI, T SUIT, HD AF TODOROKI, T SUIT, HD TI THERAPEUTIC GAIN OF LOCAL AND RADICAL RESECTION COMBINED WITH POSTOPERATIVE RADIATION FOR MURINE FIBROSARCOMAS SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Article DE ADVANTAGE OF POSTOPERATIVE RADIOTHERAPY; TUMOR CONTROL VS TREATMENT MORBIDITY; FIBROSARCOMA (FSAII) ID RECTAL-CANCER; TIME INTERVAL; NECK-CANCER; SURGERY; IRRADIATION; DISEASE; SARCOMA; TRIAL; MOUSE; HEAD AB Resection of 8-mm fibrosarcomas (FSaII) growing in the right leg of syngeneic C3H/Sed mice was performed under a dissecting (x8) microscope. Local and radical resection achieved 20% (5/25) and 48% (12/25) tumor control, respectively. TCD80s (average dose expected to control 80% of irradiated tumors) for radiation alone given as one fraction per day for 5 consecutive days were 73.1 and 118.0 Gy for the microscopic and 8-mm tumors, respectively. Radiation therapy started at 4 or 7 days following local or radical resection enhanced both the local tumor control and the treatment-related morbidity represented by leg shortening. From enhancement ratios (ERs) for tumor control (TCD80 for radiation alone/ TCD80 for postoperative radiation) and for leg shortening (dose for 5-mm leg shortening for radiation alone/postoperative radiation) values, therapeutic gain factors (TGFs) were derived as ER tumor/ER leg shortening. These were 1.3 and 1.4 for local and radical resection followed by radiation started on the 7th postoperative day, respectively. Corresponding figures for radiation started on the 4th postoperative day resulted in 1.2 for both resection procedures. C1 UNIV TSUKUBA,INST CLIN MED,DEPT SURG,TSUKUBA,IBARAKI 30031,JAPAN. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,EDWIN L STEELE LAB RADIAT BIOL,BOSTON,MA 02114. NR 15 TC 3 Z9 3 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 0022-4790 J9 J SURG ONCOL JI J. Surg. Oncol. PD OCT PY 1992 VL 51 IS 2 BP 126 EP 133 DI 10.1002/jso.2930510213 PG 8 WC Oncology; Surgery SC Oncology; Surgery GA JR769 UT WOS:A1992JR76900011 PM 1405652 ER PT J AU PETERSEN, MJ HOPPEL, BE MEGERMAN, J ORKIN, RW ROSEN, BR ABBOTT, WM AF PETERSEN, MJ HOPPEL, BE MEGERMAN, J ORKIN, RW ROSEN, BR ABBOTT, WM TI MAGNETIC-RESONANCE-IMAGING OF SMALL ARTERIES SO JOURNAL OF SURGICAL RESEARCH LA English DT Article ID CEREBRAL ARTERIOGRAPHY; COMPLICATIONS; ANGIOGRAPHY; FLOW C1 MASSACHUSETTS GEN HOSP,DEPT SURG,ACC 458,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. FU NCI NIH HHS [CA-40303]; NHLBI NIH HHS [HL-39810, HL-34780] NR 19 TC 2 Z9 2 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD OCT PY 1992 VL 53 IS 4 BP 391 EP 395 DI 10.1016/0022-4804(92)90066-9 PG 5 WC Surgery SC Surgery GA JT354 UT WOS:A1992JT35400013 PM 1405619 ER PT J AU RABINOWITZ, WM EDDINGTON, DK DELHORNE, LA CUNEO, PA AF RABINOWITZ, WM EDDINGTON, DK DELHORNE, LA CUNEO, PA TI RELATIONS AMONG DIFFERENT MEASURES OF SPEECH RECEPTION IN SUBJECTS USING A COCHLEAR IMPLANT SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID WORD RECOGNITION; SINGLE-CHANNEL; CONSONANT RECOGNITION; PERCEPTION; PERFORMANCE; PROCESSOR; IDENTIFICATION; COMMUNICATION; FEATURES; FORMANT AB A comprehensive set of speech reception measures were obtained in a group of about 20 postlingually deafened adult users of the Ineraid multichannel cochlear implant. The measures included audio, visual, and audiovisual recognition of words embedded in two types of sentences (with differing degrees of difficulty) and audio-only recognition of isolated monosyllabic words, consonant identification (12 alternatives, /Ca/), and vowel identification (8 alternatives, /bVt/). For most implantees, the audiovisual gains in the sentence tests were very high. Quantitative relations among audio-only scores were assessed using power-law transformations suggested by Boothroyd and Nittrouer [J. Acoust. Soc. Am. 84, 101-114 (1988)] that can account for the benefit of sentence context (via a factor k) and the relation between word and phoneme recognition (via a factor j). Across the broad range of performance that existed among the subjects, substantial order was observed among measures of speech reception along the continuum from recognition of words in sentences, words in isolation, speech segments, and the retrieval of underlying phonetic features. Correlations exceeded 0.85 among direct and sentence-derived measures of isolated word recognition as well as among direct and word-derived measures of segmental recognition. Results from a variety of other studies involving presentation of limited auditory signals, single-channel and multichannel implants, and tactual systems revealed a similar pattern among word recognition, overall consonant identification performance, and consonantal feature recruitment. Finally, improving the reception of consonantal place cues was identified as key to producing the greatest potential gains in speech reception. C1 HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02115. MASSACHUSETTS EYE & EAR INFIRM,COCHLEAR IMPLANT RES LAB,BOSTON,MA 02114. RP RABINOWITZ, WM (reprint author), MIT,ELECTR RES LAB,ROOM 36-789,50 VASSAR ST,CAMBRIDGE,MA 02139, USA. FU NIDCD NIH HHS [P01 DC00361] NR 55 TC 52 Z9 52 U1 1 U2 1 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD OCT PY 1992 VL 92 IS 4 BP 1869 EP 1881 DI 10.1121/1.405252 PN 1 PG 13 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA JT538 UT WOS:A1992JT53800007 PM 1401531 ER PT J AU BURSTEIN, S SEMIGRAN, MJ DEC, GW BOUCHER, CA FIFER, MA AF BURSTEIN, S SEMIGRAN, MJ DEC, GW BOUCHER, CA FIFER, MA TI POSITIVE INOTROPIC AND LUSITROPIC EFFECTS OF INTRAVENOUS FLOSEQUINAN IN PATIENTS WITH HEART-FAILURE SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID PRESSURE-VOLUME RELATIONS; DIASTOLIC FUNCTION; LEFT-VENTRICLE; INTACT DOG; VASODILATOR; NITROPRUSSIDE; LOAD; NICARDIPINE; METABOLITE; RELAXATION AB Objectives. This study was designed to assess the direct effects of flosequinan on myocardial function. Background. Flosequinan has been shown to improve symptoms and exercise tolerance in patients with heart failure. Although previous studies have established that flosequinan is a vasodilator, it is not known to what extent direct actions of the drug on myocardial contractility or diastolic properties contribute to its beneficial hemodynamic effects. Methods. Nitroprusside and intravenous flosequinan were administered sequentially to 18 patients with severe heart failure (New York Heart Association functional class III or IV, left ventricular ejection fraction 0.14 +/- 0.02). Micromanometer left ventricular pressure and radionuclide volume data were combined to construct pressure-volume loops during 1) a baseline period, 2) nitroprusside infusion, 3) a second baseline period, and 4) flosequinan infusion. Results. The peak rate of left ventricular pressure development increased from 899 +/- 84 to 1,070 +/- 94 mm Hg/s (p < 0.05) with flosequinan. The baseline left ventricular end-systolic pressure-volume relation was constructed in 15 patients from the two baseline pressure-volume loops and from that obtained during afterload manipulation with nitroprusside. During flosequinan administration, the relation between end-systolic pressure and volume was shifted upward and leftward, indicating enhanced contractility, in 14 of 15 patients (p < 0.001). The maximal rate of decrease in left ventricular pressure during isovolumetric relaxation increased in magnitude with flosequinan from 882 +/- 63 to 1,026 +/- 68 mm Hg/s (p < 0.05). Conclusions. These results indicate that intravenous flosequinan has positive inotropic and lusitropic effects in patients with heart failure. Further studies are needed to asses the direct myocardial effects of oral flosequinan. C1 MASSACHUSETTS GEN HOSP,DEPT MED,CARDIAC UNIT,WACC 478,15 PARKMAN ST,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 41 TC 15 Z9 15 U1 0 U2 1 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 OCT PY 1992 VL 20 IS 4 BP 822 EP 829 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA JQ473 UT WOS:A1992JQ47300010 PM 1527293 ER PT J AU HUTTER, AM AF HUTTER, AM TI PRESIDENTS PAGE - HEART HOUSE - THE DEDICATION OF A 3RD WING SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material RP HUTTER, AM (reprint author), MASSACHUSETTS GEN HOSP,ACC BLDG,SUITE 467,15 PARKMAN ST,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD OCT PY 1992 VL 20 IS 4 BP 1019 EP 1021 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA JQ473 UT WOS:A1992JQ47300038 ER PT J AU MORRIS, DH SORENSEN, G STODDARD, AM FITZGERALD, G AF MORRIS, DH SORENSEN, G STODDARD, AM FITZGERALD, G TI COMPARISON BETWEEN FOOD CHOICES OF WORKING ADULTS AND DIETARY PATTERNS RECOMMENDED BY THE NATIONAL-CANCER-INSTITUTE SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID UNITED-STATES; FIBER INTAKE; REPRODUCIBILITY; QUESTIONNAIRE; CONSUMPTION; GUIDELINES; VALIDITY; RISK; FAT C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT EPIDEMIOL & CANC CONTROL,BOSTON,MA 02115. MAINSTREAM NUTR,WINNIPEG R3R 2C9,MANITOBA,CANADA. UNIV MASSACHUSETTS,SCH PUBL HLTH,AMHERST,MA 01003. NR 16 TC 12 Z9 12 U1 0 U2 0 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD OCT PY 1992 VL 92 IS 10 BP 1272 EP 1274 PG 3 WC Nutrition & Dietetics SC Nutrition & Dietetics GA JT698 UT WOS:A1992JT69800022 PM 1401670 ER PT J AU BROWN, D WANECK, GL AF BROWN, D WANECK, GL TI GLYCOSYL-PHOSPHATIDYLINOSITOL ANCHORED MEMBRANE-PROTEINS SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article DE CELL POLARITY; KIDNEY; ENDOCYTOSIS; ANTIGEN PRESENTATION; PHOSPHOLIPASES ID T-CELL ACTIVATION; HUMAN-ERYTHROCYTE ACETYLCHOLINESTERASE; PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA; DECAY-ACCELERATING FACTOR; EPITHELIAL-CELLS; HEYMANN NEPHRITIS; PHOSPHOLIPASE-C; CARBONIC-ANHYDRASE; GLYCOSYLPHOSPHATIDYLINOSITOL ANCHOR; APICAL DISTRIBUTION AB Many proteins of eukaryotic cells are anchored to membranes by covalent linkage to glycosyl-phosphatidylinositol (GPI). These proteins lack a transmembrane domain, have no cytoplasmic tail, and are, therefore, located exclusively on the extracellular side of the plasma membrane. GPI-anchored proteins form a diverse family of molecules that includes membrane-associated enzymes, adhesion molecules, activation antigens, differentiation markers, protozoan coat components, and other miscellaneous glycoproteins. In the kidney, several GPI-anchored proteins have been identified, including uromodulin (Tamm-Horsfall glycoprotein), carbonic anhydrase type IV, alkaline phosphatase, Thy-1, BP-3, aminopeptidase P, and dipeptidylpeptidase. GPI-anchored proteins can be released from membranes with specific phospholipases and can be recovered from the detergent-insoluble pellet after Triton X-114 treatment of membranes. All GPI-anchored proteins are initially synthesized with a transmembrane anchor, but after translocation across the membrane of the endoplasmic reticulum, the ecto-domain of the protein is cleaved and covalently linked to a preformed GPI anchor by a specific transamidase enzyme. Although it remains obscure why so many proteins are endowed with a GPI anchor, the presence of a GPI anchor does confer some functional characteristics to proteins: ( 1) it is a strong apical targeting signal in polarized epithelial cells; (2) GPI-anchored proteins do not cluster into clathrin-coated pits but instead are concentrated into specialized lipid domains in the membrane, including so-called smooth pinocytotic vesicles, or caveoli; (3) GPI-anchored proteins can act as activation antigens in the immune system; (4) when the GPI anchor is cleaved by PI-phospholipase C or PI-phospholipase D, second messengers for signal transduction may be generated; (5) the GPI anchor can modulate antigen presentation by major histocompatibility complex molecules. Finally, at least one human disease, paroxysmal nocturnal hemoglobinuria, is a result of defective GPI anchor addition to plasma membrane proteins. C1 MASSACHUSETTS GEN HOSP,RENAL UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,SURG SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CTR CANC,BOSTON,MA 02114. NR 89 TC 77 Z9 80 U1 3 U2 6 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD OCT PY 1992 VL 3 IS 4 BP 895 EP 906 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA JU826 UT WOS:A1992JU82600002 PM 1450366 ER PT J AU CANESSA, M ZERBINI, G LAFFEL, LMB AF CANESSA, M ZERBINI, G LAFFEL, LMB TI SODIUM ACTIVATION KINETICS OF RED-BLOOD-CELL NA+/LI+ COUNTERTRANSPORT IN DIABETES - METHODOLOGY AND CONTROVERSY SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article DE SODIUM-LITHIUM COUNTERTRANSPORT; INSULIN; DIABETES; RED BLOOD CELL; SODIUM KINETICS ID GLOMERULAR-FILTRATION RATE; DEPENDENT LITHIUM EFFLUX; ESSENTIAL-HYPERTENSION; HUMAN-ERYTHROCYTES; INTERINDIVIDUAL VARIATIONS; NONLINEAR-REGRESSION; NA+/H+ EXCHANGE; INSULIN; NEPHROPATHY; TRANSPORT AB Although many studies report an elevated V(max) of red blood cell Na/Li countertransport (CTT) activity in patients with insulin-dependent diabetes mellitus (IDDM) complicated by renal disease, divergent reports exist. This article reviews the technical issues and selection criteria that fuel this controversy. In addition, new studies from this laboratory indicate that insulin in vitro and in the nonfasted state modulate CTT activity and may contribute to the discrepant findings. Incubation of red blood cells from fasted controls with physiologic concentrations of insulin induced a twofold increase in the K(m) for external Na+. Similarly, Na+ activation kinetics of Li+ efflux showed saturation between 50 and 150 mM Na+ in fasted controls whereas saturation, postprandially, occurred between 100 and 150 mM Na+ as a result of an increase in K(m). To clarify the role of prandial status on the measurement of Na+/Li+ CTT activity in diabetes, Na+ activation kinetics were investigated in 34 nonfasting patients with IDDM. Li+ efflux was fully saturated between 80 and 150 mM Na+ in the normoalbuminuric subjects (N = 22), whereas saturation occurred between 150 and 280 mM Na+ in the patients with diabetic nephropathy (N = 14). Patients with nephropathy have higher values of K(m) for Na+ than do the patients free of renal complications (86 +/- 9.5 versus 41.3 +/- 3.4 mM Na+, respectively; P < 0.000012). The higher K(m) prevented complete saturation of Li+ efflux at 150 mM extracellular Na+ concentration and contributed to the underestimation of V(max) at 150 mM Na+ selectively in persons with renal complications. To ensure full saturation of Li+ efflux, a new assay was developed in which the extracellular Na+ concentration is increased isosmotically to 280 mM. Standardization of the assay for red blood cell Na+/Li+ CTT activity by this new method is recommended in order to accommodate changes in K(m), ensure saturation kinetics, and reduce technical difficulties inherent in other protocols. C1 HARVARD UNIV, SCH MED, DEPT MED, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED,JOSLIN DIABET CTR,DEPT PEDIAT,DIV RES, EPIDEMIOL SECT, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED,JOSLIN DIABET CTR,DEPT PEDIAT,DIV RES, GENET SECT, BOSTON, MA 02115 USA. RP CANESSA, M (reprint author), HARVARD UNIV, BRIGHAM & WOMENS HOSP, SCH MED, DIV ENDOCRINE HYPERTENS, 221 LONGWOOD AVE, BOSTON, MA 02115 USA. FU NHLBI NIH HHS [1R01 HL42120, 2RSS HL 35664]; NIDDK NIH HHS [1RO1 DK41526] NR 39 TC 37 Z9 37 U1 0 U2 0 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 EI 1533-3450 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD OCT PY 1992 VL 3 IS 4 SU S BP S41 EP S49 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA JU848 UT WOS:A1992JU84800007 PM 1457760 ER PT J AU INGELFINGER, JR JUNG, F TANG, SS AF INGELFINGER, JR JUNG, F TANG, SS TI MOLECULAR-BIOLOGY TECHNIQUES AND THEIR APPLICABILITY TO THE STUDY OF DIABETES AND HYPERTENSION - THE RENIN-ANGIOTENSIN SYSTEM AS AN EXAMPLE SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article; Proceedings Paper CT 3RD INTERNATIONAL SYMP ON HYPERTENSION ASSOCIATED WITH DIABETES MELLITUS : PAST AND FUTURE CY NOV 21-23, 1991 CL BOSTON, MA DE MESSENGER RNA; GENE EXPRESSION; RENIN-ANGIOTENSIN SYSTEM; DIABETES; REVIEW ID AORTIC SMOOTH-MUSCLE; MESSENGER-RNA; BLOOD-PRESSURE; CONVERTING ENZYME; SODIUM-REGULATION; GENE-EXPRESSION; TRANSGENIC MICE; MOUSE-TISSUES; II RECEPTOR; RAT RENIN AB Recently developed molecular biology techniques lend themselves to the study of both normal physiology and pathophysiology. This review discusses a number of such techniques and their applicability to the study of diabetes and hypertension with the renin-angiotensin system as an example. The demonstration of specific mRNA in tissue provides strong evidence that the protein for which it encodes is expressed there. The contribution of several methods to demonstrate mRNA expression including Northern analysis, slot blot analysis, solution hybridization, in situ hybridization, run-on assays, and polymerase chain reaction are discussed in the light of how these are used to study renin-angiotensin system mechanisms. Additionally, recent developments in the study of gene transfer and identification of genes are reviewed. RP INGELFINGER, JR (reprint author), MASSACHUSETTS GEN HOSP,PEDIAT RENAL RES LAB,BARTLETT 4X,ROOM 411,BOSTON,MA 02114, USA. FU NHLBI NIH HHS [HL-40210] NR 69 TC 3 Z9 3 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD OCT PY 1992 VL 3 IS 4 SU S BP S18 EP S26 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA JU848 UT WOS:A1992JU84800004 PM 1281007 ER PT J AU KAHN, CR SAAD, MJA AF KAHN, CR SAAD, MJA TI ALTERATIONS IN INSULIN-RECEPTOR AND SUBSTRATE PHOSPHORYLATION IN HYPERTENSIVE RATS SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article; Proceedings Paper CT 3RD INTERNATIONAL SYMP ON HYPERTENSION ASSOCIATED WITH DIABETES MELLITUS : PAST AND FUTURE CY NOV 21-23, 1991 CL BOSTON, MA DE INSULIN RECEPTOR KINASE; INSULIN RESISTANCE; INSULIN RECEPTOR SUBSTRATE; HYPERTENSION; SPONTANEOUSLY HYPERTENSIVE RAT ID TYROSINE KINASE-ACTIVITY; SYMPATHETIC NERVOUS-SYSTEM; STIMULATED GLUCOSE-UPTAKE; BETA-SUBUNIT; 3T3-L1 ADIPOCYTES; P21RAS ACTIVATION; PLASMA-MEMBRANE; PHOSPHOLIPASE-C; CELL-MEMBRANES; BINDING REGION AB Insulin stimulates tyrosine phosphorylation of the insulin receptor and of an endogenous substrate of approximately 185 kd (insulin receptor substrate 1 or IRS-1) in most cell types. Tyrosine phosphorylation of insulin receptor and of IRS-1 have been implicated in insulin signal transmission based on studies with insulin receptor mutants. In the study presented here, the levels and phosphorylation state of the insulin receptor and IRS-1 in liver and muscle after insulin stimulation in vivo have been examined in spontaneously hypertensive rats (SHR) by immunoblotting with antipeptide antibodies to insulin receptor and IRS-1 and antiphosphotyrosine antibodies. It was found that the levels of insulin receptor and IRS-1 protein in liver and muscle are similar in controls (Wistar-Kyoto rats) and SHR. By contrast, there is a decrease in autophosphorylation in the liver and muscle of SHR and a parallel decrease in phosphorylation of IRS-1. These data indicate that reduced insulin receptor kinase activity and reduced substrate phosphorylation may play an important role in the impaired insulin action in the hypertensive rat. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP KAHN, CR (reprint author), BRIGHAM & WOMENS HOSP,JOSLIN DIABET CTR,DEPT MED,DIV RES,1 JOSLIN PL,BOSTON,MA 02115, USA. FU NIDDK NIH HHS [DK 36836, DK 33201] NR 55 TC 19 Z9 19 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD OCT PY 1992 VL 3 IS 4 SU S BP S69 EP S77 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA JU848 UT WOS:A1992JU84800011 PM 1457763 ER PT J AU KROLEWSKI, AS DORIA, A MAGRE, J WARRAM, JH HOUSMAN, D AF KROLEWSKI, AS DORIA, A MAGRE, J WARRAM, JH HOUSMAN, D TI MOLECULAR GENETIC APPROACHES TO THE IDENTIFICATION OF GENES INVOLVED IN THE DEVELOPMENT OF NEPHROPATHY IN INSULIN-DEPENDENT DIABETES-MELLITUS SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article; Proceedings Paper CT 3RD INTERNATIONAL SYMP ON HYPERTENSION ASSOCIATED WITH DIABETES MELLITUS : PAST AND FUTURE CY NOV 21-23, 1991 CL BOSTON, MA DE NEPHROPATHY IN INSULIN-DEPENDENT DIABETES-MELLITUS; GENETICS; METHODS OF MOLECULAR GENETICS; ANGIOTENSINOGEN GENE; INSULIN RECEPTOR GENE ID FRAGMENT-LENGTH-POLYMORPHISMS; POLYMERASE CHAIN-REACTION; CONVERTING ENZYME GENE; PROTEIN KINASE-C; RENIN GENE; ESSENTIAL-HYPERTENSION; ANGIOTENSINOGEN GENE; DNA POLYMORPHISMS; KIDNEY-DISEASE; BLOOD-PRESSURE AB Genetic factors contribute significantly to the development of diabetic nephropathy in patients with insulin-dependent diabetes mellitus. This report discusses some models of diabetic nephropathy that incorporate genetic susceptibility and presents strategies for identifying the responsible genes. To identify variation at a locus, newly developed methods are discussed that employ denaturing gradient gel electrophoresis to study sequence differences in both polymerase chain reaction-amplified DNA fragments and genomic DNA. These techniques are illustrated with studies of the angiotensinogen gene and the insulin receptor gene. In preliminary data from a comparison between individuals with and without diabetic nephropathy, no DNA sequence difference in that part of the angiotensinogen gene that codes for angiotensin I was found. However, with a probe corresponding to exons 7 and 8 of the insulin receptor gene and denaturing gradient gel electrophoresis of RsaI digestions of genomic DNA, different distributions of a DNA polymorphism were found in patients with fast as compared with slowly progressing nephropathy. The interpretation of this finding and the need for further studies are discussed. In conclusion, the advent of methods of molecular genetics makes possible studies on genetic determinants of diabetic nephropathy. However, more clinical and epidemiologic data are needed to find out how many genes are involved and how they interact with exposure to diabetes. Foremost, DNA from families with two or more siblings with diabetic nephropathy must be collected to permit the necessary genetic studies. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. MIT,CTR CANC RES,CAMBRIDGE,MA 02139. RP KROLEWSKI, AS (reprint author), HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,DIV RES,1 JOSLIN PL,BOSTON,MA 02115, USA. RI MAGRE, Jocelyne/D-4788-2015 FU PHS HHS [R01 41526] NR 57 TC 35 Z9 35 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD OCT PY 1992 VL 3 IS 4 SU S BP S9 EP S17 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA JU848 UT WOS:A1992JU84800003 PM 1457765 ER PT J AU KROLEWSKI, AS AF KROLEWSKI, AS TI HYPERTENSION ASSOCIATED WITH DIABETES-MELLITUS - PAST AND FUTURE SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Editorial Material ID OBESITY; NEPHROPATHY; INSULIN; LINK C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. RP KROLEWSKI, AS (reprint author), HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02115, USA. NR 9 TC 1 Z9 1 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD OCT PY 1992 VL 3 IS 4 SU S BP S1 EP S1 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA JU848 UT WOS:A1992JU84800001 PM 1457751 ER PT J AU SIEGEL, JE KROLEWSKI, AS WARRAM, JH WEINSTEIN, MC AF SIEGEL, JE KROLEWSKI, AS WARRAM, JH WEINSTEIN, MC TI COST-EFFECTIVENESS OF SCREENING AND EARLY TREATMENT OF NEPHROPATHY IN PATIENTS WITH INSULIN-DEPENDENT DIABETES-MELLITUS SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article; Proceedings Paper CT 3RD INTERNATIONAL SYMP ON HYPERTENSION ASSOCIATED WITH DIABETES MELLITUS : PAST AND FUTURE CY NOV 21-23, 1991 CL BOSTON, MA DE COST-EFFECTIVENESS; NEPHROPATHY; INSULIN-DEPENDENT DIABETES-MELLITUS; ANTIHYPERTENSIVE TREATMENT ID CORONARY HEART-DISEASE; MICROALBUMINURIA; PREVENTION; PREVALENCE; POPULATION; ECONOMICS; HEALTH; GUIDE AB Studies have demonstrated that "antihypertensive" treatment with angiotensin-converting enzyme inhibitors (ACEI) may retard the progress of nephropathy in patients with insulin-dependent diabetes mellitus. To obtain an indication of the potential effect of ACEI treatment and as a guide to future research, the effects of screening and early ACEI treatment programs were estimated using cost-effectiveness models. The preliminary analysis suggests that the early treatment of insulin-dependent diabetes mellitus patients with ACEI is likely to be a very cost-effective use of health care resources. The cost-effectiveness ratio for screening and treatment at the stage of microalbuminuria ($7,900 to $16,500 per year of life saved) compares favorably with those of other medical life-saving interventions. Less-aggressive programs (screening followed by treatment at the stage of proteinuria) would improve life expectancy to a lesser extent but could save net health care costs as well as years of life. Although more exact and comprehensive cost-effectiveness analysis must await clinical trials, these illustrative results demonstrate the range of cost-effectiveness that can be expected from these programs and identify data needed for more decisive policy conclusions. C1 JOSLIN DIABET CTR,EPIDEMIOL & GENET SECT,BOSTON,MA. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP SIEGEL, JE (reprint author), HARVARD UNIV,SCH PUBL HLTH,DEPT HLTH POLICY & MANAGEMENT,677 HUNTINGTON AVE,BOSTON,MA 02115, USA. FU NIDDK NIH HHS [R01 DK 41526] NR 23 TC 60 Z9 60 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD OCT PY 1992 VL 3 IS 4 SU S BP S111 EP S119 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA JU848 UT WOS:A1992JU84800017 PM 1457753 ER PT J AU WARRAM, JH LAFFEL, LMB GANDA, OP CHRISTLIEB, AR AF WARRAM, JH LAFFEL, LMB GANDA, OP CHRISTLIEB, AR TI CORONARY-ARTERY DISEASE IS THE MAJOR DETERMINANT OF EXCESS MORTALITY IN PATIENTS WITH INSULIN-DEPENDENT DIABETES-MELLITUS AND PERSISTENT PROTEINURIA SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article; Proceedings Paper CT 3RD INTERNATIONAL SYMP ON HYPERTENSION ASSOCIATED WITH DIABETES MELLITUS : PAST AND FUTURE CY NOV 21-23, 1991 CL BOSTON, MA DE INSULIN-DEPENDENT DIABETES; PERSISTENT PROTEINURIA; CORONARY ARTERY DISEASE; HYPERTENSION; SERUM CHOLESTEROL ID MYOCARDIAL-INFARCTION; BLOOD-PRESSURE; NEPHROPATHY; SURVIVAL; ONSET AB The goal of this review was to assess the magnitude of coronary artery disease (CAD) mortality and its determinants in insulin-dependent diabetes mellitus (IDDM) patients with persistent proteinuria. By reanalyzing data from two previously published studies of patients with nephropathy, it was found that these patients had extremely high CAD mortality rates in comparison with IDDM patients without proteinuria, but only after the age of 35 yr. In addition, the risk of CAD death was associated with high serum cholesterol levels but was unrelated to systemic blood pressure, smoking habits, and obesity. Further studies of the determinants of CAD in patients with IDDM and proteinuria are urgently needed. Except for efforts to lower serum cholesterol, it is not known whether any other measure can be undertaken to reduce the extremely high mortality due to CAD that afflicts IDDM patients with persistent proteinuria, in particular those patients whose renal failure might have been "successfully" postponed by antihypertensive therapy. C1 JOSLIN DIABET CTR,DIV CLIN,BOSTON,MA. RP WARRAM, JH (reprint author), JOSLIN DIABET CTR,DIV RES,1 JOSLIN PL,BOSTON,MA 02215, USA. NR 22 TC 25 Z9 25 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD OCT PY 1992 VL 3 IS 4 SU S BP S104 EP S110 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA JU848 UT WOS:A1992JU84800016 PM 1457752 ER PT J AU DRUKER, BJ SIBERT, L ROBERTS, TM AF DRUKER, BJ SIBERT, L ROBERTS, TM TI POLYOMAVIRUS MIDDLE T-ANTIGEN NPTY MUTANTS SO JOURNAL OF VIROLOGY LA English DT Article ID PHOSPHATIDYLINOSITOL KINASE-ACTIVITY; RECOMBINANT RETROVIRUSES; MURINE RETROVIRUS; VIRUS GENOME; RAT-CELLS; TRANSFORMATION; PROTEIN; GENE; PP60C-SRC; PRODUCT AB A polyomavirus middle T-antigen (MTAg) mutant containing a substitution of Leu for Pro at amino acid 248 has previously been described as completely transformation defective (B. J. Druker, L. Ling, B. Cohen, T. M. Roberts, and B. S. Schaffhausen, J. Virol. 64:4454-4461, 1990). This mutant had no alterations in associated proteins or associated kinase activities compared with wild-type MTAg. Pro-248 lies in a tetrameric sequence, NPTY, which is reminiscent of the so-called NPXY sequence in the low-density-lipoprotein receptor. In the low-density-lipoprotein receptor, mutations in the NPXY motif but not in the surrounding amino acids abolish receptor function, apparently by decreasing receptor internalization (W. Chen, J. L. Goldstein, and M. S. Brown, J. Biol. Chem. 265:3116-3123, 1990). To determine whether this sequence represents a functional motif in MTAg as well, a series of single amino acid substitutions was constructed in this region of MTAg. All of the mutations of N, P, T, or Y, including the relatively conservative substitution of Ser for Thr at amino acid 249, resulted in a transformation-defective MTAg, whereas mutations outside of this sequence allowed mutants to retain near-wild-type transformation capabilities. Transformation-defective mutants with mutations in the NPTY region behaved similarly to the mutant with the original Pro-248-to-Leu-248 mutation when assayed for associated proteins and activities in vitro; that is, they retained a full complement of wild-type activities and associated proteins. Further, insertion of the tetrameric sequence NPTY downstream of the mutated motif restored transforming abilities to these mutants. Thus, the tetrameric sequence NPTY in MTAg appears to represent a well-defined functional motif of MTAg. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP DRUKER, BJ (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELLULAR & MOLEC BIOL,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA-30002, KO8 CA-01422] NR 47 TC 27 Z9 28 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 OCT PY 1992 VL 66 IS 10 BP 5770 EP 5776 PG 7 WC Virology SC Virology GA JN267 UT WOS:A1992JN26700008 PM 1326642 ER PT J AU BERGERON, L SODROSKI, J AF BERGERON, L SODROSKI, J TI DISSOCIATION OF UNINTEGRATED VIRAL-DNA ACCUMULATION FROM SINGLE-CELL LYSIS INDUCED BY HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN PERIPHERAL-BLOOD; HTLV-III/LAV ENVELOPE; AVIAN-LEUKOSIS VIRUS; SOLUBLE CD4; T-CELL; SYNCYTIUM FORMATION; INFECTED-CELLS; AIDS PATIENTS; HIV-1; GLYCOPROTEIN AB Acute cytopathic retroviral infections are accompanied by the accumulation, due to superinfection, of large amounts of unintegrated viral DNA in the cells. The cytopathic effects of human immunodeficiency virus type 1 (HIV-1) infection are specific for cells that express the CD4 viral receptor and consist of syncytium formation and single-cell lysis. Here we investigated the relationship between superinfection and single-cell lysis by HIV-1. Antiviral agents were added to C8166 or Jurkat lymphocytes after HIV-1 infection had occurred. Treatment with azidothymidine or a neutralizing anti-gp120 monoclonal antibody reduced or eliminated, respectively, the formation of unintegrated viral DNA but did not inhibit single-cell killing. Furthermore, in the infected Jurkat cells, the levels of unintegrated viral DNA peaked several days before significant single-cell lysis was observed. Essentially complete superinfection resistance was established before the occurrence of single-cell killing. These results demonstrate that single-cell lysis by HIV-1 can be dissociated from superinfection and unintegrated viral DNA accumulation. These results also indicate that single-cell killing may involve envelope glycoprotein-receptor interactions not accessible to the exterior-of the cell. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HUMAN RETROVIROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,BOSTON,MA 02115. FU NIAID NIH HHS [AI 24755] NR 70 TC 47 Z9 47 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 1992 VL 66 IS 10 BP 5777 EP 5787 PG 11 WC Virology SC Virology GA JN267 UT WOS:A1992JN26700009 PM 1527842 ER PT J AU HAMMOND, TG MAJEWSKI, R AF HAMMOND, TG MAJEWSKI, R TI ANALYSIS AND ISOLATION OF RENAL TUBULAR CELLS BY FLOW-CYTOMETRY SO KIDNEY INTERNATIONAL LA English DT Note ID KIDNEY PROXIMAL TUBULE; BRUSH-BORDER MEMBRANE; MONOCLONAL-ANTIBODIES; ALKALINE-PHOSPHATASE; NEPHRON; LOCALIZATION; CORTEX; KALLIKREIN; CULTURE; ENZYMES AB The cells of the renal cortex have rich heterogeneity of structure and function. Flow cytometry, the technique of rapid laser-based single cell analysis, can give information about cellular mixtures not obtainable by any other means. We examined a variety of fluorescent markers to identify populations of renal cells by flow cytometry. Cellular digests of rat cortex were fluorescently stained with either enzymatic activity probes, or polyclonal antibodies. Fluorescent staining for the proximal marker gamma-glutamyl-transpeptidase (tau-GT) was an order of magnitude brighter than autofluorescence, and stained 71 +/- 11% of the cells. Second, we colocalized enzymatic and antibody markers. There was tight colocalization of tau-GT enzyme activity, detected with fluorogenic substrates, with specific surface binding of tau-GT antibodies. Third, populations of fluorescently labelled cells can be rapidly isolated by flow cytometry sorting. Flow cytometry sorting isolated 10(7) cells positive for the proximal tubular marker tau-GT in a little under one hour. The sorted cells were viable with 99 +/- 2% trypan blue exclusion (N = 8). Sodium-dependent phloridzin-inhibitable glucose uptake was present in sorted cells, with greater uptake/mg protein than in unsorted controls. The sorted cells grew in culture as a monolayer of tightly adherent cuboidal cells. Hence, flow cytometry allows us to quantitate the heterogeneity in mixed renal cellular digests. Flow cytometry allows us to rapidly isolate millions of cells according to fluorescently tagged markers. The isolated cells are viable, retain sodium-dependent transport properties, and grow in culture. C1 UNIV WISCONSIN,SCH MED,DEPT MED,CELL BIOL LAB,MADISON,WI 53792. WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI 53705. RP HAMMOND, TG (reprint author), UNIV WISCONSIN,SCH MED,CTR CLIN SCI H4510,DEPT MED,NEPHROL SECT,600 HIGHLAND AVE,MADISON,WI 53792, USA. NR 31 TC 10 Z9 10 U1 1 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD OCT PY 1992 VL 42 IS 4 BP 997 EP 1005 DI 10.1038/ki.1992.379 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA JN529 UT WOS:A1992JN52900023 PM 1360553 ER PT J AU GUNNING, ME BRENNER, BM AF GUNNING, ME BRENNER, BM TI NATRIURETIC PEPTIDES AND THE KIDNEY - CURRENT CONCEPTS SO KIDNEY INTERNATIONAL LA English DT Article ID MEDULLARY COLLECTING DUCT; CONGESTIVE-HEART-FAILURE; INDUCED CENTRAL HYPERVOLEMIA; ATRIOPEPTIN-LIKE PROTEIN; GUANYLATE-CYCLASE; PORCINE BRAIN; HEMODYNAMIC-RESPONSES; ATRIAL PEPTIDES; CARDIAC HORMONE; NORMAL HUMANS C1 HARVARD UNIV,SCH MED,DEPT MED,DIV RENAL,JOSLIN DIABET CTR,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CTR STUDY KIDNEY DIS,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT MED,DIV RENAL,BOSTON,MA 02115. RP GUNNING, ME (reprint author), HARVARD UNIV,NEW ENGLAND DEACONESS HOSP,SCH MED,DEPT MED,DIV RENAL,LMOB 9D,185 PILGRIM ST,BOSTON,MA 02215, USA. NR 80 TC 19 Z9 21 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD OCT PY 1992 VL 42 SU 38 BP S127 EP S133 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA JN707 UT WOS:A1992JN70700018 PM 1405363 ER PT J AU NADOL, JB CHIONG, CM OJEMANN, RG MCKENNA, MJ MARTUZA, RL MONTGOMERY, WW LEVINE, RA RONNER, SF GLYNN, RJ AF NADOL, JB CHIONG, CM OJEMANN, RG MCKENNA, MJ MARTUZA, RL MONTGOMERY, WW LEVINE, RA RONNER, SF GLYNN, RJ TI PRESERVATION OF HEARING AND FACIAL-NERVE FUNCTION IN RESECTION OF ACOUSTIC NEUROMA SO LARYNGOSCOPE LA English DT Article ID AUDITORY EVOKED-POTENTIALS; TUMOR SURGERY; REMOVAL; ANGLE; SCHWANNOMAS AB The surgical results in 78 recent cases of total removal of unilateral acoustic neuroma in which an attempt was made to preserve cochlear function have been added to the authors' previous series of 66 cases to evaluate the factors influencing the ability to preserve useful hearing. Useful hearing was defined by speech reception threshold no poorer than 70 dB and a discrimination score of at least 15%. Analysis using a logistic regression model showed that certain pre-operative clinical parameters such as tumor size, speech discrimination score, and gender were significantly correlated with hearing outcome. Favorable outcome was significantly correlated with smaller tumor size, higher preoperative speech discrimination score, and male sex. From this data, an explicit formula was devised for predicting hearing outcome for an individual patient. In four cases with useful hearing preserved, there was improvement of greater than 15 percentage points in speech discrimination scores. While preoperative auditory brainstem responses were not predictive of hearing preservation, monitoring of intraoperative auditory evoked potentials was predictive of hearing outcome in selected cases. Specifically, when wave V was unchanged at the end of the operation, even if it may have been transiently lost during surgery, useful hearing was invariably preserved. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. EATON PEABODY LAB AUDITORY PHYSIOL,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,NEUROSURG SERV,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROL,BOSTON,MA 02114. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. NR 24 TC 154 Z9 156 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD OCT PY 1992 VL 102 IS 10 BP 1153 EP 1158 DI 10.1288/00005537-199210000-00010 PG 6 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA JT185 UT WOS:A1992JT18500010 PM 1405966 ER PT J AU VOGLER, WR HARRINGTON, DP WINTON, EF LAZARUS, HM BENNETT, JM CASSILETH, PA OKEN, MM AF VOGLER, WR HARRINGTON, DP WINTON, EF LAZARUS, HM BENNETT, JM CASSILETH, PA OKEN, MM TI PHASE-II CLINICAL-TRIAL OF CARBOPLATIN IN RELAPSED AND REFRACTORY LEUKEMIA SO LEUKEMIA LA English DT Article ID BONE-MARROW SUPPORT; IFOSFAMIDE; INFUSION; TOXICITY AB Carboplatin is a second-generation platinum complex drug which has demonstrated activity against a variety of neoplasms including acute leukemia, particularly when given by continuous intravenous (i.v.) infusion. Adults with acute myelogenous leukemia (AML) or acute lymphoblastic leukemia (ALL), either refractory or in first or second relapse, were given a continuous i.v. infusion of carboplatin at a dose of 315 mg/m2 daily for 5 days. A second course was given if the bone marrow al day 14 showed persistent leukemia. If the marrow was hypoplastic, treatment was delayed until marrow recovery was documented. Those with residual leukemia were given a second course. Those achieving complete remission (CR) were given an additional course as consolidation. Of the 46 eligible patients entered (36 AML and 10 ALL) eight achieved CR (17%) of which 6 were AML and 2 ALL. Of nine primary refractory patients, two achieved CR, one AML and one ALL. Excluding the inevaluable patients (protocol violations, patient refused further therapy, early deaths prior to day 14, the CR rate was eight of 28 (29%). All except two CRs required two courses of induction. The non-hematologic toxicity was minimal except for renal and auditory toxicity. Renal toxicity greater than grade 2 was seen in 17 patients and was associated with concomitant use of nephrotoxic antibiotics. In two patients, renal failure was a major factor in the cause of death. Ototoxicity was observed in 11 patients, but was grade 3 in only three. There were 18 deaths during the study. Fourteen died of infection, two died of infection and hemorrhage, one died of hemorrhage while aplastic, and one died of other causes. This trial indicates that carboplatin is an active agent in acute leukemia and warrants further investigation. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. CASE WESTERN RESERVE UNIV,CLEVELAND,OH 44106. UNIV ROCHESTER,CTR CANC,ROCHESTER,NY 14627. UNIV PENN,CTR CANC,PHILADELPHIA,PA 19104. NORTHWESTERN UNIV,MED CTR,CHICAGO,IL 60611. RP VOGLER, WR (reprint author), EMORY UNIV,POB AE,ATLANTA,GA 30322, USA. FU NCI NIH HHS [CA 21115, CA 14548, CA 23318] NR 10 TC 23 Z9 23 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0887-6924 J9 LEUKEMIA JI Leukemia PD OCT PY 1992 VL 6 IS 10 BP 1072 EP 1075 PG 4 WC Oncology; Hematology SC Oncology; Hematology GA JV085 UT WOS:A1992JV08500015 PM 1405761 ER PT J AU BARUT, BA ZON, LI COCHRAN, MK PAUL, SR CHAUHAN, D MOHRBACHER, A FINGEROTH, J ANDERSON, KC AF BARUT, BA ZON, LI COCHRAN, MK PAUL, SR CHAUHAN, D MOHRBACHER, A FINGEROTH, J ANDERSON, KC TI ROLE OF INTERLEUKIN-6 IN THE GROWTH OF MYELOMA-DERIVED CELL-LINES SO LEUKEMIA RESEARCH LA English DT Article DE INTERLEUKIN-6; MULTIPLE MYELOMA; EPSTEIN-BARR VIRUS; INTERLEUKIN-6 RECEPTOR; MYELOMA LINES; LEUKEMIA ID HUMAN MULTIPLE-MYELOMA; STIMULATORY FACTOR-II; BONE-MARROW; MONOCLONAL-ANTIBODY; PLASMA-CELLS; B-CELLS; IDIOTYPE-BEARING; PERIPHERAL-BLOOD; LYMPHOID-CELLS; EXPRESSION AB The role of interleukin 6 (IL-6) in the growth of five multiple myeloma-derived cell lines was characterized. The U266 and RPMI 8226 cell lines demonstrated increased DNA synthesis when cultured with exogenous IL-6, expressed IL-6 cell surface receptors (IL-6Rs) and expressed mRNA for IL-6R. However, these cells did not secrete detectable IL-6 protein, and a neutralizing antibody to IL-6 did not inhibit their growth. Three other myeloma-derived cell lines ARH-77, IM-9 and HS-Sultan did not respond to exogenous IL-6, secrete IL-6 or express cell surface IL-6Rs. The IL-6 responsive cell lines bore late B-cell surface antigens (Ags), CD38 and PCA-1, whereas those lines which were non-IL-6 responsive strongly expressed B1 (CD20) and B4 (CD19) Ags, representing earlier stages in B-cell differentiation. Finally, the two IL-6 responsive cell lines did not express Epstein-Barr virus (EBV) proteins; in contrast, EBV encoded proteins typically expressed during latency could be detected in the three non-IL-6 responsive lines, confirming infection with virus. These studies clarify the heterogeneity observed in the myeloma cell line phenotype and biology and suggest that the U266 and RPMI 8226 cell lines, which express IL-6 cell surface receptors and are IL-6 responsive, may be useful for further study of IL-6 signal transduction in and related IL-6 mediated growth of myeloma in vivo. In contrast, those cell lines which are IL-6-independent provide a model for further study of EBV transformation and IL-6-dependent growth mechanisms in malignancy. 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 INFECT DIS,BOSTON,MA 02115. CHILDRENS HOSP MED CTR,DEPT HEMATOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED & PEDIAT,BOSTON,MA 02115. FU NCI NIH HHS [CA50947]; NHLBI NIH HHS [HL02347] NR 50 TC 51 Z9 51 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 OCT PY 1992 VL 16 IS 10 BP 951 EP 959 DI 10.1016/0145-2126(92)90073-G PG 9 WC Oncology; Hematology SC Oncology; Hematology GA JT916 UT WOS:A1992JT91600001 PM 1405708 ER PT J AU CURWIN, J JANG, IK FUSTER, V AF CURWIN, J JANG, IK FUSTER, V TI EXPANDED USE OF THROMBOLYTIC THERAPY SO MAYO CLINIC PROCEEDINGS LA English DT Editorial Material ID TISSUE PLASMINOGEN-ACTIVATOR; MYOCARDIAL-INFARCTION; VASCULITIS; BLANCHE C1 MASSACHUSETTS GEN HOSP,CARDIAC UNIT,BULFINCH 1,32 FRUIT ST,BOSTON,MA 02114. RI Fuster, Valentin/H-4319-2015 OI Fuster, Valentin/0000-0002-9043-9986 NR 14 TC 1 Z9 1 U1 0 U2 1 PU MAYO CLINIC PROCEEDINGS PI ROCHESTER PA 660 SIEBENS BLDG MAYO CLINIC, ROCHESTER, MN 55905 SN 0025-6196 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD OCT PY 1992 VL 67 IS 10 BP 1004 EP 1005 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA JQ841 UT WOS:A1992JQ84100010 PM 1434847 ER PT J AU WILLIAMS, GR HARNEY, JW MOORE, DD LARSEN, PR BRENT, GA AF WILLIAMS, GR HARNEY, JW MOORE, DD LARSEN, PR BRENT, GA TI DIFFERENTIAL CAPACITY OF WILD-TYPE PROMOTER ELEMENTS FOR BINDING AND TRANSACTIVATION BY RETINOIC ACID AND THYROID-HORMONE RECEPTORS SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID PHOSPHOENOLPYRUVATE CARBOXYKINASE GENE; 5' FLANKING REGION; GROWTH-HORMONE; RESPONSE ELEMENT; NEGATIVE REGULATION; T3 RECEPTOR; DNA-BINDING; RAT; EXPRESSION; TRANSCRIPTION AB Retinoic acid receptor (RAR) and thyroid hormone receptor (T3R) are structurally similar and can bind as homodimers or T3R-RAR heterodimers to a single synthetic DNA response element. The interaction of these two types of receptors with wild type elements, however, has not been systematically investigated. Promoter elements from genes regulated by retinoic acid (RA) or thyroid hormone (T3) were tested for response to T3 and RA in transient transfections in both JEG and COS cells. The elements were classified as primarily responsive to RA or to T3 or responsive to both ligands. Binding of highly purified RARalpha and T3Ralpha to the various elements was assessed using the gel shift assay. Those elements predominantly responsive to one ligand showed preferential binding to the appropriate receptor. A series of point mutations were introduced into the rat GH T3 response element to further define sequence requirements for response to both RA and T3. Down-mutations in any of the three hexamers (previously demonstrated to be required for full response to T3 and full binding of T3R) also decreased RA induction and RAR binding. However, only one of two sets of up-mutations for T3 response also increased RA induction, demonstrating differences in hexamer preference between RAR and T3R. Variation in spacing of the three hexamers did not influence RA vs. T3 induction or RAR vs. T3R binding according to the predictions of a simple hexamer spacing model. There was a strong correlation between the extent of T3R dimer binding and strength of T3 induction for a subset of elements studied in JEG cells (r = 0.97, P < 0.01) and a weaker but significant correlation in COS cells (r = 0.65, P < 0.05)). In contrast, RAR dimer binding by the wild type elements did not quantitatively correlate with RA induction in either JEG (r = 0.13, P > 0.05) or COS cells (r = 0.21, P > 0.05). These results suggests that RAR interacts with a heterodimer partner(s) which influences binding site specificity, whereas T3R heterodimer partner(s) is less likely to alter binding site recognition. The observed difference in COS and JEG cells as well as the weak T3R binding-function relationship of the malic enzyme element, however, suggest that the influence of T3R heterodimer partner(s) on binding site specificity is likely to vary with cell type and the specific element tested. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DIV THYROID,75 FRANCIS ST,BOSTON,MA 02115. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MOLEC BIOL,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. FU NIDDK NIH HHS [DK-36256, DK-44128] NR 52 TC 68 Z9 68 U1 0 U2 1 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD OCT PY 1992 VL 6 IS 10 BP 1527 EP 1537 DI 10.1210/me.6.10.1527 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JV676 UT WOS:A1992JV67600001 PM 1333048 ER PT J AU RIVKEES, SA REPPERT, SM AF RIVKEES, SA REPPERT, SM TI RFL9 ENCODES AN A2B-ADENOSINE RECEPTOR SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID ADENOSINE RECEPTOR; MOLECULAR-CLONING; HUMAN-FIBROBLASTS; CYCLIC-AMP; BRAIN; ADENOSINE-A1-RECEPTORS; ACCUMULATION; A2-RECEPTORS; SUBCLASSES; CELLS AB We recently reported the cloning of a cDNA (designated RFL9) that encodes a novel A2-adenosine receptor subtype. We now fully characterize the pharmacological properties of RFL9 in stably transfected CHO cells by examining cAMP responses to drug treatments. The pharmacological profile of cAMP responses in RFL9-transfected cells was similar to that expected for A2b-adenosine receptors and distinct from that of CHO cells transfected with the A2a-adenosine receptor. When RFL9-transfected cells were compared with VA 13 fibroblasts, the human cell line in which endogenous A2b-adenosine receptors were originally characterized, the dose-response curves of cAMP responses to drug treatments were highly correlated. Northern blot analysis of RNA prepared from VA 13 fibroblasts revealed specific hybridizing transcripts when probed for RFL9, but no hybridizing signal for A2a-adenosine receptor mRNA. Using degenerate oligonucleotide primers designed to detect adenosine receptors by the polymerase chain reaction, only one cDNA fragment homologous to the rat A2b-adenosine receptor was isolated from VA 13 cells. These results strongly suggest that RFL9 encodes the proposed A2b-adenosine receptor subtype. The identification of the cDNA for an A2b-adenosine receptor will allow more rigorous characterization of its anatomical distribution and functional properties. C1 MASSACHUSETTS GEN HOSP, DEV CHRONOBIOL LAB, BOSTON, MA 02114 USA. HARVARD UNIV, BOSTON, MA 02114 USA. FU NIDDK NIH HHS [DK-42125]; PHS HHS [K08D00924] NR 31 TC 89 Z9 91 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 OCT PY 1992 VL 6 IS 10 BP 1598 EP 1604 DI 10.1210/me.6.10.1598 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JV676 UT WOS:A1992JV67600007 PM 1333049 ER PT J AU ANTHONY, J NEAR, R WONG, SL IIDA, E ERNST, E WITTEKIND, M HABER, E NG, SC AF ANTHONY, J NEAR, R WONG, SL IIDA, E ERNST, E WITTEKIND, M HABER, E NG, SC TI PRODUCTION OF STABLE ANTI-DIGOXIN-FV IN ESCHERICHIA-COLI SO MOLECULAR IMMUNOLOGY LA English DT Article ID SINGLE-CHAIN FV; FUSION PROTEIN; BINDING; FRAGMENT; POLYMERASE; EXPRESSION; SEQUENCE; SITES; HEAVY; GENES AB We have created a bacterial expression-export system and have used it to express (14 mg l-1) the variable region fragment (Fv) of an anti-digoxin antibody (26-10) in Escherichia coli. The expression-export plasmid contains a T7 promoter and the E. coli signal sequences ompA [Movva et al., J. biol. Chem. 255,27-29 (1980)] and phoA [Inouye et al., J. Bacteriol. 149, 434-439 (1982)] fused to heavy chain (V(H)) and light chain (V(L)) variable region sequences to generate an artificial cistron. The 26-10 Fv protein made using this system was soluble, unlike many other expression systems which produce insoluble proteins in the form of inclusion bodies. The 26-10 V(H) and V(L) proteins were cleaved at their mature N-termini and exported into the bacterial periplasm where they could be easily extracted and affinity purified on ouabain-Sepharose. 26-10 Fv bound to digoxin with similar affinity and specificity as the whole 26-10 antibody (K(a) for Fv, 1.3 x 10(9) M-1, K(a) for IgG, 7 x 10(9) M-1). 26-10 Fv appears to be remarkably stable in comparison with other Fv fragments. The half-life for chain dissociation of 26-10 Fv was 48 hr compared to the reported 1.5 hr half-life of McPC603 Fv. We present the proton NMR spectra of the 26-10 Fv as preliminary evidence that this expression-export system can be used to facilitate the analysis of the solution structure of 26-10 Fv by NMR. C1 BRISTOL MYERS SQUIBB PHARMACEUT RES INST,DEPT MOLEC BIOL MACROMOLEC,POB 4000,PRINCETON,NJ 08543. BRISTOL MYERS SQUIBB PHARMACEUT RES INST,DEPT MACROMOLEC PROT NMR,PRINCETON,NJ 08543. MASSACHUSETTS GEN HOSP,CELLULAR & MOLEC BIOL RES LAB,BOSTON,MA 02114. UNIV CALGARY,DEPT BIOL SCI,CALGARY T2N 1N4,ALBERTA,CANADA. HARVARD UNIV,SCH PUBL HLTH,CAMBRIDGE,MA 02138. FU NHLBI NIH HHS [HL-19259] NR 31 TC 36 Z9 36 U1 0 U2 1 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 OCT PY 1992 VL 29 IS 10 BP 1237 EP 1247 DI 10.1016/0161-5890(92)90060-B PG 11 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA JM628 UT WOS:A1992JM62800010 PM 1528194 ER PT J AU SANDERSON, IR OUELLETTE, AJ CARTER, EA HARMATZ, PR AF SANDERSON, IR OUELLETTE, AJ CARTER, EA HARMATZ, PR TI ONTOGENY OF CLASS-II MHC MESSENGER-RNA IN THE MOUSE SMALL INTESTINAL EPITHELIUM SO MOLECULAR IMMUNOLOGY LA English DT Article ID HLA-DR MOLECULES; INVARIANT CHAIN; IA-ANTIGEN; BETA-CHAIN; CELLS; GENE; EXPRESSION; ASSOCIATION; MACROPHAGE; SEQUENCE AB MHC Class II (Ia) and invariant chain cooperate in the presentation of exogenous antigen by antigen presenting cells to T-helper cells. Both glycoproteins have been identified in the small intestine of the mature mouse. In this study, we examine the ontogeny of mRNA for three molecules; (Ii31, Ii41 and I-A-beta) in whole intestine and in isolated epithelial cells. When RNA from whole intestine was analysed in northern blots using cDNA probe, Ii31 mRNA was present in Day 10 mice and at each 5 day time point thereafter; Ii41 and I-A-beta were not detected by this technique. To examine ontogeny of Ii chain mRNA in enterocytes, RNA was purified from an enriched population of epithelial cells isolated after systemic perfusion with 30 mM EDTA in Day 21 and Day 28 and adult mice. Ii chain mRNA was not detected until Day 28 by blot hybridization. Reverse transcription of mRNA and amplification of the resultant cDNA by PCR revealed Ii41 and I-A-beta as well as Ii31. RNA from Day 21 epithelial cells required five additional amplification cycles to attain cDNA levels equivalent to those found in Day 28 cells for Ii chain, and 10 additional cycles for I-A-beta. In conclusion, Ii31, Ii41 and I-A-beta mRNA increase rapidly in the enterocyte after weaning. C1 MASSACHUSETTS GEN HOSP,COMBINED PROGRAM PEDIAT GASTROENTEROL & NUTR,BOSTON,MA 02114. SHRINERS BURN INST,COMBINED PROGRAM PEDIAT GASTROENTEROL & NUTR,BOSTON,MA. FU NICHD NIH HHS [HD12437]; NIDDK NIH HHS [DK33506, DK34854] NR 29 TC 12 Z9 12 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD OCT PY 1992 VL 29 IS 10 BP 1257 EP 1263 DI 10.1016/0161-5890(92)90062-3 PG 7 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA JM628 UT WOS:A1992JM62800012 PM 1326714 ER PT J AU MCCLATCHEY, AI MCKENNAYASEK, D CROS, D WORTHEN, HG KUNCL, RW DESILVA, SM CORNBLATH, DR GUSELLA, JF BROWN, RH AF MCCLATCHEY, AI MCKENNAYASEK, D CROS, D WORTHEN, HG KUNCL, RW DESILVA, SM CORNBLATH, DR GUSELLA, JF BROWN, RH TI NOVEL MUTATIONS IN FAMILIES WITH UNUSUAL AND VARIABLE DISORDERS OF THE SKELETAL-MUSCLE SODIUM-CHANNEL SO NATURE GENETICS LA English DT Article ID HYPERKALEMIC PERIODIC PARALYSIS; PARAMYOTONIA-CONGENITA; MALIGNANT HYPERTHERMIA; ALPHA-SUBUNIT; GENE; LINKAGE; CHROMOSOME-17; HETEROGENEITY; SUBTYPES; LOCUS AB Mutations in the skeletal muscle sodium channel gene (SCN4A) have been described in paramyotonia congenita (PMC) and hyperkalaemic periodic paralysis (HPP). We have found two mutations in SCN4A which affect regions of the sodium channel not previously associated with a disease phenotype. Furthermore, affected family members display an unusual mixture of clinical features reminiscent of PMC, HPP and of a third disorder, myotonia congenita (MC). The highly variable individual expression of these symptoms, including in some cases apparent non-penetrance, implies the existence of modifying factors. Mutations in SCN4A can produce a broad range of phenotypes in muscle diseases characterized by episodic abnormalities of membrane excitability. C1 MASSACHUSETTS GEN HOSP,MOLEC NEUROGENET LAB,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT CLIN NEUROPHYSIOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DAY NEUROMUSCULAR RES LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. CAMBRIDGE CITY HOSP,CAMBRIDGE,MA 02142. