FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Li, KK Varvares, MA Meara, JG AF Li, KK Varvares, MA Meara, JG TI Descending necrotizing mediastinitis: A complication of dental implant surgery SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK LA English DT Article ID OSSEOINTEGRATED IMPLANTS; ODONTOGENIC INFECTION; FATAL MEDIASTINITIS AB Background. The placement of osseointegrated dental implants is considered a minimally invasive procedure with a low complication rate. Reported complications include local trauma to neurovascular structures, mandible fractures, sinusitis, and localized gingivitis. Major life-threatening complications are extremely rare. Severe infection has not been reported in a review of the English literature. Method. Case study. Results. We present a case of life-threatening deep neck space infection resulting in descending necrotizing mediastinitis following osseointegrated dental implant placement. Treatment included intravenous antibiotics, aggressive neck debridement, and removal of the infected dental implants. Conclusion. Severe infection can result from the placement of dental implants. Principles of treatment include antibiotics, surgical drainage and debridement, and careful assessment and removal of the involved implants. (C) 1996 John Wiley & Sons, Inc. C1 ST LOUIS UNIV,SCH MED,HLTH SCI CTR,DEPT OTOLARYNGOL,ST LOUIS,MO. RP Li, KK (reprint author), HARVARD UNIV,DEPT OTOLARYNGOL,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,243 CHARLES ST,BOSTON,MA 02114, USA. NR 20 TC 16 Z9 16 U1 0 U2 1 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1043-3074 J9 HEAD NECK-J SCI SPEC JI Head Neck-J. Sci. Spec. Head Neck PD MAR-APR PY 1996 VL 18 IS 2 BP 192 EP 196 DI 10.1002/(SICI)1097-0347(199603/04)18:2<192::AID-HED11>3.3.CO;2-N PG 5 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA TX645 UT WOS:A1996TX64500015 PM 8647686 ER PT J AU Egan, BM Hennes, MMI Stepniakowski, KT OShaughnessy, IM Kissebah, AH Goodfriend, TL AF Egan, BM Hennes, MMI Stepniakowski, KT OShaughnessy, IM Kissebah, AH Goodfriend, TL TI Obesity hypertension is related more to insulin's fatty acid than glucose action SO HYPERTENSION LA English DT Article; Proceedings Paper CT 49th Annual Fall Conference and Scientific Sessions of the Council-for-High-Blood-Pressure-Research CY SEP 16-22, 1995 CL NEW ORLEANS, LA SP Council High Blood Pressure Res DE obesity; insulin; glucose; fatty acids, nonesterified ID DEPENDENT DIABETES-MELLITUS; CHRONIC HYPERINSULINEMIA; BLOOD-PRESSURE; PLASMA-GLUCOSE; RESISTANCE; PYRAZINOYLGUANIDINE; METABOLISM; ACTIVATION; MECHANISM; FOREARM AB Although resistance to insulin-mediated glucose disposal has emerged as a link between abdominal obesity and hypertension, abnormalities of nonesterified fatty acid metabolism may play a greater role. Analyses were performed on existing data from 17 abdominally obese subjects (11 hypertensive, 6 normotensive) to determine whether fatty acid concentration and turnover were related to blood pressure independently of hyperinsulinemia and resistance to insulin-mediated glucose disposal. Glucose utilization, fatty acid concentration, and fatty acid turnover were obtained fasting and during euglycemic hyperinsulinemia at 10 and 40 mU . m(-2) . min(-1). Analyses were also performed on another group of 30 subjects with a wide range of risk factors who had blood pressure data as well as glucose and fatty acid measurements during an insulin tolerance test. Fatty acid concentration and turnover were markedly more resistant to suppression by insulin in obese hypertensive than in lean or obese normotensive individuals. In the 17 obese subjects, blood pressure measured at screening, in the laboratory, and over a period of 24 hours correlated significantly with fatty acid concentration and turnover but not with glucose disposal measured during the hyperinsulinemic clamp. These correlations remained significant after fasting insulin, the insulin area under the curve during an oral glucose tolerance test, and glucose disposal during the clamp were controlled for. In the second group of subjects, plasma fatty acids 15 minutes after intravenous insulin also correlated with blood pressure. These correlations remained significant after insulin and an index of sensitivity to insulin-mediated glucose disposal were statistically controlled for. The data indicate that blood pressure is related to the effects of insulin on fatty acid metabolism. The findings raise the possibility that resistance of hormone-sensitive lipase to insulin participates in elevating the blood pressure of abdominally obese hypertensive subjects by increasing fatty acid concentration and turnover. C1 MED UNIV S CAROLINA,DEPT MED,CHARLESTON,SC 29425. MED COLL WISCONSIN,DEPT MED,DIV ENDOCRINOL METAB & CLIN NUTR,MILWAUKEE,WI 53226. UNIV WISCONSIN,DEPT MED,MADISON,WI. UNIV WISCONSIN,DEPT PHARMACOL,MADISON,WI 53706. WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI 53705. RP Egan, BM (reprint author), MED UNIV S CAROLINA,DEPT PHARMACOL,DIV CLIN PHARMACOL,171 ASHLEY AVE,CSB 826H,CHARLESTON,SC 29425, USA. FU PHS HHS [R01-34989, R01-43164] NR 41 TC 57 Z9 60 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0194-911X J9 HYPERTENSION JI Hypertension PD MAR PY 1996 VL 27 IS 3 BP 723 EP 728 PN 2 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA TY065 UT WOS:A1996TY06500045 PM 8613231 ER PT J AU Taplin, ME Frantz, ME Canning, C Ritz, J Blumberg, RS Balk, SP AF Taplin, ME Frantz, ME Canning, C Ritz, J Blumberg, RS Balk, SP TI Evidence against T-cell development in the adult human intestinal mucosa based upon lack of terminal deoxynucleotidyltransferase expression SO IMMUNOLOGY LA English DT Article ID RECEPTOR-GAMMA-DELTA; INTRAEPITHELIAL LYMPHOCYTES; ANTIGEN RECEPTOR; GUT EPITHELIUM; ATHYMIC MICE; ALPHA-BETA; PERIPHERAL-BLOOD; DIFFERENTIATION; GENE; SELECTION AB Several lines of evidence indicate that a subset of murine intestinal intraepithelial lymphocytes (iIEL), particularly those which express the CD8 alpha alpha homodimer, mature extrathymically. This study confirms that a small fraction of adult human iIEL also express the CD8 alpha alpha homodimer and demonstrates that most of these cells in the small intestine are T cells using the alpha beta T-cell receptor (TCR). Whether these cells or other subsets of adult human iIEL mature extrathymically in the intestine was asses sed by measuring the expression of terminal deoxynucleotidyltransferase (TdT), an enzyme expressed exclusively by immature lymphocytes. Very low levels of TdT message could be detected by polymerase chain reaction (PCR) amplification in some iIEL samples. The level of TdT expression was assayed by competitive PCR amplification and compared with thymocytes and peripheral blood lymphocytes. These measurements indicated that the number of immature T cells expressing TdT in the intestinal epithelium was less than one cell per 10(7) lymphocytes. This demonstrates that there are few if any TdT expressing immature T cells in the adult human intestinal mucosa and indicates, therefore, that T-cell development in the intestinal mucosa does not contribute significantly to the T-cell repertoire of the adult human intestine. C1 BETH ISRAEL HOSP,DIV HEMATOL ONCOL,BOSTON,MA 02215. DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DIV GASTROENTEROL,BOSTON,MA 02115. RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NCI NIH HHS [CA41619]; NHLBI NIH HHS [HL 07516]; NIAID NIH HHS [AI33911] NR 35 TC 15 Z9 15 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD MAR PY 1996 VL 87 IS 3 BP 402 EP 407 DI 10.1046/j.1365-2567.1996.496571.x PG 6 WC Immunology SC Immunology GA UB061 UT WOS:A1996UB06100010 PM 8778025 ER PT J AU Rock, KL AF Rock, KL TI A new foreign policy: MHC class I molecules monitor the outside world SO IMMUNOLOGY TODAY LA English DT Review ID HISTOCOMPATIBILITY COMPLEX-MOLECULES; TOXIC LYMPHOCYTES-T; EXOGENOUS ANTIGEN; CELLS RECOGNIZE; MACROPHAGES; INDUCTION; PROTEINS; BETA-2-MICROGLOBULIN; PHAGOCYTOSIS; DEGRADATION AB Although most cells exclusively use their major histocompatibility complex (MHC) class I molecules to present peptides from endogenous proteins, phagocytes also use them to present exogenous antigens. Here, Kenneth Rock describes how this novel antigen-presenting pathway may play an important role in immune surveillance for intracellular bacteria or parasites, as well as for viral infections and tumors affecting somatic tissues. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RP Rock, KL (reprint author), DANA FARBER CANC INST,DIV LYMPHOCYTE BIOL,BOSTON,MA 02115, USA. NR 56 TC 361 Z9 365 U1 2 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0167-5699 J9 IMMUNOL TODAY JI Immunol. Today PD MAR PY 1996 VL 17 IS 3 BP 131 EP 137 DI 10.1016/0167-5699(96)80605-0 PG 7 WC Immunology SC Immunology GA TX680 UT WOS:A1996TX68000009 PM 8820271 ER PT J AU Fenton, MJ Vermeulen, MW AF Fenton, MJ Vermeulen, MW TI Immunopathology of tuberculosis: Roles of macrophages and monocytes SO INFECTION AND IMMUNITY LA English DT Review ID TUMOR-NECROSIS-FACTOR; LIVE MYCOBACTERIUM-TUBERCULOSIS; PHAGOSOME-LYSOSOME FUSION; NITRIC-OXIDE SYNTHASE; DELTA-T-CELLS; COMPLEMENT RECEPTORS; INTERFERON-GAMMA; MANNOSE RECEPTOR; IFN-GAMMA; BACTERICIDAL ACTIVITY C1 MASSACHUSETTS GEN HOSP,PULM RES LAB,PULM & CRIT CARE UNIT,BOSTON,MA 02129. BOSTON UNIV,SCH MED,CTR PULM,BOSTON,MA 02118. FU NHLBI NIH HHS [HL-51957] NR 97 TC 195 Z9 198 U1 0 U2 9 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAR PY 1996 VL 64 IS 3 BP 683 EP 690 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA TX566 UT WOS:A1996TX56600001 PM 8641767 ER PT J AU Perera, PY Qureshi, N Vogel, SN AF Perera, PY Qureshi, N Vogel, SN TI Paclitaxel (taxol)-induced NF-kappa B translocation in murine macrophages SO INFECTION AND IMMUNITY LA English DT Article ID LIPID-A; LIPOPOLYSACCHARIDE ANTAGONISTS; TRANSCRIPTION FACTOR; GENE-EXPRESSION; NUCLEAR FACTOR; PROTEINS; TAXOL; CELLS; SPHAEROIDES; ACTIVATION AB Interaction of bacterial lipopolysaccharide (LPS) with macrophages results in the Induction of a cascade of cytokines that mediate the varied effects of LPS. An early intracellular signaling event that follows receptor engagement is the activation of transcription factor NF-kappa B. NF-kappa B has been shown to be important for the induction of many LPS-inducible cytokine genes, including tumor necrosis factor alpha, interleukin-1 beta, and interleukin-6. Previously, we and others have shown that the antitumor agent paclitaxel (Taxol) is able to mimic bacterial LPS in its ability to activate murine macrophages, In this report, we have extended these findings by demonstrating that paclitaxel, like LPS, is able to stimulate the translocation of primarily p50-p65 heterodimers of NF-kappa B to the nucleus. This activation is dose dependent and requires a concentration of greater than or equal to 5 mu M paclitaxel. The kinetics of NF-kappa B activation by paclitaxel are slower than those of LPS: by 15 min poststimulation, LPS-induced IVF-KB activation was readily detected, whereas the paclitaxel-induced NF-kappa B activation was minimal. Moreover, paclitaxel- and protein-free LPS-induced translocation of NF-kappa B was seen only in macrophages derived from LPS-responsive C3H/OuJ mice and not from the LPS-hyporesponsive C3H/HeJ mice, a finding that is consistent with those of previous genetic studies linking paclitaxel responsiveness to the Lps gene. Finally, the LPS structural antagonist Rhodobacter sphaeroides diphosphoryl lipid A inhibited both LPS- and paclitaxel-induced NF-kappa B activation, suggesting a common receptor component in this activation. C1 UNIFORMED SERV UNIV HLTH SCI,DEPT MICROBIOL & IMMUNOL,BETHESDA,MD 20814. WILLIAM S MIDDLETON MEM VET HOSP,MYCOBACTERIOL RES LAB,MADISON,WI 53705. UNIV WISCONSIN,SCH AGR & LIFE SCI,DEPT BACTERIOL,MADISON,WI 53706. FU NIAID NIH HHS [AI18797]; NIGMS NIH HHS [GM50870] NR 48 TC 61 Z9 62 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAR PY 1996 VL 64 IS 3 BP 878 EP 884 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA TX566 UT WOS:A1996TX56600029 PM 8641795 ER PT J AU Norman, DC Yoshikawa, TT AF Norman, DC Yoshikawa, TT TI Fever in the elderly SO INFECTIOUS DISEASE CLINICS OF NORTH AMERICA LA English DT Article ID UNKNOWN ORIGIN; TEMPERATURE; BACTEREMIA; INFECTIONS; PYREXIA; ADULTS AB Atypical presentation of infection is common in older adults, particularly the very old (80+ years), who are frail and suffer from multiple medical problems, including cognitive impairment. Fever is the cardinal manifestation of infection, but this important diagnostic sign may be blunted or even absent in a significant number of infected elderly patients. This article focuses exclusively on aspects of fever in association with aging and elderly persons. C1 UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA 90073. GEORGE WASHINGTON UNIV,SCH MED,WASHINGTON,DC. US DEPT VET AFFAIRS,WASHINGTON,DC. RP Norman, DC (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,OFF CHIEF STAFF,WILSHIRE & SAWTELLE BLVD,LOS ANGELES,CA 90073, USA. NR 38 TC 48 Z9 48 U1 2 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0891-5520 J9 INFECT DIS CLIN N AM JI Infect. Dis. Clin. North Am. PD MAR PY 1996 VL 10 IS 1 BP 93 EP & DI 10.1016/S0891-5520(05)70288-9 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA UA702 UT WOS:A1996UA70200008 PM 8698997 ER PT J AU Castigli, E Young, F Carossino, AM Alt, FW Geha, RS AF Castigli, E Young, F Carossino, AM Alt, FW Geha, RS TI CD40 expression and function in murine B cell ontogeny SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE B cell precursors; B cell transgenics; lymphoid development; RAG-2-deficient mice ID NECROSIS FACTOR-ALPHA; MOUSE BONE-MARROW; DIFFERENTIATION; PROLIFERATION; MICE; LYMPHOCYTES; ENHANCEMENT; PRECURSORS; CYTOKINES; GROWTH AB The CD40 antigen, a member of the nerve growth factor/tumor necrosis factor receptor family, is expressed on all mature B lymphocytes and plays a crucial role in B cell activation, T cell-dependent antigen-driven isotype switching and germinal center formation, We have analyzed CD40 expression and function during mouse B cell development by examining B cell precursors in normal mice and in transgenic animals in which B cell development is frozen at discrete stages, These models included RAG-2(-/-) mice, and transgenic littermates that express a mu heavy chain and/or the bcl-2 proto-oncogene transgene, CD40 was undetectable at the pro-B cell stage, but was expressed, although at low levels, on pre-B cells, However, pre-B cells