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21205. TEMPLE UNIV,DEPT NEUROL,PHILADELPHIA,PA 19140. NR 20 TC 115 Z9 123 U1 0 U2 0 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD OCT PY 1992 VL 2 IS 2 BP 148 EP 152 DI 10.1038/ng1092-148 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA JR084 UT WOS:A1992JR08400016 PM 1338909 ER PT J AU RAO, MS SYMES, A MALIK, N SHOYAB, M FINK, JS LANDIS, SC AF RAO, MS SYMES, A MALIK, N SHOYAB, M FINK, JS LANDIS, SC TI ONCOSTATIN M REGULATES VIP EXPRESSION IN A HUMAN NEUROBLASTOMA CELL-LINE SO NEUROREPORT LA English DT Article DE NEUROTRANSMITTER REGULATION; VIP; CNTF; CDF/LIF ID LEUKEMIA-INHIBITORY FACTOR; CONDITIONED MEDIUM; DIFFERENTIATION; CYTOKINES; RECEPTOR; CULTURE AB ONCOSTATIN-M (OM), a recently described glycoprotein cytokine, is structurally and functionally related to cholinergic differentiation factor/leukemia inhibitory factor (CDF/LIF) and ciliary neurotrophic factor (CNTF). To determine whether OM, like CDF/LIF and CNTF, possesses trophic or differentiative functions for neurons we examined the effects of recombinant human OM on ciliary neuron survival and neurotransmitter expression in sympathetic neurons. Like CDF/LIF, but in contrast to CNTF, OM had no effect on ciliary neuronal survival at any concentration tested. OM produced small but reproducible increases in choline acetyl transferase (ChAT) activity and vasoactive intestinal peptide (VIP) levels in rat sympathetic neuron Cultures, but this effect was significantly less than that of CNTF or CDF/LIF. To determine if human OM would elicit a more robust response from human cells, we utilized a human neuroblastoma cell line, NBFL, that responds to CNTF and CDF/LIF by altering vasoactive intestinal peptide (VIP) levels. OM specifically elevated VIP and c-fos mRNA levels in NBFL cells and was as potent as CDF/LIF in this assay. Our data provides evidence that OM acts on neurons and identifies a neural cell line responsive to OM, CNTF, CDF/LIF. C1 CALTECH,DIV BIOL,PASADENA,CA 91125. MASSACHUSSETTS GEN HOSP,MOLEC BIOL UNIT,BOSTON,MA. BRISTOL MYERS SQUIBB RES INST,SEATTLE,MA. CASE WESTERN RESERVE UNIV,SCH MED,DEPT NEUROSCI,CLEVELAND,OH 44106. RI Symes, Aviva/S-7471-2016 OI Symes, Aviva/0000-0003-2557-9939 NR 23 TC 58 Z9 61 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 OCT PY 1992 VL 3 IS 10 BP 865 EP 868 DI 10.1097/00001756-199210000-00011 PG 4 WC Neurosciences SC Neurosciences & Neurology GA JV072 UT WOS:A1992JV07200011 PM 1421089 ER PT J AU NISHIZAWA, S PETERSON, JW SHIMOYAMA, I UEMURA, K LOFTUS, CM MAYBERG, MR AF NISHIZAWA, S PETERSON, JW SHIMOYAMA, I UEMURA, K LOFTUS, CM MAYBERG, MR TI RELATION BETWEEN PROTEIN-KINASE-C AND CALMODULIN SYSTEMS IN CEREBROVASCULAR CONTRACTION - INVESTIGATION OF THE PATHOGENESIS OF VASOSPASM AFTER SUBARACHNOID HEMORRHAGE SO NEUROSURGERY LA English DT Article DE CALMODULIN; CALMODULIN ANTAGONIST; PROTEIN KINASE-C; SUBARACHNOID HEMORRHAGE; VASOSPASM ID LIGHT CHAIN PHOSPHORYLATION; SIGNAL TRANSDUCTION; SMOOTH-MUSCLE; ACTIVATION; MESSENGER AB THE PROTEIN KINASE C (PKC) and calmodulin systems each play a role in vascular contraction. However, the correlation of these two systems in producing contraction has been unclear. To clarify the pathophysiology of vasospasm after subarachnoid hemorrhage, the authors demonstrated tonic contraction of the cerebral artery in a study of isometric tension, and investigated the correlation of the PKC and calmodulin systems in producing the contraction. To develop better management for vasospasm, they also examined the effect of calmodulin antagonists on tonic contraction. The development of isometric tension in canine basilar arteries was measured, with the following results: 1) tonic contraction was dependent on the PKC system, but initiation of the contraction by the calmodulin system was necessary for the subsequent PKC-dependent tonic contraction; 2) specific calmodulin antagonists like chlorpromazine and pimozide partially inhibited the tonic contraction associated with PKC activation; 3) another calmodulin antagonist, trifluoperazine, inhibited the PKC system as well. On the basis of these results, the authors conclude that the PKC system plays a role in the development of vasospasm. In the early phase of contraction, the calmodulin system contributes to the subsequent fully-activated, PKC-induced tonic contraction. To manage vasospasm, a specific calmodulin antagonist would therefore not be sufficient. Suppression of both the calmodulin and PKC systems with trifluoperazine in the earliest stage of vasospasm is recommended. C1 MASSACHUSETTS GEN HOSP, CEREBROVASC BIOPHYS LAB, BOSTON, MA 02114 USA. RP NISHIZAWA, S (reprint author), HAMAMATSU UNIV SCH MED, DEPT NEUROSURG, 3600 HANDACHO, HAMAMATSU, SHIZUOKA 43131, JAPAN. NR 16 TC 30 Z9 31 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD OCT PY 1992 VL 31 IS 4 BP 711 EP 716 PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA JR981 UT WOS:A1992JR98100014 PM 1407457 ER PT J AU YOSHIDA, A CHENG, HM LASHKARI, K KWONG, KK OGASAWARA, H AGUAYO, JB MCMEEL, JW AF YOSHIDA, A CHENG, HM LASHKARI, K KWONG, KK OGASAWARA, H AGUAYO, JB MCMEEL, JW TI COMPARISON BETWEEN B-SCAN ULTRASOUND AND MRI IN THE DETECTION OF DIABETIC VITREOUS HEMORRHAGE SO OPHTHALMIC SURGERY AND LASERS LA English DT Note ID INTRAOCULAR TUMORS; RESONANCE; MELANOMAS; DISEASE AB The efficacy of proton magnetic resonance imaging (MRI) was evaluated and compared with that of B-scan ultrasound in the detection and differentiation of diabetic vitreous hemorrhage. Although conventional spin-echo MRI could not locate vitreous hemorrhages, gradient-recalled-echo (GRE) MRI readily did so. The aberrant signals appeared to originate from the interfacing between hemorrhages and the vitreous, and possibly also from the paramagnetic effect of the ferrous ion. The information provided by boundary/susceptibility detection, unique to the GRE sequence, is useful in delineating the extent of vitreous hemorrhage and hemolysis. However, for the diagnosis and follow up of diabetic vitreous hemorrhages, MRI appears no more informative than B-scan ultra-sonography. C1 HARVARD UNIV,SCH MED,HOWE LAB OPHTHALMOL,243 CHARLES ST,BOSTON,MA 02115. RETINA ASSOCIATES,BOSTON,MA. EYE FDN KANSAS CITY,KANSAS CITY,MO. HARVARD UNIV,SCH MED,EYE RES INST,BOSTON,MA 02115. MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. ASAHIKAWA MED COLL,DEPT OPHTHALMOL,ASAHIKAWA 07811,JAPAN. UNIV MISSOURI,SCH MED,DEPT OPHTHALMOL,KANSAS CITY,MO 64108. FU NEI NIH HHS [EY07620] NR 12 TC 1 Z9 1 U1 1 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0022-023X J9 OPHTHALMIC SURG LAS JI Ophthalmic Surg. Lasers PD OCT PY 1992 VL 23 IS 10 BP 693 EP 696 PG 4 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA JT853 UT WOS:A1992JT85300011 PM 1436971 ER PT J AU SPRINGFIELD, DS AF SPRINGFIELD, DS TI ALLOGRAFT BONES AND SOFT-TISSUES - THE BENEFITS OF CLINICAL RESEARCH SO ORTHOPEDICS LA English DT Editorial Material RP SPRINGFIELD, DS (reprint author), MASSACHUSETTS GEN HOSP,DEPT ORTHOPED,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0147-7447 J9 ORTHOPEDICS JI Orthopedics PD OCT PY 1992 VL 15 IS 10 BP 1141 EP 1142 PG 2 WC Orthopedics SC Orthopedics GA JT576 UT WOS:A1992JT57600002 PM 1409124 ER PT J AU MANKIN, HJ SPRINGFIELD, DS GEBHARDT, MC TOMFORD, WW AF MANKIN, HJ SPRINGFIELD, DS GEBHARDT, MC TOMFORD, WW TI CURRENT STATUS OF ALLOGRAFTING FOR BONE-TUMORS SO ORTHOPEDICS LA English DT Article AB Over the past 20 years the Orthopaedic Oncology Unit of the Massachusetts General Hospital has performed over 660 massive cadaveric allograft transplantations, mostly for patients with bone tumors. The overall success rate for such procedures is around 80%, with most of the failures occurring in the first 3 years as a result of fracture (19%), nonunion (14%), and infection (10%). With longer follow up, late occurring osteoarthritis has been noted in approximately 17% of those patients at risk, suggesting that the articular surface begins to "wear" at 5 years. Some problems remain with the procedure, and more study of such aspects as the immune mechanism, cryopreservation of cartilage, maintaining the status and safety of the bone banking system, and improving the techniques of surgery ultimately may lead to a more uniform and predictable success rate. RP MANKIN, HJ (reprint author), MASSACHUSETTS GEN HOSP,ORTHOPED SERV,ORTHOPED ONCOL UNIT,BOSTON,MA 02114, USA. FU PHS HHS [R01-21896] NR 0 TC 88 Z9 97 U1 0 U2 4 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0147-7447 J9 ORTHOPEDICS JI Orthopedics PD OCT PY 1992 VL 15 IS 10 BP 1147 EP 1154 PG 8 WC Orthopedics SC Orthopedics GA JT576 UT WOS:A1992JT57600003 PM 1409125 ER PT J AU TOMFORD, WW SPRINGFIELD, DS MANKIN, HJ AF TOMFORD, WW SPRINGFIELD, DS MANKIN, HJ TI FRESH AND FROZEN ARTICULAR-CARTILAGE ALLOGRAFTS SO ORTHOPEDICS LA English DT Article AB Fresh and frozen cartilage allografts both function well to relieve joint pain due to cartilage injury. Fresh cartilage allografts appear to remain alive for many months and are most applicable to small injuries such as osteochondritis dissecans, traumatic defects, and osteonecrosis. Frozen cartilage allografts have been used mostly for treatment of bone tumors which most often involve the subchondral and the metaphyseal areas of the long bones, particularly around the knee and hip. Frozen cartilage allografts appear to survive well and maintain joint space for several years. Deterioration of either type of graft does not appear to result in joint pain, making these grafts useful for long periods of time. RP TOMFORD, WW (reprint author), MASSACHUSETTS GEN HOSP,DEPT ORTHOPED SURG,BOSTON,MA 02114, USA. NR 0 TC 32 Z9 33 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0147-7447 J9 ORTHOPEDICS JI Orthopedics PD OCT PY 1992 VL 15 IS 10 BP 1183 EP 1188 PG 6 WC Orthopedics SC Orthopedics GA JT576 UT WOS:A1992JT57600006 PM 1409128 ER PT J AU CHANDLER, HP AF CHANDLER, HP TI USE OF ALLOGRAFTS AND PROSTHESES IN THE RECONSTRUCTION OF FAILED TOTAL HIP REPLACEMENTS SO ORTHOPEDICS LA English DT Article RP CHANDLER, HP (reprint author), MASSACHUSETTS GEN HOSP,WANG AMBULATORY CARE CTR,15 PARKMAN ST,LEVEL 5,BOSTON,MA 02114, USA. NR 0 TC 9 Z9 9 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0147-7447 J9 ORTHOPEDICS JI Orthopedics PD OCT PY 1992 VL 15 IS 10 BP 1207 EP 1218 PG 12 WC Orthopedics SC Orthopedics GA JT576 UT WOS:A1992JT57600008 PM 1409130 ER PT J AU SPRINGFIELD, DS AF SPRINGFIELD, DS TI AUTOGENOUS BONE-GRAFTS - NONVASCULAR AND VASCULAR SO ORTHOPEDICS LA English DT Article AB Nonvascularized autogenous bone grafts have been used for at least 150 years. Vascularized bone grafts were first done only 17 years ago. We now know that bone grafts act through osteoconductive and osteoinductive mechanisms to produce new bone. Autogenous bone grafts remain the gold standard against which allografts and artificial graft materials should be measured. RP SPRINGFIELD, DS (reprint author), MASSACHUSETTS GEN HOSP,DEPT ORTHOPED,BOSTON,MA 02114, USA. NR 0 TC 14 Z9 14 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0147-7447 J9 ORTHOPEDICS JI Orthopedics PD OCT PY 1992 VL 15 IS 10 BP 1237 EP 1241 PG 5 WC Orthopedics SC Orthopedics GA JT576 UT WOS:A1992JT57600010 PM 1409132 ER PT J AU BILITCH, M FURMAN, S GROSS, J FRAME, R JOHNSTON, D PARSONNET, V ROTHBART, ST ZIMMERMAN, J KAWANISHI, DT WIDERHORN, J SONG, SL HASHIMOTO, KK BUCKINGHAM, TA GOLDIN, MD WILMER, EA DENKER, ST LIPTON, IH MALONEY, JD CASTLE, LW HARTHORNE, JW RUSKIN, JN GARAN, H MCGOVERN, BA GRIFFIN, JC SCHEINMAN, MM LESH, MD DORIAN, P NEWMAN, D DENES, P DAHL, W SAKSENA, S KROL, RB FOGOROS, RN AF BILITCH, M FURMAN, S GROSS, J FRAME, R JOHNSTON, D PARSONNET, V ROTHBART, ST ZIMMERMAN, J KAWANISHI, DT WIDERHORN, J SONG, SL HASHIMOTO, KK BUCKINGHAM, TA GOLDIN, MD WILMER, EA DENKER, ST LIPTON, IH MALONEY, JD CASTLE, LW HARTHORNE, JW RUSKIN, JN GARAN, H MCGOVERN, BA GRIFFIN, JC SCHEINMAN, MM LESH, MD DORIAN, P NEWMAN, D DENES, P DAHL, W SAKSENA, S KROL, RB FOGOROS, RN TI PERFORMANCE OF IMPLANTABLE CARDIAC-RHYTHM MANAGEMENT DEVICES SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY LA English DT Article C1 MONTEFIORE MED CTR,BRONX,NY 10467. NEWARK BETH ISRAEL MED CTR,CTR PACEMAKER,NEWARK,NJ 07112. UNIV SO CALIF,SCH MED,CTR PACEMAKER,LOS ANGELES,CA 90033. RUSH PRESBYTERIAN ST LUKES MED CTR,CHICAGO,IL 60612. ST LUKES HOSP,MILWAUKEE,WI 53215. TORONTO GEN HOSP,TORONTO M5G 1L7,ONTARIO,CANADA. CLEVELAND CLIN EDUC FDN,CLEVELAND,OH 44106. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. UNIV CALIF SAN FRANCISCO,MOFFITT HOSP,SAN FRANCISCO,CA 94120. ST MICHAELS HOSP,TORONTO M5B 1W8,ONTARIO,CANADA. ST PAUL RAMSEY MED CTR,ST PAUL,MN 55101. EASTERN HEART INST,PASSAIC,NJ. ALLEGHENY GEN HOSP,PITTSBURGH,PA 15212. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FUTURA PUBL CO PI ARMONK PA 135 BEDFORD RD, PO BOX 418, ARMONK, NY 10504-0418 SN 0147-8389 J9 PACE JI PACE-Pacing Clin. Electrophysiol. PD OCT PY 1992 VL 15 IS 10 BP 1540 EP 1542 PN 1 PG 3 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical SC Cardiovascular System & Cardiology; Engineering GA JU923 UT WOS:A1992JU92300019 ER PT J AU AMBROSINO, DM SOOD, SK LEE, MC CHEN, D COLLARD, HR BOLON, DL JOHNSON, C DAUM, RS AF AMBROSINO, DM SOOD, SK LEE, MC CHEN, D COLLARD, HR BOLON, DL JOHNSON, C DAUM, RS TI IGG1, IGG2 AND IGM RESPONSES TO 2 HAEMOPHILUS-INFLUENZAE TYPE-B CONJUGATE VACCINES IN YOUNG INFANTS SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article ID MEMBRANE PROTEIN COMPLEX; POLYSACCHARIDE; CELLS; IMMUNOGENICITY; INTERLEUKIN-4; EFFICACY; CHILDREN; ANTIBODY; SUBCLASS AB PRP-meningococcal outer membrane protein complex (PRP-OMPC) and oliogosaccharide linked to variant diphtheria toxin (HbOC) Haemophilus influenzae type b (HIB) conjugate vaccines have both been licensed for United States infants at 2 months of age. Differences in serologic responses for these vaccines have been noted with PRP-OMPC producing an early response at 2 months of age and HbOC producing a higher response after a third dose at 6 months of age. To further characterize the nature of these distinct responses, we measured the IgG1, IgG2 and IgM anti-HIB concentrations by enzyme-linked immunosorbent assay after administration of both vaccines. PRP-OMPC produced an IgM and IgG1 anti-HIB response following the initial dose at 2 months of age. After two doses of HbOC an increase in IgG 1 and IgM were noted and after a third dose at 6 months of age an IgG2 anti-HIB response occurred. In addition 33 study subjects were boosted with PRP-OMPC at age 18 months and compared with 34 subjects who received only a primary dose. The anti-HIB IgG1 and IgG2 concentrations following the booster dose were both significantly higher for the primed group (P = 0.0001 and P = 0.001, respectively). Both HIB conjugate vaccines produce predominantly IgG1 anti-HIB antibody responses. The early response to PRP-OMPC vaccine at 2 months of age may result from adjuvant characteristics of the OMPC. C1 PRAXIS BIOL,ROCHESTER,NY. UNIV CHICAGO,WYLER CHILDRENS HOSP,DEPT PEDIAT,CHICAGO,IL 60637. LONG ISL JEWISH MED CTR,ALBERT EINSTEIN COLL MED,SCHNEIDER CHILDRENS HOSP,NEW HYDE PK,NY 11042. RP AMBROSINO, DM (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,INFECT DIS LAB,44 BINNEY ST,BOSTON,MA 02115, USA. FU NIAID NIH HHS [AI29623] NR 19 TC 21 Z9 21 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 OCT PY 1992 VL 11 IS 10 BP 855 EP 859 DI 10.1097/00006454-199210000-00010 PG 5 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA JT864 UT WOS:A1992JT86400010 PM 1408486 ER PT J AU STRICKLAND, EM FARES, M KREBS, DE RILEY, PO GIVENSHEISS, DL HODGE, WA MANN, RW AF STRICKLAND, EM FARES, M KREBS, DE RILEY, PO GIVENSHEISS, DL HODGE, WA MANN, RW TI INVIVO ACETABULAR CONTACT PRESSURES DURING REHABILITATION .1. ACUTE PHASE SO PHYSICAL THERAPY LA English DT Article DE ACETABULUM; ARTHROPLASTY; HIP PROSTHESIS; LOWER EXTREMITY, HIP; REHABILITATION AB The authors conducted a two-part study to compare in vivo acetabular contact pressures during the acute and postacute phases of rehabilitation. This report compares in vivo acetabular pressures generated during selected "inpatient" rehabilitation activities and their relationship to pain, range of motion, and other clinical indicators A pressure-instrumented Moore-type endoprosthesis was implanted in a 73 -year-old woman who bad sustained a femoral neck fracture. Acetabular contact Pressures during the first 2 weeks after surgery were rank-ordered Clinical data, including range of motion, manual muscle test grade, use of pain medication, and independence in gait, were collected simultaneously Acetabular pressures did not follow the predicted rank order corresponding to the commonly prescribed temporal order of inpatient rehabilitation activities. Isometric hip extension and active hip flexion generated the highest pressures of all the studied activities, including those measured during gait activities. Isometric exercises, therefore may not be entirely benign preparation for ambulatory activity Clinical data did not correspond with peak pressure data, suggesting that observed responses to rehabilitation may not be dependable criteria for progressing the acute hip rehabilitation protocol We discuss applications for rehabilitation programs based on hip contact pressure data as an initial attempt to formulate more defensible rehabilitation approaches for patients with acutely painful hips C1 MASSACHUSETTS GEN HOSP,INST HLTH PROFESS,15 RIVER ST,BOSTON,MA 02108. DEPT VET AFFAIRS MED CTR,DEPT PHYS THERAPY,BOSTON,MA 02130. BOSTON UNIV,BOSTON,MA 02215. MASSACHUSETTS GEN HOSP,BIOMOT LAB,BOSTON,MA 02114. HARMARVILLE OUTPATIENT REHABIL CTR,WASHINGTON,PA 15301. WHEELING JESUIT COLL,DEPT PHYS THERAPY,WHEELING,WV 26003. MIT,DEPT MECH ENGN,CAMBRIDGE,MA 02139. MIT,NEWMAN LAB BIOMECH & HUMAN REHABIL,CAMBRIDGE,MA 02139. HARVARD UNIV,MIT,CTR REHABIL ENGN,CAMBRIDGE,MA 02138. RI Givens, Deborah/E-3123-2011; Riley, Patrick/B-3053-2009 NR 26 TC 31 Z9 32 U1 0 U2 2 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 OCT PY 1992 VL 72 IS 10 BP 691 EP 699 PG 9 WC Orthopedics; Rehabilitation SC Orthopedics; Rehabilitation GA JQ604 UT WOS:A1992JQ60400002 PM 1528962 ER PT J AU GIVENSHEISS, DL KREBS, DE RILEY, PO STRICKLAND, EM FARES, M HODGE, WA MANN, RW AF GIVENSHEISS, DL KREBS, DE RILEY, PO STRICKLAND, EM FARES, M HODGE, WA MANN, RW TI INVIVO ACETABULAR CONTACT PRESSURES DURING REHABILITATION .2. POSTACUTE PHASE SO PHYSICAL THERAPY LA English DT Article DE ACETABULUM; ARTHROPLASTY; HIP PROSTHESIS; PROSTHESIS; REHABILITATION ID GAIT AB The authors conducted a two-part study to compare in vivo acetabular contact pressures during the acute and postacute phases of rehabilitation in a single subject with a pressure-instrumented femoral prosthesis. This report compares six common hip rehabilitation activities for resultant in vivo hip pressure magnitudes during the first 5 years after discharged from an acute care hospital. These activities were full, partial, touch-down, and non-weight-bearing ambulation and isometric hip abduction and straight-leg-raising exercises. A pressure instrumented femoral endoprosthesis implanted in a 73-year-old woman who bad sustained a femoral neck fracture provided data for the activities. The activities were rank ordered and compared over time according to peak pressure magnitude. Prescribed weight bearing and exercise type were not good predictors of hip peak pressures in this patient. Maximum pressures occurred by 1 year postdischarge for most activities, with a tendency to stabilize or decline thereafter. Resisted isometric hip abduction exercise demonstrated the most variation over time. The results suggest that hip pressures may be limited by controlling muscle force and movement velocity during postoperative hip rehabilitation activities. C1 MASSACHUSETTS GEN HOSP,INST HLTH PROFESS,15 RIVER ST,BOSTON,MA 02108. HARMARVILLE OUT PATIENT REHABIL CTR,WASHINGTON,PA 15301. WHEELING JESUIT COLL,DEPT PHYS THERAPY,WHEELING,WV 26003. MASSACHUSETTS GEN HOSP,BIOMOT LAB,BOSTON,MA 02114. DEPT VET AFFAIRS MED CTR,DEPT PHYS THERAPY,BOSTON,MA 02130. BOSTON UNIV,BOSTON,MA 02215. MIT,DEPT MECH ENGN,CAMBRIDGE,MA 02139. MIT,NEWMAN LAB BIOMECH & HUMAN REHABIL,CAMBRIDGE,MA 02139. HARVARD UNIV,MIT,CTR REHABIL ENGN,CAMBRIDGE,MA 02138. RI Givens, Deborah/E-3123-2011; Riley, Patrick/B-3053-2009 NR 16 TC 23 Z9 24 U1 0 U2 2 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 OCT PY 1992 VL 72 IS 10 BP 700 EP 705 PG 6 WC Orthopedics; Rehabilitation SC Orthopedics; Rehabilitation GA JQ604 UT WOS:A1992JQ60400003 PM 1528963 ER PT J AU KREBS, DE MANN, RW GIVENSHEISS, DL STRICKLAND, EM AF KREBS, DE MANN, RW GIVENSHEISS, DL STRICKLAND, EM TI INVIVO ACETABULAR CONTACT PRESSURES DURING REHABILITATION .2. POSTACUTE PHASE - RESPONSE SO PHYSICAL THERAPY LA English DT Letter C1 HARMARVILLE OUTPATIENT REHABIL CTR,WASHINGTON,PA 15301. WHEELING JESUIT COLL,DEPT PHYS THERAPY,WHEELING,WV 26003. DEPT VET AFFAIRS MED CTR,DEPT PHYS THERAPY,BOSTON,MA 02130. MIT,DEPT MECH ENGN,CAMBRIDGE,MA 02139. MIT,NEWMAN LAB BIOMECH & HUMAN REHABIL,CAMBRIDGE,MA 02139. HARVARD UNIV,MIT,CTR REHABIL ENGN,CAMBRIDGE,MA 02138. RP KREBS, DE (reprint author), MASSACHUSETTS GEN HOSP,INST HLTH PROFESS,15 RIVER ST,BOSTON,MA 02108, USA. NR 10 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 OCT PY 1992 VL 72 IS 10 BP 708 EP 710 PG 3 WC Orthopedics; Rehabilitation SC Orthopedics; Rehabilitation GA JQ604 UT WOS:A1992JQ60400005 ER PT J AU KUBASEK, WL SHIRLEY, BW MCKILLOP, A GOODMAN, HM BRIGGS, W AUSUBEL, FM AF KUBASEK, WL SHIRLEY, BW MCKILLOP, A GOODMAN, HM BRIGGS, W AUSUBEL, FM TI REGULATION OF FLAVONOID BIOSYNTHETIC GENES IN GERMINATING ARABIDOPSIS SEEDLINGS SO PLANT CELL LA English DT Article ID CHALCONE-SYNTHASE GENE; BLUE-LIGHT REGULATION; TRANSCRIPTIONAL REGULATION; ANTHOCYANIN PRODUCTION; ULTRAVIOLET-LIGHT; EXPRESSION; PHYTOCHROME; THALIANA; ACTIVATION; RESPONSES AB Many higher plants, including Arabidopsis, transiently display purple anthocyanin pigments just after seed germination. We observed that steady state levels of mRNAs encoded by four flavonoid biosynthetic genes, PAL1 (encoding phenylalanine ammonia-lyase 1), CHS (encoding chalcone synthase), CHI (encoding chalcone isomerase), and DFR (encoding dihydroflavonol reductase), were temporally regulated, peaking in 3-day-old seedlings grown in continuous white light. Except for the case of PAL1 mRNA, mRNA levels for these flavonoid genes were very low in seedlings grown in darkness. Light induction studies using seedlings grown in darkness showed that PAL1 mRNA began to accumulate before CHS and CHI mRNAs, which, in turn, began to accumulate before DFR mRNA. This order of induction is the same as the order of the biosynthetic steps in flavonoid biosynthesis. Our results suggest that the flavonoid biosynthetic pathway is coordinately regulated by a developmental timing mechanism during germination. Blue light and UVB light induction experiments using red light- and dark-grown seedlings showed that the flavonoid biosynthetic genes are induced most effectively by UVB light and that blue light induction is mediated by a specific blue light receptor. C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. CARNEGIE INST WASHINGTON,DEPT PLANT BIOL,STANFORD,CA 94350. RI Winkel, Brenda/A-6602-2008 OI Winkel, Brenda/0000-0003-3481-024X NR 40 TC 229 Z9 245 U1 3 U2 16 PU AMER SOC PLANT PHYSIOLOGISTS PI ROCKVILLE PA 15501 MONONA DRIVE, ROCKVILLE, MD 20855 SN 1040-4651 J9 PLANT CELL JI Plant Cell PD OCT PY 1992 VL 4 IS 10 BP 1229 EP 1236 PG 8 WC Biochemistry & Molecular Biology; Plant Sciences; Cell Biology SC Biochemistry & Molecular Biology; Plant Sciences; Cell Biology GA JV121 UT WOS:A1992JV12100007 ER PT J AU GIRAUDAT, J HAUGE, BM VALON, C SMALLE, J PARCY, F GOODMAN, HM AF GIRAUDAT, J HAUGE, BM VALON, C SMALLE, J PARCY, F GOODMAN, HM TI ISOLATION OF THE ARABIDOPSIS-ABI3 GENE BY POSITIONAL CLONING SO PLANT CELL LA English DT Article ID POLYMORPHISM LINKAGE MAP; ABSCISIC-ACID; TRANSCRIPTIONAL ACTIVATOR; VICIA-FABA; THALIANA; PROTEIN; BINDING; MUTANTS; MAIZE; MUTATIONS AB Arabidopsis abi3 mutants are altered in various aspects of seed development and germination that reflect a decreased responsiveness to the hormone abscisic acid. The ABI3 gene has been isolated by positional cloning. A detailed restriction fragment length polymorphism (RFLP) map of the abi3 region was constructed. An RFLP marker closely linked to the abi3 locus was identified, and by analyzing an overlapping set of cosmid clones containing this marker, the abi3 locus was localized within a 35-kb region. An 11-kb subfragment was then shown to complement the mutant phenotype in transgenic plants, thereby further delimiting the position of the locus. A candidate ABI3 gene was identified within this fragment as being expressed in developing fruits. The primary structure of the encoded protein was deduced from sequence analysis of a corresponding cDNA clone. In the most severe abi3-4 allele, the size of this predicted protein was reduced by 40% due to the presence of a point mutation that introduced a premature stop codon. The predicted ABI3 protein displays discrete regions of high similarity to the maize viviparous-1 protein. C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. RP GIRAUDAT, J (reprint author), INST SCI VEGETALES,CNRS,UPR 40,F-91198 GIF SUR YVETTE,FRANCE. RI parcy, francois/A-6031-2009; Parcy, francois/G-9177-2011 NR 43 TC 671 Z9 713 U1 6 U2 47 PU AMER SOC PLANT PHYSIOLOGISTS PI ROCKVILLE PA 15501 MONONA DRIVE, ROCKVILLE, MD 20855 SN 1040-4651 J9 PLANT CELL JI Plant Cell PD OCT PY 1992 VL 4 IS 10 BP 1251 EP 1261 DI 10.1105/tpc.4.10.1251 PG 11 WC Biochemistry & Molecular Biology; Plant Sciences; Cell Biology SC Biochemistry & Molecular Biology; Plant Sciences; Cell Biology GA JV121 UT WOS:A1992JV12100009 PM 1359917 ER PT J AU HARRIS, NR WEBB, MS MAY, JW AF HARRIS, NR WEBB, MS MAY, JW TI INTRAOPERATIVE PHYSIOLOGICAL BLOOD-FLOW STUDIES IN THE TRAM FLAP SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID VASCULAR TERRITORIES; TRANSVERSE C1 MASSACHUSETTS GEN HOSP,SUITE 453,15 PARKMAN ST,BOSTON,MA 02114. NR 12 TC 36 Z9 37 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 OCT PY 1992 VL 90 IS 4 BP 553 EP 558 DI 10.1097/00006534-199210000-00001 PG 6 WC Surgery SC Surgery GA JR216 UT WOS:A1992JR21600001 PM 1409989 ER PT J AU ROCK, KL ROTHSTEIN, L BENACERRAF, B AF ROCK, KL ROTHSTEIN, L BENACERRAF, B TI ANALYSIS OF THE ASSOCIATION OF PEPTIDES OF OPTIMAL LENGTH TO CLASS-I MOLECULES ON THE SURFACE OF CELLS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ANTIGEN PRESENTATION; MAJOR HISTOCOMPATIBILITY COMPLEX; H-2; BETA-2-MICROGLOBULIN; CYTOTOXIC LYMPHOCYTE-T ID HISTOCOMPATIBILITY COMPLEX BINDING; ANTIGEN PRESENTATION; SYNTHETIC PEPTIDES; LYMPHOCYTES-T; MHC MOLECULES; HEAVY-CHAINS; BETA-2-MICROGLOBULIN; REASSOCIATION; HYBRIDOMAS AB The association of major histocompatibility complex (MHC) class I molecules on the surface of cells with synthetic antigenic peptides of eight or nine amino acid residues was examined. Peptides were synthesized that correspond to the antigenic sequences from ovalbumin and influenza nucleoprotein believed to be naturally processed and presented by cells with K(b) and D(b) MHC class I molecules, respectively. Consistent with the results of others, these peptides were 10(3)-10(5) times more active in stimulating specific T cells as compared to peptides of longer sequences. When cells are incubated with these peptides at <0.01-0.1 muM, the association of the peptides with class I molecules is dependent on (i) the reassociation of free beta2-microglobulin from the extracellular fluids, (ii) a process that requires cells to be metabolically active, or (iii) stabilization of class I heterodimers by chemical crosslinking. In contrast, when cells are incubated with these peptides at >0.1-1.0 muM, the peptides associate with class I molecules in the absence of exogenous beta2-microglobulin, energy, or chemical crosslinking. Antigen competition experiments suggest that the class I molecules that bind peptides offered at high concentration become only transiently receptive to binding peptide. The concentration of peptides required for presentation to T cells under these conditions corresponds to those that stabilize K(b) molecules on the surface of RMA-S mutant cells in the absence of exogenous beta2-microglobulin. These results support the concept that the receptivity of class I molecules on cells is determined by the dissociation of beta2-microglobulin from MHC class I that lacks bound peptides. 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,BOSTON,MA 02115, USA. FU NIAID NIH HHS [AI20248] NR 34 TC 39 Z9 39 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 OCT 1 PY 1992 VL 89 IS 19 BP 8918 EP 8922 DI 10.1073/pnas.89.19.8918 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JQ934 UT WOS:A1992JQ93400013 PM 1409586 ER PT J AU VANTVEER, LJ LUTZ, PM ISSELBACHER, KJ BERNARDS, R AF VANTVEER, LJ LUTZ, PM ISSELBACHER, KJ BERNARDS, R TI STRUCTURE AND EXPRESSION OF MAJOR HISTOCOMPATIBILITY COMPLEX-BINDING PROTEIN-2, A 275-KDA ZINC FINGER PROTEIN THAT BINDS TO AN ENHANCER OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I GENES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE MBP-2 MAJOR HISTOCOMPATIBILITY COMPLEX ENHANCER BINDING PROTEIN ID NF-KAPPA-B; COMPLETE NUCLEOTIDE-SEQUENCE; DNA-BINDING; REGULATORY SEQUENCE; NUCLEAR FACTOR; PROMOTER; SUBUNIT; REL; RECOGNIZE; MEMBER AB We have isolated a cDNA encoding a transcription factor that binds to the enhancer of major histocompatibility complex (MHC) class I genes. MHC-binding protein 2 (MBP-2) is a 275-kDa protein, containing two sets of widely separated zinc ringers and a stretch of highly acidic amino acids, a putative transactivation domain. The two zinc finger regions, when expressed individually as bacterial fusion proteins, bind with highest affinity to the MHC class I gene enhancer. Several proteins found in mammalian nuclear extracts bind the MHC class I enhancer in an electrophoresis mobility shift assay. Only one of these, a ubiquitously expressed factor, forming a slow-migrating retarded complex, can be supershifted by a MBP-2 antiserum. The same antiserum also precipitates a protein of >250 kDa from COS cells transfected with a MBP-2 expression vector. Our data indicate that MBP-2 is a transcription factor involved in the regulation of MHC class I gene expression. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,CTR CANC,DIV MOLEC GENET,BOSTON,MA 02129. OI Bernards, Rene/0000-0001-8677-3423 NR 24 TC 49 Z9 50 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 OCT 1 PY 1992 VL 89 IS 19 BP 8971 EP 8975 DI 10.1073/pnas.89.19.8971 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JQ934 UT WOS:A1992JQ93400024 PM 1409593 ER PT J AU WEAVER, DR RIVKEES, SA REPPERT, SM AF WEAVER, DR RIVKEES, SA REPPERT, SM TI D1-DOPAMINE RECEPTORS ACTIVATE C-FOS EXPRESSION IN THE FETAL SUPRACHIASMATIC NUCLEI SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CIRCADIAN-RHYTHMS; BIOLOGICAL CLOCK; MELATONIN RECEPTORS; GENE-EXPRESSION; COCAINE USE; RAT; BRAIN; ENTRAINMENT; SYNAPTOGENESIS; PROTEIN AB The existence of an activatable dopamine system within the hypothalamic suprachiasmatic nuclei (SCN), the site of a biological clock, was investigated in rats during fetal life. In situ hybridization studies revealed that D1-dopamine receptor mRNA was highly expressed in the fetal SCN and not expressed in other hypothalamic regions. Cocaine injected into pregnant rats or directly into rat fetuses on day 20 of gestation selectively activated c-fos gene expression in the fetal SCN; cocaine did not induce c-fos expression elsewhere in the fetal brain or in the maternal SCN. This cocaine-induced activation of c-fos expression in fetal SCN was mediated in part through D1-dopamine receptors, as the cocaine-induced activation was partially blocked by the D1-dopamine receptor antagonist SCH 23390. In addition, the selective D1-dopamine receptor agonist SKF 38393 induced high levels of c-fos expression in the fetal SCN. The presence of an activatable dopamine system within the fetal SCN provides a mechanism through which maternal signals could entrain the fetal biological clock and through which maternally administered psychotropic drugs could alter normal development of the circadian timing system. C1 MASSACHUSETTS GEN HOSP,DEV CHRONOBIOL LAB,JACKSON 1226,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. FU NICHD NIH HHS [HD14427, K08 HD00924] NR 38 TC 72 Z9 74 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 OCT 1 PY 1992 VL 89 IS 19 BP 9201 EP 9204 DI 10.1073/pnas.89.19.9201 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JQ934 UT WOS:A1992JQ93400071 PM 1384044 ER PT J AU FIELD, SJ JOHNSON, RS MORTENSEN, RM PAPAIOANNOU, VE SPIEGELMAN, BM GREENBERG, ME AF FIELD, SJ JOHNSON, RS MORTENSEN, RM PAPAIOANNOU, VE SPIEGELMAN, BM GREENBERG, ME TI GROWTH AND DIFFERENTIATION OF EMBRYONIC STEM-CELLS THAT LACK AN INTACT C-FOS GENE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ANTISENSE RNA; INVITRO; JUN; FIBROBLASTS; EXPRESSION; PROTEINS AB The c-fos protooncogene encodes a transcription factor that is thought to play a critical role in proliferation and differentiation as well as in the physiological response of mature cells to their environment. To test directly the role of c-fos in growth and differentiation, we generated mouse embryonic stem cell lines in which both copies of the c-fos gene were specifically disrupted by homologous recombination. Remarkably, the disruption of both copies of c-fos in these cells has no detectable effect on embryonic stem cell viability, growth rate, or differentiation potential. Embryonic stem cells lacking c-fos can differentiate into a wide range of cell types in tissue culture and also in chimeric mice. We conclude that despite a large body of literature suggesting an important role for c-fos in cell growth and differentiation, in at least some cell types this gene is not essential for these processes. C1 HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOLEC GENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. TUFTS UNIV,SCH VET MED,BOSTON,MA 02111. BRIGHAM & WOMENS HOSP,DIV ENDOCRINE,BOSTON,MA 02115. TUFTS UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02111. OI Johnson, Randall/0000-0002-4084-6639 FU NICHD NIH HHS [HD27295] NR 35 TC 61 Z9 61 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 OCT 1 PY 1992 VL 89 IS 19 BP 9306 EP 9310 DI 10.1073/pnas.89.19.9306 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JQ934 UT WOS:A1992JQ93400093 PM 1329091 ER PT J AU BURGESS, KE YAMAMOTO, M PRASAD, KVS RUDD, CE AF BURGESS, KE YAMAMOTO, M PRASAD, KVS RUDD, CE TI CD5 ACTS AS A TYROSINE KINASE SUBSTRATE WITHIN A RECEPTOR COMPLEX COMPRISING T-CELL RECEPTOR ZETA-CHAIN CD3 AND PROTEIN-TYROSINE KINASES P56LCK AND P59FYN SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE SIGNAL TRANSDUCTION; CD5 ID ANTIGEN RECEPTOR; MONOCLONAL-ANTIBODY; MOLECULAR-CLONING; LYMPHOCYTES-T; SURFACE; ACTIVATION; PHOSPHORYLATION; IDENTIFICATION; STIMULATION; ASSOCIATION AB T-cell antigens including CD2, CD4, CD6, CD8, and CD28 serve as coreceptors with the T-cell receptor (TCR)/CD3 complex in control of T-cell growth. The molecular basis by which these antigens fulfill this role has remained a major issue. An initial clue to this question came with our finding that the sensitivity of in vitro kinase labeling (specifically using protein-tyrosine kinase p56lck) allowed detection of a physical association between CD4-p56lck and the TCR/CD3 complexes. Another T-cell antigen, CD5, is structurally related to the macrophage scavenger receptor family and, as such, can directly stimulate and/or potentiate T-cell proliferation. In this study, we reveal that in Brij 96-based cell lysates, anti-CD5 antibodies coprecipitated TCR zeta chain (TCRzeta)/CD3 subunits as well as the protein-tyrosine kinases p56lck and p59fyn. Conversely, anti-CD3 antibody coprecipitated CD5, p56lck, and p59fyn. Indeed, anti-CD5 and anti-CD3 gel patterns were virtually identical, except for a difference in relative intensity of polypeptides. Anti-CD4 coprecipitated p56lck, p32, and CD3/TCRzeta subunits but precipitated less CD5, suggesting the existence of CD4-TCRzeta/CD3 complexes distinct from the CD5-TCRzeta/CD3 complexes. Consistent with the formation of a multimeric CD5-TCRzeta/CD3 complex, anti-CD5 crosslinking induced tyrosine phosphorylation of numerous T-cell substrates, similar to those phosphorylated by TCRzeta/CD3 ligation. Significantly, as for TCRzeta, CD5 was found to act as a tyrosine kinase substrate induced by TCR/CD3 ligation. The kinetics of phosphorylation of CD5 (t1/2, = 20 sec) was among the earliest of activation events, more rapid than seen for TCRzeta (t1/2 = 1 min). CD5 represents a likely TCR/CD3-associated substrate for protein-tyrosine kinases (p56lck or p59fyn) and an alternative signaling pathway within a multimeric TCR complex. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,44 BINNEY ST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. NR 37 TC 111 Z9 111 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 OCT 1 PY 1992 VL 89 IS 19 BP 9311 EP 9315 DI 10.1073/pnas.89.19.9311 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JQ934 UT WOS:A1992JQ93400094 PM 1384049 ER PT J AU LEE, JP CHO, H BANNWARTH, W KITAS, EA WALSH, CT AF LEE, JP CHO, H BANNWARTH, W KITAS, EA WALSH, CT TI NMR ANALYSIS OF REGIOSELECTIVITY IN DEPHOSPHORYLATION OF A TRIPHOSPHOTYROSYL DODECAPEPTIDE AUTOPHOSPHORYLATION SITE OF THE INSULIN-RECEPTOR BY A CATALYTIC FRAGMENT OF LAR PHOSPHOTYROSINE PHOSPHATASE SO PROTEIN SCIENCE LA English DT Article DE LAR PTPASE; LEUKOCYTE ANTIGEN RELATED PHOSPHOTYROSINE PHOSPHATASE; REGIOSELECTIVE DEPHOSPHORYLATION ID PROTEIN TYROSINE PHOSPHATASES; SIGNAL TRANSDUCTION; PHOSPHORYLATION; KINASE; P34CDC2; FAMILY; CD45; IDENTIFICATION; SPECTROSCOPY; RELAXATION AB An autophosphorylation site in the activated insulin receptor tyrosine kinase domain has three tyrosines phosphorylated when fully activated. To begin to examine recognition of triphosphotyrosyl sites by protein tyrosine phosphatases in possible control of signal transduction a triphosphotyrosyl dodecapeptide TRDIpYETDpYpYRK corresponding to residues 1, 142-1,153 of the insulin receptor was prepared and incubated with the 40-kDa catalytic domain of the human PTPase LAR. To assess regioselectivity of recognition, the three diphosphotyrosyl regioisomers, and the three monophosphotyrosyl regioisomers were prepared and assayed. All seven peptides were PTPase substrates. To identify any preferences in dephosphorylation at pY5, pY9, or pY10, H-1-NMR analyses were conducted during enzyme incubations and distinguishing fingerprint regions determined for each of the seven phosphotyrosyl peptides. LAR PTPase shows strong preference for dephosphorylation first at pY5 (at tri-, di-, and monophosphotyrosyl levels). Initially this regioselectivity gives the Y5(pY9)(pY10) diphospho regioisomer, followed by equal dephosphorylation at pY9 or pY10 to give the corresponding monophosphoryl species on the way to fully dephosphorylated product. The NMR methodology is applicable to other peptides with multiple sites of phosphorylation that undergo attack by any phosphatase. C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,240 LONGWOOD AVE,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HOFFMANN LA ROCHE AG,CENT RES DEPT,BASEL,SWITZERLAND. FU NCRR NIH HHS [1 S10 RR04862-01]; NIGMS NIH HHS [GM20011, GM 14216-02] NR 34 TC 12 Z9 12 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD OCT PY 1992 VL 1 IS 10 BP 1353 EP 1362 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JW799 UT WOS:A1992JW79900015 PM 1303753 ER PT J AU FARAONE, SV BIEDERMAN, J CHEN, WJ KRIFCHER, B KEENAN, K MOORE, C SPRICH, S TSUANG, MT AF FARAONE, SV BIEDERMAN, J CHEN, WJ KRIFCHER, B KEENAN, K MOORE, C SPRICH, S TSUANG, MT TI SEGREGATION ANALYSIS OF ATTENTION-DEFICIT HYPERACTIVITY DISORDER SO PSYCHIATRIC GENETICS LA English DT Article ID CONDUCT DISORDER; CHILDHOOD HYPERACTIVITY; FAMILIAL ASSOCIATION; COMPLEX SEGREGATION; LOGISTIC-MODELS; CHILDREN; PARENTS; PSYCHOPATHOLOGY; METHYLPHENIDATE; TRAITS AB Although family, twin and adoption studies suggest that genetic factors are involved in attention deficit hyperactivity disorder, further evidence is needed to demonstrate that its familial transmission is consistent with known genetic mechanisms. We applied segregation analysis to a sample of 257 children and their 808 first-degree relatives. Interviews of subjects with DSM-III-R-based structured interviews provided the basis for psychiatric diagnosis. We analyzed these family data with the mixed model, as implemented in the computer program POINTER and a Class A regressive logistic model as implemented in the computer program REGTL. Our results indicate that the familial distribution of DSM-III-R attention deficit hyperactivity disorder is consistent with the effects of a single major gene. We can reject multifactorial polygenic transmission, non-familial environmental transmission, and cultural transmission. C1 MASSACHUSETTS GEN HOSP,PSYCHIAT SERV,PEDIAT PSYCHOPHARMACOL UNIT ACC725,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. BROCKTON W ROXBURY VET AFFAIRS MED CTR,PSYCHIAT SERV,BROCKTON,MA. NR 58 TC 114 Z9 117 U1 0 U2 2 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0955-8829 J9 PSYCHIATR GENET JI Psychiatr. Genet. PD OCT PY 1992 VL 2 IS 4 BP 257 EP 275 DI 10.1097/00041444-199210000-00004 PG 19 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA JY262 UT WOS:A1992JY26200004 ER PT J AU BUMP, EA CERCE, BA ALSARRAF, R PIERCE, SM KOCH, CJ AF BUMP, EA CERCE, BA ALSARRAF, R PIERCE, SM KOCH, CJ TI RADIOPROTECTION OF DNA IN ISOLATED-NUCLEI BY NATURALLY-OCCURRING THIOLS AT INTERMEDIATE OXYGEN-TENSION SO RADIATION RESEARCH LA English DT Article ID RADIATION-SENSITIZING AGENTS; DOUBLE-STRAND BREAKAGE; MAMMALIAN-CELLS; ENDOGENOUS GLUTATHIONE; BUTHIONINE SULFOXIMINE; ENHANCEMENT RATIO; EXOGENOUS THIOLS; X-RAYS; RADIOSENSITIZATION; MISONIDAZOLE C1 UNIV PENN,RADIAT ONCOL,PHILADELPHIA,PA 19104. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. RP BUMP, EA (reprint author), HARVARD UNIV,SCH MED,JOINT CTR RADIAT THERAPY,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA49498, CA46776, CA42391] NR 49 TC 28 Z9 28 U1 0 U2 0 PU RADIATION RESEARCH SOC PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD OCT PY 1992 VL 132 IS 1 BP 94 EP 104 DI 10.2307/3578339 PG 11 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA JU547 UT WOS:A1992JU54700014 PM 1410281 ER PT J AU MOLGAARD, CP YUCEL, EK GELLER, SC KNOX, TA WALTMAN, AC AF MOLGAARD, CP YUCEL, EK GELLER, SC KNOX, TA WALTMAN, AC TI ACCESS-SITE THROMBOSIS AFTER PLACEMENT OF INFERIOR VENA-CAVA FILTERS WITH 12-14-F DELIVERY SHEATHS SO RADIOLOGY LA English DT Article DE EMBOLISM, PULMONARY; EXTREMITIES, THROMBOSIS; INTERVENTIONAL PROCEDURES, COMPLICATIONS; THROMBOSIS, US; THROMBOSIS, VENOUS; VENAE-CAVAE, FILTERS ID KIMRAY-GREENFIELD FILTER; FEMORAL VEIN-THROMBOSIS; PERCUTANEOUS PLACEMENT; CLINICAL-EXPERIENCE; INSERTION AB Inferior vena cava filters were placed in 60 patients. Ultrasound (US) of the venous access site was performed before and 3-5 days after filter placement to determine the prevalence of occlusive and nonocclusive access-site thrombosis (AST). Prevalence of symptoms attributable to AST was also evaluated at 1-month clinical follow-up in 58 of the 60 patients. All filters were placed with delivery sheaths with outer diameters of 12-14 F. US depicted development of occlusive AST in six of the 60 patients (10%). Nonocclusive AST developed in 15 (25%). Symptoms related to AST occurred in two of 58 patients (3%). There was a substantially increased prevalence of occlusive thrombus in patients in whom partially occluding thrombus or extrinsic compression in the inferior vena cava or ipsilateral iliofemoral veins was demonstrated on vena cavograms obtained before filter placement. The prevalence of both symptoms attributable to AST and US-detected occlusive thrombus in this series with smaller delivery systems is lower than that reported after percutaneous placement of stainless steel Greenfield filters via 29.5-F (outer diameter) sheaths. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. NEW ENGLAND MED CTR,DEPT MED,BOSTON,MA 02111. NR 23 TC 39 Z9 39 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 OCT PY 1992 VL 185 IS 1 BP 257 EP 261 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA JN608 UT WOS:A1992JN60800047 PM 1523320 ER PT J AU KOPANS, DB AF KOPANS, DB TI PREOPERATIVE NEEDLE LOCALIZATION SO RADIOLOGY LA English DT Letter ID BREAST-LESIONS; WIRE RP KOPANS, DB (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114, USA. NR 6 TC 1 Z9 1 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 OCT PY 1992 VL 185 IS 1 BP 285 EP 286 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA JN608 UT WOS:A1992JN60800059 PM 1523330 ER PT J AU BARBER, DL DANDREA, AD AF BARBER, DL DANDREA, AD TI THE ERYTHROPOIETIN RECEPTOR AND THE MOLECULAR-BASIS OF SIGNAL TRANSDUCTION SO SEMINARS IN HEMATOLOGY LA English DT Article ID COLONY-STIMULATING FACTOR; PROTEIN TYROSINE PHOSPHORYLATION; MURINE ERYTHROLEUKEMIA-CELLS; BETA-CHAIN GENE; KINASE-ACTIVITY; EXPRESSION CLONING; GROWTH-FACTOR; IMMATURE ERYTHROBLASTS; INTERLEUKIN-3 RECEPTOR; RAF-1 PROTOONCOGENE C1 HARVARD UNIV,CHILDRENS HOSP,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,44 BINNEY ST,BOSTON,MA 02115. NR 90 TC 20 Z9 21 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD OCT PY 1992 VL 29 IS 4 BP 293 EP 304 PG 12 WC Hematology SC Hematology GA JR383 UT WOS:A1992JR38300004 PM 1485183 ER PT J AU DAGOSTINO, RB LANGE, N RYAN, L AF DAGOSTINO, RB LANGE, N RYAN, L TI PAPERS FROM THE SYMPOSIUM ON LONGITUDINAL DATA-ANALYSIS, 19-21 JUNE 1991 - OVERVIEW SO STATISTICS IN MEDICINE LA English DT Editorial Material ID GENERALIZED LINEAR-MODELS; DISTRIBUTIONS; EM C1 BROWN UNIV,DIV BIOL & MED,DEPT COMMUNITY HLTH,PROVIDENCE,RI 02912. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,BOSTON,MA 02115. RP DAGOSTINO, RB (reprint author), BOSTON UNIV,DEPT MATH,111 CUMMINGTON ST,BOSTON,MA 02215, USA. RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 NR 16 TC 1 Z9 1 U1 0 U2 0 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 OCT-NOV PY 1992 VL 11 IS 14-15 BP 1801 EP 1805 DI 10.1002/sim.4780111404 PG 5 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 KC111 UT WOS:A1992KC11100002 ER PT J AU MOSKOWITZ, MA AF MOSKOWITZ, MA TI TIRILAZAD MESYLATE DOES NOT IMPROVE EARLY CEREBRAL METABOLIC RECOVERY FOLLOWING COMPRESSION ISCHEMIA IN DOGS - EDITORIAL COMMENT SO STROKE LA English DT Editorial Material ID PEROXIDATION INHIBITOR U74006F; LIPID-PEROXIDATION; FOREBRAIN ISCHEMIA; GERBILS; RATS RP MOSKOWITZ, MA (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH NEUROSURG & NEUROL,DEPT NEUROL,BOSTON,MA 02114, USA. NR 14 TC 1 Z9 1 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 OCT PY 1992 VL 23 IS 10 BP 1485 EP 1486 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA JQ018 UT WOS:A1992JQ01800018 ER PT J AU HARMS, BA ANDERSEN, AB STARLING, JR FISCHER, JE BACKER, J MICHELASSI, F AF HARMS, BA ANDERSEN, AB STARLING, JR FISCHER, JE BACKER, J MICHELASSI, F TI THE W-ILEAL RESERVOIR - LONG-TERM ASSESSMENT AFTER PROCTOCOLECTOMY FOR ULCERATIVE-COLITIS AND FAMILIAL POLYPOSIS SO SURGERY LA English DT Article; Proceedings Paper CT 49TH ANNUAL MEETING OF THE CENTRAL SURGICAL ASSOC CY MAR 05-07, 1992 CL MADISON, WI SP CENT SURG ASSOC ID POUCH-ANAL ANASTOMOSIS; RESTORATIVE PROCTOCOLECTOMY; MUCOSAL PROCTECTOMY; COLECTOMY AB Background. This report examines the viability of the W reservoir as a reliable option for the treatment of ulcerative colitis and familial polyposis and studies W reservoir adaptation as reflected by changes in compliance and stool frequency. Methods. Since 1984, 109 patients have undergone proctocolectomy with W reservoir reconstruction. Ileal reservoir static compliance was measured in 70 and 57 patients at 2 and 12 months after ileostomy takedown and in 25 patients at 3 years. Compliance was calculated as the change in volume over change in pressure. Results. Twenty-four-hour stool frequency decreased from 7.3 +/- 0.2 at 2 months to 4.9 +/- 0.2 at 1 year for patients with ulcerative colitis and from 6.3 +/- 0.4 to 3.4 +/- 0.4 for patients with familial polyposis (p less-than-or-equal-to 0.05). Compliance increased from 12.7 +/- 0.6 ml/mm Hg to 14.3 +/- 0.6 ml/mm Hg between 2 months and 1 year. No significant increase in compliance occurred after 1 year. Ninety-six percent of patients were continent during the day at 12 months although 10% experienced occasional minor leakage at night. Average postoperative morbidity (for example, small-bowel obstruction, anastomotic complications) was 35%. No operative deaths, pelvic sepsis, or reservoir loss occurred. Conclusions. We conclude that W ileal reservoirs (1) are an excellent option for ileal reservoir reconstruction, (2) have optimal functional and compliance properties versus lower capacity designs and straight ileoanal pull-through procedures, and (3) maintain stable compliance characteristics and functional reservoir volume after the initial year of adaptation. C1 WILLIAM S MIDDLETON MEM VET ADM MED CTR,SURG SERV,MADISON,WI 53705. UNIV CINCINNATI,MED CTR,DEPT SURG,CINCINNATI,OH 45267. RP HARMS, BA (reprint author), UNIV WISCONSIN HOSP,DEPT SURG,H4-740,600 HIGHLAND AVE,MADISON,WI 53792, USA. NR 20 TC 16 Z9 16 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0039-6060 J9 SURGERY JI Surgery PD OCT PY 1992 VL 112 IS 4 BP 638 EP 648 PG 11 WC Surgery SC Surgery GA JR111 UT WOS:A1992JR11100005 PM 1329244 ER PT J AU BARRETT, BB ANDERSEN, JW ANDERSON, KC AF BARRETT, BB ANDERSEN, JW ANDERSON, KC TI BACTERIAL-CONTAMINATION OF BLOOD COMPONENTS SO TRANSFUSION LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 4 Z9 4 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 OCT PY 1992 VL 32 IS 8 SU S BP S41 EP S41 PG 1 WC Hematology SC Hematology GA JW378 UT WOS:A1992JW37800152 ER PT J AU YONG, WH RITZENTHALER, JA STOWELL, CP AF YONG, WH RITZENTHALER, JA STOWELL, CP TI INCREASED PLATELETPHERESIS YIELD WITHOUT EXCESSIVE REDUCTION OF PERIPHERAL PLATELET COUNT BY PROTOCOL MODIFICATION OF THE COBE SPECTRA 1000 SO TRANSFUSION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BLOOD TRANSFUS SERV,BOSTON,MA 02114. NR 0 TC 0 Z9 0 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 OCT PY 1992 VL 32 IS 8 SU S BP S61 EP S61 PG 1 WC Hematology SC Hematology GA JW378 UT WOS:A1992JW37800228 ER PT J AU HOLZ, GG HABENER, JF AF HOLZ, GG HABENER, JF TI SIGNAL TRANSDUCTION CROSSTALK IN THE ENDOCRINE SYSTEM - PANCREATIC BETA-CELLS AND THE GLUCOSE COMPETENCE CONCEPT SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Article ID INSULIN-SECRETION; GLUCOKINASE GENE; TRANSPORTERS; EXPRESSION AB Crosstalk between intracellular signalling systems is recognized as the principal means by which a cell orchestrates coordinate responses to stimulation by neurotransmitters, hormones or growth factors. The functional consequences of crosstalk are evident at multiple levels within a given signalling cascade, including the regulation of receptor-ligand interactions, guanine nucleotide-binding proteins, enzyme activities, ion channel function and gene expression. Here we focus on the pancreatic beta-cells of the islets of Langerhans to illustrate the important role crosstalk plays in the regulation of glucose-induced insulin secretion. Recent studies indicating a synergistic interaction in beta-cells between the glucose-regulated ATP-dependent signalling system and the hormonally regulated cAMP-dependent signalling system are emphasized. This interaction gives beta-cells the ability to match the ambient concentration of glucose to an appropriate insulin secretory response, a process we refer to as the induction of glucose competence. The glucose competence concept may provide new insights into the etiology and treatment of non-insulin-dependent diabetes mellitus (Type II diabetes). C1 HARVARD UNIV,SCH MED,HOWARD HUGHES MED INST,BOSTON,MA 02115. RP HOLZ, GG (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,DEPT MOLEC ENDOCRINOL,BOSTON,MA 02114, USA. RI Holz, George/A-3386-2012 FU NIDDK NIH HHS [R01 DK045817-06A2, R01 DK045817] NR 31 TC 109 Z9 109 U1 0 U2 1 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 OCT PY 1992 VL 17 IS 10 BP 388 EP 393 DI 10.1016/0968-0004(92)90006-U PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JU181 UT WOS:A1992JU18100006 PM 1455507 ER PT J AU DULIC, V LEES, E REED, SI AF DULIC, V LEES, E REED, SI TI ASSOCIATION OF HUMAN CYCLIN-E WITH A PERIODIC G(1)-S PHASE PROTEIN-KINASE SO SCIENCE LA English DT Article ID SACCHAROMYCES-CEREVISIAE; CELL-CYCLE; CDC28 MUTATION; YEAST; GENE; COMPLEMENTATION; HOMOLOG; POLYMERASE; MITOSIS; FAMILY AB G1 cyclins control the G1 to S phase transition in the budding yeast, Saccharomyces cerevisiae. Cyclin E was discovered in the course of a screen for human complementary DNAs that rescue a deficiency of G1 cyclin function in budding yeast. The amounts of both the cyclin E protein and an associated protein kinase activity fluctuated periodically through the human cell cycle; both were maximal in late G1 and early S phases. Cyclin E-associated kinase activity was correlated with the appearance of complexes containing cyclin E and the cyclin-dependent kinase Cdk2. Thus, the cyclin E-Cdk2 complex may constitute a human G1-S phase-specific regulatory protein kinase. C1 Scripps Res Inst, RES INST, DEPT MOLEC BIOL, LA JOLLA, CA 92037 USA. MASSACHUSETTS GEN HOSP, CTR CANC, BOSTON, MA 02129 USA. OI Dulic, Vjekoslav/0000-0003-1201-3901 FU NCI NIH HHS [CA55339]; NIGMS NIH HHS [GM38328, GM46006] NR 27 TC 824 Z9 841 U1 2 U2 3 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD SEP 25 PY 1992 VL 257 IS 5078 BP 1958 EP 1961 DI 10.1126/science.1329201 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JP594 UT WOS:A1992JP59400035 PM 1329201 ER PT J AU HARLOW, E AF HARLOW, E TI RETINOBLASTOMA - FOR OUR EYES ONLY SO NATURE LA English DT Editorial Material ID GENE-PRODUCT; CELL-CYCLE; TRANSCRIPTION FACTOR; SUSCEPTIBILITY GENE; PROTEIN; CANCER; PHOSPHORYLATION; SEQUENCE; COMPLEX; BIND RP HARLOW, E (reprint author), MASSACHUSETTS GEN HOSP,CTR CANC,BLDG 149,13TH ST,BOSTON,MA 02129, USA. NR 23 TC 30 Z9 31 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 SEP 24 PY 1992 VL 359 IS 6393 BP 270 EP 271 DI 10.1038/359270a0 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JP503 UT WOS:A1992JP50300026 PM 1406928 ER PT J AU COGGINS, CH DALEY, GQ MEEHAN, S AF COGGINS, CH DALEY, GQ MEEHAN, S TI A 72-YEAR-OLD WOMAN WITH ORTHOSTATIC HYPOTENSION, SYNCOPE, AND MARKED PROTEINURIA - SYSTEMIC AMYLOIDOSIS, AL KAPPA-TYPE, WITH INVOLVEMENT OF HEART, AUTONOMIC NERVES, KIDNEYS, AND LUNGS SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Discussion ID FAT TISSUE ASPIRATE; DIAGNOSIS; LIGHT C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP COGGINS, CH (reprint author), MASSACHUSETTS GEN HOSP,RENAL UNIT,BOSTON,MA 02114, USA. NR 8 TC 1 Z9 1 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 24 PY 1992 VL 327 IS 13 BP 943 EP 950 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA JP014 UT WOS:A1992JP01400008 ER PT J AU LEWANDOWSKI, ED AF LEWANDOWSKI, ED TI METABOLIC HETEROGENEITY OF CARBON SUBSTRATE UTILIZATION IN MAMMALIAN HEART - NMR DETERMINATIONS OF MITOCHONDRIAL VERSUS CYTOSOLIC COMPARTMENTATION SO BIOCHEMISTRY LA English DT Article ID PERFUSED RAT-HEART; FATTY-ACID METABOLISM; PYRUVATE-DEHYDROGENASE; OXIDATION; MYOCARDIUM; GLYCOLYSIS; ISCHEMIA; C-13; DICHLOROACETATE; CYCLE AB Carbon-13(C-13) nuclear magnetic resonance (NMR) spectroscopy can be used to target specific pathways of intermediary metabolism within intact tissues and was employed in this study to evaluate the compartmentation of pyruvate metabolism between the cytosol and mitochondrial matrix. The distribution of C-13 into the tissue alanine, lactate, and glutamate pools was evaluated during metabolism of [3-C-13]pyruvate in intact, isolated perfused rabbit hearts with and without activation of pyruvate dehydrogenase activity by dichloroacetate (5 mM). Equilibrium between the intracellular alanine and pyruvate pools was in evidence from the rapid evolution of the steady-state C-13 signal arising from the 3-carbon of alanine in intact hearts perfused with 2.5 mM 99.4% [3-C-13]pyruvate. Augmented pyruvate oxidation, in response to perfusion with dichloroacetate, was evident within C-13 NMR spectra of intact hearts as a relative increase in signal intensity of 53-62% (p < 0.05) from the 4-carbon resonance of C-13-enriched glutamate when compared to the unaffected alanine signal. The increased bulk flow of [3-C-13]pyruvate into the tricarboxylic acid cycle in response to dichloroacetate resulted in elevated fractional enrichment of glutamate from 68% in controls to 83% in the treated group (p < 0.04), via interconversion with alpha-ketoglutarate, without changes in the actual tissue content of glutamate. Evidence of metabolic heterogeneity of cytosolic and mitochondrial pyruvate pools was also obtained from analysis of tissue extracts with in vitro NMR spectroscopy. Although dichloroacetate increased the percentage of labeled acetyl CoA units entering the tricarboxylic acid cycle from 83% to 94% (p<0.03), indirect assessment from the observed enrichment levels of alanine showed the fractional enrichment of intracellular pyruvate in both groups to be on the order of only 60%. Lactate formation from labeled pyruvate, as opposed to endogenous pyruvate, was yet lower in the cytosol at 21-24%, remaining unaffected by the manipulation of pyruvate dehydrogenase activity. The results are consistent with different pools of pyruvate within the myocyte that are associated with either glycolytic metabolism within the cytosol or preferential oxidation within the mitochondrial matrix. Therefore, the metabolic fate of pyruvate is closely associated with the original carbohydrate source (endogenous versus exogenous) and the intracellular compartmentation of metabolic events. This metabolic heterogeneity was detected by virtue of communication between the cytosol and mitochondrial matrix as translated into the fractional C-13 enrichments of the primarily cytosolic alanine and glutamate pools which are then detectable by NMR spectroscopy. C1 BAYLOR COLL MED,DEPT MED,CARDIOL SECT,HOUSTON,TX 77030. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP LEWANDOWSKI, ED (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,CTR NMR,BLDG 149,13TH ST,BOSTON,MA 02129, USA. NR 35 TC 55 Z9 55 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 SEP 22 PY 1992 VL 31 IS 37 BP 8916 EP 8923 DI 10.1021/bi00152a031 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JP507 UT WOS:A1992JP50700031 PM 1390679 ER PT J AU MIRALPEIX, M SUN, XJ BACKER, JM MYERS, MG ARAKI, E WHITE, MF AF MIRALPEIX, M SUN, XJ BACKER, JM MYERS, MG ARAKI, E WHITE, MF TI INSULIN STIMULATES TYROSINE PHOSPHORYLATION OF MULTIPLE HIGH-MOLECULAR-WEIGHT SUBSTRATES IN FAO HEPATOMA-CELLS SO BIOCHEMISTRY LA English DT Article ID GROWTH FACTOR-I; ENDOGENOUS SUBSTRATE; 3T3-L1 ADIPOCYTES; SIGNAL TRANSDUCTION; RECEPTOR KINASE; RAT HEPATOMA; PROTEIN; BINDING; PHOSPHOTYROSINE; ANTIBODIES AB Insulin rapidly Stimulates tyrosine phosphorylation of cellular proteins which migrate between 165 and 190 kDa during SDS-PAGE. These proteins, collectively called pp185, were originally found in anti-phosphotyrosine antibody (alpha-PY) immunoprecipitates from insulin-stimulated Fao rat hepatoma cells. Recently, we purified and cloned IRS-1, one of the phosphoproteins that binds to alpha-PY and migrates near 180 kDa following insulin stimulation of rat liver [Sun, X. J., et al. (1991) Nature 352, 73-77]. IRS-1 and pp185 undergo tyrosine phosphorylation immediately after insulin stimulation and show an insulin dose response similar to that of insulin receptor autophosphorylation. However, IRS-1 was consistently 10 kDa smaller than the apparent molecular mass of pp185. The pp185 contained some immunoblottable IRS-1; however, cell lysates depleted of IRS-1 with anti-IRS-1 antibody still contained the high molecular weight forms of pp185 (HMW-pp185). Furthermore, the tryptic phosphopeptide map of IRS-1 was distinct from that of HMW-pp185, suggesting that at least two substrates migrate in this region during SDS-PAGE. Moreover, the phosphatidylinositol 3'-kinase and its 85-kDa associated protein (p85) bound to IRS-1 in Fao cells, but weakly or not at all to HMW-pp185. Our results show that Fao cells contain at least two insulin receptor substrates, IRS-1 and HMW-pp185, which may play unique roles in insulin signal transmission. C1 HARVARD UNIV,SCH MED,DEPT MED,JOSLIN DIABET CTR,DIV RES,1 JOSLIN PL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,PROGRAM CELL & DEV BIOL,BOSTON,MA 02115. FU NIDDK NIH HHS [DK 43808] NR 46 TC 36 Z9 37 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD SEP 22 PY 1992 VL 31 IS 37 BP 9031 EP 9039 DI 10.1021/bi00152a046 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JP507 UT WOS:A1992JP50700046 PM 1382584 ER PT J AU VECSEI, L BEAL, MF AF VECSEI, L BEAL, MF TI BEHAVIORAL AND PHARMACOLOGICAL EFFECTS OF CENTRALLY ADMINISTERED AMINOOXYACETIC ACID IN RATS SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Note DE AMINOOXYACETIC ACID; GABA (GAMMA-AMINOBUTYRIC ACID); LEARNING; PENTOBARBITAL; SEIZURES; SUBSTANCE-P ID ASPARTATE AB In the present experiment unilateral intrastriatal injections of aminooxyacetic acid (1, 2.5, 5 mumol) to freely moving animals and pentobarbital-anesthetized rats produced contralateral jerks and dose-dependent mortality, but no barrel rotation. At 10-12 days there were no significant differences in exploratory activity, passive avoidance behavior, and elevated plus-maze test in aminooxyacetic acid-treated animals as compared with controls. However freely moving animals microinjected with aminooxyacetic acid (but not the pentobarbital-pretreated group) had impaired learning activity in an active avoidance conditioning test, and showed reduced striatal concentrations of substance P and GABA. Intrastriatal injections of aminooxyacetic acid therefore result in both acute and chronic behavioral changes which are attenuated by pentobarbital anesthesia. C1 MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114. UNIV PECS,SCH MED,DEPT NEUROL,H-7622 PECS,HUNGARY. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. RI Vecsei, Laszlo/B-2066-2010 OI Vecsei, Laszlo/0000-0001-8037-3672 NR 10 TC 5 Z9 5 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD SEP 22 PY 1992 VL 220 IS 2-3 BP 259 EP 262 DI 10.1016/0014-2999(92)90756-T PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA JQ470 UT WOS:A1992JQ47000020 PM 1385183 ER PT J AU ROSENZWEIG, AC FREDERICK, CA LIPPARD, SJ AF ROSENZWEIG, AC FREDERICK, CA LIPPARD, SJ TI CRYSTALLIZATION AND PRELIMINARY-X-RAY ANALYSIS OF THE METHANE MONOOXYGENASE HYDROXYLASE PROTEIN FROM METHYLOCOCCUS-CAPSULATUS (BATH) SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Note DE CRYSTALLIZATION; METHANE MONOOXYGENASE; HYDROXYLASE; METHYLOCOCCUS-CAPSULATUS (BATH); METHYLOSINUS-TRICHOSPORIUM OB3B; X-RAY CRYSTALLOGRAPHY ID METHYLOSINUS-TRICHOSPORIUM OB3B; MONO-OXYGENASE; COMPONENT-C; OXO; PURIFICATION; RESOLUTION; REDUCTASE; CENTERS; MOSSBAUER; CLUSTER C1 MIT,DEPT CHEM,CAMBRIDGE,MA 02139. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. FU NCI NIH HHS [CA 09112]; NIGMS NIH HHS [GM 32134] NR 25 TC 7 Z9 7 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD SEP 20 PY 1992 VL 227 IS 2 BP 583 EP 585 DI 10.1016/0022-2836(92)90913-5 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JQ373 UT WOS:A1992JQ37300024 PM 1404375 ER PT J AU HINDS, PW MITTNACHT, S DULIC, V ARNOLD, A REED, SI WEINBERG, RA AF HINDS, PW MITTNACHT, S DULIC, V ARNOLD, A REED, SI WEINBERG, RA TI REGULATION OF RETINOBLASTOMA PROTEIN FUNCTIONS BY ECTOPIC EXPRESSION OF HUMAN CYCLINS SO CELL LA English DT Article ID LARGE-T-ANTIGEN; ADENOVIRUS E1A PROTEINS; CELL-CYCLE; GENE-PRODUCT; SUSCEPTIBILITY GENE; SACCHAROMYCES-CEREVISIAE; G1-SPECIFIC CYCLINS; CANDIDATE ONCOGENE; KINASE COMPLEX; G1 PHASE AB The retinoblastoma susceptibility gene (RB) product, the retinoblastoma protein (pRb), functions as a regulator of cell proliferation. Introduction of the RB gene into SAOS-2 osteosarcoma cells, which lack functional pRb, prevents cell cycle progression. Such growth-suppressive functions can be modulated by phosphorylation of pRb, which occurs via cell cycle-regulated kinases. We show that constitutively expressed cyclins A and E can overcome pRb-mediated suppression of proliferation. pRb becomes hyperphosphorylated in cells overexpressing these cyclins, and this phosphorylation is essential for cyclin A- and cyclin E-mediated rescue of pRb-blocked cells. This suggests that G1 and S phase cyclins can act as regulators of pRb function in the cell cycle by promoting pRb phosphorylation. C1 SCRIPPS RES INST, DEPT MOLEC BIOL, LA JOLLA, CA 92037 USA. MASSACHUSETTS GEN HOSP, ENDOCRINE UNIT, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02114 USA. RP HINDS, PW (reprint author), WHITEHEAD INST, 9 CAMBRIDGE CTR, CAMBRIDGE, MA 02142 USA. OI Dulic, Vjekoslav/0000-0003-1201-3901 FU NCI NIH HHS [CA55909]; NIGMS NIH HHS [GM38328, GM46006] NR 68 TC 934 Z9 936 U1 2 U2 18 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD SEP 18 PY 1992 VL 70 IS 6 BP 993 EP 1006 DI 10.1016/0092-8674(92)90249-C PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA JN781 UT WOS:A1992JN78100014 PM 1388095 ER PT J AU HARDIN, JA SHERR, DH DEMARIA, MA LOPEZ, PA AF HARDIN, JA SHERR, DH DEMARIA, MA LOPEZ, PA TI A SIMPLE FLUORESCENCE METHOD FOR SURFACE-ANTIGEN PHENOTYPING OF LYMPHOCYTES UNDERGOING DNA FRAGMENTATION SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE APOPTOSIS; THYMOCYTE; MULTICOLOR FLOW CYTOMETRY ID INDUCE DEATH; APOPTOSIS; CELLS; ACTIVATION; THYMOCYTES; LEADS AB Apoptosis, a metabolically active process of programmed cell death characterized by DNA fragmentation, is believed to play an important role in development of lymphocyte repertoires and in embryogenesis. Studies of this phenomenon would be greatly facilitated by the development of a simple assay capable of identifying and isolating intact apoptotic cells. A rapid fluorescence assay which identifies relatively small, intact cells containing fragmented DNA is described in this report. Thymocytes in which DNA fragmentation is induced by culture with or without dexamethasone are readily identified by their bright blue fluorescence after a 15 min treatment with Hoechst 33342, a DNA binding fluorochrome which diffuses through cell membranes. Since Hoechst 33342 staining does not require destruction of the cell membrane, it is possible to directly phenotype cell surface antigen expression on Hoechst 33342(bright) lymphocytes by conventional immunofluorescence techniques and to evaluate membrane integrity of Hoechst 33342 high, cells by dye exclusion criteria. The advantages of this system are that it: (1) is rapid and simple, (2) quantitates the percentage of cells fragmenting their DNA and presumably undergoing apoptosis, (3) permits standard immunofluorescence staining of cell surface markers to identify even minor cell subsets of presumably apoptotic cells within heterogeneous populations, (4) provides the tools (fluorescence activated cell sorting) for purifying intact cells containing fragmented DNA for further biochemical studies, and (5) provides a means for identifying cells which exclude vital dyes and in which DNA fragmentation will eventually result in cell death. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,200 LONGWOOD AVE,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,FLOW CYTOMETRY FACIL,BOSTON,MA 02115. FU NIAID NIH HHS [AI 23978] NR 24 TC 63 Z9 63 U1 0 U2 1 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 SEP 18 PY 1992 VL 154 IS 1 BP 99 EP 107 DI 10.1016/0022-1759(92)90217-H PG 9 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA JP567 UT WOS:A1992JP56700013 PM 1401949 ER PT J AU MAY, JW AF MAY, JW TI BREAST RECONSTRUCTION SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Note RP MAY, JW (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 17 PY 1992 VL 327 IS 12 BP 858 EP 858 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA JN120 UT WOS:A1992JN12000006 ER PT J AU HALES, CA MARK, EJ KAZEMI, H SYSTROM, DM MILLS, JA AF HALES, CA MARK, EJ KAZEMI, H SYSTROM, DM MILLS, JA TI A 68-YEAR-OLD WOMAN WITH RHEUMATOID-ARTHRITIS AND PULMONARY-HYPERTENSION - RHEUMATOID LUNG-DISEASE, WITH PLEURITIS, INTERSTITIAL LYMPHOCYTIC INFILTRATE, ARTERIAL-HYPERTENSION, AND VENOUS SCLEROSIS SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Discussion ID ANTICENTROMERE ANTIBODY; OCCLUSIVE DISEASE; CREST SYNDROME; MANIFESTATIONS; BRONCHIOLITIS; SARCOIDOSIS C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP HALES, CA (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 38 TC 6 Z9 6 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 17 PY 1992 VL 327 IS 12 BP 873 EP 880 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA JN120 UT WOS:A1992JN12000009 ER PT J AU WARREN, HS DANNER, RL MUNFORD, RS AF WARREN, HS DANNER, RL MUNFORD, RS TI ANTIENDOTOXIN MONOCLONAL-ANTIBODIES - REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 NIH,BETHESDA,MD 20205. UNIV TEXAS,SW MED CTR,DALLAS,TX 75235. RP WARREN, HS (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 17 PY 1992 VL 327 IS 12 BP 890 EP 890 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA JN120 UT WOS:A1992JN12000018 ER PT J AU SKALNIK, DG NEUFELD, EJ AF SKALNIK, DG NEUFELD, EJ TI SEQUENCE-SPECIFIC BINDING OF HMG-I(Y) TO THE PROXIMAL PROMOTER OF THE GP91-PHOX GENE SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID PROTEIN HMG-I; BASE-PAIRS; DNA; EXPRESSION; CLONING; INVITRO; MOTIF; CDNA C1 HARVARD UNIV,CHILDRENS HOSP,SCH MED,DANA FARBER CANC INST,DEPT PEDIAT,DIO HEMATOL ONCOL,BOSTON,MA 02115. RI Neufeld, Ellis/F-9331-2011 NR 26 TC 22 Z9 22 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 SEP 16 PY 1992 VL 187 IS 2 BP 563 EP 569 DI 10.1016/0006-291X(92)91231-E PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA JN585 UT WOS:A1992JN58500001 PM 1530615 ER PT J AU EMANUEL, EJ EMANUEL, LL AF EMANUEL, EJ EMANUEL, LL TI MODELS OF THE PHYSICIAN-PATIENT RELATIONSHIP - REPLY SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP EMANUEL, EJ (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115, USA. NR 4 TC 0 Z9 0 U1 1 U2 4 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 SEP 16 PY 1992 VL 268 IS 11 BP 1412 EP 1413 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA JM849 UT WOS:A1992JM84900016 ER PT J AU MACINTYRE, EA SMIT, L RITZ, J KIRSCH, IR STROMINGER, JL AF MACINTYRE, EA SMIT, L RITZ, J KIRSCH, IR STROMINGER, JL TI DISRUPTION OF THE SCL LOCUS IN T-LYMPHOID MALIGNANCIES CORRELATES WITH COMMITMENT TO THE T-CELL RECEPTOR-ALPHA-BETA LINEAGE SO BLOOD LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; SITE-SPECIFIC RECOMBINATION; LOOP-HELIX PROTEINS; TRANSCRIPTIONAL ENHANCER; GAMMA-DELTA; CHROMOSOMAL TRANSLOCATION; DNA-BINDING; TAL-1 GENE; CHAIN GENE; C-ALPHA C1 USN,MED ONCOL BRANCH,NCI,BETHESDA,MD 20814. HARVARD UNIV,DEPT BIOCHEM & MOLEC BIOL,CAMBRIDGE,MA 02138. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NCI NIH HHS [CA47554] NR 51 TC 58 Z9 59 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 SEP 15 PY 1992 VL 80 IS 6 BP 1511 EP 1520 PG 10 WC Hematology SC Hematology GA JN507 UT WOS:A1992JN50700019 PM 1387813 ER PT J AU ARCECI, RJ STIEGLITZ, K BIERER, BE AF ARCECI, RJ STIEGLITZ, K BIERER, BE TI IMMUNOSUPPRESSANTS FK506 AND RAPAMYCIN FUNCTION AS REVERSAL AGENTS OF THE MULTIDRUG RESISTANCE PHENOTYPE SO BLOOD LA English DT Article ID HAMSTER OVARY CELLS; POLYMERASE CHAIN-REACTION; MDR1 GENE-EXPRESSION; P-GLYCOPROTEIN; DOXORUBICIN RESISTANCE; DRUG-RESISTANCE; CYCLOSPORINE-A; HUMAN-TUMORS; ADRIAMYCIN RESISTANCE; QUANTITATIVE-ANALYSIS C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT HEMATOL ONCOL,BOSTON,MA 02115. CHILDRENS HOSP MED CTR,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DIV HEMATOL ONCOL,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 [CA39542, CA48162]; NIGMS NIH HHS [GM38156] NR 56 TC 113 Z9 115 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD SEP 15 PY 1992 VL 80 IS 6 BP 1528 EP 1536 PG 9 WC Hematology SC Hematology GA JN507 UT WOS:A1992JN50700021 PM 1381629 ER PT J AU DEBOER, M BOLSCHER, BGJM DINAUER, MC ORKIN, SH SMITH, CIE AHLIN, A WEENING, RS ROOS, D AF DEBOER, M BOLSCHER, BGJM DINAUER, MC ORKIN, SH SMITH, CIE AHLIN, A WEENING, RS ROOS, D TI SPLICE SITE MUTATIONS ARE A COMMON CAUSE OF X-LINKED CHRONIC GRANULOMATOUS-DISEASE SO BLOOD LA English DT Article ID CYTOCHROME-B; CHROMOSOMAL LOCATION; HUMAN-NEUTROPHILS; MCLEOD SYNDROME; GENE; CHAIN; DEFICIENCIES; COMPONENTS; DELETION; ABSENCE C1 NETHERLANDS RED CROSS,BLOOD TRANSFUS SERV,CENT LAB,POB 9190,1006 AD AMSTERDAM,NETHERLANDS. UNIV AMSTERDAM,EXPTL & CLIN IMMUNOL LAB,AMSTERDAM,NETHERLANDS. INDIANA UNIV,JAMES WHITCOMB RILEY HOSP CHILDREN,SCH MED,DEPT PEDIAT,HB WELLS CTR PEDIAT RES,INDIANAPOLIS,IN 46223. HOWARD HUGHES MED INST,BOSTON,MA. SACHS CHILDRENS HOSP,DEPT PEDIAT,STOCKHOLM,SWEDEN. UNIV AMSTERDAM,ACAD MED CTR,EMMA CHILDRENS HOSP,1105 AZ AMSTERDAM,NETHERLANDS. HUDDINGE HOSP,KAROLINSKA INST,DEPT CLIN IMMUNOL,NOVUM,S-14186 HUDDINGE,SWEDEN. HUDDINGE HOSP,KAROLINSKA INST,CTR BIOTECHNOL,NOVUM,S-14186 HUDDINGE,SWEDEN. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PEDIAT,BOSTON,MA 02115. CHILDRENS HOSP MED CTR,DIV HEMATOL ONCOL,BOSTON,MA 02115. NR 34 TC 46 Z9 47 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 SEP 15 PY 1992 VL 80 IS 6 BP 1553 EP 1558 PG 6 WC Hematology SC Hematology GA JN507 UT WOS:A1992JN50700024 PM 1520880 ER PT J AU SEIZINGER, BR AF SEIZINGER, BR TI ANTIONCOGENES AND THE DEVELOPMENT OF TUMORS IN THE HUMAN NERVOUS-SYSTEM SO CANCER LA English DT Article; Proceedings Paper CT NATIONAL CONF ON INTEGRATION OF MOLECULAR GENETICS INTO CANCER MANAGEMENT CY APR 10-12, 1991 CL MIAMI, FL ID RETINOBLASTOMA SUSCEPTIBILITY GENE; BILATERAL ACOUSTIC NEUROFIBROMATOSIS; ENDOCRINE NEOPLASIA; TYPE-1 GENE; CELL-CYCLE; VONRECKLINGHAUSEN NEUROFIBROMATOSIS; P53 GENE; PRODUCT; CHROMOSOME-17; MUTATIONS AB Two distinct mechanisms of tumorigenesis have been identified in humans. One mechanism is associated with the activation of growth-promoting factors such as protooncogenes, growth factors, and growth factor receptors. However, there is overwhelming evidence for the existence of an alternative tumor mechanism that is related to the loss or inactivation of genes that normally suppress cell growth. These genes have been called "antioncogenes" or "tumor-suppressor" genes. They appear to be involved fundamentally in the development of many human cancers. This article reviews the potential importance of tumor-suppressor genes in tumor development and growth control in the human nervous system. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP SEIZINGER, BR (reprint author), MASSACHUSETTS GEN HOSP,MOLEC NEUROONCOL LAB,BOSTON,MA 02114, USA. FU NCI NIH HHS [CA49455] NR 55 TC 9 Z9 9 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 SEP 15 PY 1992 VL 70 IS 6 SU S BP 1782 EP 1787 DI 10.1002/1097-0142(19920915)70:4+<1782::AID-CNCR2820701620>3.0.CO;2-5 PG 6 WC Oncology SC Oncology GA JP334 UT WOS:A1992JP33400018 PM 1516032 ER PT J AU BOUCHER, Y JAIN, RK AF BOUCHER, Y JAIN, RK TI MICROVASCULAR PRESSURE IS THE PRINCIPAL DRIVING FORCE FOR INTERSTITIAL HYPERTENSION IN SOLID TUMORS - IMPLICATIONS FOR VASCULAR COLLAPSE SO CANCER RESEARCH LA English DT Article ID RAT MAMMARY-TUMORS; FLUID PRESSURE; BLOOD-FLOW; RADIATION RESPONSE; CARCINOMA; MACROMOLECULES; RESISTANCE; TRANSPORT; PERFUSION; GROWTH AB The interstitial fluid pressure (IFP) has been found to be as high as 20 to 50 mm Hg in both experimental and human solid tumors. While the IFP is an important determinant of the delivery of therapeutic agents to neoplastic cells in vivo, the mechanisms responsible for interstitial hypertension are not completely understood. The high vascular permeability of tumor blood vessels and the absence of a functional lymphatic circulation suggest that the hydrostatic microvascular pressure (MVP) is the main force governing IFP in tumors. To test this hypothesis, we simultaneously measured IFP and MVP in 13 tissue-isolated R3230AC mammary adenocarcinomas transplanted in rats. The MVP in superficial postcapillary venules of diameters between 25 and 250-mu-m was measured with the micropuncture technique. MVP was compared to the IFP in the periphery (measured with micropuncture technique) and in the center (measured with wick-in-needle technique). Similar to our previous study, IFP rose rapidly and reached maximum values at a depth of 0.2 to 1.0 mm from the tumor surface. These maximum IFP values [16.5 +/- 7.1 mm Hg (SD)] were equal to IFP in the tumor center 118.4 +/- 9.3 mm Hg] [R2 = 0.86, P > 0.8]. Superficial MVP (17.3 +/- 6.1 mm Hg) was equal to both central (P > 0.9) and superficial IFP (P > 0.7). These results demonstrate that the main driving force for IFP in tumors is the MVP. Furthermore, the concept that blood vessel collapse is induced by higher hydrostatic pressures in the tumor interstitium compared to that in the vascular lumen is not supported by the present finding that elevated IFP is accompanied by equally elevated MVP. RP BOUCHER, Y (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,STEELE LAB,BOSTON,MA 02114, USA. FU NCI NIH HHS [CA-36902, CA-37239, CA-49792] NR 32 TC 333 Z9 338 U1 0 U2 14 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 15 PY 1992 VL 52 IS 18 BP 5110 EP 5114 PG 5 WC Oncology SC Oncology GA JN053 UT WOS:A1992JN05300043 PM 1516068 ER PT J AU MOK, CH TSAO, SW KNAPP, RC FISHBAUGH, PM LAU, CC AF MOK, CH TSAO, SW KNAPP, RC FISHBAUGH, PM LAU, CC TI UNIFOCAL ORIGIN OF ADVANCED HUMAN EPITHELIAL OVARIAN CANCERS SO CANCER RESEARCH LA English DT Note ID P53 GENE; CARCINOMA; MUTATIONS AB Ovarian cancers are often diagnosed at a late stage, after the cancer cells have spread to extraovarian sites. Failure to diagnose these tumors earlier may reflect the lack of symptoms and the need for a sensitive, reliable screening test. Alternatively, this can be explained by the hypothesis that some of the extraovarian tumor implants do not represent metastatic spread from the primary cancer but instead are multiple primary tumors developing simultaneously in the peritoneal epithelium. If this is the case, some patients with advanced ovarian cancer may never have had a stage I disease, making early detection theoretically impossible. In this study, we examined the mutational pattern of the p53 gene in 9 patients with epithelial ovarian cancers using tissue collected from different sites within the same patient. In all 9 cases, the mutational pattern of the p53 gene was identical in cancer cells from different sites within the same patient, strongly suggesting that these ovarian tumors were of unifocal origin and that cancer tissues collected from different sites are derived from a single origin. C1 BRIGHAM & WOMENS HOSP,DEPT OBSTET GYNECOL & REPROD BIOL,GYNECOL ONCOL LAB,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV GYNECOL ONCOL,BOSTON,MA 02115. NR 16 TC 117 Z9 117 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 15 PY 1992 VL 52 IS 18 BP 5119 EP 5122 PG 4 WC Oncology SC Oncology GA JN053 UT WOS:A1992JN05300045 PM 1516069 ER PT J AU OH, Y MATALON, S KLEYMAN, TR BENOS, DJ AF OH, Y MATALON, S KLEYMAN, TR BENOS, DJ TI BIOCHEMICAL-EVIDENCE FOR THE PRESENCE OF AN AMILORIDE BINDING-PROTEIN IN ADULT ALVEOLAR TYPE-II PNEUMOCYTES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BLADDER MEMBRANE-VESICLES; EPITHELIAL SODIUM-CHANNEL; ISOLATED RAT LUNG; ION-TRANSPORT; NA+ CHANNELS; CELLS; LOCALIZATION; ANTIBODIES; ANALOGS; ABSORPTION AB An amiloride binding protein in adult rat and rabbit alveolar type II (ATII) cells was characterized using three different antibodies against epithelial Na+ channel proteins. We found that 1) polyclonal antibodies raised against epithelial Na+ channel proteins from bovine kidney cross-react with a 135-kDa protein in ATII membrane vesicles on Western blots; 2) using the photoreactive amiloride analog, 2'-methoxy-5'-nitrobenzamil (NMBA), in combination with anti-amiloride antibodies, we found that NMBA specifically labeled the same M(r) protein; and 3) monoclonal anti-idiotypic antibodies directed against anti-amiloride antibodies also recognized this same M(r) protein on Western blots. We also demonstrated a low benzamil affinity binding site (apparent K(d) = 370 nM) in rabbit ATII cell membranes and both high and low benzamil affinity binding sites (apparent K(d) = 6 nM and 230 nM) in bovine kidney membranes using [H-3]Br-benzamil as a ligand. Pharmacological inhibitory profiles for displacing bound [H-3]Br-benzamil were also different between ATII cells and bovine kidneys. These observations indicate that adult ATII pneumocytes express a population of epithelial Na+ channels having a low affinity to benzamil and amiloride and a pharmacological inhibitory profile different from that in bovine kidney. C1 UNIV ALABAMA,DEPT PHYSIOL & BIOPHYS,BIRMINGHAM,AL 35294. UNIV ALABAMA,DEPT ANESTHESIOL,BIRMINGHAM,AL 35294. UNIV ALABAMA,DEPT PEDIAT,BIRMINGHAM,AL 35294. UNIV PENN,DEPT MED,PHILADELPHIA,PA 19104. UNIV PENN,DEPT PHYSIOL,PHILADELPHIA,PA 19104. VET AFFAIRS MED CTR,PHILADELPHIA,PA 19104. FU NHLBI NIH HHS [HL-31197]; NIDDK NIH HHS [DK-37206] NR 41 TC 28 Z9 28 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 SEP 15 PY 1992 VL 267 IS 26 BP 18498 EP 18504 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JN502 UT WOS:A1992JN50200042 PM 1326526 ER PT J AU EGERTON, M BURGESS, WH CHEN, D DRUKER, BJ BRETSCHER, A SAMELSON, LE AF EGERTON, M BURGESS, WH CHEN, D DRUKER, BJ BRETSCHER, A SAMELSON, LE TI IDENTIFICATION OF EZRIN AS AN 81-KDA TYROSINE-PHOSPHORYLATED PROTEIN IN T-CELLS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ANTIGEN RECEPTOR; PHOSPHOLIPASE C-GAMMA-1; KINASE SUBSTRATE; LPR/LPR MICE; ZETA-CHAIN; ACTIVATION; FAMILY; STIMULATION; PHOSPHATASE; BAND-4.1 AB We have used APT affinity purification to isolate tyrosine-phosphorylated proteins from MRL lpr/lpr (lpr) mouse T cells. One such protein is pp81 ezrin, previously identified as a tyrosine-phosphorylated protein in epidermal growth factor-stimulated A431 carcinoma cells. Biochemical analyses in A431 and gastric parietal cells have revealed ezrin to be a cytoskeleton-associated cytosolic protein. In Jurkat T cells, however, using similar methods we have shown ezrin to be a cytosolic protein with no measurable cytoskeletal association. We also observed no increases in ezrin tyrosine phosphorylation in TCR-stimulated Jurkat T cells, unless the cells were pretreated with protein tyrosine phosphatase inhibitors, suggesting that T cell ezrin tyrosine phosphorylation is tightly controlled by protein tyrosine phosphatases. The fraction of tyrosine phosphorylated ezrin in lpr T cells was 5 to 10 times that observed in Jurkat T cells, which along with constitutive TCR-zeta phosphorylation and pp60fyn over-expression, is a feature of the lpr defect. C1 AMER RED CROSS LABS,ROCKVILLE,MD 20855. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELLULAR & MOLEC BIOL,BOSTON,MA 02115. CORNELL UNIV,BIOCHEM MOLEC & CELL BIOL SECT,ITHACA,NY 14853. RP EGERTON, M (reprint author), NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892, USA. NR 36 TC 77 Z9 78 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 15 PY 1992 VL 149 IS 6 BP 1847 EP 1852 PG 6 WC Immunology SC Immunology GA JN121 UT WOS:A1992JN12100004 PM 1381389 ER PT J AU VIDARD, L ROCK, KL BENACERRAF, B AF VIDARD, L ROCK, KL BENACERRAF, B TI HETEROGENEITY IN ANTIGEN PROCESSING BY DIFFERENT TYPES OF ANTIGEN-PRESENTING CELLS - EFFECT OF CELL-CULTURE ON ANTIGEN PROCESSING ABILITY SO JOURNAL OF IMMUNOLOGY LA English DT Article ID RESTRICTED LYMPHOCYTES-T; HLA-DR MOLECULES; DENDRITIC CELLS; CLASS-I; IMMUNOGENIC PEPTIDES; PROTEIN ANTIGENS; LANGERHANS CELLS; SELF-PEPTIDES; B-CELLS; BINDING AB The ability of normal B cells, peritoneal macrophages, and splenic APC to process and present OVA to a panel of T-T hybridomas with different specificities was investigated. In all cases, B cells were less efficient than unfractionated splenocytes in presenting OVA or its peptides. However, when the presentation of native Ag was compared to the presentation of peptides, it was obvious that there were marked differences in the ability of these two APC populations to generate different epitopes from OVA. Leupeptin inhibits the processing of selected epitopes from native OVA differently when it was presented by spleen cells or B cells, suggesting that these two APC populations differ in their protease content. The effect of in vitro culture on the ability of splenic and peritoneal APC to process OVA was also investigated. Native OVA presentation by macrophages and spleen cells was affected by in vitro culture, more for some epitopes than for other epitopes. In contrast, presentation of exogenous peptides by paraformaldehyde-fixed APC was either not affected by previous culturing for 3 days, or very much improved. Altogether, these data demonstrate that different epitopes on the same protein may be independently and differentially processed by B cells and spleen cells. Furthermore, the precise peptides that are produced may vary with the physiologic state of the APC. C1 INST CURIE,UNITE IMMUNOGENET,CNRS,URA 1413,F-75231 PARIS 05,FRANCE. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RP VIDARD, L (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 37 TC 84 Z9 84 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 15 PY 1992 VL 149 IS 6 BP 1905 EP 1911 PG 7 WC Immunology SC Immunology GA JN121 UT WOS:A1992JN12100012 PM 1517561 ER PT J AU FINBERG, RW WHITE, W NICHOLSONWELLER, A AF FINBERG, RW WHITE, W NICHOLSONWELLER, A TI DECAY-ACCELERATING FACTOR EXPRESSION ON EITHER EFFECTOR OR TARGET-CELLS INHIBITS CYTOTOXICITY BY HUMAN NATURAL-KILLER-CELLS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA; HOMOLOGOUS RESTRICTION FACTOR; COMPLEMENT TRANSMEMBRANE CHANNELS; LARGE GRANULAR LYMPHOCYTES; MEMBRANE ATTACK COMPLEX; CYTOLYTIC LYMPHOCYTES; FACTOR DAF; REGULATORY PROTEIN; HUMAN-ERYTHROCYTES; C-3 CONVERTASES AB Previous studies have shown that freshly isolated CD16+ NK cells are deficient in the expression of decay-accelerating factor (DAF), or CD55, a membrane regulator of C3 activation. In this study we investigated the significance, for NK cell-mediated lysis, of DAF expression on the target and effector cells. The effect of DAF expression on the susceptibility of NK cell targets was investigated by several means: first, DAF- cell lines were cloned from K562; second, the cloned DAF- cells were reconstituted with exogenous purified DAF; and third, anti-DAF F(ab')2 was used to block DAF function on the DAF+ K562 cells. Consistently, the presence of DAF in the target cell membrane, either naturally occurring or experimentally incorporated, afforded the target cell protection against lysis, and this protection could be blocked with anti-DAF. Similarly, targets for antibody-dependent cell-mediated cytotoxicity with exogenous DAF incorporated in their plasma membrane became less sensitive to antibody-dependent cell-mediated cytotoxicity by NK cells compared with the same target cells without incorporated DAF in their membranes. DAF incorporated in the plasma membranes of the effector NK cells made the NK cells less effective at killing K562 targets. The known function of DAF is to regulate C3 activation, and we were able to demonstrate that the isolated NK cell is capable of releasing C3. It is also possible that the participation of DAF in NK cell function represents a new, noncomplement-dependent function for DAF. C1 BETH ISRAEL HOSP,DEPT MED,DIV INFECT DIS,330 BROOKLINE AVE,BOSTON,MA 02215. BETH ISRAEL HOSP,HARVARD THORDIKE LAB,BOSTON,MA 02215. BETH ISRAEL HOSP,CHARLES A DANA RES INST,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,INFECT DIS LAB,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. RI Finberg, Robert/E-3323-2010 FU NHLBI NIH HHS [HL-33768] NR 34 TC 57 Z9 58 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 15 PY 1992 VL 149 IS 6 BP 2055 EP 2060 PG 6 WC Immunology SC Immunology GA JN121 UT WOS:A1992JN12100031 PM 1381394 ER PT J AU WRIGHT, TL AF WRIGHT, TL TI CHRONIC HEPATITIS-B AND HEPATITIS-C - WHAT IS THE STATUS OF DRUG-THERAPY SO POSTGRADUATE MEDICINE LA English DT Article ID ALPHA-INTERFERON THERAPY; CHRONIC ACTIVE HEPATITIS; RANDOMIZED CONTROLLED TRIAL; HUMAN-LEUKOCYTE INTERFERON; PLACEBO-CONTROLLED TRIAL; CHRONIC NON-A; VIRUS-INFECTION; ALFA THERAPY; GAMMA-INTERFERON; BETA-INTERFERON AB Chronic hepatitis remains difficult to treat. Use of interferon has been successful against both hepatitis B and C viruses, but the outcome of long-term administration has yet to be determined. Not all patients respond to interferon, however, and some have side effects that cause them to discontinue therapy. Dr Wright discusses the results of studies to evaluate therapy with alpha, beta, and gamma interferon as well as with other agents, such as ribavirin, thymosin, and ursodeoxycholic acid. C1 UNIV CALIF SAN FRANCISCO,SCH MED,DIV GASTROENTEROL & HEPATOL,SAN FRANCISCO,CA 94143. RP WRIGHT, TL (reprint author), SAN FRANCISCO VET AFFAIRS MED CTR,DIV GASTROENTEROL 111B,4150 CLEMENT ST,SAN FRANCISCO,CA 94121, USA. NR 32 TC 7 Z9 7 U1 0 U2 0 PU MCGRAW HILL HEALTHCARE PUBLICATIONS PI MINNEAPOLIS PA 4530 WEST 77TH ST, MINNEAPOLIS, MN 55435-5000 SN 0032-5481 J9 POSTGRAD MED JI Postgrad. Med. PD SEP 15 PY 1992 VL 92 IS 4 BP 75 EP 80 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA JP735 UT WOS:A1992JP73500008 PM 1382288 ER PT J AU GALVIN, K KRISHNA, S PONCHEL, F FROHLICH, M CUMMINGS, DE CARLSON, R WANDS, JR ISSELBACHER, KJ PILLAI, S OZTURK, M AF GALVIN, K KRISHNA, S PONCHEL, F FROHLICH, M CUMMINGS, DE CARLSON, R WANDS, JR ISSELBACHER, KJ PILLAI, S OZTURK, M TI THE MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I ANTIGEN-BINDING PROTEIN-P88 IS THE PRODUCT OF THE CALNEXIN GENE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE HUMAN CALNEXIN; CHAPERONE; IMMUNOGLOBULINS; ENDOPLASMIC RETICULUM ID HUMAN HEPATOCELLULAR-CARCINOMA; ENDOPLASMIC-RETICULUM; HEAVY-CHAINS; CELL-LINE; ANTIBODIES; EXPRESSION; MEMBRANE AB A 90-kDa phosphoprotein (p90) of the endoplasmic reticulum was identified by a monoclonal antibody generated against human hepatoma cells. Pulse-chase experiments with [P-32]phosphate and [S-35]methionine demonstrated that p90 formed both stable and transient complexes with other cellular proteins, suggesting its role as a molecular chaperone. This protein associates with heavy chains of major histocompatibility complex class I proteins, suggesting that it is the human homolog of the recently described 88-kDa protein that transiently associates with murine class I molecules in the endoplasmic reticulum. The p90 protein also associates in B lymphocytes with membrane immunoglobulin-mu heavy chains and may serve as a chaperone for many membrane-bound polypeptides. A partial human p90 cDNA was cloned from a lambda-gt11 expression library and identified as the human homolog of calnexin, a major canine calcium-binding protein found to be associated with the signal-sequence receptor in endoplasmic reticulum membranes. C1 MASSACHUSETTS GEN HOSP,CTR CANC,149 13TH ST,BOSTON,MA 02129. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. RI ozturk, mehmet/G-3330-2014 FU NCI NIH HHS [CA49832, CA54567, CA35711] NR 19 TC 74 Z9 76 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 SEP 15 PY 1992 VL 89 IS 18 BP 8452 EP 8456 DI 10.1073/pnas.89.18.8452 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JN503 UT WOS:A1992JN50300010 PM 1326756 ER PT J AU KAYE, RE FRUMAN, DA BIERER, BE ALBERS, MW ZYDOWSKY, LD HO, SI JIN, YJ CASTELLS, MC SCHREIBER, SL WALSH, CT BURAKOFF, SJ AUSTEN, KF KATZ, HR AF KAYE, RE FRUMAN, DA BIERER, BE ALBERS, MW ZYDOWSKY, LD HO, SI JIN, YJ CASTELLS, MC SCHREIBER, SL WALSH, CT BURAKOFF, SJ AUSTEN, KF KATZ, HR TI EFFECTS OF CYCLOSPORINE-A AND FK506 ON FC-EPSILON RECEPTOR TYPE-I-INITIATED INCREASES IN CYTOKINE MESSENGER-RNA IN MOUSE BONE MARROW-DERIVED PROGENITOR MAST-CELLS - RESISTANCE TO FK506 IS ASSOCIATED WITH A DEFICIENCY IN FK506-BINDING PROTEIN FKBP12 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE IMMUNOPHILIN; CYCLOPHILIN; CALCINEURIN; CYTOKINE; EXOCYTOSIS ID BASOPHILIC LEUKEMIA-CELLS; SULFATE-E-PROTEOGLYCAN; MOLECULAR-CLONING; DIFFERENTIAL RELEASE; W/WV MICE; DI-B; HISTAMINE; CYCLOPHILIN; FK-506; INTRAPERITONEAL AB The inhibitory effects of cyclosporin A (CsA) and FK506 on Fc(epsilon) receptor type I-initiated increases in cytokine mRNA and the expression of their intracellular binding proteins were studied in interleukin 3 (IL-3)-dependent, mouse bone marrow-derived mast cells (BMMCs). In BMMCs sensitized with IgE anti-trinitrophenyl, CsA inhibited trinitrophenylated bovine serum albumin-induced increases in mRNA for IL-1-beta, tumor necrosis factor-alpha (TNF-alpha), and IL-6 in a dose-related manner (IC50 values of 4, 65, and 130 nM, respectively). FK506 did not inhibit hapten-specific increases of mRNA for TNF-alpha or IL-6, and for IL-1-beta the IC50 was >50-fold higher than that of CsA. Neither agent inhibited exocytosis of the endogenous secretory granule mediators beta-hexosaminidase and histamine at the IC50 values for inhibition of increases in cytokine mRNA. BMMCs expressed cyclophilin, and CsA inhibited the phosphatase activity of cellular calcineurin with an IC50 of almost-equal-to 8 nM. That CsA inhibited IL-1-beta mRNA accumulation in IgE-activated BMMCs with an IC50 similar to that for inhibition of calcineurin activity, whereas the IC50 values were almost-equal-to 20-fold higher for the inhibition of TNF-alpha and IL-6 mRNA, suggests that the induction of TNF-alpha and IL-6 is less dependent upon calcineurin activity than is the induction of IL-1-beta. BMMCs were deficient in the 12-kDa FK506-binding protein FKBP12, but not FKBP13, as assessed by RNA and protein blot analyses. FK506 did not inhibit calcineurin phosphatase activity in BMMCs, even at drug concentrations of 1000 nM. The resistance of BMMCs to inhibition of Fc(epsilon) receptor type I-mediated increases in cytokine mRNA by FK506 is most likely due to their deficiency of FKBP12 and the related inability to inhibit the activity of calcineurin. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT RHEUMATOL & IMMUNOL,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DIV HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,DEPT CHEM,CAMBRIDGE,MA 02138. RP KAYE, RE (reprint author), HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115, USA. FU NIAID NIH HHS [AI07306, AI22531, AI23401] NR 41 TC 73 Z9 73 U1 1 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 SEP 15 PY 1992 VL 89 IS 18 BP 8542 EP 8546 DI 10.1073/pnas.89.18.8542 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JN503 UT WOS:A1992JN50300028 PM 1382293 ER PT J AU KAWAKAMI, A TIAN, QS DUAN, XC STREULI, M SCHLOSSMAN, SF ANDERSON, P AF KAWAKAMI, A TIAN, QS DUAN, XC STREULI, M SCHLOSSMAN, SF ANDERSON, P TI IDENTIFICATION AND FUNCTIONAL-CHARACTERIZATION OF A TIA-1-RELATED NUCLEOLYSIN SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE APOPTOSIS; PROGRAMMED CELL DEATH; CYTOLYTIC LYMPHOCYTES; CYTOTOXIC GRANULES ID NATURAL-KILLER CELLS; TOXIC LYMPHOCYTES-T; DNA FRAGMENTATION; TARGET-CELLS; PERFORIN; GRANULES; LYSIS; CYTOLYSIS; APOPTOSIS; MECHANISM AB We recently reported the molecular cloning of a cytotoxic granule-associated RNA-binding protein designated TIA-1. The ability of recombinant TIA-1 to induce DNA fragmentation in permeabilized cells suggested that this protein is the granule component responsible for inducing apoptosis in cytolytic lymphocyte (CTL) targets. Here we report the characterization of a cDNA encoding a TIA-1-related protein designated TIAR. The deduced amino acid sequence of TIAR reveals it to be a 42-kDa protein possessing three RNA-binding domains and a carboxyl-terminal auxiliary domain. Although the RNA-binding domains of TIA-1 and TIAR share >85% amino acid homology, their carboxyl-terminal auxiliary domains are only 51% homologous. The carboxyl terminus of TIAR contains a lysosome-targeting motif, indicating that TIAR is probably a cytotoxic granule-associated protein. Like TIA-1, purified recombinant TIAR induced DNA fragmentation in permeabilized target cells. Although immunoblotting analysis of post-nuclear supernatants revealed TIA-1 protein to be restricted to CTLs, PCR analysis revealed the expression of TIA-1 and TIAR mRNA transcripts in a wide variety of cell types. Our data suggest that the granules of CTLs contain at least two candidate nucleolysins involved in CTL killing. C1 BRIGHAM & WOMENS HOSP,DEPT RHEUMATOL & IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP KAWAKAMI, A (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA53595]; NIAID NIH HHS [AI 12069] NR 28 TC 144 Z9 147 U1 0 U2 4 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 SEP 15 PY 1992 VL 89 IS 18 BP 8681 EP 8685 DI 10.1073/pnas.89.18.8681 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JN503 UT WOS:A1992JN50300056 PM 1326761 ER PT J AU KOWALL, NW QUIGLEY, BJ LU, F KOSOFSKY, BE FERRANTE, RJ AF KOWALL, NW QUIGLEY, BJ LU, F KOSOFSKY, BE FERRANTE, RJ TI SUBSTANCE-P AND SUBSTANCE-P RECEPTOR HISTOCHEMISTRY IN HUMAN NEURODEGENERATIVE DISEASES SO REGULATORY PEPTIDES LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,DEPT NEUROPATHOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RI Kowall, Neil/G-6364-2012 OI Kowall, Neil/0000-0002-6624-0213 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-0115 J9 REGUL PEPTIDES JI Regul. Pept. PD SEP 15 PY 1992 SU 1 BP S27 EP S27 PG 1 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA JR149 UT WOS:A1992JR14900027 ER PT J AU SODROSKI, J AF SODROSKI, J TI THE HUMAN T-CELL LEUKEMIA-VIRUS (HTLV) TRANSACTIVATOR (TAX) PROTEIN SO BIOCHIMICA ET BIOPHYSICA ACTA LA English DT Review ID LONG-TERMINAL-REPEAT; TROPICAL SPASTIC PARAPARESIS; MULTIPLE-SCLEROSIS PATIENTS; NF-KAPPA-B; COMPLETE NUCLEOTIDE-SEQUENCE; HUMAN INTERLEUKIN-2 RECEPTOR; TRANS-ACTIVATOR PROTEIN; CORD BLOOD-LYMPHOCYTES; DNA-BINDING SUBUNIT; OPEN READING FRAME RP SODROSKI, J (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PATHOL,DIV HUMAN RETROVIROL,BOSTON,MA 02115, USA. NR 187 TC 53 Z9 53 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 SEP 14 PY 1992 VL 1114 IS 1 BP 19 EP 29 DI 10.1016/0304-419X(92)90003-H PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA JQ099 UT WOS:A1992JQ09900002 PM 1390868 ER PT J AU DANDREA, AD MOREAU, JF SHOWERS, MO AF DANDREA, AD MOREAU, JF SHOWERS, MO TI MOLECULAR MIMICRY OF ERYTHROPOIETIN BY THE SPLEEN FOCUS-FORMING VIRUS GP55-GLYCOPROTEIN - THE 1ST STAGE OF FRIEND VIRUS-INDUCED ERYTHROLEUKEMIA SO BIOCHIMICA ET BIOPHYSICA ACTA LA English DT Review ID COLONY-STIMULATING FACTOR; RECEPTOR-BETA-CHAIN; ERYTHROID PROGENITOR CELLS; PAPILLOMAVIRUS-E5 TRANSFORMING PROTEIN; TYROSINE KINASE-ACTIVITY; LONG TERMINAL REPEAT; GM-CSF RECEPTOR; INTERLEUKIN-2 RECEPTOR; SIGNAL TRANSDUCTION; IL-2 RECEPTOR RP DANDREA, AD (reprint author), HARVARD UNIV,CHILDRENS HOSP,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,44 BINNEY ST,BOSTON,MA 02115, USA. NR 105 TC 14 Z9 14 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 SEP 14 PY 1992 VL 1114 IS 1 BP 31 EP 41 DI 10.1016/0304-419X(92)90004-I PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA JQ099 UT WOS:A1992JQ09900003 PM 1390869 ER PT J AU VAULA, G MORTILLA, M TUPLER, R LUKIW, W TANZI, R NEE, L POLINSKY, R FONCIN, JF BRUNI, AC MONTESI, MP SORBI, S STGEORGEHYSLOP, P AF VAULA, G MORTILLA, M TUPLER, R LUKIW, W TANZI, R NEE, L POLINSKY, R FONCIN, JF BRUNI, AC MONTESI, MP SORBI, S STGEORGEHYSLOP, P TI A NOVEL BUT NONPATHOGENIC MUTATION IN EXON-4 OF THE HUMAN AMYLOID PRECURSOR PROTEIN (APP) GENE SO NEUROSCIENCE LETTERS LA English DT Article DE DNA SEQUENCE VARIANT; FAMILIAL ALZHEIMER DISEASE; BETA-AMYLOID PRECURSOR PROTEIN GENE ID ONSET ALZHEIMERS-DISEASE AB Mutations in the beta-amyloid precursor protein (APP) gene have been associated with both familial Alzheimer disease (FAD) and with hereditary cerebral haemorrhage. The polymerase chain reaction was used to both amplify and sequence exon 4 of the APP gene from genomic DNA of subjects with FAD and normal control subjects. A novel, rare, conservative DNA sequence variant was discovered at nucleotide 459 of codon 153 (valine) in exon 4 of the APP gene in an affected member of a large FAD pedigree. Segregation studies indicate that this mutation is likely to be non-pathogenic, but must be recognized and discriminated from pathogenic mutations during sequencing studies of the APP gene in patients with FAD. C1 UNIV TORONTO,FAC MED,DEPT MED & NEUROL,CTR RES NEUROELEGENERAT DIS,TANZ NEUROSCI BLDG,TORONTO M5P 3G3,ONTARIO,CANADA. MASSACHUSETTS GEN HOSP,MOLEC NEUROGENET LAB,BOSTON,MA 02129. SANDOZ INC,SANDOZ RES INST,E HANOVER,NJ 07936. HOP LA PITIE SALPETRIERE,EPHE,NEUROHISTOL LAB,PARIS,FRANCE. USSL 17 & SMID SUD CTR,CATANZARO,ITALY. UNIV FLORENCE,DEPT NEUROL,I-50121 FLORENCE,ITALY. RI Tupler, Rossella/C-9500-2015; OI Tupler, Rossella/0000-0002-3797-1789; sorbi, sandro/0000-0002-0380-6670 NR 13 TC 11 Z9 11 U1 1 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD SEP 14 PY 1992 VL 144 IS 1-2 BP 46 EP 48 DI 10.1016/0304-3940(92)90712-G PG 3 WC Neurosciences SC Neurosciences & Neurology GA JQ144 UT WOS:A1992JQ14400011 PM 1436713 ER PT J AU WEINRAUCH, LA GLEASON, RE DELIA, JA AF WEINRAUCH, LA GLEASON, RE DELIA, JA TI VENTRICULAR ARRHYTHMIA AND LONG-TERM SURVIVAL WITH MAINTENANCE DIALYSIS SO LANCET LA English DT Letter RP WEINRAUCH, LA (reprint author), DEACONESS HOSP,JOSLIN DIABET CTR,DIV NEPHROL,JOHN COOK RENAL UNIT,BOSTON,MA 02215, USA. OI Weinrauch, Larry/0000-0003-1357-9528 NR 3 TC 0 Z9 0 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 SEP 12 PY 1992 VL 340 IS 8820 BP 670 EP 670 DI 10.1016/0140-6736(92)92200-Y PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA JM851 UT WOS:A1992JM85100025 PM 1381036 ER PT J AU GUDAS, JM FRIDOVICHKEIL, JL DATTA, MW BRYAN, J PARDEE, AB AF GUDAS, JM FRIDOVICHKEIL, JL DATTA, MW BRYAN, J PARDEE, AB TI CHARACTERIZATION OF THE MURINE THYMIDINE KINASE-ENCODING GENE AND ANALYSIS OF TRANSCRIPTION START POINT HETEROGENEITY SO GENE LA English DT Article DE INTRON; EXON; HOUSEKEEPING PROMOTER; CHIMERIC GENES; TRANSFECTION; TATA-LESS; PRIMER EXTENSION ID MOUSE THYMIDYLATE SYNTHASE; SERUM-STIMULATED CELLS; MESSENGER-RNA; EUKARYOTIC GENOMES; 5'-FLANKING REGION; BINDING PROTEINS; PROMOTER REGION; RECEPTOR GENE; S-PHASE; Z-DNA AB We have determined the molecular organization and transcription start points (tsp) for the murine gene (TK) encoding thymidine kinase. The exon/intron structure and sequences present at the splice junctions of the mammalian TK genes have been highly conserved; however, the promoter sequences of these genes have diverged widely. Both the human and Chinese hamster TK promoter regions contain CCAAT and TATA consensus motifs, whereas the mouse promoter has neither element. This difference between species is reflected in that, unlike the hamster and human TK genes, transcription initiates from numerous specific tsp within a 100-bp region in the mouse TK gene. The complex pattern of tsp seen in the endogenous gene was not maintained in transfected cell lines containing TK promoter=beta-globin (HBB) fusions. Transcription from the murine TK=HBB fusion genes initiated from a small number of tsp that were clustered downstream from the ATG in hybrids containing TK coding sequences, and in the HBB 5' UTR in hybrids that did not. Few or no specific tsp were detected from the upstream sites used in the endogenous mouse TK gene. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELL GROWTH & REGULAT,BOSTON,MA 02115. FU NCI NIH HHS [CA08317-03, T32CA09361]; NIGMS NIH HHS [GM 24571] NR 52 TC 17 Z9 18 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD SEP 10 PY 1992 VL 118 IS 2 BP 205 EP 216 DI 10.1016/0378-1119(92)90190-Z PG 12 WC Genetics & Heredity SC Genetics & Heredity GA JM798 UT WOS:A1992JM79800007 PM 1511894 ER PT J AU SAMEL, A HELLER, H AF SAMEL, A HELLER, H TI HIV-RELATED HERPES-SIMPLEX VIRUS-INFECTION SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Note RP SAMEL, A (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 10 PY 1992 VL 327 IS 11 BP 775 EP 775 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA JL661 UT WOS:A1992JL66100006 ER PT J AU KOERNER, FC GOLDBERG, DE EDGERTON, SM SCHWARTZ, LH AF KOERNER, FC GOLDBERG, DE EDGERTON, SM SCHWARTZ, LH TI PS2 PROTEIN AND STEROID-HORMONE RECEPTORS IN INVASIVE BREAST CARCINOMAS SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article; Proceedings Paper CT 2ND INTERNATIONAL WORKSHOP ON THE EPIDEMIOLOGY OF CERVICAL CANCER AND HUMAN PAPILLOMAVIRUS CY NOV 25-28, 1991 CL BRUSSELS, BELGIUM SP COMMISS EUROPEAN COMMUNITIES, EUROPE AGAINST CANC PROGRAM, MINIST PUBLIC HLTH & ENVIRONM BELGIUM, DANISH CANC REGISTRY, DANISH CANC SOC ID CANCER CELL-LINE; ESTROGEN-RECEPTOR; GENE-EXPRESSION; GROWTH-FACTORS; MCF-7; ANTIBODIES; TUMORS AB We have used immunohistochemical and hormone-binding techniques to determine the presence of estrogen receptors, estrogen-receptor protein, progesterone receptors and pS2 protein in 97 invasive breast cancers. Our group of tumors displayed the same frequency of estrogen receptors and progesterone receptors as other comparable groups, but it contained more tumors containing pS2 protein. We also observed staining of morphologically normal cells in lobules adjacent to the tumors and in several fibroadenomas; both findings vary from some other reports. We attribute these variations to the use of a sensitive immunohistochemical method and choice of the lowest possible threshold to classify a tumor as pS2-positive. If we used a higher threshold, then about 95% of the tumors containing pS2 protein also contained estrogen receptor protein. Our results add further weight to the assertion that tumors containing pS2 protein also display estrogen receptors. The data also provide theoretical and indirect support to the clinical prediction that tumors containing pS2 protein are more likely to respond to hormonal therapy and may have a more indolent course than tumors lacking the molecule. C1 HOP TENON,SERV RADIOTHERAPIE,F-75970 PARIS 20,FRANCE. RP KOERNER, FC (reprint author), MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114, USA. NR 27 TC 37 Z9 37 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD SEP 9 PY 1992 VL 52 IS 2 BP 183 EP 188 DI 10.1002/ijc.2910520205 PG 6 WC Oncology SC Oncology GA JM713 UT WOS:A1992JM71300004 PM 1521907 ER PT J AU FERRIS, FL KASSOFF, A BUZNEY, SM MCMEEL, JW WEITER, JJ DOYLE, GJ IMMERMAN, RL FRIEDMAN, GR KLEIN, ML DREYER, R CHENOWETH, R HANDELMAN, I HOHL, R BIESBROECK, R SIPPERLEY, J GARCIA, CA BLOOME, MA RUIZ, RS RIEKHOF, FT BOHART, WA GOODART, RA CLARKE, DH ORTH, DH FLOOD, TP PACKO, KH MALHOTRA, J RAHMANI, A WINTER, EJ BHATIA, H MURPHY, RP FINE, SL ELMAN, MJ PROUT, TE PATZ, A RICE, TA NEWSOME, D AIELLO, LM RAND, LI SHAH, ST COOPPAN, R CAVALLERANO, J POOLE, R SILVER, P BRIONES, J WAFAI, MZ ASMAL, AC FRANKLIN, RM AREND, L BERGSMA, D TURKISH, L BEER, P CARROLL, D THOMAS, E BURTON, TC ABRAMS, GW KIM, HJ WILLIAMS, GA TOPPING, TM REESER, FH AABERG, TM BRINTON, GS KINGHAM, JK MEREDITH, TA MARGHERIO, RR MURPHY, PL COX, MS TRESE, M WINOKUR, S AI, E SORENSON, R ARSHAM, G CAVENDER, J KOPELOW, SM SHABO, AL BRIONES, JC HORNICHTER, RD BLAIR, NP GOLDBERG, MF LINDBERG, CR ROSS, NL HAUSER, LE CUNHAVAZ, J ERNEST, JT LIANG, JC COHEN, SB VYGANTAS, C WILLIAMS, G FLYNN, HW BLANKENSHIP, GW KNOBLOCH, WH RAMSAY, RC CANTRILL, HL GOETZ, FC HOOGWERF, B BERROCAL, J PEREZ, R UMPIERRE, AR KINYOUN, JL KALINA, RE WELLS, CG GUZAK, SV PALMER, J MYERS, FL BRESNICK, GH CHANDRA, SR DAVIS, MD KLEIN, R STEVENS, TS WALLOW, IH DIXON, R EHRLICH, E EWART, R FRANK, RN LUCAS, S WHITEHOUSE, F WEISS, H BALLEN, AE TESKE, M WARTH, M BENSON, WE TASMAN, WS BROWN, GC MCNAMARA, JA LITTLE, HL JACK, RL BASSO, L MILLER, DT GUNTER, E BAYSE, DD HANNON, WH MYRICK, JE KNATTERUD, GL FISHER, MR PRIOR, MJ BARTON, F KUFERA, J MILLER, TW HOOPER, JK CROW, RS BAKER, RR PRINEAS, R DAVIS, MD HUBBARD, LD MAGLI, YL SEGAL, P MOWERY, RL CHEW, EY SEIGEL, DG CASSEL, G AF FERRIS, FL KASSOFF, A BUZNEY, SM MCMEEL, JW WEITER, JJ DOYLE, GJ IMMERMAN, RL FRIEDMAN, GR KLEIN, ML DREYER, R CHENOWETH, R HANDELMAN, I HOHL, R BIESBROECK, R SIPPERLEY, J GARCIA, CA BLOOME, MA RUIZ, RS RIEKHOF, FT BOHART, WA GOODART, RA CLARKE, DH ORTH, DH FLOOD, TP PACKO, KH MALHOTRA, J RAHMANI, A WINTER, EJ BHATIA, H MURPHY, RP FINE, SL ELMAN, MJ PROUT, TE PATZ, A RICE, TA NEWSOME, D AIELLO, LM RAND, LI SHAH, ST COOPPAN, R CAVALLERANO, J POOLE, R SILVER, P BRIONES, J WAFAI, MZ ASMAL, AC FRANKLIN, RM AREND, L BERGSMA, D TURKISH, L BEER, P CARROLL, D THOMAS, E BURTON, TC ABRAMS, GW KIM, HJ WILLIAMS, GA TOPPING, TM REESER, FH AABERG, TM BRINTON, GS KINGHAM, JK MEREDITH, TA MARGHERIO, RR MURPHY, PL COX, MS TRESE, M WINOKUR, S AI, E SORENSON, R ARSHAM, G CAVENDER, J KOPELOW, SM SHABO, AL BRIONES, JC HORNICHTER, RD BLAIR, NP GOLDBERG, MF LINDBERG, CR ROSS, NL HAUSER, LE CUNHAVAZ, J ERNEST, JT LIANG, JC COHEN, SB VYGANTAS, C WILLIAMS, G FLYNN, HW BLANKENSHIP, GW KNOBLOCH, WH RAMSAY, RC CANTRILL, HL GOETZ, FC HOOGWERF, B BERROCAL, J PEREZ, R UMPIERRE, AR KINYOUN, JL KALINA, RE WELLS, CG GUZAK, SV PALMER, J MYERS, FL BRESNICK, GH CHANDRA, SR DAVIS, MD KLEIN, R STEVENS, TS WALLOW, IH DIXON, R EHRLICH, E EWART, R FRANK, RN LUCAS, S WHITEHOUSE, F WEISS, H BALLEN, AE TESKE, M WARTH, M BENSON, WE TASMAN, WS BROWN, GC MCNAMARA, JA LITTLE, HL JACK, RL BASSO, L MILLER, DT GUNTER, E BAYSE, DD HANNON, WH MYRICK, JE KNATTERUD, GL FISHER, MR PRIOR, MJ BARTON, F KUFERA, J MILLER, TW HOOPER, JK CROW, RS BAKER, RR PRINEAS, R DAVIS, MD HUBBARD, LD MAGLI, YL SEGAL, P MOWERY, RL CHEW, EY SEIGEL, DG CASSEL, G TI ASPIRIN EFFECTS ON MORTALITY AND MORBIDITY IN PATIENTS WITH DIABETES-MELLITUS - EARLY TREATMENT DIABETIC-RETINOPATHY STUDY REPORT-14 SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID VASCULAR-DISEASE; FOLLOW-UP; PLATELETS; AGGREGATION AB Objectives.-This report presents information on the effects of aspirin on mortality, the occurrence of cardiovascular events, and the incidence of kidney disease in the patients enrolled in the Early Treatment Diabetic Retinopathy Study (ETDRS). Study Design.-This multicenter, randomized clinical trial of aspirin vs placebo was sponsored by the National Eye Institute. Patients.-Patients (N=3711) were enrolled in 22 clinical centers between April 1980 and July 1985. Men and women between the ages of 18 and 70 years with a clinical diagnosis of diabetes mellitus were eligible. Approximately 30% of all patients were considered to have type I diabetes mellitus, 31 % type II, and in 39% type I or II could not be determined definitely. Intervention.-Patients were randomly assigned to aspirin or placebo (two 325-mg tablets once per day). Main Outcome Measures.-Mortality from all causes was specified as the primary outcome measure for assessing the systemic effects of aspirin. Other outcome variables included cause-specific mortality and cardiovascular events. Results.-The estimate of relative risk for total mortality for aspirin-treated patients compared with placebo-treated patients for the entire study period was 0.91 (99% confidence interval, 0.75 to 1.11). Larger differences were noted for the occurrence of fatal and nonfatal myocardial infarction; the estimate of relative risk was 0.83 for the entire follow-up period (99% confidence interval, 0.66 to 1.04). Conclusions.-The effects of aspirin on any of the cardiovascular events considered in the ETDRS were not substantially different from the effects observed in other studies that included mainly nondiabetic persons. Furthermore, there was no evidence of harmful effects of aspirin. Aspirin has been recommended previously for persons at risk for cardiovascular disease. The ETDRS results support application of this recommendation to those persons with diabetes at increased risk of cardiovascular disease. C1 UNION UNIV, ALBANY, NY 12208 USA. RETINA FDN RETINA ASSOCIATES, EYE RES INST, BOSTON, MA USA. GOOD SAMARITAN HOSP, PORTLAND, OR 97210 USA. UNIV TEXAS, HERMANN EYE CTR, HOUSTON, TX 77025 USA. HOLY CROSS HOSP, SALT LAKE CITY, UT USA. INGALLS MEM HOSP, HARVEY, IL USA. JOHNS HOPKINS UNIV HOSP, WILMER INST, BALTIMORE, MD 21205 USA. JOSLIN DIABET CTR, BEETHAM EYE INST, BOSTON, MA USA. LOUISIANA STATE UNIV, CTR EYE, NEW ORLEANS, LA USA. MED COLL WISCONSIN, MILWAUKEE, WI 53226 USA. MICHIGAN STATE UNIV, ASSOCIATED RETINA CONSULTANTS, E LANSING, MI 48824 USA. PACIFIC PRESBYTERIAN MED CTR, SAN FRANCISCO, CA USA. UNIV CALIF LOS ANGELES, CTR HLTH SCI, JULES STEIN EYE INST, LOS ANGELES, CA 90024 USA. UNIV ILLINOIS, CHICAGO, IL 60680 USA. UNIV MIAMI, SCH MED, BASCOM PALMER EYE INST, MIAMI, FL 33152 USA. UNIV MINNESOTA, CTR ECG CODING, MINNEAPOLIS, MN 55455 USA. UNIV PUERTO RICO, RIO PIEDRAS, PR 00931 USA. UNIV WASHINGTON, SEATTLE, WA 98195 USA. UNIV WISCONSIN, CTR FUNDUS PHOTOG READING, MADISON, WI 53706 USA. WAYNE STATE UNIV, KRESGE EYE INST, DETROIT, MI 48202 USA. WILLS EYE HOSP & RES INST, PHILADELPHIA, PA 19107 USA. ZWENG MEM RETINAL RES FDN, MENLO PK, CA USA. CTR DIS CONTROL, CENT LAB, ATLANTA, GA 30333 USA. MARYLAND MED RES INST, COORDINATING CTR, BALTIMORE, MD USA. US PHS, CTR DRUG DISTRIBUT, PERRY POINT, MD USA. RP FERRIS, FL (reprint author), NEI, BIOMETRY & EPIDEMIOL PROGRAM, ROOM 6A-24, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. NR 35 TC 267 Z9 275 U1 1 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 9 PY 1992 VL 268 IS 10 BP 1292 EP 1300 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA JL608 UT WOS:A1992JL60800030 ER PT J AU LOCKE, SE KOWALOFF, HB HOFF, RG SAFRAN, C POPOVSKY, MA COTTON, DJ FINKELSTEIN, DM PAGE, PL SLACK, WV AF LOCKE, SE KOWALOFF, HB HOFF, RG SAFRAN, C POPOVSKY, MA COTTON, DJ FINKELSTEIN, DM PAGE, PL SLACK, WV TI COMPUTER-BASED INTERVIEW FOR SCREENING BLOOD-DONORS FOR RISK OF HIV TRANSMISSION SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID HISTORIES; ANTIBODIES; HEADACHE; SYSTEM; AIDS AB Objective.-To test the ability of a computer-based interview to detect factors related to the risk of the human immunodeficiency virus (HIV) among potential blood donors and to determine donor reactions to the use of the interview. Design.-A comparison of the rate of detection of HIV-related factors elicited by a computer interview with that obtained by standard American Red Cross procedures for assessment of donor suitability, including a randomized crossover trial in which the order of the two methods was reversed. Information obtained by the computer was not available to influence the use of blood components for transfusion. Setting.-The computer interview was administered to donors at an American Red Cross blood donor center and at a mobile blood drive at a hospital. Subjects.-Consecutive sample of 294 male and female blood donors 18 to 75 years of age. Main Outcome Measures.-Subjects' responses to the computer-based interview as well as responses to the standard Red Cross written questionnaires and face-to-face interviews were used for donor assessment. Results.-The interview took an average of 8 minutes to complete. From among 272 donors who provided complete data, the computer identified 12 donors who reported either behaviors associated with a risk of HIV acquisition or symptoms compatible with the acquired immunodeficiency syndrome; none of these donors had been so identified either by routine written questionnaires or by face-to-face interviews used to screen potential blood donors. Only one of the 12 identified donors used the confidential unit exclusion procedure to prevent use of his donated unit. The rate of elicitation of HIV-related factors by the computer interview was 12 (4.4%) of 272 (95% confidence interval [CI], 2.3% to 7.6%), compared with two (0.13%) of 1536 (95% confidence upper bound, 0.28%) using the standard Red Cross procedure (P<.0001). Tests for antibodies to HIV were negative in blood samples from all of the 272 subjects studied. The subjects enjoyed the computer interview and judged it to be more private than the standard donor assessment method. They also predicted that donors would be more honest with the computer interview than with a human interviewer. Conclusions.-Computer-based screening elicits more HIV-related factors in the health histories of blood donors than do the standard questionnaire and interviewing methods currently in use. Computer-based screening is also acceptable to blood donors. C1 BETH ISRAEL HOSP,CTR CLIN COMP,350 LONGWOOD AVE,BOSTON,MA 02115. BETH ISRAEL HOSP,DEPT PSYCHIAT,BOSTON,MA 02215. BETH ISRAEL HOSP,DEPT MED,BOSTON,MA 02215. BETH ISRAEL HOSP,DEPT PATHOL,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT HLTH POLICY & MANAGEMENT,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,CTR BIOSTAT,BOSTON,MA 02114. TUFTS UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02111. AMER RED CROSS,BLOOD SERV,DEDHAM,MA. FU AHRQ HHS [HS06288] NR 33 TC 156 Z9 157 U1 1 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 9 PY 1992 VL 268 IS 10 BP 1301 EP 1305 DI 10.1001/jama.268.10.1301 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA JL608 UT WOS:A1992JL60800031 PM 1507376 ER PT J AU DATTA, R HALLAHAN, DE KHARBANDA, SM RUBIN, E SHERMAN, ML HUBERMAN, E WEICHSELBAUM, RR KUFE, DW AF DATTA, R HALLAHAN, DE KHARBANDA, SM RUBIN, E SHERMAN, ML HUBERMAN, E WEICHSELBAUM, RR KUFE, DW TI INVOLVEMENT OF REACTIVE OXYGEN INTERMEDIATES IN THE INDUCTION OF C-JUN GENE-TRANSCRIPTION BY IONIZING-RADIATION SO BIOCHEMISTRY LA English DT Article ID PROTEIN-KINASE-C; MYELOID-LEUKEMIA CELLS; DNA-BINDING ACTIVITY; HUMAN-IMMUNODEFICIENCY-VIRUS; FACTOR-KAPPA-B; MONOCYTIC DIFFERENTIATION; N-ACETYLCYSTEINE; GROWTH-FACTORS; FOS GENE; EXPRESSION AB Previous work has demonstrated that the cellular response to ionizing radiation includes transcriptional activation of the c-jun gene. The signaling events responsible for this response, however, remain unclear. The present studies have examined the effects of ionizing radiation on c-jun expression in a variant of HL-60 cells, designated HL-525, which is deficient in protein kinase C (PKC)-mediated signal transduction. The results demonstrate that these cells express low levels of PKC-alpha and PKC-beta-transcripts and exhibit an attenuated induction of c-jun expression following treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA). In contrast, HL-525 cells respond to ionizing radiation with an increase in c-jun mRNA which is more pronounced than that in wild-type HL-60 cells. These cells similarly respond to ionizing radiation with increased expression of the jun-B, jun-D, c-fos, and fos-B genes. Nuclear run-on assays demonstrate that X-ray-induced c-jun expression in HL-525 cells is regulated by increases in the rate of c-jun gene transcription. Moreover, mRNA stability studies in irradiated HL-525 cells demonstrate that the half-life of c-jun transcripts is prolonged compared to that in wild-type cells. Studies with N-acetyl-L-cysteine (NAC), an antioxidant, suggest that X-ray-induced transcriptional activation of the c-jun gene is mediated at least in part through the formation of reactive oxygen intermediates (ROIs). In this context, H2O2 also induced c-jun expression in HL-525 cells, and this effect was inhibited by NAC. We further demonstrate that the induction of c-jun expression by X-rays, as well as H2O2, is inhibited (1) by prolonged exposure to TPA or bryostatin and (2) by H7, a nonspecific inhibitor of PKC-like protein kinases, but not HA1004, a more selective inhibitor of cyclic nucleotide-dependent protein kinase activity. Taken together, these results indicate that ionizing radiation induces c-jun gene transcription through the formation of ROIs and that a protein kinase, perhaps a PKC isoform distinct from PKC-alpha and PKC-beta, is also involved in this signaling pathway. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,CLIN PHARMACOL LAB,BOSTON,MA 02115. UNIV CHICAGO,DEPT RADIAT & CELLULAR ONCOL,CHICAGO,IL 60637. UNIV CHICAGO,PRITZKER SCH MED,CHICAGO,IL 60637. UNIV CHICAGO,DEPT MOLEC GENET & CELL BIOL,CHICAGO,IL 60637. ARGONNE NATL LAB,DIV BIOL & MED RES,ARGONNE,IL 60439. FU NCI NIH HHS [CA41068, CA55241] NR 49 TC 165 Z9 165 U1 1 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD SEP 8 PY 1992 VL 31 IS 35 BP 8300 EP 8306 DI 10.1021/bi00150a025 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JM572 UT WOS:A1992JM57200025 PM 1525167 ER PT J AU REED, GL MATSUEDA, GR HABER, E AF REED, GL MATSUEDA, GR HABER, E TI PLATELET FACTOR-XIII INCREASES THE FIBRINOLYTIC RESISTANCE OF PLATELET-RICH CLOTS BY ACCELERATING THE CROSS-LINKING OF ALPHA-2-ANTIPLASMIN TO FIBRIN SO THROMBOSIS AND HAEMOSTASIS LA English DT Article ID PLASMINOGEN-ACTIVATOR; HUMAN-PLASMA; ALPHA-2-PLASMIN INHIBITOR; STABILIZING FACTOR; CROSS-LINKING; THROMBOLYSIS; ANTIBODY; LYSIS; UROKINASE; MEMBRANE AB Platelet clots resist fibrinolysis by plasminogen activators. We hypothesized that platelet factor XIII may enhance the fibrinolytic resistance of platelet-rich clots by catalyzing the crosslinking of alpha-2-antiplasmin (alpha-2AP) to fibrin. Analysis of plasma clot structure by polyacrylamide gel electrophoresis and immunoblotting revealed accelerated alpha-2AP-fibrin crosslinking in platelet-rich compared with platelet-depleted plasma clots. A similar study of clots formed with purified fibrinogen (depleted of factor XIII activity), isolated platelets, and specific factor XIII inhibitors indicated that this accelerated crosslinking was due to the catalytic activity of platelet factor XIII. Moreover, when washed platelets were aggregated by thrombin, there was evidence of platelet factor XIII-mediated crosslinking between platelet alpha-2AP and platelet fibrin(ogen). Specific inhibition (by a monoclonal antibody) of the alpha-2AP associated with washed platelet aggregates accelerated the fibrinolysis of the platelet aggregate. Thus in platelet-rich plasma clots, and in thrombin-induced platelet aggregates, platelet factor XIII actively formed alpha-2AP-fibrin crosslinks, which appeared to enhance the resistance of platelet-rich clots to fibrinolysis. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP REED, GL (reprint author), MASSACHUSETTS GEN HOSP,CARDIAC UNIT,275 CAMBRIDGE ST,BOSTON,MA 02114, USA. FU NHLBI NIH HHS [HL-02348, HL-28015] NR 42 TC 58 Z9 60 U1 0 U2 1 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 45, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD SEP 7 PY 1992 VL 68 IS 3 BP 315 EP 320 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA JN058 UT WOS:A1992JN05800017 PM 1279832 ER PT J AU IMURA, Y STASSEN, JM VREYS, I LESAFFRE, E GOLD, HK COLLEN, D AF IMURA, Y STASSEN, JM VREYS, I LESAFFRE, E GOLD, HK COLLEN, D TI SYNERGISTIC ANTITHROMBOTIC PROPERTIES OF G4120, A RGD-CONTAINING SYNTHETIC PEPTIDE, AND ARGATROBAN, A SYNTHETIC THROMBIN INHIBITOR, IN A HAMSTER FEMORAL VEIN PLATELET-RICH THROMBOSIS MODEL SO THROMBOSIS AND HAEMOSTASIS LA English DT Article ID ARG-GLY-ASP; GLYCOPROTEIN-IIB/IIIA RECEPTOR; PLASMINOGEN-ACTIVATOR; MONOCLONAL-ANTIBODY; CANINE PREPARATION; FACTOR BINDING; AGGREGATION; MECHANISMS; FIBRINOGEN; HIRUDIN AB The synergistic antithrombotic properties of G4120, a synthetic Arg-Gly-Asp (RGD) containing peptide which strongly inhibits platelet aggregation, and of Argatroban, a synthetic thrombin inhibitor, were examined in a reproducible quantitative hamster femoral vein platelet-rich mural thrombosis model. Bolus injections of G4120 and Argatroban inhibit thrombus formation in a dose-dependent way; 50% inhibition (ID50) is obtained with 11-mu-g/kg G4120 and with 2 mg/kg Argatroban. Combined bolus injections of 3-mu-g/kg G4120 with 0.5, 0.75 or 1 mg/kg Argatroban and of 1 mg/kg Argatroban with 1.5 or 3-mu-g/kg G4120 caused linear dose-dependent inhibition of thrombus formation, whereas 3-mu-g/kg G4120 or 1 mg/kg Argatroban alone had very little effect (<20% inhibition). ID50 was obtained with the combination of 3-mu-g/kg G4120 and 0.5 mg/kg Argatroban, corresponding to an equi-effective fractional combination of 0.62 with a 95% confidence interval of 0.50 to 0.74. Alternatively the ID50 was obtained with the combination of 1 mg/kg Argatroban and 1.3-mu-g/kg G4120, corresponding to an equi-effective fractional combination of 0.52 with a 95% confidence interval of 0.18 to 0.86. In both instances these results are indicative of a significant synergistic interaction. Bolus injection of 10 mg/kg aspirin, 100 U/kg heparin or the combination did not inhibit thrombus formation. The synergistic effect of the combination of platelet inhibiting RGD-peptides and synthetic thrombin inhibitors could be useful in the prevention of arterial occlusion with platelet-rich thrombus in patients with ischemic heart disease following thrombolytic therapy or angioplasty, although this combination is not expected to reverse platelet thrombus formation. C1 CATHOLIC UNIV LEUVEN,CTR THROMBOSIS & VASC RES,B-3000 LOUVAIN,BELGIUM. CATHOLIC UNIV LEUVEN,DIV EPIDEMIOL,B-3000 LOUVAIN,BELGIUM. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CARDIAC UNIT,BOSTON,MA 02114. NR 37 TC 24 Z9 24 U1 0 U2 1 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 45, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD SEP 7 PY 1992 VL 68 IS 3 BP 336 EP 340 PG 5 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA JN058 UT WOS:A1992JN05800021 PM 1440501 ER PT J AU SCHEIBE, RJ WAGNER, JA AF SCHEIBE, RJ WAGNER, JA TI RETINOIC ACID REGULATES BOTH EXPRESSION OF THE NERVE GROWTH-FACTOR RECEPTOR AND SENSITIVITY TO NERVE GROWTH-FACTOR SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PC12 PHEOCHROMOCYTOMA CELLS; HIGH-AFFINITY RECEPTORS; NGF RECEPTOR; TERATOCARCINOMA CELLS; MOLECULAR-CLONING; TRK PROTOONCOGENE; NEURITE OUTGROWTH; GENE-TRANSFER; DEVELOPMENTAL EXPRESSION; TYROSINE PHOSPHORYLATION AB In PC12 cells, retinoic acid (RA) stimulates the expression of p75NGFR, a component of the nerve growth factor (NGF) receptor, as indicated by a rapid increase in p75NGFR mRNA, an increase in the binding of I-125-labeled NGF to p75NGFR, and an increase in the binding of NGF to low affinity sites. RA-treated cells are more sensitive to NGF, but not to either fibroblast growth factor or phorbol 12-myristate 13-acetate, showing that RA has a specific effect on the responsiveness of PC12 cells to NGF. Exposure to RA leads neither to an increase in the expression of mRNA for trk, another component of the NGF receptor, nor to an increase in binding to high affinity receptors, suggesting that an increase in the expression of p75NGFR is sufficient to make cells more sensitive to NGF. This work suggests that, in addition to having direct effects on gene expression, RA can indirectly modulate differentiation of neurons by modifying their expression of cell surface receptors to peptide growth factors. C1 CORNELL UNIV,SCH MED,DEPT CELL BIOL & ANAT,NEW YORK,NY 10021. HARVARD UNIV,SCH MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. FU NCI NIH HHS [CA 22427, CA 40929] NR 67 TC 61 Z9 61 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 SEP 5 PY 1992 VL 267 IS 25 BP 17611 EP 17616 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JM223 UT WOS:A1992JM22300023 PM 1325442 ER PT J AU BUSCHMAN, E ARCECI, RJ CROOP, JM CHE, MX ARIAS, IM HOUSMAN, DE GROS, P AF BUSCHMAN, E ARCECI, RJ CROOP, JM CHE, MX ARIAS, IM HOUSMAN, DE GROS, P TI MDR2 ENCODES P-GLYCOPROTEIN EXPRESSED IN THE BILE CANALICULAR MEMBRANE AS DETERMINED BY ISOFORM-SPECIFIC ANTIBODIES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MULTIDRUG-RESISTANCE GENE; BACTERIAL TRANSPORT PROTEINS; ATP-DEPENDENT TRANSPORT; MONOCLONAL-ANTIBODIES; MOUSE MDR1; CONJUGATED HYPERBILIRUBINEMIA; SECRETORY EPITHELIUM; CHINESE-HAMSTER; ORGANIC-ANIONS; HUMAN-CELLS AB We have produced antibodies specific for the three P-glycoprotein (P-gp) isoforms encoded by the mouse mdr1, mdr2, and mdr3 genes. The anti-Mdr2 and anti-Mdr3 antibodies were generated against synthetic peptides derived from the "linker" region, whereas the anti-Mdr1 antibody was raised against a fusion protein containing the amino terminus of Mdr1. Western blot analysis showed that the three antibodies could discriminate between the three isoforms in membrane fractions from Hamster cells transfected with the corresponding full-length or chimeric mdr cDNAs. Immunocytochemistry studies of mdr-transfected cells showed that the three antibodies specifically recognized each P-gp isoform expressed in whole cells. Immunoblotting of normal mouse tissues revealed that the Mdr2 isoform was expressed at very high levels in liver canalicular membrane vesicles (CMV) but not in membrane vesicles prepared from the basolateral (sinusoidal) domain (SMV). Mdr3 was detected in intestinal brush border membrane vesicles and also in CMV, although at levels much lower than Mdr2. Mdr1 was not detected in CMV or SMV but was detected in endometrial tissue from the gravid uterus. Photolabeling experiments with [I-125]iodoarylazidoprazosin followed by immunoprecipitation with isoform-specific antibodies indicated that, in CMV, Mdr3 but not Mdr2 could bind the drug analogue. C1 MCGILL UNIV,DEPT BIOCHEM,MONTREAL H3G 1Y6,QUEBEC,CANADA. HARVARD UNIV,CHILDRENS HOSP,SCH MED,DEPT PEDIAT HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. TUFTS UNIV,SCH MED,DEPT PHYSIOL,BOSTON,MA 02111. MIT,CTR CANC RES,CAMBRIDGE,MA 02139. FU NCI NIH HHS [CA48162, CA011227]; PHS HHS [35652] NR 54 TC 125 Z9 126 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 SEP 5 PY 1992 VL 267 IS 25 BP 18093 EP 18099 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JM223 UT WOS:A1992JM22300094 PM 1381362 ER PT J AU ALANI, E THRESHER, R GRIFFITH, JD KOLODNER, RD AF ALANI, E THRESHER, R GRIFFITH, JD KOLODNER, RD TI CHARACTERIZATION OF DNA-BINDING AND STRAND-EXCHANGE STIMULATION PROPERTIES OF Y-RPA, A YEAST SINGLE-STRAND-DNA-BINDING PROTEIN SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE Y-RPA; SSB; STRAND EXCHANGE; DNA BINDING; ELECTRON MICROSCOPY ID SIMIAN VIRUS-40 DNA; REPLICATION FACTOR-A; RECA-PROTEIN; ESCHERICHIA-COLI; SACCHAROMYCES-CEREVISIAE; COOPERATIVE BINDING; INVITRO REPLICATION; MULTIPLE STAGES; SV40 ORIGIN; RECOMBINATION C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELLULAR & MOLEC BIOL,BOSTON,MA 02115. UNIV N CAROLINA,LINEBERGER COMPREHENS CANC RES CTR,CHAPEL HILL,NC 27599. FU NCI NIH HHS [CA09361]; NIGMS NIH HHS [GM29383, GM31819] NR 53 TC 148 Z9 149 U1 1 U2 5 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD SEP 5 PY 1992 VL 227 IS 1 BP 54 EP 71 DI 10.1016/0022-2836(92)90681-9 PG 18 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JN259 UT WOS:A1992JN25900006 PM 1522601 ER PT J AU LUISIDELUCA, C KOLODNER, RD AF LUISIDELUCA, C KOLODNER, RD TI EFFECT OF TERMINAL NONHOMOLOGY ON INTRAMOLECULAR RECOMBINATION OF LINEAR PLASMID SUBSTRATES IN ESCHERICHIA-COLI SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE INTRAMOLECULAR RECOMBINATION; PLASMID RECOMBINATION; RECA-INDEPENDENT; EXOVIII; RECB RECC SBCA ID GENETIC-RECOMBINATION; EXONUCLEASE-VIII; PHAGE-LAMBDA; RECA PROTEIN; BACTERIOPHAGE-LAMBDA; BETA-PROTEIN; DUPLEX DNA; MODEL; K-12; MUTATIONS C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELLULAR & MOLEC BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. FU NIGMS NIH HHS [GM10522, GM26017] NR 49 TC 24 Z9 24 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD SEP 5 PY 1992 VL 227 IS 1 BP 72 EP 80 DI 10.1016/0022-2836(92)90682-A PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JN259 UT WOS:A1992JN25900007 PM 1522602 ER PT J AU DENT, P HASER, W HAYSTEAD, TAJ VINCENT, LA ROBERTS, TM STURGILL, TW AF DENT, P HASER, W HAYSTEAD, TAJ VINCENT, LA ROBERTS, TM STURGILL, TW TI ACTIVATION OF MITOGEN-ACTIVATED PROTEIN-KINASE KINASE BY V-RAF IN NIH 3T3 CELLS AND INVITRO SO SCIENCE LA English DT Article ID GROWTH; DEFINITION AB Mitogen-activated protein (MAP) kinases are 42- and 44-kD serine-threonine protein kinases that are activated by tyrosine and threonine phosphorylation in cells stimulated with mitogens and growth factors. MAP kinase and the protein kinase that activates it (MAP kinase kinase) were constitutively activated in NIH 3T3 cells infected with viruses containing either of two oncogenic forms (p35EC12, p37(22W)) of the c-Raf-1 protein kinase. The v-Raf proteins purified from cells infected with ECl 2 or 22W viruses activated MAP kinase kinase from skeletal muscle in vitro. Furthermore, a bacterially expressed v-Raf fusion protein (glutathione S-transferase-p37(22W)) also activated MAP kinase kinase in vitro. These findings suggest that one function of c-Raf-1 in mitogenic signaling is to phosphorylate and activate MAP kinase kinase. C1 UNIV VIRGINIA,DEPT INTERNAL MED,CHARLOTTESVILLE,VA 22908. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. UNIV VIRGINIA,DEPT PHARMACOL,CHARLOTTESVILLE,VA 22908. FU NCI NIH HHS [CA50661]; NICHD NIH HHS [HD24926]; NIDDK NIH HHS [DK41077] NR 27 TC 645 Z9 651 U1 1 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 SEP 4 PY 1992 VL 257 IS 5075 BP 1404 EP 1407 DI 10.1126/science.1326789 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JL612 UT WOS:A1992JL61200035 PM 1326789 ER PT J AU KOPANS, DB AF KOPANS, DB TI AUTHOR OF CANADIAN BREAST-CANCER STUDY RETRACTS WARNINGS - REPLY SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter RP KOPANS, DB (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 4 TC 8 Z9 8 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 SEP 2 PY 1992 VL 84 IS 17 BP 1367 EP 1368 DI 10.1093/jnci/84.17.1367 PG 2 WC Oncology SC Oncology GA JK698 UT WOS:A1992JK69800022 ER PT J AU FARBER, NJ DAVIS, EB ROBINSON, EJ WEINER, J BOYER, EG AF FARBER, NJ DAVIS, EB ROBINSON, EJ WEINER, J BOYER, EG TI STUDENTS ATTITUDES TOWARD INFORMED CONSENT AND THE PHYSICIAN-PATIENT RELATIONSHIP IN REGARD TO HUMAN TISSUE RESEARCH SO ACADEMIC MEDICINE LA English DT Note C1 MED COLL PENN,PHILADELPHIA,PA 19129. ST JOSEPHS UNIV,DEPT MANAGEMENT & INFORMAT SYST,PHILADELPHIA,PA 19131. MINOT STATE UNIV,COLL BUSINESS,MINOT,ND. DREXEL UNIV,DEPT MANAGEMENT,PHILADELPHIA,PA 19104. RP FARBER, NJ (reprint author), VET AFFAIRS MED CTR,DEPT MED,GEN MED SECT,UNIV & WOODLAND AVE,PHILADELPHIA,PA 19104, USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 SN 1040-2446 J9 ACAD MED JI Acad. Med. PD SEP PY 1992 VL 67 IS 9 BP 612 EP 613 DI 10.1097/00001888-199209000-00018 PG 2 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA JP883 UT WOS:A1992JP88300021 PM 1520425 ER PT J AU YOSHIMURA, N MATSUBARA, O TAMURA, A KASUGA, T MARK, EJ AF YOSHIMURA, N MATSUBARA, O TAMURA, A KASUGA, T MARK, EJ TI WEGENERS GRANULOMATOSIS - ASSOCIATED WITH DIFFUSE PULMONARY HEMORRHAGE SO ACTA PATHOLOGICA JAPONICA LA English DT Article DE WEGENERS GRANULOMATOSIS; DIFFUSE PULMONARY HEMORRHAGE (DPH); PULMONARY CAPILLARITIS ID CAPILLARITIS; VASCULITIS AB The authors report a case of Wegner's granulomatosis with the unusual manifestation of diffuse pulmonary hemorrhage. A 58-year-old man complained of bloody sputum and fever. Chest X-ray films showed multiple nodular shadows in both lung fields. He was diagnosed as having Wegener's granulomatosis by transbronchial lung biopsy, which revealed necrotizing granulomatous inflammation with necrotizing vasculitis. Despite treatment with cyclophosphamide and prednisolone, his condition rapidly deteriorated. An extensive diffuse alveolar shadow appeared in both lung fields in chest X-ray films, anemia became worse, and he died of respiratory failure. Autopsy revealed diffuse alveolar hemorrhage with necrotizing capillaritis in addition to the typical pathological findings in Wegener's granulomatosis. The capillaritis was characterized by neutrophilic infiltration of alveolar septa, and fibrin thrombi in alveolar capillaries. Diffuse pulmonary hemorrhage is uncommon in Wegener's granulomatosis. However, once diffuse pulmonary hemorrhage occurs, the respiratory condition rapidly deteriorates and is life-threatening. Therefore, accurate diagnosis and appropriate treatment are required. C1 TOKYO MED & DENT UNIV,FAC MED,DEPT PATHOL,1-5-45 YUSHIMA,BUNKYO KU,TOKYO 113,JAPAN. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. NR 10 TC 13 Z9 13 U1 1 U2 2 PU BLACKWELL SCIENCE PI CARLTON PA 54 UNIVERSITY ST, P O BOX 378, CARLTON VICTORIA 3053, AUSTRALIA SN 0001-6632 J9 ACTA PATHOL JAPON PD SEP PY 1992 VL 42 IS 9 BP 657 EP 661 PG 5 WC Pathology SC Pathology GA JY693 UT WOS:A1992JY69300006 PM 1476061 ER PT J AU REID, CL OTTO, CM DAVIS, KB LABOVITZ, A KISSLO, KB MCKAY, CR DIVER, DJ BERMAN, A SAFIAN, RD GROSSMAN, W COME, PC DOUGLAS, P MCKAY, RG SLATER, A WILLIAMS, DO DREW, TM CARNEVALE, R CIMINI, D HARDINK, D CANNON, P HOMMA, S BERKE, A KELLER, A ESCALA, E TRESGALLO, M BASHORE, TM DAVIDSON, CJ HARRISON, JK KISSLO, J KISSLO, K BRINKER, JA WEISS, JL RAQUENO, J DOWGER, B LAMBREW, CT CUTLER, J SZE, K TOOKER, N HOLMES, DR NISHIMURA, R REEDER, G MATHESON, SJ SCHREIFELS, S MEYER, L BLOCK, PC PALACIOS, IF WEYMAN, A BLOCK, EH PETITCLERC, R BROUILLETE, M SLATER, JN FEIT, F KRONZON, I ATTUBATO, MJ GINDEA, A BILYK, F KERN, MJ LABOVITZ, A STONNER, T MECHEM, C ALDERMAN, EL SCHNITTGER, I SCHWARZKOPF, A ROD, JL COMESS, K FERGUSON, J MASSUMI, A TREISTMAN, B HERNANDEZ, G WILANSKY, S HARLAN, M DEAN, LS BAXLEY, W NANDA, N KIRKLIN, JW SAENZ, C HELMCKE, FR MELUCH, FT BUCHBINDER, M PETERSON, K DITTRICH, H DAILY, E HILL, J MIRANDA, A PEPINE, C GEISER, E SCOTTFRANCO, E DEMARIA, AN WISENBAUGH, T BERK, M OBRIEN, M WEINER, BH PAPE, L BORBONE, ML NABEL, EG ARMSTRONG, WF GALEANA, A BUDA, A GALEANA, A RAHIMTOOLA, SH KAWANISHI, DT REID, C CHANDRARATNA, PAN MORRISON, E POWERS, ER SMUCKER, M GIBSON, R TEDESCO, C STEWART, DK ONEIL, W HAUSER, A DUDLETS, P PAVILEDES, G MARGULIS, A VANDERBERG, B WALLER, BF KENNEDY, JW GILLESPIE, MJ MICKEL, M SOLOMON, RE AF REID, CL OTTO, CM DAVIS, KB LABOVITZ, A KISSLO, KB MCKAY, CR DIVER, DJ BERMAN, A SAFIAN, RD GROSSMAN, W COME, PC DOUGLAS, P MCKAY, RG SLATER, A WILLIAMS, DO DREW, TM CARNEVALE, R CIMINI, D HARDINK, D CANNON, P HOMMA, S BERKE, A KELLER, A ESCALA, E TRESGALLO, M BASHORE, TM DAVIDSON, CJ HARRISON, JK KISSLO, J KISSLO, K BRINKER, JA WEISS, JL RAQUENO, J DOWGER, B LAMBREW, CT CUTLER, J SZE, K TOOKER, N HOLMES, DR NISHIMURA, R REEDER, G MATHESON, SJ SCHREIFELS, S MEYER, L BLOCK, PC PALACIOS, IF WEYMAN, A BLOCK, EH PETITCLERC, R BROUILLETE, M SLATER, JN FEIT, F KRONZON, I ATTUBATO, MJ GINDEA, A BILYK, F KERN, MJ LABOVITZ, A STONNER, T MECHEM, C ALDERMAN, EL SCHNITTGER, I SCHWARZKOPF, A ROD, JL COMESS, K FERGUSON, J MASSUMI, A TREISTMAN, B HERNANDEZ, G WILANSKY, S HARLAN, M DEAN, LS BAXLEY, W NANDA, N KIRKLIN, JW SAENZ, C HELMCKE, FR MELUCH, FT BUCHBINDER, M PETERSON, K DITTRICH, H DAILY, E HILL, J MIRANDA, A PEPINE, C GEISER, E SCOTTFRANCO, E DEMARIA, AN WISENBAUGH, T BERK, M OBRIEN, M WEINER, BH PAPE, L BORBONE, ML NABEL, EG ARMSTRONG, WF GALEANA, A BUDA, A GALEANA, A RAHIMTOOLA, SH KAWANISHI, DT REID, C CHANDRARATNA, PAN MORRISON, E POWERS, ER SMUCKER, M GIBSON, R TEDESCO, C STEWART, DK ONEIL, W HAUSER, A DUDLETS, P PAVILEDES, G MARGULIS, A VANDERBERG, B WALLER, BF KENNEDY, JW GILLESPIE, MJ MICKEL, M SOLOMON, RE TI INFLUENCE OF MITRAL-VALVE MORPHOLOGY ON MITRAL BALLOON COMMISSUROTOMY - IMMEDIATE AND 6-MONTH RESULTS FROM THE NHLBI BALLOON VALVULOPLASTY REGISTRY SO AMERICAN HEART JOURNAL LA English DT Article ID FACTORS DETERMINING RESTENOSIS; FOLLOW-UP; STENOSIS; VALVOTOMY; CATHETER; ECHOCARDIOGRAPHY; REPLACEMENT; ADULTS; AREA AB Echocardiographic data were analyzed in 555 patients undergoing mitral balloon commissurotomy (MBC). Patients were enrolled in the National Heart, Lung, and Blood Institute Balloon Valvuloplasty Registry from 24 centers. There were 456 women and 99 men with a mean age of 54 years. Before MBC the two-dimensional echocardiographic variables of mitral valve thickness, mobility, calcification, and subvalvular disease were evaluated and assigned scores of 1 to 4. The mitral valve morphology score was related to mitral valve area (MVA) measured after MBC by cardiac catheterization. The leaflet mobility score was related to the immediate post-MBC MVA: 2.2 +/- 0.8 cm2 for grade 1, 1.9 +/- 0.7 cm2 for grade 2, 1.7 +/- 0.7 cm2 for grade 3, and 1.9 +/- 0.9 cm2 for grade 4 (p < 0.001). Results of the MVA after MBC showed a similiar relationship for each echocardiographic variable. The total morphology score (sum of the four variables) showed a weak relationship to MVA immediately after MBC (r = -0.24), which was persistent at 6 months after MBC (r = -0.25). Multiple regression analysis showed that the MVA after MBC is predicted by pre-MBC MVA (p < 0.001), left atrial size (p = 0.01), balloon diameter (p = 0.02), cardiac output (p = 0.004), and leaflet mobility (p = 0.01). The R2 of the model was 0.31 (p < 0.001). Total morphology score, leaflet thickness, calcification, and subvalvular disease were not important univariate or multivariate predictors of the results of MBC. These data suggest that although mitral valve morphology, particularly leaflet mobility, relates to MVA after MBC, other variables such as the severity and duration of disease are also important and are influenced by the larger balloon sizes used in the procedure. Mitral valve morphology should not be used alone in the selection of patients for MBC. C1 BETH ISRAEL HOSP,BOSTON,MA 02215. BROWN UNIV,PROVIDENCE,RI 02912. COLUMBIA UNIV,NEW YORK,NY 10027. DUKE UNIV,MED CTR,DURHAM,NC 27710. JOHNS HOPKINS UNIV,BALTIMORE,MD 21218. MAINE MED CTR,PORTLAND,ME 04102. UNIV VIRGINIA,CHARLOTTESVILLE,VA 22903. UNIV WASHINGTON,SEATTLE,WA 98195. WILLIAM BEAUMONT HOSP,ROYAL OAK,MI 48072. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. MONTREAL HEART INST,MONTREAL H1T 1C8,QUEBEC,CANADA. NYU,NEW YORK,NY 10003. ST LOUIS UNIV,ST LOUIS,MO 63103. STANFORD UNIV,STANFORD,CA 94305. SANTA CLARA VALLEY MED CTR,SAN JOSE,CA 95128. TEXAS HEART INST,HOUSTON,TX 77025. UNIV IOWA,IOWA CITY,IA 52242. ST VINCENT PROFESS BLDG,CORE PATHOL LAB,INDIANAPOLIS,IN. UNIV ALABAMA,BIRMINGHAM,AL 35294. UNIV CALIF SAN DIEGO,LA JOLLA,CA 92093. UNIV FLORIDA,GAINESVILLE,FL 32611. UNIV KENTUCKY,LEXINGTON,KY 40506. UNIV MASSACHUSETTS,AMHERST,MA 01003. UNIV MICHIGAN,ANN ARBOR,MI 48109. UNIV SO CALIF,LOS ANGELES,CA 90089. NHLBI,BETHESDA,MD 20892. RP REID, CL (reprint author), UNIV CALIF IRVINE,IRVINE MED CTR,DIV CARDIOL,101 CITY DR,ORANGE,CA 92668, USA. FU NHLBI NIH HHS [N01-HV-78100] NR 27 TC 32 Z9 33 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD SEP PY 1992 VL 124 IS 3 BP 657 EP 665 DI 10.1016/0002-8703(92)90274-Y PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA JL615 UT WOS:A1992JL61500016 PM 1514494 ER PT J AU WOLFSDORF, JI EHRLICH, S LANDY, HS CRIGLER, JF AF WOLFSDORF, JI EHRLICH, S LANDY, HS CRIGLER, JF TI OPTIMAL DAYTIME FEEDING REGIMEN TO PREVENT POSTPRANDIAL HYPOGLYCEMIA IN TYPE-1 GLYCOGEN-STORAGE-DISEASE SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE TYPE-1 GLYCOGEN STORAGE DISEASE; GSD; POSTPRANDIAL HYPOGLYCEMIA; OPTIMAL FEEDING REGIMEN; GLUCOSE THERAPY; UNCOOKED CORNSTARCH ID GLUCOSE-PRODUCTION; UNCOOKED CORNSTARCH; GLYCEMIC THRESHOLDS; CHILDREN; CARBOHYDRATE; DEXTROSE; SYMPTOMS AB To determine the optimal daytime dietary regimen for type 1 glycogen storage disease (GSD), we used uncooked cornstarch (UCS) at a basal glucose production rate (GPR) in single and divided doses, with mixed meals at 0700 and 1700 h. This regimen was compared with a 1.5 times larger single dose of UCS at 0700 h, and with dextrose at GPR at 1200 h. Two-hour UCS loads (amount equal to GPR in 2 h) given with a mixed meal at 0700 h and 180 min later maintained mean blood glucose (BG) concentrations at greater-than-or-equal-to 4.2 mmol/L for 300 min. BG was significantly greater from 240 to 300 min compared with a single 4-h UCS load, and at 300 min compared with a single 6-h UCS load. Similar effects were noted when the divided UCS regimen was given with a mixed meal at 1700 h, but not when isoenergetic amounts of dextrose were given on the same schedules with a mixed meal at 1200 h. A daytime schedule of six UCS feedings (with the three main meals and 180 min later) at GPR maintains BG at concentrations that should minimize biochemical abnormalities and optimize clinical outcome in patients with GSD. C1 HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. JOSLIN DIABET CTR,BOSTON,MA. RP WOLFSDORF, JI (reprint author), CHILDRENS HOSP MED CTR,DEPT MED,DIV ENDOCRINOL,300 LONGWOOD AVE,BOSTON,MA 02115, USA. FU NCRR NIH HHS [RR02172] NR 30 TC 17 Z9 17 U1 0 U2 0 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-2310, BETHESDA, MD 20814-3998 SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD SEP PY 1992 VL 56 IS 3 BP 587 EP 592 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA JL271 UT WOS:A1992JL27100019 PM 1503073 ER PT J AU HARRIS, NL AF HARRIS, NL TI EPSTEIN-BARR-VIRUS IN LYMPHOMA PROTAGONIST OR PASSENGER SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Editorial Material ID REED-STERNBERG CELLS; HODGKINS-DISEASE; B-CELL; LYMPHOPROLIFERATIVE DISORDERS; EXPRESSION; MALIGNANCIES RP HARRIS, NL (reprint author), MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114, USA. NR 29 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD SEP PY 1992 VL 98 IS 3 BP 278 EP 281 PG 4 WC Pathology SC Pathology GA JN580 UT WOS:A1992JN58000002 PM 1326890 ER PT J AU GIBAS, A BLEWETT, DR SCHOENFELD, DA DIENSTAG, JL AF GIBAS, A BLEWETT, DR SCHOENFELD, DA DIENSTAG, JL TI PREVALENCE AND INCIDENCE OF VIRAL-HEPATITIS IN HEALTH-WORKERS IN THE PREHEPATITIS-B VACCINATION ERA SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE HEPATITIS-A; HEPATITIS-B; OCCUPATIONAL DISEASES; PERSONNEL, HOSPITAL ID PLACEBO-CONTROLLED TRIAL; HOSPITAL PERSONNEL; HEMODIALYSIS UNITS; MEDICAL STAFF; RISK; INFECTION; EPIDEMIOLOGY; EFFICACY; VIRUS; IMMUNIZATION AB To assess the impact of hepatitis B virus on health workers, the authors studied baseline prevalences of hepatitis B serologic markers and undertook prospective surveillance to assess hepatitis B attack rates in 837 health workers and 994 blood-donor controls between 1977 and 1982, before the introduction of hepatitis B vaccine. The baseline prevalence of all hepatitis B markers was 14% in health workers and 6% in controls (p < 0.001); exposure to hepatitis B virus was related to the intensity of blood exposure and its duration. In contrast, the frequency of exposure to hepatitis A virus, a nonblood-borne agent, was lower in health workers (11%) than in controls (16%) (p < 0.01) and increased as a function of age. Multivariate logistic regression analysis identified occupational categories with frequent blood contact, rather than duration of exposure, as being the dominant variable for exposure to hepatitis B virus; for hepatitis A virus exposure, age was the most significant variable. Among health workers susceptible to hepatitis B, the incidence of new definite hepatitis B infections was 1.0% per year in 362 health workers (804 person-years of follow-up observation) with frequent blood contact versus 0% per year in 258 health workers (534 person-years of observation) with limited blood contact (p = 0.017). For definite plus probable cases combined, the incidence of new hepatitis B infections was 1.5% per year versus 0.2% per year for the groups with frequent and limited blood exposures, respectively (p = 0.0013). There were no new cases of hepatitis A or B or seroconversions in controls and only one case of hepatitis A acquired outside the hospital by a health worker. These data confirm the high prevalence of hepatitis B exposure and document in a prospective study the high incidence over time of new hepatitis B virus infections in health workers unprotected by vaccination. Such findings reiterate the need for aggressive vaccination programs in health workers exposed to blood. C1 MASSACHUSETTS GEN HOSP,MED SERV,GASTROINTESTINAL UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,COMP SCI LAB,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CTR BIOSTAT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CTR LIVER BILIARY PANCREAS,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. FU NCRR NIH HHS [M01RR01066, RR05486]; PHS HHS [T32-KD07191] NR 28 TC 34 Z9 37 U1 0 U2 0 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 SEP 1 PY 1992 VL 136 IS 5 BP 603 EP 610 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA KN667 UT WOS:A1992KN66700011 PM 1442723 ER PT J AU RAEHL, CL PITTERLE, ME BOND, CA AF RAEHL, CL PITTERLE, ME BOND, CA TI LEGAL STATUS AND FUNCTIONS OF HOSPITAL-BASED PHARMACY TECHNICIANS AND THEIR RELATIONSHIP TO CLINICAL PHARMACY SERVICES SO AMERICAN JOURNAL OF HOSPITAL PHARMACY LA English DT Article DE JOB DESCRIPTION; LAWS; PERSONNEL, PHARMACY; PHARMACEUTICAL CARE; PHARMACISTS, HOSPITAL; PHARMACY, INSTITUTIONAL, HOSPITAL; REGULATIONS; STATES; UNITED-STATES AB The relationships among (1) laws and regulations governing hospital-based pharmacy technicians, (2) functions pharmacy technicians perform, and (3) pharmacists' provision of clinical pharmacy services were studied. A state-level technician-restriction score was developed, based on state rules and regulations in effect in 1989. Scoring included (1) type of supervision required for hospital-based pharmacy technicians, (2) ratio of technicians to pharmacists, (3) pharmacist-only reconstitution of injectable products, and (4) pharmacist-only counting and pouring. Actual use of hospital pharmacy technicians was measured with the technician-use index, and overall provision of clinical pharmacy services was measured with the pharmaceutical-care index. Based on the technician-restriction scores, 25 states and the District of Columbia were categorized as having less restrictive laws and 25 states as having more restrictive laws. Technician use varied with hospital size, teaching affiliation, ownership, type of drug delivery system, and education level of the director of pharmacy. Use of pharmacy technicians increased with the severity of hospital-patient illness treated. A fair correlation was found between the pharmaceutical-care index and the technician-use index. A positive association was found between pharmacy technician use and pharmacists' provision of clinical pharmacy services. C1 WILLIAM S MIDDLETON MEM VET ADM MED CTR,ARRHYTHMIA CLIN,MADISON,WI 53705. RP RAEHL, CL (reprint author), UNIV WISCONSIN,SCH PHARM,425 N CHARTER ST,MADISON,WI 53706, USA. NR 9 TC 6 Z9 8 U1 0 U2 1 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 SEP PY 1992 VL 49 IS 9 BP 2179 EP 2187 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA JL261 UT WOS:A1992JL26100014 PM 1524058 ER PT J AU PITTERLE, ME BOND, CA RAEHL, CL AF PITTERLE, ME BOND, CA RAEHL, CL TI PHARMACEUTICAL-CARE INDEX FOR MEASURING COMPREHENSIVE PHARMACEUTICAL SERVICES SO AMERICAN JOURNAL OF HOSPITAL PHARMACY LA English DT Note C1 UNIV WISCONSIN,SCH PHARM,425 N CHARTER ST,MADISON,WI 53706. UNIV WISCONSIN,SCH MED,SCH MED,MADISON,WI 53706. WILLIAM S MIDDLETON MEM VET ADM MED CTR,ARRHYTHMIA CLIN,MADISON,WI 53705. NR 8 TC 7 Z9 7 U1 0 U2 1 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 SEP PY 1992 VL 49 IS 9 BP 2226 EP 2229 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA JL261 UT WOS:A1992JL26100024 PM 1524067 ER PT J AU WEN, SF PARTHASARATHY, R ILIOPOULOS, O OBERLEY, TD AF WEN, SF PARTHASARATHY, R ILIOPOULOS, O OBERLEY, TD TI ACUTE-RENAL-FAILURE FOLLOWING BINGE DRINKING AND NONSTEROIDAL ANTIINFLAMMATORY DRUGS SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE ACUTE RENAL FAILURE; BACK PAIN; ALCOHOL; BINGE DRINKING; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; PROSTAGLANDIN ID ANTI-INFLAMMATORY DRUGS; NEPHROTIC SYNDROME; INDOMETHACIN; ANGIOTENSIN; PROSTAGLANDINS; ULTRAFILTRATION; PROTEINURIA; ARTERIOLES; NECROSIS; DISEASE C1 UNIV WISCONSIN,CTR HLTH SCI,DEPT MED,MADISON,WI 53706. UNIV WISCONSIN,CTR HLTH SCI,DEPT PATHOL,MADISON,WI 53706. WILLIAM S MIDDLETON MEM VET ADM MED CTR,PATHOL SERV,MADISON,WI 53705. NR 32 TC 27 Z9 27 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD SEP PY 1992 VL 20 IS 3 BP 281 EP 285 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA JN139 UT WOS:A1992JN13900012 PM 1519610 ER PT J AU WALL, C CASSELBRANT, ML AF WALL, C CASSELBRANT, ML TI SYSTEM-IDENTIFICATION OF PERILYMPHATIC FISTULA IN AN ANIMAL-MODEL SO AMERICAN JOURNAL OF OTOLOGY LA English DT Article AB An acute animal model has been developed in the chinchilla for the study of perilymphatic fistulas. Micropunctures were made in three sites to simulate bony, round window, and oval window fistulas. The eye movements in response to pressure applied to the external auditory canal were recorded after micropuncture induction and in preoperative controls. The main pressure stimulus was a pseudorandom binary sequence (PRBS) that rapidly changed between plus and minus 200 mm of water. The PRBS stimulus, with its wide frequency bandwidth, produced responses clearly above the preoperative baseline in 78 percent of the runs. The response was better between 0.5 and 3.3 Hz than it was below 0.5 Hz. The direction of horizontal eye movement was toward the side of the fistula with positive pressure applied in 92 percent of the runs. Vertical eye movements were also observed. The ratio of vertical eye displacement to horizontal eye displacement depended upon the site of the micropuncture induction. Thus, such a ratio measurement may be clinically useful in the noninvasive localization of perilymphatic fistulas in humans. C1 HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02115. UNIV PITTSBURGH,SCH MED,DEPT OTOLARYNGOL,DIV PEDIAT OTOLARYNGOL,PITTSBURGH,PA 15261. RP WALL, C (reprint author), MASSACHUSETTS EYE & EAR INFIRM,VESTIBULAR LAB,243 CHARLES ST,BOSTON,MA 02114, USA. NR 11 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0192-9763 J9 AM J OTOL JI Am. J. Otol. PD SEP PY 1992 VL 13 IS 5 BP 443 EP 448 PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA JM982 UT WOS:A1992JM98200010 PM 1443080 ER PT J AU GWOSDOW, AR OCONNELL, NA SPENCER, JA KUMAR, MSA AGARWAL, RK BODE, HH ABOUSAMRA, AB AF GWOSDOW, AR OCONNELL, NA SPENCER, JA KUMAR, MSA AGARWAL, RK BODE, HH ABOUSAMRA, AB TI INTERLEUKIN-1-INDUCED CORTICOSTERONE RELEASE OCCURS BY AN ADRENERGIC MECHANISM FROM RAT ADRENAL-GLAND SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE EPINEPHRINE; PHENTOLAMINE; PROPRANOLOL ID CORTISOL SECRETION; CHROMAFFIN CELLS; CORTEX; STIMULATION; STEROIDOGENESIS; PURIFICATION; INNERVATION; MEDULLA; AXIS; BETA AB Interleukin-1 (IL-1) has been shown to stimulate corticosterone release from the adrenal gland directly, and indirectly through activation of the hypothalamic-pituitary-adrenal axis. The aim of this paper was to determine whether IL-1-stimulated corticosterone release occurs indirectly through the local release of catecholamines from the rat adrenal gland. To accomplish this, experiments were conducted on both quartered rat adrenal glands and primary cultures of dispersed adrenal cells. Incubation of quartered adrenals with adrenocorticotropic hormone (ACTH, 10(-12) to 10(-8) M) or IL-1beta (10(-12) to 10(-8) M) resulted in dose-dependent increases (P < 0.05) in corticosterone release. Corticosterone release stimulated by 10(-8) M doses of ACTH and IL-1beta began to rise 30 min after incubation and peaked at 2 h. In primary cultures of adrenal cells, IL-1alpha and IL-1beta elevated corticosterone release after a 24-h incubation period. ACTH elevated corticosterone levels at 4 and 24 h. The stimulatory effect of IL-1 on corticosterone release was mimicked by epinephrine (10(-6) M), and was selectively blocked by the alpha-adrenergic antagonist phentolamine (10(-5) M). The beta-adrenergic antagonist propranolol (10(-5) M) did not change IL-1-induced corticosterone release. Neither phentolamine nor propranolol had an effect on ACTH-stimulated corticosterone release. Both IL-1alpha and IL-1beta significantly increased (P < 0.05) epinephrine levels after a 24-h incubation period compared with media-treated controls. These observations suggest that locally released catecholamines mediate the stimulatory effect of IL-1 on corticosterone release through an alpha-adrenergic receptor in the rat adrenal gland. C1 SHRINERS BURN INST,BOSTON,MA 02114. RP GWOSDOW, AR (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BULFINCH 3,FRUIT ST,BOSTON,MA 02114, USA. FU NIDDK NIH HHS [1 R29-DK-41419-01A1] NR 32 TC 59 Z9 61 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 SEP PY 1992 VL 263 IS 3 BP E461 EP E466 PN 1 PG 6 WC Physiology SC Physiology GA JP901 UT WOS:A1992JP90100030 PM 1329524 ER PT J AU KRAUT, JA HART, D NORD, EP AF KRAUT, JA HART, D NORD, EP TI BASOLATERAL NA+-INDEPENDENT CL--HCO3- EXCHANGE IN PRIMARY CULTURES OF RAT IMCD CELLS SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE CHLORIDE-BICARBONATE ION EXCHANGE; INNER MEDULLARY COLLECTING DUCT CELL; INTRACELLULAR PH; SODIUM INDEPENDENCE ID MEDULLARY COLLECTING DUCT; KIDNEY EPITHELIAL-CELLS; PROXIMAL CONVOLUTED TUBULE; INTRACELLULAR PH; CL-HCO3 EXCHANGE; CYTOPLASMIC-PH; H+ SECRETION; MEMBRANE; ANTIPORT; MECHANISM AB The role of anion exchange in the regulation of intracellular pH (pH(i)) under base load and steady-state conditions was investigated in confluent monolayers of rat inner medullary collecting duct (IMCD) cells in primary culture using the pH-sensitive fluoroprobe 2,7-bis(carboxyethyl)-5(6')-carboxyfluorescein (BCECF). Recovery of pH(i) after imposition of a base load induced either by replacement of HCO3-/CO2 by N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES) at the same extracellular pH (pH(O)) or deletion of Cl- from a HCO3-/CO2-buffered solution had an absolute requirement for Cl-, was Na+ independent, and was inhibited approximately 90% by 50 muM 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS). When pH(O) was decreased by lowering HCO3- concentration in the constant presence of 5% CO2, the rate of decrement in pH(i) was significantly blunted in the absence of Cl-. Imposition of a positive or negative diffusion potential of equal but opposite magnitude did not modify the anion exchange rate, confirming the electroneutrality of the process. Under steady-state conditions, pH(i) of cells bathed in a HCO3-/CO2-buffered solution was 7.33 +/- 0.06, significantly lower than that of cells bathed in a nominally HCO3-/CO2-free buffer (7.50 +/- 0.04), indicating that under physiological conditions the pathway functions as a base extruder. In studies performed on cells grown on permeable supports, the anion exchange pathway was found to be confined exclusively to the basolateral-equivalent cell surface. In summary, confluent monolayers of rat IMCD cells in primary culture possess a Na+-independent, DIDS-inhibitable electroneutral Cl--HCO3- exchange pathway that is confined to the basolateral cell surface. The transporter is an important determinant of steady-state pH(i) and is the predominant mechanism whereby the cell recovers from imposed elevations in pH(i). C1 UNIV CALIF LOS ANGELES,SCH MED,W LOS ANGELES VET AFFAIRS MED CTR,MED & RES SERV,LOS ANGELES,CA 90073. SUNY STONY BROOK,SCH MED,DEPT MED,DIV NEPHROL,STONY BROOK,NY 11794. FU NIDDK NIH HHS [DK-41585, DK-36351] NR 28 TC 15 Z9 15 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 SEP PY 1992 VL 263 IS 3 BP F401 EP F410 PN 2 PG 10 WC Physiology SC Physiology GA JP902 UT WOS:A1992JP90200100 PM 1415568 ER PT J AU MOLITORIS, BA DAHL, R GEERDES, A AF MOLITORIS, BA DAHL, R GEERDES, A TI CYTOSKELETON DISRUPTION AND APICAL REDISTRIBUTION OF PROXIMAL TUBULE NA+-K+-ATPASE DURING ISCHEMIA SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE ACTIN; FODRIN; UVOMORULIN; MEMBRANE FLUIDITY; 1,6-DIPHENYL-1,3,5-HEXATRIENE POLARIZATION ID RENAL CONVOLUTED TUBULES; EPITHELIAL-CELL POLARITY; CORTICAL BRUSH-BORDER; IMMUNOFERRITIN DETERMINATION; PLASMA-MEMBRANES; FODRIN; NA+,K+-ATPASE; MAINTENANCE; CHOLESTEROL; MECHANISM AB The polar distribution of Na+-K+-ATPase to the basolateral membrane of proximal tubule cells is essential for the efficient and vectorial reabsorption of Na+ and may be dependent on the formation of a metabolically stable, detergent-insoluble complex of Na-K+-ATPase with the actin membrane cytoskeleton. The present studies utilized immunocytochemical techniques to demonstrate and quantify the apical redistribution of Na+-K+-ATPase during mild ischemia (15 min) that occurred in proximal (1.3 +/- 0.9 vs. 4.5 +/- 1.1 particles/100 mum surface membrane, P < 0.01) but not distal tubule cells. Treatment of control apical membranes with 2-(2-methoxyethoxy)ethyl 8-(cis-2-n-octylcyclopropyl) octanoate (A2C), a fluidizing agent, markedly increased membrane fluidity without any effect on Na+-K+-ATPase activity. In brush-border membrane vesicles isolated after ischemia, however, A2C further increased an already elevated Na-K+-ATPase activity. During ischemia, total cellular Na+-K+-ATPase activity remained unaltered, but the Triton X-100-soluble (noncytoskeleton associated) fraction of Na+-K+-ATPase increased significantly following 15 and 30 min. There was a corresponding decrease in the Triton X-100-insoluble fraction of Na+-K+-ATPase, with the ratio of detergent-soluble to -insoluble Na+-K+-ATPase increasing from 13 +/- 2 to 32 +/- 5% (P < 0.01) during 30 min of ischemia. Western blot analysis of the Triton X-100-soluble fraction, following 30 min of ischemic injury, revealed the presence of Na+-K+-ATPase, actin, fodrin, and uvomorulin. However, in a fraction highly enriched for Na+-K+-ATPase, neither actin, fodrin, nor uvomorulin was detected. Taken together, these data suggest that in proximal tubule cells, as in Madin-Darby canine kidney cells, Na+-K+-ATPase exists primarily in a cytoskeletal-associated form. During ischemic injury, the actin cytoskeleton is disrupted, and Na+-K+-ATPase dissociates from the actin cortical cytoskeleton and is then free to redistribute to the apical membrane in proximal but not distal tubule cells. C1 UNIV COLORADO,HLTH SCI CTR,DEPT CELLULAR & STRUCT BIOL,DENVER,CO 80220. UNIV COLORADO,HLTH SCI CTR,DEPT MED,DENVER,CO 80220. RP MOLITORIS, BA (reprint author), DENVER VET AFFAIRS MED CTR,111C 1055 CLERMONT ST,DENVER,CO 80220, USA. FU NIDDK NIH HHS [DK-41126] NR 29 TC 124 Z9 124 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 SEP PY 1992 VL 263 IS 3 BP F488 EP F495 PN 2 PG 8 WC Physiology SC Physiology GA JP902 UT WOS:A1992JP90200111 PM 1329535 ER PT J AU LEUNG, FW SU, KC PASSARO, E GUTH, PH AF LEUNG, FW SU, KC PASSARO, E GUTH, PH TI REGIONAL DIFFERENCES IN GUT BLOOD-FLOW AND MUCOSAL DAMAGE IN RESPONSE TO ISCHEMIA AND REPERFUSION SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE REFLECTANCE SPECTROPHOTOMETRY; XANTHINE OXIDASE; SMALL INTESTINAL BLOOD FLOW; COLON BLOOD FLOW ID ENDOSCOPIC REFLECTANCE SPECTROPHOTOMETRY; INDUCED GASTRIC-LESIONS; XANTHINE-OXIDASE; SMALL-INTESTINE; RADICALS; INJURY; RAT; INFLAMMATION; HEMODYNAMICS; ULCER AB Ischemia and reperfusion of the small intestine and colon in rats were produced by reversible occlusion (for 30 min and 1 or 3 h) of the superior mesenteric artery and the aorta above the inferior mesenteric artery. Despite a greater reduction of mucosal perfusion in the colon than in the small intestine with 30 min of ischemia, the depth of mucosal damage was significantly smaller in the former than in the latter. Thirty minutes of ischemia followed by 1 h of reperfusion induced an increase in polymorphonuclear leukocyte infiltration in both locations. Exacerbation of mucosal injury occurred only in the small intestine, suggesting that reperfusion injury is independent of polymorphonuclear leukocyte infiltration. Reperfusion after 1 or 3 h of ischemia did not exacerbate mucosal damage in either location. Allopurinol significantly diminished the exacerbation of injury after reperfusion in the small intestine. The protective effect of allopurinol, however, was neither associated with an improvement in perfusion nor a reduction in polymorphonuclear leukocyte infiltration. These data indicate that there is a window (30 min) of reperfusion injury in the small intestine, but there is no evidence of reperfusion injury in the colon. C1 W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,CTR ULCER RES & EDUC,LOS ANGELES,CA 90073. RP LEUNG, FW (reprint author), SEPULVEDA VET AFFAIRS MED CTR,DIV GASTROENTEROL,16111 PLUMMER ST,SEPULVEDA,CA 91343, USA. NR 26 TC 36 Z9 40 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 SEP PY 1992 VL 263 IS 3 BP G301 EP G305 PN 1 PG 5 WC Physiology SC Physiology GA JP901 UT WOS:A1992JP90100051 PM 1415542 ER PT J AU ALLYN, JW TEPLICK, R STEINBERG, JB MUNFAKH, NA GEFFIN, GA TITUS, J DAGGETT, WM AF ALLYN, JW TEPLICK, R STEINBERG, JB MUNFAKH, NA GEFFIN, GA TITUS, J DAGGETT, WM TI NOREPINEPHRINE INCREASES THE ECONOMY OF PRESSURE DEVELOPMENT IN ISOLATED CANINE HEARTS SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE MYOCARDIAL OXYGEN CONSUMPTION; OXYGEN WASTING; EFFICIENCY OF PRESSURE DEVELOPMENT ID DOG LEFT-VENTRICLE; VOLUME AREA; OXYGEN-CONSUMPTION; O-2 CONSUMPTION; MECHANICAL ENERGY; INOTROPIC AGENTS; FORCE; COST; PHOSPHORYLATION; ENERGETICS AB To test for oxygen wasting by norepinephrine (NE) without relying on normalization by measures of performance such as the pressure-volume area, myocardial oxygen consumption (MVO2) was determined for isovolumic beats at five different left ventricular (LV) end-diastolic volumes (EDV) in nine isolated cross-perfused canine hearts in each of three states: a basal anesthetic state (B); after depression with halothane (H); and after adding NE to increase contractility back to the B state (H + NE). The end-diastolic and peak systolic pressure-volume lines were identical for B and H + NE. The R2 for a linear regression of MVO2 per beat for B vs. H + NE for beats originating at the same ED and developing similar (within 10%) peak isovolumic pressures for all hearts was 0.85. The slope and intercept were 0.83 and 0.01, which are significantly less than one (P < 0.001) and greater than zero (P < 0.001), respectively. These data suggest that NE increases both the economy of pressure development as well as activation energy of an isovolumically contracting LV. C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. NR 21 TC 2 Z9 2 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 SEP PY 1992 VL 263 IS 3 BP H715 EP H721 PN 2 PG 7 WC Physiology SC Physiology GA JP902 UT WOS:A1992JP90200013 PM 1415595 ER PT J AU GOFF, DC HENDERSON, DC AMICO, E AF GOFF, DC HENDERSON, DC AMICO, E TI CIGARETTE-SMOKING IN SCHIZOPHRENIA - RELATIONSHIP TO PSYCHOPATHOLOGY AND MEDICATION SIDE-EFFECTS SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID PARKINSONS-DISEASE; TARDIVE-DYSKINESIA; DOPAMINE NEURONS; SUBSTANCE USE; NICOTINE; CAFFEINE; INPATIENTS; CHLORPROMAZINE; DEPRESSION; DRUG AB Objective: The authors' goal was to study the relationship between smoking status and clinical characteristics in schizophrenic patients. Method: Seventy-eight schizophrenic outpatients were assessed by a single rater using the Brief Psychiatric Rating Scale (BPRS), the Abnormal Involuntary Movement Scale, and the Simpson-Angus Scale for extrapyramidal symptoms. Current smokers (N=58) were compared with nonsmokers (N=20) on clinical variables by independent t tests and chi-square tests. Differences in outcome variables were tested by multiple analysis of covariance (ANCOVA) with smoking status and gender as factors and age, neuroleptic dose, and caffeine consumption as covariates. Results: Seventy-four percent of patients were current smokers and reported a mean of 19 cigarettes smoked per day. Compared to nonsmokers, current smokers were significantly more likely to be men, to be younger, and to have had an earlier age at onset and a greater number of previous hospitalizations. Current smokers and nonsmokers received mean neuroleptic doses of 1160 and 542 mg/day (chlorpromazine equivalents); the difference was significant. Current smokers also displayed significantly less parkinsonism and more akathisia and had higher total scores on the BPRS. Overall multiple ANCOVA demonstrated a significant main effect for smoking status but not gender or the interaction between gender and smoking status. Univariate ANCOVAs demonstrated a significant main effect of smoking status only for the Simpson-Angus Scale score. Conclusions: Cigarette smokers receive significantly higher neuroleptic doses, in part because of a smoking-induced increase in neuroleptic metabolism. Smoking is also associated with significant reduction in levels of parkinsonism. Smoking status is a significant factor that should be considered in assessment of neuroleptic dose requirements and neuroleptic side effects. C1 MASSACHUSETTS GEN HOSP,ERICH LINDEMANN MENTAL HLTH CTR,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,PSYCHIAT SERV,BOSTON,MA 02114. NR 62 TC 377 Z9 386 U1 2 U2 13 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 SEP PY 1992 VL 149 IS 9 BP 1189 EP 1194 PG 6 WC Psychiatry SC Psychiatry GA JK722 UT WOS:A1992JK72200010 PM 1503131 ER PT J AU POWELL, PP WANG, CC JONES, R AF POWELL, PP WANG, CC JONES, R TI DIFFERENTIAL REGULATION OF THE GENES ENCODING PLATELET-DERIVED GROWTH-FACTOR RECEPTOR AND ITS LIGAND IN RAT LUNG DURING MICROVASCULAR AND ALVEOLAR WALL REMODELING IN HYPEROXIA SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID SMOOTH-MUSCLE CELLS; ENDOTHELIAL-CELLS; PDGF RECEPTOR; MESSENGER-RNA; DIFFERENT ISOFORMS; A-CHAIN; EXPRESSION; FIBROBLASTS; INJURY; EXPOSURE AB The growth factors that operate while the lung remodels in hyperoxia are not known. At the lung periphery, high oxygen levels cause cell hypertrophy and hyperplasia, and this results in a thickening of the alveolar-capillary membrane and the walls of its associated microvessels. The present study examines gene expression of platelet-derived growth factor (PDGF) receptor and its ligand in this region of the lung of rats breathing 87% oxygen and compares this with the levels of expression in normal lung. In similar peripheral lung tissue, the proliferative response of specific cell populations has been assessed by [H-3]thymidine incorporation and autoradiography. Normal lung expresses PDGF alpha-receptor subunit transcripts of 6.5 and 4.7 kb and PDGF beta-receptor transcripts of 5.5 and 4.5 kb. PDGF A-chain transcripts of 2.9, 2.3, and 1.7 kb are also expressed, each being at 10-fold higher levels than the single 3.5-kb transcript detected for PDGF B-chain. Within hours of breathing high concentrations of oxygen, mRNA levels change rapidly for the PDGF receptor subunits. These levels return to normal after 1 day and then decline over the next 28 days of exposure. PDGF A-chain mRNA increases 12 to 18 h after exposure, but then returns to normal levels. It is the PDGF B-chain mRNA that responds most to hyperoxia by increasing 10-fold on day 3. This increase immediately precedes the proliferative response on day 4 of microvascular adventitial fibro-blasts, precursor smooth muscle cells, and epithelial cells but not smooth muscle cells, which do not proliferate until day 28. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,MOLEC & CELL BIOL UNIT,BOSTON,MA 02114. FU NHLBI NIH HHS [HL RO1 34552] NR 40 TC 24 Z9 24 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD SEP PY 1992 VL 7 IS 3 BP 278 EP 285 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA JW362 UT WOS:A1992JW36200008 PM 1325810 ER PT J AU KATSANTONIS, GP MAAS, C CUSUMANO, J FRIEDMAN, WH AF KATSANTONIS, GP MAAS, C CUSUMANO, J FRIEDMAN, WH TI COMPARISON OF ACCURACY OF CT AND ROUTINE RADIOGRAPHY IN CHRONIC HYPERPLASTIC RHINOSINUSITIS SO AMERICAN JOURNAL OF RHINOLOGY LA English DT Article ID COMPUTERIZED-TOMOGRAPHY; SINUS AB In this retrospective study, the computer tomographic scans (CT) and routine sinus x-rays of 57 patients with chronic hyperplastic rhinosinusitis who subsequently underwent surgical intervention were reviewed by the otolaryngologist and the radiologist. The diagnostic accuracy of these modalities for each sinus (maxillary, ethmoid, sphenoid, and frontal) were determined by comparison with the operative findings and histopathology. The diagnostic accuracy of CT for the maxillary, ethmoid, sphenoid, and frontal sinuses approached 100%. The diagnostic accuracy of conventional radiographs was 85.59% for the maxillary, 86.84% for the sphenoid, 84.84% for the frontal, and 60.57% for the ethmoid sinuses. The accuracy of routine x-rays for ethmoid sinus disease was even lower when only partial or "patchy" involvement was present. We discuss the importance of CT scans in diagnosing early stages of sinusitis. C1 DEACONESS MED CTR,DEPT RADIOL,ST LOUIS,MO. DEACONESS MED CTR,ST LOUIS,MO. ST LOUIS UNIV,SCH MED,DEPT OTOLARYNGOL,ST LOUIS,MO 63104. RP KATSANTONIS, GP (reprint author), PK CENT INST,6125 CLAYTON AVE,SUITE 430,ST LOUIS,MO 63139, USA. NR 11 TC 0 Z9 0 U1 0 U2 0 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 SEP-OCT PY 1992 VL 6 IS 5 BP 173 EP 177 DI 10.2500/105065892781874531 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA JX310 UT WOS:A1992JX31000004 ER PT J AU STOMPER, PC CONNOLLY, JL AF STOMPER, PC CONNOLLY, JL TI DUCTAL CARCINOMA INSITU OF THE BREAST - CORRELATION BETWEEN MAMMOGRAPHIC CALCIFICATION AND TUMOR SUBTYPE SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID INTRADUCTAL CARCINOMA; FOLLOW-UP; LESIONS; BIOPSY; ABNORMALITIES AB OBJECTIVE. Histologic subtypes of ductal carcinoma in situ of the breast have been correlated with disease progression after local excision only. This study was undertaken to determine how the predominant type of calcification seen on mammography correlates with the predominant histologic tumor subtype, knowledge that could aid in the development of clinical criteria for selecting patients for appropriate local treatment. MATERIALS AND METHODS. A prospective double-blind study was performed to correlate the mammographic and histologic findings in 66 consecutive cases of ductal carcinoma in situ, or ductal carcinoma in situ associated with small invasive foci (n = 11), in which microcalcifications seen on mammograms were found in the ductal carcinoma during histologic evaluation of excisional biopsy specimens. Microcalcifications were categorized as predominantly linear or granular and were correlated with the predominant histologic subtype of ductal carcinoma in situ in the tissue containing the calcifications seen on mammograms. RESULTS. Predominantly linear calcifications were present in 47% (18/38) of ductal comedocarcinomas in situ compared with 18% (5/28) of cribriform, solid, or papillary subtypes (p = .01). Predominantly granular calcifications were present in 53% (20/38) of comedocarcinomas compared with 82% (23/28) of the noncomedo types (p = .01). In 94% (16/17) of cribriform ductal carcinomas in situ, granular microcalcifications were seen on mammograms. Seventy-eight percent (18/23) of linear calcifications in ductal carcinoma in situ were associated with the comedo subtype, whereas 53% (23/43) of the granular calcifications were associated with noncomedo subtypes. CONCLUSION. We conclude that the comedo subtype of ductal carcinoma in situ is more likely to be accompanied by linear calcifications than are the noncomedo subtypes, and noncomedo ductal carcinoma in situ is more likely to be associated with granular calcifications than is the comedo subtype when microcalcifications are seen on mammograms. However, there is considerable overlap, and the predominant histologic subtype cannot be predicted on the basis of the microcalcification type with a high degree of accuracy. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT DIAGNOST RADIOL,BOSTON,MA 02115. HARVARD UNIV,BETH ISRAEL HOSP,DEPT PATHOL,SCH MED,BOSTON,MA 02215. SUNY BUFFALO,SCH MED & BIOMED SCI,BUFFALO,NY 14260. NR 18 TC 85 Z9 98 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 SEP PY 1992 VL 159 IS 3 BP 483 EP 485 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA JJ983 UT WOS:A1992JJ98300008 PM 1323923 ER PT J AU BARBORIAK, DP RIVITZ, SM CHEW, FS AF BARBORIAK, DP RIVITZ, SM CHEW, FS TI SACRAL NEUROFIBROMA SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Note ID TUMORS C1 HARVARD UNIV,SCH MED,DEPT,BOSTON,MA 02115. RP BARBORIAK, DP (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,32 FRUIT ST,BOSTON,MA 02114, USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD SEP PY 1992 VL 159 IS 3 BP 600 EP 600 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA JJ983 UT WOS:A1992JJ98300033 PM 1503033 ER PT J AU HAYES, AM JARAMILLO, D LEVY, HL KNISELY, AS AF HAYES, AM JARAMILLO, D LEVY, HL KNISELY, AS TI NEONATAL HEMOCHROMATOSIS - DIAGNOSIS WITH MR IMAGING SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID PERINATAL HEMOCHROMATOSIS; TRANSFERRIN-RECEPTOR; IRON C1 CHILDRENS HOSP PITTSBURGH,DEPT PATHOL,3705 5TH AVE & DESOTO ST,PITTSBURGH,PA 15213. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CHILDRENS SERV,BOSTON,MA 02114. CHILDRENS HOSP MED CTR,DEPT RADIOL,BOSTON,MA 02115. NR 8 TC 45 Z9 45 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 SEP PY 1992 VL 159 IS 3 BP 623 EP 625 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA JJ983 UT WOS:A1992JJ98300038 PM 1503038 ER PT J AU FERRUCCI, JT AF FERRUCCI, JT TI 92ND ANNUAL-MEETING OF THE ARRS - SECRETARY REPORT SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Editorial Material RP FERRUCCI, JT (reprint author), MASSACHUSETTS GEN HOSP,AMER ROENTGEN RAY SOC,DEPT RADIOL,32 FRUIT ST,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD SEP PY 1992 VL 159 IS 3 BP 661 EP 662 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA JJ983 UT WOS:A1992JJ98300044 ER PT J AU STERN, DN SONG, MJ LANDIS, WJ AF STERN, DN SONG, MJ LANDIS, WJ TI TUBULE FORMATION AND ELEMENTAL DETECTION IN DEVELOPING OPOSSUM ENAMEL SO ANATOMICAL RECORD LA English DT Article ID ELECTRON-PROBE MICROANALYSIS; GROWTH PLATE CARTILAGE; RAT INCISOR; SECRETORY AMELOBLASTS; DIDELPHIS-MARSUPIALIS; MINERAL PHASE; PROTEOGLYCANS; ORGAN; CALCIUM; MICROSCOPY AB Most marsupials and some placental mammals possess enamel characterized by the presence of tubules, and the cellular origin of these structures has been the subject of a number of previous studies (See, for example, Lester, 1970; Azevedo and Goldberg, 1987). In the present report, tooth germs of the American opossum were examined to determine the structure and composition of enamel tubules during development and to analyze the enamel matrix relative to that of placental mammals with atubular enamel. For this purpose, tissues prepared by aqueous (decalcified and undecalcified) and anhydrous (undecalcified) methods were investigated by conventional transmission (TEM) and high voltage electron microscopy (HVEM), as well as by electron probe x-ray microanalysis (EPMA), selected-area electron diffraction (SAED), and electron spectroscopic imaging (ESI). Results indicate that most enamel tubules in the opossum begin as cytoplasmic remnants of Tomes' processes of ameloblasts. During development of the matrix, some of the tubules do not appear to be continuous throughout the prismatic layer. Sulfur is detectable around the lumen of the tubule in decalcified sections by EPMA and in and around the tubule by ESI. Calcium/phosphorus (Ca/P) molar ratios of the mineralizing matrix are generally higher than those found in enamel of other mammals and appear to decrease rather than increase with enamel maturation. The summary of data indicates the presence of sulfated glycoproteins or proteoglycans in this tissue, specifically around enamel tubules. Calcium and phosphorus are also present within the tubules, with the sulfated groups possibly binding calcium to prevent mineralization of the enamel tubules themselves. C1 HARVARD UNIV,DEPT BIOL,CAMBRIDGE,MA 02138. HARVARD UNIV,MARY INGRAHAM BUNTING INST,CAMBRIDGE,MA 02138. HARVARD UNIV,SCH MED,DEPT ORTHOPAED SURG,BOSTON,MA 02115. CHILDRENS HOSP MED CTR,BOSTON,MA 02115. NEW YORK STATE DEPT HLTH,WADSWORTH CTR LABS & RES,NIH BIOTECHNOL HVEM RESOURCE,ALBANY,NY 12201. RP STERN, DN (reprint author), FORSYTH DENT CTR,140 FENWAY,BOSTON,MA 02115, USA. FU NIADDK NIH HHS [AM34078, AM34081]; NIDCR NIH HHS [DE07894] NR 83 TC 1 Z9 1 U1 1 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0003-276X J9 ANAT REC JI Anat. Rec. PD SEP PY 1992 VL 234 IS 1 BP 34 EP 48 DI 10.1002/ar.1092340105 PG 15 WC Anatomy & Morphology SC Anatomy & Morphology GA JH164 UT WOS:A1992JH16400004 PM 1329577 ER PT J AU FERRARI, LR DONLON, JV AF FERRARI, LR DONLON, JV TI METOCLOPRAMIDE REDUCES THE INCIDENCE OF VOMITING AFTER TONSILLECTOMY IN CHILDREN SO ANESTHESIA AND ANALGESIA LA English DT Article ID STRABISMUS SURGERY; DROPERIDOL; LIDOCAINE AB The efficacy of intravenous metoclopramide in controlling vomiting in children after tonsillectomy was determined in a prospective randomized, double-blind investigation. One hundred two unpremedicated, ASA physical status I or II children between the ages of 1 and 15 yr who were undergoing surgical removal of the tonsils, with or without adenoidectomy, were studied. Anesthesia was induced either with halothane, nitrous oxide, and oxygen by mask or by intravenous thiopental and was maintained with halothane, nitrous oxide, oxygen, and intravenous morphine (0.1 mg/kg). Each child randomly received either 0.15 mg/kg of metoclopramide or saline solution placebo intravenously after transfer to the postanesthesia care unit. All episodes of vomiting were recorded for 24 h after completion of surgery. The incidence of vomiting in the saline solution group was 70%, compared with 47% in the metoclopramide group (P = 0.026). The authors conclude that the administration of intravenous metoclopramide in a dose of 0.15 mg/kg on arrival in the postanesthesia care unit significantly decreases the incidence of vomiting in children after tonsillectomy. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP FERRARI, LR (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT ANESTHESIA,243 CHARLES ST,BOSTON,MA 02114, USA. NR 14 TC 69 Z9 72 U1 2 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD SEP PY 1992 VL 75 IS 3 BP 351 EP 354 PG 4 WC Anesthesiology SC Anesthesiology GA JK361 UT WOS:A1992JK36100006 PM 1510255 ER PT J AU DERSHWITZ, M DIBIASE, PM ROSOW, CE WILSON, RS SANDERSON, PE JOSLYN, AF AF DERSHWITZ, M DIBIASE, PM ROSOW, CE WILSON, RS SANDERSON, PE JOSLYN, AF TI ONDANSETRON DOES NOT AFFECT ALFENTANIL-INDUCED VENTILATORY DEPRESSION OR SEDATION SO ANESTHESIOLOGY LA English DT Article; Proceedings Paper CT 1991 ANNUAL MEETING OF THE AMERICAN SOC OF ANESTHESIOLOGISTS CY NOV, 1991 CL SAN FRANCISCO, CA SP AMER SOC ANESTHESIOLOGISTS DE ANALGESICS, OPIOIDS, ALFENTANIL; ANTIEMETICS, ONDANSETRON; ANTAGONISTS, SEROTONIN, ONDANSETRON; VENTILATION ID MORPHINE AB Ondansetron is a selective 5-hydroxytryptamine type 3 receptor antagonist effective as an antiemetic in patients experiencing postoperative or cancer chemotherapy-induced nausea and vomiting. Currently, no information is available regarding the interaction of ondansetron with opioids, although a serotonin antagonist might be expected to modify some opioid actions. This study was designed to measure the effects of ondansetron on alfentanil-induced ventilatory depression and sedation in healthy male volunteers. Ventilatory drive (measured as the end-tidal CO2 necessary to produce a minute ventilation of 151/min) was determined in 29 subjects using a modification of the Read rebreathing technique. Sedation was measured by asking the subjects to complete visual analog scales. Alfentanil was administered as a bolus (5-mu-g/kg) followed by a continuous infusion (0.25-0.75-mu-g.kg-1.min-1) for at least 90 min. Study medication (ondansetron 8 or 16 mg or vehicle placebo) was then administered in a randomized, double-blind manner, and the alfentanil was infused for an additional 15 min. Measurements of ventilatory drive and sedation were made at baseline, during alfentanil infusion, after study medication, and at 30-min intervals after alfentanil was discontinued. Alfentanil produced significant ventilatory depression (P < 0.001) and sedation (P < 0.001) in all three groups. Neither placebo nor ondansetron produced further change in the intensity of either alfentanil effect. After discontinuation of the opioid, both ventilatory depression and sedation decreased, and the rate of recovery was not significantly different between groups. The data indicate that alfentanil-induced sedation and ventilatory depression are not significantly affected by the subsequent administration of ondansetron. C1 HARVARD UNIV,SCH MED,DEPT ANAESTHESIA,BOSTON,MA 02115. GLAXO INC,RES TRIANGLE PK,NC. RP DERSHWITZ, M (reprint author), MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114, USA. NR 20 TC 15 Z9 15 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1992 VL 77 IS 3 BP 447 EP 452 DI 10.1097/00000542-199209000-00007 PG 6 WC Anesthesiology SC Anesthesiology GA JL527 UT WOS:A1992JL52700007 PM 1387767 ER PT J AU KIM, CS ARNOLD, FJ ITANI, MS MARTYN, JAJ AF KIM, CS ARNOLD, FJ ITANI, MS MARTYN, JAJ TI DECREASED SENSITIVITY TO METOCURINE DURING LONG-TERM PHENYTOIN THERAPY MAY BE ATTRIBUTABLE TO PROTEIN-BINDING AND ACETYLCHOLINE-RECEPTOR CHANGES SO ANESTHESIOLOGY LA English DT Article; Proceedings Paper CT 1991 ANNUAL MEETING OF THE AMERICAN SOC OF ANESTHESIOLOGISTS CY NOV, 1991 CL SAN FRANCISCO, CA SP AMER SOC ANESTHESIOLOGISTS DE DRUG INTERACTIONS, METOCURINE; PHENYTOIN; MUSCLE, SKELETAL, ACETYLCHOLINE RECEPTORS; NEUROMUSCULAR RELAXANTS, METOCURINE; PHARMACODYNAMICS, METOCURINE; PROTEINS, ALPHA-1-ACID GLYCOPROTEIN; RECEPTORS, NICOTINIC; ACETYLCHOLINE ID INDUCED NEUROMUSCULAR BLOCKADE; PHARMACOKINETIC DRUG-INTERACTIONS; ALPHA-1-ACID GLYCOPROTEIN; D-TUBOCURARINE; PLASMA-BINDING; BURN INJURY; RESISTANCE; MUSCLE; CARBAMAZEPINE; SERUM AB Long-term phenytoin therapy induces resistance to the neuromuscular blocking effects of metocurine. The hypothesis that this is attributable to increased plasma protein binding of the drug (decreased free fraction) related to increased concentrations of alpha-1-acid glycoprotein (AAG) or attributable to the proliferation of acetylcholine receptors (AChR) at the muscle membrane was tested in the rat. After 14 days of phenytoin 40 mg.kg-1, administered intraperitoneally twice daily (n = 12), the neuromuscular pharmacodynamics were evaluated and compared with those of time-matched controls (n - 10). Protein binding was measured by equilibrium dialysis, AAG concentrations by radial immunodiffusion assay, and AChR by I-125-alpha-bungarotoxin binding. The effective dose for 50% inhibition of baseline twitch height (ED50) was significantly greater in the phenytoin group than in the control group (15.03 +/- 1.65-mu-g.kg-1 vs. 9.98 +/- 0.69-mu-g.kg-1, respectively). The concentrations of AAG increased gradually from 133.8 +/- 7.8-mu-g.ml-1 at day 0, to 343.1 +/- 58.0-mu-g.ml-1 at day 7, to 1,729.5 +/- 422.3-mu-g.ml-1 at day 14 in the phenytoin group. The induction of AAG concentrations in plasma was dependent on plasma phenytoin concentrations and was most prominent after 14 days of phenytoin (r = 0.77; P < 0.01; n = 22). The free fraction of metocurine was significantly decreased in the phenytoin group compared to the control group (67.2 +/- 0.18% vs. 74.5 +/- 2.5%). There was a significant negative correlation between increased AAG concentrations and decreased free fraction (r = 0.65). The spontaneous recovery of twitch to 75% of full recovery was significantly faster (22.7 +/- 3.3 min vs. 36.0 +/- 4.3 min) and was seen at greater total (42.6 +/- 2.5 ng.ml-1 vs. 32.3 +/- 2.8 ng.ml-1) and greater unbound (29.9 ng.ml-1 +/- 2.9 vs. 22.2 +/- 1.9 ng.ml-1) plasma metocurine concentrations in the phenytoin group. Concurrently, the AChR number on the muscle membrane was significantly increased in the phenytoin group (2.67 +/- 0.23 fmole/mg protein vs. 1.84 +/- 0.26 fmole/mg protein). A higher free fraction of metocurine required for a given twitch inhibition, together with an increased plasma protein binding of metocurine in the phenytoin group, suggests a pharmacodynamic and pharmacokinetic mechanism for the resistance that may include increased AChR numbers at the muscle membrane and increased plasma protein binding of metocurine related to augmented AAG concentrations. C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,CLIN PHARMACOL LAB,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,ANESTHESIA SERV,BOSTON,MA 02114. SHRINERS BURN INST,ANESTHESIA SERV,CINCINNATI,OH 45219. HARVARD UNIV,SCH MED,DEPT ANAESTHESIOL,BOSTON,MA 02115. AMER CYANAMID CO,LEDERLE LABS,DIV MED RES,PEARL RIVER,NY 10965. FU NIGMS NIH HHS [GMR01-31569] NR 42 TC 43 Z9 45 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1992 VL 77 IS 3 BP 500 EP 506 DI 10.1097/00000542-199209000-00015 PG 7 WC Anesthesiology SC Anesthesiology GA JL527 UT WOS:A1992JL52700015 PM 1519788 ER PT J AU TALAL, N FLESCHER, E DANG, H AF TALAL, N FLESCHER, E DANG, H TI EVIDENCE FOR POSSIBLE RETROVIRAL INVOLVEMENT IN AUTOIMMUNE-DISEASES SO ANNALS OF ALLERGY LA English DT Article ID PRIMARY SJOGRENS-SYNDROME; MAMMARY-TUMOR VIRUS; PROTEIN-KINASE-C; T-CELLS; LUPUS-ERYTHEMATOSUS; ANTIBODIES; INHIBITION; INFECTION; DELETION; PEPTIDE C1 AUDIE L MURPHY MEM VET ADM MED CTR,CLIN IMMUNOL SECT,SAN ANTONIO,TX 78284. RP TALAL, N (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV CLIN IMMUNOL,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. FU NIDCR NIH HHS [1R01 DE90311-01] NR 25 TC 19 Z9 19 U1 0 U2 0 PU AMER COLL ALLERGY ASTHMA IMMUNOLOGY PI ARLINGTON HTS PA 85 WEST ALGONQUIN RD SUITE 550, ARLINGTON HTS, IL 60005 SN 0003-4738 J9 ANN ALLERGY JI Ann. Allergy PD SEP PY 1992 VL 69 IS 3 BP 221 EP 224 PG 4 WC Allergy SC Allergy GA JP903 UT WOS:A1992JP90300012 PM 1326239 ER PT J AU TRIGGS, WJ MACDONELL, RAL CROS, D CHIAPPA, KH SHAHANI, BT DAY, BJ AF TRIGGS, WJ MACDONELL, RAL CROS, D CHIAPPA, KH SHAHANI, BT DAY, BJ TI MOTOR INHIBITION AND EXCITATION ARE INDEPENDENT EFFECTS OF MAGNETIC CORTICAL STIMULATION SO ANNALS OF NEUROLOGY LA English DT Article ID BRAIN-STIMULATION; NEURON DISEASE; COIL STIMULATION; CLINICAL-EVALUATION; SILENT PERIOD; INTACT MAN; CORTEX; CONDUCTION; MUSCLES; MONKEY AB We administered magnetic cortical stimulation (MCS) during voluntary contraction of intrinsic hand muscles to 8 patients with motor neuron disease (MND), 5 patients with pure lower motor neuron syndromes (LMN), a patient with severe subacute sensory neuropathy (SSN), and 10 healthy volunteers. Patients with MND had clinical evidence of upper MND and elevated thresholds for (3 patients) or absence of (5 patients) motor evoked potentials (MEPs). MCS during sustained contraction inhibited electromyographic activity in 6 of 8 patients with MND, without preceding MEPs. MCS had no effect on the electromyogram (EMG) of the other 2 patients with MND. In normal subjects and patients with LMN, inhibition of EMG was never seen without a preceding MEP, regardless of stimulus intensity. In the patient with SSN, MCS elicited normal MEPs and inhibited the EMG in a pattern similar to normal subjects, whereas supramaximal electrical stimulation of median and ulnar nerves failed to inhibit the EMG despite normal M and F responses. Our findings indicate that the inhibitory effects of MCS on EMG are not dependent solely on changes in afferent feedback caused by the muscle twitch produced by the MEP, or on Renshaw cell inhibition. We suggest that some of the inhibitory and excitatory effects of MCS on the motor system are mediated by distinct cortical elements, which may have different susceptibilities to pathophysiological processes in MND. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,EMG UNIT,BIGELOW 12,FRUIT ST,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CLIN NEUROPHYSIOL LABS,BOSTON,MA 02114. NR 36 TC 123 Z9 123 U1 0 U2 2 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD SEP PY 1992 VL 32 IS 3 BP 345 EP 351 DI 10.1002/ana.410320307 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA JN145 UT WOS:A1992JN14500006 PM 1416804 ER PT J AU CANELLOS, GP AF CANELLOS, GP TI CURRENT THERAPEUTIC STRATEGIES IN HODGKINS-DISEASE SO ANNALS OF ONCOLOGY LA English DT Editorial Material RP CANELLOS, GP (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV MED ONCOL,BOSTON,MA 02115, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD SEP PY 1992 VL 3 SU 4 BP S67 EP S68 PG 2 WC Oncology SC Oncology GA JX396 UT WOS:A1992JX39600018 ER PT J AU VARVARES, MA CHENEY, ML GOODMAN, ML CEISLER, E MONTGOMERY, WW AF VARVARES, MA CHENEY, ML GOODMAN, ML CEISLER, E MONTGOMERY, WW TI CHONDROBLASTOMA OF THE TEMPORAL BONE - CASE-REPORT AND LITERATURE-REVIEW SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE CHONDROBLASTOMA; CONNECTIVE TISSUE NEOPLASMS; TEMPORAL BONE ID SKULL AB Chondroblastoma is a rare tumor of bone that represents approximately 1% of all primary bone tumors. In the temporal bone, only 33 have been reported. We present a case of chondroblastoma of the temporal bone, followed by a literature review and analysis of reported cases. We conclude that the best chance for a prolonged disease-free interval is total excision using a combined otolaryngologic and neurosurgical approach. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OTOLARYNGOL,243 CHARLES ST,BOSTON,MA 02114. NR 17 TC 21 Z9 21 U1 0 U2 0 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD SEP PY 1992 VL 101 IS 9 BP 763 EP 769 PG 7 WC Otorhinolaryngology SC Otorhinolaryngology GA JN792 UT WOS:A1992JN79200009 PM 1514755 ER PT J AU LAURETANO, AM CUNNINGHAM, MJ WEBER, AL AF LAURETANO, AM CUNNINGHAM, MJ WEBER, AL TI INTRAPAROTID HEMATOMA SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article ID FINE-NEEDLE ASPIRATION; SALIVARY-GLAND LESIONS; PAROTID TUMORS; CT SIALOGRAPHY; TOMOGRAPHY; HEAD; NECK AB With the possible exception of the often clinically apparent hemangioma-lymphangioma, the presence of a unilateral parotid mass in a child is of diagnostic concern. This is particularly true of a child in whom a firm mass arises within a short period of time without associated infectious or inflammatory symptoms.1 C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 17 TC 2 Z9 2 U1 0 U2 1 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD SEP PY 1992 VL 101 IS 9 BP 791 EP 793 PG 3 WC Otorhinolaryngology SC Otorhinolaryngology GA JN792 UT WOS:A1992JN79200014 PM 1514759 ER PT J AU PFALLER, MA DUPONT, B KOBAYASHI, GS MULLER, J RINALDI, MG ESPINELINGROFF, A SHADOMY, S TROKE, PF WALSH, TJ WARNOCK, DW AF PFALLER, MA DUPONT, B KOBAYASHI, GS MULLER, J RINALDI, MG ESPINELINGROFF, A SHADOMY, S TROKE, PF WALSH, TJ WARNOCK, DW TI STANDARDIZED SUSCEPTIBILITY TESTING OF FLUCONAZOLE - AN INTERNATIONAL COLLABORATIVE STUDY SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID ANTIFUNGAL AGENTS; FUNGAL-INFECTIONS; AMPHOTERICIN-B; TRIAZOLES; IMIDAZOLE; INVITRO AB An international collaborative study of broth dilution (MIC) and disk diffusion susceptibility testing of fluconazole was conducted by using a chemically defined medium (High-Resolution Antifungal Assay Medium; Oxoid Ltd., Basingstoke, United Kingdom) and standard test methods performed in eight reference laboratories. Ten yeast isolates were tested by each test method in duplicate on each of 3 separate days. The intralaboratory reproducibility of the MIC test was excellent; 95.7% of the replicate tests (n = 220) were within 2 doubling dilutions of the other values in the set for the eight laboratories. The intralaboratory reproducibility of the disk test was also good, with 91% of the replicate tests (n = 234) agreeing with each other within an arbitrarily chosen value of 4 mm. Interlaboratory agreement of MIC test results was acceptable, with 84% of the MICs agreeing within 2 doubling dilutions. In contrast, the interlaboratory agreement of the disk test was not good, with only 59% of test results agreeing within 4 mm. Comparison of the rank order of MICs obtained in each laboratory with the reference rank order gave an agreement of 70 to 80% (median, 80%) with the MIC test and 70 to 90% (median, 80%) with the disk test. These preliminary results are encouraging for the development of standardized testing methods for testing fluconazole. C1 WASHINGTON UNIV,SCH MED,DIV LAB MED,ST LOUIS,MO 63110. WASHINGTON UNIV,SCH MED,DEPT MED,ST LOUIS,MO 63110. WASHINGTON UNIV,SCH MED,DEPT PATHOL,ST LOUIS,MO 63110. DEPT VET AFFAIRS MED CTR,SAN ANTONIO,TX. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT MED,RICHMOND,VA 23298. BRISTOL ROYAL INFIRM & GEN HOSP,DEPT MICROBIOL,REG MYCOL LAB,BRISTOL BS2 8HW,AVON,ENGLAND. HOSP INST PASTEUR,F-75015 PARIS,FRANCE. UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX 78284. UNIV FREIBURG,INST MED MICROBIOL & HYG,MYCOL SECT,W-7800 FREIBURG,GERMANY. PFIZER LTD,SANDWICH,ENGLAND. NCI,BETHESDA,MD 20892. RP PFALLER, MA (reprint author), OREGON HLTH SCI UNIV,DEPT PATHOL,PORTLAND,OR 97201, USA. NR 30 TC 74 Z9 75 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 SEP PY 1992 VL 36 IS 9 BP 1805 EP 1809 PG 5 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA JM247 UT WOS:A1992JM24700002 PM 1416871 ER PT J AU BLAEHR, H ANDERSEN, CB LADEFOGED, J LANGHOFF, E AF BLAEHR, H ANDERSEN, CB LADEFOGED, J LANGHOFF, E TI HUMAN PROXIMAL TUBULAR CELLS MODULATE ALLOGEN RESPONSES OF LEUKOCYTES INVITRO SO APMIS LA English DT Article DE CYTOKINES; INDOMETHACIN; LEUKOCYTES; TUBULAR CELLS ID II HLA-ANTIGENS; EPITHELIAL-CELLS; HUMAN-KIDNEY; MONOCLONAL-ANTIBODIES; MEDIATED LYSIS; RAT-KIDNEY; EXPRESSION; CULTURE; MOLECULES; CYTOKINES AB The interaction between proximal tubular cells and leukocytes was examined. In co-cultures of tubular cells and allogenic leukocytes, tubular cells expressed MHC antigens and ICAM-1. A small number of leukocytes adhered to tubular cells and induced cytotoxic damage. Thus, 65% of the tubular cells were viable after co-culturing with allogenic leukocytes. These cells had low alloreactive capacity, which was not due to lack of interleukin-1 or interferon-gamma. The presence of tubular cells modulated the immune response of leukocytes by reducing the effect of mitogen by 80%, allogens by 65% and interleukin-2 by 40%. A soluble factor released in the co-cultures was a likely mediator, since addition of supernatants from co-cultures suppressed mitogen responses by 27% compared to leukocytes cultured alone. This mediator might be prostaglandin, because addition of indomethacin to co-cultures increased the growth response of leukocytes. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PATHOL,BOSTON,MA 02115. RIGSHOSP,DEPT MED P,DIV NEPHROL,DK-2100 COPENHAGEN,DENMARK. KAS HERLEV,DEPT PATHOL,DK-2730 HERLEV,DENMARK. NR 25 TC 2 Z9 2 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0903-4641 J9 APMIS JI APMIS PD SEP PY 1992 VL 100 IS 9 BP 832 EP 838 PG 7 WC Immunology; Microbiology; Pathology SC Immunology; Microbiology; Pathology GA JV385 UT WOS:A1992JV38500010 PM 1356367 ER PT J AU VEGABORACHOWITZ, C KENNEY, M AF VEGABORACHOWITZ, C KENNEY, M TI WORKING WITH BILINGUAL LANGUAGE DISABILITY - DUNCAN,DM SO APPLIED PSYCHOLINGUISTICS LA English DT Book Review RP VEGABORACHOWITZ, C (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0142-7164 J9 APPL PSYCHOLINGUIST JI Appl. Psycholinguist. PD SEP PY 1992 VL 13 IS 3 BP 399 EP 400 DI 10.1017/S0142716400005695 PG 2 WC Linguistics; Psychology, Experimental SC Linguistics; Psychology GA KB875 UT WOS:A1992KB87500007 ER PT J AU BIEDERMAN, J FARAONE, SV KEENAN, K BENJAMIN, J KRIFCHER, B MOORE, C SPRICHBUCKMINSTER, S UGAGLIA, K JELLINEK, MS STEINGARD, R SPENCER, T NORMAN, D KOLODNY, R KRAUS, I PERRIN, J KELLER, MB TSUANG, MT AF BIEDERMAN, J FARAONE, SV KEENAN, K BENJAMIN, J KRIFCHER, B MOORE, C SPRICHBUCKMINSTER, S UGAGLIA, K JELLINEK, MS STEINGARD, R SPENCER, T NORMAN, D KOLODNY, R KRAUS, I PERRIN, J KELLER, MB TSUANG, MT TI FURTHER EVIDENCE FOR FAMILY-GENETIC RISK-FACTORS IN ATTENTION-DEFICIT HYPERACTIVITY DISORDER - PATTERNS OF COMORBIDITY IN PROBANDS AND RELATIVES IN PSYCHIATRICALLY AND PEDIATRICALLY REFERRED SAMPLES SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID OBSESSIVE-COMPULSIVE DISORDER; MAJOR AFFECTIVE-DISORDERS; LA-TOURETTES SYNDROME; CONDUCT DISORDER; CO-MORBIDITY; FOLLOW-UP; DEPRESSIVE-DISORDERS; MULTIPLE THRESHOLDS; GENERAL-POPULATION; CHILDREN AB We examined 140 probands with attention deficit hyperactivity disorder, 120 normal controls, and their 822 first-degree relatives using "blind" raters and structured diagnostic interviews. Compared with controls, probands with attention deficit hyperactivity disorder were more likely to have conduct, mood, and anxiety disorders. Compared with relatives of controls, relatives of probands with attention deficit hyperactivity disorder had a higher risk for attention deficit hyperactivity disorder, antisocial disorders, major depressive disorder, substance dependence, and anxiety disorders. Patterns of comorbidity indicate that attention deficit hyperactivity disorder and major depressive disorders may share common familial vulnerabilities, that attention deficit hyperactivity disorder plus conduct disorder may be a distinct subtype, and that attention deficit hyperactivity disorder and anxiety disorders are transmitted independently in families. These results extend previous findings indicating family-genetic influences in attention deficit hyperactivity disorder by using both pediatrically and psychiatrically referred proband samples. The distributions of comorbid illnesses in families provide further validation for subgrouping probands with attention deficit hyperactivity disorder by comorbidity. C1 MASSACHUSETTS GEN HOSP,CHILDRENS SERV,BOSTON,MA 02114. HARVARD COMMUNITY HLTH PLAN,DEPT PEDIAT,BOSTON,MA. HARVARD UNIV,SCH MED,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. VET AFFAIRS MED CTR,PSYCHIAT SERV,BROCKTON,MA. RP BIEDERMAN, J (reprint author), MASSACHUSETTS GEN HOSP,PEDIAT PSYCHOPHARMACOL UNIT ACC 725,PSYCHIAT UNIT,FRUIT ST,BOSTON,MA 02114, USA. OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [R01 MH-41314-01A2] NR 85 TC 534 Z9 541 U1 2 U2 19 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 SEP PY 1992 VL 49 IS 9 BP 728 EP 738 PG 11 WC Psychiatry SC Psychiatry GA JM052 UT WOS:A1992JM05200009 PM 1514878 ER PT J AU WILENS, TE BIEDERMAN, J BALDESSARINI, RJ MCDERMOTT, SP PUOPOLO, PR FLOOD, JG AF WILENS, TE BIEDERMAN, J BALDESSARINI, RJ MCDERMOTT, SP PUOPOLO, PR FLOOD, JG TI FLUOXETINE INHIBITS DESIPRAMINE METABOLISM SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Letter ID DEPRESSION; PLASMA RP WILENS, TE (reprint author), MASSACHUSETTS GEN HOSP,PEDIAT PSYCHOPHARMACOL UNIT ACC 725,BOSTON,MA 02114, USA. FU NIMH NIH HHS [MH-47370, MH-31154] NR 6 TC 12 Z9 12 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD SEP PY 1992 VL 49 IS 9 BP 752 EP 752 PG 1 WC Psychiatry SC Psychiatry GA JM052 UT WOS:A1992JM05200013 PM 1514882 ER PT J AU HAUSER, SL DOOLITTLE, TH LOPEZBRESNAHAN, M SHAHANI, B SCHOENFELD, D SHIH, VE GROWDON, J LEHRICH, JR AF HAUSER, SL DOOLITTLE, TH LOPEZBRESNAHAN, M SHAHANI, B SCHOENFELD, D SHIH, VE GROWDON, J LEHRICH, JR TI AN ANTISPASTICITY EFFECT OF THREONINE IN MULTIPLE-SCLEROSIS SO ARCHIVES OF NEUROLOGY LA English DT Article ID SPASTICITY; TRYPTOPHAN; INGESTION AB To determine whether the naturally occurring amino acid threonine, a potential precursor for glycine biosynthesis in the spinal cord, has an effect on spasticity in multiple sclerosis, 26 ambulatory patients were entered into a randomized crossover trial. Threonine administered at a total daily dose of 7.5 g reduced signs of spasticity on clinical examination, although no symptomatic improvement could be detected by the examining physician or the patient. In contrast to the side effects of sedation and increased motor weakness associated with antispasticity drugs commonly used for the treatment of multiple sclerosis, no side effects or toxic effects of threonine were identified. Levels of threonine were elevated in serum and cerebrospinal fluid during treatment, but glycine levels did not change. Enhancement by threonine of glycinergic postsynaptic inhibition of the motor reflex arc in the spinal cord may represent a nonsedating, nontoxic approach to the management of spasticity in multiple sclerosis. RP HAUSER, SL (reprint author), MASSACHUSETTS GEN HOSP,DEPT NEUROL,NEUROIMMUNOL UNIT,WARREN 324,BOSTON,MA 02114, USA. RI Hauser, Stephen/J-2978-2016 FU NINDS NIH HHS [NS05096, NS29568] NR 25 TC 25 Z9 25 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 SEP PY 1992 VL 49 IS 9 BP 923 EP 926 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA JM337 UT WOS:A1992JM33700009 PM 1520082 ER PT J AU NEUMANN, R BELKIN, M LOEWENTHAL, E GORODETSKY, R AF NEUMANN, R BELKIN, M LOEWENTHAL, E GORODETSKY, R TI A LONG-TERM FOLLOW-UP OF METALLIC INTRAOCULAR FOREIGN-BODIES, EMPLOYING DIAGNOSTIC-X-RAY SPECTROMETRY SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID BETA-THALASSEMIA MAJOR; IRON DEPOSITION; SKIN IRON; SIDEROSIS AB We describe 10 eyes harboring metallic intraocular foreign bodies (IOFBs) for 9 to 46 years that had undergone diagnostic x-ray spectrometry to measure metal dissolution 9 years before this study. Findings from the present clinical and laboratory examinations, including perimetry, electroretinography electrooculography, and diagnostic x-ray spectrometry examinations are reported. Deterioration in visual acuity consequent to metal dissolution of the IOFB was found in only one eye. Visual fields and electrophysiologic performances deteriorated in two other eyes for reasons that were probably unrelated to IOFB dissolution. Visual functions remained stable during the follow-up period in seven eyes, although excess copper levels were demonstrated in one of them. Eight of 10 eyes retained visual acuity of 6/24 or better. Diagnostic x-ray spectrometry confirmed siderosis in one patient and ruled out metallosis in the two patients with deteriorated vision for reasons that were unrelated to metallosis. The favorable outcome of this series of patients may influence one to consider a more conservative approach in the decision to remove IOFBs. A careful, life-long follow-up might be considered with periodic electroretinographic and diagnostic x-ray spectrometry examinations; the IOFB should be promptly removed if and when metallosis with damage to visual functions is demonstrated. C1 HADASSAH UNIV HOSP,SHARETT INST ONCOL,RADIOBIOL LAB,JERUSALEM,ISRAEL. CHAIM SHEBA MED CTR,SACKLER SCH MED,IL-52621 TEL HASHOMER,ISRAEL. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,UVEITIS & IMMUNOL SERV,BOSTON,MA 02114. RP NEUMANN, R (reprint author), TEL AVIV UNIV,MAURICE & GABRIELA GOLDSCHLEGER EYE RES INST,IL-52621 TEL HASHOMER,ISRAEL. NR 18 TC 12 Z9 12 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD SEP PY 1992 VL 110 IS 9 BP 1269 EP 1272 PG 4 WC Ophthalmology SC Ophthalmology GA JL634 UT WOS:A1992JL63400024 PM 1520114 ER PT J AU KAISER, PK PINEDA, R ALBERT, DM SHORE, JW AF KAISER, PK PINEDA, R ALBERT, DM SHORE, JW TI BLACK CORNEA AFTER LONG-TERM EPINEPHRINE USE SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article AB Fifteen years after a partial maxillectomy and radiation therapy for left antral carcinoma, a 53-year-old woman presented to the Eye Plastics and Orbit Service of the Massachussetts Eye and Ear Infirmary, Boston, with phthisis and a large, black corneal lesion in the left eye. She had been treated for unilateral glaucoma in the left eye for more than 10 years with topically administered epinephrine borate, timolol maleate, and pilocarpine hydrochloride. Clinically, the lesion was smooth, black, and homogeneous, and was thought to represent uveal prolapse covered by a thin layer of epithelium. An eyelid-sparing anterior exenteration was performed. Histopathologic examination revealed an acellular, homogeneous substance that stained positively with the Fontana Masson stain for melanin and bleached with potassium permanganate, findings consistent with corneal adrenochrome deposition. Since adrenochrome can be easily dissected free from the cornea, this case illustrates that misdiagnosing adrenochrome deposition may lead to unnecessary surgery. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,BOSTON,MA 02114. NR 10 TC 7 Z9 7 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD SEP PY 1992 VL 110 IS 9 BP 1273 EP 1275 PG 3 WC Ophthalmology SC Ophthalmology GA JL634 UT WOS:A1992JL63400025 PM 1520115 ER PT J AU EISEMAN, B AF EISEMAN, B TI THE PUZZLE PEOPLE - MEMOIRS OF A TRANSPLANT SURGEON SO ARCHIVES OF SURGERY LA English DT Editorial Material C1 DENVER VET AFFAIRS HOSP,DENVER,CO. RP EISEMAN, B (reprint author), UNIV COLORADO,HLTH SCI CTR,DEPT SURG,DENVER,CO 80262, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD SEP PY 1992 VL 127 IS 9 BP 1009 EP 1011 PG 3 WC Surgery SC Surgery GA JM014 UT WOS:A1992JM01400001 PM 1514901 ER PT J AU BERGAN, JJ WILSON, SE WOLF, G DEUPREE, RH TAYLOR, LM ETHEREDGE, SN TWOMEY, PL BERKOWITZ, H CROSS, A RAMAURTHY, S LITTOOY, F DALSING, M REILLY, K TYTLE, T JACOCKS, A LEVEEN, R PERLOFF, L FIELDS, W GOLDMAN, M SOBEL, M POGANY, A EFFENY, D HARLEY, J ZIERLER, E FORTNER, G STERN, D PETERS, G WHITE, G CRUMMY, AB ACHER, C AF BERGAN, JJ WILSON, SE WOLF, G DEUPREE, RH TAYLOR, LM ETHEREDGE, SN TWOMEY, PL BERKOWITZ, H CROSS, A RAMAURTHY, S LITTOOY, F DALSING, M REILLY, K TYTLE, T JACOCKS, A LEVEEN, R PERLOFF, L FIELDS, W GOLDMAN, M SOBEL, M POGANY, A EFFENY, D HARLEY, J ZIERLER, E FORTNER, G STERN, D PETERS, G WHITE, G CRUMMY, AB ACHER, C TI UNEXPECTED, LATE CARDIOVASCULAR EFFECTS OF SURGERY FOR PERIPHERAL ARTERY DISEASE SO ARCHIVES OF SURGERY LA English DT Article ID AORTOILIAC OCCLUSIVE DISEASE; AORTIC-ANEURYSM RESECTION; MYOCARDIAL-INFARCTION; CIGARETTE-SMOKING; SURGICAL STRESS; CARDIAC RISK; RESPONSES; SURVIVAL; OPERATION; HUMANS AB In reviewing late morbidity of a multicenter clinical trial comparing balloon angioplasty (percutaneous transluminal angioplasty) with bypass surgery for lower-extremity ischemia, an unexpectedly high incidence of adverse systemic events in surgical patients was uncovered. The study was prospective and randomized, and included a total of 263 patients, with follow-up from 2 to 6 years. When end points of related deaths, amputations, and intervention failures were summed, surgery was favored over percutaneous transluminal angioplasty at 4 years. Progression of cardiac and renal dysfunction and mortality differed between groups. A total of 42 deaths were in the group who underwent surgery and 27 in those who underwent percutaneous transluminal angioplasty. The percentage difference in death rate between the two groups increased each year to reach 10% at 5 years. A significant difference in renal function was noted in nine patients who underwent surgery and zero who underwent percutaneous transluminal angioplasty. Myocardial infarctions were greater on follow-up of surgical patients. After 6 years, congestive heart failure had occurred in 19 patients who underwent surgery and eight who underwent percutaneous transluminal angioplasty. The trends in this study of patients with only moderately severe peripheral arterial disease suggest an increased rate of deterioration of cardiac and renal function in patients who have arterial operations. In surgical patients, mortality was 13.1% per year, whereas it was 8.4% for patients treated with percutaneous transluminal angioplasty. Future intervention studies should include long-term follow-up of such cardiovascular events. C1 VET AFFAIRS MED CTR,PITTSBURGH,PA. VET ADM MED CTR BRENTWOOD,LOS ANGELES,CA 90073. VET ADM MED CTR,PHILADELPHIA,PA 19104. VET ADM MED CTR,W HAVEN,CT 06516. EDWARD HINES VET ADM MED CTR,HINES,IL. RICHARD L ROUDEBUSH VET ADM MED CTR,INDIANAPOLIS,IN 46202. VET ADM MED CTR,OKLAHOMA CITY,OK 73104. VET ADM MED CTR,RICHMOND,VA 23249. VET ADM MED CTR,SAN FRANCISCO,CA 94121. VET ADM MED CTR,SEATTLE,WA 98108. VET ADM MED CTR,ALBUQUERQUE,NM 87108. WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI. NR 23 TC 21 Z9 22 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD SEP PY 1992 VL 127 IS 9 BP 1119 EP 1124 PG 6 WC Surgery SC Surgery GA JM014 UT WOS:A1992JM01400018 PM 1387528 ER PT J AU WESTERMAN, EM MILES, JM BACKONJA, M SUNDSTROM, WR AF WESTERMAN, EM MILES, JM BACKONJA, M SUNDSTROM, WR TI NEUROPATHOLOGIC FINDINGS IN MULTIINFARCT DEMENTIA ASSOCIATED WITH ANTICARDIOLIPIN ANTIBODY - EVIDENCE FOR ENDOTHELIAL INJURY AS THE PRIMARY EVENT SO ARTHRITIS AND RHEUMATISM LA English DT Article ID ANTIPHOSPHOLIPID ANTIBODIES; GROWTH-FACTOR; THROMBOSIS; BINDING AB Objective. There are few reports describing histopathologic changes associated with the antiphospholipid antibody syndrome. We describe a patient with multi-infarct dementia and antiphospholipid antibody syndrome, in whom a brain biopsy was performed. Methods. Biopsy material from the left frontal cortex, including meninges, cortex, and underlying subcortical white matter, was investigated. Microscopic examination and special staining were performed. Results. Microscopic examination showed lumenal occlusion by thrombi, and marked endothelial hyperplasia of small meningeal and cortical arterioles Conclusion. These findings suggest that the pathogenesis of this cerebral vasculopathy is noninflammatory and is associated with reactive endothelial hyperplasia and thrombosis of small arterioles. C1 WILLIAM S MIDDLETON MEM VET ADM MED CTR,NEUROL & RHEUMATOL SERV,MADISON,WI. UNIV WISCONSIN,CTR CLIN SCI,DEPT PATHOL,MADISON,WI 53706. UNIV WISCONSIN,CTR CLIN SCI,DEPT LAB MED,MADISON,WI 53706. NR 14 TC 59 Z9 60 U1 2 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1992 VL 35 IS 9 BP 1038 EP 1041 DI 10.1002/art.1780350908 PG 4 WC Rheumatology SC Rheumatology GA JQ530 UT WOS:A1992JQ53000007 PM 1418019 ER PT J AU FLESCHER, E DAUPHINEE, MJ FOSSUM, D LEDBETTER, J TALAL, N AF FLESCHER, E DAUPHINEE, MJ FOSSUM, D LEDBETTER, J TALAL, N TI SIGNAL TRANSDUCTION IN SJOGRENS-SYNDROME T-CELLS - ABNORMALITIES ASSOCIATED WITH A NEWLY DESCRIBED HUMAN A-TYPE RETROVIRUS SO ARTHRITIS AND RHEUMATISM LA English DT Article ID PROTEIN KINASE-C; HUMAN IMMUNODEFICIENCY VIRUS; FREE CALCIUM; LYMPHOCYTES-T; ACTIVATION; RECEPTOR; INTERLEUKIN-2; PERTURBATION; STIMULATION; ANTIBODIES AB Objective. To study the effects of a novel A-type retrovirus, detected in cocultures of lip biopsy specimens from Sjogren's syndrome (SS) patients and a human T cell line, on the infected T cells. Methods. Interleukin-2 (IL-2) and IL-6 secretion were measured by bioassay and enzyme-linked immunosorbent assay, respectively, in the infected and noninfected cell lines. Surface antigen expression was determined by flow cytometry, using monoclonal antibodies. Protein kinase C (PKC) activity was measured using an enzyme assay kit, and calcium mobilization was assessed with a fluorescent probe. Results. Infected cells expressed less CD4 and IL-6 receptor, but more HLA-DR, compared with noninfected cells. Infected cells also produced less IL-2 and displayed reduced PKC activation and calcium mobilization. A similar defect in calcium mobilization was detected in T cells from SS patients. Conclusion. These data suggest a possible involvement of the newly described retrovirus in T cell abnormalities. C1 BRISTOL MYERS SQUIBB PHARMACEUT RES INST,SEATTLE,WA. AUDIE L MURPHY MEM VET ADM MED CTR,CLIN IMMUNOL SECT,SAN ANTONIO,TX 78284. RP FLESCHER, E (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV CLIN IMMUNOL,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. FU NIDCR NIH HHS [R01-DE09311] NR 35 TC 10 Z9 10 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1992 VL 35 IS 9 BP 1068 EP 1074 DI 10.1002/art.1780350912 PG 7 WC Rheumatology SC Rheumatology GA JQ530 UT WOS:A1992JQ53000011 PM 1418023 ER PT J AU DANG, H LAZARIDIS, K TALAL, N AF DANG, H LAZARIDIS, K TALAL, N TI INDUCTION OF AUTOANTIBODIES IN NORMAL BALB/C MICE BY PERTURBATION OF THE IDIOTYPE NETWORK SO ARTHRITIS AND RHEUMATISM 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 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1992 VL 35 IS 9 SU S BP S155 EP S155 PG 1 WC Rheumatology SC Rheumatology GA JR158 UT WOS:A1992JR15800714 ER PT J AU DANG, H LAZARIDIS, K AUFDEMORTE, T MCGUFF, H TALAL, N AF DANG, H LAZARIDIS, K AUFDEMORTE, T MCGUFF, H TALAL, N TI PCR ANALYSIS OF CYTOKINES PRODUCED IN SALIVARY-GLANDS OF SJOGRENS-SYNDROME (SS) PATIENTS SO ARTHRITIS AND RHEUMATISM 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 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1992 VL 35 IS 9 SU S BP S103 EP S103 PG 1 WC Rheumatology SC Rheumatology GA JR158 UT WOS:A1992JR15800402 ER PT J AU FLESCHER, E VELAROCH, NE TALAL, N AF FLESCHER, E VELAROCH, NE TALAL, N TI DECREASED EXPRESSION OF THE OCT-1 TRANSCRIPTION FACTOR REGULATING THE T-CELL INTERLEUKIN-2 (IL-2) GENE IN SJOGRENS-SYNDROME (SS) SO ARTHRITIS AND RHEUMATISM 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 LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1992 VL 35 IS 9 SU S BP S61 EP S61 PG 1 WC Rheumatology SC Rheumatology GA JR158 UT WOS:A1992JR15800162 ER PT J AU FRASER, PA FICI, D AWDEH, Z YUNIS, EJ ALPER, CA AF FRASER, PA FICI, D AWDEH, Z YUNIS, EJ ALPER, CA TI HLA-BW42 PHENOTYPES AND HAPLOTYPES AND RESISTANCE TO RHEUMATOID-ARTHRITIS (RA) IN POPULATIONS OF BLACK-AFRICAN DESCENT SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,DEPT RHEUMATOL & IMMUNOL,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1992 VL 35 IS 9 SU S BP S337 EP S337 PG 1 WC Rheumatology SC Rheumatology GA JR158 UT WOS:A1992JR15801563 ER PT J AU KAWAKAMI, A TIAN, O DUAN, X STREULI, M SCHLOSSMAN, SF ANDERSON, P AF KAWAKAMI, A TIAN, O DUAN, X STREULI, M SCHLOSSMAN, SF ANDERSON, P TI THE NUCLEOLYSINS - A FAMILY OF CYTOTOXIC GRANULE-ASSOCIATED RNA-BINDING PROTEINS THAT INDUCE DNA-FRAGMENTATION IN CTL TARGET-CELLS SO ARTHRITIS AND RHEUMATISM 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 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1992 VL 35 IS 9 SU S BP S61 EP S61 PG 1 WC Rheumatology SC Rheumatology GA JR158 UT WOS:A1992JR15800158 ER PT J AU NIJIMA, Y SHI, L DOSHEN, J SCHLOSSMAN, SF MORIMOTO, C AF NIJIMA, Y SHI, L DOSHEN, J SCHLOSSMAN, SF MORIMOTO, C TI PROTEIN TYROSINE KINASE ACTIVATION INDUCED BY LIGATION OF VLA MOLECULES ON T-CELLS SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,DIV TUMOR IMMUNOL,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1992 VL 35 IS 9 SU S BP S312 EP S312 PG 1 WC Rheumatology SC Rheumatology GA JR158 UT WOS:A1992JR15801414 ER PT J AU SUGITA, K HIROSE, T NOJIMA, Y ROTHSTEIN, DM SCHLOSSMAN, SF MORIMOTO, C AF SUGITA, K HIROSE, T NOJIMA, Y ROTHSTEIN, DM SCHLOSSMAN, SF MORIMOTO, C TI CD27, A MEMBER OF THE NERVE GROWTH-FACTOR RECEPTOR FAMILY, IS EXCLUSIVELY EXPRESSED ON CD45RA+ CD4 T-CELL CLONES AND INVOLVED IN SUPPRESSOR FUNCTION SO ARTHRITIS AND RHEUMATISM 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 LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1992 VL 35 IS 9 SU S BP S138 EP S138 PG 1 WC Rheumatology SC Rheumatology GA JR158 UT WOS:A1992JR15800609 ER PT J AU TANAKA, T KAMEOKA, J SCHLOSSMAN, SF MORIMOTO, C AF TANAKA, T KAMEOKA, J SCHLOSSMAN, SF MORIMOTO, C TI CD26 EXPRESSION ENHANCES IL-2 SYNTHESIS IN A TRANSFECTED T-CELL LINE SO ARTHRITIS AND RHEUMATISM 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 LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1992 VL 35 IS 9 SU S BP S127 EP S127 PG 1 WC Rheumatology SC Rheumatology GA JR158 UT WOS:A1992JR15800544 ER PT J AU WEINBLATT, M POLISSON, R BLOTNER, S SOSMAN, L ALIABADI, P BAKER, N WEISSMAN, B AF WEINBLATT, M POLISSON, R BLOTNER, S SOSMAN, L ALIABADI, P BAKER, N WEISSMAN, B TI THE EFFECTS OF DRUG-THERAPY ON RADIOGRAPHIC PROGRESSION - RESULTS OF A 9 MONTH RANDOMIZED TRIAL COMPARING METHOTREXATE (MTX) TO AURANOFIN (AU) SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. AMER CYANAMID CO,LEDERLE LABS,PEARL RIVER,NY 10965. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1992 VL 35 IS 9 SU S BP S234 EP S234 PG 1 WC Rheumatology SC Rheumatology GA JR158 UT WOS:A1992JR15801179 ER PT J AU YAMIN, R SANDELL, LJ GOLDRING, MB AF YAMIN, R SANDELL, LJ GOLDRING, MB TI INTERLEUKIN-1 AND INTERFERON-GAMMA SUPPRESS THE EXPRESSION OF 5'-REGULATORY SEQUENCES IN THE TYPE-II COLLAGEN GENE IN HUMAN CHONDROCYTES SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. UNIV WASHINGTON,SEATTLE,WA 98195. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1992 VL 35 IS 9 SU S BP S49 EP S49 PG 1 WC Rheumatology SC Rheumatology GA JR158 UT WOS:A1992JR15800088 ER PT J AU MCCORMICK, S GOFF, DC AF MCCORMICK, S GOFF, DC TI POSSESSION STATES - APPROACHES TO CLINICAL-EVALUATION AND CLASSIFICATION SO BEHAVIOURAL NEUROLOGY LA English DT Review DE CLINICAL CLASSIFICATION; POSSESSION DISORDERS; THERAPEUTIC GUIDELINES ID MULTIPLE PERSONALITY-DISORDER; CHRONICALLY PSYCHOTIC-PATIENTS; DSM-III-R; SPIRIT POSSESSION; DISSOCIATIVE STATES; PSYCHOPATHOLOGY; SCHIZOPHRENIA; COMMUNITY; SYMPTOMS; EPILEPSY AB The fields of anthropology and sociology have produced a large quantity of literature on possession states, physicians however rarely report on such phenomena. As a result clinical description of possession states has suffered, even though these states may be more common and less deviant than supposed. Both ICD-10 and DSM-IV may include specific criteria for possession disorders. The authors briefly review Western notions about possession and kindred states and present guidelines for evaluation and classification. C1 FREEDOM TRAIL CLIN,ERICH LINDEMANN MENTAL HLTH CTR,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02114. NR 70 TC 6 Z9 6 U1 1 U2 4 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0953-4180 J9 BEHAV NEUROL JI Behav. Neurol. PD FAL PY 1992 VL 5 IS 3 BP 161 EP 167 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA KC203 UT WOS:A1992KC20300004 PM 24487741 ER PT J AU MEDYNSKI, D AF MEDYNSKI, D TI GENETIC APPROACHES TO PROTEIN-STRUCTURE AND FUNCTION - POINT MUTATIONS AS MODIFIERS OF PROTEIN FUNCTION SO BIO-TECHNOLOGY LA English DT Review ID TRANSFER-RNA GENES; ESCHERICHIA-COLI; SIGNAL TRANSDUCTION; RECEPTOR; SUPPRESSOR; CONSTRUCTION; ANTAGONIST; REPRESSOR; BINDING; DOMAIN AB In this review, I summarize data in the biological literature which underscore the utility of a genetic approach to protein structure/function problems, with emphasis on binding phenomena, particularly of cytokine and growth factor/receptor interactions. Useful parallels or contrasts to chemical ligand/receptor systems and DNA binding protein interactions are examined where they simplify the analysis of protein ligand/receptor interactions. This approach was prompted by the fact that purely rational approaches, based on resolution of the three dimensional structure of proteins, are limited because such data is available for fewer than 3% of the 17,000 proteins for which the amino acid sequence has been deduced by molecular biology techniques. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NR 49 TC 9 Z9 9 U1 0 U2 0 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 0733-222X J9 BIO-TECHNOL JI Bio-Technology PD SEP PY 1992 VL 10 IS 9 BP 1002 EP 1006 DI 10.1038/nbt0992-1002 PG 5 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA KR583 UT WOS:A1992KR58300028 PM 1368997 ER PT J AU BAUER, MS SOLOWAY, A DRATMAN, MB KREIDER, M AF BAUER, MS SOLOWAY, A DRATMAN, MB KREIDER, M TI EFFECTS OF HYPOTHYROIDISM ON RAT CIRCADIAN ACTIVITY AND TEMPERATURE RHYTHMS AND THEIR RESPONSE TO LIGHT SO BIOLOGICAL PSYCHIATRY LA English DT Article ID SEASONAL AFFECTIVE-DISORDER; MELATONIN SUPPRESSION; EUROPEAN STARLINGS; DEPRESSED-PATIENTS; PINEAL-GLAND; THYROXINE; ABNORMALITIES; PACEMAKER; ILLNESS; PHOTOREFRACTORINESS AB Male rats made hypothyroid by administration of propylthiouracil plus sodium ipodate in drinking water were compared to controls in terms of period of circadian activity and temperature rhythms, amount of gross motor activity, and mean temperature. Animals were studied under entrainment, constant darkness (DD), and constant dim light (LL). There was no difference in the period of the circadian activity rhythm between groups in DD. However, hypothyroid rats showed significant blunting of the period-lengthening response to increasing ambient illumination. As expected, the period of the circadian temperature rhythm increased in controls with increasing ambient illumination. In contrast, the period of the circadian temperature rhythm in hypothyroid animals actually shortened under LL compared to DD. This blunting of the period-lengthening response to increasing ambient illumination of both activity and temperature rhythms in hypothyroid animals could not be explained by differences in activity level or mean temperature between the groups. C1 DEPT VET AFFAIRS MED CTR,PHILADELPHIA,PA. BROWN UNIV,DEPT PSYCHIAT & HUMAN BEHAV,PROVIDENCE,RI 02912. UNIV PENN,DEPT PSYCHIAT,PHILADELPHIA,PA 19104. MED COLL PENN,DEPT MED,PHILADELPHIA,PA 19129. RP BAUER, MS (reprint author), DEPT VET AFFAIRS MED CTR,PROVIDENCE,RI 02908, USA. FU NIMH NIH HHS [MH00720, MH45252, MH44210] NR 51 TC 8 Z9 9 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD SEP 1 PY 1992 VL 32 IS 5 BP 411 EP 425 DI 10.1016/0006-3223(92)90129-N PG 15 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA JX843 UT WOS:A1992JX84300004 PM 1486147 ER PT J AU PETROS, WP RABINOWITZ, J STUART, AR GILBERT, CJ KANAKURA, Y GRIFFIN, JD PETERS, WP AF PETROS, WP RABINOWITZ, J STUART, AR GILBERT, CJ KANAKURA, Y GRIFFIN, JD PETERS, WP TI DISPOSITION OF RECOMBINANT HUMAN GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR IN PATIENTS RECEIVING HIGH-DOSE CHEMOTHERAPY AND AUTOLOGOUS BONE-MARROW SUPPORT SO BLOOD LA English DT Article ID BREAST-CANCER; PHARMACOKINETICS; TRANSPLANTATION; TOXICITY C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. RP PETROS, WP (reprint author), DUKE UNIV,MED CTR,DEPT MED,BONE MARROW TRANSPLANT PROGRAM,BOX 3961,DURHAM,NC 27710, USA. NR 15 TC 25 Z9 26 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 SEP 1 PY 1992 VL 80 IS 5 BP 1135 EP 1140 PG 6 WC Hematology SC Hematology GA JL367 UT WOS:A1992JL36700006 PM 1515635 ER PT J AU TRIPPETT, T SCHLEMMER, S ELISSEYEFF, Y GOKER, E WACHTER, M STEINHERZ, P TAN, C BERMAN, E WRIGHT, JE ROSOWSKY, A SCHWEITZER, B BERTINO, JR AF TRIPPETT, T SCHLEMMER, S ELISSEYEFF, Y GOKER, E WACHTER, M STEINHERZ, P TAN, C BERMAN, E WRIGHT, JE ROSOWSKY, A SCHWEITZER, B BERTINO, JR TI DEFECTIVE TRANSPORT AS A MECHANISM OF ACQUIRED-RESISTANCE TO METHOTREXATE IN PATIENTS WITH ACUTE LYMPHOCYTIC-LEUKEMIA SO BLOOD LA English DT Article ID CROSS-RESISTANCE; FLOW-CYTOMETRY; CELL-LINES; TRIMETREXATE; ANTIFOLATE C1 MEM SLOAN KETTERING CANC CTR,PROGRAM MOLEC PHARMACOL & THERAPEUT,1275 YORK AVE,NEW YORK,NY 10021. MEM SLOAN KETTERING CANC CTR,DEPT PEDIAT,NEW YORK,NY 10021. MEM SLOAN KETTERING CANC CTR,DEPT MED,NEW YORK,NY 10021. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. FU NCI NIH HHS [CA 19589] NR 23 TC 69 Z9 70 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 SEP 1 PY 1992 VL 80 IS 5 BP 1158 EP 1162 PG 5 WC Hematology SC Hematology GA JL367 UT WOS:A1992JL36700009 PM 1381235 ER PT J AU LIBOI, E JUBINSKY, P ANDREWS, NC NATHAN, DG MATHEYPREVOT, B AF LIBOI, E JUBINSKY, P ANDREWS, NC NATHAN, DG MATHEYPREVOT, B TI ENHANCED EXPRESSION OF INTERLEUKIN-3 AND GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR RECEPTOR SUBUNITS IN MURINE HEMATOPOIETIC-CELLS STIMULATED WITH HEMATOPOIETIC GROWTH-FACTORS SO BLOOD LA English DT Article ID GM-CSF; ERYTHROPOIETIN RECEPTOR; IL-3 RECEPTOR; MULTI-CSF; LINES; CLONING; PROLIFERATION; CULTURE; PROTEIN; CDNA C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,D1630A,44 BINNEY ST,BOSTON,MA 02115. CHILDRENS HOSP MED CTR,DIV PEDIAT HEMATOL & ONCOL,BOSTON,MA 02115. OI Andrews, Nancy/0000-0003-0243-4462 FU NHLBI NIH HHS [P01 HL32262-10]; NIGMS NIH HHS [F32 GM13452] NR 32 TC 34 Z9 34 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 SEP 1 PY 1992 VL 80 IS 5 BP 1183 EP 1189 PG 7 WC Hematology SC Hematology GA JL367 UT WOS:A1992JL36700013 PM 1387562 ER PT J AU FREEDMAN, AS MUNRO, JM RHYNHART, K SCHOW, P DALEY, J LEE, N SVAHN, J ELISEO, L NADLER, LM AF FREEDMAN, AS MUNRO, JM RHYNHART, K SCHOW, P DALEY, J LEE, N SVAHN, J ELISEO, L NADLER, LM TI FOLLICULAR DENDRITIC CELLS INHIBIT HUMAN LYMPHOCYTE-B PROLIFERATION SO BLOOD LA English DT Article ID ACQUIRED IMMUNODEFICIENCY SYNDROME; EPSTEIN-BARR VIRUS; GERMINAL-CENTERS; IMMUNE-RESPONSES; T-CELLS; IMMUNOLOGICAL MEMORY; HOMOSEXUAL MEN; HUMAN TONSILS; ACTIVATION; ANTIGEN C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. 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 52 TC 23 Z9 23 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 SEP 1 PY 1992 VL 80 IS 5 BP 1284 EP 1288 PG 5 WC Hematology SC Hematology GA JL367 UT WOS:A1992JL36700027 PM 1515644 ER PT J AU HERBERT, V AF HERBERT, V TI IRON DISORDERS CAN MIMIC ANYTHING, SO ALWAYS TEST FOR THEM SO BLOOD REVIEWS LA English DT Review ID DIETARY IRON; EXTRINSIC TAG; VITAMIN-C; ABSORPTION; HEMOCHROMATOSIS; BIOAVAILABILITY; SUPEROXIDE; DIAGNOSIS AB Routinely measuring iron status is necessary because not only are about 6% of Americans in significant negative iron balance, but about 1% have iron overload. Serum ferritin is in equilibrium with body iron stores, and is the only blood test that measures them. Barring inflammation, each one ng (0.0179 pmol) ferritin/ml of serum indicates approximately 10 mg (0.179 mmol) of body iron stores. Very early Stage I positive balance is best recognized by measuring saturation of iron binding capacity. Conversely, serum ferritin best recognizes early (Stage I and II) negative balance. Deviations from normal are: 1. Both stages of iron depletion (i.e. low stores, no dysfunction). Negative iron balance Stage I is reduced iron absorption producing moderately depleted iron stores. Stage II is severely depleted stores, without dysfunction. These stages include over half of all cases of negative iron balance. Treated with iron, they never progress to dysfunction, i.e. to disease. 2. Both stages of iron deficiency. Deficiency is inadequate iron for normal function, i.e. dysfunction, disease. Negative balance Stage III is dysfunction without anemia; Stage IV is with anemia. 3. Positive iron balance: Stage I is a multi-year period without dysfunction. Supplements of iron and/or vitamin C promote progression to dysfunction (disease). Iron removal prevents progression. Stage II is iron overload disease, encompassing years of insidiously progressive damage to tissues and organs from iron overload. Iron removal arrests progression. C1 MT SINAI MED CTR,COMM STRENGTHEN NUTR,BRONX,NY 10468. BRONX VET AFFAIRS MED CTR,HEMATOL & NUTR LAB,BRONX,NY 10468. RP HERBERT, V (reprint author), MT SINAI MED SCH,COMM STRENGTHEN NUTR,BRONX,NY 10468, USA. NR 70 TC 2 Z9 2 U1 2 U2 5 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH, MIDLOTHIAN, SCOTLAND EH1 3AF SN 0268-960X J9 BLOOD REV JI Blood Rev. PD SEP PY 1992 VL 6 IS 3 BP 125 EP 132 DI 10.1016/0268-960X(92)90024-K PG 8 WC Hematology SC Hematology GA JP229 UT WOS:A1992JP22900001 PM 1422281 ER PT J AU OTT, RJ TAIT, D FLOWER, MA BABICH, JW LAMBRECHT, RM AF OTT, RJ TAIT, D FLOWER, MA BABICH, JW LAMBRECHT, RM TI TREATMENT PLANNING FOR I-131 METAIODOBENZYLGUANIDINE RADIOTHERAPY OF NEURAL CREST TUMORS USING I-124 METAIODOBENZYLGUANIDINE POSITRON EMISSION TOMOGRAPHY SO BRITISH JOURNAL OF RADIOLOGY LA English DT Article DE NEURAL CREST TUMORS; METAIODOBENZYLGUANIDINE THERAPY; PET ID METAIODOBENZYLGUANIDINE; CHILDHOOD; CAMERA; PET AB Patients designated to receive I-131-meta-iodobenzylguanadine (mIBG) for the treatment of neural crest tumours have been scanned with I-124-mIBG using the MUP-PET positron camera. Uptake was detected in tumour sites in lung, liver and abdomen. The tomographic images produced have allowed estimates to be made of the concentration of mIBG in both tumour and normal tissue. From these data it is possible to predict the radiation doses that would be achieved using therapy levels (up to 11 GBq) of I-131-mIBG. The levels of tumour uptake are between 0.5 and 2.0 kBq/g indicating that the radiation doses to tumour would be in the range 3 Gy to 7.5 Gy. C1 INST CANC RES,DEPT RADIOTHERAPY,SUTTON SM2 5PX,SURREY,ENGLAND. ROYAL MARSDEN HOSP,SUTTON,SURREY,ENGLAND. MASSACHUSETTS GEN HOSP,DIV NUCL MED,BOSTON,MA 02114. LUCAS HTS RES LABS,SYDNEY,AUSTRALIA. RP OTT, RJ (reprint author), INST CANC RES,DEPT PHYS,SUTTON SM2 5PX,SURREY,ENGLAND. NR 14 TC 47 Z9 47 U1 0 U2 1 PU BRITISH INST RADIOLOGY PI LONDON PA 36 PORTLAND PLACE, LONDON, ENGLAND W1N 4AT SN 0007-1285 J9 BRIT J RADIOL JI Br. J. Radiol. PD SEP PY 1992 VL 65 IS 777 BP 787 EP 791 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA JN725 UT WOS:A1992JN72500010 PM 1393416 ER PT J AU WINAWER, SJ ZAUBER, AG OBRIEN, MJ GOTTLIEB, LS STERNBERG, SS STEWART, ET BOND, JH SCHAPIRO, M PANISH, JF WAYE, JD KURTZ, RC SHIKE, M HO, MN LIGHTDALE, CJ EDELMAN, M COHEN, A FLEISHER, M MCMAHAN, RA KOSKELLA, K MILLER, C WAYE, JD LEWIS, BS SZPORN, A KHILNANI, M YESSAYAN, S ANSEL, H EWING, S DOBSON, T HOGAN, W STONE, J HELM, J NOWAK, T STEWART, T KOMOROWSKI, R GEENEN, J VENU, R JOHNSON, K SCHUSTER, T DEBOER, N ACKROYD, F SHELLITO, P HALL, D DICKERSIN, GR HORTON, N SHERMAN, J HAMLIN, JA GELLER, S KOJIMOTO, MA AUSLANDER, M KASIMIAN, D KUSSIN, L SCOGGINS, C MAGRATH, C AF WINAWER, SJ ZAUBER, AG OBRIEN, MJ GOTTLIEB, LS STERNBERG, SS STEWART, ET BOND, JH SCHAPIRO, M PANISH, JF WAYE, JD KURTZ, RC SHIKE, M HO, MN LIGHTDALE, CJ EDELMAN, M COHEN, A FLEISHER, M MCMAHAN, RA KOSKELLA, K MILLER, C WAYE, JD LEWIS, BS SZPORN, A KHILNANI, M YESSAYAN, S ANSEL, H EWING, S DOBSON, T HOGAN, W STONE, J HELM, J NOWAK, T STEWART, T KOMOROWSKI, R GEENEN, J VENU, R JOHNSON, K SCHUSTER, T DEBOER, N ACKROYD, F SHELLITO, P HALL, D DICKERSIN, GR HORTON, N SHERMAN, J HAMLIN, JA GELLER, S KOJIMOTO, MA AUSLANDER, M KASIMIAN, D KUSSIN, L SCOGGINS, C MAGRATH, C TI THE NATIONAL POLYP STUDY - DESIGN, METHODS, AND CHARACTERISTICS OF PATIENTS WITH NEWLY DIAGNOSED POLYPS SO CANCER LA English DT Article; Proceedings Paper CT NATIONAL CONF ON COLORECTAL CANCER CY MAR 20-22, 1991 CL NEW ORLEANS, LA SP AMER CANC SOC DE NATIONAL POLYP STUDY; COLORECTAL POLYPS; COLORECTAL ADENOMAS ID COLORECTAL ADENOMAS; COLONIC POLYPS; LARGE-BOWEL; MALIGNANT TRANSFORMATION; CANCER; RISK; COLONOSCOPY; SURVEILLANCE; POLYPECTOMY; LESIONS AB The National Polyp Study (NPS) is a multicenter prospective randomized trial designed to evaluate follow-up surveillance strategies in patients who have undergone polypectomy for the control of large bowel cancer. The study design was developed by a joint research committee from American Gastroenterological Association, the American Society for Gastrointestinal Endoscopy, and the American College of Gastroenterology. Subjects who met the eligibility criteria were randomized into two different treatment arms. Eligibility criteria included: removal of one or more adenomas; complete colonoscopy; no prior polypectomy, inflammatory bowel disease, or familial polyposis; and no history of colon cancer. The treatment arms consisted of a frequent follow-up (1 and 3 years after initial polypectomy) and a less frequent follow-up (3 years). Follow-up examinations included fecal occult blood tests, air-contrast barium enema, and colonoscopy. The latter was done on 9112 referred patients at the seven participating centers from November 1980 until February 1990 who had no history of polypectomy, colon cancer, familial polyposis, or inflammatory bowel disease. Of these patients, 4763 (52.3%) had no polyps; 549 (6.0%) had an invasive cancer; 776 (8.5%) had nonadenomatous polyps; 208 (2.3%) had incomplete examinations; 184 (2.0%) had other findings; and 2632 (28.9%) had one or more adenomas, of which 1418 (53.9%) were randomized to one of the two treatment arms. This article reports the background, rationale, objectives, methods, and organization of this study and includes patient characteristics on initial presentation. Future data provided by the NPS may help in the development of recommendations for surveillance guidelines for such patients. This study also provides a framework to address questions regarding the natural history of adenomas and their relationship with colorectal cancer. C1 STRANG CLIN,NEW YORK,NY. MILWAUKEE CTY MED CTR,MILWAUKEE,WI. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. CEDARS SINAI MED CTR,LOS ANGELES,CA 90048. VALLEY PRESBYTERIAN HOSP,VAN NUYS,CA. MALLORY INST PATHOL,BOSTON,MA. RP WINAWER, SJ (reprint author), MEM SLOAN KETTERING CANC CTR,DEPT MED,GASTROENTEROL SERV,1275 YORK AVE,NEW YORK,NY 10021, USA. FU NCI NIH HHS [CA 26852] NR 51 TC 106 Z9 109 U1 1 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD SEP 1 PY 1992 VL 70 IS 5 SU S BP 1236 EP 1245 DI 10.1002/1097-0142(19920901)70:3+<1236::AID-CNCR2820701508>3.0.CO;2-4 PG 10 WC Oncology SC Oncology GA JL193 UT WOS:A1992JL19300006 PM 1511370 ER PT J AU MAYER, RJ AF MAYER, RJ TI CHEMOTHERAPY FOR METASTATIC COLORECTAL-CANCER SO CANCER LA English DT Article; Proceedings Paper CT NATIONAL CONF ON COLORECTAL CANCER CY MAR 20-22, 1991 CL NEW ORLEANS, LA SP AMER CANC SOC DE COLORECTAL CANCER; CHEMOTHERAPY; METASTATIC DISEASE ID PROSPECTIVE RANDOMIZED TRIAL; CONTINUOUS-INFUSION 5-FLUOROURACIL; INTENSIVE COURSE 5-FLUOROURACIL; FLUOROURACIL PLUS CISPLATIN; ATLANTIC ONCOLOGY PROGRAM; STREPTOZOTOCIN MOF-STREP; LARGE-BOWEL CARCINOMA; HIGH-DOSE LEUCOVORIN; PHASE-II EVALUATION; METHYL-CCNU AB The systemic management of patients with colorectal cancer continues to focus on the use of 5-fluorouracil (5-FU). In the setting of metastatic disease, parenteral 5-FU has been shown to be superior to oral 5-FU; however, survival duration seems similar whether such parenteral 5-FU is administered in a "loading," weekly, or continuous infusion manner. The addition of other cytotoxic agents such as semustine, mitomycin C, or cisplatin to 5-FU does not appear to increase the response rate or prolong survival. The results of five randomized trials assessing the value of intraarterial hepatic infusions of 5-FU or floxuridine show that such regional chemotherapy increases the likelihood of hepatic response compared with systemic treatment but has little effect on survival and is associated with significant toxicity. Recent efforts in the management of patients with advanced disease have been directed at optimizing the activity of 5-FU by (1) enhancing the inhibition of DNA synthesis through the concomitant administration of folinic acid; (2) increasing drug incorporation into RNA through pretreatment with methotrexate or phosphonacetyl-L-aspartate; and (3) improving the drug's activity through the synergistic action of alpha-2a-interferon. Although the results of some of these investigations have been promising, only the 5-FU and folinic acid combination consistently has appeared to be superior to single-agent 5-FU. These different approaches to biochemical modulation are being compared in ongoing cooperative group trials. RP MAYER, RJ (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. NR 102 TC 44 Z9 44 U1 2 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD SEP 1 PY 1992 VL 70 IS 5 SU S BP 1414 EP 1424 DI 10.1002/1097-0142(19920901)70:3+<1414::AID-CNCR2820701533>3.0.CO;2-I PG 11 WC Oncology SC Oncology GA JL193 UT WOS:A1992JL19300031 PM 1511393 ER PT J AU SOTOMAYOR, EA TEICHER, BA SCHWARTZ, GN HOLDEN, SA MENON, K HERMAN, TS FREI, E AF SOTOMAYOR, EA TEICHER, BA SCHWARTZ, GN HOLDEN, SA MENON, K HERMAN, TS FREI, E TI MINOCYCLINE IN COMBINATION WITH CHEMOTHERAPY OR RADIATION-THERAPY INVITRO AND INVIVO SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE MINOCYCLINE; CHEMOTHERAPY; RADIATION THERAPY ID MOUSE MAMMARY-TUMOR; COLLAGENASE ACTIVITY; ANGIOGENESIS INHIBITION; EXTRACELLULAR-MATRIX; HEPARIN FRAGMENT; LUNG-TUMOR; CELLS; MECHANISM; CORTISONE; GROWTH AB In the present study the potential of minocycline, a semisynthetic tetracycline that inhibits collagenase activity in vivo, as an adjuvant to standard anticancer therapies was explored in vitro and in vivo. In EMT-6 cells, minocycline proved to be only minimally cytotoxic, producing a 50% cell kill at concentrations of 132 and 220-mu-M in normally oxygenated and hypoxic cells, respectively, after 24 h exposure to the drug. In vitro, there appeared to be no interaction between minocycline and cisplatin (CDDP), melphalan, 4-hydroperoxycyclophosphamide, or radiation. In tumor-cell survival studies using the FSaIIC murine fibrosarcoma, short-term treatment with minocycline (5 x 5 mg/kg given over 24 h) was only minimally cytotoxic and did not alter the tumor response to a range of radiation doses. However, when minocycline (5 x 5 mg/kg given over 24 h) was added to treatment with cyclophosphamide, there was a 4-fold increase in FSaIIC tumor-cell killing across the dose range of cyclophosphamide doses tested, whereas the killing of bone marrow granulocyte macrophage colony-forming units (CFU-GM) remained unchanged. The Lewis lung carcinoma was used to assess the response of both the primary tumor and metastatic lung disease to treatment with minocycline (I 4 x 5 mg/kg) given alone or in combination with several cytotoxic anticancer drugs or with radiation delivered locally to the primary tumor. Of the various therapies tested, minocycline proved to be especially effective as an addition to treatment with cyclophosphamide both in increasing the response of the primary tumor and in reducing the number of lung metastases. The tumor growth delay produced by melphalan, radiation, Adriamycin, and bleomycin was also increased by the addition of minocycline to these therapies. These results indicate that minocycline given in clinically achievable doses may be an effective addition to some standard therapeutic regimens and that the mechanism of modulation by minocycline is likely to involve an effect of the drug on the host and not its direct interaction with other therapeutic modalities at the level of the tumor cell. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115. JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. FU NCI NIH HHS [R01-CA47379]; OHS HRSA HHS [P01-STAMP] NR 62 TC 40 Z9 40 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD SEP PY 1992 VL 30 IS 5 BP 377 EP 384 DI 10.1007/BF00689966 PG 8 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA JG989 UT WOS:A1992JG98900008 PM 1505076 ER PT J AU RASMUSSEN, RA COUNTS, SL LAMBERT, JM COLLINSON, AR AF RASMUSSEN, RA COUNTS, SL LAMBERT, JM COLLINSON, AR TI BLOCKED RICIN-CONJUGATED-T CELL IMMUNOTOXINS - EFFECT OF ANTI-CD6-BLOCKED RICIN ON NORMAL-T CELL-FUNCTION SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Article DE CD6; IMMUNOTOXIN; BLOCKED RICIN; T-CELLS ID BONE-MARROW TRANSPLANTATION; A-CHAIN IMMUNOTOXIN; GALACTOSE-BINDING SITES; HUMAN PERIPHERAL-BLOOD; NATURAL-KILLER CELLS; VERSUS-HOST DISEASE; MONOCLONAL-ANTIBODIES; B-CHAIN; DEPLETION; ANTIGEN AB The biological properties of an immunotoxin composed of an anti-CD6 monoclonal antibody conjugated to whole ricin, which had been modified so that the galactose-binding sites of the B chain were blocked ("blocked ricin"), were examined. Treatment of peripheral blood lymphocytes with anti-CD6-blocked ricin for a 24-h period prevented T cell proliferation induced by phytohemagglutinin in a dose-dependent manner with concentrations causing 50% inhibition (IC50) ranging from 5 pM to 30 pM. In contrast, treatment with either blocked ricin alone or with a control immunotoxin prepared with a B-cell-lineage-restricted monoclonal antibody gave IC50 values of approximately 2 nM. Although shortening the duration of the anti-CD6-blocked ricin treatment to as little as 3 h had little significant effect on the observed inhibition, T cell viability experiments demonstrated that the magnitude of immunotoxin-induced killing after a given time period is significantly higher when the target cells become activated. Thus, from the initial concentration of cells treated with anti-CD6-blocked ricin placed in culture, 40%-45% viable cells remained after 2 days yet only 3%-9% remained if phorbol ester and Ca2+ ionophore were added; activation of T cells after mock treatment using blocked ricin plus nonconjugated anti-CD6 demonstrated that this effect was not the result of activation alone-. The toxicity of anti-CD6-blocked ricin was also measured by inhibition of PHA-induced clonogenic growth of normal T cells. Continuous treatment of the cells using anti-CD6-blocked ricin at 0.1 nM resulted in a surviving fraction of about 3.5 x 10(-3); when immunotoxin treatment was for 24 h or less, the surviving fraction was only about 10(-1). As an indication of the unique specificity of anti-CD6-blocked ricin, immunotoxin pretreatment of potential responder cells prevented the generation of allogeneic cytolytic T lymphocytes in mixed lymphocyte cultures yet had little effect on the generation of interleukin-2-induced lymphokine-activated killer cell activity. We conclude that anti-CD6-blocked ricin demonstrates a cellular specificity and potency that make it a highly promising anti-T cell reagent. C1 IMMUNOGEN INC,CAMBRIDGE,MA 02139. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RP RASMUSSEN, RA (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,44 BINNEY ST,BOSTON,MA 02115, USA. NR 45 TC 5 Z9 5 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-7004 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD SEP PY 1992 VL 35 IS 5 BP 355 EP 363 DI 10.1007/BF01741150 PG 9 WC Oncology; Immunology SC Oncology; Immunology GA JM929 UT WOS:A1992JM92900010 PM 1394340 ER PT J AU BRACHMAN, DG GRAVES, D VOKES, E BECKETT, M HARAF, D MONTAG, A DUNPHY, E MICK, R YANDELL, D WEICHSELBAUM, RR AF BRACHMAN, DG GRAVES, D VOKES, E BECKETT, M HARAF, D MONTAG, A DUNPHY, E MICK, R YANDELL, D WEICHSELBAUM, RR TI OCCURRENCE OF P53 GENE DELETIONS AND HUMAN PAPILLOMA-VIRUS INFECTION IN HUMAN HEAD AND NECK-CANCER SO CANCER RESEARCH LA English DT Note ID CARCINOMA CELL-LINES; CERVICAL CARCINOMAS; RAS MUTATIONS; LUNG-CANCER; DNA; PROTEIN; ASSOCIATION; RADIATION; FREQUENT AB Little is known regarding the molecular genetic events in head and neck carcinoma. Epidemiological evidence suggests that both alcohol and tobacco use are related to the development of these neoplasms, and viral infections have also been postulated to play a role in some tumors. Loss of p53 tumor suppressor gene function has been found in many malignancies and can occur through either gene mutation or by interaction with the E6 protein of oncogenic human papilloma viruses (HPV). Because the mucosal surfaces of the head and neck are exposed to mutagens and HPVs, we studied DNA derived from 30 stage I-IV squamous cell carcinomas of the head and neck (9 primary tumors and 21 early passage cell lines) for p53 gene mutations as well as for the presence of oncogenic HPV DNA. Exons 2 through 11 of the p53 gene were examined using single strand conformation polymorphism analysis followed by direct genomic sequencing of all variants. HPV detection was done using polymerase chain reaction amplification with HPV E6 region type specific primers as well as L1 region degenerate ("consensus") primers; HPV type was determined by restriction fragment length polymorphism analysis of the amplified fragment as well as by Southern blotting of genomic DNA. Sixteen of 30 tumors (53%) had p53 mutations and oncogenic HPV DNA was detected in 3 of 30 (10%) tumors, none of which had p53 mutations. The p53 mutational spectrum observed was characterized by equal frequencies of transversions (6 of 16), transitions (5 of 16), and deletions (5 of 16). This distribution of mutations differs from the spectrum of p53 mutation reported in esophageal (P = 0.05) and lung (P = 0.02) cancers, two other tobacco associated neoplasms. A previously undescribed clustering of 3 mutations at codon 205 was also observed. A trend toward a shorter time to tumor recurrence after treatment was noted for those patients with tumors exhibiting p53 gene mutations, and no relationship between p53 mutations and tumor stage or node status was noted. Alteration in p53 gene function appears common in head and neck cancer, and the mutational spectrum observed may reflect the role of different mutagens or mutagenic processes than those responsible for the p53 mutations in lung and esophageal neoplasms. C1 UNIV CHICAGO HOSP & CLIN,DEPT PATHOL,CHICAGO,IL 60637. UNIV CHICAGO HOSP & CLIN,DEPT MED,CHICAGO,IL 60637. MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP BRACHMAN, DG (reprint author), UNIV CHICAGO HOSP & CLIN,DEPT RADIAT & CELLULAR ONCOL,CHICAGO,IL 60637, USA. FU NCI NIH HHS [CA 41068] NR 44 TC 199 Z9 200 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 1 PY 1992 VL 52 IS 17 BP 4832 EP 4836 PG 5 WC Oncology SC Oncology GA JK679 UT WOS:A1992JK67900043 PM 1324797 ER PT J AU DATTA, R HASS, R GUNJI, H WEICHSELBAUM, R KUFE, D AF DATTA, R HASS, R GUNJI, H WEICHSELBAUM, R KUFE, D TI DOWN-REGULATION OF CELL-CYCLE CONTROL GENES BY IONIZING-RADIATION SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID PROTEIN-KINASE-C; FISSION YEAST; SACCHAROMYCES-CEREVISIAE; JUN PROTOONCOGENE; BINDING-ACTIVITY; GROWTH-FACTORS; DNA DAMAGE; RAD9 GENE; EXPRESSION; CDC2 AB The cellular responses to ionizing radiation include growth arrest, DNA repair, and lethality. However, little is known about the signaling events responsible for these responses. The present studies have examined the effects of ionizing radiation on the expression of genes involved in cell cycle control. The results demonstrate that the treatment of asynchronous cells with 20 Gy ionizing radiation is associated with transient down-regulation of the cdc2, cyclin A, cyclin B, and cdc25 genes. This effect was associated with transient induction of the c-jun gene. RNA stability studies demonstrate that the down-regulation of gene expression following ionizing radiation exposure is at least in part due to a decrease in transcript half-life. Other studies were performed with elutriated cells enriched for populations in G1 and S phases. Treatment of G1 enriched cell populations with 10 Gy resulted in a selective decrease in cyclin B mRNA levels, whereas this effect on cyclin B expression was less pronounced at 5 Gy and undetectable at 1 Gy. Similar results were obtained with S phase enriched cells. Taken together with clonogenic survival studies, these findings indicate that down-regulation of cell cycle control gene expression is associated with lethality, whereas lower doses of ionizing radiation have little, if any, effect on the expression of these genes. The findings also suggest that DNA damage may activate signaling events which regulate expression of cell cycle control genes. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,CLIN PHARMACOL LAB,44 BINNEY ST,BOSTON,MA 02115. UNIV CHICAGO,DEPT RADIAT & CELLULAR ONCOL,CHICAGO,IL 60637. PRITZKER SCH MED,CHICAGO,IL 60637. RI Hass, Ralf/F-3197-2012 OI Hass, Ralf/0000-0002-2481-7547 FU NCI NIH HHS [CA55241, CA41068] NR 45 TC 58 Z9 59 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 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD SEP PY 1992 VL 3 IS 9 BP 637 EP 644 PG 8 WC Cell Biology SC Cell Biology GA JM592 UT WOS:A1992JM59200008 PM 1419913 ER PT J AU WANG, YS SMITH, JA KAMRADT, T GEFTER, ML PERKINS, DL AF WANG, YS SMITH, JA KAMRADT, T GEFTER, ML PERKINS, DL TI SILENCING OF IMMUNODOMINANT EPITOPES BY CONTIGUOUS SEQUENCES IN COMPLEX SYNTHETIC PEPTIDES SO CELLULAR IMMUNOLOGY LA English DT Article ID T-CELL HYBRIDOMAS; A-BETA; ANTIGEN; RECOGNITION; DETERMINANTS; MOLECULES; SPECIFICITIES; PROLIFERATION; POLYMORPHISM; COMPETITION C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,IMMUNOGENET & TRANSPLANTAT LAB,75 FRANCIS ST,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02114. TUFTS UNIV,SCH MED,DIV RHEUMATOL & IMMUNOL,MEDFORD,MA 02155. MIT,DEPT PLANT BIOL,CAMBRIDGE,MA 02139. FU NIAID NIH HHS [R29 AI31527] NR 30 TC 17 Z9 17 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD SEP PY 1992 VL 143 IS 2 BP 284 EP 297 DI 10.1016/0008-8749(92)90026-L PG 14 WC Cell Biology; Immunology SC Cell Biology; Immunology GA JL406 UT WOS:A1992JL40600004 PM 1380894 ER PT J AU PRICE, BD AF PRICE, BD TI SIGNALING ACROSS THE ENDOPLASMIC-RETICULUM MEMBRANE - POTENTIAL MECHANISMS SO CELLULAR SIGNALLING LA English DT Review DE ENDOPLASMIC RETICULUM; GRPS; SIGNALING; PHOSPHORYLATION; G-PROTEINS; PROTEIN TRANSPORT; PROTEIN KINASES ID GLUCOSE-REGULATED PROTEIN; IMMUNOGLOBULIN HEAVY-CHAIN; BINDING-PROTEIN; GTP; IDENTIFICATION; EXPRESSION; IDENTITY; CALCIUM; STRESS; KINASE AB The endoplasmic reticulum (ER) is a membrane-bound organelle responsible for the synthesis, assembly and post-translational modification of proteins destined for the lysosomes, Golgi and for secretion. The processes which occur in the lumen of the ER are vital to the correct functioning of the cell, and mechanisms must exist to enable the cell to monitor events within the lumen of the ER. How the cell is able to do this is not known, but it would apparently require the passage of signals from the lumen of the ER to the cytosol, from where signals can be sent to, for example, the nucleus to effect changes in transcription. Here, it is suggested that the membrane of the ER may contain the components (i.e. receptors, kinases, etc.) required for transmembrane signalling in much the same way as the plasma membrane does. This hypothesis will be discussed in relation to known ER proteins which might act as signalling proteins. RP PRICE, BD (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,STRESS PROTEIN GRP JF 205,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [R29 CA44940]; PHS HHS [R01 47407] NR 35 TC 7 Z9 8 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0898-6568 J9 CELL SIGNAL JI Cell. Signal. PD SEP PY 1992 VL 4 IS 5 BP 465 EP 470 DI 10.1016/0898-6568(92)90015-Z PG 6 WC Cell Biology SC Cell Biology GA JR488 UT WOS:A1992JR48800001 PM 1419486 ER PT J AU MINOTTI, JR PILLAY, P CHANG, L WELLS, L MASSIE, BM AF MINOTTI, JR PILLAY, P CHANG, L WELLS, L MASSIE, BM TI NEUROPHYSIOLOGICAL ASSESSMENT OF SKELETAL-MUSCLE FATIGUE IN PATIENTS WITH CONGESTIVE-HEART-FAILURE SO CIRCULATION LA English DT Article DE MUSCLE ACTIVATION; FATIGUE, CENTRAL; TRANSMISSION, NEUROMUSCULAR; FATIGUE, MUSCLE ID BLOOD-FLOW; EXERCISE; ABNORMALITIES; DYSFUNCTION; METABOLISM; CAPACITY AB Background. Recent research has demonstrated that patients with congestive heart failure (CHF) exhibit significant functional impairment of skeletal muscle and that these changes may be important determinants of exercise capacity. Although muscle strength may be mildly reduced, the most significant abnormality is markedly enhanced muscle fatigue. The goal of the present study is to determine whether accelerated fatigue is caused by impaired muscle activation, as a result of inadequate central motor drive or neuromuscular transmission, or by a change in the muscle itself. Methods and Results. The study population consisted of nine patients with New York Heart Association class I-III CHF and eight sedentary, age- and sex-matched control subjects. Maximal voluntary contraction force of the foot dorsiflexors (primarily the tibialis anterior) was quantified as a measure of muscle strength, isometric endurance was quantified by the time required for force to decline to 60% of maximal during a sustained maximal contraction, and dynamic endurance was defined as the number of maximal contractions required for force to decline to 60% of maximal under a protocol of six repetitions per minute with an incremental duty cycle. The degree of central motor drive failure was quantified by the degree of force augmentation produced by a superimposed tetanic stimulus delivered to the peroneal nerve during the initial maximal voluntary contraction and at the time when force during the sustained isometric contraction declined to 60% of maximal. Neuromuscular junction transmission was examined by quantifying the amplitude of the compound muscle action potential (M wave) in response to a single nerve stimulus during fatiguing exercise. Muscle strength was relatively preserved in the CHF patients versus the control subjects (93+/-41 versus 105+/-34 lb; p=NS), but isometric endurance (time to decline to 60%, 34+/-15 versus 54+/-19 seconds;p<0.02) and dynamic endurance (number of repetitions before decline to 60%, 30+/-6 versus 43+/-7 contractions; p<0.001) were both impaired. Tetanic nerve stimulation increased force by similar degrees in the two groups, and the amplitude of the M wave did not decline in either group during exercise. Conclusions. These findings indicate that enhanced muscle fatigue in patients with CHF is not caused by impaired central motor drive or an abnormality of neuromuscular junction transmission but rather by an abnormality in the muscle itself. C1 UNIV CALIF SAN FRANCISCO,DEPT MED,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,CARDIOVASC RES INST,SAN FRANCISCO,CA 94143. SAN FRANCISCO VET AFFAIRS MED CTR,DEPT PHYS THERAPY,SAN FRANCISCO,CA 94121. RP MINOTTI, JR (reprint author), SAN FRANCISCO VET AFFAIRS MED CTR,CARDIOL SECT 111C,450 CLEMENT ST,SAN FRANCISCO,CA 94121, USA. FU NHLBI NIH HHS [K 08-HL-02446]; PHS HHS [25847] NR 28 TC 77 Z9 78 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP PY 1992 VL 86 IS 3 BP 903 EP 908 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JM270 UT WOS:A1992JM27000023 PM 1516203 ER PT J AU PUOPOLO, PR CHAMBERLIN, P FLOOD, JG AF PUOPOLO, PR CHAMBERLIN, P FLOOD, JG TI DETECTION AND CONFIRMATION OF COCAINE AND COCAETHYLENE IN SERUM EMERGENCY TOXICOLOGY SPECIMENS SO CLINICAL CHEMISTRY LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; PLASMA AB We report the performance of a liquid chromatography (LC) assay for detection and confirmation of cocaine and cocaethylene in serum. A photodiode array (PDA) detector monitors the cyano column effluent at 230 nm for analyte detection. Confirmation of a peak's identity is performed by use of only the 226-254-nm segment of the spectra rather than a broader range such as 210-340 nm. Use of the narrower range improves the assay's sensitivity by almost 10-fold. Analyte values of 10-mu-g/L are confirmed routinely. Intra-assay imprecision at 100, 20, and 10-mu-g/L for cocaine is 5.1%, 5.7%, and 6.6% (CV), respectively. Absolute recovery of the analytes exceeds 80%. In a split-sample study (33 positives and 74 negatives), each of this method's cocaine findings were confirmed. Cocaethylene was found in 15 of these samples. A complete chromatogram can be available 15 min after the start of the procedure. The method's focus on the active drug (rather than urinary metabolites) and its ability to detect and confirm many other drugs make it well suited for emergency toxicology testing. C1 MASSACHUSETTS GEN HOSP,CHEM LAB,GRAY 5,BOSTON,MA 02114. NR 15 TC 15 Z9 15 U1 0 U2 3 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 SEP PY 1992 VL 38 IS 9 BP 1838 EP 1842 PG 5 WC Medical Laboratory Technology SC Medical Laboratory Technology GA JN322 UT WOS:A1992JN32200043 PM 1526022 ER PT J AU OSCHERWITZ, SL RINALDI, MG AF OSCHERWITZ, SL RINALDI, MG TI DISSEMINATED SPOROTRICHOSIS IN A PATIENT INFECTED WITH HUMAN-IMMUNODEFICIENCY-VIRUS SO CLINICAL INFECTIOUS DISEASES LA English DT Letter ID KETOCONAZOLE C1 AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX. NR 10 TC 21 Z9 22 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD SEP PY 1992 VL 15 IS 3 BP 568 EP 569 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA JK474 UT WOS:A1992JK47400046 PM 1520820 ER PT J AU BURGESON, RE NIMNI, ME AF BURGESON, RE NIMNI, ME TI COLLAGEN TYPES - MOLECULAR-STRUCTURE AND TISSUE DISTRIBUTION SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID II ACHONDROGENESIS-HYPOCHONDROGENESIS; XII COLLAGEN; VIII COLLAGEN; X COLLAGEN; ALPORT SYNDROME; CARTILAGE; IDENTIFICATION; CLONING; TENDONS; DOMAINS AB The collagens are products of a superfamily of closely related genes. Currently, there are 13 described collagens encompassing at least 25 separate genes. The collagen molecules can be categorized into four classes. Class I consists of molecules that form the banded collagen fibers that are readily seen by routine electron microscopy. The banded fibers are heterogenous with respect to collagen type, containing at least two and often three collagen types in each fibril. This multiplicity is believed to effect the rate of fibril growth and the final fibril diameter. Class II contains collagens that adhere to the surface of the banded fibrils. The function of these molecules is not yet known. The third Class consists of molecules that form independent fiber systems. These include the basement membrane, beaded filaments, anchoring fibrils, and the network surrounding hypertrophic chondrocytes. The last class contains several collagens with unknown fiber forms, and whose functions are unclear. Tissues contain multiple fiber forms and therefore many individual collagen types. Bone is no different, and there are presently four known collagens in the bone cortex. This article summarizes knowledge of the structures and functions of the collagen superfamily. C1 UNIV SO CALIF,SCH MED,DEPT MED,LOS ANGELES,CA 90033. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT DERMATOL,CUTANEOUS BIOL RES CTR,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ANAT & CELLULAR BIOL,BOSTON,MA 02114. UNIV SO CALIF,SCH MED,DEPT BIOCHEM,LOS ANGELES,CA 90033. ORTHOPED HOSP,LOS ANGELES,CA 90007. NR 40 TC 94 Z9 94 U1 3 U2 18 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD SEP PY 1992 IS 282 BP 250 EP 272 PG 23 WC Orthopedics; Surgery SC Orthopedics; Surgery GA JM402 UT WOS:A1992JM40200033 PM 1516320 ER PT J AU TAUBER, J JABBUR, N FOSTER, CS AF TAUBER, J JABBUR, N FOSTER, CS TI IMPROVED DETECTION OF DISEASE PROGRESSION IN OCULAR CICATRICIAL PEMPHIGOID SO CORNEA LA English DT Article DE CICATRICIAL PEMPHIGOID; STAGING AB Cicatricial pemphigoid is an autoimmune systemic disease characterized by chronic conjunctival cicatrization. The natural history is one of variable degrees of progressive scarring of the ocular surface and visual loss. Previous reports have shown systemic chemotherapy to be efficacious in halting cicatrization in progressive cases. This observation makes it of critical importance to be able to detect progression of the disease as early as possible so as to allow for earlier institution of treatment. Our experience in previous studies has led us to believe that disease staging systems currently in use are relatively insensitive in detecting disease progression. We present a revised staging system that combines the strengths of the staging systems in use today and extends their sensitivity. C1 MASSACHUSETTS EYE & EAR INFIRM,IMMUNOL SERV,243 CHARLES ST,BOSTON,MA 02114. NR 0 TC 54 Z9 56 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0277-3740 J9 CORNEA JI Cornea PD SEP PY 1992 VL 11 IS 5 BP 446 EP 451 DI 10.1097/00003226-199209000-00015 PG 6 WC Ophthalmology SC Ophthalmology GA JK374 UT WOS:A1992JK37400015 PM 1424674 ER PT J AU CONN, AKT AF CONN, AKT TI FINK,MITCHELL,P. SO CRITICAL CARE MEDICINE LA English DT Item About an Individual RP CONN, AKT (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD SEP PY 1992 VL 20 IS 9 BP 1206 EP 1206 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA JN869 UT WOS:A1992JN86900005 ER PT J AU FINI, ME YUE, BYJT SUGAR, J AF FINI, ME YUE, BYJT SUGAR, J TI COLLAGENOLYTIC GELATINOLYTIC METALLOPROTEINASES IN NORMAL AND KERATOCONUS CORNEAS SO CURRENT EYE RESEARCH LA English DT Article ID MATRIX METALLOPROTEINASES; V COLLAGEN; EXPRESSION; INHIBITOR; MEMBRANE; HETEROGENEITY; FAMILY; CELLS AB Cells of keratoconus corneas have been reported to produce higher levels of collagenolytic/gelatinolytic enzymatic activities than do cells of normal corneas. The current study investigates the contribution of 1) specific enzyme gene products, and 2) the degree to which these proteins are present in the activated forms, to the increased enzymatic activities. We demonstrate that two neutral gelatinolytic enzymes, a 66/59 kD form and a 92 kD form, can be directly extracted from both normal and keratoconus corneas. These enzymes are identified as the pro- and activated forms of MMP-2 and as the pro-form of MMP-9, specific members of the matrix metalloproteinase family. Normal and keratoconus corneas show no significant differences in amounts or types of extractable neutral gelatinases, nor in the amounts or types that they synthesize in culture. Furthermore, in both the normal and keratoconus corneas, gelatinases are found primarily in the inactive form. These studies suggest the possible importance of changes in proteinase inhibitor levels to the characteristic biochemical features of keratoconus corneas. C1 HARVARD UNIV,SCH MED,DEPT DERMATOL,BOSTON,MA 02115. UNIV ILLINOIS,COLL MED,DEPT OPHTHALMOL & VISUAL SCI,CHICAGO,IL 60680. RP FINI, ME (reprint author), MASSACHUSETTS GEN HOSP,HARVARD CUTANEOUS BIOL RES CTR,BLDG 149,3RD FLOOR,13TH ST,BOSTON,MA 02129, USA. FU NEI NIH HHS [EY08408, EY03890] NR 35 TC 78 Z9 78 U1 0 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0271-3683 J9 CURR EYE RES JI Curr. Eye Res. PD SEP PY 1992 VL 11 IS 9 BP 849 EP 862 DI 10.3109/02713689209033483 PG 14 WC Ophthalmology SC Ophthalmology GA JU196 UT WOS:A1992JU19600004 PM 1424728 ER PT J AU GODDARD, DH GROSSMAN, SL NEWTON, R CLARK, MA BOMALASKI, JS AF GODDARD, DH GROSSMAN, SL NEWTON, R CLARK, MA BOMALASKI, JS TI REGULATION OF SYNOVIAL CELL-GROWTH - BASIC FIBROBLAST GROWTH-FACTOR SYNERGIZES WITH INTERLEUKIN 1-BETA STIMULATING PHOSPHOLIPASE-A2 ENZYME-ACTIVITY, PHOSPHOLIPASE-A2 ACTIVATING PROTEIN-PRODUCTION AND RELEASE OF PROSTAGLANDIN-E2 BY RHEUMATOID-ARTHRITIS SYNOVIAL-CELLS IN CULTURE SO CYTOKINE LA English DT Article DE CYTOKINES; EICOSANOIDS; ARACHIDONIC ACID; CYCLOOXYGENASE; PLATELET-DERIVED GROWTH FACTOR ID TUMOR NECROSIS FACTOR; SUBENDOTHELIAL EXTRACELLULAR-MATRIX; SWISS 3T3 CELLS; ARACHIDONIC-ACID; FACTOR-BETA; PHOSPHOLIPASE-A2-ACTIVATING PROTEIN; ENDOTHELIAL-CELLS; RECEPTOR EXPRESSION; HEPARAN-SULFATE; MODULATION C1 DUPONT MERCK PHARMACEUT CO,DEPT MED PROD,GLENDOLDEN,PA. SCHERING PLOUGH CORP,BLOOMFIELD,NJ 07003. MED COLL PENN,VET AFFAIRS MED CTR,PHILADELPHIA,PA 19129. UNIV PENN,PHILADELPHIA,PA 19104. RP GODDARD, DH (reprint author), WINTHROP UNIV HOSP,DEPT MED,DIV RHEUMATOL IMMUNOL ALLERGY,222 STN PLAZA N,SUITE 430,MINEOLA,NY 11501, USA. FU NIAMS NIH HHS [AR 39382] NR 48 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 1043-4666 J9 CYTOKINE JI Cytokine PD SEP PY 1992 VL 4 IS 5 BP 377 EP 384 DI 10.1016/1043-4666(92)90081-2 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA JR616 UT WOS:A1992JR61600007 PM 1420999 ER PT J AU STAINIER, DYR FISHMAN, MC AF STAINIER, DYR FISHMAN, MC TI PATTERNING THE ZEBRAFISH HEART TUBE - ACQUISITION OF ANTEROPOSTERIOR POLARITY SO DEVELOPMENTAL BIOLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; MYOSIN HEAVY-CHAINS; RETINOIC ACID; XENOPUS-LAEVIS; IMMUNOCHEMICAL ANALYSIS; CELL-DIFFERENTIATION; GROWTH-FACTORS; MOUSE EMBRYOS; EXPRESSION; MESODERM RP STAINIER, DYR (reprint author), MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,149 13TH ST,BOSTON,MA 02129, USA. NR 46 TC 142 Z9 144 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD SEP PY 1992 VL 153 IS 1 BP 91 EP 101 DI 10.1016/0012-1606(92)90094-W PG 11 WC Developmental Biology SC Developmental Biology GA JM416 UT WOS:A1992JM41600008 PM 1516755 ER PT J AU DESTREE, OHJ LAM, KT PETERSONMADURO, LJ EIZEMA, K DILLER, L GRYKA, MA FREBOURG, T SHIBUYA, E FRIEND, SH AF DESTREE, OHJ LAM, KT PETERSONMADURO, LJ EIZEMA, K DILLER, L GRYKA, MA FREBOURG, T SHIBUYA, E FRIEND, SH TI STRUCTURE AND EXPRESSION OF THE XENOPUS RETINOBLASTOMA GENE SO DEVELOPMENTAL BIOLOGY LA English DT Article ID CASEIN KINASE-II; SV40 T-ANTIGEN; C-MYC; SUSCEPTIBILITY GENE; NEURAL INDUCTION; ENCODED PROTEIN; CELL-CYCLE; PRODUCT; PHOSPHORYLATION; SEQUENCE C1 MASSACHUSETTS GEN HOSP,CTR CANC,BOSTON,MA 02129. HARVARD UNIV,SCH MED,DEPT ANAT,BOSTON,MA 02129. CHILDRENS HOSP,DEPT PEDIAT,BOSTON,MA 02129. DANA FARBER CANC INST,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02129. RP DESTREE, OHJ (reprint author), NETHERLANDS INST DEV BIOL,HUBRECHT LAB,UPPSALALAAN 8,3584 CT UTRECHT,NETHERLANDS. NR 54 TC 42 Z9 42 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD SEP PY 1992 VL 153 IS 1 BP 141 EP 149 DI 10.1016/0012-1606(92)90098-2 PG 9 WC Developmental Biology SC Developmental Biology GA JM416 UT WOS:A1992JM41600012 PM 1516743 ER PT J AU BONORA, E DELPRATO, S BONADONNA, RC GULLI, G SOLINI, A SHANK, ML GHIATAS, AA LANCASTER, JL KILCOYNE, RF ALYASSIN, AM DEFRONZO, RA AF BONORA, E DELPRATO, S BONADONNA, RC GULLI, G SOLINI, A SHANK, ML GHIATAS, AA LANCASTER, JL KILCOYNE, RF ALYASSIN, AM DEFRONZO, RA TI TOTAL-BODY FAT-CONTENT AND FAT TOPOGRAPHY ARE ASSOCIATED DIFFERENTLY WITH INVIVO GLUCOSE-METABOLISM IN NONOBESE AND OBESE NONDIABETIC WOMEN SO DIABETES LA English DT Article ID ADIPOSE-TISSUE DISTRIBUTION; INSULIN RESISTANCE; CARDIOVASCULAR-DISEASE; PLASMA-LIPIDS; ABDOMINAL FAT; RISK-FACTORS; COMPUTED-TOMOGRAPHY; TOLERANCE; MEN; HYPERINSULINEMIA AB In this study, total body fat content and fat topography were related to glucose metabolism in the basal and insulin-stimulated states in 18 nonobese and 18 obese premenopausal nondiabetic women. All subjects received a euglycemic insulin (20 mU . min-1 . m2) clamp study in combination with [3-H-3]-D-glucose infusion and indirect calorimetry to quantitate total body glucose uptake, glucose oxidation, and nonoxidative glucose disposal. Total body fat content was determined with tritiated water, whereas body fat distribution was estimated from the WHR, the STR, and the VSR (measured by magnetic resonance imaging). In the postabsorptive state, total body glucose utilization, glucose oxidation, and nonoxidative glucose disposal rates were similar in nonobese and obese women, whereas during the insulin clamp all three metabolic parameters were reduced significantly in the obese group. In nonobese women, total body fat content was related inversely to both total and nonoxidative glucose disposal during the insulin clamp, whereas no relationship was found between glucose metabolism (total, oxidative, and nonoxidative) and WHR, STR, or VSR. In contrast, in obese women, no relationship was observed between total body fat content and any measure of insulin-mediated glucose metabolism. However, both WHR and VSR were related inversely to total, oxidative, and nonoxidative glucose disposal rates during the insulin clamp. These results suggest that total body fat content and body fat topography are associated differently with insulin-mediated glucose metabolism in nonobese and obese women. In the nonobese women, total body fat mass appears to be a primary determinant of tissue sensitivity to insulin, whereas in obese women, body fat topography exerts a more dominant effect. C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV DIABET,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. RI Lancaster, Jack/F-2994-2010; Del Prato, Stefano/K-3405-2016; Solini, Anna/K-4666-2016; OI Del Prato, Stefano/0000-0002-5388-0270; Solini, Anna/0000-0002-7855-8253; BONORA, Enzo/0000-0003-1074-5164 FU NCRR NIH HHS [M01-RR-01346]; NIDDK NIH HHS [DK-24092] NR 52 TC 147 Z9 147 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD SEP PY 1992 VL 41 IS 9 BP 1151 EP 1159 DI 10.2337/diabetes.41.9.1151 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JK179 UT WOS:A1992JK17900018 PM 1499866 ER PT J AU NEIL, GA SUMMERS, RW CHEYNE, BA CAPENTER, C HUANG, WL KANSAS, GS WALDSCHMIDT, TJ AF NEIL, GA SUMMERS, RW CHEYNE, BA CAPENTER, C HUANG, WL KANSAS, GS WALDSCHMIDT, TJ TI CD5+ B-CELLS ARE DECREASED IN PERIPHERAL-BLOOD OF PATIENTS WITH CROHNS-DISEASE SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE CD5 SURFACE MARKER; B-CELLS; CROHNS DISEASE ID FLOW CYTOMETRIC ANALYSIS; HUMAN-FETAL SPLEEN; ULCERATIVE-COLITIS; LYMPHOCYTES-B; IMMUNE SYSTEM; T9 ANTIGEN; EXPRESSION; SUBPOPULATIONS; SUBSETS AB B cells bearing the CD5 surface marker comprise a substantial minority of the circulating lymphocyte population in healthy individuals. These recently described cells have been implicated in T-independent humoral responses, immunoregulation, and autoimmunity. We undertook to enumerate circulating CD5+ B cells by three-color fluorescence activated flow cytometry in 28 patients with Crohn's disease (CD). None of the CD patients were using immunosuppressive medication. The CD patients were subdivided into "inactive" and "active" groups based upon their Crohn's disease activity index (CDAI). Thirty-two normal subjects served as a control population. The percentage of CD19+ B cells was significantly reduced in both active and inactive CD patients as compared with normal controls (P less-than-or-equal-to 0.01). CD5+ B cells were likewise found to be significantly decreased in both inactive and active CD patients (P less-than-or-equal-to 0.01) as compared with normal controls. The proportion of CD5+ B cells was significantly lower in the peripheral blood of active as compared with inactive CD patients (P less-than-or-equal-to 0.05). The finding that CD5+ B cells are reduced in CD may provide an important clue to immunological dysfunction in inflammatory bowel disease and merits further study. C1 UNIV IOWA HOSP & CLIN,DEPT INTERNAL MED,CLIFTON CTR DIGEST DIS,4612 JOHN COLLOTON PAVILL,IOWA CITY,IA 52242. UNIV IOWA,DEPT INTERNAL MED,IOWA CITY,IA 52242. UNIV IOWA,DEPT PATHOL,IOWA CITY,IA 52242. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV EXPTL MED & CANC RES,BOSTON,MA 02115. NR 29 TC 11 Z9 11 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD SEP PY 1992 VL 37 IS 9 BP 1390 EP 1395 DI 10.1007/BF01296009 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA JK862 UT WOS:A1992JK86200013 PM 1380423 ER PT J AU SCHMIDT, J LEWANDROWSKI, K CASTILLO, CF MANDAVILLI, U COMPTON, CC WARSHAW, AL RATTNER, DW AF SCHMIDT, J LEWANDROWSKI, K CASTILLO, CF MANDAVILLI, U COMPTON, CC WARSHAW, AL RATTNER, DW TI HISTOPATHOLOGIC CORRELATES OF SERUM AMYLASE ACTIVITY IN ACUTE EXPERIMENTAL PANCREATITIS SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE ACUTE PANCREATITIS; EXPERIMENTAL PANCREATITIS; SERUM AMYLASE; HISTOPATHOLOGY; CORRELATION ID TESTS; RAT; DIAGNOSIS; ETIOLOGY; ASSAYS; LIPASE; PLASMA; FLUID; CELLS AB The association of serum amylase activity with the extent of pancreatic injury in acute pancreatitis is unclear. To clarify this relationship, we induced acute pancreatitis ranging from mild to lethal in 118 Sprague-Dawley rats (350-450 g). This was achieved by controlled intraductal infusion of low- or high-dose bile salt, with or without enterokinase, followed by intravenous cerulein or saline for 6 hr. Serum amylase was measured at baseline and 6 hr. Pancreatic histopathology was evaluated by two blinded pathologists employing total surface scoring (N = 118) and morphometric 20-field documentation (N = 22). Serum amylase correlated best with edema (r = 0.61) and fat necrosis (r = 0.58), less well with acinar necrosis (r = 0.53) and inflammation (r = 0.50), and poorly with hemorrhage (r = 0.33) and perivascular infiltrate (r = 0.31). Inasmuch as edema and fat necrosis are not important determinants of severity, these observations could explain the poor prognostic value of serum amylase activity in patients with acute pancreatitis. C1 HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, DEPT SURG, BOSTON, MA 02114 USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, DEPT PATHOL, BOSTON, MA 02114 USA. NR 36 TC 49 Z9 61 U1 0 U2 1 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD SEP PY 1992 VL 37 IS 9 BP 1426 EP 1433 DI 10.1007/BF01296014 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA JK862 UT WOS:A1992JK86200018 PM 1380425 ER PT J AU BACKER, JM MYERS, MG SHOELSON, SE CHIN, DJ SUN, XJ MIRALPEIX, M HU, P MARGOLIS, B SKOLNIK, EY SCHLESSINGER, J WHITE, MF AF BACKER, JM MYERS, MG SHOELSON, SE CHIN, DJ SUN, XJ MIRALPEIX, M HU, P MARGOLIS, B SKOLNIK, EY SCHLESSINGER, J WHITE, MF TI PHOSPHATIDYLINOSITOL 3'-KINASE IS ACTIVATED BY ASSOCIATION WITH IRS-1 DURING INSULIN STIMULATION SO EMBO JOURNAL LA English DT Article DE INSULIN; IRS-1; PHOSPHATIDYLINOSITOL 3'-KINASE; SIGNAL TRANSDUCTION; TYROSINE PHOSPHORYLATION ID RECEPTOR TYROSINE KINASES; GROWTH-FACTOR RECEPTORS; PDGF RECEPTOR; BINDING-SITE; MIDDLE-T; SIGNAL TRANSDUCTION; INTACT-CELLS; PROTEIN; PHOSPHORYLATION; 3-KINASE AB IRS-1 undergoes rapid tyrosine phosphorylation during insulin stimulation and forms a stable complex containing the 85 kDa subunit (p85) of the phosphatidylinositol (PtdIns) 3'-kinase, but p85 is not tyrosyl phosphorylated. IRS-1 contains nine tyrosine phosphorylation sites in YXXM (Tyr-Xxx-Xxx-Met) motifs. Formation of the IRS-1 - PtdIns 3'-kinase complex in vitro is inhibited by synthetic peptides containing phosphorylated YXXM motifs, suggesting that the binding of PtdIns 3'-kinase to IRS-1 is mediated through the SH2 (src homology-2) domains of p85. Furthermore, overexpression of IRS-1 potentiates the activation of PtdIns 3-kinase in insulin-stimulated cells, and tyrosyl phosphorylated IRS-1 or peptides containing phosphorylated YXXM motifs activate PtdIns 3'-kinase in vitro. We conclude that the binding of tyrosyl phosphorylated IRS-1 to the SH2 domains of p85 is the critical step that activates PtdIns 3'-kinase during insulin stimulation. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. NYU,SCH MED,DEPT PHARMACOL,NEW YORK,NY 10016. RP BACKER, JM (reprint author), BRIGHAM & WOMENS HOSP,DEPT MED,JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02115, USA. OI Hu, Patrick/0000-0002-5611-8062 FU NIDDK NIH HHS [DK 36836, DK-38712, DK-43808] NR 49 TC 899 Z9 905 U1 1 U2 19 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD SEP PY 1992 VL 11 IS 9 BP 3469 EP 3479 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA JJ039 UT WOS:A1992JJ03900035 PM 1380456 ER PT J AU WEISS, J HARRIS, PE HALVORSON, LM CROWLEY, WF JAMESON, JL AF WEISS, J HARRIS, PE HALVORSON, LM CROWLEY, WF JAMESON, JL TI DYNAMIC REGULATION OF FOLLICLE-STIMULATING HORMONE-BETA MESSENGER-RIBONUCLEIC-ACID LEVELS BY ACTIVIN AND GONADOTROPIN-RELEASING-HORMONE IN PERIFUSED RAT PITUITARY-CELLS SO ENDOCRINOLOGY LA English DT Article ID LUTEINIZING-HORMONE; ENDOGENOUS INHIBIN; SECRETION; SUBUNIT; IMMUNONEUTRALIZATION; TRANSCRIPTION; CULTURES; INVITRO; ALPHA AB Maintenance of FSH biosynthesis require, ongoing exposure pulsatile GnRH. Recent data demonstrate that activin also stimulates FSH biosynthesis. We used a perifused pituitary system to examine regulation of FSH-beta-mRNA levels by pulsatile GnRH and activin. Hourly pulses of 10 nm GnRH increased FSH-beta-mRNA levels by 3-fold. In the same experiment, continuous infusion of 50 ng/ml activin elicited a 50-fold increase in FSH-beta-mRNA. This magnitude of response to activin in perifusion was unexpected, as only a 2.7-fold increase in FSH-beta-mRNA was observed when activin was administered to pituitary cells that were cultured in dishes. Since perifusion columns, unlike culture dishes, are exposed to a continuous supply of fresh medium, we examined the possibility that endogenous factors produced by pituitary cells cultured in dishes were stimulating the cells in a paracrine fashion, thereby precluding the full response to exogenously added activin. The kinetics of FSH-beta-mRNA expression were examined immediately after Pituitary dispersion and at different times after culturing the cells in plates. FSH-beta-mRNA levels fell rapidly after dispersion to 8% of initial levels and remained low over 8 h. Thereafter, FSH-beta-mRNA levels increased slowly and exceeded initial levels by the second day of culture. In a parallel set of experiments, when medium conditioned by exposure to plated cells was applied to the perifusion system, FSH-beta-mRNA levels were selectively stimulated (6-fold). These data suggest the removal during dispersion and subsequent accumulation in culture of pituitary-derived factors that are important for the maintenance of FSH-beta-mRNA levels. We conclude that activin plays a greater role in the regulation of FSH-beta-mRNA levels than was suggested by previous experiments employing static culture systems in which autocrine or paracrine stimulation may have obscured the effects of exogenously added activin. C1 MASSACHUSETTS GEN HOSP,DEPT MED,THYROID UNIT,BOSTON,MA 02114. RP WEISS, J (reprint author), MASSACHUSETTS GEN HOSP,DEPT MED,REPROD ENDOCRINE UNIT,BHX-5,BOSTON,MA 02114, USA. OI Jameson, James/0000-0001-9538-4059 FU NICHD NIH HHS [HD-29164, P30 HD028138, U54 HD028138, HD-28138, R01 HD015788] NR 16 TC 66 Z9 67 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD SEP PY 1992 VL 131 IS 3 BP 1403 EP 1408 DI 10.1210/en.131.3.1403 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JK945 UT WOS:A1992JK94500054 PM 1505470 ER PT J AU TSUJI, M SHIMA, H YONEMURA, CY BRODY, J DONAHOE, PK CUNHA, GR AF TSUJI, M SHIMA, H YONEMURA, CY BRODY, J DONAHOE, PK CUNHA, GR TI EFFECT OF HUMAN RECOMBINANT MULLERIAN INHIBITING SUBSTANCE ON ISOLATED EPITHELIAL AND MESENCHYMAL CELLS DURING MULLERIAN DUCT REGRESSION IN THE RAT SO ENDOCRINOLOGY LA English DT Article ID BASEMENT-MEMBRANE PROTEOGLYCAN; PARAMESONEPHRIC DUCTS; CHANGING PATTERNS; GRANULOSA-CELLS; ORGAN-CULTURE; IV COLLAGEN; ADULT-RAT; GROWTH; FETAL; FIBRONECTIN AB The effect of human recombinant Mullerian Inhibiting Substance (MIS) on the regression of the Mullerian duct (MD) of female rat fetuses was examined in vitro to determine whether MIS acts on MD epithelium and/or mesenchyme at the critical periods of sexual differentiation. Urogenital ridges (URs) of female rat fetuses at 14.5- to 18.5-days of gestation (plug day = 0) were cultured for 3 days with or without recombinant human MIS in CMRL 1066 medium with 10% female fetal calf serum. In URs from 14.5- and 15.5-day-old fetuses, the cranial portion of the MD regressed almost completely during the 3-day culture period in the presence of MIS, whereas the caudal half to third of the MD remained intact but tapered to a fine point cranially. MDs survived in URs from 16.5-day-old fetuses cultured in the presence of MIS except that the cranial portion of the MDs was deformed. MIS did not elicit regression of MDs in URs obtained from 17.5- and 18.5-day-old fetuses, but instead caused the MD epithelium to form bulges projecting into the mesenchyme. MD epithelium at 15.5-days of gestation was separated from the surrounding UR mesenchyme, and both components (MD epithelium and mesenchyme) were cultured separately for 3 days in the presence or absence of MIS. Both epithelial and mesenchymal cells survived in the presence or absence of MIS. MD epithelium formed typical epithelial colonies, whereas UR mesenchyme spread as fibroblastic cells. Analysis of labeling index after incorporation of [H-3] thymidine demonstrated that MD epithelial DNA synthesis was not influenced by MIS. In contrast, mesenchymal labeling index was reduced significantly by MIS. This effect of MIS on UR mesenchyme in conjunction with earlier histological observations of mesenchymal condensation during MD regression and an absence of direct effects of MIS on the epithelium suggests that MIS elicits its effect on the MD epithelium via the surrounding mesenchyme. C1 UNIV CALIF SAN FRANCISCO, DEPT ANAT, SAN FRANCISCO, CA 94143 USA. UNIV CALIF SAN FRANCISCO, CTR REPROD ENDOCRINOL, SAN FRANCISCO, CA 94143 USA. MASSACHUSETTS GEN HOSP, DEPT SURG, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02115 USA. FU NCI NIH HHS [CA-05388]; NICHD NIH HHS [HD-21919, HD-17491] NR 56 TC 45 Z9 47 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD SEP PY 1992 VL 131 IS 3 BP 1481 EP 1488 DI 10.1210/en.131.3.1481 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JK945 UT WOS:A1992JK94500066 PM 1505479 ER PT J AU XANTHOPOULOS, KG CANNON, PD ROBINSON, GS MIRKOVITCH, J DARNELL, JE AF XANTHOPOULOS, KG CANNON, PD ROBINSON, GS MIRKOVITCH, J DARNELL, JE TI TRANSIENTLY AND STABLY INTRODUCED CCAAT ENHANCER-BINDING-PROTEIN GENES ARE CONSTITUTIVELY EXPRESSED IN CULTURED-CELLS SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article ID TRANSCRIPTION FACTOR; REGULATED EXPRESSION; C/EBP FAMILY; LIVER; ALPHA-1-ANTITRYPSIN; TRANSTHYRETIN; PROMOTER; MEMBER; SITES; DIFFERENTIATION AB CCAAT/enhancer-binding protein (C/EBP) is expressed in certain cell types including hepatocytes and adipocytes. In order to understand the mechanisms that control the expression of the mouse C/EBP gene in the liver as well as in adipocytes, we have studied both the endogenous gene and transfected C/EBP gene constructs. The initiation site of transcription was identified and a strong liver-specific DNase-I hypersensitive site located at -3 kb, which does not appear to contribute functionally to the regulation of the gene in a variety of either transiently or stably transfected cells with constructs which include sequences up to 6-kb upstream of the transcription start. C/EBP gene expression during the transition from preadipocytes to adipocytes was shown to be controlled at the level of transcription. However, adipocytes stably transfected with constructs that include -3.3 kb upstream of the C/EBP gene do not express the reporter genes in a differentiation-specific manner. We detected several DNA-binding proteins that interact with the upstream sites of the C/EBP gene. Those include two labile and two heat-stable site-specific DNA-binding proteins that are present in nuclear extracts from several tissues and cultured cell lines. C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. SYNTEX INC,PALO ALTO,CA 94304. HARVARD UNIV,SCH MED,DANA FABER CANC INST,BOSTON,MA 02115. ROCKEFELLER UNIV,NEW YORK,NY 10021. RP XANTHOPOULOS, KG (reprint author), KAROLINSKA INST,CTR BIOTECHNOL,S-14157 HUDDINGE,SWEDEN. FU NCI NIH HHS [CA 16007, CA 16006, CA 16008] NR 28 TC 9 Z9 9 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD SEP 1 PY 1992 VL 208 IS 2 BP 501 EP 509 DI 10.1111/j.1432-1033.1992.tb17214.x PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JM097 UT WOS:A1992JM09700039 PM 1325913 ER PT J AU CARRERA, AC BAKER, C ROBERTS, TM PARDOLL, DM AF CARRERA, AC BAKER, C ROBERTS, TM PARDOLL, DM TI TYROSINE KINASE TRIGGERING IN THYMOCYTES UNDERGOING POSITIVE SELECTION SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article ID CELL ANTIGEN RECEPTOR; T-CELL; TRANSGENIC MICE; SIGNAL TRANSDUCTION; PROTEIN-KINASE; LYMPHOCYTES-T; PHOSPHORYLATION; ACTIVATION; EXPRESSION; THYMUS AB Developing T cells undergo distinct selection processes that determine the T cell receptor (TcR) repertoire. One of these processes is positive selection. Positive selection involves the differentiation to mature T cells of thymocytes bearing TcR capable of recognizing antigens in the context of self-major histocompatibility complex (MHC) molecules. To study the potential involvement of tyrosine phosphorylation in the mechanism of positive selection, we have analyzed the activities of the tyrosine kinases pp56lck and pp59fyn in thymocytes expressing a unique TcR specific for HY antigen+ H-2 D(b). Thymocytes undergoing positive selection displayed higher kinase specific activities of pp56lck and pp59fyn than nonselecting thymocytes. Furthermore, these increases in kinase activities were found only in the CD4+CD8+ subpopulation of thymocytes, where the selection process is believed to occur. These data suggest that tyrosine phosphorylation is part of the intracellular signals involved in MHC class 1-driven positive selection from CD4+CD8+ immature thymocytes to CD4-CD8+ mature cells. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT ONCOL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT MOLEC BIOL & GENET,BALTIMORE,MD 21205. RP CARRERA, AC (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELLULAR & MOLEC BIOL,44 BINNEY ST,BOSTON,MA 02115, USA. OI Carrera, Ana/0000-0002-3999-5434 FU NCI NIH HHS [CA43803] NR 35 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 SEP PY 1992 VL 22 IS 9 BP 2289 EP 2294 DI 10.1002/eji.1830220917 PG 6 WC Immunology SC Immunology GA JN490 UT WOS:A1992JN49000016 PM 1516620 ER PT J AU ROBBINS, J HAMILTON, JW LOF, GL KEMPSTER, GB AF ROBBINS, J HAMILTON, JW LOF, GL KEMPSTER, GB TI OROPHARYNGEAL SWALLOWING IN NORMAL ADULTS OF DIFFERENT AGES SO GASTROENTEROLOGY LA English DT Article ID SPHINCTER PRESSURE; DE-GLUTITION; DISORDERS C1 UNIV WISCONSIN,DEPT NEUROL,MADISON,WI 53706. UNIV WISCONSIN,DEPT MED,MADISON,WI 53706. UNIV WISCONSIN,DEPT COMMUN DISORDERS,MADISON,WI 53706. WILLIAM S MIDDLETON MEM VET ADM MED CTR,NEUROL RES LABS,MADISON,WI 53705. GOVERNOR STATE UNIV,DIV COMMUN DISORDERS,UNIV PK,IL. FU NINDS NIH HHS [NS24427] NR 32 TC 311 Z9 324 U1 0 U2 5 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 SEP PY 1992 VL 103 IS 3 BP 823 EP 829 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA JK851 UT WOS:A1992JK85100012 PM 1499933 ER PT J AU KOIZUMI, M KING, N LOBB, R BENJAMIN, C PODOLSKY, DK AF KOIZUMI, M KING, N LOBB, R BENJAMIN, C PODOLSKY, DK TI EXPRESSION OF VASCULAR ADHESION MOLECULES IN INFLAMMATORY BOWEL-DISEASE SO GASTROENTEROLOGY LA English DT Article ID CELL-ADHESION; FUNCTIONAL-CHARACTERIZATION; SOLUBLE FORM; T-CELLS; SPONTANEOUS COLITIS; ENDOTHELIAL-CELLS; INTEGRIN VLA-4; SIALYL-LEX; ELAM-1; RECOGNITION C1 MASSACHUSETTS EYE & EAR INFIRM,NERPRC,CTR STUDY INFLAMMATORY BOWEL DIS,GASTROINTESTINAL UNIT,BOSTON,MA 02114. NEW ENGLAND REG PRIMATE RES CTR,SOUTHBOROUGH,MA 01772. BIOGEN INC,CAMBRIDGE,MA. FU NIDDK NIH HHS [DK34422, P30DK43351] NR 23 TC 183 Z9 186 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 SEP PY 1992 VL 103 IS 3 BP 840 EP 847 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA JK851 UT WOS:A1992JK85100014 PM 1379955 ER PT J AU SCHMIDT, J FERNANDEZDELCASTILLO, C RATTNER, DW LEWANDROWSKI, K COMPTON, CC WARSHAW, AL AF SCHMIDT, J FERNANDEZDELCASTILLO, C RATTNER, DW LEWANDROWSKI, K COMPTON, CC WARSHAW, AL TI TRYPSINOGEN-ACTIVATION PEPTIDES IN EXPERIMENTAL RAT PANCREATITIS - PROGNOSTIC IMPLICATIONS AND HISTOPATHOLOGIC CORRELATES SO GASTROENTEROLOGY LA English DT Article ID PROTEASE INHIBITORS; SERUM; SEVERITY; PLASMA; RADIOIMMUNOASSAY; ELASTASE-1; PREDICTION; COMPLEXES; ENZYMES C1 HARVARD UNIV, MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,WACC 336, BOSTON, MA 02114 USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, DEPT PATHOL, BOSTON, MA 02114 USA. NR 41 TC 102 Z9 105 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD SEP PY 1992 VL 103 IS 3 BP 1009 EP 1016 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA JK851 UT WOS:A1992JK85100035 PM 1499902 ER PT J AU HANSEN, TE BROWN, WL WEIGEL, RM CASEY, DE AF HANSEN, TE BROWN, WL WEIGEL, RM CASEY, DE TI UNDERRECOGNITION OF TARDIVE-DYSKINESIA AND DRUG-INDUCED PARKINSONISM BY PSYCHIATRIC-RESIDENTS SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article ID INDUCED MOVEMENT-DISORDERS AB Recognition of tardive dyskinesia (TD) and other neuroleptic drug-induced, extrapyramidal side effects presents a major challenge in modern clinical psychopharmacology. Failure to recognize these disorders can lead to poor patient care and may contribute to societal pressure for external control of psychiatric practice. This study reports the occurrence of tardive dyskinesia and drug-induced parkinsonism (DIP) in 101 in-patients, and documents underrecognition of both disorders by resident physicians. Researchers noted TD in 28% of cases and residents only described TD (or symptoms of TD) in 12%. The researcher determined DIP prevalence rate of 26% contrasted with an 11% rate found by residents. Patients with psychotic disorders were more likely than other patients to have researcher-identified TD, whereas DIP (researcher cases) occurred more often in patients with affective diagnoses. Residents tended to miss milder cases of TD, and to miss DIP in younger patients and in patients with affective disorders. Improved teaching and clinical exams are recommended to improve recognition. RP HANSEN, TE (reprint author), OREGON HLTH SCI UNIV,PORTLAND VET AFFAIRS MED CTR,116A-P POB 1034,PORTLAND,OR 97207, USA. FU NIMH NIH HHS [MH36657] NR 19 TC 27 Z9 28 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0163-8343 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD SEP PY 1992 VL 14 IS 5 BP 340 EP 344 DI 10.1016/0163-8343(92)90069-M PG 5 WC Psychiatry SC Psychiatry GA JK455 UT WOS:A1992JK45500008 PM 1355749 ER PT J AU HOVIG, E SMITHSORENSEN, B GEBHARDT, MC RYBERG, D LOTHE, R BORRESEN, AL AF HOVIG, E SMITHSORENSEN, B GEBHARDT, MC RYBERG, D LOTHE, R BORRESEN, AL TI NO ALTERATIONS IN EXON 21 OF THE RBI GENE IN SARCOMAS AND CARCINOMAS OF THE BREAST, COLON, AND LUNG SO GENES CHROMOSOMES & CANCER LA English DT Article ID HUMAN RETINOBLASTOMA GENE; DENATURANT GEL-ELECTROPHORESIS; HUMAN PROSTATE CARCINOMA; TUMOR-SUPPRESSOR GENE; TRANSCRIPTION FACTOR; SUSCEPTIBILITY GENE; DNA-SEQUENCE; CELL-CYCLE; PRODUCT; PROTEIN AB Studies of mutant genotypes of the retinoblastoma susceptibility gene (RB1) in different solid tumors have mainly been concentrated on the demonstration of loss of heterozygosity (LOH) at both internal and external polymorphic sites. One reason for this is the complex organization of the gene. The p105RB protein has been shown to interact with both DNA and regulatory cellular proteins and oncoproteins. The amino acids encoded by exon 21 are implicated in several of these interactions. Both point mutations and intragenic deletions involving exon 21 have previously been reported in human tumors. We have examined RB1 exon 21 from a number of human tumor types where significant LOH in or around the RB1 gene has been reported. DNA from 78 primary tumors was amplified using the polymerase chain reaction (PCR) with primers covering exon 21, followed by constant denaturant gel electrophoresis (CDGE). The 78 tumors included 11 breast carcinomas, 30 nonsmall cell lung carcinomas, 6 colon carcinomas, and 31 sarcomas. The small cell lung cancer cell line NCl-H209, previously shown to harbour a point mutation in codon 706: TGT- > TTT (Cys- > Phe), was detected using CDGE. Apart from this control mutant cell line, we did not detect any mutations in the examined region in any of the tumors. C1 MASSACHUSETTS GEN HOSP,CTR CANC,BOSTON,MA. MASSACHUSETTS GEN HOSP,ORTHOPAED ONCOL SERV,BOSTON,MA. NATL INST OCCUPAT HLTH,DEPT TOXICOL,OSLO,NORWAY. RP HOVIG, E (reprint author), NORWEGIAN RADIUM HOSP,INST CANC RES,DEPT GENET,N-0310 OSLO 3,NORWAY. RI Hovig, Eivind/H-2474-2011 OI Hovig, Eivind/0000-0002-9103-1077 NR 51 TC 11 Z9 11 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 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD SEP PY 1992 VL 5 IS 2 BP 97 EP 103 DI 10.1002/gcc.2870050202 PG 7 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA JM782 UT WOS:A1992JM78200001 PM 1381957 ER PT J AU OLIVIERO, S ROBINSON, GS STRUHL, K SPIEGELMAN, BM AF OLIVIERO, S ROBINSON, GS STRUHL, K SPIEGELMAN, BM TI YEAST GCN4 AS A PROBE FOR ONCOGENESIS BY AP-1 TRANSCRIPTION FACTORS - TRANSCRIPTIONAL ACTIVATION THROUGH AP-1 SITES IS NOT SUFFICIENT FOR CELLULAR-TRANSFORMATION SO GENES & DEVELOPMENT LA English DT Article DE YEAST GCN4; JUN; FOS; AP-1 TRANSCRIPTION FACTORS; ONCOGENESIS; CELLULAR TRANSFORMATION ID DNA-BINDING PROTEIN; RAT EMBRYO CELLS; C-JUN ACTIVITY; LEUCINE ZIPPER; FOS PROTEIN; ADIPOCYTE DIFFERENTIATION; DIMERIZATION SPECIFICITY; GLUCOCORTICOID RECEPTOR; GENE-EXPRESSION; MESSENGER-RNAS AB The Jun and Fos oncoproteins belong to the AP-1 family of transcriptional activators and are believed to induce cellular transformation by inappropriately activating genes involved in cell replication. To determine whether transcriptional activation through AP-1 sites is sufficient for transforming activity, we examined the properties of an autonomous and heterologous AP-1 protein, yeast GCN4, in rat embryo fibroblasts. GCN4 induces transcriptional activation through AP-1 sites but, unlike Jun and Fos, fails to induce cellular transformation, in cooperation with Ha-ras. Jun-GCN4 and Fos-GCN4 homodimers independently induce cellular transformation indicating that the amino-terminal regions of Jun and Fos each contain regulatory functions that are required for oncogenesis but are distinct from generic transcriptional activation domains. In addition, these observations have implications for the nature of the oncogenically relevant target genes that respond to Jun and Fos. C1 UNIV PADUA,DIPARTIMENTO BIOL,I-35121 PADUA,ITALY. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV NAVAL ARCHITECTURE,BOSTON,MA 02115. RP OLIVIERO, S (reprint author), HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115, USA. OI oliviero, salvatore/0000-0002-3405-765X FU NICHD NIH HHS [HD 24926]; NIGMS NIH HHS [GM30186, GM46555] NR 65 TC 59 Z9 59 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0890-9369 J9 GENE DEV JI Genes Dev. PD SEP PY 1992 VL 6 IS 9 BP 1799 EP 1809 DI 10.1101/gad.6.9.1799 PG 11 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA JM569 UT WOS:A1992JM56900017 PM 1516834 ER PT J AU DEAR, KBG SALAZAR, M WATSON, ALM GELMAN, RS BRONSON, R YUNIS, EJ AF DEAR, KBG SALAZAR, M WATSON, ALM GELMAN, RS BRONSON, R YUNIS, EJ TI TRAITS THAT INFLUENCE LONGEVITY IN MICE - A 2ND LOOK SO GENETICS LA English DT Article ID HISTOCOMPATIBILITY COMPLEX; LIFE-SPAN AB Analysis of genetic interactions in the F2 of an intercross of (C57BL/6 X DBA/2) F1J revealed influences of genetic factors on life span. Females lived longer than males. Dilute brown females died sooner than females of other colors. H-2b/H-2b males died sooner than H-2b/H-2d or H-2d/H-2d males, except that among dilute brown males those of typeH-2b/H-2d died sooner. Cluster analysis suggested that male and female genotypes each fall into two groups, with female dilute brown mice having shorter lives than other females, and male H-2b/H-2b mice except dilute brown and dilute brown H-2b/H-2d mice having shorter lives than other males. The association of heterozygosity with life span was clearer in females than in males, yet the longest-lived female genotype was homozygous H-2d/H-2d, of dominant Black phenotype at the Brown locus of chromosome 4, and homozygous dd at the Dilute locus of chromosome 9. The shortest-lived females were dilute brown H-2b/H-2b. The longest-lived and shortest-lived male genotypes were dilute brown H-2d/H-2d and dilute brown H-2b/H-2d, respectively. Although histological findings at postmortem differed between the sexes, there was no association of particular disorders with other genetic markers. The importance of H-2 in males was confirmed, but the allelic effects were perturbed, possibly by the absence of Sendai infection in this experiment. Overall our studies suggest that genetic influences on life span involve interactions between loci, and allelic interactions may change with viral infections or other environmental factors. C1 HARVARD UNIV,SCH PUBL HLTH,CAMBRIDGE,MA 02138. TUFTS UNIV,SCH VET MED,MEDFORD,MA 02155. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP DEAR, KBG (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA-06516]; PHS HHS [R01-A602329-1J] NR 22 TC 11 Z9 11 U1 0 U2 0 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 SN 0016-6731 J9 GENETICS JI Genetics PD SEP PY 1992 VL 132 IS 1 BP 229 EP 239 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA JK869 UT WOS:A1992JK86900020 PM 1398056 ER PT J AU CHEN, ZY POWELL, JF HSU, YPP BREAKEFIELD, XO CRAIG, IW AF CHEN, ZY POWELL, JF HSU, YPP BREAKEFIELD, XO CRAIG, IW TI ORGANIZATION OF THE HUMAN MONOAMINE-OXIDASE GENES AND LONG-RANGE PHYSICAL MAPPING AROUND THEM SO GENOMICS LA English DT Article ID LARGE DNA-MOLECULES; HUMAN X-CHROMOSOME; NORRIE DISEASE; CPG ISLANDS; PEPTIDE SEQUENCES; A GENE; LOCUS; DELETION; METHYLATION; SEPARATION C1 HARVARD UNIV,SCH MED,NEUROSCI PROGRAM,BOSTON,MA 02115. VET ADM MED CTR W ROXBURY,RES SERV,BOSTON,MA 02132. INST PSYCHIAT,DEPT NEUROSCI,LONDON SE5 8AF,ENGLAND. MASSACHUSETTS GEN HOSP,CTR NEUROSCI,BOSTON,MA 02114. RP CHEN, ZY (reprint author), BIOCHEM DEPT,GENET LAB,S PARKS RD,OXFORD OX1 3QU,ENGLAND. RI Powell, John/G-4412-2011 OI Powell, John/0000-0001-6124-439X FU NINDS NIH HHS [NS-21921] NR 65 TC 59 Z9 59 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD SEP PY 1992 VL 14 IS 1 BP 75 EP 82 DI 10.1016/S0888-7543(05)80286-1 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA JK971 UT WOS:A1992JK97100013 PM 1427833 ER PT J AU CHUNG, JY MAGRAW, MM AF CHUNG, JY MAGRAW, MM TI A GROUP-APPROACH TO PSYCHOSOCIAL ISSUES FACED BY HIV-POSITIVE WOMEN SO HOSPITAL AND COMMUNITY PSYCHIATRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; IMMUNE-DEFICIENCY SYNDROME; SEX-DIFFERENCES; UNITED-STATES; GROUP-PSYCHOTHERAPY; RISK REDUCTION; MEDICAL-CARE; AIDS RISK; MEN; INFECTION AB Women now constitute the fastest-growing population of persons with AIDS in the U.S. The psychosocial problems of women with AIDS and HIV infection are underrecognized, and economic, personal, and social resources to meet their needs are often inadequate. The authors describe development of a group for HIV-infected women and discuss issues raised by group members. HIV-infected women often feel isolated and experience stigma and shame. Their roles as caregivers and as wives and mothers are often changed or lost, and they experience anxiety and confusion about options for sexual activity. They sometimes fear transmitting HIV to family members through non-sexual contact. Physicians may discount their symptoms and may need to be educated about gynecological problems associated with HIV. Other issues involve coping with being both ill and a mother, disclosing information to children about the illness, and loss of reproductive choice. C1 MASSACHUSETTS GEN HOSP,DEPT SOCIAL SERV,BOSTON,MA 02114. RP CHUNG, JY (reprint author), UNIV MINNESOTA,DEPT PSYCHIAT,420 DELAWARE ST SE,MAYO BLDG,BOX 393,MINNEAPOLIS,MN 55455, USA. FU NIMH NIH HHS [MH18006-04] NR 38 TC 53 Z9 53 U1 0 U2 5 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0022-1597 J9 HOSP COMMUNITY PSYCH PD SEP PY 1992 VL 43 IS 9 BP 891 EP 894 PG 4 WC Public, Environmental & Occupational Health; Psychiatry SC Public, Environmental & Occupational Health; Psychiatry GA JK866 UT WOS:A1992JK86600006 PM 1427696 ER PT J AU ALTERMAN, AI DROBA, M MCLELLAN, AT AF ALTERMAN, AI DROBA, M MCLELLAN, AT TI RESPONSE TO DAY-HOSPITAL TREATMENT BY PATIENTS WITH COCAINE AND ALCOHOL DEPENDENCE SO HOSPITAL AND COMMUNITY PSYCHIATRY LA English DT Note C1 VET AFFAIRS MED CTR,PHILADELPHIA,PA. UNIV PENN,SCH MED,DEPT PSYCHIAT,PHILADELPHIA,PA 19104. INST PENN HOSP,PHILADELPHIA,PA 19139. RP ALTERMAN, AI (reprint author), UNIV PENN,ADDICT RES CTR,UNIV & WOODLAND AVE,PHILADELPHIA,PA 19104, USA. FU NIDA NIH HHS [DA05186]; PHS HHS [07257-04] NR 7 TC 10 Z9 10 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0022-1597 J9 HOSP COMMUNITY PSYCH PD SEP PY 1992 VL 43 IS 9 BP 930 EP 932 PG 3 WC Public, Environmental & Occupational Health; Psychiatry SC Public, Environmental & Occupational Health; Psychiatry GA JK866 UT WOS:A1992JK86600016 PM 1427705 ER PT J AU TANG, SS DIAMANT, D ROGG, H SCHUNKERT, H LORELL, BH INGELFINGER, JR AF TANG, SS DIAMANT, D ROGG, H SCHUNKERT, H LORELL, BH INGELFINGER, JR TI RAT HEARTS CONTAIN ANGIOTENSIN-II (ANG-II) RECEPTORS THAT ARE DOWN-REGULATED AND DIFFERENTIALLY EXPRESSED DURING HYPERTROPHY SO HYPERTENSION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. BETH ISRAEL HOSP,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 0 TC 7 Z9 7 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0194-911X J9 HYPERTENSION JI Hypertension PD SEP PY 1992 VL 20 IS 3 BP 418 EP 418 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JL733 UT WOS:A1992JL73300101 ER PT J AU PALMER, MR BROWNELL, GL AF PALMER, MR BROWNELL, GL TI ANNIHILATION DENSITY DISTRIBUTION CALCULATIONS FOR MEDICALLY IMPORTANT POSITRON EMITTERS SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article ID RANGE AB The effect of positron range on the image-plane resolution of tomographic images is evaluated through calculations based on a model which employs beta-decay energy spectra and an empirical range formula. Predicted range distribution functions are compared with published measurements for three medically important positron emitters; C-11, Ga-68, and Rb-82. The effect of tomographic slice thickness on point-source annihilation distribution functions is also demonstrated. Line-spread functions are calculated using the model, for the above isotopes as well as for F-18, O-15, and N-13. Image-plane resolution predictions are made for high-resolution positron cameras for various positron emitting isotopes with end-point energies up to 4 Mev. C1 MASSACHUSETTS GEN HOSP,DIV RADIOL SCI & TECHNOL,BOSTON,MA 02114. MIT,DEPT NUCL ENGN,CAMBRIDGE,MA 02139. RP PALMER, MR (reprint author), UNIV BRITISH COLUMBIA,DEPT ELECT ENGN,VANCOUVER V6T 1W5,BC,CANADA. NR 20 TC 42 Z9 42 U1 0 U2 1 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 SN 0278-0062 J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD SEP PY 1992 VL 11 IS 3 BP 373 EP 378 DI 10.1109/42.158941 PG 6 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA JQ647 UT WOS:A1992JQ64700008 PM 18222879 ER PT J AU DEGLIESPOSTI, MA ABRAHAM, LJ MCCANN, V SPIES, T CHRISTIANSEN, FT DAWKINS, RL AF DEGLIESPOSTI, MA ABRAHAM, LJ MCCANN, V SPIES, T CHRISTIANSEN, FT DAWKINS, RL TI ANCESTRAL HAPLOTYPES REVEAL THE ROLE OF THE CENTRAL MHC IN THE IMMUNOGENETICS OF IDDM SO IMMUNOGENETICS LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; DEPENDENT DIABETES-MELLITUS; FRAGMENT LENGTH POLYMORPHISM; HLA-DQ ALLELES; CLASS-II; GENE; SUSCEPTIBILITY; ASSOCIATION; DISEASE; IDENTIFICATION AB The major histocompatibility complex (MHC) contains multiple and diverse genes which may be relevant to the induction and regulation of autoimmune responses in insulin dependent diabetes mellitus (IDDM). In addition to HLA class I and II, the possible candidates include TNF, C4, and several other poorly defined polymorphic genes in the central MHC region. This study describes two approaches which take advantage of the fact that the relevant genes are carried by highly conserved ancestral haplotypes such as 8.1 (HLA-B8, TNFS, C4AQ0, C4B1, DR3, DQ2). First, three "diabetogenic" haplotypes (two Caucasoid and one Mongoloid) have been compared and it has been shown that all three share a rare allele of BAT3 as well as sharing DR3, DQ2. In 43 sequential patients with IDDM the cross product ratio for BAT3S was 4.8 (p<0.01) and 6.9 for HLA-B8 plus BAT3S (p<0.001). Second, partial or recombinant ancestral haplotypes with either HLA class I (HLA-B8) or II (HLA-DR3, DQ2) alleles were identified. Third, using haplotypic polymorphisms such as the one in BAT3, we have shown that all the patients carrying recombinants of the 8.1 ancestral haplotype share the central region adjacent to HLA-B. These findings suggest that both HLA and non-HLA genes are involved in conferring susceptibility to IDDM, and that the region between HLA-B and BAT3 contains some of the relevant genes. By contrast, similar approaches suggest that protective genes map to the HLA class II region. C1 ROYAL PERTH HOSP,DEPT CLIN IMMUNOL,GPO BOX X2213,PERTH,WA 6001,AUSTRALIA. ROYAL PERTH HOSP,DIABET UNIT,PERTH,WA 6001,AUSTRALIA. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. RI Degli-Esposti, Mariapia/E-9529-2013; Degli-Esposti, Mariapia/H-9073-2014 NR 41 TC 97 Z9 98 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0093-7711 J9 IMMUNOGENETICS JI Immunogenetics PD SEP PY 1992 VL 36 IS 6 BP 345 EP 356 PG 12 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA JM094 UT WOS:A1992JM09400001 PM 1356098 ER PT J AU SEBOUN, E JOSHI, N HAUSER, SL AF SEBOUN, E JOSHI, N HAUSER, SL TI HAPLOTYPIC ORIGIN OF BETA-CHAIN GENES EXPRESSED BY HUMAN T-CELL CLONES SO IMMUNOGENETICS LA English DT Article ID FRAGMENT LENGTH POLYMORPHISM; ANTIGEN RECEPTOR GENES; HUMAN PERIPHERAL-BLOOD; V-BETA; TRANSGENIC MICE; MULTIPLE-SCLEROSIS; ALLELIC EXCLUSION; HUMAN FAMILIES; ALPHA-CHAIN; RESTRICTION AB A contribution of allelic variation of T-cell receptor (Tcr) genes to the immune response has not been studied. Here we report that the presence of insertion-deletion-related polymorphisms (IDRP) of the Tcr beta-chain (Tcrb) can be utilized to distinguish the parental origin of the gene complex that undergoes rearrangement in individual T-cell clones. Phytohemagglutinin stimulated clones from an individual heterozygous for an IDRP located between the variable (V) and diversity (D) - joining (J) region genes were studied for the presence of V to DJ rearrangements in each of the two parental chromosomes. Results indicate that single rearrangements were present in the majority of clones, in contrast to the double rearrangements of D to J genes that were generally present. In this individual, V to DJ rearrangement also occured with different frequencies on each of the two germline genes. IDRP clonotyping of the Tcrb complex should prove generally applicable to the study of the influence of allelic variation of Tcrb genes in selection of the expressed T-cell repertoire. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,NEUROIMMUNOL UNIT,32 FRUIT ST,BOSTON,MA 02114. RI Hauser, Stephen/J-2978-2016 NR 39 TC 4 Z9 4 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0093-7711 J9 IMMUNOGENETICS JI Immunogenetics PD SEP PY 1992 VL 36 IS 6 BP 363 EP 368 PG 6 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA JM094 UT WOS:A1992JM09400003 PM 1326480 ER PT J AU MILLER, VL BEER, KB LOOMIS, WP OLSON, JA MILLER, SI AF MILLER, VL BEER, KB LOOMIS, WP OLSON, JA MILLER, SI TI AN UNUSUAL PAGC-TNPHOA MUTATION LEADS TO AN INVASION-DEFECTIVE AND VIRULENCE-DEFECTIVE PHENOTYPE IN SALMONELLAE SO INFECTION AND IMMUNITY LA English DT Article ID EPITHELIAL-CELL MONOLAYER; OUTER-MEMBRANE PROTEIN; YERSINIA-ENTEROCOLITICA; ESCHERICHIA-COLI; MOLECULAR CHARACTERIZATION; TYPHIMURIUM VIRULENCE; ALKALINE-PHOSPHATASE; MUTANTS; MACROPHAGES; EXPRESSION AB Two phenotypes believed to contribute to the pathogenesis of Salmonella infections are macrophage survival and invasion of epithelial cells. It was recently observed that the Salmonella macrophage survival factor PagC has significant amino acid similarity to the Yersinia invasion factor Ail. This observation raised the possibilities that macrophage survival is in part determined by the pathway of entry and that PagC confers an entry mechanism that does not trigger the microbicidal activities of the macrophage. Thus, we sought to investigate the role of PagC in invasion by examining (i) the invasion phenotype of pagC mutants and (ii) the invasion phenotype of Escherichia coli carrying pagC. A previously identified invasion-defective TnphoA insertion mutant of Salmonella enteritidis was found to have TnphoA inserted into the signal sequence-encoding region of pagC; the pagC allele from this mutant, SM5T, was designated pagC64. In contrast, Salmonella typhimurium carrying the pagC1 allele (a TnphoA insertion mutation, downstream of the region encoding the signal sequence) was not defective for invasion. Further analysis of these two pagC alleles suggested that the invasion-defective phenotype associated with pagC64 is not due to the loss of PagC function but rather is due to the synthesis of a hybrid PagC-alkaline phosphatase protein that is aberrantly localized, most likely to the inner membrane, and thus may prevent proper localization or function of a factor(s) required for efficient invasion. The observation that pagC did not confer an invasive phenotype to E. coli further suggests that PagC is not an invasion factor. A cloned pagC gene complemented the macrophage survival defect of S. typhimurium pagC1 mutants, but the cloned ail gene did not. Together these results suggest that the structural similarity between PagC and Ail may not extend to a similarity in function. Interestingly, S. enteritidis carrying the pagC64 allele that results in both an invasion defect and a macrophage survival defect was less virulent for mice infected intragastrically or intraperitoneally than was S. enteritidis carrying the pagC1 allele that results only in a macrophage survival defect. C1 UNIV CALIF LOS ANGELES,INST MOLEC BIOL,LOS ANGELES,CA 90024. MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA 02114. RP MILLER, VL (reprint author), UNIV CALIF LOS ANGELES,DEPT MICROBIOL & MOLEC GENET,405 HILGARD AVE,LOS ANGELES,CA 90024, USA. OI Miller, Virginia/0000-0002-9522-1767 FU NIAID NIH HHS [R01 AI-31403, R01 AI-30479, K11 AI-00917] NR 42 TC 46 Z9 48 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD SEP PY 1992 VL 60 IS 9 BP 3763 EP 3770 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA JJ861 UT WOS:A1992JJ86100042 PM 1323535 ER PT J AU PAUL, SR MERBERG, D FINNERTY, H MORRIS, GE MORRIS, JC JONES, SS TURNER, KJ WOOD, CR AF PAUL, SR MERBERG, D FINNERTY, H MORRIS, GE MORRIS, JC JONES, SS TURNER, KJ WOOD, CR TI MOLECULAR-CLONING OF THE CDNA-ENCODING A RECEPTOR TYROSINE KINASE-RELATED MOLECULE WITH A CATALYTIC REGION HOMOLOGOUS TO C-MET SO INTERNATIONAL JOURNAL OF CELL CLONING LA English DT Article DE TYROSINE KINASE; MOLECULAR CLONING; POLYMERASE CHAIN REACTION ID POLYMERASE CHAIN-REACTION; GROWTH-FACTOR RECEPTOR; SEQUENCE-ANALYSIS; FULL-LENGTH; FAMILY; GENE; IDENTIFICATION; EXPRESSION; CELLS; LINE AB Receptor tyrosine kinases mediate a range of growth and differentiation processes in multiple biological systems. In this work, we report the identification of a novel tyrosine kinase-related molecule, nyk-r, and the molecular cloning of its complete cDNA. Its extracellular domain bears no apparent homology with other receptor families, but its intracellular kinase-related region has considerable similarity with members of the insulin-receptor family such as c-met and trk B. Also, the nyk-r gene is expressed in a wide range of tissues and cell lines. C1 GENET INST, CAMBRIDGE, MA USA. HARVARD UNIV, SCH MED, DANA FARBER CANC INST, BOSTON, MA 02115 USA. HARVARD UNIV, CHILDRENS HOSP, SCH MED, BOSTON, MA 02115 USA. NR 37 TC 25 Z9 28 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 0737-1454 J9 INT J CELL CLONING PD SEP PY 1992 VL 10 IS 5 BP 309 EP 314 PG 6 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA JP045 UT WOS:A1992JP04500008 PM 1333503 ER PT J AU HERZOG, DB KELLER, MB STROBER, M YEH, C PAI, SY AF HERZOG, DB KELLER, MB STROBER, M YEH, C PAI, SY TI THE CURRENT STATUS OF TREATMENT FOR ANOREXIA-NERVOSA AND BULIMIA-NERVOSA SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Article ID PSYCHOLOGICAL TREATMENTS; ANTIDEPRESSANTS; PSYCHOTHERAPY AB A survey investigating the current status of treatment for anorexia nervosa and bulimia nervosa was distributed at the International Conference on Eating Disorders in 1988 and again in 1990. Respondents answered questions regarding treatments they had endorsed for their last patient with anorexia nervosa and/or bulimia nervosa. One hundred and seven medical doctors and psychologists completed the survey in 1988 and 1 15 in 1990. The results indicate that: (1) less than 50% of the respondents believe there is a consensus regarding the treatment of eating disorders; (2) talking therapy is overwhelmingly endorsed for the treatment of both anorexia and bulimia nervosa; (3) there is a trend in clinical practice towards using drug therapy more frequently in treating patients with bulimia nervosa than in treating patients with anorexia nervosa; (4) physicians are more likely than psychologists to endorse drug therapy when treating patients with anorexia and/or bulimia nervosa; and (5) about one third of the respondents endorse drug therapy for treating anorexia nervosa. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. BROWN UNIV,DEPT PSYCHIAT & HUMAN BEHAV,PROVIDENCE,RI 02912. UNIV CALIF LOS ANGELES,INST NEUROPSYCHIAT,DEPT PSYCHIAT & BIOBEHAV SCI,LOS ANGELES,CA 90024. RP HERZOG, DB (reprint author), MASSACHUSETTS GEN HOSP,EATING DISORDERS UNIT,ACC 725,15 PARKMAN ST,BOSTON,MA 02114, USA. NR 14 TC 24 Z9 24 U1 1 U2 1 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0276-3478 J9 INT J EAT DISORDER JI Int. J. Eating Disord. PD SEP PY 1992 VL 12 IS 2 BP 215 EP 220 DI 10.1002/1098-108X(199209)12:2<215::AID-EAT2260120211>3.0.CO;2-Y PG 6 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA JH665 UT WOS:A1992JH66500010 ER PT J AU SHOTT, SR CUNNINGHAM, MJ AF SHOTT, SR CUNNINGHAM, MJ TI APNEA AND THE ELONGATED UVULA SO INTERNATIONAL JOURNAL OF PEDIATRIC OTORHINOLARYNGOLOGY LA English DT Article DE APNEA; RESPIRATORY DISTRESS; UVULA; SOFT PALATE ID MUSCULUS UVULAE; PULMONARY-EDEMA; LARYNGOSPASM; CHILDREN AB Four cases of respiratory distress and apnea associated with an elongated uvula are presented. In all cases, the uvula was found to intermittently fall onto the epiglottis and vocal cords. In all four patients, resection of the uvula led to resolution of all airway symptoms. It is hypothesized that the uvula, touching the vocal cords, caused intermittent laryngospasm and subsequent symptoms of cough, airway obstruction, and cyanosis. The anatomic reasons for such phenomenon are discussed. C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOL & LARYNGOL,BOSTON,MA 02114. RP SHOTT, SR (reprint author), CHILDRENS HOSP MED CTR,DEPT PEDIAT OTOLARYNGOL & MAXILLOFACIAL SURG,BETHESDA & ELLAND AVE,CINCINNATI,OH 45229, USA. NR 10 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-5876 J9 INT J PEDIATR OTORHI JI Int. J. Pediatr. Otorhinolaryngol. PD SEP PY 1992 VL 24 IS 2 BP 183 EP 189 DI 10.1016/0165-5876(92)90145-F PG 7 WC Otorhinolaryngology; Pediatrics SC Otorhinolaryngology; Pediatrics GA JK035 UT WOS:A1992JK03500010 PM 1428598 ER PT J AU KOSTER, HR KENYON, KR AF KOSTER, HR KENYON, KR TI COMPLICATIONS OF SURGERY ASSOCIATED WITH OCULAR TRAUMA SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article RP KOSTER, HR (reprint author), MASSACHUSETTS EYE & EAR INFIRM,CORNEA SERV,BOSTON,MA 02114, USA. NR 0 TC 4 Z9 5 U1 0 U2 1 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD FAL PY 1992 VL 32 IS 4 BP 157 EP 178 DI 10.1097/00004397-199223000-00011 PG 22 WC Ophthalmology SC Ophthalmology GA JU631 UT WOS:A1992JU63100012 PM 1399345 ER PT J AU HETH, CA SCHMID, SY AF HETH, CA SCHMID, SY TI PROTEIN-PHOSPHORYLATION IN RETINAL-PIGMENT EPITHELIUM OF LONG-EVANS AND ROYAL COLLEGE OF SURGEONS RATS SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE RETINAL PIGMENT EPITHELIUM; LE AND RCS RATS; PHAGOCYTOSIS; PHOSPHORYLATION; 2-DIMENSIONAL GEL ELECTROPHORESIS ID ROD OUTER SEGMENTS; CELL-SURFACE PROTEINS; DYSTROPHIC RATS; RCS-RAT; PHAGOCYTOSIS; RPE; INGESTION; CULTURE; KINASE AB Cultures of retinal pigment epithelium (RPE) from normal Long-Evans (LE) and dystrophic Royal College of Surgeons (RCS) rats were incubated with P-32-orthophosphate and then phagocytically challenged with isolated rod outer segments (ROS) or polystyrene latex spheres (PSL). The P-32 incorporation into individual proteins was quantified by image analysis of two-dimensional gel autoradiograms, and changes in phosphorylation were identified by comparison with unchallenged control cultures. Phosphorylation changes that were similar in response to either ROS or PSI, were classified as nonspecific and omitted from further analysis; those associated solely with ROS exposure were classified as ROS specific and compared between the two strains. None of the 30 ROS-specific changes in protein phosphorylation identified in normal LE RPE were the same as in RCS RPE. However, unique ROS-specific changes in phosphorylation were observed in 13 RCS RPE proteins. Three RCS proteins showed ROS-specific decreases; ten showed ROS-specific increases. Six of these ten RCS proteins with increased phosphorylation showed ROS-specific decreases in LE RPE. No other correspondence in ROS-specific changes was found among the remaining LE or RCS RPE proteins, but several RCS proteins were phosphorylated at abnormal levels under control conditions. Even though ROS-induced changes in phosphorylation were aberrant in RCS RPE, their presence indicated that a ROS-specific transmembrane signal was generated after interaction with ROS. The abnormal increases and decreases observed in ROS-specific phosphorylation in the RCS suggested that the defect in ROS phagocytosis was associated with the misregulation or malfunction of both protein kinases and phosphatases. RP HETH, CA (reprint author), HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BERMAN GUND LAB STUDY RETINAL DEGENERAT,BOSTON,MA 02114, USA. FU NEI NIH HHS [EYO8091, EY05790, EYO1687] NR 29 TC 23 Z9 24 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD SEP PY 1992 VL 33 IS 10 BP 2839 EP 2847 PG 9 WC Ophthalmology SC Ophthalmology GA JP059 UT WOS:A1992JP05900011 PM 1526733 ER PT J AU BRADY, TJ WEISSKOFF, RM ROSEN, BR AF BRADY, TJ WEISSKOFF, RM ROSEN, BR TI FUTURE OF MR IMAGING IS LINKED TO FUNCTIONAL IMAGING SO JMRI-JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Editorial Material DE EDITORIALS; FUNCTIONAL STUDIES; RAPID IMAGING; UTILIZATION RP BRADY, TJ (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BLDG 149,13TH ST,BOSTON,MA 02129, USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU SOC MAGNETIC RESONANCE IMAGING PI EASTON PA 1991 NORTHAMPTON ST, EASTON, PA 18042-3189 SN 1053-1807 J9 JMRI-J MAGN RESON IM JI JMRI-J. Magn. Reson. Imaging PD SEP-OCT PY 1992 VL 2 IS 5 BP 497 EP 498 DI 10.1002/jmri.1880020502 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA JP256 UT WOS:A1992JP25600001 PM 1392239 ER PT J AU TANGEL, DJ MEZZANOTTE, WS SANDBERG, EJ WHITE, DP AF TANGEL, DJ MEZZANOTTE, WS SANDBERG, EJ WHITE, DP TI INFLUENCES OF NREM SLEEP ON THE ACTIVITY OF TONIC VS INSPIRATORY PHASIC MUSCLES IN NORMAL MEN SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE TENSOR PALATINI; GENIOGLOSSUS; INSPIRATORY RESISTIVE LOADING; ELECTROMYOGRAPHY ID NEGATIVE AIRWAY PRESSURE; ELECTROMYOGRAPHIC ACTIVITY; VENTILATORY RESPONSE; GENIOGLOSSUS MUSCLE; RESISTANCE; PATHOGENESIS; WAKEFULNESS; ACTIVATION; PATTERN AB Studies of sleep influences on human pharyngeal and other respiratory muscles suggest that the activity of these muscles may be affected by nonrapid-eye-movement (NREM) sleep in a nonuniform manner. This variable sleep response may relate to the pattern of activation of the muscle (inspiratory phasic vs. tonic) and peripheral events occurring in the airway. Furthermore, the ability of these muscles to respond to respiratory stimuli during NREM sleep may also differ. To systematically investigate the effect of NREM sleep on respiratory muscle activity, we studied two tonic muscles [tensor palatini (TP), masseter (M)] and two inspiratory phasic ones [genioglossus (GG), diaphragm (D)], also measuring the response of these muscles to inspiratory resistive loading (12 cmH2O.l-1.s) during wakefulness and NREM sleep. Seven normal male subjects were studied on a single night with intramuscular electrodes placed in the TP and GG and surface electrodes placed over the D and M. Sleep stage, inspiratory airflow, and moving time average electromyograph (EMG) of the above four muscles were continuously recorded. The EMG of both tonic muscles fell significantly (P < 0.05) during NREM sleep [TP awake, 4.3 +/- 0.05 (SE) arbitrary units, stage 2, 1.1 +/- 0.2; stage 3/4, 1.0 +/- 0.2. Masseter awake, 4.8 +/- 0.6; stage 2, 3.3 +/- 0.5; stage 3/4, 3.1 +/- 0.5]. On the other hand, the peak phasic EMG of both inspiratory phasic muscles (GG and D) was well maintained. In addition, the peak phasic activity of both the GG and D increased in response to inspiratory resistive loading during NREM sleep, whereas no such response was observed in the tonic activity of the TP or M. We conclude 1) sleep has a differential effect on the basal activity of tonic vs. inspiratory phasic muscles and 2) tonic muscles are unable to respond to inspiratory resistive loading ring NREM sleep. This sleep-induced decrement in the basal activity of tonic muscles and their inability to respond to a respiratory stimulus may have important consequences on upper airway patency during sleep. C1 UNIV COLORADO,HLTH SCI CTR,DENVER,CO 80220. RP TANGEL, DJ (reprint author), DENVER VET AFFAIRS MED CTR,NATL JEWISH CTR IMMUNOL & RESP,DIV PULM,RESP CARE 111A,DENVER,CO 80220, USA. FU NHLBI NIH HHS [HL-07085] NR 30 TC 79 Z9 79 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 SEP PY 1992 VL 73 IS 3 BP 1058 EP 1066 PG 9 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA JP517 UT WOS:A1992JP51700042 PM 1400018 ER PT J AU BROWN, EN CZEISLER, CA AF BROWN, EN CZEISLER, CA TI THE STATISTICAL-ANALYSIS OF CIRCADIAN PHASE AND AMPLITUDE IN CONSTANT-ROUTINE CORE-TEMPERATURE DATA SO JOURNAL OF BIOLOGICAL RHYTHMS LA English DT Article DE BAYESIAN ANALYSIS; CIRCADIAN RHYTHMS; CORRELATED NOISE; HARMONIC REGRESSION; INTERNAL TIME; KALMAN FILTER; MAXIMUM-LIKELIHOOD ESTIMATION; MONTE-CARLO METHODS ID BRIGHT LIGHT; RHYTHMS; REGRESSION; PACEMAKER; EXPOSURE; MODELS; SHIFTS AB Accurate estimation of the phases and amplitude of the endogenous circadian pacemaker from constant-routine core-temperature series is crucial for making inferences about the properties of the human biological clock from data collected under this protocol. This paper presents a set of statistical methods based on a harmonic-regression-plus-correlated-noise model for estimating the phases and the amplitude of the endogenous circadian pacemaker from constant-routine core-temperature data. The methods include a Bayesian Monte Carlo procedure for computing the uncertainty in these circadian functions. We illustrate the techniques with a detailed study of a single subject's core-temperature series and describe their relationship to other statistical methods for circadian data analysis. In our laboratory, these methods have been successfully used to analyze more than 300 constant routines and provide a highly reliable means of extracting phase and amplitude information from core-temperature data. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT MED,DIV ENDOCRINE,BOSTON,MA 02115. RP BROWN, EN (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ANESTHESIA,BOSTON,MA 02114, USA. FU NIA NIH HHS [NIA-1-R01-AG06072]; NIDDK NIH HHS [NIDDK 5-T32-DK-07529]; NIGMS NIH HHS [NIGM 2T GM07753-06, T32 GM007753] NR 35 TC 169 Z9 169 U1 0 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 SN 0748-7304 J9 J BIOL RHYTHM JI J. Biol. Rhythms PD FAL PY 1992 VL 7 IS 3 BP 177 EP 202 DI 10.1177/074873049200700301 PG 26 WC Biology; Physiology SC Life Sciences & Biomedicine - Other Topics; Physiology GA JN163 UT WOS:A1992JN16300001 PM 1421473 ER PT J AU CHAIKOF, EL MERRILL, EW CALLOW, AD CONNOLLY, RJ VERDON, SL RAMBERG, K AF CHAIKOF, EL MERRILL, EW CALLOW, AD CONNOLLY, RJ VERDON, SL RAMBERG, K TI PEO ENHANCEMENT OF PLATELET DEPOSITION, FIBRINOGEN DEPOSITION, AND COMPLEMENT C3 ACTIVATION SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH LA English DT Article ID OXIDE) POLYSILOXANE NETWORKS; POLY(ETHYLENE OXIDE) AB Whereas it has been commonly thought that adding polyethylene oxide PEO to a surface would diminish the capacity of the surface to cause deposition of platelets and of fibrinogen, and to activate complement C3, we present data showing exactly the opposite. These unexpected results are obtained with low molecular weight (2000) PEO, and are not found with higher molecular weight (20,000) PEO. C1 MIT,DEPT CHEM ENGN,CAMBRIDGE,MA 02139. MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02118. TUFTS UNIV,NEW ENGLAND MED CTR,SCH MED,BOSTON,MA 02111. NR 10 TC 33 Z9 34 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9304 J9 J BIOMED MATER RES JI J. Biomed. Mater. Res. PD SEP PY 1992 VL 26 IS 9 BP 1163 EP 1168 DI 10.1002/jbm.820260906 PG 6 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA JJ464 UT WOS:A1992JJ46400005 PM 1429764 ER PT J AU SCHMALZRIED, TP HARRIS, WH AF SCHMALZRIED, TP HARRIS, WH TI THE HARRIS-GALANTE POROUS-COATED ACETABULAR COMPONENT WITH SCREW FIXATION - RADIOGRAPHIC ANALYSIS OF 83 PRIMARY HIP REPLACEMENTS AT A MINIMUM OF 5 YEARS SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID 10-YEAR FOLLOW-UP; BONE; RESORPTION; MIGRATION; SOCKET AB The results of eighty-three consecutive primary total hip arthroplasties in which a Harris-Galante porous-coated acetabular component had been used were reviewed after a minimum of five years. In all patients, the stated diameter of the acetabular component (the diameter printed on the packaging for the implant) used was equal to the stated diameter of the reamer (the diameter printed on the reamer) that had been used last in the preparation of the acetabulum. As there was little or no press-fit stability, stability was obtained initially with multiple transfixing screws. No component was revised because of loosening, and none were radiographically loose at an average of sixty-eight months and a maximum of seven years after the operation. There was no evidence of disruption of the titanium porous mesh, and no screw had bent or broken. Two sockets, however, had been revised because of failure of the liner-locking mechanism as well as disassociation of the polyethylene liner from the titanium-alloy shell. Lysis of bone occurred in only one patient, around one screw. Areas of non-contact (gaps) between the porous mesh at the periphery of the acetabular component and the bone were seen on the immediate postoperative radiographs of nearly half of the patients. New areas of radiolucency, which had not been seen immediately postoperatively, were identified at two years in forty-nine hips. These radiolucent lines were never wider than one millimeter and were most frequently located in zone 3 and, less frequently, in zone 1. At the time of the most recent follow-up evaluation, a progressive radiolucent line was identified around twenty-two components and a discontinuous radiolucent line was present in all three zones around eleven components. No continuous radiolucent line was identified at the mesh-bone interface of any component. These results are superior to our results with cemented acetabular components after a similar period of follow-up. A longer period of follow-up is needed before the importance of these thin radiolucent lines can be determined, but experience with cemented acetabular components indicates that progressive or extensive radiolucent lines, or both, may represent resorption of bone at the porous mesh-bone interface and this can lead to loosening of the component. Our data suggest that the technique used for implantation may be important not only for the initial fixation and ingrowth of bone, but also for the long-term durability of the fixation of a porous-coated acetabular component. An initial peripheral gap between the porous coating of a Harris-Galante acetabular component and bone may have prognostic importance in terms of the subsequent development of a progressive radiolucent line. A progressive radiolucent line developed around only six (14 per cent) of the forty-two components that were not associated with an initial peripheral gap, but a progressive radiolucent line developed around sixteen (39 per cent) of the forty-one components that were associated with such a gap (p < 0.025). C1 MASSACHUSETTS GEN HOSP,ORTHOPAED BIOMECH LAB,BOSTON,MA 02114. NR 37 TC 162 Z9 166 U1 1 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 SEP PY 1992 VL 74A IS 8 BP 1130 EP 1139 PG 10 WC Orthopedics; Surgery SC Orthopedics; Surgery GA JV595 UT WOS:A1992JV59500002 PM 1400541 ER PT J AU GELBERMAN, RH CHU, CR WILLIAMS, CS SEILER, JG AMIEL, D AF GELBERMAN, RH CHU, CR WILLIAMS, CS SEILER, JG AMIEL, D TI ANGIOGENESIS IN HEALING AUTOGENOUS FLEXOR-TENDON GRAFTS SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID TUMOR ANGIOGENESIS; PATELLAR TENDON; LIGAMENT; TISSUES; GROWTH AB On the basis of recent evidence that flexor tendon grafts may heal without the ingrowth of vascular adhesions, eighteen autogenous donor tendons of intrasynovial and extrasynovial origin were transferred to the synovial sheaths in the forepaws of nine dogs, and controlled passive mobilization was instituted early in the postoperative period. The angiogenic responses of the tendon grafts were determined with perfusion studies with India ink followed by cleaing of the tissues with the Spalteholz technique at two, four, and six weeks. A consistent pattern of neovascularization was noted in the donor tendons of extrasynovial origin. Vascular adhesions arising from the flexor digitorum superficialis and the tendon sheath enveloped the tendon grafts by two weeks. By six weeks, the vascularity of the tendon grafts of extrasynovial origin appeared completely integrated with that of the surrounding tissues. Examination of cross sections revealed that the segments of tendon had been completely vascularized by obliquely oriented intratendinous vessels. In contrast, the flexor tendon grafts of intrasynovial origin healed without ingrowth of vascular adhesions. Primary intrinsic neovascularization took place from the proximal and, to a lesser extent, distal sites of the sutures. Examination of cross sections revealed vessels extending through the surface layer of the tendon graft, with small vessels penetrating the interior of the tendons at regular intervals. CLINICAL RELEVANCE: We believe that this is the first study to demonstrate a distinction between the angiogenic responses of flexor tendon grafts of intrasynovial and extrasynovial origin in a clinically relevant tendon-graft model. These data suggest that donor tendon grafts of intrasynovial origin may become incorporated without the formation of adhesions or the development of avascular necrosis. Thus, there is a potential for improved digital function when tendon grafts of similar anatomical and functional origin to the replaced tendon are used. RP GELBERMAN, RH (reprint author), MASSACHUSETTS GEN HOSP,DEPT ORTHOPAED SURG,WACC-527,BOSTON,MA 02114, USA. FU NIAMS NIH HHS [5R01-AR33097] NR 41 TC 51 Z9 54 U1 0 U2 1 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD SEP PY 1992 VL 74A IS 8 BP 1207 EP 1216 PG 10 WC Orthopedics; Surgery SC Orthopedics; Surgery GA JV595 UT WOS:A1992JV59500011 PM 1383229 ER PT J AU LEE, SW TOMASETTO, C PAUL, D KEYOMARSI, K SAGER, R AF LEE, SW TOMASETTO, C PAUL, D KEYOMARSI, K SAGER, R TI TRANSCRIPTIONAL DOWN-REGULATION OF GAP-JUNCTION PROTEINS BLOCKS JUNCTIONAL COMMUNICATION IN HUMAN MAMMARY-TUMOR CELL-LINES SO JOURNAL OF CELL BIOLOGY LA English DT Article ID SUPPRESSOR GENES; INTERCELLULAR COMMUNICATION; TRANSFORMED-CELLS; GROWTH; CDNA; CLONING; PHOSPHORYLATION; CARCINOGENESIS; TRANSFECTION; INHIBITION AB Subtractive hybridization, selecting for mRNAs expressed in normal human mammary epithelial cells (NMECs) but not in mammary tumor cell lines (TMECs), led to the cloning of the human gap junction gene connexin 26 (Cx26), identified by its sequence similarity to the rat gene. Two Cx26 transcripts derived from a single gene are expressed in NMECs but neither is expressed in a series of TMECs. Northern analysis using rat Cx probes showed that Cx43 mRNA is also expressed in the normal cells, but not in the tumor lines examined. Connexin genes Cx31.1, Cx32, Cx33, Cx37, and Cx40 are not expressed in either normal cells or the tumor lines examined. In cell-cell communication studies, the normal cells transferred Lucifer yellow, while tumor cells failed to show dye transfer. Both Cx26 and Cx43 proteins were immunolocalized to membrane sites in normal cells but were not found in tumor cells. Further analysis demonstrated that Cx26 is a cell-cycle regulated gene expressed at a moderate level during G1 and S, and strongly up-regulated in late S and G2, as shown with lovastatin-synchronized NMECs. Cx43, on the contrary is constitutively expressed at a uniform low level throughout the cell cycle. Treatment of normal and tumor cells with a series of drugs: 5dB-cAMP, retinoic acid, okadaic acid, estradiol, or TGF(b) had no connexin-inducing effect in tumor cells. However, PMA induced re-expression of the two Cx26 transcripts but not of Cx43 in several TMECs. Thus Cx26 and Cx43 are both downregulated in tumor cells but respond differentially to some signals. Modulation of gap-junctional activity by drug therapy may have useful clinical applications in cancer. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOLEC GENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT ANAT & CELLULAR BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. RI Tomasetto, Catherine/J-2783-2014 OI Tomasetto, Catherine/0000-0002-1811-5848 FU NCI NIH HHS [CA39814] NR 34 TC 215 Z9 236 U1 0 U2 2 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 SEP PY 1992 VL 118 IS 5 BP 1213 EP 1221 DI 10.1083/jcb.118.5.1213 PG 9 WC Cell Biology SC Cell Biology GA JL550 UT WOS:A1992JL55000018 PM 1324944 ER PT J AU CARPEN, O PALLAI, P STAUNTON, DE SPRINGER, TA AF CARPEN, O PALLAI, P STAUNTON, DE SPRINGER, TA TI ASSOCIATION OF INTERCELLULAR-ADHESION MOLECULE-1 (ICAM-1) WITH ACTIN-CONTAINING CYTOSKELETON AND ALPHA-ACTININ SO JOURNAL OF CELL BIOLOGY LA English DT Article ID TRANSMEMBRANE LINKAGE; FOCAL ADHESIONS; SMOOTH-MUSCLE; RECEPTOR; LFA-1; PROTEINS; SPECTRIN; SURFACE; CELLS; IMMUNOGLOBULIN AB We have studied the cytoskeletal association of intercellular adhesion molecule-1 (ICAM-1, CD54), an integral membrane protein that functions as a counter-receptor for leukocyte integrins (CD11/CD18). A linkage between ICAM-1 and cytoskeletal elements was suggested by studies showing a different ICAM-1 staining pattern for COS cells transfected with wild-type ICAM-1 or with an ICAM-1 construct that replaces the cytoplasmic and transmembrane domains of ICAM-1 with a glycophosphatidylinositol (GPI) anchor. Wild-type ICAM-1 appeared to localize most prominently in microvilli whereas GPI-ICAM-1 demonstrated a uniform cell surface distribution. Disruption of microfilaments with cytochalasin B (CCB) changed the localization of wild-type ICAM-1 but had no effect on GPI-ICAM-1. Some B-cell lines demonstrated a prominent accumulation of ICAM-1 into the uropod region whereas other cell surface proteins examined were not preferentially localized. CCB also induced redistribution of ICAM-1 in these cells. For characterization of cytoskeletal proteins interacting with ICAM-1, a 28-residue peptide that encompasses the entire predicted cytoplasmic domain (ICAM-1,478-505) was synthesized, coupled to Sepharose-4B, and used as an affinity matrix. One of the most predominant proteins eluted either with soluble ICAM-1,478-505-peptide or EDTA, was 100 kD, had a pI of 5.5, and in Western blots reacted with alpha-actinin antibodies. A direct association between alpha-actinin and ICAM-1 was demonstrated by binding of purified alpha-actinin to ICAM-1,478-505-peptide and to immunoaffinity purified ICAM-1 and by a strict colocalization of ICAM-1 with alpha-actinin, but not with the cytoskeletal proteins talin, tensin, and vinculin. The region of ICAM-1,478-505 interacting with alpha-actinin was mapped to the area close to the membrane spanning region. This region contains several positively charged residues and appears to mediate a charged interaction with alpha-actinin which is not highly dependent on the order of the residues. C1 BOEHRINGER INGELHEIM PHARMACEUT INC,RIDGEFIELD,CT 06877. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. FU NCI NIH HHS [CA31798] NR 62 TC 269 Z9 272 U1 0 U2 6 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 SEP PY 1992 VL 118 IS 5 BP 1223 EP 1234 DI 10.1083/jcb.118.5.1223 PG 12 WC Cell Biology SC Cell Biology GA JL550 UT WOS:A1992JL55000019 PM 1355095 ER PT J AU PRICE, BD MANNHEIMRODMAN, LA CALDERWOOD, SK AF PRICE, BD MANNHEIMRODMAN, LA CALDERWOOD, SK TI BREFELDIN-A, THAPSIGARGIN, AND AIF4- STIMULATE THE ACCUMULATION OF GRP78 MESSENGER-RNA IN A CYCLOHEXIMIDE DEPENDENT MANNER, WHILE INDUCTION BY HYPOXIA IS INDEPENDENT OF PROTEIN-SYNTHESIS SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID GLUCOSE-REGULATED PROTEIN; CHAIN-BINDING-PROTEIN; CALCIUM IONOPHORE A23187; LUMINAL ER PROTEINS; ENDOPLASMIC-RETICULUM; HEAT-SHOCK; SECRETORY PROTEINS; MAMMALIAN-CELLS; TUMOR PROMOTER; GENES AB The glucose regulated proteins (GRPs) are major structural components of the endoplasmic reticulum (ER) and are involved in the import, folding, and processing of ER proteins. Expression of the glucose regulated proteins (GRP78 and GRP94) is greatly increased after cells are exposed to stress agents (including A23187 and tunicamycin) which inhibit ER function. Here, we demonstrate that three novel inhibitors of ER function, thapsigargin (which inhibits the ER Ca2+-ATPase), brefeldin A (an inhibitor of vesicle transport between the ER and Golgi) and AlF4-, (which inhibits trimeric G-proteins), can increase the expression of both GRP78 and 94. The common characteristic shared by activators of GRP expression is that they disrupt some function of the ER. The increased levels of GRPs may be a response to the accumulation of aberrant proteins in the ER or they may be increased in response to structural/functional damage to the ER. The increased accumulation of GRP78 mRNA after exposure of cells to either thapsigargin, brefeldin A, AlF4-, A23187, or tunicamycin can be blocked by pre-incubation in cycloheximide. In contrast, accumulation of GRPs after exposure to hypoxia was independent of cycloheximide. In addition, the protein kinase inhibitor genistein blocked the thapsigargin induced accumulation of GRP78-mRNA, whereas the protein phosphatase inhibitor okadaic acid caused increased accumulation of GRP78 mRNA. The data indicates that there are at least 2 mechanisms for induced expression of GRPs, one of which involves a phosphorylation step and requires new protein synthesis (e.g., thapsigargin, A23187) and one which is independent of both these steps (hypoxia). RP PRICE, BD (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,JOINT CTR RADIAT THERAPY,STRESS PROT GRP,BOSTON,MA 02115, USA. FU NCI NIH HHS [R29CA44940]; PHS HHS [R0147407] NR 43 TC 81 Z9 81 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD SEP PY 1992 VL 152 IS 3 BP 545 EP 552 DI 10.1002/jcp.1041520314 PG 8 WC Cell Biology; Physiology SC Cell Biology; Physiology GA JK153 UT WOS:A1992JK15300013 PM 1506413 ER PT J AU VACANTI, CA ROBERTS, JT AF VACANTI, CA ROBERTS, JT TI BLIND ORAL INTUBATION - THE DEVELOPMENT AND EFFICACY OF A NEW APPROACH SO JOURNAL OF CLINICAL ANESTHESIA LA English DT Article DE INTUBATION, BLIND, ORAL, ENDOTRACHEAL; LARYNGOSCOPY; FIBEROPTIC; TRACHEA AB Study Objective: To develop an approach to blind oral intubation. With the aid of a fiberoptic laryngoscope and stylet within an endotracheal tube, a video camera, a monitor, and a recorder to correlate the effects of various manipulations of the airway on access to the trachea, a suitable approach was devised. We then evaluated its efficacy. Design: Randomized, prospective comparison of regimens. Setting: Patient surgery at a university-affiliated teaching hospital. Patients: One hundred adult patients with no known abnormalities of the upper airway by history or on physical examination, scheduled to undergo elective surgery, and without evidence of major cardiac disease or need for a rapid-sequence induction of anesthesia. Interventions: Fifty patients in each of two groups were given fentanyl 5 mug/kg intravenously (IV), followed 2 minutes later by thiopental sodium 5 mg/kg and succinylcholine 2 mg/kg. Patients in Group 1 (the controls) were orally intubated via direct laryngoscopy using a Macintosh #3 blade. Patients in Group 2 (the experimentals) were intubated orally with the approach developed without the use of a laryngoscope. Intubations were deemed successful if they were performed within 1 minute after the mouth was opened. Measurements and Main Results: All the patients in Group 1 were successfully intubated within 1 minute, while 49 of the 50 patients in Group 2 were successfully intubated within 1 minute. Conclusions: Blind oral tracheal intubation can be successfully performed in a safe and effective manner after appropriate teaching of the technique. RP VACANTI, CA (reprint author), MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,32 FRUIT ST,BOSTON,MA 02114, USA. NR 0 TC 6 Z9 8 U1 0 U2 0 PU BUTTERWORTH-HEINEMANN PI WOBURN PA 225 WILDWOOD AVE #UNITB PO BOX 4500, WOBURN, MA 01801-2084 SN 0952-8180 J9 J CLIN ANESTH JI J. Clin. Anesth. PD SEP-OCT PY 1992 VL 4 IS 5 BP 399 EP 401 DI 10.1016/0952-8180(92)90165-W PG 3 WC Anesthesiology SC Anesthesiology GA JX170 UT WOS:A1992JX17000011 PM 1389195 ER PT J AU BILLER, BMK BAUM, HBA ROSENTHAL, DI SAXE, VC CHARPIE, PM KLIBANSKI, A AF BILLER, BMK BAUM, HBA ROSENTHAL, DI SAXE, VC CHARPIE, PM KLIBANSKI, A TI PROGRESSIVE TRABECULAR OSTEOPENIA IN WOMEN WITH HYPERPROLACTINEMIC AMENORRHEA SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BONE-MINERAL CONTENT; POSTMENOPAUSAL WOMEN; PREMENOPAUSAL WOMEN; ANOREXIA-NERVOSA; DENSITY; MASS; OSTEOPOROSIS; HYPOGONADISM; MEN; PREVALENCE AB Reductions in cortical and trabecular bone mass have been documented in young women with hyperprolactinemic amenorrhea. It is unknown whether trabecular osteopenia is progressive or reversible with treatment of hyperprolactinemia. In addition, it is not known whether clinical or hormonal variables can predict trabecular bone density (BD) changes. Therefore, we investigated prospectively trabecular BD by computed tomography in 52 hyperprolactinemic women and 41 controls. The mean follow-up interval was 1.8 +/- 0.1 (SEM) yr. Patient groups were defined as follows: group 1, amenorrhea during the entire study; group 2, restoration of menses during the study by treatment of hyperprolactinemia; group 3, regular menses despite hyperprolactinemia, with no history of prior amenorrhea; group 4, history of prior amenorrhea, but menses restored with treatment of hyperprolactinemia before study entry; and group 5, oligomenorrhea. Groups 1, 2, and 4 had significant (P = 0.0006) initial spinal osteopenia [mean BD 141 +/- 7 (SEM), 144 +/- 9, and 151 +/- 5 mg/cc K2HPO4, respectively] compared with controls or with group 3 (170 +/- 4 and 173 +/- 8 mg/cc K2HPO4, respectively). Group 5 had an initial mean BD which was midway between that of the amenorrheic and eumenorrheic women (156 +/- 13 mg/cc K2HPO4). Group 1 had a significant (P = 0.04) decrease in mean BD to 132 +/- 8 mg/cc K2HPO4 over 1.7 +/- 0.2 yr, with BD in 42% of the group more than 2 SD below the control mean at the final study point. The mean BD in group 2 increased to 155 +/- 9 mg/cc K2HPO4, approaching significance (P = 0.07) when compared with the initial BD. Five of the nine patients in this group (56%) had an increase in BD greater than the variation expected for the computed tomography technique. However, 44% of the group 2 patients had a spinal BD which remained more than 1 SD below the normal mean. There was no change in BD in the other groups. Among the variables found to correlate positively with the slope of BD in one or more of the groups were: initial percent ideal body weight (P = 0.03, r = 0.623), final serum free testosterone levels (P = 0.001, r = 0.808), and final serum dehydroepiandrosterone sulfate levels (P = 0.03, r = 0.756). We conclude that in women with hyperprolactinemia: 1) menstrual status is the most important predictor of progressive spinal osteopenia, 2) factors other than hypoestrogenemia, including body composition and serum androgen levels, may be important in preventing bone loss, and 3) in a subset of patients, spinal BD remains lower than normal despite therapy, suggesting that there is permanent osteopenia before menopause. C1 MASSACHUSETTS GEN HOSP, DEPT RADIOL, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02115 USA. RP BILLER, BMK (reprint author), MASSACHUSETTS GEN HOSP, DEPT MED, NEUROENDOCRINE UNIT, JACKSON 10, BOSTON, MA 02114 USA. FU NCRR NIH HHS [RR-01066]; NICHD NIH HHS [HD21204]; NIDDK NIH HHS [DK07028] NR 38 TC 102 Z9 106 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 SEP PY 1992 VL 75 IS 3 BP 692 EP 697 DI 10.1210/jc.75.3.692 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JM350 UT WOS:A1992JM35000003 PM 1517356 ER PT J AU JAY, N MANSFIELD, MJ BLIZZARD, RM CROWLEY, WF SCHOENFELD, D RHUBIN, L BOEPPLE, PA AF JAY, N MANSFIELD, MJ BLIZZARD, RM CROWLEY, WF SCHOENFELD, D RHUBIN, L BOEPPLE, PA TI OVULATION AND MENSTRUAL FUNCTION OF ADOLESCENT GIRLS WITH CENTRAL PRECOCIOUS PUBERTY AFTER THERAPY WITH GONADOTROPIN-RELEASING-HORMONE AGONISTS SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID SEXUAL PRECOCITY; LHRH AGONIST; MENARCHE; CYCLES AB Chronic GmRH agonist (GnRHa) administration has been shown to suppress pituitary-gonadal function in children with central precocious puberty (CPP), but long term data after the reactivation of gonadarche posttherapy are not yet available. This study evaluated the menstrual function of 46 girls with CPP who had been treated for at least 2 yr with GnRHa (deslorelin or histrelin, sc, daily) and were up to 7 yr posttreatment, including 21 postmenarcheal girls who collected weekly overnight urine samples for 12 consecutive weeks to assess rates of ovulation by urinary pregnanediol-3-beta-glucuronide measurements. Menarche occurred at age 12.1 +/- 1.0 yr (mean +/- SD), on the average 1.2 +/- 0.8 yr posttherapy (range, 0.1-4.3 yr). Menstrual cycle lengths became increasingly regular, with cycles of 25- to 35-day duration reported by 41% of the girls in the first year postmenarche and 65% of the girls studied 3 or more years postmenarche. Ovulation was demonstrated in 50% of the girls studied within 1 yr of menarche and in 90% of the girls studied 2 yr or more postmenarche, including 5 girls who reported pregnancies. The development of regular ovulatory menstrual function in these girls with CPP is in accord with previously documented patterns in normal adolescents. While these data provide further evidence supporting the safety of long term GnRHa therapy, continued studies will be necessary to characterize fully the reproductive function in CPP patients through adolescence and adulthood. C1 UNIV VIRGINIA, CHILDRENS MED CTR, DIV ENDOCRINOL & DIABET, CHARLOTTESVILLE, VA 22908 USA. HYGEIA SCI, NEWTON, MA 02160 USA. CHILDRENS HOSP MED CTR, DIV ENDOCRINOL, BOSTON, MA 02115 USA. MASSACHUSETTS GEN HOSP, PEDIAT UNIT, BOSTON, MA 02114 USA. CHILDRENS HOSP MED CTR, DIV ADOLESCENT MED, BOSTON, MA 02115 USA. CHILDRENS HOSP MED CTR, DEPT MED, BOSTON, MA 02115 USA. MASSACHUSETTS GEN HOSP, GEN CLIN RES CTR, BOSTON, MA 02114 USA. FU NCRR NIH HHS [RR-01066, RR-02172]; NICHD NIH HHS [HD-18169] NR 25 TC 55 Z9 57 U1 1 U2 3 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 SEP PY 1992 VL 75 IS 3 BP 890 EP 894 DI 10.1210/jc.75.3.890 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JM350 UT WOS:A1992JM35000037 PM 1517382 ER PT J AU KIM, JH SEIBEL, MM MACLAUGHLIN, DT DONAHOE, PK RANSIL, BJ HAMETZ, PA RICHARDS, CJ AF KIM, JH SEIBEL, MM MACLAUGHLIN, DT DONAHOE, PK RANSIL, BJ HAMETZ, PA RICHARDS, CJ TI THE INHIBITORY EFFECTS OF MULLERIAN-INHIBITING SUBSTANCE ON EPIDERMAL GROWTH-FACTOR INDUCED PROLIFERATION AND PROGESTERONE PRODUCTION OF HUMAN GRANULOSA-LUTEAL CELLS SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CULTURED GRANULOSA; OOCYTE MEIOSIS; RAT OVARY; HORMONE; BOVINE; FETAL; IMMUNOASSAY; INVITRO; PHOSPHORYLATION; FIBROBLAST AB This study was undertaken to determine if Mullerian-inhibiting substance (MIS) could block basal and/or epidermal growth factor (EGF)-induced proliferation and progesterone production by cultured human granulosa-luteal cells. Cells from follicles of individual patients were pooled, counted, and aliquoted into Ham's F-10 medium containing 10% MIS-free female fetal calf serum at 37 C in 95% air and 5% CO2. After assessing viability, cells were counted on days 4, 8, 12, and 16 of culture. EGF was added every other day at 0.2, 2, and 20 ng/mL beginning on culture day 4. The greatest stimulatory effect of EGF on cell proliferation was observed at 20 ng/mL on days 12 and 16. EGF increased progesterone production per cell after 4 days exposure, but this effect was lost after 8 days. Granulosa-luteal cells were cultured with 0.2, 2, and 20 ng/mL immunoaffinity purified recombinant human MIS (rhMIS) or conditioned medium from Chinese hamster ovary cells transfected with the human MIS gene, beginning on culture day 4. rhMIS demonstrated its greatest inhibitory effect on cell proliferation at 20 ng/mL on day 16. The rhMIS decreased progesterone production per cell after 4 days exposure, but only in the higher doses. Maintaining EGF at 20 ng/mL and varying rhMIS yielded significant reduction in EGF-mediated proliferation and progesterone production per cell at 2 and 20 ng/mL rhMIS. These experiments demonstrate rhMIS inhibits basal and EGF-stimulated human granulosa-luteal cell proliferation and progesterone production. C1 HARVARD UNIV, FAULKNER HOSP, FAULKNER CTR REPROD MED, DEACONESS SURG PROGRAM, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, PEDIAT SURG RES LAB, BOSTON, MA 02114 USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, DEPT SURG, BOSTON, MA 02114 USA. BETH ISRAEL HOSP, DANA RES INST, DEPT MED, BOSTON, MA 02114 USA. NR 43 TC 74 Z9 78 U1 1 U2 3 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 SEP PY 1992 VL 75 IS 3 BP 911 EP 917 DI 10.1210/jc.75.3.911 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JM350 UT WOS:A1992JM35000041 PM 1517385 ER PT J AU HARRIS, PE ALEXANDER, JM BIKKAL, HA HSU, DW HEDLEYWHYTE, ET KLIBANSKI, A JAMESON, JL AF HARRIS, PE ALEXANDER, JM BIKKAL, HA HSU, DW HEDLEYWHYTE, ET KLIBANSKI, A JAMESON, JL TI GLYCOPROTEIN HORMONE ALPHA-SUBUNIT PRODUCTION IN SOMATOTROPH ADENOMAS WITH AND WITHOUT GS-ALPHA MUTATIONS SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID SECRETING PITUITARY-ADENOMAS; MESSENGER-RNA LEVELS; SIGNAL TRANSDUCTION; ADENYLYL CYCLASE; GENE-EXPRESSION; RAT PITUITARY; CYCLIC-AMP; TUMORS; CELL; GH AB Activating mutations of the Gs-alpha subunit have been identified in a subset of somatotroph adenomas. The mutant form of the Gs-alpha subunit causes persistent activation of adenylyl cyclase and consequently results in high intracellular levels of cAMP. Because cAMP is known to stimulate the synthesis of the glycoprotein hormone (GPH) alpha-subunit as well as GH, we examined somatotroph tumors with and without Gs-alpha mutations for GPH alpha-subunit production. GPH alpha-subunit production was assessed in vivo by measuring serum hormone levels and in vitro by analyzing hormone secretion by cultured pituitary tumor cells. DNA was extracted from the pituitary tumors of 26 acromegalic patients. The Gs-alpha gene was amplified by the polymerase chain reaction and screened for mutations at codons 201 and 227 using oligonucleotide specific hybridization. Nine of the 26 tumors (35%) had point mutations at Arg 201. Seven of these tumors contained a CGT to TGT mutation (Arg to Cys) and 2 contained a CGT to CAT mutation (Arg to His). No mutations were detected at codon 227. There were no significant differences in age, sex distribution, tumor size, or serum levels of GH or insulin-like growth factor-1 between the groups of patients with or without Gs-alpha mutations. The mean serum level of the free GPH alpha-subunit was 1.9-fold higher in the group with Gsa mutations (0.48 +/-0.37-mu-g/L) than in patients without mutations (0.25 +/- 0.17) (P < 0.05). In pituitary tumor cell culture, 75% of somatotroph tumors with Gs-alpha mutations secreted free GPH alpha-subunit into the media compared with 45% of tumors without Gs-alpha mutations. The amount of GPH alpha-subunit secretion was 12-fold greater in the group of tumors containing the Gs-alpha mutation (P < 0.05). Immunocytochemical detection of the free GPH alpha-subunit was similar in the two groups of patients with 75% positive for the GPH alpha-subunit in tumors with Gs-alpha mutations and 67% positive in tumors without mutations (P = 0.69). We conclude that GPH alpha-subunit production occurs in somatotroph tumors with and without Gs-alpha mutations. The increased levels of GPH alpha-subunit secretion in vivo and in vitro suggest that the Gs-alpha mutation may increase the amount of preexisting GPH alpha-subunit biosynthesis in the tumors, perhaps via activation of the cAMP pathway. C1 HARVARD UNIV, MASSACHUSETTS GEN HOSP,SCH MED,THYROID UNIT, JACKSON 1021, BOSTON, MA 02114 USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, NEUROENDOCRINE UNIT, BOSTON, MA 02114 USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, NEUROPATHOL UNIT, BOSTON, MA 02114 USA. OI Jameson, James/0000-0001-9538-4059 FU NICHD NIH HHS [HD-23519, HD-28138]; NIDDK NIH HHS [DK-40947] NR 33 TC 45 Z9 46 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 SEP PY 1992 VL 75 IS 3 BP 918 EP 923 DI 10.1210/jc.75.3.918 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JM350 UT WOS:A1992JM35000042 PM 1517386 ER PT J AU EGLOW, R POTHOULAKIS, C ITZKOWITZ, S ISRAEL, EJ OKEANE, CJ GONG, DH GAO, N XU, YL WALKER, WA LAMONT, JT AF EGLOW, R POTHOULAKIS, C ITZKOWITZ, S ISRAEL, EJ OKEANE, CJ GONG, DH GAO, N XU, YL WALKER, WA LAMONT, JT TI DIMINISHED CLOSTRIDIUM-DIFFICILE TOXIN-A SENSITIVITY IN NEWBORN RABBIT ILEUM IS ASSOCIATED WITH DECREASED TOXIN-A RECEPTOR SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE BRUSH BORDER RECEPTOR; CLOSTRIDIUM-DIFFICILE; DEVELOPMENT; ENTEROTOXIN-A; TOXIN RECEPTOR ID RAT SMALL-INTESTINE; STABLE ENTERO-TOXIN; CLINDAMYCIN-ASSOCIATED COLITIS; DEVELOPMENTAL-CHANGES; CYTO-TOXIN; HAMSTERS; DIARRHEA; PERMEABILITY; COLONIZATION; FIBROBLASTS AB Human infants are relatively resistant to Clostridium difficile-associated diarrhea and colitis compared to adults. In that toxin A is the major cause of intestinal damage with this organism, we compared toxin A receptor binding and biological effects in newborn vs adult rabbit ileum. Purified toxin A (M(r) 308 kD) was labeled with tritium or biotin with full retention of biologic activity. Appearance of specific toxin A brush border (BB) binding was strongly age dependent with minimal [H-3] toxin A specific binding at 2 and 5 d of life, followed by gradual increase in binding to reach adult levels at 90 d. Absence of toxin A binding sites in newborn and presence in adult rabbits was confirmed by immunohistochemical studies using biotinylated toxin A. Toxin A (50 ng to 20-mu-g/ml) inhibited protein synthesis in 90-d-old rabbit ileal loops in a dose-dependent fashion. In contrast, inhibition of protein synthesis in 5-d-old rabbit ileum occurred only at the highest toxin A doses (5 and 20-mu-g/ml) and at all doses tested was significantly less than the adult rabbit ileum. In addition, toxin A (5-mu-g/ml) caused severe mucosal damage in adult rabbit ileal explants but had no discernable morphologic effect on 5-d-old rabbit intestine. Our data indicate that newborn rabbit intestine lacks BB receptors for toxin A. The absence of the high-affinity BB receptor for toxin A in the newborn period may explain lack of biologic responsiveness to purified toxin, and the absence of disease in human infants infected with this pathogen. C1 BOSTON UNIV HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02118. BOSTON UNIV HOSP,SCH MED,GASTROENTEROL SECT,BOSTON,MA 02118. HARVARD UNIV,MT SINAI MED CTR,SCH MED,BOSTON,MA 02115. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DIV PEDIAT GASTROENTEROL,BOSTON,MA 02115. FU NCI NIH HHS [CA-42581]; NIDDK NIH HHS [DK-08395, DK-34583] NR 55 TC 87 Z9 90 U1 2 U2 4 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 1992 VL 90 IS 3 BP 822 EP 829 DI 10.1172/JCI115957 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA JN959 UT WOS:A1992JN95900020 PM 1325998 ER PT J AU ZEMELMAN, BV WALKER, WA CHU, SHW AF ZEMELMAN, BV WALKER, WA CHU, SHW TI EXPRESSION AND DEVELOPMENTAL REGULATION OF NA+, K+ ADENOSINE-TRIPHOSPHATASE IN THE RAT SMALL-INTESTINE SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE SODIUM PUMP; ION TRANSPORT; GLUCOCORTICOID; ISOZYMES; GENE EXPRESSION ID TISSUE-SPECIFIC EXPRESSION; NA,K-ATPASE ALPHA-SUBUNIT; 2 MOLECULAR-FORMS; BETA-SUBUNIT; CATALYTIC SUBUNIT; GENE-EXPRESSION; MESSENGER-RNAS; C+ CELLS; BRAIN; SODIUM AB The Na+,K+-ATPase ion pump plays a critical role in fluid and electrolyte physiology of the small intestine. Here we show that, of the three known alpha-isotypes (alpha-1, alpha-2, and alpha-3) of the sodium pump found in the rat, only alpha-1 is expressed in the small intestine. The expression of this isotype, considered at the level of mRNA, is under developmental control, with the adult intestine exhibiting approximately a threefold increase in alpha-1 message over the neonate. Cortisone treatment of the neonate results in near-adult levels of alpha-1 mRNA expression. An increase in the abundance of alpha-1 isotype parallels the changes in its mRNA expression. Beta-subunit mRNA is expressed coordinately with the alpha-1 subunit mRNA. A four- to five-fold rise in the Na+,K+-ATPase activity is also developmentally induced. C1 MIT,CTR CANC RES,DEPT BIOL,CAMBRIDGE,MA 02139. MASSACHUSETTS GEN HOSP,COMBINED PROGRAM PEDIAT GASTROENTEROL & NUTR,DEV GASTROENTEROL LAB,BOSTON,MA 02115. CHILDRENS HOSP MED CTR,BOSTON,MA 02115. FU NICHD NIH HHS [HD12437]; NIDDK NIH HHS [DK37521, DK33506] NR 44 TC 23 Z9 23 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 1992 VL 90 IS 3 BP 1016 EP 1022 DI 10.1172/JCI115914 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA JN959 UT WOS:A1992JN95900042 PM 1325991 ER PT J AU LOEFFLER, JS ALEXANDER, E SHEA, WM WEN, PY FINE, HA KOOY, HM BLACK, PM AF LOEFFLER, JS ALEXANDER, E SHEA, WM WEN, PY FINE, HA KOOY, HM BLACK, PM TI RADIOSURGERY AS PART OF THE INITIAL MANAGEMENT OF PATIENTS WITH MALIGNANT GLIOMAS SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID INTRACRANIAL ARTERIOVENOUS-MALFORMATIONS; STANDARD LINEAR-ACCELERATOR; THERAPY-ONCOLOGY-GROUP; STEREOTAXIC RADIOSURGERY; RADIATION-THERAPY; RADIOTHERAPY; GLIOBLASTOMA; SURVIVAL; QUALITY; BRAIN C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,CTR BRAIN TUMOUR,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,CHILDRENS HOSP,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT RADIAT ONCOL,BOSTON,MA 02115. RP LOEFFLER, JS (reprint author), HARVARD UNIV,SCH MED,JOINT CTR RADIAT THERAPY,50 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [K11 CAO 1492] NR 23 TC 198 Z9 202 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP PY 1992 VL 10 IS 9 BP 1379 EP 1385 PG 7 WC Oncology SC Oncology GA JL392 UT WOS:A1992JL39200004 PM 1325539 ER PT J AU HAYS, DM LANDSVERK, J SALLAN, SE HEWETT, KD PATENAUDE, AF SCHOONOVER, D ZILBER, SL RUCCIONE, K SIEGEL, SE AF HAYS, DM LANDSVERK, J SALLAN, SE HEWETT, KD PATENAUDE, AF SCHOONOVER, D ZILBER, SL RUCCIONE, K SIEGEL, SE TI EDUCATIONAL, OCCUPATIONAL, AND INSURANCE STATUS OF CHILDHOOD-CANCER SURVIVORS IN THEIR 4TH AND 5TH DECADES OF LIFE SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID HODGKINS-DISEASE; ADULT SURVIVORS; BRAIN-TUMORS; SEQUELAE; ADJUSTMENT; CHILDREN; QUALITY C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. RP HAYS, DM (reprint author), CHILDRENS HOSP,BOX 54700,MAIL STOP 54,LOS ANGELES,CA 90054, USA. FU NCI NIH HHS [CA44133] NR 34 TC 79 Z9 79 U1 1 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP PY 1992 VL 10 IS 9 BP 1397 EP 1406 PG 10 WC Oncology SC Oncology GA JL392 UT WOS:A1992JL39200007 PM 1517782 ER PT J AU KUERBITZ, SJ CIVIN, CI KRISCHER, JP RAVINDRANATH, Y STEUBER, CP WEINSTEIN, HJ WINICK, N RAGAB, AH GRESIK, MV CRIST, WM AF KUERBITZ, SJ CIVIN, CI KRISCHER, JP RAVINDRANATH, Y STEUBER, CP WEINSTEIN, HJ WINICK, N RAGAB, AH GRESIK, MV CRIST, WM TI EXPRESSION OF MYELOID-ASSOCIATED AND LYMPHOID-ASSOCIATED CELL-SURFACE ANTIGENS IN ACUTE MYELOID-LEUKEMIA OF CHILDHOOD - A PEDIATRIC ONCOLOGY GROUP-STUDY SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; ACUTE MYELOBLASTIC-LEUKEMIA; ACUTE NONLYMPHOCYTIC LEUKEMIA; MIXED LINEAGE LEUKEMIA; HUMAN-BONE MARROW; MONOCLONAL-ANTIBODIES; DIFFERENTIATION ANTIGENS; HEMATOPOIETIC DIFFERENTIATION; PROGNOSTIC-SIGNIFICANCE; LYMPHOCYTIC-LEUKEMIA C1 JOHNS HOPKINS UNIV HOSP,CTR ONCOL,BALTIMORE,MD 21205. UNIV FLORIDA,PEDIAT ONCOL GRP,STAT OFF,GAINESVILLE,FL 32611. WAYNE STATE UNIV,SCH MED,DETROIT,MI 48201. BAYLOR COLL MED,HOUSTON,TX 77030. UNIV TEXAS,HLTH SCI CTR,SW MED SCH,DALLAS,TX 75235. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. EMORY UNIV,SCH MED,ATLANTA,GA 30322. UNIV TENNESSEE CTR HLTH SCI,ST JUDE CHILDRENS RES HOSP,COLL MED,MEMPHIS,TN 38163. FU NCI NIH HHS [CA-29139, CA-29691, CA-28476] NR 66 TC 50 Z9 52 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 SEP PY 1992 VL 10 IS 9 BP 1419 EP 1429 PG 11 WC Oncology SC Oncology GA JL392 UT WOS:A1992JL39200010 PM 1517785 ER PT J AU NIERENBERG, AA AF NIERENBERG, AA TI THE MEDICAL CONSEQUENCES OF THE SELECTION OF AN ANTIDEPRESSANT SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID FATAL TOXICITY; DEPRESSION; INHIBITORS; BUPROPION; OVERDOSE AB Patients who take antidepressants risk developing adverse drug reactions with medical sequelae. I will review noncardiac adverse drug reactions to antidepressants organized around (1) the effect of antidepressants on neurotransmitter systems and monoamine oxidase along with effects on concomitant physiologic systems, (2) side effects that are seen clinically but may or may not be related to antidepressant effects on neurotransmitter systems, (3) medical conditions that affect the choice of certain antidepressants, (4) antidepressant toxicity with overdose, and (5) recommendations for using antidepressants with the least probability of causing severe adverse drug reactions. C1 MASSACHUSETTS GEN HOSP,CLIN PSYCHOPHARMACOL UNIT,DEPRESS RES PROGRAM,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. RP NIERENBERG, AA (reprint author), MCLEAN HOSP,TREATMENT RESISTANT DEPRESS PROGRAM,115 MILL ST,BELMONT,MA 02178, USA. NR 34 TC 6 Z9 6 U1 0 U2 1 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD SEP PY 1992 VL 53 SU S BP 19 EP 24 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA JP332 UT WOS:A1992JP33200003 PM 1522076 ER PT J AU KALIN, NH SHELTON, SE SNOWDON, CT AF KALIN, NH SHELTON, SE SNOWDON, CT TI AFFILIATIVE VOCALIZATIONS IN INFANT RHESUS MACAQUES (MACACA-MULATTA) SO JOURNAL OF COMPARATIVE PSYCHOLOGY LA English DT Article ID CONTACT CALLS; MONKEYS; SEPARATION; COMMUNICATION; PRIMATE; CUES AB In Experiment 1, infant rhesus monkeys (Macaca mulatta) were separated and then reunited with mothers, united with a male, or placed in an empty cage. Infants girned more when with mothers or the male than when alone. Girns declined over time when infants were united with the male. Coo rates were high when the infant was alone or with the male. Shrieks, barks, and fear-related behavior were higher with the male. In Experiment 2 the vocalizations of infants were examined during separation when alone or when mothers or a male were in the same room. Infants cooed more when mothers or a male were present. Cooing increased over time, with a greater increase in the mothers' presence. Girns were given to both mothers and males, but more were given to mothers. Coos and girns are both affiliative vocalizations but are differentially modulated as infants cease cooing when they receive contact comfort. C1 UNIV WISCONSIN,DEPT PSYCHOL,MADISON,WI 53792. WILLIAM S MIDDLETON MEM VET ADM MED CTR,PSYCHIAT SERV,MADISON,WI 53705. RP KALIN, NH (reprint author), UNIV WISCONSIN,DEPT PSYCHIAT,ROOM D6-250,CLIN SCI CTR,MADISON,WI 53792, USA. FU NIMH NIH HHS [MH 00-177, MH 29-775, MH 46-983] NR 21 TC 23 Z9 23 U1 0 U2 0 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 SEP PY 1992 VL 106 IS 3 BP 254 EP 261 DI 10.1037//0735-7036.106.3.254 PG 8 WC Behavioral Sciences; Psychology; Psychology, Multidisciplinary; Zoology SC Behavioral Sciences; Psychology; Zoology GA JK696 UT WOS:A1992JK69600006 PM 1395495 ER PT J AU ROGOWSKA, J WOLF, GL AF ROGOWSKA, J WOLF, GL TI TEMPORAL CORRELATION IMAGES DERIVED FROM SEQUENTIAL MR SCANS SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE MAGNETIC RESONANCE IMAGING, TECHNIQUES; MAGNETIC RESONANCE IMAGING, PHYSICS AND INSTRUMENTATION; ANIMAL STUDIES; KIDNEYS AB In this paper a new technique is presented for measuring the local temporal changes and correlation between them on spatially aligned image sequences. A temporal correlation image is derived from a sequence of static images (frames). The method is illustrated in an application to the dynamic MRI of the rabbit kidney following bolus injection of Gd-DTPA. The similarity maps clearly separate the dynamic response of the cortex to the indicator from that of the medulla and, therefore, segment the kidney into two regions. Regions with different temporal dynamics can be displayed in different colors using a lookup table designed for that purpose. RP ROGOWSKA, J (reprint author), MASSACHUSETTS GEN HOSP,CTR IMAGING & PHARMACEUT RES,DEPT RADIOL,BLDG 149,13TH ST,BOSTON,MA 01907, USA. NR 16 TC 23 Z9 23 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD SEP-OCT PY 1992 VL 16 IS 5 BP 784 EP 788 DI 10.1097/00004728-199209000-00021 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA JN448 UT WOS:A1992JN44800021 PM 1522274 ER PT J AU CORNELL, JE YOUNG, DM SEAMAN, SL KIRK, RE AF CORNELL, JE YOUNG, DM SEAMAN, SL KIRK, RE TI POWER COMPARISONS OF 8 TESTS FOR SPHERICITY IN REPEATED MEASURES DESIGNS SO JOURNAL OF EDUCATIONAL STATISTICS LA English DT Article DE SPHERICITY; LIKELIHOOD RATIO TEST; LOCALLY BEST INVARIANT TEST ID MULTISAMPLE SPHERICITY; VALIDITY-CONDITIONS; MULTIVARIATE TESTS; INVARIANT TEST; F-TESTS; COVARIANCE; UNIVARIATE; DISTRIBUTIONS; ROBUSTNESS AB A Monte Carlo simulation was conducted to investigate the relative power of eight tests for sphericity in randomized block designs. Box's (1954) epsilon values of epsilon = .35, .55, .75, .80, .85, .90, .95, and 1.00 were used to quantify departures from sphericity for rank-1 population covariance matrices of dimension p = 3, 5, 7, and 9. Sample covariance matrices were generated for samples of size n = 10, 15, 20, and 30. The locally best invariant test demonstrated substantial power to detect departures from sphericity-regardless of p-for both small and large samples for rank-1 alternatives. Recommendations are made regarding the use of preliminary tests. C1 BAYLOR UNIV,INST GRAD STAT,WACO,TX 76798. RP CORNELL, JE (reprint author), AUDIE L MURPHY MEM VET ADM MED CTR,GERIATR RES EDUC & CLIN CTR 182,7400 MERTON MINTER BLVD,SAN ANTONIO,TX 78284, USA. NR 50 TC 8 Z9 8 U1 1 U2 4 PU AMER EDUCATIONAL RESEARCH ASSOC PI WASHINGTON PA 1230 17TH ST NW, WASHINGTON, DC 20036-3078 SN 0362-9791 J9 J EDUC STAT PD FAL PY 1992 VL 17 IS 3 BP 233 EP 249 DI 10.3102/10769986017003233 PG 17 WC Education & Educational Research; Social Sciences, Mathematical Methods SC Education & Educational Research; Mathematical Methods In Social Sciences GA JL543 UT WOS:A1992JL54300001 ER PT J AU STASHENKO, P YU, SM WANG, CY AF STASHENKO, P YU, SM WANG, CY TI KINETICS OF IMMUNE CELL AND BONE RESORPTIVE RESPONSES TO ENDODONTIC INFECTIONS SO JOURNAL OF ENDODONTICS LA English DT Article ID RAT PERIAPICAL LESIONS; INFLAMMATORY CELLS; MONONUCLEAR-CELLS; ACTIVATING FACTOR; IDENTIFICATION; INTERLEUKIN-1; IDENTITY; INVITRO AB Infection of the dental pulp stimulates a host immune response in the periapical region (the periapical ''lesion'') with the concomitant resorption of bone. The cell composition of human or rat periapical lesions is mixed, consisting of T, B, and ''null'' lymphocytes, plasma cells, macrophages, polymorphonuclear leukocytes, and mast cells. Cells are thus present which mediate a broad spectrum of immunological phenomena. In order to determine which of these mechanisms contribute to periapical bone resorption, a rat model system has been used in which periapical lesions are induced by pulp exposure and infection from the oral environment. In this model, a rapid period of lesion expansion and bone destruction occurs between days 1 and 15 after exposure (active phase), with a chronic phase characterized by lesion stabilization commencing thereafter. Phenotypic analysis of the cellular infiltrate has shown that T helper cells predominate during the active phase, whereas increased numbers of T suppressor cells are associated with chronicity. Extracts of periapical lesions contain bone-resorbing activity, as determined by the release of Ca-45 from prelabeled rat long bones in organ culture. Higher levels of bone-resorbing activity are present during the active than in the chronic phase. Characterization of bone-resorbing activity indicates the presence of resorptive mediators which are heat labile and protease sensitive and which are distinct from lipopolysaccharide. Preliminary biochemical fractionation indicates that resorptive mediators fractionate in the 15,000- to 60,000-dalton molecular mass range, presumably cytokines such as interleukin 1 and tumor necrosis factor. These studies demonstrate the utility of the rat model for studying mechanisms of periapical lesion pathogenesis and implicate T helper cell-mediated activities, in particular those leading to macrophage activation and cytokine production, in periapical lesion expansion. C1 HARVARD UNIV,SCH DENT MED,CAMBRIDGE,MA 02138. RP STASHENKO, P (reprint author), FORSYTH DENT CTR,DEPT IMMUNOL,140 FENWAY,BOSTON,MA 02115, USA. FU NIDCR NIH HHS [DE-09018] NR 20 TC 53 Z9 56 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0099-2399 J9 J ENDODONT JI J. Endod. PD SEP PY 1992 VL 18 IS 9 BP 422 EP 426 DI 10.1016/S0099-2399(06)80841-1 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA KG638 UT WOS:A1992KG63800001 PM 9796508 ER PT J AU MOLINA, IJ KENNEY, DM ROSEN, FS REMOLDODONNELL, E AF MOLINA, IJ KENNEY, DM ROSEN, FS REMOLDODONNELL, E TI T-CELL LINES CHARACTERIZE EVENTS IN THE PATHOGENESIS OF THE WISKOTT-ALDRICH SYNDROME SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID LYMPHOCYTE SURFACE SIALOGLYCOPROTEIN; MONOCLONAL-ANTIBODY; PRIMARY IMMUNODEFICIENCIES; ANTIGEN; ABNORMALITIES; GLYCOPROTEIN; BIOSYNTHESIS; LEUKOSIALIN; ACTIVATION; PLATELETS AB The Wiskott-Aldrich syndrome (WAS) is a severe immunodeficiency and platelet deficiency disease arising from an X-linked defect. The disease is correctable by transplantation of hematopoietic stem cells, but the product of the defective gene is unidentified and the number of defects in patient blood cells is large. The current hurdle is the need to identify the early pathogenic event(s) that are the cause of other defects. As a step toward this goal, we have generated and examined a panel of interleukin 2-dependent allospecific T cell lines from peripheral lymphocytes of seven WAS patients and five normal individuals. WAS cell lines, like normal lines, undergo vigorous proliferation when challenged with specific allostimulant or with phorbol myristate acetate and ionomycin. Both normal and WAS T cell lines express cell surface molecules CD2, CD3, T cell receptor-alpha/beta human histocompatibility leukocyte