failed to respond to CD40 triggering either by expression of CD23 or by proliferation in the presence of IL-4. Overexpression of bcl-2 increased the density of CD40 expression on pre-B cells: these cells respond to CD40 ligation by expressing CD23 and by proliferating in the presence of IL-4. C1 HARVARD UNIV,CHILDRENS HOSP,HOWARD HUGHES MED INST,CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. RP Castigli, E (reprint author), HARVARD UNIV,DIV IMMUNOL,300 LONGWOOD AVE,BOSTON,MA 02115, USA. FU NIAID NIH HHS [AI 3154] NR 20 TC 20 Z9 20 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD MAR PY 1996 VL 8 IS 3 BP 405 EP 411 DI 10.1093/intimm/8.3.405 PG 7 WC Immunology SC Immunology GA TZ608 UT WOS:A1996TZ60800014 PM 8671627 ER PT J AU Teicher, BA Northey, D Yuan, J Frei, E AF Teicher, BA Northey, D Yuan, J Frei, E TI High-dose therapy stem cell support: Comparison of mice and humans SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID COLONY-STIMULATING FACTOR; BONE-MARROW TRANSPLANTATION; HEMATOPOIETIC PROGENITOR CELLS; BREAST-CANCER; CYTO-TOXICITY; INVIVO; INTERLEUKIN-1; CYCLOPHOSPHAMIDE; CHEMOTHERAPY; INVITRO AB A murine high-dose therapy/stem cell support model is described using female BALB/c mice bearing the EMT-6 mammary carcinoma. Peripheral blood cells were prepared in syngeneic donor animals mobilized by treatment with cyclophosphamide and rhG-CSF. The most effective support regimen includes administration of fluid by gavage, rhG-CSF twice per day for 12 days and peripheral blood cells administered i.v. on the day after cytotoxic therapy. Dose escalations of 2.2- to 13-fold over the usual conventional dose were possible in mice treated with single doses of cyclophosphamide, carmustine, melphalan, thiotepa, carboplatin or total body radiation, which compare favorably with dose escalations achievable in humans. Depletion and recovery rates of white blood cells and granulocytes in the mice were similar to those seen in humans. Rapid weight loss is a major factor in limiting further dose escalation. Single high-dose therapy with cyclophosphamide, melphalan, thiotepa and carboplatin, but not 5-fluorouracil, produced longer tumor growth delays than standard regimens of the same drugs. For melphalan and thiotepa, there was a direct correlation between drug dose, tumor growth delay and tumor surviving fraction. With cyclophosphamide, the tumor growth delay with high-dose therapy was greater than expected from the dose increase and the tumor surviving fraction data. (C) 1996 Wiley-Liss, Inc. C1 JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. RP Teicher, BA (reprint author), CHILDRENS HOSP,DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [P01-CA38493] NR 28 TC 9 Z9 9 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD MAR 1 PY 1996 VL 65 IS 5 BP 695 EP 699 DI 10.1002/(SICI)1097-0215(19960301)65:5<695::AID-IJC22>3.0.CO;2-5 PG 5 WC Oncology SC Oncology GA TX822 UT WOS:A1996TX82200022 PM 8598324 ER PT J AU Rogowska, J Batchelder, K Gazelle, GS Halpern, EF Connor, W Wolf, GL AF Rogowska, J Batchelder, K Gazelle, GS Halpern, EF Connor, W Wolf, GL TI Evaluation of selected two-dimensional segmentation techniques for computed tomography quantitation of lymph nodes SO INVESTIGATIVE RADIOLOGY LA English DT Article DE image segmentation; quantitative computed tomography; lymphography ID IMAGE SEGMENTATION AB RATIONALE AND OBJECTIVES. AS contrast agents that selectively target normal lymph nodes are undergoing development and evaluation, it has become important to accurately and reproducibly determine nodal boundaries to study. the agents and determine such values as lymph node area or mean nodal contrast concentration. This study was performed to evaluate the accuracy of different two-dimensional computer segmentation methods, tested on acrylic phantoms constructed to imitate the appearance of lymph nodes surrounded bg fat. METHODS. Five segmentation techniques (manual tracing, semiautomatic local criteria threshold selection, Sobel/watershed technique, interactive deformable contour algorithm and thresholding) were evaluated using phantoms, Subsequently, the first three methods were applied to the images of enhanced lymph nodes in rabbits. RESULTS. Minimum errors in phantom area measurement (<5%) and interoperator variation (<5%) were seen with the Sobel/watershed technique and the interactive deformable contour algorithm, These two techniques were significantly better than thresholding and semiautomated thresholding based on local properties. CONCLUSION. Methods based on Sobel edge detection offer more objective tools than thresholding methods for segmenting objects similar to lymph nodes in computed tomography images, Both methods, Sobel/watershed and interactive deformable contour algorithm, are fast and have simple user interfaces. C1 HAYDEN IMAGE PROCESS GRP,BOULDER,CO. RP Rogowska, J (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CTR IMAGING & PHARMACEUT RES,BLDG 149,13TH ST,BOSTON,MA 02129, USA. NR 22 TC 29 Z9 29 U1 0 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0020-9996 J9 INVEST RADIOL JI Invest. Radiol. PD MAR PY 1996 VL 31 IS 3 BP 138 EP 145 DI 10.1097/00004424-199603000-00004 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA TZ863 UT WOS:A1996TZ86300004 PM 8675421 ER PT J AU Yang, BX Brown, D Verkman, AS AF Yang, BX Brown, D Verkman, AS TI The mercurial insensitive water channel (AQP-4) forms orthogonal arrays in stably transfected Chinese hamster ovary cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID COLLECTING DUCT; FREEZE-FRACTURE; PARTICLES; MEMBRANE; VASOPRESSIN; TRANSPORT; PROTEIN; CHIP28; RAT; RECONSTITUTION AB The mercurial insensitive water channel (MIWC, AQP-4) is a water-selective transporter expressed at the basolateral plasma membrane of principal cells in kidney collecting duct, airway epithelium, and gastric parietal cells, as web as in astrocytes and skeletal muscle plasmalemma. Because these sites correspond to membranes where orthogonal arrays of particles (OAPs) have been observed by freeze-fracture electron microscopy, we tested the hypothesis that MIWC forms OAPs. Chinese hamster ovary cells were stably transfected with the coding sequence of rat MIWC under a cytomegalovirus promoter. Immunostaining of clonal cell populations showed MIWC expression at the plasma membrane. A single band at 31 kDa was detected on immunoblot. Cell fractionation by sucrose gradient centrifugation indicated strong MIWC expression in plasma membrane fractions with lesser expression in Golgi. Functional analysis by stopped-flow light scattering showed high mercurial insensitive water permeability in plasma membrane vesicles. Freeze-fracture electron microscopy showed distinct OAPs on the plasma membrane P-face of MIWC-expressing cells with morphology indistinguishable from that in basolateral membrane of kidney collecting duct; the E-face showed corresponding linear grooves (spacing, similar to 8 nm) in transfected cells and collecting duct. OAPs were not observed in control (empty vector-transfected) cells or CHIP28 (AQP1)-transfected cells in which disorganized intramembrane particle aggregates were found. These results provide direct evidence that a molecular water channel can spontaneously assemble in regular arrays. C1 UNIV CALIF SAN FRANCISCO,CARDIOVASC RES INST,DEPT MED,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,CARDIOVASC RES INST,DEPT PHYSIOL,SAN FRANCISCO,CA 94143. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,RENAL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. FU NHLBI NIH HHS [HL42368]; NIDDK NIH HHS [DK35124, DK36451] NR 50 TC 184 Z9 191 U1 1 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 MAR 1 PY 1996 VL 271 IS 9 BP 4577 EP 4580 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TX697 UT WOS:A1996TX69700003 PM 8617713 ER PT J AU Allen, PG Laham, LE Way, M Janmey, PA AF Allen, PG Laham, LE Way, M Janmey, PA TI Binding of phosphate, aluminum fluoride, or beryllium fluoride to F-actin inhibits severing by gelsolin SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN-PLASMA GELSOLIN; ATP HYDROLYSIS; ADP-ACTIN; INORGANIC-PHOSPHATE; POLYMERIZATION; FILAMENTS; NUCLEOTIDE; MODULATION; MICROTUBULES; MECHANISM AB Actin exhibits ATPase activity of unknown function that increases when monomers polymerize into filaments. Differences in the kinetics of ATP hydrolysis and the release of the hydrolysis products ADP and inorganic phosphate suggest that phosphate-rich domains exist in newly polymerized filaments. We examined whether the enrichment of phosphate on filamentous ADP-actin might modulate the severing activity of gel-solin, a protein previously shown to bind differently to ATP and ADP actin monomers. Binding of phosphate, or the phosphate analogs aluminum fluoride and beryllium fluoride, to actin filaments reduces their susceptibility to severing by gelsolin. The concentration and pH dependence of inhibition suggest that HPO42- binding to actin filaments generates this resistant state. We also provide evidence for two different binding sites for beryllium fluoride on actin. Actin has been postulated to contain two P-i binding sites. Our data suggest that they are sequentially occupied following ATP hydrolysis by HPO42- which is subsequently titrated to H2PO4-. We speculate that beryllium fluoride and aluminum fluoride bind to the HPO42- binding site. The cellular consequences of this model of phosphate release are discussed. C1 HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. CHILDRENS HOSP,DANA FARBER CANC INST,BOSTON,MA 02115. EUROPEAN MOLEC BIOL LAB,D-69012 HEIDELBERG,GERMANY. RP Allen, PG (reprint author), BRIGHAM & WOMENS HOSP,DIV EXPT MED,LMRC 301,221 LONGWOOD AVE,BOSTON,MA 02115, USA. FU NHLBI NIH HHS [HL 07680]; NIAMS NIH HHS [AR 38910] NR 42 TC 17 Z9 17 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 MAR 1 PY 1996 VL 271 IS 9 BP 4665 EP 4670 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TX697 UT WOS:A1996TX69700020 PM 8617730 ER PT J AU Mulroy, WF Harris, WH AF Mulroy, WF Harris, WH TI Revision total hip arthroplasty with use of so-called second-generation cementing techniques for aseptic loosening of the femoral component - A fifteen-year-average follow-up study SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID BONE-CEMENT; FIXATION AB We reviewed the results in a consecutive series of forty-three unselected hips (forty-one patients) after revision of the femoral component, because of aseptic loosening, with use of so-called second-generation cementing techniques, This series was previously reported on after average follow-up intervals of six and 11.7 years; we now report the results after an average duration of follow-up of 15.1 years (range, 14.2 to 17.5 years). None of the eight patients (eight hips) who had died before this review had had a reoperation. Over the course of the study period, repeat revision was done after four (11 per cent) of the thirty-six index procedures that were the first femoral revision and after three of the seven that were a second or third revision, Of the thirty-five hips in the thirty-three surviving patients, seven (20 per cent) had a repeat revision of the femoral component because of aseptic loosening, The average age at the time of the index revision for this group of patients was fifty-one years, This young age has been associated with distinctly poorer results after revision. In two additional hips (two patients), there was radiographic evidence of loosening of the femoral component. Therefore, the rate of loosening of the femoral component was 26 per cent (nine of thirty-five hips) at an average of 15.1 years. These results support the concept that so-called second-generation cementing techniques have decreased the prevalence of aseptic loosening after femoral revision, compared with the shorter-term results that have been reported after revision with use of so-called first-generation cementing techniques. C1 MASSACHUSETTS GEN HOSP,ORTHOPAED BIOMECH LAB,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT ORTHOPAED SURG,HIP & IMPLANT UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 35 TC 128 Z9 141 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 MAR PY 1996 VL 78A IS 3 BP 325 EP 330 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA UA585 UT WOS:A1996UA58500002 PM 8613438 ER PT J AU McLaughlin, JR Harris, WH AF McLaughlin, JR Harris, WH TI Revision of the femoral component of a total hip arthroplasty with the calcar-replacement femoral component - Results after a mean of 10.8 years postoperatively SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID IMPROVED CEMENTING TECHNIQUES AB Patients who have major loss of bone in the region of the medial aspect of the femoral neck, shortening of the limb, or a high center of the hip joint constitute a special challenge for surgeons performing revision total hip replacements. The use of a so-called calcar-replacement femoral component is one approach to these problems. Of forty-eight hips (forty-four patients) that had been treated consecutively with a total revision arthroplasty with insertion of a calcar-replacement femoral component with cement, thirty-eight hips (thirty-five patients) were followed for a mean of 10.8 years (range, 5.8 to 16.6 years), Ten of the forty-eight hips did not qualify for this study, including nine hips in eight patients who had died before the minimum five-year duration of follow-up and one hip in a patient who had refused follow-up, Of the thirty-eight hips that were followed, seven (18 per cent) had had a repeat revision because of aseptic loosening of the femoral component, one (3 per cent) had been revised again because of lysis around a well fixed femoral component, and an additional four (11 per cent) had a component that was loose according to radiographic criteria. Thus, twenty-six (68 per cent) of the thirty-eight index femoral components were rigidly fixed according to radiographic criteria, and thirty (79 per cent) were still in place. The clinical results were very good for the thirty hips that had not been revised, The mean Harris hip-rating for these patients increased from 50 points preoperatively to 84 points at the most recent follow-up evaluation. C1 MASSACHUSETTS GEN HOSP,ORTHOPAED BIOMECH LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 33 TC 34 Z9 37 U1 0 U2 0 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD MAR PY 1996 VL 78A IS 3 BP 331 EP 339 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA UA585 UT WOS:A1996UA58500003 PM 8613439 ER PT J AU Takeshita, H Gebhardt, MC Springfield, DS Kusuzaki, K Mankin, HJ AF Takeshita, H Gebhardt, MC Springfield, DS Kusuzaki, K Mankin, HJ TI Experimental models for the study of drug resistance in osteosarcoma: P-glycoprotein-positive, murine osteosarcoma cell lines SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID BLOOD-BRAIN-BARRIER; HIGH-DOSE VERAPAMIL; MULTIDRUG-RESISTANCE; EXPRESSION; GENE; CHEMOTHERAPY; ADRIAMYCIN; CANCER; CIRCUMVENTION; SARCOMA AB P-glycoprotein is an adenosine triphosphate-dependent drug-efflux pump that extrudes drugs from cells and causes drug resistance, P-glycoprotein is believed to mediate drug resistance in a wide variety of tumors. Ln this study, we developed two P-glycoprotein-positive, murine osteosarcoma cell lines that were resistant to Adriamycin (doxorubicin) (MOS/ADR1 and MOS/ADR2). We created the cell lines by short-term pulse exposures of the parent cell line to Adriamycin followed by single-cell cloning. The MOS/ADR1 and MOS/ADR2 cells were sevenfold and eighteenfold more resistant to Adriamycin than the cells from the parent line. Expression of P-glycoprotein, as examined with an immunofluorescence method was detected in most of the MOS/ADR1 and MOS/ADR2 cells but not in the parent cells. After the cells had been incubated with Adriamycin for one hour, there was less accumulation of the drug in the resistant cell lines than in the parent cell line. The reduced accumulation was due to the increased efflux of Adriamycin. The Adriamycin-resistant cell lines demonstrated greater alkaline phosphatase activity than the parent cell line and produced more differentiated osteoblastic sarcomas in mice. Dose-survival studies with use of a tetrazolium colorimetric assay showed that the MOS/ADR1 cells were cross-resistant to vincristine, vinblastine, etoposide, bleomycin, mitomycin C, and actinomycin D but not to dacarbazine, cisplatin, carboplatin, cytosine arabinoside, carmustine, cyclophosphamide, ifosfamide, methotrexate, and 5-fluorouracil. Although the MOS/ADR2 cells exhibited a similar spectrum of cross-resistance, they were more resistant than the MOS/ADR1 cells. We also tested the effect of three different resistance-modifying agents on the reversal of resistance to Adriamycin. We found that verapamil and trifluoperazine substantially reversed resistance to Adriamycin in the P-glycoprotein-positive cell lines, whereas cyclosporin A was relatively ineffective. Because these cell lines retain the histological and biochemical features of bone-producing sarcomas and display the multidrug-resistant phenotype, they may be useful models for additional investigations of drug resistance in osteosarcoma. CLINICAL RELEVANCE: Recent investigations have shown that turner cells have energy-dependent, so-called pump mechanisms in their membranes that actively transport certain classes of chemotherapeutic drugs from the tells, rendering them resistant to treatment. At least some human osteosarcomas possess one of these pumps, the P-glycoprotein pump, and this pump mag. be partially responsible for the observed drug resistance in the current treatment regimens for osteosarcoma. These newly described P-glycoprotein-positive multidrug-resistant osteosarcoma cell lines are useful models for the further characterization of drug resistance in osteosarcoma and for the development of treatment protocols. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,ORTHOPAED RES LABS,BOSTON,MA. NR 41 TC 42 Z9 43 U1 0 U2 0 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD MAR PY 1996 VL 78A IS 3 BP 366 EP 375 PG 10 WC Orthopedics; Surgery SC Orthopedics; Surgery GA UA585 UT WOS:A1996UA58500007 PM 8613443 ER PT J AU Fang, LST AF Fang, LST TI Coronary artery bypass grafting in patients with chronic renal failure: A reappraisal - Invited commentary SO JOURNAL OF CARDIAC SURGERY LA English DT Editorial Material RP Fang, LST (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FUTURA PUBL CO PI ARMONK PA 135 BEDFORD RD, PO BOX 418, ARMONK, NY 10504-0418 SN 0886-0440 J9 J CARDIAC SURG JI J. Card. Surg. PD MAR-APR PY 1996 VL 11 IS 2 BP 134 EP 135 DI 10.1111/j.1540-8191.1996.tb00027.x PG 2 WC Cardiac & Cardiovascular Systems; Surgery SC Cardiovascular System & Cardiology; Surgery GA UR419 UT WOS:A1996UR41900010 ER PT J AU Champliaud, MF Lunstrum, GP Rousselle, P Nishiyama, T Keene, DR Burgeson, RE AF Champliaud, MF Lunstrum, GP Rousselle, P Nishiyama, T Keene, DR Burgeson, RE TI Human amnion contains a novel laminin variant, laminin 7, which like laminin 6, covalently associates with laminin 5 to promote stable epithelial-stromal attachment SO JOURNAL OF CELL BIOLOGY LA English DT Article ID BULLOUS PEMPHIGOID ANTIGEN; AMINO-ACID SEQUENCE; PROTEIN S-LAMININ; ANCHORING FIBRILS; CELL-ADHESION; VII COLLAGEN; CHROMOSOMAL ASSIGNMENT; BASEMENT-MEMBRANES; GLOBULAR DOMAIN; SYNAPTIC CLEFT AB Stable attachment of external epithelia to the basement membrane and underlying stroma is mediated by transmembrane proteins such as the integrin alpha 6 beta 4 and bullous pemphigoid antigen 2 within the hemidesmosomes along the basolateral surface of the epithelial cell and their ligands that include a specialized subfamily of laminins. The laminin 5 molecule (previously termed kalinin/nicein/epiligrin) is a member of this epithelial-specific subfamily. Laminin 5 chains are not only considerably truncated within domains III-VI, but are also extensively proteolytically processed in vitro and in vivo. As a result, the domains expected to be required for the association of laminins with other basement membrane components are lacking in the mature laminin 5 molecule, Therefore, the tight binding of laminin to the basement membrane may occur by a unique mechanism. To examine laminin 5 in tissue, we chose human amnion as the source, because of Its availability and the similarity of the amni otic epithelial basement membrane with that of skin. We isolated the laminin 5 contained within the basement membrane of human amnion. In addition to monomeric laminin 5, we find that much of the laminin 5 isolated is covalently adducted with laminin 6 (alpha 3 beta 1 gamma 1) and a novel laminin isotype we have termed laminin 7 (alpha 3 beta 2 gamma 1), We propose that the association between laminin 5 and laminins 6 and 7 is a mechanism used in amnion to allow stable association of laminin 5 with the basement membrane. The beta 2 chain is seen at the human amniotic epithelial-stromal interface and at the dermal-epidermal junction of fetal and adult bovine skin by immunofluorescence, but is not present, or only weakly present, in neonatal human skin. C1 MASSACHUSETTS GEN HOSP,CUTANEOUS BIOL RES CTR,BOSTON,MA 02129. HARVARD UNIV,SCH MED,DEPT DERMATOL,BOSTON,MA 02115. SHRINERS HOSP CRIPPLED CHILDRENS,PORTLAND,OR 97201. CNRS,INST BIOL & CHIM PROT,F-69637 LYON 07,FRANCE. RI Nishiyama, Toshio/C-5434-2013; OI Rousselle, Patricia/0000-0003-0275-4562 FU NIAMS NIH HHS [AR35689] NR 54 TC 198 Z9 203 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD MAR PY 1996 VL 132 IS 6 BP 1189 EP 1198 DI 10.1083/jcb.132.6.1189 PG 10 WC Cell Biology SC Cell Biology GA UB512 UT WOS:A1996UB51200016 PM 8601594 ER PT J AU Bartolazzi, A Nocks, A Aruffo, A Spring, F Stamenkovic, I AF Bartolazzi, A Nocks, A Aruffo, A Spring, F Stamenkovic, I TI Glycosylation of CD44 is implicated in CD44-mediated cell adhesion to hyaluronan SO JOURNAL OF CELL BIOLOGY LA English DT Article ID LYMPHOCYTE HOMING RECEPTOR; HUMAN TRANSFERRIN RECEPTORS; SITE-DIRECTED MUTAGENESIS; EXTRACELLULAR DOMAIN; ACID BINDING; MOLECULE; ACTIVATION; ANTIBODY; PROTEOGLYCAN; RECOGNITION AB CD44-mediated cell adhesion to hyaluronate is controlled by mechanisms which are poorly understood. In the present work we examine the role of N-linked glycosylation and Ser-Gly motifs in regulating CD44-hyaluronate interaction. Our results show that treatment of a panel of human cell lines which constitutively express CD44 with the inhibitor of N-linked glycosylation tunicamycin results in the loss of attachment of these cells to hyaluronate-coated substrate. In contrast, treatment of the same cells with deoxymannojirimycin, which inhibits the conversion of high mannose oligosaccharides to complex N-linked carbohydrates, results in either no change or an increase in CD44-mediated adhesion to hyaluronate, suggesting that complex N-linked oligosaccharides may not be required for and may even inhibit CD44-HA interaction. Using human melanoma cells stably transfected with CD44 N-linked glycosylation site-specific mutants, we show that integrity of five potential N-linked glycosylation sites within the hyaluronate recognition domain of CD44 is critical for hyaluronate binding, Mutation of any one of these potential N-linked glycosylation sites abrogates CD44-mediated melanoma cell attachment to hyaluronate-coated surfaces, suggesting that all five sites are necessary to maintain the HA-recognition domain in the appropriate conformation, We also demonstrate that mutation of serine residues which constitute the four Ser-Gly motifs in the membrane proximal domain, and provide potential sites for glycosaminoglycan side chain attachment, impairs hyaluronate binding. Taken together, these observations indicate that changes in glycosylation of CD44 can have profound effects on its interaction with hyaluronic acid and suggest that glycosylation may provide an important regulatory mechanism of CD44 function. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,BOSTON,MA 02129. BRISTOL MYERS SQUIBB PHARMACEUT RES INST,SEATTLE,WA 98121. INT BLOOD GRP,REFERENCE LAB,BRISTOL BS10 5ND,AVON,ENGLAND. FU NCI NIH HHS [CA55735] NR 44 TC 132 Z9 133 U1 0 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD MAR PY 1996 VL 132 IS 6 BP 1199 EP 1208 DI 10.1083/jcb.132.6.1199 PG 10 WC Cell Biology SC Cell Biology GA UB512 UT WOS:A1996UB51200017 PM 8601595 ER PT J AU Pullan, S Wilson, J Metcalfe, A Edwards, GM Goberdhan, N Tilly, J Hickman, JA Dive, C Streuli, CH AF Pullan, S Wilson, J Metcalfe, A Edwards, GM Goberdhan, N Tilly, J Hickman, JA Dive, C Streuli, CH TI Requirement of basement membrane for the suppression of programmed cell death in mammary epithelium SO JOURNAL OF CELL SCIENCE LA English DT Article DE mammary gland; breast; apoptosis; Bcl-2; bar; extracellular matrix; basement membrane; integrin ID EXTRACELLULAR-MATRIX COMPONENTS; GENE-EXPRESSION; APOPTOSIS; INVOLUTION; DIFFERENTIATION; SURVIVAL; BREAST AB Apoptosis is an active mechanism of cell death required for normal tissue homeostasis. Cells require survival signals to avoid the engagement of apoptosis. In the mammary gland, secretory epithelial cells are removed by apoptosis during involution. This cell loss coincides with matrix metalloproteinase activation and basement membrane degradation. In this paper we describe studies that confer a new role for basement membrane in the regulation of cell phenotype. We demonstrate that first passage epithelial cells isolated from pregnant mouse mammary gland die by apoptosis in culture, but that cell death is suppressed by basement membrane. The correct type of extracellular matrix was required, since only a basement membrane, not plastic or a collagen I matrix, lowered the rate of apoptosis. Attachment to a matrix per se was not sufficient for survival, since apoptotic cells were observed when still attached to a collagen I substratum. Experiments with individually isolated cells confirmed the requirement of basement membrane for survival, and demonstrated that survival is enhanced by cell-cell contact. A function-blocking anti-beta(1) integrin antibody doubled the rate of apoptosis in single cells cultured with basement membrane, indicating that integrin-mediated signals contributed to survival. We examined the cell death-associated genes bcl-2 and bar in mammary epithelia, and found that although the expression of Bcl-2 did not correlate with cell survival, increased levels of Bar mere associated with apoptosis. We propose that basement membrane provides a survival stimulus for epithelial cells in vivo, and that loss of interaction with this type of matrix acts as a control point for cell deletions that occur at specific times during development, such as in mammary gland involution. C1 UNIV MANCHESTER,SCH BIOL SCI,MANCHESTER M13 9PT,LANCS,ENGLAND. UNIV MANCHESTER,CANC RES CAMPAIGN MOLEC & CELLULAR PHARMACOL GRP,MANCHESTER M13 9PT,LANCS,ENGLAND. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT OBSTET & GYNAECOL,VINCENT CTR REPROD BIOL,BOSTON,MA 02114. FU Wellcome Trust NR 37 TC 218 Z9 223 U1 1 U2 6 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD MAR PY 1996 VL 109 BP 631 EP 642 PN 3 PG 12 WC Cell Biology SC Cell Biology GA UB095 UT WOS:A1996UB09500010 PM 8907708 ER PT J AU Marra, F Bonewald, LF ParkSnyder, S Park, IS Woodruff, KA Abboud, HE AF Marra, F Bonewald, LF ParkSnyder, S Park, IS Woodruff, KA Abboud, HE TI Characterization and regulation of the latent transforming growth factor-beta complex secreted by vascular pericytes SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID MOLECULAR-WEIGHT COMPLEX; SMOOTH-MUSCLE CELLS; FAT-STORING CELLS; LIVER-REGENERATION; ENDOTHELIAL-CELLS; HEPATIC-FIBROSIS; BINDING-PROTEIN; MESANGIAL CELLS; TGF-BETA; FACTOR-BETA-1 AB Transforming growth factor-beta (TGF-beta) stimulates the accumulation of extracellular matrix in renal and hepatic disease. Kidney glomerular mesangial cells (GMC) and liver fat-storing cells (FSC) produce latent or inactive TGF-beta. In this study, we characterized the latent TGF-beta complexes secreted by these cells. Human FSC produce a single latent TGF-beta complex, predominantly of the TGF-beta 1 isoform, whereas GMC secrete multiple complexes of latent TGF-beta, containing beta 1 and beta 2 isoforms. At least four forms were identified in GMC using ion exchange chromatography, including a peak not previously described in other cell types which eluted at 0.12 M NaCl, and predominantly of the beta 2 isoform. Both cell types secrete the latent TGF-beta 1 binding protein of 190 kDa, as part of a high molecular weight TGF-beta complex. Epidermal growth factor stimulates the secretion of latent TGF-beta and latent TGF-beta binding protein in both cell types. Secretion of the latent TGF-beta in both cell types was found to be associated with secretion of decorin. This study shows that vascular pericytes from the kidney and the liver have distinctly different profiles of latent TGF-beta complexes, with GMC secreting a unique form of latent TGF-beta 2. The regulatory effect of epidermal growth factor and platelet-derived growth factor has potential implication