antigen class I, CD45 and CD11a, and varying ratios of CD4 and CD8, and are negative for natural killer cell and monocyte surface molecules. WAS T cell lines express CD43 (sialophorin/leukosialin) with molecular weight and in an amount comparable with normal T cell lines. WAS T cell lines thus do not express defects in CD43 (decreased amount, abnormal molecular weight), previously documented in WAS circulating lymphocytes. On the other hand, as detected by scanning electron microscopy, WAS cell lines exhibit severe morphological abnormalities, including decreased size and density of the microvillus surface projections. The morphological abnormalities of WAS T cell lines are similar to, or more extensive than, those previously reported for WAS peripheral lymphocytes, indicating that the generation of morphological (cytoarchitectural) defects is an early pathogenic event in this disease. The findings suggest that the gene that is defective in the WAS encodes a protein that normally functions to maintain or regulate the cytoskeletal structure of blood cells. C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,800 HUNTINGTON AVE,BOSTON,MA 02115. CHILDRENS HOSP MED CTR,DIV IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. FU NHLBI NIH HHS [HL-29583]; NIAID NIH HHS [AI-31541]; NIGMS NIH HHS [GM-37298] NR 27 TC 111 Z9 112 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 SEP 1 PY 1992 VL 176 IS 3 BP 867 EP 874 DI 10.1084/jem.176.3.867 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA JK427 UT WOS:A1992JK42700025 PM 1512549 ER PT J AU LEONG, GB AF LEONG, GB TI A PSYCHIATRIC-STUDY OF PERSONS CHARGED WITH ARSON SO JOURNAL OF FORENSIC SCIENCES LA English DT Article DE PSYCHIATRY; CRIMINALISTICS; ARSON; FIRESETTING; PSYCHOSIS; PYROMANIA; HOMELESSNESS ID PYROMANIA AB A total of 29 court-referred individuals charged with arson were psychiatrically studied. From this pre-trial cohort from a large heterogeneous urban population base, a higher rate of psychosis was found than in other recent studies. However, consistent with these studies was the rarity of the diagnosis of pyromania. An important finding of this study was the substantial number of fires set by individuals who are homeless mentally disordered or substance abusing, or both. C1 UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA 90024. RP LEONG, GB (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,PSYCHIAT SERV B116A12,LOS ANGELES,CA 90073, USA. NR 19 TC 24 Z9 24 U1 0 U2 2 PU AMER SOC TESTING MATERIALS PI W CONSHOHOCKEN PA 100 BARR HARBOR DR, W CONSHOHOCKEN, PA 19428-2959 SN 0022-1198 J9 J FORENSIC SCI JI J. Forensic Sci. PD SEP PY 1992 VL 37 IS 5 BP 1319 EP 1326 PG 8 WC Medicine, Legal SC Legal Medicine GA JY406 UT WOS:A1992JY40600024 PM 1402754 ER PT J AU WILLIAMS, JW ROBERTS, L DISTELL, B SIMEL, DL AF WILLIAMS, JW ROBERTS, L DISTELL, B SIMEL, DL TI DIAGNOSING SINUSITIS BY X-RAY - IS A SINGLE WATERS VIEW ADEQUATE SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE SINUSITIS; RADIOGRAPHY; DIAGNOSIS; INTRAOBSERVER VARIABILITY; INTEROBSERVER VARIABILITY; WATERS VIEW AB Objective: To determine whether a single Waters view (occipitomental) radiograph could be substituted for a four-view sinus series to diagnose sinusitis, and to determine the inter- and intraobserver variabilities for sinus radiography. Design: Radiographs were interpreted by radiologists blinded to the clinical history, and results were recorded on a standardized form. Setting: Veterans Affairs Medical Center. Participants: Staff attending radiologists, an attending radiologist with special training in skull radiology, and a senior radiology resident. Measurements and main results: The agreement between the Waters view and the four-view sinus series was moderate to substantial (simple agreement = 75 - 84%, kappa = 0.5- 0.68). However, agreement varied by sinus and, after correction for chance agreement, was substantial only for the maxillary sinuses (kappa = 0.72 - 0.87). Intraobserver agreement (kappa = 0.72 - 0.84) was superior to interobserver agreement (kappa = 0.49 - 0.59) for the four-view sinus series. Conclusions: Substituting a single Waters view for a four-view sinus series may be an acceptable strategy for diagnosing maxillary sinusitis. RP WILLIAMS, JW (reprint author), AUDIE L MURPHY MEM VET ADM MED CTR,11C,7400 MERTON MINTON BLVD,SAN ANTONIO,TX 78284, USA. RI Williams, Jr., John/A-3696-2008 OI Williams, Jr., John/0000-0002-5267-5558 NR 0 TC 34 Z9 36 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 SEP-OCT PY 1992 VL 7 IS 5 BP 481 EP 485 DI 10.1007/BF02599447 PG 5 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA JN983 UT WOS:A1992JN98300002 PM 1403202 ER PT J AU REPKE, H GABUZDA, D PALU, G EMMRICH, F SODROSKI, J AF REPKE, H GABUZDA, D PALU, G EMMRICH, F SODROSKI, J TI EFFECTS OF CD4 SYNTHETIC PEPTIDES ON HIV TYPE-I ENVELOPE GLYCOPROTEIN FUNCTION SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; RECOMBINANT SOLUBLE CD4; SYNCYTIUM FORMATION; BINDING-SITE; MEMBRANE-FUSION; GP120 BINDING; INFECTION; RECEPTOR; BLOCKS; CELLS AB Benzylated derivatives of a peptide (CD4(81-92)) representing the CDR3-like region of CD4 were previously found to inhibit gp120 binding, HIV-1 infectivity, and syncytium formation. These results have been interpreted to indicate a role for the corresponding CD4 region in these processes. The peptide (T(b)YIC(b)E(b)VEDQK(Ac)EE) is the prototype of a series of similar CD4(81-92) derivatives. We report that this peptide noncompetitively inhibits binding to CD4 of both gp120 and a mAb (MAX.16H5), both of which recognize the CDR2-like region of CD4. The binding of an antibody (Leu 3a) that is directed against a different area of the D1 domain of CD4 was also inhibited. The peptide derivative inhibited both HIV-1- and HTLV-1-mediated syncytium formation in the same concentration range. Nonbenzylated cyclic and linear peptides representing the CDR3-like region of CD4 (CD4(84-101)) had only minor effects on gp120 binding which were not sequence specific. The results of this study suggest that the effects of benzylated CD4(81-92) derivatives on HIV-1 binding or fusion should not be used to reach conclusions about the function of the corresponding CD4 region. C1 UNIV PADUA,INST MICROBIOL,I-35100 PADUA,ITALY. MAX PLANCK SOC,CLIN RES UNIT RHEUMATOL,ERLANGEN,GERMANY. RP REPKE, H (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HUMAN RETROVIROL,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [P30 CA 06516]; NIAID NIH HHS [AI 24755, P30 AI 28691] NR 41 TC 28 Z9 28 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 1992 VL 149 IS 5 BP 1809 EP 1816 PG 8 WC Immunology SC Immunology GA JJ890 UT WOS:A1992JJ89000047 PM 1354681 ER PT J AU GOLDEN, MP KIM, SY HAMMER, SM LADD, EA SCHAFFER, PA DELUCA, N ALBRECT, MA AF GOLDEN, MP KIM, SY HAMMER, SM LADD, EA SCHAFFER, PA DELUCA, N ALBRECT, MA TI ACTIVATION OF HUMAN-IMMUNODEFICIENCY-VIRUS BY HERPES-SIMPLEX VIRUS SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID LONG TERMINAL REPEAT; ALPHA-PROTEIN ICP27; GENE-EXPRESSION; DELETION MUTANTS; REGULATORY PROTEIN-ICP4; RNA-SYNTHESIS; TYPE-1 ICP27; TRANS; CELLS; TRANSACTIVATION AB Heterologous viruses have been examined for their ability to accelerate the course of infection with the human immunodeficiency virus (HIV) type 1. In this study, ACH-2 cells persistently infected with HIV-1 exhibited augmented HIV-1 replication as a result of superinfection with herpes simplex virus (HSV) type 1. Using HSV-1 mutants with deletions in the genes encoding immediate-early proteins ICP0, ICP4, and ICP27, it was found that ICP0 and ICP27, but not ICP4, were essential for up-regulation of HIV replication. Northern blot analysis showed that this activation of HIV was characterized by an initial rise in the level of the small, subgenomic (2.0 and 4.3 kb) mRNA species, followed by an increase in the level of unspliced genomic (9.2 kb) mRNA. Such a shift in transcriptional phase recapitulates the early-to-late transition seen in single-step growth curves of acute HIV-1 infection. Thus, HSV can activate HIV-1 from latency in ACH-2 cells. this activation of HIV is independent of productive HSV replication since the DELTA-ICP4 deletion mutant is replication-incompetent, and this activation is evident as an increase in the steady-state levels of HIV transcripts. C1 NEW ENGLAND DEACONESS HOSP,DANA FARBER CANC INST,DEPT INFECT DIS,DIV INFECT DIS,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA 02115. FU NHLBI NIH HHS [HL-43510]; NIAID NIH HHS [AI-01015, AI-30897] NR 39 TC 96 Z9 97 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 SEP PY 1992 VL 166 IS 3 BP 494 EP 499 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA JK029 UT WOS:A1992JK02900005 PM 1354237 ER PT J AU PLATT, R ZUCKER, JR ZALEZNIK, DF HOPKINS, CC DELLINGER, EP KARCHMER, AW BRYAN, CS BURKE, JF WIKLER, MA MARINO, SK HOLBROOK, KF TOSTESON, TD AF PLATT, R ZUCKER, JR ZALEZNIK, DF HOPKINS, CC DELLINGER, EP KARCHMER, AW BRYAN, CS BURKE, JF WIKLER, MA MARINO, SK HOLBROOK, KF TOSTESON, TD TI PROPHYLAXIS AGAINST WOUND-INFECTION FOLLOWING HERNIORRHAPHY OR BREAST SURGERY SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article AB The effect of perioperative antibiotic prophylaxis on definite wound infections was assessed for 3202 herniorrhaphies or selected breast surgery procedures. Patients were identified preoperatively and monitored for greater-than-or-equal-to 4 weeks. Thirty-four percent of patients (1077/3202) received prophylaxis at the discretion of the surgeon; 86 definite wound infections (2.7%) were identified. Prophylaxis recipients were at higher risk for infection, with a higher proportion of mastectomies, longer procedures, and other factors. Patients who received prophylaxis experienced 41% fewer definite wound infections (odds ratio [OR], 0.59; 95% confidence interval [CI], 0.35-0.99; P = .04) and 65% fewer definite wound infections requiring parenteral antibiotic therapy (OR, 0.35; 95% Cl, 0.15-0.88; P = .02) after adjustment for duration of surgery and type of procedure. Additional adjustment for age, body mass index, the presence of drains, diabetes, and exposure to corticosteroids did not change the magnitude of this effect meaningfully. The effect of prophylaxis was similar for all procedures studied. In the absence of formal guidelines, surgeons at these institutions administered prophylaxis preferentially to patients at highest risk. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. HARVARD UNIV,SCH MED,INFECT CONTROL UNIT,BOSTON,MA 02115. BETH ISRAEL HOSP,DEPT MED,BOSTON,MA 02215. BETH ISRAEL HOSP,INFECT CONTROL UNIT,BOSTON,MA 02215. NEW ENGLAND DEACONESS HOSP,DEPT MED,BOSTON,MA 02215. NEW ENGLAND DEACONESS HOSP,INFECT CONTROL UNIT,BOSTON,MA 02215. MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,INFECT CONTROL UNIT,BOSTON,MA 02114. UNIV WASHINGTON,DEPT SURG,SEATTLE,WA 98195. UNIV WASHINGTON,HARBORVIEW MED CTR,SEATTLE,WA 98104. UNIV S CAROLINA,DEPT MED,COLUMBIA,SC 29208. SK&F LABS,DIV ANTIINFECT,PHILADELPHIA,PA 19101. RP PLATT, R (reprint author), BRIGHAM & WOMENS HOSP,CHANNING LAB,DEPT MED,180 LONGWOOD AVE,BOSTON,MA 02115, USA. NR 8 TC 53 Z9 54 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 SEP PY 1992 VL 166 IS 3 BP 556 EP 560 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA JK029 UT WOS:A1992JK02900015 PM 1500739 ER PT J AU SIBER, GR THOMPSON, C FLEISHER, G AF SIBER, GR THOMPSON, C FLEISHER, G TI DETOXIFICATION OF MENINGOCOCCAL ENDOTOXIN BY POLYMYXIN-B - REPLY SO JOURNAL OF INFECTIOUS DISEASES LA English DT Letter C1 HARVARD UNIV,CHILDRENS HOSP,SCH MED,DIV EMERGENCY MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV INFECT DIS,BOSTON,MA 02115. NR 6 TC 1 Z9 1 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD SEP PY 1992 VL 166 IS 3 BP 682 EP 683 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA JK029 UT WOS:A1992JK02900043 ER PT J AU PREZIOSO, JA FITZGERALD, GB WICK, MM AF PREZIOSO, JA FITZGERALD, GB WICK, MM TI MELANOMA CYTOTOXICITY OF BUTHIONINE SULFOXIMINE (BSO) ALONE AND IN COMBINATION WITH 3,4-DIHYDROXYBENZYLAMINE AND MELPHALAN SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID MURINE TUMOR-CELLS; L-PHENYLALANINE MUSTARD; CYTO-TOXICITY; GLUTATHIONE SYNTHESIS; CELLULAR GLUTATHIONE; L-DOPA; ANALOGS; 5-S-CYSTEINYLDOPA; INHIBITION; TYROSINASE AB Buthionine sulfoximine (BSO), a specific inhibitor of glutathione synthesis, showed variable growth-inhibitory activity in different tumor cell lines with a high degree of inhibitory activity against melanoma-derived cell lines. A correlation between BSO growth-inhibitory effects and cellular glutathione peroxidase activity was observed. In contrast no correlation was demonstrated between the response to BSO and cellular tyrosinase, gamma-glutamylcysteine synthetase, glutathione transferase, gamma-glutamyl transpeptidase, or glutathione reductase activities. BSO enhanced 3,4-dihydroxybenzylamine (3,4-DHBA) (fourfold) and melphalan (threefold) in vitro cytotoxic activity as determined by inhibition of DNA synthesis in human melanoma cells and this enhancement was dependent on the duration of exposure to drug. BSO demonstrated in vivo antitumor activity in B16 melanoma-bearing mice prolonging survival by 29% and in combination with 3,4-DHBA resulted in a slight (48% versus 38%) increase in life span as compared to 3,4-DHBA alone. The combination of BSO and melphalan, however, increased the life span of B16 melanoma-bearing mice by 170%, as compared to melphalan alone (80%). These studies demonstrate a unique in vivo antimelanoma activity of BSO. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,MOLEC DERMATOL ONCOL LAB,44 BINNEY ST,ROOM 1720,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT DERMATOL,BOSTON,MA 02115. FU NCI NIH HHS [CA24988] NR 35 TC 32 Z9 32 U1 0 U2 1 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 SEP PY 1992 VL 99 IS 3 BP 289 EP 293 DI 10.1111/1523-1747.ep12616629 PG 5 WC Dermatology SC Dermatology GA JL546 UT WOS:A1992JL54600008 PM 1512464 ER PT J AU PUGLIESE, A EISENBARTH, GS AF PUGLIESE, A EISENBARTH, GS TI TYPE-I DIABETES-MELLITUS - LESSONS FOR HUMAN AUTOIMMUNITY SO JOURNAL OF LABORATORY AND CLINICAL MEDICINE LA English DT Article ID INSULIN; SUSCEPTIBILITY; PROGRESSION; RELATIVES C1 HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,IMMUNOL & IMMUNOGENET SECT,1 JOSLIN PL,BOSTON,MA 02115. NR 21 TC 5 Z9 5 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0022-2143 J9 J LAB CLIN MED JI J. Lab. Clin. Med. PD SEP PY 1992 VL 120 IS 3 BP 363 EP 366 PG 4 WC Medical Laboratory Technology; Medicine, General & Internal; Medicine, Research & Experimental SC Medical Laboratory Technology; General & Internal Medicine; Research & Experimental Medicine GA JM663 UT WOS:A1992JM66300007 PM 1517681 ER PT J AU BRYAN, CL CAMPBELL, GD LAWRENCE, RA JENKINSON, SG AF BRYAN, CL CAMPBELL, GD LAWRENCE, RA JENKINSON, SG TI DIPHOSPHORYL LIPID-A PROTECTS RATS FROM LETHAL HYPEROXIA SO JOURNAL OF LABORATORY AND CLINICAL MEDICINE LA English DT Article ID TUMOR NECROSIS FACTOR; ENDOGENOUS ANTIOXIDANT ENZYMES; NON-TOXIC FORMS; OXYGEN-TOXICITY; BACTERIAL-ENDOTOXIN; CHEMICAL-STRUCTURE; DEFICIENT RATS; LUNG INJURY; MICE AB Bacterial endotoxin has been shown to protect rats from lethal hyperoxia. The structure of endotoxin contains diphosphoryl lipid A (DPL) as the lipid backbone stripped of protein and polysoccharides. DPL is the component of the endotoxin molecule that has been demonstrated (in previous studies) to be responsible for the immunologic, mitogenic, pyrogenic, and lethal properties of endotoxin. Monophosphoryl lipid A (MPL) is a nonpyrogenic, nontoxic modification of the DPL molecule that retains its immunostimulatory and mitogenic properties. We hypothesized that DPL may be the actual active component of endotoxin that protects rats from lethal hyperoxia. We also hypothesized that the protection from hyperoxic that is afforded by the DPL component may be related to endogenous release of tumor necrosis factor-alpha which should allow MPL to also be protective. To test these hypotheses, we performed a series of experiments in which rats were treated with endotoxin, DPL, MPL or vehicle and exposed to room air or hyperoxia. We found that DPL and endotoxin both protected rats from lethal hyperoxia, but MPL alone was not protective. Even though MPL was not protective, DPL and MPL both increased endogenous release of tumor necrosis factor-alpha early after injection (peak DPL level, 3619 +/- 1500 pg/ml, peak MPL level, 4038 +/- 500 pg/ml). Protection in both the endotoxin- and DPL-treated animals was associated with increases in lung antioxidant enzyme activities. We concluded that DPL protects rats from hyperoxic but that MPL is not protective in spite of its immunostimulatory and mitogenic effects. C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED PULM DIS CRIT CARE,SAN ANTONIO,TX 78284. MCCLELLAN VET ADM HOSP,LITTLE ROCK,AR. RP BRYAN, CL (reprint author), AUDIE L MURPHY MEM VET ADM MED CTR,PULM DIS SECT 111E,7400 MERTON MINTER BLVD,SAN ANTONIO,TX 78284, USA. NR 26 TC 2 Z9 3 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0022-2143 J9 J LAB CLIN MED JI J. Lab. Clin. Med. PD SEP PY 1992 VL 120 IS 3 BP 444 EP 452 PG 9 WC Medical Laboratory Technology; Medicine, General & Internal; Medicine, Research & Experimental SC Medical Laboratory Technology; General & Internal Medicine; Research & Experimental Medicine GA JM663 UT WOS:A1992JM66300018 ER PT J AU VOLOVSEK, A SUBRAMANIAN, R REBOUSSIN, D AF VOLOVSEK, A SUBRAMANIAN, R REBOUSSIN, D TI EFFECTS OF DURATION OF ISCHEMIA DURING PRECONDITIONING ON MECHANICAL FUNCTION, ENZYME-RELEASE AND ENERGY-PRODUCTION IN THE ISOLATED WORKING RAT-HEART SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE PRECONDITIONING; ISCHEMIA; REPERFUSION; MYOCARDIAL ENZYMES; ADENINE NUCLEOTIDES; ISOLATED RAT HEART ID MYOCARDIAL PROTECTION; ISCHEMIC MYOCARDIUM; REPERFUSION; METABOLISM; GLYCOGEN; DAMAGE C1 WILLIAM S MIDDLETON MEM VET ADM MED CTR, DEPT PATHOL & LAB MED, MADISON, WI 53705 USA. UNIV WISCONSIN, SCH MED, MADISON, WI 53706 USA. UNIV WISCONSIN, DEPT STAT, MADISON, WI 53706 USA. NR 27 TC 45 Z9 45 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD SEP PY 1992 VL 24 IS 9 BP 1011 EP 1019 DI 10.1016/0022-2828(92)91867-5 PG 9 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA JR559 UT WOS:A1992JR55900008 PM 1433317 ER PT J AU VILENSKY, JA MOORE, AM EIDELBERG, E WALDEN, JG AF VILENSKY, JA MOORE, AM EIDELBERG, E WALDEN, JG TI RECOVERY OF LOCOMOTION IN MONKEYS WITH SPINAL-CORD LESIONS SO JOURNAL OF MOTOR BEHAVIOR LA English DT Article DE MOTOR CONTROL; PRIMATES; SPINAL CORD; STEPPING ID CATS; BEHAVIOR; GAIT; SIZE AB This study reanalyzes kinematically (via film) the pre- and postoperative locomotor behavior of 4 of the 10 monkeys with partial spinal cord lesions (T8) briefly described by Eidelberg, Walden, and Nguyen (1981). The behavior of the remaining 6 monkeys is qualitatively described. The analysis reveals that 5 of the animals initially exhibited unilateral hind limb stepping. Hind and forelimb cycle durations often differed postoperatively; the hind limbs commonly showed increased values, whereas forelimb cycle durations were reduced. Ipsilateral interlimb phase values were usually inconsistent. A review of prior studies of primate spinal cord lesions indicates that sparing of the ventrolateral quadrant may not be essential for locomotor recovery (cf. Eidelberg, Walden, and Nguyen, 1981). Furthermore, this review as well as the kinematic analysis indicates that primates with very significant spinal lesions can still exhibit locomotor movements. Thus, although the primate's spinal cord seems less able than other mammals' to readily organize locomotor movements (Eidelberg, Walden, & Nguyen, 1981), the total absence of stepping in primates with completely transected cords is unexpected and warrants further research. C1 INDIANA UNIV,SCH MED,DEPT ANAT,INDIANAPOLIS,IN 46202. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DIV NEUROSURG,SAN ANTONIO,TX 78284. NR 33 TC 47 Z9 50 U1 0 U2 0 PU HELDREF PUBLICATIONS PI WASHINGTON PA 1319 EIGHTEENTH ST NW, WASHINGTON, DC 20036-1802 SN 0022-2895 J9 J MOTOR BEHAV JI J. Mot. Behav. PD SEP PY 1992 VL 24 IS 3 BP 288 EP 296 PG 9 WC Neurosciences; Psychology; Psychology, Experimental; Sport Sciences SC Neurosciences & Neurology; Psychology; Sport Sciences GA JN510 UT WOS:A1992JN51000007 ER PT J AU KOBLER, JB GUINAN, JJ VACHER, SR NORRIS, BE AF KOBLER, JB GUINAN, JJ VACHER, SR NORRIS, BE TI ACOUSTIC REFLEX FREQUENCY-SELECTIVITY IN SINGLE STAPEDIUS MOTONEURONS OF THE CAT SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID AUDITORY-NERVE FIBERS; CHRONIC COCHLEAR PATHOLOGY; TUNING CURVES; STEREOCILIA DAMAGE; MUSCLE; THRESHOLDS; KETAMINE; TAILS; LEVEL AB 1. The sound frequency selectivities of single stapedius motoneurons were investigated in ketamine anesthetized and in decerebrate cats by recording from axons in the small nerve fascicles entering the stapedius muscle. 2. Stapedius motoneuron tuning curves (TCs) were very broad, similar to the tuning of the overall acoustic reflexes as determined by electromyographic recordings. The lowest thresholds were usually for sound frequencies between 1 and 2 kHz, although many TCs also had a second sensitive region in the 6- to 12-kHz range. The broad tuning of stapedius motoneurons implies that inputs derived from different cochlear frequency regions (which are narrowly tuned) must converge at a point central to the stapedius motoneuron outputs, possibly at the motoneuron somata. 3. There were only small differences in tuning among the four previously described groups of stapedius motoneurons categorized by sensitivity to ipsilateral and contralateral sound. The gradation in high-frequency versus low-frequency sensitivity across motoneurons suggests there are not distinct subgroups of stapedius motoneurons, based on their TCs. 4. The thresholds and shapes of stapedius motoneuron TCs support the hypothesis that the stapedius acoustic reflex is triggered by summed activity of low-spontaneous-rate auditory nerve fibers with both low and high characteristic frequencies (CFs). Excitation of high-CF auditory nerve fibers by sound in their TC "tails" is probably an important factor in eliciting the reflex. 5. In general, the most sensitive frequency for stapedius motoneurons is higher than the frequency at which stapedius contractions produce the greatest attenuation of middle ear transmission. We argue that this is true because the main function of the stapedius acoustic reflex is to reduce the masking of responses to high-frequency sounds produced by low-frequency sounds. C1 MASSACHUSETTS EYE & EAR INFIRM,EATON PEABODY LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT ANAT & CELLULAR BIOL,BOSTON,MA 02115. MIT,DEPT ELECT ENGN & COMP SCI,CAMBRIDGE,MA 02139. MIT,ELECTR RES LAB,CAMBRIDGE,MA 02139. FU FIC NIH HHS [3 FO5 TWO3605-01S1]; NIDCD NIH HHS [P01 DC-00119] NR 37 TC 21 Z9 21 U1 1 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD SEP PY 1992 VL 68 IS 3 BP 807 EP 817 PG 11 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA JP925 UT WOS:A1992JP92500014 PM 1432049 ER PT J AU ASSAD, JA COREY, DP AF ASSAD, JA COREY, DP TI AN ACTIVE MOTOR MODEL FOR ADAPTATION BY VERTEBRATE HAIR-CELLS SO JOURNAL OF NEUROSCIENCE LA English DT Article ID TRANSDUCTION CHANNELS; MECHANOELECTRICAL TRANSDUCTION; BULLFROGS SACCULUS; MECHANICAL STIMULATION; CALCIUM; BUNDLE; STEREOCILIA; DISPLACEMENT; SENSITIVITY; DEPENDENCE AB Bullfrog saccular hair cells adapt to maintained displacements of their stereociliary bundles by shifting their sensitive range, suggesting an adjustment in the tension felt by the transduction channels. It has been suggested that steady-state tension is regulated by the balance of two calcium-sensitive processes: passive "slipping" and active "tensioning." Here we propose a mathematical model for an adaptation motor that regulates tension, and describe some quantitative tests of the model. Slipping and tensioning rates were determined at membrane potentials of -80 and +80 mV. With these, the model predicts that the I(X) curve (relating bundle displacement and channel open probability) should shift negatively by 124 nm when the cell is depolarized, with an exponential time course that is slower on depolarization from -80 to +80 mV than on repolarization. This was observed: on depolarization, the I(X) curve shifted by an average of 139 nm, and displayed the expected difference in rates at the two potentials. Because the negative shift of the I(X) curve on depolarization represents an increase in the tension on transduction channels, the model also predicts this tension should cause an unrestrained bundle to pivot negatively by 99 nm on depolarization. Such movement was observed using high-resolution video microscopy; its amplitude was variable but ranged up to about 100 nm, and its time course was asymmetric in the same way as that of the I(X) curve shift. In additional comparisons, the active bundle movements and I(X) curve shift exhibited a similar steady-state voltage dependence, and were both reversibly abolished by reduced bath Ca2+ or by the transduction channel blocker streptomycin. Lastly, among different cells, the amplitude of the movement increased with the size of the transduction current. Thus, a quantitative mechanical model for adaptation also accounts for the observed mechanical behavior of the bundle, suggesting that the same mechanism is responsible for both, and that adaptation is mediated by an active, force-producing mechanism. C1 MASSACHUSETTS GEN HOSP,HOWARD HUGHES MED INST,WELLMAN 414,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT NEUROBIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02115. OI Corey, David/0000-0003-4497-6016 FU NIDCD NIH HHS [DC00304] NR 47 TC 183 Z9 184 U1 3 U2 5 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD SEP PY 1992 VL 12 IS 9 BP 3291 EP 3309 PG 19 WC Neurosciences SC Neurosciences & Neurology GA JN807 UT WOS:A1992JN80700001 PM 1527581 ER PT J AU ARONIN, N DIFIGLIA, M AF ARONIN, N DIFIGLIA, M TI THE SUBCELLULAR-LOCALIZATION OF THE G-PROTEIN-G(I-ALPHA) IN THE BASAL GANGLIA REVEALS ITS POTENTIAL ROLE IN BOTH SIGNAL TRANSDUCTION AND VESICLE TRAFFICKING SO JOURNAL OF NEUROSCIENCE LA English DT Article ID GTP-BINDING PROTEIN; GUANINE-NUCLEOTIDE-BINDING; BETA-ADRENERGIC RECEPTORS; RAT-BRAIN; ALPHA-SUBUNITS; DOPAMINE RECEPTOR; SYNAPTIC VESICLES; CHOLINERGIC NEURONS; MONKEY NEOSTRIATUM; MOLECULAR-CLONING AB The G-protein G(i) is known to mediate signal transduction in cells by coupling its 41 kDa alpha-subunit to plasma membrane-bound receptors and inhibiting adenylyl cyclase or affecting ion channel function. Although this G-protein has been functionally associated with D2/dopamine and mu-opioid receptors in striatal membranes, its localization to neurons of the neostriatum, a brain region rich in adenylyl cyclase activity, has not been established. Light and electron microscopic study of the basal ganglia was conducted using the immunoperoxidase method and an antiserum directed against the alpha-subunit of G(i). In the neostriatum, immunoreactivity was localized to medium-sized spiny and aspiny neurons and axon terminals that formed symmetric synapses. Some astrocytes and glial processes that encapsulated axospinous complexes were also labeled. Immunoreactive axon terminals were numerous in the globus pallidus and substantia nigra, where they exhibited a dense pattern of distribution characteristic of neostriatal spiny projection neurons. G(i)alpha immunoreactivity was distributed to multiple subcellular compartments. In neostriatal somata and dendrites, labeling was present intermittently along plasma membranes, and on rough and smooth endoplasmic reticulum and microtubules. In axon terminals, reaction product appeared on plasma membranes and heavily labeled the membranes of synaptic vesicles. The presence of G(i)alpha in axon terminals was confirmed in purified synaptosome preparations. G-proteins consistent with the masses of G(o)alpha and G(i)alpha, respectively, were ADP-ribosylated in the presence of pertussis toxin in striatal synaptosomes. Western blot analysis in purified synaptosome preparations of the neostriatum, globus pallidus, and substantia nigra with the same antiserum used in the immunohistochemistry demonstrated a predominant 41 kDa protein corresponding to the molecular mass of G(i)alpha. Immunohistochemical localization of G(i)alpha with the immunogold method in a crude striatal synaptosome preparation showed gold particles associated with synaptic vesicles and plasma membranes. Results provide the first direct evidence that G(i)alpha is localized to medium-sized neostriatal projection neurons and interneurons, where it is likely to function in membrane-bound signal transduction at the postsynaptic and presynaptic level. The presence of G(i)alpha in synaptic vesicle membranes points to another potentially important role for this G-protein in vesicle trafficking, such as that recently shown for smaller-molecular-mass G-proteins. C1 UNIV MASSACHUSETTS,SCH MED,DEPT MED,NEUROENDOCRINE LAB,WORCESTER,MA 01655. MASSACHUSETTS GEN HOSP,DEPT NEUROL,CELLULAR NEUROBIOL LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. UNIV MASSACHUSETTS,SCH MED,DEPT PHYSIOL,WORCESTER,MA 01655. FU NINDS NIH HHS [NS 16367] NR 52 TC 52 Z9 52 U1 0 U2 0 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD SEP PY 1992 VL 12 IS 9 BP 3435 EP 3444 PG 10 WC Neurosciences SC Neurosciences & Neurology GA JN807 UT WOS:A1992JN80700012 PM 1527588 ER PT J AU ROE, AW PALLAS, SL KWON, YH SUR, M AF ROE, AW PALLAS, SL KWON, YH SUR, M TI VISUAL PROJECTIONS ROUTED TO THE AUDITORY PATHWAY IN FERRETS - RECEPTIVE-FIELDS OF VISUAL NEURONS IN PRIMARY AUDITORY-CORTEX SO JOURNAL OF NEUROSCIENCE LA English DT Article ID LATERAL GENICULATE-NUCLEUS; MONKEY STRIATE CORTEX; SINGLE-CELL PROPERTIES; CORTICAL-NEURONS; W-CELLS; SOMATOSENSORY CORTEX; RETINAL PROJECTIONS; OCULAR DOMINANCE; GANGLION-CELLS; ORIENTATION SELECTIVITY AB How does cortex that normally processes inputs from one sensory modality respond when provided with input from a different modality? We have addressed such a question with an experimental preparation in which retinal input is routed to the auditory pathway in ferrets. Following neonatal surgical manipulations, a specific population of retinal ganglion cells is induced to innervate the auditory thalamus and provides visual input to cells in auditory cortex (Sur et al., 1988). We have now examined in detail the visual response properties of single cells in primary auditory cortex (A1) of these rewired animals and compared the responses to those in primary visual cortex (V1) of normal animals. Cells in Al of rewired animals differed from cells in normal V1: they exhibited larger receptive field sizes and poorer visual responsivity, and responded with longer latencies to electrical stimulation of their inputs. However, striking similarities were also found. Like cells in normal V1, A1 cells in rewired animals exhibited orientation and direction selectivity and had simple and complex receptive field organizations. Furthermore, the degree of orientation and directional selectivity as well as the proportions of simple, complex, and nonoriented cells found in A1 and V1 were very similar. These results have significant implications for possible commonalities in intracortical processing circuits between sensory cortices, and for the role of inputs in specifying intracortical circuitry. C1 MASSACHUSETTS GEN HOSP,DEPT BRAIN & COGNIT SCI,BOSTON,MA 02114. FU NEI NIH HHS [EY 06121, EY 07719] NR 96 TC 85 Z9 86 U1 0 U2 5 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD SEP PY 1992 VL 12 IS 9 BP 3651 EP 3664 PG 14 WC Neurosciences SC Neurosciences & Neurology GA JN807 UT WOS:A1992JN80700032 PM 1527604 ER PT J AU SOUTHEE, AE KAPLAN, WD JOCHELSON, MS GONIN, R DWYER, JAP ANTMAN, KH ELIAS, AD AF SOUTHEE, AE KAPLAN, WD JOCHELSON, MS GONIN, R DWYER, JAP ANTMAN, KH ELIAS, AD TI GALLIUM IMAGING IN METASTATIC AND RECURRENT SOFT-TISSUE SARCOMA SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article ID UNRESECTABLE SARCOMA; GA-67; SCINTIGRAPHY; IFOSFAMIDE; MESNA AB Fifty-six patients with metastatic or recurrent soft-tissue sarcoma were evaluated by Ga-67-citrate imaging. Prior to entry on the therapy protocol, 52/56 (93%) patients had true-positive Ga-67 studies. Two of four patients with liposarcoma, one of twelve with leiomyosarcoma and one with an epithelioid sarcoma had false-negative studies; 89/105 disease sites (85%) were Ga-67 positive, including 100% of pleural lesions, 94% in bone, 88% in the abdomen, 85% in soft tissue, 78% in lung parenchyma and 56% of liver metastases. There was significant association between Ga-67 avidity and tumor grade with the exception of mesothelioma. No relationship was seen between Ga-67 avidity and tumor cell type, disease site or lesion size. Following therapy, Ga-67 correctly identified 11/12 sites of active disease in 8/9 patients. Mean pre- and post-therapy Ga-67 avidity scores did not differ significantly. Gallium-67 appears to have an important role in the evaluation of patients presenting with either primary or metastatic soft-tissue sarcoma. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV BIOSTAT & EPIDEMIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,DEPT RADIOL,JOINT PROGRAM NUCL MED,BOSTON,MA 02115. NR 16 TC 22 Z9 23 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 SEP PY 1992 VL 33 IS 9 BP 1594 EP 1599 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA JM032 UT WOS:A1992JM03200007 PM 1517831 ER PT J AU TRIPPEL, SB WHELAN, MC KLAGSBRUN, M DOCTROW, SR AF TRIPPEL, SB WHELAN, MC KLAGSBRUN, M DOCTROW, SR TI INTERACTION OF BASIC FIBROBLAST GROWTH-FACTOR WITH BOVINE GROWTH PLATE CHONDROCYTES SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE BASIC FIBROBLAST GROWTH FACTOR; CHONDROCYTES ID SUBENDOTHELIAL EXTRACELLULAR-MATRIX; HEPARIN-LIKE MOLECULES; FACTOR RECEPTOR; TERMINAL DIFFERENTIATION; ARTICULAR CHONDROCYTES; ENDOTHELIAL-CELLS; HORMONE RECEPTORS; DNA-SYNTHESIS; BINDING; PURIFICATION AB The basic fibroblast growth factor (bFGF) family of peptides influences a wide range of cellular actions. To better understand the possible role of bFGF in the growth plate, we have characterized the interaction of this growth factor with isolated bovine growth plate chondrocytes. Basic FGF interacts with two classes of binding sites on these cells. One is consistent with high-affinity bFGF receptors and the other with low-affinity heparin-like binding sites on the chondrocyte surface. Radiolabeled bFGF binding studies revealed approximately 4 x 10(6) binding sites per cell, with a K(d) of approximately 42 nM. Graded concentrations of heparin or NaCl competed with [I-125]-labeled bFGF in a dose-dependent fashion, reducing [I-125]-labeled bFGF binding by 75 and 97%, respectively. The data suggest the presence of a high-capacity, low-affinity class of binding sites with the properties of a heparin-like moiety. Affinity cross-linking of [I-125]-labeled bFGF to chondrocytes labeled two principal species with apparent molecular masses of 135 and 160 kDa. Labeled bFGF was specifically displaced from both species by subnanomolar concentrations of unlabeled bFGF. These high-affinity, low-capacity binding sites are characteristic of classical bFGF receptors. Binding of [I-125]-labeled bFGF to these sites was also influenced by heparin, consistent with coregulation of binding to the two classes of binding sites. The data suggest that bFGF participates in the regulation of skeletal growth at the growth plate and that this regulation may involve bFGF interaction with at least two distinct classes of C1 HARVARD UNIV,CAMBRIDGE,MA 02138. CHILDRENS HOSP MED CTR,DEPT SURG,BOSTON,MA 02115. RP TRIPPEL, SB (reprint author), MASSACHUSETTS GEN HOSP,DEPT ORTHOPAED,BOSTON,MA 02114, USA. FU NCI NIH HHS [CA-37392]; NIAMS NIH HHS [AR31068] NR 59 TC 11 Z9 11 U1 0 U2 0 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 SN 0736-0266 J9 J ORTHOPAED RES JI J. Orthop. Res. PD SEP PY 1992 VL 10 IS 5 BP 638 EP 646 DI 10.1002/jor.1100100506 PG 9 WC Orthopedics SC Orthopedics GA JJ896 UT WOS:A1992JJ89600005 PM 1323648 ER PT J AU TAUBMAN, MA HAFFAJEE, AD SOCRANSKY, SS SMITH, DJ EBERSOLE, JL AF TAUBMAN, MA HAFFAJEE, AD SOCRANSKY, SS SMITH, DJ EBERSOLE, JL TI LONGITUDINAL MONITORING OF HUMORAL ANTIBODY IN SUBJECTS WITH DESTRUCTIVE PERIODONTAL-DISEASES SO JOURNAL OF PERIODONTAL RESEARCH LA English DT Article DE PERIODONTITIS; ANTIBODY; LONGITUDINAL; DISEASE ACTIVITY ID GINGIVAL CREVICULAR FLUID; LOCALIZED JUVENILE PERIODONTITIS; GENERALIZED SEVERE PERIODONTITIS; HUMAN IMMUNE-RESPONSES; ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; ORAL MICROORGANISMS; SERUM ANTIBODIES; IMMUNOLOGICAL FEATURES; HEALTHY-SUBJECTS; YOUNG-ADULTS AB Fifty-one subjects (16-61 years old) with evidence of prior destructive periodontal disease were monitored clinically and immunologically at bi-monthly intervals for up to 5 yr. Periodontal disease activity, determined as new attachment loss, was detected in 33 of these subjects. Only 4 of 51 subjects failed to show an elevated serum antibody level to any of the 18 subgingival species tested. The antibody level threshold established for periodontally healthy subjects was exceeded most often in diseased subjects with serum antibody to Actinobacillus sp., P gingivalis, E. corrodens, C. concisus, F. nucleatum and P intermedia in that order. In general, most serum antibody levels to subgingival species remained relatively consistent for periods as long as 5 yr. However, major increases and decreases in antibody could be detected to at most one or two species in individual subjects. In addition, prolonged, steady increases and decreases in antibody to specific species could be detected in certain subjects. These findings suggest that major changes occurring in serum antibody may reflect fluctuations in the nature of the infection. Differences were observed in the antibody level to specific species when subjects were divided into subsets on the basis of clinical criteria. These included high levels of antibody to A. actinomycetemcomitans Y4 in LJP and RPP subjects and to A. actinomycetemcomitans 29523 in LJP and GJP subjects. RP TAUBMAN, MA (reprint author), FORSYTH DENT CTR,140 THE FENWAY,BOSTON,MA 02115, USA. FU NIDCR NIH HHS [DE-04881] NR 30 TC 50 Z9 52 U1 0 U2 3 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0022-3484 J9 J PERIODONTAL RES JI J. Periodont. Res. PD SEP PY 1992 VL 27 IS 5 BP 511 EP 521 DI 10.1111/j.1600-0765.1992.tb01825.x PG 11 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA JP639 UT WOS:A1992JP63900008 PM 1403580 ER PT J AU SVIRSKY, MA LANE, H PERKELL, JS WOZNIAK, J AF SVIRSKY, MA LANE, H PERKELL, JS WOZNIAK, J TI EFFECTS OF SHORT-TERM AUDITORY DEPRIVATION ON SPEECH PRODUCTION IN ADULT COCHLEAR IMPLANT USERS SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID POSTLINGUALLY DEAFENED ADULTS; ADVENTITIOUSLY DEAF; FUNDAMENTAL-FREQUENCY; VOICE; INFORMATION; CANDIDATES; FEEDBACK; HEARING; FEMALE AB Speech production parameters of three postlingually deafened adults who use cochlear implants were measured: after 24 h of auditory deprivation (which was achieved by turning the subject's speech processor off); after turning the speech processor back on; and after turning the speech processor off again. The measured parameters included vowel acoustics [F 1, F 2, F 0, sound-pressure level (SPL), duration and H 1-H 2, the amplitude difference between the first two spectral harmonics, a correlate of breathiness] while reading word lists, and average airflow during the reading of passages. Changes in speech processor state (on-to-off or vice versa) were accompanied by numerous changes in speech production parameters. Many changes were in the direction of normalcy, and most were consistent with long-term speech production changes in the same subjects following activation of the processors of their cochlear implants [Perkell et al., J. Acoust. Soc. Am. 91, 2961-2978 (1992)]. Changes in mean airflow were always accompanied by H 1-H 2 (breathiness) changes in the same direction, probably due to underlying changes in laryngeal posture. Some parameters (different combinations of SPL, F 0, H 1-H 2 and formants for different subjects) showed very rapid changes when turning the speech processor on or off. Parameter changes were faster and more pronounced, however, when the speech processor was turned on than when it was turned off. The picture that emerges from the present study is consistent with a dual role for auditory feedback in speech production: long-term calibration of articulatory parameters as well as feedback mechanisms with relatively short time constants. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,BOSTON,MA 02114. NORTHEASTERN UNIV,BOSTON,MA 02115. RP SVIRSKY, MA (reprint author), MIT,ELECTR RES LAB,CAMBRIDGE,MA 02139, USA. RI Svirsky, Mario/A-4160-2008 OI Svirsky, Mario/0000-0002-9238-0682 FU NIDCD NIH HHS [DC00361] NR 43 TC 56 Z9 56 U1 0 U2 5 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD SEP PY 1992 VL 92 IS 3 BP 1284 EP 1300 DI 10.1121/1.403923 PG 17 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA JM605 UT WOS:A1992JM60500008 PM 1401516 ER PT J AU HERZOG, DB KELLER, MB SACKS, NR YEH, CJ LAVORI, PW AF HERZOG, DB KELLER, MB SACKS, NR YEH, CJ LAVORI, PW TI PSYCHIATRIC COMORBIDITY IN TREATMENT-SEEKING ANOREXICS AND BULIMICS SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE COMORBIDITY; ANOREXIA; BULIMIA ID MAJOR AFFECTIVE-DISORDER; EATING DISORDERS; FOLLOW-UP; PERSONALITY-DISORDERS; FAMILY HISTORY; NERVOSA; DEPRESSION; WOMEN; ABUSE; DIAGNOSIS AB Current and lifetime psychiatric diagnoses were compared in 229 female patients seeking treatment for current episodes of anorexia nervosa (N = 41), bulimia nervosa (N = 98) and mixed anorexia nervosa and bulimia nervosa (N = 90). All subjects were interviewed with the Schedule for Affective Disorders and Schizophrenia-Lifetime Version, which was modified to include a section for DSM-III-R eating disorders, the Longitudinal Interval Follow-up Evaluation, and the Structured Interview for DSM-III Personality Disorders. Seventy-three percent of the anorexia nervosa subjects, 60% of the bulimia nervosa subjects, and 82% of the mixed anorexia nervosa and bulimia nervosa subjects had a current comorbid Axis I diagnosis. Major depression was the most commonly diagnosed comorbid disorder. Low rates of alcohol and substances abuse disorder were diagnosed, and personality disorder occurred in a minority of the sample. The subjects with mixed disorder manifested a higher lifetime prevalence of kleptomania than either the anorexics or the bulimics. High levels of comorbidity were noted across the eating disorder samples. Mixed disorder subjects manifested die most comorbid psychopathology and especially warrant further study. C1 BROWN UNIV,DEPT PSYCHIAT,PROVIDENCE,RI 02912. BROWN UNIV,DEPT PSYCHIAT & HUMAN BEHAV,PROVIDENCE,RI 02912. MASSACHUSETTS GEN HOSP,EATING DISORDERS UNIT,BOSTON,MA 02114. RP HERZOG, DB (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,EATING DISORDERS UNIT,ACC 725,15 PARKMAN ST,BOSTON,MA 02114, USA. NR 62 TC 194 Z9 196 U1 2 U2 12 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 SEP PY 1992 VL 31 IS 5 BP 810 EP 818 DI 10.1097/00004583-199209000-00006 PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA JM584 UT WOS:A1992JM58400006 PM 1400111 ER PT J AU NICKMAN, SL AF NICKMAN, SL TI DEBATE - EFFECTS OF WATCHING VIOLENCE SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Letter RP NICKMAN, SL (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD SEP PY 1992 VL 31 IS 5 BP 988 EP 988 DI 10.1097/00004583-199209000-00034 PG 1 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA JM584 UT WOS:A1992JM58400031 PM 1400136 ER PT J AU POWELL, AC GARAN, H MCGOVERN, BA FALLON, JT KRISHNAN, SC RUSKIN, JN AF POWELL, AC GARAN, H MCGOVERN, BA FALLON, JT KRISHNAN, SC RUSKIN, JN TI LOW-ENERGY CONVERSION OF ATRIAL-FIBRILLATION IN THE SHEEP SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID MALIGNANT VENTRICULAR ARRHYTHMIAS; CONCENTRATION-DEPENDENT INCREASE; SINUS RHYTHM; LIDOCAINE CAUSES; DEFIBRILLATION; DOGS; CARDIOVERSION; QUINIDINE; REQUIREMENTS; MAINTENANCE AB Objectives. In this study, the feasibility, efficacy and safety of low energy internal atrial cardioversion were investigated in a sheep model. The relation between the level of energy used for atrial defibrillation and the probability of successful cardioversion was examined. Background. Atrial fibrillation is a common clinical arrhythmia that frequently recurs after termination with high energy external cardioversion. In some patients with drug-refractory and poorly tolerated atrial fibrillation, an automatic implantable cardioverter may prove useful by providing rapid restoration of sinus rhythm. Methods. In 16 pentobarbital-anesthetized sheep, a right atrial spring electrode was implanted percutaneously and a left thoracic cutaneous patch electrode was placed on the thorax. Sustained atrial fibrillation was induced by rapid atrial pacing and terminated by biphasic cathodal shocks synchronized to the R wave of the surface electrocardiogram (ECG). Results. During 768 defibrillation attempts in 16 sheep, the percent of successful cardioversion attempts increased in a dose-response manner, reaching a plateau at the average energy level of 5 J. With greater-than-or-equal-to 1.5 and greater-than-or-equal-to 2.5 J energy levels, cardioversion was achieved, respectively, in >50% and >80% of attempts. Ventricular fibrillation occurred in 18 (2.4%) of 768 cardioversion attempts; in all 18 cases, the shock was poorly synchronized with the ECG R wave. Conclusions. Low energy cardioversion of atrial fibrillation to sinus rhythm is feasible with use of a right atrial spring/cutaneous patch electrode configuration. The percent of successful cardioversion attempts depends on the level of energy output, and there is a risk of ventricular fibrillation if cardioversion is poorly synchronized with ventricular depolarization. C1 MASSACHUSETTS GEN HOSP,CARDIAC UNIT,CARDIAC ARRHYTHMIA SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 31 TC 75 Z9 75 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD SEP PY 1992 VL 20 IS 3 BP 707 EP 711 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA JL257 UT WOS:A1992JL25700028 PM 1512352 ER PT J AU WATTS, DT HOWELL, T PRIEFER, BA AF WATTS, DT HOWELL, T PRIEFER, BA TI GERIATRICIANS ATTITUDES TOWARD ASSISTING SUICIDE OF DEMENTIA PATIENTS SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID EUTHANASIA; MEDICINE; DEATH AB Objective: To identify geriatricians' attitudes toward assisting suicide of dementia patients, with particular reference to the case of janet Adkins/Dr. Kevorkian. Design: Mailed questionnaire survey. Setting: Four distinct geographical regions of the US: Far West, Midwest, Southeast, and Northeast. Participants: All 1,381 ABIM-certified internist geriatricians in the four regions; 727 (52.6%) responded. Main Outcome Measures: Positive, negative, or unsure responses to questionnaire items; comparison of responses be tween geographical regions. Results: Sixty-six percent of respondents felt that Dr. Kevorkian's assistance of Janet Adkins' suicide was not justifiable, while 14% stated it was morally justifiable. Twenty-nine percent felt janet Adkins' decision to commit suicide was morally wrong, while 49% stated it was not morally wrong. If the responding geriatricians themselves were diagnosed as having a dementing illness, 41% would consider suicide a possible option; 39% would not consider suicide. Twenty-six percent favored easing restrictions on physician-assisted suicide of competent dementia patients, while 57% opposed this. If current restrictions were eased, 21% would consider assisting suicide of competent dementia patients, and 66% would not, Respondents' attitudes showed some significant (P less-than-or-equal-to 0.05) variations by geographical region. Where regional differences were observed, respondents in the Midwest tended to show more conservative attitudes toward physician-assisted suicide than those in the Far West and Northeast. Conclusions: Most responding geriatricians would not consider assisting suicide of dementia patients, and most oppose easing restrictions on physician-assisted suicide. Many, however, could accept the (unassisted) suicide of a competent dementia patient, and many would consider suicide themselves if stricken with dementia. C1 MENDOTA MENTAL HLTH INST,MADISON,WI 53704. WILLIAM S MIDDLETON MEM VET ADM MED CTR,CTR GERIATR RES EDUC & CLIN,MADISON,WI 53705. UNIV WISCONSIN,DEPT PSYCHIAT,MADISON,WI 53792. UNIV WISCONSIN,DEPT FAMILY MED & PRACTICE,MADISON,WI 53792. RP WATTS, DT (reprint author), UNIV WISCONSIN,DEPT MED J52,600 HIGHLAND AVE,MADISON,WI 53792, USA. NR 15 TC 18 Z9 18 U1 1 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 1992 VL 40 IS 9 BP 878 EP 885 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA JM869 UT WOS:A1992JM86900004 PM 1512382 ER PT J AU CATALANO, PJ RYAN, LM AF CATALANO, PJ RYAN, LM TI BIVARIATE LATENT VARIABLE MODELS FOR CLUSTERED DISCRETE AND CONTINUOUS OUTCOMES SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE DEVELOPMENTAL TOXICITY; LINEAR MODEL; LITTER EFFECTS; PROBIT MODEL; QUASI-LIKELIHOOD; RANDOM EFFECTS ID LONGITUDINAL DATA-ANALYSIS; DEVELOPMENTAL TOXICITY; TERATOLOGICAL EXPERIMENTS; MULTIPLE ENDPOINTS; RESPONSES; REGRESSION AB We use the concept of a latent variable to derive the joint distribution of a continuous and a discrete outcome, and then extend the model to allow for clustered data. The model Can be parameterized in a way that allows one to write the joint distribution as a product of a standard random effects model for the continuous variable and a correlated probit model for the discrete variable. This factorization suggests a convenient approach to parameter estimation using quasi-likelihood techniques. Our approach is motivated by the analysis of developmental toxicity experiments for which a number of discrete and continuous outcomes are measured on offspring clustered within litters. Fetal weight and malformation data illustrate the results. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. RP CATALANO, PJ (reprint author), HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,BOSTON,MA 02115, USA. RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 NR 27 TC 117 Z9 117 U1 1 U2 12 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD SEP PY 1992 VL 87 IS 419 BP 651 EP 658 DI 10.2307/2290200 PG 8 WC Statistics & Probability SC Mathematics GA JK444 UT WOS:A1992JK44400009 ER PT J AU POSER, CM BENEDIKZ, J HIBBERD, PL AF POSER, CM BENEDIKZ, J HIBBERD, PL TI THE EPIDEMIOLOGY OF MULTIPLE-SCLEROSIS - THE ICELAND MODEL - ONSET-ADJUSTED PREVALENCE RATE AND OTHER METHODOLOGICAL CONSIDERATIONS SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article DE EPIDEMIOLOGY; MULTIPLE SCLEROSIS; ICELAND; ONSET ADJUSTED PREVALENCE; AGE ADJUSTMENT; COMPARISON POPULATIONS; ETHNIC DIVERSITY ID NORTHEAST SCOTLAND; AGE AB The epidemiology of multiple sclerosis (MS) is characterized by the fact that there is an uneven distribution of the disease throughout the world. The two most commonly used indices of its frequency are the incidence and prevalence rates. The incidence rate reflects, to a great extent, the influence of environmental factors in triggering the clinical manifestations of the disease, if it is based upon the actual date of the initiation of symptoms, rather than the date of diagnosis. The prevalence rate is currently based on the date of diagnosis and includes all MS patients who are alive on a particular date, without regard to their ethnic origin, the site and the duration of residence or any other factors that may have influenced the acquisition of the disease. We propose that in order to make the concept of the prevalence rate possibly more meaningful, the term should refer, retrospectively, to all patients whose symptoms eventually led to the diagnosis of MS, even though the diagnosis was not yet established on an earlier prevalence day. In addition, only patients of the same ethnic background who have spent their prepuberal years in the geographical area under study should be included. We are calling this measure the onset-adjusted prevalence rate. Another problem encountered in epidemiological studies of MS relates to the common practice of adjusting prevalence data obtained for age and sex in one area to what is referred to as a "standard" American (or world) population, groups of great ethnic and age diversity. It is also curious that in many studies the bases for comparison of populations are census data obtained many years previously. We suggest that age and sex adjustment should be applied only to similar ethnic groups born and raised under different environmental conditions. We believe that data obtained by calculating an onset-adjusted prevalence rate restricted to a homogeneous group of patients sharing the same environment during the prepuberal years may provide valuable etiological clues. C1 MASSACHUSETTS GEN HOSP,INFECT DIS SECT,BOSTON,MA 02114. HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DEPT MED,BOSTON,MA 02215. UNIV ICELAND,SCH MED,REYKJAVIK,ICELAND. UNIV ICELAND,NEUROL SERV,REYKJAVIK,ICELAND. RP POSER, CM (reprint author), HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DEPT NEUROL,NEUROL UNIT,330 BROOKLING AVE,BOSTON,MA 02215, USA. NR 29 TC 31 Z9 31 U1 0 U2 0 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 SEP PY 1992 VL 111 IS 2 BP 143 EP 152 DI 10.1016/0022-510X(92)90062-P PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA JQ379 UT WOS:A1992JQ37900003 PM 1431981 ER PT J AU MCDOUGAL, WS AF MCDOUGAL, WS TI LATE DECOMPENSATION OF NEOBLADDER - COMMENT SO JOURNAL OF UROLOGY LA English DT Editorial Material RP MCDOUGAL, WS (reprint author), MASSACHUSETTS GEN HOSP,DEPT UROL,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-5347 J9 J UROLOGY JI J. Urol. PD SEP PY 1992 VL 148 IS 3 BP 810 EP 810 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA JL738 UT WOS:A1992JL73800019 ER PT J AU IMBALZANO, AN DELUCA, NA AF IMBALZANO, AN DELUCA, NA TI SUBSTITUTION OF A TATA BOX FROM A HERPES-SIMPLEX VIRUS LATE GENE IN THE VIRAL THYMIDINE KINASE PROMOTER ALTERS ICP4 INDUCIBILITY BUT NOT TEMPORAL EXPRESSION SO JOURNAL OF VIROLOGY LA English DT Article ID IMMEDIATE-EARLY PROTEIN; DNA-BINDING PROPERTIES; TRANSCRIPTIONAL CONTROL SIGNALS; TEMPERATURE-SENSITIVE MUTANTS; MAJOR REGULATORY PROTEIN; GLYCOPROTEIN-C GENE; TYPE-1 LATE GENE; MACROMOLECULAR-SYNTHESIS; INVITRO TRANSCRIPTION; NUCLEOTIDE-SEQUENCE AB The role of cis-acting promoter elements associated with herpes simplex virus type 1 (HSV-1) early and late genes was evaluated during productive infection with regard to activation of gene expression by the HSV-1 transactivator ICP4 and control of temporal regulation. A set of recombinant viruses was constructed such that expression of an HSV-1 early gene, thymidine kinase (tk), was placed under the control of either the tk TATA box or the TATA box from the late gene, glycoprotein C (gC), in the presence or absence of the upstream Sp1 and CCAAT sites normally found in the tk promoter. The presence of Spl sites in the promoter or replacement of the tk TATA box with the gC TATA box resulted in a decreased activation of tk mRNA expression by ICP4. Substitution of the A+T-rich region from the gC TATA box in the context of the remainder of the surrounding tk sequences resulted in a promoter that bound recombinant TATA-binding protein (TBP) better at lower concentrations than the wild-type tk promoter did. These results indicate that tk promoters that are better able to utilize TBP are less responsive to ICP4 activation and suggest that activation by ICP4 involves the general transcription factors that interact with TBP or TBP itself Additionally, all of the viruses expressed tk at early times postinfection, indicating that cis-acting promoter elements that control the level of expression of HSV-1 early and late genes do not determine temporal regulation. C1 HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOLEC GENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. FU NIAID NIH HHS [AI27431] NR 61 TC 35 Z9 35 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 SEP PY 1992 VL 66 IS 9 BP 5453 EP 5463 PG 11 WC Virology SC Virology GA JJ198 UT WOS:A1992JJ19800034 PM 1323706 ER PT J AU MARSHALL, WL DIAMOND, DC KOWALSKI, MM FINBERG, RW AF MARSHALL, WL DIAMOND, DC KOWALSKI, MM FINBERG, RW TI HIGH-LEVEL OF SURFACE CD4 PREVENTS STABLE HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION OF T-CELL TRANSFECTANTS SO JOURNAL OF VIROLOGY LA English DT Article ID AVIAN-LEUKOSIS VIRUS; ENVELOPE GLYCOPROTEIN; MESSENGER-RNA; HTLV-III/LAV; EXPRESSION; HIV; RECEPTOR; PROTEIN; TYPE-1; AIDS AB CD4 is the principal receptor for the human immunodeficiency virus (HIV). We have isolated and studied CD4-expressing tumor cell clones made by expressing CD4 in the T-cell tumor line HSB. Two clones, one designated HSBCD4, a clone expressing low levels of CD4, and the other, HSB10 x CD4, a high-expresser CD4+ clone, were studied for their ability to bind and replicate HIV. In contrast to many other CD4+ cells that down-modulate CD4 following HIV infection, the HSB10 x CD4 clones continued to express high levels of surface CD4 following infection with HIV. Unlike infection of HSBCD4 or many other human CD4+ cells, HIV infection of HSB10 x CD4 clone was short lived: p24 antigen, provirus, or coculturable virus was present for less than 14 days following infection with several strains of HIV-1 or with HIV-2. When infection was initiated by transfection of proviral DNA, high and low CD4 expressers initially produced p24 antigen at approximately the same level. However, high CD4 expressers produced coculturable virus only during the first few days following transfection, whereas low CD4 expressers transfected with HIV continued to produce virus beyond 6 weeks. Monoclonal antibody-mediated down-modulation of CD4 surface expression on HSB10 x CD4 clones permitted these formerly HIV-resistant cells to become persistently infected with HIV. Thus, high concentrations of CD4 on the surface of an HIV-infected cell prevent persistent HIV infection of CD4+ cells. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,INFECT DIS LAB,BOSTON,MA 02115. BAXTER HYLAND DIV,DUARTE,CA 91010. RI Finberg, Robert/E-3323-2010 FU NCI NIH HHS [P30CA0656, CA34979]; NIAID NIH HHS [P30AI28691] NR 44 TC 30 Z9 30 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 1992 VL 66 IS 9 BP 5492 EP 5499 PG 8 WC Virology SC Virology GA JJ198 UT WOS:A1992JJ19800039 PM 1501285 ER PT J AU THALI, M FURMAN, C HELSETH, E REPKE, H SODROSKI, J AF THALI, M FURMAN, C HELSETH, E REPKE, H SODROSKI, J TI LACK OF CORRELATION BETWEEN SOLUBLE CD4-INDUCED SHEDDING OF THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 EXTERIOR ENVELOPE GLYCOPROTEIN AND SUBSEQUENT MEMBRANE-FUSION EVENTS SO JOURNAL OF VIROLOGY LA English DT Article ID PRINCIPAL NEUTRALIZING DOMAIN; HUMAN MONOCLONAL-ANTIBODY; BINDING-SITE; HTLV-III/LAV; HUMAN CD4; RECEPTOR-BINDING; T4 MOLECULE; CHEMICAL SYNTHESIS; HIV-1 INFECTIVITY; AIDS PATIENTS AB The noncovalent association of the gp120 and gp41 envelope glycoproteins of human immunodeficiency virus type 1 (HIV-1) is disrupted by soluble CD4 binding, resulting in shedding of the gp120 exterior envelope glycoprotein. This observation has led to the speculation that interaction of gp120 with the CD4 receptor triggers shedding of the exterior envelope glycoprotein, allowing exposure of gp41 domains necessary for membrane fusion steps involved in virus entry or syncytium formation. To test this hypothesis, a set of HIV-1 envelope glycoprotein mutants were used to examine the relationship of soluble CD4-induced shedding of the gp120 glycoprotein to envelope glycoprotein function in syncytium formation and virus entry. All mutants with a threefold or greater reduction in CD4-binding ability exhibited marked decreases in gp120 shedding in response to soluble CD4, even though several of these mutants exhibited significant levels of envelope glycoprotein function. Conversely, most fusion-defective mutants with wild-type gp120-CD4 binding affinity, including those with changes in the V3 loop, efficiently shed gp120 following soluble CD4 binding. Thus, soluble CD4-induced shedding of gp120 is not a generally useful marker for conformational changes in the HIV-1 envelope glycoproteins necessary for the virus entry or syncytium formation processes. Some gp120 mutants, despite being expressed on the cell surface and capable of efficiently binding soluble CD4, exhibited decreased gp120 shedding. These mutants were still sensitive to neutralization by soluble CD4, indicating that, for envelope glycoproteins exhibiting high affinity for soluble CD4, competitive inhibition may be more important than gp120 shedding for the antiviral effect. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HUMAN RETROVIROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. FU NIAID NIH HHS [AI24755] NR 75 TC 83 Z9 83 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 SEP PY 1992 VL 66 IS 9 BP 5516 EP 5524 PG 9 WC Virology SC Virology GA JJ198 UT WOS:A1992JJ19800042 PM 1501286 ER EF