for the pathophysiology of liver regeneration and chronic liver and kidney diseases. (C) 1996 Wiley-Liss, Inc. C1 UNIV TEXAS, HLTH SCI CTR, DEPT MED, SAN ANTONIO, TX 78284 USA. AUDIE L MURPHY MEM VET ADM MED CTR, SAN ANTONIO, TX 78284 USA. RI Marra, Fabio/K-7263-2016 OI Marra, Fabio/0000-0001-8629-0878 FU NIDCR NIH HHS [DE-08569]; NIDDK NIH HHS [DK-33665, DK-43988] NR 46 TC 32 Z9 32 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD MAR PY 1996 VL 166 IS 3 BP 537 EP 546 PG 10 WC Cell Biology; Physiology SC Cell Biology; Physiology GA TX603 UT WOS:A1996TX60300008 PM 8600157 ER PT J AU Denman, WT Goudsouzian, NG Gelb, C AF Denman, WT Goudsouzian, NG Gelb, C TI Comparison of neuromuscular, cardiovascular, and histamine-releasing properties of doxacurium and pipecuronium SO JOURNAL OF CLINICAL ANESTHESIA LA English DT Article DE anesthesia; general; histamine; effects, releasing properties; neuromuscular relaxants; doxacurium; pipecuronium ID NITROUS-OXIDE; CLINICAL-PHARMACOLOGY; FENTANYL ANESTHESIA; CHLORIDE; PANCURONIUM; VECURONIUM; BROMIDE; HUMANS; TUBOCURARINE; BLOCKING AB Study Objectives: To determine the neuromuscular, cardiovascular, and histamine-releasing properties of doxacurium and pipecuronium at three times effective ED(95) doses (3XED(95)). Design: Prospective, randomized clinical trial of adult patients. Setting: University teaching hospital. Patients: 20 ASA status I and II adult patients. Intervention: Subjects were anesthetized with thiopental sodium, fentanyl, and nitrous oxide and oxygen (N2O:O-2). Plasma samples were taken preoperatively, after thiopental, and 2 and 5 minutes after dozacurium 75 mu g/kg or pipecuronium 123 mu g/kg were given for the determination of histamine levels. The ulnar nerve was stimulated via surface electrodes using train-of-four stimulation at 0.1 Hz. The force of contraction of adductor pollicis was recorded using a mechanomyograph. Recovery of the twitch response was followed and if necessary, neuromuscular block was antagonized with neostigmine and glycopyrrolate. Measurements and Main Results: Three patients in the doxacurium group and one patient in the pipecuronium group exhibited a marked increase in plasma histamine levels. In both groups statistically significant changes were seen in heart rate (HR) measurements (p < 0.02). Doxacurium had a slower onset than pipecuronium [3.1 +/- 0.2 min vs. 1.8 +/- 0.1 min (p < 0.0003)] and a more rapid recovery [72 +/- 8 min vs. 123 +/- 9 min (p < 0.01)]. Conclusion: Neither drug caused a clinically significant change in HR or histamine release. In the doses chosen for this study, the rate of onset of block is slower with doxacurium while recovery is more rapid. Histamine release in three patients was caused by thiopental, while In a fourth patient it may have been due to doxacurium. RP Denman, WT (reprint author), HARVARD UNIV,DEPT ANESTHESIA,MASSACHUSETTS GEN HOSP,SCH MED,FRUIT ST,BOSTON,MA 02114, USA. NR 24 TC 5 Z9 6 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 MAR PY 1996 VL 8 IS 2 BP 113 EP 118 DI 10.1016/0952-8180(95)00194-8 PG 6 WC Anesthesiology SC Anesthesiology GA TX571 UT WOS:A1996TX57100006 PM 8695092 ER PT J AU Siris, E Weinstein, RS Altman, R Conte, JM Favus, M Lombardi, A Lyles, K McIlwain, H Murphy, WA Reda, C Rude, R Seton, M Tiegs, R Thompson, D Tucci, JR Yates, AJ Zimering, M AF Siris, E Weinstein, RS Altman, R Conte, JM Favus, M Lombardi, A Lyles, K McIlwain, H Murphy, WA Reda, C Rude, R Seton, M Tiegs, R Thompson, D Tucci, JR Yates, AJ Zimering, M TI Comparative study of alendronate versus etidronate for the treatment of Paget's disease of bone SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HISTOMORPHOMETRY; BISPHOSPHONATE; METABOLISM; DISODIUM AB Alendronate, an aminobisphosphonate, is much more potent than etidronate, an older bisphosphonate, in inhibiting osteoclast-mediated bone resorption, and unlike etidronate, therapeutic doses of alendronate are not associated with abnormal mineralization. In the present study, we compared the effectiveness, safety, and tolerability of 6 months of daily oral administration of alendronate (40 mg) with those of etidronate (400 mg) in 89 patients with clinically active Paget's disease. The primary efficacy end point was the percent change in serum alkaline phosphatase. Other end points included changes in urinary deoxypyridinoline excretion, pain, functional impairment scores, and radiological osteolysis. Tetracycline-labeled bone biopsies were obtained for histomorphometric analysis from a subset of 43 patients at the 6-month visit. The alendronate-treated group had significantly greater decreases in both serum alkaline phosphatase (79% vs. 44%) and urinary deoxypyridinoline (75% vs. 51%) than the etidronate-treated group (P < 0.001 in both cases). Normalization of serum alkaline phosphatase was much more frequent in alendronate-treated patients (63.4% vs. 17.0%; P < 0.001). Alendronate was well tolerated and had a safety profile similar to that of etidronate. Histomorphometry revealed decreased bone turnover and no qualitative abnormalities, including no direct negative effects on bone mineralization, with alendronate treatment. One patient receiving etidronate developed frank osteomalacia. Alendronate appears to be a highly effective treatment for Paget's disease of bone that offers an important therapeutic advance over etidronate. C1 COLUMBIA UNIV, COLL PHYS & SURG, DEPT MED, NEW YORK, NY USA. UNIV ARKANSAS MED SCI HOSP, DIV ENDOCRINOL METAB, LITTLE ROCK, AR USA. UNIV MIAMI, SCH MED, DEPT MED, MIAMI, FL USA. RHEUMATOL ASSOCIATES, PROVIDENCE, RI USA. UNIV CHICAGO, DEPT MED, CHICAGO, IL 60637 USA. MERCK RES LABS, RAHWAY, NJ USA. DUKE UNIV, MED CTR, CTR AGING, DURHAM, NC USA. VET ADM MED CTR, CTR GERIATR RES EDUC & CLIN, DURHAM, NC 27705 USA. HABANA MED CTR, TAMPA, FL USA. UNIV TEXAS, MD ANDERSON CANC CTR, DIV DIAGNOST IMAGING, HOUSTON, TX USA. UNIV SO CALIF, LOS ANGELES, CA USA. MASSACHUSETTS GEN HOSP, ARTHRITIS UNIT, BOSTON, MA USA. MAYO CLIN, DIV ENDOCRINOL, ROCHESTER, MN USA. ROGER WILLIAMS HOSP, DEPT MED, PROVIDENCE, RI USA. VET ADM MED CTR, LYONS, NJ USA. NR 24 TC 146 Z9 148 U1 2 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAR PY 1996 VL 81 IS 3 BP 961 EP 967 DI 10.1210/jc.81.3.961 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TZ906 UT WOS:A1996TZ90600018 PM 8772558 ER PT J AU Wright, NM Papadea, N Willi, S Veldhuis, JD Pandey, JP Key, LL Bell, NH AF Wright, NM Papadea, N Willi, S Veldhuis, JD Pandey, JP Key, LL Bell, NH TI Demonstration of a lack of racial difference in secretion of growth hormone despite a racial difference in bone mineral density premenopausal in women - A clinical research center study SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID WHITE-CHILDREN; BODY HABITUS; BLACK; MASS; RACE; AGE; SEX; RADIOIMMUNOASSAY; DEFICIENCY; ESTRADIOL AB We previously found GH secretion to be higher in black than white men. Therefore, we performed studies to determine whether this racial difference in GH secretion also occurs in women. Measurements of GH were obtained at 20-min intervals over 24 h and analyzed by deconvolution in 12 healthy black and 12 healthy white premenopausal women. Bone mineral density (BMD) was determined by dual energy x-ray absorptiometry, and GM allotypes were measured as a genetic marker for race. Racial distribution of the groups, as determined by analysis of GM haplotypes, were typical for black and white American populations. Twenty-four-hour integrated GH concentration, GH secretory burst amplitude, burst frequency, half-duration, mass, and half-life were not different in the two groups. Serum testosterone was modestly, but significantly, greater in the black than in the white women (1.1 +/- 0.1 vs. 0.9 +/- 0.1 nmol/L; P < 0.05). Serum 17 beta-estradiol and insulin-like growth factor (IGF)-binding protein-3 were not different in the two groups. However, the IGF-I/IGF-binding protein-3 molar ratio was significantly greater in the black than the white women (2.0 +/- 0.1 vs. 1.6 +/- 0.1; P < 0.02). The BMD of total body (1.12 +/- 0.02 vs. 1.07 +/- 0.02 g/cm(2); P < 0.05) and total hip (0.96 +/- 0.04 vs. 0.86 +/- 0.04 g/cm(2); P < 0.05) were greater in the black (n = 13) than in the white (n = 12) women. There was a trend toward greater BMD of the forearm in the black women (0.58 +/- 0.01 vs. 0.56 +/- 0.01 g/cm(2); P = 0.06) and no racial difference in the BMD of the spine. When examining all subjects together, the BMD of the total body, trochanter, and spine correlated with total integrated GH secretion. Thus, the racial difference in GH secretion that we had previously found in men does not occur in women despite the higher BMD values at several skeletal sites in black women. C1 MED UNIV S CAROLINA, DEPT MICROBIOL & IMMUNOL, CHARLESTON, SC 29425 USA. MED UNIV S CAROLINA, DEPT MED & PHARMACOL, CHARLESTON, SC 29425 USA. RALPH H JOHNSON DEPT VET AFFAIRS MED CTR, CHARLESTON, SC 29425 USA. UNIV VIRGINIA, SCH MED, DEPT INTERNAL MED, CHARLOTTESVILLE, VA 22908 USA. RP Wright, NM (reprint author), MED UNIV S CAROLINA, DEPT PEDIAT, 171 ASHLEY AVE, CHARLESTON, SC 29425 USA. FU NCRR NIH HHS [MO1-RR-01070]; NIAMS NIH HHS [R01-AR-36066]; NICHD NIH HHS [1K04-HD-00634] NR 33 TC 29 Z9 29 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAR PY 1996 VL 81 IS 3 BP 1023 EP 1026 DI 10.1210/jc.81.3.1023 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TZ906 UT WOS:A1996TZ90600029 PM 8772569 ER PT J AU Finkelstein, JS Klibanski, A Neer, RM AF Finkelstein, JS Klibanski, A Neer, RM TI A longitudinal evaluation of bone mineral density in adult men with histories of delayed puberty SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID MASS ACCUMULATION; WOMEN; OSTEOPOROSIS; HIP; FRACTURES; CHILDREN; CALCIUM; SPINE; PREVENTION; PREDICTION AB We have previously demonstrated that men with histories of constitutionally delayed puberty have significantly lower spinal and radial bone mineral density than normal men. Because these men were in their mid-twenties, it is possible that bone density was decreased because bone development was still incomplete. In addition, there is no information on the bone density of the proximal femur, the most important clinical site for osteoporotic fractures, in men with histories of delayed puberty. To address these issues, we performed repeat measurements of radial and spinal bone mineral density 2 yr after the initial evaluations in 18 men with histories of delayed puberty. Bone mineral density of the femoral neck was also measured at the time of follow-up evaluations. The mean radial bone mineral density at the time of the repeat evaluations was similar to the mean value from the initial evaluations (0.74 +/- 0.08 vs. 0.74 +/- 0.07 g/cm(2)) and the mean change was 0.00 +/- 0.04 g/cm(2). Similarly, the mean spinal bone mineral density at the time of the repeat evaluations was similar to the mean value from the initial evaluations (1.02 +/- 0.10 vs. 1.01 +/- 0.10 g/cm(2)) and the mean change was -0.01 +/- 0.04 g/cm(2). Bone mineral density of the femoral neck was significantly lower in the men with histories of delayed puberty than in normal men (0.88 +/- 0.11 vs. 0.98 +/- 0.14 g/cm(2); P < 0.02). These data indicate that bone accretion is complete by the mid-twenties in men with histories of constitutionally delayed puberty and that their bone mineral density does not improve with time. In addition, these men have decreased bone density of the femoral neck, which might increase their risk for hip fractures when they are older. C1 MASSACHUSETTS GEN HOSP, DEPT MED, NEUROENDOCRINE UNIT, BOSTON, MA 02114 USA. RP Finkelstein, JS (reprint author), MASSACHUSETTS GEN HOSP, DEPT MED, ENDOCRINE UNIT, BULFINCH 3, BOSTON, MA 02114 USA. FU NCRR NIH HHS [RR-1066]; NICHD NIH HHS [HD-21204]; NIDDK NIH HHS [1-R29-DK/43341-01A2] NR 34 TC 115 Z9 117 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAR PY 1996 VL 81 IS 3 BP 1152 EP 1155 DI 10.1210/jc.81.3.1152 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TZ906 UT WOS:A1996TZ90600051 PM 8772591 ER PT J AU Fischman, AJ AF Fischman, AJ TI Positron emission tomography in the clinical evaluation of metastatic cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID F-18 FLUORODEOXYGLUCOSE; NECK TUMORS; MUSCULOSKELETAL TUMORS; PROLIFERATIVE ACTIVITY; GLUCOSE-UTILIZATION; MALIGNANT-LYMPHOMA; BREAST-CARCINOMA; FLOW-CYTOMETRY; PET; HEAD RP Fischman, AJ (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA, USA. NR 48 TC 24 Z9 25 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR PY 1996 VL 14 IS 3 BP 691 EP 696 PG 6 WC Oncology SC Oncology GA TZ732 UT WOS:A1996TZ73200001 PM 8622012 ER PT J AU Hayes, DF AF Hayes, DF TI Should we treat her, too? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID BREAST-CANCER; EXPRESSION; HER-2/NEU; ANTIBODY; ONCOGENE; THERAPY RP Hayes, DF (reprint author), DANA FARBER CANC INST,BREAST EVALUAT CTR,BOSTON,MA 02115, USA. NR 23 TC 8 Z9 8 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR PY 1996 VL 14 IS 3 BP 697 EP 699 PG 3 WC Oncology SC Oncology GA TZ732 UT WOS:A1996TZ73200002 PM 8622013 ER PT J AU Goodson, JM AF Goodson, JM TI Principles of pharmacologic intervention SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE periodontal disease therapy; delivery systems; tetracycline; chlorhexidine ID CHLORHEXIDINE; DELIVERY; FIBERS AB Compared to studies with conventional maintenance, relatively few studies have been conducted that have tested pharmacologic intervention as a means for supportive periodontal care. Despite the scarcity of data, several principles have begun to emerge. First, it is clear that removal of subgingival calculus is necessary for the highest level of a long-term effectiveness. Hence, pharmacologic intervention appears best suited as an adjunctive therapy directed toward ''problem sites''; sites that fail to respond adequately to conventional maintenance procedures. Intrapocket drug delivery systems appear to offer particular promise since therapy can be directed to selected sites that appear to be failing. Additional effectiveness may also be obtained by use of chlorhexidine mouth rinses for short periods of time during healing to control re-infection. Eradication of reservoirs of infection throughout the mouth also appears to be an important principle related to long-term stabilization. Studies to date suggest that superior clinical response can be obtained by intrapocket delivery systems. Furthermore, up to 2 years of periodontal stabilization can be achieved by these means and longer disease-free maintenance intervals can be established. Additional clinical trials will be necessary to fully optimize and understand this therapeutic approach, but initial studies have reported promising results. RP Goodson, JM (reprint author), FORSYTH DENT CTR,140 FENWAY,BOSTON,MA 02138, USA. NR 17 TC 2 Z9 2 U1 0 U2 2 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0303-6979 J9 J CLIN PERIODONTOL JI J. Clin. Periodontol. PD MAR PY 1996 VL 23 IS 3 BP 268 EP 272 DI 10.1111/j.1600-051X.1996.tb02087.x PN 2 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA UD214 UT WOS:A1996UD21400007 PM 8707988 ER PT J AU Gibbons, RJ AF Gibbons, RJ TI Role of adhesion in microbial colonization of host tissues: A contribution of oral microbiology SO JOURNAL OF DENTAL RESEARCH LA English DT Article ID EPITHELIAL SURFACES; BACTERIAL ADHERENCE; APATITIC SURFACES; DETERMINANT; ADSORPTION; ATTACHMENT; SALIVARIUS C1 FORSYTH DENT CTR, BOSTON, MA 02115 USA. NR 34 TC 35 Z9 37 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-0345 EI 1544-0591 J9 J DENT RES JI J. Dent. Res. PD MAR PY 1996 VL 75 IS 3 BP 866 EP 870 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA UY933 UT WOS:A1996UY93300002 PM 8675796 ER PT J AU Emanuele, NV Jurgens, J LaPaglia, N Williams, DW Kelley, MR AF Emanuele, NV Jurgens, J LaPaglia, N Williams, DW Kelley, MR TI The effect of castration on steady state levels of luteinizing hormone-releasing hormone (LHRH) mRNA and proLHRH processing: Time course study utilizing semi-quantitative reverse transcription/polymerase chain reaction SO JOURNAL OF ENDOCRINOLOGY LA English DT Article ID FOLLICLE-STIMULATING-HORMONE; MALE-RAT; MESSENGER-RNA; GENE-EXPRESSION; PREOPTIC AREA; ANTERIOR-PITUITARY; GONADAL-STEROIDS; INSITU HYBRIDIZATION; BASAL HYPOTHALAMUS; PULSE-GENERATOR AB Many studies have consistently shown that castration induces a prompt increase in serum levels and pituitary content of the gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), as well as a concomitant rise in steady state levels of the messenger RNAs directing their synthesis. The reports of effects of castration on the overall physiology of hypothalamic luteinizing hormone-releasing hormone (LHRH)-steady state levels of LHRH mRNA, post-translational processing and secretion-have, however, not been consistent. The goal of the studies reported here was to provide the first analysis of the effect of castration, at multiple post-operative time points, on steady state levels of LHRH mRNA and on the levels of hypothalamic proLHRH. All these data are correlated with hypothalamic levels of the mature LHRH decapeptide and with serum and pituitary levels of immunoreactive LH and FSH. Adult male rats were either castrated or sham-castrated (controls) and then sacrificed at 1, 3, 5, 7, 14, 21 or 28 days postoperatively. As expected, there was a prompt and sustained rise in serum immunoreactive LH and FSH in castrates compared with sham-operated animals. Intrapituitary LH levels rose above levels in the sham-operated animals by 14 days post castration. Intra-pituitary FSH showed a biphasic response, first falling significantly below control levels, then rising above control levels at 21 days. Steady state levels of LHRH mRNA in castrates, measured by reverse transcription/polymerase chain reaction, were increased about 2-fold above control levels by 1 day postoperatively, but were virtually identical to control levels at each of the other time points despite marked changes in the gonadotropins. ProLHRH content in castrates was 1.8-times that seen in controls at 1 day post castration (P<0.05), concomitant with the rise in steady state levels of LHRH mRNA at that time point. However, proLHRH content in castrates was no different from that seen in controls at each of the later time points examined. LHRH content was' unchanged through 7 days after castration, but then fell significantly to 57% of control levels in hypothalami from animals gonadectomized 14 to 21 days previously (P<0.001 vs control), and to 54% of sham-operated levels at 28 days postoperatively (P<0.001). We conclude that: (1) changes in steady state levels of LHRH mRNA after castration are small and transient and (2) increased proLHRH coupled with unchanged LHRH levels at 1 day post castration, and castrate animal proLHRH at control levels coupled with falling LHRH at later post-castration time points indicate that the effect of gonadectomy on post-translational processing of proLHRH to LHRH is, likewise, small and transient. In aggregate our data suggest that most of the increase in serum LH and FSH seen in male rats after castration is not mediated at the hypothalamic level. C1 US DEPT VET AFFAIRS,VET AFFAIRS EDWARD HINES JR HOSP,MED SERV,HINES,IL 60141. LOYOLA UNIV,STRITCH SCH MED,DEPT MED,MAYWOOD,IL 60153. LOYOLA UNIV,STRITCH SCH MED,PROGRAM MOLEC BIOL,MAYWOOD,IL 60153. INDIANA UNIV,SCH MED,SECT PEDIAT ENDOCRINOL,INDIANAPOLIS,IN 46202. RP Emanuele, NV (reprint author), US DEPT VET AFFAIRS,VET AFFAIRS EDWARD HINES JR HOSP,RES SERV,ROOSEVELT RD & 5TH AVE,HINES,IL 60141, USA. NR 43 TC 18 Z9 18 U1 0 U2 4 PU J ENDOCRINOLOGY LTD PI BRISTOL PA 17/18 THE COURTYARD, WOODLANDS, ALMONDSBURY, BRISTOL, ENGLAND BS12 4NQ SN 0022-0795 J9 J ENDOCRINOL JI J. Endocrinol. PD MAR PY 1996 VL 148 IS 3 BP 509 EP 515 DI 10.1677/joe.0.1480509 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UA501 UT WOS:A1996UA50100015 PM 8778229 ER PT J AU Zhao, JL Freeman, GJ Gray, GS Nadler, LM Glimcher, LH AF Zhao, JL Freeman, GJ Gray, GS Nadler, LM Glimcher, LH TI A cell type-specific enhancer in the human B7.1 gene regulated by NF-kappa B SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID CTLA-4 COUNTER-RECEPTOR; LYMPHOCYTES-T; TYROSINE PHOSPHORYLATION; COSTIMULATORY ACTIVITY; ANTIGEN PRESENTATION; ALPHA GENE; ACTIVATION; EXPRESSION; INDUCTION; PROMOTER AB The costimulatory molecule B7.1 provides a second signal critical for T cell activation. The distribution of this integral membrane protein is restricted to certain tissues where its level of expression is modulated by multiple exogenous stimuli. To identify the molecular basis for specificity and inducibility, the chromatin cofiguration of the human B7.1 gene was examined in intact nuclei from various cell types. The identification of a tissue-specific deoxyribonuclease I hypersensitive site similar to 3kb upstream of the transcription start site led to the characterization of a cell type-specific enhancer region. This 183-bp region was both cell type specific and responsive to two distinct stimuli, lipopolysaccharide and dibutyryl cAMP, known to regulate B7.1 expression. Deletional and site-directed mutagenesis revealed the presence of multiple functionally critical cis elements within this region, one of which was a nuclear factor (NF)-kappa B consensus sequence. In B7.1-positive B cells, this element bound several members of the NF-kappa B family, transcription factors already implicated in signal transduction pathways relevant to B7.1 expression. This is the first description, to our knowledge, of regulatory elements that control expression of a gene encoding a B7 costimulatory molecule. C1 HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. REPLIGEN CORP,DEPT THERAPEUT RES,CAMBRIDGE,MA 02139. FU NCI NIH HHS [CA-34183, CA-40416]; NIAID NIH HHS [AI-21569] NR 72 TC 71 Z9 73 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAR 1 PY 1996 VL 183 IS 3 BP 777 EP 789 DI 10.1084/jem.183.3.777 PG 13 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA UC775 UT WOS:A1996UC77500010 PM 8642282 ER PT J AU Carlesso, N Frank, DA Griffin, JD AF Carlesso, N Frank, DA Griffin, JD TI Tyrosyl phosphorylation and DNA binding activity of signal transducers and activators of transcription (STAT) proteins in hematopoietic cell lines transformed by Bcr/Abl SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; COLONY-STIMULATING FACTOR; PHILADELPHIA-CHROMOSOME; KINASE-ACTIVITY; INTERLEUKIN-3; EXPRESSION; GROWTH; GENE; ESTABLISHMENT; P210BCR/ABL AB Bcr/Abl is a chimeric oncogene that can cause both acute and chronic human leukemias. Bcr/Abl-encoded proteins exhibit elevated kinase activity compared to c-Abl, but the mechanisms of transformation are largely unknown. Some of the biological effects of Bcr/Abl overlap with those of hematopoietic cytokines, particularly interleukin 3 (IL-3). Such effects include mitogenesis, enhanced survival, and enhanced basophilic differentiation. Therefore, it has been suggested that p210Bcr/Abl and the IL-3 receptor may activate some common signal transduction pathways. An important pathway for IL-3 signaling involves activation of the Janus family kinases (JAKs) and subsequent tyrosyl phosphorylation of STAT proteins (signal transducers and activators of transcription). This pathway directly links growth factor receptors to gene transcription. We analyzed JAK activation, STAT protein phosphorylation, and the formation of specific DNA-binding complexes containing STAT proteins, in a series of leukemia cell lines transformed by Bcr/Abl or other oncogenes. We also examined these events in cell lines transformed by a temperature sensitive (ts) mutant of Bcr/Abl, where the kinase activity of Abl could be regulated. STAT1 and STAT5 were found to be constitutively phosphorylated in 32D, Ba/F3, and TF-1 cells transformed by Bcr/Abl, but not in the untransformed parental cell lines in the absence of IL-3. Phosphorylation of STAT1 and STAT5 was also observed in the human leukemia cell lines K562 and BV173, which express the Bcr/Abl oncogene, but not in several Bcr/Abl-negative leukemia cell lines. Phosphorylation of STAT1 and STAT5 was directly due to the tyrosine kinase activity of Bcr/Abl since it could be activated or deactivated by temperature shifting of cells expressing the Bcr/Abl tr mutant. DNA-STAT complexes were detected in all Bcr/Abl-transformed cell lines and they were supershifted by antibodies against STAT1 and STAT5. DNA-STAT complexes in 32Dp210Bcr/Abl cells were similar, but not identical, to those formed after IL-3 stimulation. It is interesting to note that JAK kinases (JAK1, JAK2, JAK3, and Tyk2) were not consistently activated in Bcr/Abl-positive cells. These data suggest that STATs can be activated directly by Bcr/Abl, possibly bypassing JAK family kinase activation. Overall, our results suggest a novel mechanism that could contribute to some of the major biological effects of Bcr/Abl transformation. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. FU NIDDK NIH HHS [R01 DK43904] NR 51 TC 377 Z9 385 U1 0 U2 8 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAR 1 PY 1996 VL 183 IS 3 BP 811 EP 820 DI 10.1084/jem.183.3.811 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA UC775 UT WOS:A1996UC77500013 PM 8642285 ER PT J AU Mizoguchi, A Mizoguchi, E Chiba, C Spiekermann, GM Tonegawa, S NaglerAnderson, C Bhan, AK AF Mizoguchi, A Mizoguchi, E Chiba, C Spiekermann, GM Tonegawa, S NaglerAnderson, C Bhan, AK TI Cytokine imbalance and autoantibody production in T cell receptor-alpha mutant mice with inflammatory bowel disease SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID PHENOL-CHLOROFORM EXTRACTION; SINGLE-STEP METHOD; IFN-GAMMA; ULCERATIVE-COLITIS; RNA ISOLATION; LYMPHOCYTES; TH1; TROPOMYOSIN; PROTEINS; CLONES AB Spontaneous inflammatory bowel disease (IBD) resembling human ulcerative colitis develops in mice mutant for the T cell receptor alpha gene (TCR-alpha(-/-)). TCR-alpha(-/-) mice lack TCR-alpha/beta(+) cells but contain TCR-gamma/delta(+) cells and a small population of a unique CD4(+), TCR-(alpha(-)/beta(+(low))) cells. Since all the immunoglobulin (Ig) classes are present in these mice, help to B cells must be provided by cells other than TCR-alpha/beta(+) cells. In the present study, we found serum levels of IgG1 and IgG2 to be markedly increased in TCR-alpha(-/-) mice with IBD as compared to TCR-alpha(-/-) mice without IBD or TCR-alpha(+/-) controls. An increase in IgG1-, IgG2a- and IgA- but not IgM-secreting mesenteric lymph node (MLN) B cells was detected in TCR-alpha(-/-) mutant mice. There was also a marked increase in MLN B cells secreting autoantibody (IgG) to tropomyosin, a cytoskeletal protein. Examination of the hyperplastic MLN showed a marked increase in the number of B, TCR-delta(+), and CD4(+) TCR-alpha(-)/beta(+) cells, similar to the cell population observed at the site of colonic inflammation. Analysis of spontaneous cytokine production by MLN cells using an enzyme-linked immunospot assay, immunohistochemistry, and reverse transcription-polymerase chain reaction showed a decrease of interleukin 2 (IL-2) but a marked increase of IL-4 and interferon gamma (IFN-gamma) production in TCR-alpha(-/-) mice with IBD as compared to TCR-alpha(-/-) mice without IBD and TCR alpha(+/-) control mice. Both TCR-alpha(-)/beta(+) and TCR-delta(+) cells were found to be capable of producing IL-4; IFN-gamma was produced mostly by non-T cells, many of which were shown to be CD3(-) NK 1.1(+) cells. We propose that the cytokine imbalance present in these mice results in expansion of B cells, production and switching of autoantibodies to IgG2 subclass, and development of IBD. It is possible that the unusual CD4(+) TCR-alpha(-)/beta(+) population and expanded TCR-gamma(-)/delta(+) population present in TCR-alpha(-/-) mice plays a central role in this abnormal immune response. C1 MASSACHUSETTS GEN HOSP,IMMUNOPATHOL UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,MUCOSAL IMMUNOL LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. MIT,CTR CANC RES,HOWARD HUGHES MED INST,CAMBRIDGE,MA 02139. MIT,DEPT BIOL,CAMBRIDGE,MA 02139. FU NIDDK NIH HHS [DK47677, DK43551] NR 37 TC 187 Z9 187 U1 1 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAR 1 PY 1996 VL 183 IS 3 BP 847 EP 856 DI 10.1084/jem.183.3.847 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA UC775 UT WOS:A1996UC77500017 PM 8642289 ER PT J AU Wetzler, LW Ho, Y Reiser, H AF Wetzler, LW Ho, Y Reiser, H TI Neisserial porins induce B lymphocytes to express costimulatory B7-2 molecules and to proliferate SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID OUTER-MEMBRANE PROTEIN; CTLA-4 COUNTER-RECEPTOR; T-CELL PROLIFERATION; STRUCTURAL GENE; INTERLEUKIN-2 PRODUCTION; POLYCLONAL ACTIVATION; GONORRHOEAE; MENINGITIDIS; CLONING; ANTIGEN AB The neisserial porins are the major protein components of the outer membrane of the pathogenic Neisseria (N. meningitidis and N. gonorrhoeae). They have been shown to be able to enhance the immune response to poorly immunogenic substances (e.g., polysaccharides, peptides, glycolipids, etc.). To explore the basis of their potent adjuvant activity, the effect of the neisserial porins on T-B cell interactions and T cell costimulation was examined. Neisserial porins increased the surface expression of the costimulatory ligand B7-2 (CD86) but did not affect the expression of B7-1 (CD80). In addition, incubation with the neisserial porins increased the T lymphocyte costimulatory ability of B lymphocytes, which was inhibited by anti-B7-2 but not anti-B7-1 monoclonal antibodies. Upregulation of B7-2 on the surface of B lymphocytes may be the mechanism behind the immunopotentiating activity of neisserial porins. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. RP Wetzler, LW (reprint author), BOSTON UNIV,BOSTON CITY HOSP,SCH MED,MAXWELL FINLAND LAB INFECT DIS,774 ALBANY ST,BOSTON,MA 02118, USA. FU NIAID NIH HHS [AI34171, AI33679] NR 62 TC 86 Z9 87 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAR 1 PY 1996 VL 183 IS 3 BP 1151 EP 1159 DI 10.1084/jem.183.3.1151 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA UC775 UT WOS:A1996UC77500047 PM 8642257 ER PT J AU Diacovo, TG Roth, SJ Morita, CT Rosat, JP Brenner, MB Springer, TA AF Diacovo, TG Roth, SJ Morita, CT Rosat, JP Brenner, MB Springer, TA TI Interactions of human alpha/beta and gamma/delta T lymphocyte subsets in shear flow with E-selectin and P-selectin SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID LEUKOCYTE ADHESION MOLECULE-1; RECEPTOR-GAMMA-DELTA; CELL RECEPTOR; RHEUMATOID-ARTHRITIS; ACTIVATED PLATELETS; GLYCOPROTEIN LIGAND; MONOCLONAL-ANTIBODY; MULTIPLE-SCLEROSIS; HOMING RECEPTOR; MYELOID CELLS AB We have compared the ability of human alpha/beta and gamma/delta T lymphocytes to adhere to selectin-bearing substrates, an interaction thought to be essential for homing and localization at sites of inflammation. Both T cell populations form rolling adhesions on E- and P-selectin substrates under physiologic now conditions. Although equivalent to alpha/beta T cells in binding to E-selectin, gamma/delta T cells demonstrated greater ability to adhere to P-selectin that was purified or expressed on the surface of activated, adherent platelets. Under static conditions, 80% of gamma/delta T cells and 53% of alpha/beta T cells formed shear-resistant adhesions to P-selectin, whereas only 30% of gamma/delta and alpha/beta T cells adhered to E-selectin. The enhanced ability of gamma/delta T cells to adhere to P-selectin cannot be attributed to differences in expression of the P-selectin glycoprotein ligand (PSGL-1), as all alpha/beta T cells versus similar to 75% of gamma/delta T cells expressed PSGL-1. Both cell populations expressed a similar percentage of the carbohydrate antigens sialyl Lewis(x) and cutaneous lymphocyte-associated antigen. Depletion of lymphocyte populations or T cell clones bearing these oligosaccharides with the monoclonal antibody CSLEX-1 and HECA-452, respectively, resulted in a substantial reduction in adhesion to E-selectin and slight reduction in adhesion to P-selectin under now conditions. Treatment of cells with an endopeptidase that selectively degrades O-sialomucins such as PSGL-1, abolished P-selectin but not E-selectin adhesion. Removal of terminal sialic acids with neuraminidase or protease treatment of cells abrogated cell adhesion to both selectin substrates. These results provide direct evidence for the presence of distinct E- and P-selectin ligands on T lymphocytes and suggest that gamma/delta T cells may be preferentially recruited to inflammatory sites during the early stages of an immune response when P-selectin is upregulated. C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT RHEUMATOL & IMMUNOL,LYMPHOCYTE BIOL SECT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DIV NEWBORN MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT CARDIOL,BOSTON,MA 02115. RI Morita, Craig/C-1365-2011 FU NHLBI NIH HHS [HL48675] NR 55 TC 57 Z9 57 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAR 1 PY 1996 VL 183 IS 3 BP 1193 EP 1203 DI 10.1084/jem.183.3.1193 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA UC775 UT WOS:A1996UC77500051 PM 8642261 ER PT J AU Lins, RE Gelberman, RH McKeown, L Katz, JN Kadiyala, RK AF Lins, RE Gelberman, RH McKeown, L Katz, JN Kadiyala, RK TI Basal joint arthritis: Trapeziectomy with ligament reconstruction and tendon interposition arthroplasty SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article AB This article provides a qualitative and quantitative outcomes assessment of a consecutive series of 27 patients (30 thumbs) with basal joint arthritis of the thumb undergoing ligament reconstruction and tendon interposition arthroplasty. Outcome analysis revealed that 24 (89%) patients were satisfied with the relief of pain provided by the arthroplasty and 23 (87%) would undergo surgery again. Eighteen (67%) thumbs were noted to have improvement in the ability to perform activities of daily living. Significant improvements were noted in web space measurements and in grip and pinch strength determination. X-ray film assessment using the trapezial space ratio averaged 0.33 +/- 0.08 in preoperative x-ray films of thumbs with stage III and IV degenerative arthritis and 0.23 +/- 0.07 in thumbs following basal joint arthroplasty. This represents a total decrease of 51% in the trapezial space ratio following arthroplasty compared to the normal values obtained in previous studies and 33% compared to the preoperative values obtained in this study. Outcomes assessment at a mean of 42 months after surgery showed that there was no significant correlation between maintenance of trapezial height and both objective and subjective clinical outcomes. Although ligament reconstruction consistently failed to restore trapezial height, primary and secondary clinical outcomes following basal joint arthritis were almost uniformly satisfactory. C1 MASSACHUSETTS GEN HOSP,DEPT ORTHOPAED SURG,BOSTON,MA 02114. FU NIAMS NIH HHS [AR36308] NR 23 TC 75 Z9 76 U1 0 U2 1 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD MAR PY 1996 VL 21A IS 2 BP 202 EP 209 DI 10.1016/S0363-5023(96)80101-8 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA UB822 UT WOS:A1996UB82200007 PM 8683047 ER PT J AU Fontaine, AA He, SQ Stadter, R Ellis, JT Levine, RA Yoganathan, AP AF Fontaine, AA He, SQ Stadter, R Ellis, JT Levine, RA Yoganathan, AP TI In vitro assessment of prosthetic valve function in mitral valve replacement with chordal preservation techniques SO JOURNAL OF HEART VALVE DISEASE LA English DT Article ID VENTRICULAR SYSTOLIC PERFORMANCE; SUBVALVULAR APPARATUS; PAPILLARY-MUSCLES; TENDINEAE; REGURGITATION; LEAFLET AB Background and aims of the study: The importance of chordal preservation techniques in maintaining improved left ventricular function after mitraI valve replacement has been well documented clinically. Currently, the choice of prosthetic valve used in chordal preservation is dependent upon the surgeon's preference, However, the transvalvular flow characteristics of common, clinically used prosthetic valves may be influenced by the mitral subvalvular apparatus, and may result in degraded valve function. The goal of this study was to perform an in vitro evaluation of the influence of chordal preservation on the transvalvular and left ventricular flow patterns of common valve prostheses. Methods: Tissue and mechanical valves have been evaluated under physiologic pulsatile flow with anterior and/or posterior chordal preservation. Flow patterns were assessed by 2-D planar flow visualization, pulsed wave Doppler velocity measurements, 2D echocardiography, and selected color Doppler flow mapping. Based on changes in transvalvular and left ventricular flow patterns, favorable prosthetic valve/ chordal preservation combinations were identified. Additionally, valve orientation was varied to determine optimal orientation. Results: Baseline results without chordal preservation indicate that the anti-anatomic orientation is preferred for the bileaflet Valve design while the tilting disc valve should be oriented with the major axis toward the posterior (free) wall of the ventricle, corroborating published conclusions by other investigators. Some form of flow restriction is observed in all test cases with chordal preservation due to the presence of the subvalvular tissue. In general, bioprostheses showed less flow restriction then the mechanical valves, particularly with lateral flow expansion. This flow restriction may influence pressure recovery downstream of the mechanical valves tested. Increased flow constriction is observed with anterior and posterior chordal preservation. Conclusions: This study favors the use of the St. Jude Medical bileaflet valve orientated in the anti-anatomic position, or the Carpentier-Edwards pericardial valve with chordal preservation. C1 GEORGIA INST TECHNOL,SCH CHEM ENGN,CARDIOVASC FLUID MECH LAB,INST BIOENGN & BIOSCI,ATLANTA,GA 30332. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 29 TC 18 Z9 19 U1 2 U2 4 PU I C R PUBLISHERS PI NORTHWOOD PA CRISPIN HOUSE, 12/A SOUTH APPROACH, MOOR PARK, NORTHWOOD, ENGLAND HA6 2ET SN 0966-8519 J9 J HEART VALVE DIS JI J. Heart Valve Dis. PD MAR PY 1996 VL 5 IS 2 BP 186 EP 198 PG 13 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA VG387 UT WOS:A1996VG38700015 PM 8665014 ER PT J AU DukeCohan, JS Morimoto, C Rocker, JA Schlossman, SF AF DukeCohan, JS Morimoto, C Rocker, JA Schlossman, SF TI Serum high molecular weight dipeptidyl peptidase IV (CD26) is similar to a novel antigen DPPT-L released from activated T cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SYSTEMIC LUPUS-ERYTHEMATOSUS; ADENOSINE-DEAMINASE; MONOCLONAL-ANTIBODIES; LYMPHOCYTES-T; HUMAN-TISSUES; EXPRESSION; FAMILY; MARKER; INVOLVEMENT; SUBSET AB This study demonstrates that the 175-kDa form of dipeptidyl peptidase IV (DPPIV) found in normal human serum is identical with a similarly-sized Ag, DPPT-L, found to be rapidly expressed on the surface of activated T cells, As activation progresses, the expression of DPPT-L reaches a peak on day 3, after which expression falls, whereas expression of the 105-kDa CD26/DPPIV detected by the mAb 1F7 increases, as does the ability to bind adenosine deaminase, The loss of DPPT-L from the surface of activated T cells correlates exactly with the appearance of DPPT-L and DPPIV activity in serum-free tissue culture medium, The release of DPPIV was generally greater from CD4(+) cells than from CD8(+) T cells, and within the CD4(+) subset, the CD45RO(+) subset was the major source, which correlated with surface expression before culture, We show that the DPPIV released from activated T cells is antigenically, biochemically, and enzymatically similar to DPPIV circulating in the serum and is distinct from the DPPIV activity of 105-kDa CD26, The T cell-released DPPIV is able to function as a costimulating molecule for the response to the recall Ag, tetanus toroid, at levels similar to those at which recombinant soluble CD26 and serum DPPIV exhibit costimulatory function, suggesting that the released DPPIV may serve an important immunoregulatory function in vivo, both locally and within the systemic circulation. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. RP DukeCohan, JS (reprint author), DANA FARBER CANC INST,DIV TUMOR IMMUNOL,44 BINNEY ST,BOSTON,MA 02115, USA. RI Duke-Cohan, Jonathan/A-5812-2010 OI Duke-Cohan, Jonathan/0000-0002-9478-9609 FU NCI NIH HHS [CA55601]; NIAID NIH HHS [AI23360-08] NR 35 TC 81 Z9 82 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 MAR 1 PY 1996 VL 156 IS 5 BP 1714 EP 1721 PG 8 WC Immunology SC Immunology GA TW699 UT WOS:A1996TW69900002 PM 8596018 ER PT J AU Wagner, L Gessl, A Parzer, SB Base, W Waldhausl, W Pasternack, MS AF Wagner, L Gessl, A Parzer, SB Base, W Waldhausl, W Pasternack, MS TI Haptoglobin phenotyping by newly developed monoclonal antibodies - Demonstration of haptoglobin uptake into peripheral blood neutrophils and monocytes SO JOURNAL OF IMMUNOLOGY LA English DT Article AB We have generated two IgG murine mAbs that recognize native human haptoglobin (Hp), These mAbs, 3A8 and 482, efficiently bind to the Hp complex regardless of the serum donor's phenotype, The specificity of mAb 3A8 was confirmed by immunoaffinity purification of 3A8-binding material from human serum and subsequent N-terminal amino acid sequencing of the invariant 40-kDa chain, mAb 3A8 and 482 were also reactive with cell-associated Hp when studied by immunocytochemistry, When human peripheral blood leukocytes were tested, 90% of granulocytes and a lesser (and variable) fraction of monocytes displayed an intense intracytoplasmatic granular staining, This was confirmed by flow cytometric analysis of permeabilized leukocytes and by demonstrating the presence of Hp (of the expected Hp serum phenotype) in extracts of washed granulocytes by immunoblotting, Leukocytes obtained from a Hp phenotype 2-2 donor, incubated in culture medium supplemented with 10% serum from a donor possessing the Hp 1-1 phenotype, contained both Hp phenotypes when analyzed by immunoblotting after a 6-h incubation period, In addition, Hp was actively exocytosed by granulocytes following their exposure to Candida albicans, These observations suggest that exogenous Hp is concentrated within granulocytes and not synthesized de novo and is, in turn, exocytosed following neutrophil activation, Northern blotting analysis is consistent with the lack of haptoglobin gene transcription in granulocytes, These findings together with the earlier observations that Hp modulates granulocyte activity suggest that Hp levels may be enhanced locally at sites of inflammation to modulate granulocyte activity. C1 MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP Wagner, L (reprint author), UNIV VIENNA,DEPT MED 3,DIV ENDOCRINOL & METAB,WAHRINGER GURTEL 18-20,A-1090 VIENNA,AUSTRIA. NR 35 TC 48 Z9 52 U1 1 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 1 PY 1996 VL 156 IS 5 BP 1989 EP 1996 PG 8 WC Immunology SC Immunology GA TW699 UT WOS:A1996TW69900038 PM 8596054 ER PT J AU Cascardi, M Riggs, DS HearstIkeda, D Foa, EB AF Cascardi, M Riggs, DS HearstIkeda, D Foa, EB TI Objective ratings of assault safety as predictors of PTSD SO JOURNAL OF INTERPERSONAL VIOLENCE LA English DT Article; Proceedings Paper CT 27th Annual Meeting of the Association-for-the-Advancement-of-Behavior-Therapy CY NOV, 1993 CL ATLANTA, GA SP Assoc Adv Behav Therapy ID POSTTRAUMATIC-STRESS-DISORDER; RAPE VICTIMS AB Pre-trauma beliefs about the safety of the world and one's own invulnerability are thought to influence post-trauma reactions. The current study examined whether two trauma characteristics that are hypothesized to relate to perceptions of safety, assault location and assailant identity, predict the rate and severity of post-traumatic stress disorder (PTSD) in female rape victims. It also attempted to reduce the confound of assault brutality Results indicated that women assaulted in locations rated as safe had significantly more severe overall PTSD symptoms than women assaulted in dangerous locations. However; contrary to our prediction, women assaulted by dangerous assailants reported significantly more severe PTSD symptoms than women assaulted by assailants rated as safe. Assault brutality and violation of safety expectations may represent two distinct aspects of the assault, both influencing the severity of post-trauma reactions. C1 HAHNEMANN UNIV,MED COLL PENN,CTR TREATMENT & STUDY ANXIETY,PHILADELPHIA,PA 19129. HAHNEMANN UNIV,MED COLL PENN,DEPT CLIN & HLTH PSYCHOL,PHILADELPHIA,PA 19129. DEPT VET AFFAIRS MED CTR,NATL CTR PTSD,WOMENS HLTH SERV DIV,BOSTON,MA. NR 24 TC 17 Z9 17 U1 3 U2 4 PU SAGE SCIENCE PRESS PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 SN 0886-2605 J9 J INTERPERS VIOLENCE JI J. Interpers. Violence PD MAR PY 1996 VL 11 IS 1 BP 65 EP 78 DI 10.1177/088626096011001005 PG 14 WC Criminology & Penology; Family Studies; Psychology, Applied SC Criminology & Penology; Family Studies; Psychology GA TW754 UT WOS:A1996TW75400005 ER PT J AU Gomez, L Rubio, MP Martin, MT Vazquez, JJ Idoate, M Pastorfide, G Pestana, A Seizinger, BR Barnhill, RL Castresana, JS AF Gomez, L Rubio, MP Martin, MT Vazquez, JJ Idoate, M Pastorfide, G Pestana, A Seizinger, BR Barnhill, RL Castresana, JS TI Chromosome 17 allelic loss and NF1-GRD mutations do not play a significant role as molecular mechanisms leading to melanoma tumorigenesis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE loss of heterozygosity; PCR-SSCP; skin cancer ID NEUROFIBROMATOSIS TYPE-1 GENE; HUMAN-MALIGNANT MELANOMA; POINT MUTATIONS; CELL-LINES; P53; HETEROZYGOSITY; POLYMORPHISMS; NEUROBLASTOMA; EXPRESSION; DELETION AB Allelic loss in human cutaneous melanoma has been detected on chromosomes 1p, 6q, 9p, 10q, and 11q, Chromosome 17 contains important tumor suppressor genes such as p53, NM23, and neurofibromatosis type 1 (NF1), which have been implicated in melanoma tumorigenesis, The role of p53 has already been studied by a number of laboratories, showing contrasting results, In the present study, two restriction fragment length polymorphism (RFLP) probes for the NM23 and NF1 genes, together with five other RFLP and four variable number of tandem repeat chromosome 17 probes, were investigated at the loss of heterozygosity (LOH) level in a Southern blot-based assay, The NF1 gene was also tested for LOH by a polymerase chain reaction (PCR)-based approach in two different experiments, using a dinucleotide repeat polymorphic probe at locus D17S250 (17q11.2q12), and an Alu probe intragenic to the NF1 gene (17q11.2). A PCR single-strand conformation polymorphism assay was included in the study for mutation detection at the NF1-GTPase-activating protein-related domain (GRD), A total of 68 melanocytic tumors were analyzed, LOH was detected in 9 of 87 informative cases (10%). LEW301 (17p11.2-pcen) presented the highest LOH frequency (22%), NM23 showed LOH in 17% of the informative cases, while NF1 did not show either LOH in the Southern blot- and PCR-based experiments or mutations at the NF1-GRD. These results are in concordance with those of previous smaller studies, but when compared with higher LOH frequencies obtained from other chromosomes, these findings indicate that the LOH values found in our study can most likely be attributed to background effect, Thus, chromosome 17 LOH is likely to play an unimportant role as a genetic event in melanoma tumorigenesis. Nevertheless, NF1 merits further study, since homozygous deletions have been detected at this locus in melanoma cell lines. C1 CSIC,INST INVEST BIOMED,E-28029 MADRID,SPAIN. CRUCES GEN HOSP,DEPT PATHOL,BARACALDO,SPAIN. UNIV BASQUE COUNTRY,SCH MED,BARACALDO,SPAIN. UNIV NAVARRA CLIN,SCH MED,DEPT HISTOL & ANAT PATHOL,PAMPLONA,SPAIN. MASSACHUSETTS GEN HOSP,MOLEC NEUROONCOL LAB,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,NEUROSURG SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138. BRIGHAM & WOMENS HOSP,DEPT PATHOL DERMATOPATHOL,BOSTON,MA. HARVARD UNIV,SCH MED,BOSTON,MA. RI Rubio, Mari-Paz/K-4364-2014; OI Rubio, Mari-Paz/0000-0003-3963-5903; Castresana, Javier S./0000-0002-2373-482X NR 35 TC 12 Z9 12 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAR PY 1996 VL 106 IS 3 BP 432 EP 436 DI 10.1111/1523-1747.ep12343578 PG 5 WC Dermatology SC Dermatology GA UB968 UT WOS:A1996UB96800008 PM 8648172 ER PT J AU Anderson, IC Mari, B Sugarbaker, D Shipp, MA AF Anderson, IC Mari, B Sugarbaker, D Shipp, MA TI Tumor stromal cell interaction in human lung cancers increases the processing and bioactivity of 72 KD type IV collagenase. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 BRIGHAM & WOMENS HOSP,DANA FARBER CANC INST,BOSTON,MA 02115. RI Mari, Bernard/F-8960-2013; Mari, Bernard/D-7445-2015 OI Mari, Bernard/0000-0002-0422-9182 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A202 EP A202 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700032 ER PT J AU Boussiotis, VA Barber, DL Freeman, GJ Lee, BJ Gribben, JG Nadler, LM AF Boussiotis, VA Barber, DL Freeman, GJ Lee, BJ Gribben, JG Nadler, LM TI Prevention of T cell clonal anergy is directly linked to Jak3 kinase activation. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A202 EP A202 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700030 ER PT J AU Boussiotis, VA Barber, DL Freeman, GJ Lee, BJ Gribben, JG Nadler, LM AF Boussiotis, VA Barber, DL Freeman, GJ Lee, BJ Gribben, JG Nadler, LM TI Differential association of T cell receptor (TCR) with protein tyrosine kinases is critical for selective signaling resulting in anergy or productive immunity. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A202 EP A202 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700031 ER PT J AU Bruening, JC Winnay, J BonnerWeir, S Accili, D Kahn, CR AF Bruening, JC Winnay, J BonnerWeir, S Accili, D Kahn, CR TI Creating polygenic models of insulin resistance and diabetes mellitus. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. JOSLIN DIABET CTR,BOSTON,MA 02215. NR 0 TC 1 Z9 1 U1 0 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A258 EP A258 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700362 ER PT J AU Burger, AJ Hamer, AW Choi, CC DElia, JA Weinrauch, LA AF Burger, AJ Hamer, AW Choi, CC DElia, JA Weinrauch, LA TI Elevated cholesterol is associated with abnormal heart rate variability in diabetics but not in patients with coronary disease. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 DEACONESS HOSP,BOSTON,MA. JOSLIN DIABET CTR,BOSTON,MA 02215. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A211 EP A211 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700084 ER PT J AU Delgado, JC Turbay, D Ahmed, AR Bohl, K Morton, E Yunis, EJ AF Delgado, JC Turbay, D Ahmed, AR Bohl, K Morton, E Yunis, EJ TI Three blistering skin diseases (pemphigoids) are associated with HLA-DQB1*0301. SO JOURNAL OF INVESTIGATIVE MEDICINE 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 SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A202 EP A202 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700033 ER PT J AU Febbo, PG Giovannucci, E Hennekens, CH Stampfer, M Brown, M Krithivas, K Kantoff, PW AF Febbo, PG Giovannucci, E Hennekens, CH Stampfer, M Brown, M Krithivas, K Kantoff, PW TI Different alleles for the type II 5-alpha reductase gene confer varying risk for prostate cancer SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 DANA FARBER CANC INST,DEPT MED ONCOL,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH PUBL HLTH,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A200 EP A200 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700023 ER PT J AU Fusunyan, RD Quinn, JJ MacDermott, RP Sanderson, IR AF Fusunyan, RD Quinn, JJ MacDermott, RP Sanderson, IR TI Butyrate alters the expression of chemokines by intestinal epithelial cells according to chromosomal location. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 LAHEY CLIN FDN,GASTROINTESTINAL UNIT,BOSTON,MA. MASSACHUSETTS GEN HOSP,COMBINED PROGRAM PEDIAT GASTROENTEROL & NUTR,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 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A201 EP A201 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700026 ER PT J AU Gentilini, A Feliers, D Woodruff, K Abboud, S AF Gentilini, A Feliers, D Woodruff, K Abboud, S TI Characterization and regulation of insulin-like growth factor binding proteins (IGFBPs) in human liver fat storing cells (FSC). SO JOURNAL OF INVESTIGATIVE MEDICINE 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 SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A302 EP A302 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700612 ER PT J AU Gribben, JG Boussiotis, V Ke, XY Freeman, G Nadler, LM AF Gribben, JG Boussiotis, V Ke, XY Freeman, G Nadler, LM TI Characterization of molecular signals that prevent the induction of anergy SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A201 EP A201 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700027 ER PT J AU Gribben, JG Nadler, LM AF Gribben, JG Nadler, LM TI Lack of PCR amplifiable minimal residual disease predicts freedom from relapse following autologous bone marrow transplantation for B-cell malignancies. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A201 EP A201 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700028 ER PT J AU Herbert, V AF Herbert, V TI Will genuine health care be overwhelmed by questionable and fraudulent care? SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 MT SINAI MED CTR,NEW YORK,NY 10029. BRONX VET AFFAIRS MED CTR,NEW YORK,NY. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A323 EP A323 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700727 ER PT J AU Jancso, A Ukiyama, E Labeots, L Morikawa, N Chen, G Haqq, CM Radek, J King, CY Donahoe, PK Weiss, MA AF Jancso, A Ukiyama, E Labeots, L Morikawa, N Chen, G Haqq, CM Radek, J King, CY Donahoe, PK Weiss, MA TI Structure-function relationships in SRY: Role of an architectural transcription factor in testis determination and ''sex reversal'' SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 UNIV CHICAGO,DEPT BIOCHEM & MOLEC BIOL,CHICAGO,IL 60637. UNIV CHICAGO,CTR MOLEC ONCOL,CHICAGO,IL 60637. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,PEDIAT SURG LABS,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 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A248 EP A248 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700302 ER PT J AU Kitch, B Thomas, M Deraska, D LloydJones, D Shaw, A Thadhani, R Vanvakas, S Finkelstein, J AF Kitch, B Thomas, M Deraska, D LloydJones, D Shaw, A Thadhani, R Vanvakas, S Finkelstein, J TI Vitamin D deficiency among medical inpatients. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. RI Lloyd-Jones, Donald/C-5899-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A225 EP A225 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700170 ER PT J AU Kotlar, TJ Albanese, C Crowley, WF Scully, RE Young, RH Jameson, JL AF Kotlar, TJ Albanese, C Crowley, WF Scully, RE Young, RH Jameson, JL TI Mutation of follicle stimulating hormone receptor in human ovarian sex cord tumors SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NORTHWESTERN UNIV,SCH MED,CHICAGO,IL. MASSACHUSETTS GEN HOSP,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 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A267 EP A267 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700408 ER PT J AU Parks, JM AF Parks, JM TI Coherently-firing cortical neurons as markers of current ''pondering'' outcome - A brain function modelling study SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT NEUROSURG,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 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A333 EP A333 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700786 ER PT J AU Soiffer, R Lynch, T Mihm, M Jung, K Kolesar, K Liebster, L Lam, P Duda, R Mentzer, S Singer, S Tanabe, K Johnson, R Sober, A Bhan, A Clift, S Cohen, L Parry, G Rokovich, J Richards, L Drayer, J Berns, A Mulligan, RC Dranoff, G AF Soiffer, R Lynch, T Mihm, M Jung, K Kolesar, K Liebster, L Lam, P Duda, R Mentzer, S Singer, S Tanabe, K Johnson, R Sober, A Bhan, A Clift, S Cohen, L Parry, G Rokovich, J Richards, L Drayer, J Berns, A Mulligan, RC Dranoff, G TI Granulocyte-macrophage colony stimulating factor based melanoma vaccines. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. ALBANY MED COLL,ALBANY,NY. WHITEHEAD INST BIOMED RES,CAMBRIDGE,MA 02142. SOMATIX THERAPY CORP,ALAMEDA,CA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A201 EP A201 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700029 ER PT J AU Turbay, D Delgado, JC Corzo, D Awdeh, Z Alper, C Lieberman, J Yunis, EJ AF Turbay, D Delgado, JC Corzo, D Awdeh, Z Alper, C Lieberman, J Yunis, EJ TI Association of tumor necrosis factor (TNF) variants with clozapine-induced agranulocytosis in two different ethnic groups. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 DANA FARBER CANC INST,CTR BLOOD RES,BOSTON,MA. LONG ISL JEWISH MED CTR,NEW YORK,NY. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A202 EP A202 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700034 ER PT J AU Weber, GF Ashkar, S Glimcher, MJ Cantor, H AF Weber, GF Ashkar, S Glimcher, MJ Cantor, H TI Interaction between CD44 and osteopontin as a potential basis for metastasis formation. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PATHOL,DIV IMMUNOPATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CHILDRENS HOSP,DEPT ORTHOPED RES,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A203 EP A203 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700036 ER PT J AU Hosokawa, Y Arnold, A AF Hosokawa, Y Arnold, A TI Cyclin D1/PRAD1 as a central target in oncogenesis SO JOURNAL OF LABORATORY AND CLINICAL MEDICINE LA English DT Review ID HUMAN BREAST-CANCER; CELL-CYCLE; RETINOBLASTOMA PROTEIN; CENTROCYTIC LYMPHOMA; CANDIDATE ONCOGENE; MOLECULAR-CLONING; CHROMOSOME 11Q13; GENE-EXPRESSION; NUCLEAR-PROTEIN; G1 CYCLIN C1 MASSACHUSETTS GEN HOSP,LAB ENDOCRINE ONCOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 67 TC 28 Z9 28 U1 0 U2 1 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 MAR PY 1996 VL 127 IS 3 BP 246 EP 252 DI 10.1016/S0022-2143(96)90092-X PG 7 WC Medical Laboratory Technology; Medicine, General & Internal; Medicine, Research & Experimental SC Medical Laboratory Technology; General & Internal Medicine; Research & Experimental Medicine GA TZ073 UT WOS:A1996TZ07300004 PM 9273357 ER PT J AU Moradpour, D Wakita, T Tokushige, K Carlson, RI Krawczynski, K Wands, JR AF Moradpour, D Wakita, T Tokushige, K Carlson, RI Krawczynski, K Wands, JR TI Characterization of three novel monoclonal antibodies against hepatitis C virus core protein SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE recombinant protein; epitope mapping; immunostaining ID NON-B-HEPATITIS; NON-A; HEPATOCELLULAR-CARCINOMA; MAMMALIAN-CELLS; CAPSID PROTEIN; EXPRESSION; IDENTIFICATION; ANTIGEN; GENOME; TRANSFORMATION AB Three novel monoclonal antibodies (MAbs) were established against a recombinant hepatitis C virus (HCV) core protein derived from cloned genotype 1b HCV cDNA. MAbs C7-50 and C8-59 recognize a conserved linear epitope represented by amino acid residues 21 to 40 of the nucleocapsid protein. MAb C8-48 is directed against a strain-specific conformational epitope located within the first 82 amine acids. A sensitive two-site MAb-based immunoradiometric assay was established using antibodies directed against distinct epitopes on the nucleocapsid protein. Processed 21 kDa core protein was detected by immunoblotting in human hepatocellular carcinoma cell lines and primary adult rat hepatocytes transfected with a cytomegalovirus promoter-driven expression construct. Immunofluorescence microscopy studies revealed a granular and vesicular cytoplasmic staining pattern. MAb C7-50 was used successfully to detect HCV core antigen in chronically infected chimpanzee liver tissue. These MAbs represent important reagents for the study of HCV biology and for the development of immunodiagnostic assays. (C) 1996 Wiley-Liss, Inc. C1 MASSACHUSETTS GEN HOSP,CTR CANC,MOLEC HEPATOL LAB,BOSTON,MA 02129. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. CTR DIS CONTROL & PREVENT,HEPATITIS BRANCH,ATLANTA,GA 30341. FU NCI NIH HHS [CA-35711]; NIAAA NIH HHS [AA-08169, AA-02666] NR 36 TC 51 Z9 53 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD MAR PY 1996 VL 48 IS 3 BP 234 EP 241 DI 10.1002/(SICI)1096-9071(199603)48:3<234::AID-JMV4>3.0.CO;2-9 PG 8 WC Virology SC Virology GA TY102 UT WOS:A1996TY10200004 PM 8801283 ER PT J AU Higgins, JD Bridger, GJ Derian, CK Beblavy, MJ Hernandez, PE Gaul, FE Abrams, MJ Pike, MC Solomon, HF AF Higgins, JD Bridger, GJ Derian, CK Beblavy, MJ Hernandez, PE Gaul, FE Abrams, MJ Pike, MC Solomon, HF TI N-terminus urea-substituted chemotactic peptides: New potent agtagonists and antagonists toward the neutrophil fMLF receptor SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID RABBIT NEUTROPHILS; CHEMOATTRACTANTS; OLIGOPEPTIDES C1 RW JOHNSON PHARMACEUT RES INST, SPRING HOUSE, PA 19477 USA. MASSACHUSETTS GEN HOSP, ARTHRIT UNIT, BOSTON, MA 02114 USA. RP Higgins, JD (reprint author), JOHNSON MATTHEY BIOMED RES, 1401 KING RD, W CHESTER, PA 19380 USA. NR 13 TC 39 Z9 39 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD MAR 1 PY 1996 VL 39 IS 5 BP 1013 EP 1015 DI 10.1021/jm950908d PG 3 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA TY544 UT WOS:A1996TY54400001 PM 8676333 ER PT J AU Burke, TR Ye, B Akamatsu, M Ford, H Yan, XJ Kole, HK Wolf, G Shoelson, SE Roller, PP AF Burke, TR Ye, B Akamatsu, M Ford, H Yan, XJ Kole, HK Wolf, G Shoelson, SE Roller, PP TI 4'-O-[2-(2-fluoromalonyl)]-L-tyrosine: A phosphotyrosyl mimic for the preparation of signal transduction inhibitory peptides SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID SOLID-PHASE SYNTHESIS; ANALOGS; ACIDS AB Development of phosphotyrosyl (pTyr) mimetics which are stable to protein-tyrosine phosphatases (PTPs), yet can retain biological potency when incorporated into peptides, is an active area of drug development. Since a majority of pTyr mimetics derive their ''phosphofunctionality'' from phosphorus-containing moieties, such as phosphonates, evolution of new inhibitors and modes of prodrug derivatization have been restricted to chemistries appropriate for phosphorus-containing moieties. A new, nonphosphorus-containing pTyr mimetic has recently been reported, L-O-(2-malonyl)tyrosine (OMT, 5), which can be incorporated into peptides that exhibit good PTP and Src homology 2 (SH2) domain inhibitory potency. For phosphonate-based pTyr mimetics such as phosphonomethyl phenylalanine (Pmp, 2), introduction of fluorines a to the phosphorus has provided higher affinity pTyr mimetics. This strategy has now been applied to OR IT, and herein is reported 4'-O-[2-(2-fluoromalonyl)]-L-tyrosine (FOMT) 6), a new fluorine-containing nonphosphorus pTyr mimetic. Incorporation of FOMT into appropriate peptides results in good inhibition of both PTP and SH2 domains. In an assay measuring the inhibition of PTP 1B-mediated dephosphorylation of phosphorylated insulin receptor, the peptide Ac-DA-D-E-X-L-amide exhibited a 10-fold enhancement in inhibitory potency for X = FOMT (19) (IC50 = 1 mu M) relative to the unfluorinated peptide, X = OMT (18) (IC50 = 10 mu M). Molecular modeling indicated that this increased affinity may be attributable to new hydrogen-bonding interactions between the fluorine and the enzyme catalytic site, and not due to lowering of pK(a) values. In a competition binding assay using the p85 PI 3-kinase C-terminal SH2 domain GST fusion construct, the inhibitory peptide, Ac-D-X-V-P-M-L-amide, showed no enhancement of inhibitory potency for X = FOMT (22) (IC50 = 18 mu M) relative to the unfluorinated peptide, X = OMT (21) (IC50 = 14 mu M). The use of FOMT would therefore appear to have particular potential for the development of PTP inhibitors. C1 NIA,GERONTOL RES CTR,NIH,DIABET UNIT,LAB CLIN PHYSIOL,BALTIMORE,MD 21224. HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02215. RP Burke, TR (reprint author), NCI,NIH,MED CHEM LAB,DIV BASIC SCI,BLDG 37,ROOM 5C06,BETHESDA,MD 20892, USA. RI Burke, Terrence/N-2601-2014 NR 34 TC 93 Z9 94 U1 0 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD MAR 1 PY 1996 VL 39 IS 5 BP 1021 EP 1027 PG 7 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA TY544 UT WOS:A1996TY54400004 PM 8676336 ER PT J AU McGuire, J AF McGuire, J TI AB 3632 mental health entitlement for special education students in California: Aspects of the Los Angeles experience SO JOURNAL OF MENTAL HEALTH ADMINISTRATION LA English DT Article AB California Assembly Bill (AB) 3632, passed in 1984, ushered in an era of entitlement to mental health services for schoolchildren with serious emotional disturbances. This article examines the development of the law, the children's public mental health context in Los Angeles County, and the significant impact of the legislation on distribution of mental health services in Los Angeles County and in one Los Angeles area community mental health center Countywide and agency data are presented that document AB 3632 and regular mental health service provision differences in gender age, ethnic, income, and language domains and, at the agency level, an increasing proportion of AB 3632 clients. Implications of AB 3632 service provision in relation to provision of mental health services to children in general are reviewed. RP McGuire, J (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,SOCIAL WORK SERV W122,11301 WILSHIRE BLVD,BLDG 500,ROOM 6651,LOS ANGELES,CA 90073, USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU SAGE SCIENCE PRESS PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 SN 0092-8623 J9 J MENT HEALTH ADMIN JI J. Ment. Health Adm. PD SPR PY 1996 VL 23 IS 2 BP 207 EP 216 DI 10.1007/BF02519111 PG 10 WC Health Policy & Services SC Health Care Sciences & Services GA UH242 UT WOS:A1996UH24200005 PM 10157408 ER PT J AU Wechsler, AF AF Wechsler, AF TI Handbook of neurological speech and language disorders - Kirshner,HS SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Book Review RP Wechsler, AF (reprint author), UNIV CALIF LOS ANGELES,SCH MED,DEPT NEUROL,W LOS ANGELES VA MED CTR,LOS ANGELES,CA 90024, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD MAR PY 1996 VL 184 IS 3 BP 201 EP 202 PG 2 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA UA384 UT WOS:A1996UA38400021 ER PT J AU Schulder, M Loeffler, JS Howes, AE Alexander, E Black, PM AF Schulder, M Loeffler, JS Howes, AE Alexander, E Black, PM TI The radium bomb: Harvey Cushing and the interstitial irradiation of gliomas SO JOURNAL OF NEUROSURGERY LA English DT Article DE Harvey Cushing; brain tumor; radiotherapy; brachytherapy; history of neurosurgery AB Harvey Cushing performed over 2000 operations on patients with brain tumors, including 832 for gliomas. He implanted radioactive radium needles, known as a 'radium bomb,' in a small number of these patients. He was not impressed with the results and did not pursue this method of treatment in a serious way. The authors present here Cushing's little-known experience with brachytherapy and discuss the reasons for his lack of interest in this technique, despite his advocacy of radiotherapy for certain lesions. An interesting perspective is offered for contemporary neurosurgeons involved in the treat ment of brain tumors with cranial irradiation. C1 BRIGHAM & WOMENS HOSP, CHILDRENS HOSP, DANA FARBER CANC INST, BRAIN TUMOR CTR, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, JOINT CTR RADIAT THERAPY, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DEPT SURG NEUROSURG, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DEPT RADIAT ONCOL, BOSTON, MA 02115 USA. RP Schulder, M (reprint author), UNIV & MED DENT NEW JERSEY, NEW JERSEY MED SCH, NEUROSURG SECT, 90 BERGEN ST, SUITE 7300, NEWARK, NJ 07013 USA. NR 15 TC 14 Z9 14 U1 0 U2 1 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD MAR PY 1996 VL 84 IS 3 BP 530 EP 532 DI 10.3171/jns.1996.84.3.0530 PG 3 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA TW713 UT WOS:A1996TW71300026 PM 8609571 ER PT J AU Newton, TL Haviland, JM Contrada, RJ AF Newton, TL Haviland, JM Contrada, RJ TI The face of repressive coping: Social context and the display of hostile expressions and social smiles SO JOURNAL OF NONVERBAL BEHAVIOR LA English DT Article ID FACIAL EXPRESSION; SELF-PRESENTATION; EMOTION; PATTERNS; BEHAVIOR; STRESS AB The present study examined the nonverbal correlates of repressive coping, extending previous research in two ways: (1) participants' nonverbal behaviors were observed in either of two conditions that differed with respect to the salience of public identity; (2) an anatomically-based facial coding system was used to assess participants' emotion expressions and symbolic communication behaviors. Sixty female undergraduates, classified as repressive, low-anxious, or high-anxious, were videotaped during the preparation and delivery of a self-disclosing speech. During both the preparation and delivery, the salience of participants' public identities was either minimized (low-salience condition) or maximized (high-salience condition). Repressors and nonrepressors exhibited similar frequencies of hostile facial expressions. Repressors differed from nonrepressors by their frequent expressions of social smiles and conversational illustrators when their public selves were most salient. These findings suggest that certain symbolic communication behaviors may be nonverbal analogues of cognitive coping processes, and they support the utility of including expressive behaviors in conceptualizations of emotion-focused coping. RP Newton, TL (reprint author), VET AFFAIRS MED CTR,WOMENS HLTH SCI DIV,NATL CTR POSTTRAUMAT STRESS DISORDER,116 B-3,BOSTON,MA 02130, USA. NR 29 TC 10 Z9 10 U1 0 U2 3 PU HUMAN SCI PRESS INC PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 SN 0191-5886 J9 J NONVERBAL BEHAV JI J. Nonverbal Behav. PD SPR PY 1996 VL 20 IS 1 BP 3 EP 22 DI 10.1007/BF02248712 PG 20 WC Psychology, Social SC Psychology GA TZ547 UT WOS:A1996TZ54700001 ER PT J AU Buerhaus, PI Clifford, JC Fay, MS Miller, JR Sporing, EM Weissman, GK AF Buerhaus, PI Clifford, JC Fay, MS Miller, JR Sporing, EM Weissman, GK TI Executive nurse leadership - The Harvard Nursing Research Institute's Conference Summary SO JOURNAL OF NURSING ADMINISTRATION LA English DT Article AB The Harvard Nursing Research Institute organized a national invitational conference on executive nursing leadership in major teaching hospitals and academic health centers, The conference brought together many of the nation's eminent nurse executives and other prominent individuals in healthcare to analyze the unique and complex challenges facing these organizations, expose participants to other perspectives, and articulate specific aims and strategies that might be taken to increase their effectiveness in lending the nursing profession's efforts to shape the ongoing transformation of the healthcare system. C1 HARVARD UNIV,SCH PUBL HLTH,DEPT HLTH POLICY & MANAGEMENT,BOSTON,MA 02115. BETH ISRAEL HOSP,BOSTON,MA 02215. DEACONESS HOSP,PATIENT CARE SERV,BOSTON,MA. HARVARD UNIV,CHILDRENS HOSP,PATIENT SERV,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. RP Buerhaus, PI (reprint author), HARVARD UNIV,NURSING RES INST,BOSTON,MA 02115, USA. NR 4 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0002-0443 J9 J NURS ADMIN JI J. Nurs. Adm. PD MAR PY 1996 VL 26 IS 3 BP 21 EP 29 DI 10.1097/00005110-199603000-00012 PG 9 WC Nursing SC Nursing GA TZ908 UT WOS:A1996TZ90800011 PM 8618120 ER PT J AU Blais, MA Benedict, KB Norman, DK AF Blais, MA Benedict, KB Norman, DK TI The perceived clarity of the axis II criteria sets SO JOURNAL OF PERSONALITY DISORDERS LA English DT Article ID DSM-III; PERSONALITY-DISORDERS; RELIABILITY AB The DSM-III-R personality disorders continue to be plagued by low diagnostic reliability. It has been suggested that the Axis II criteria sets themselves contribute to this low reliability by being unclear and poorly worded. To date there has been no direct empirical exploration of the perceived clarity of these criteria, in this study, groups of mental health professionals and lay persons rated the DSM-III-R FD criteria and the criteria for major depressive disorder (MDD) for clarity and understandability, The results showed that the lay group rated all 11 of Axis II criteria sets as being significantly more clear than did the mental health professionals. No difference was seen between the two groups on their ratings of the MDD criteria. Furthermore, professional group rated the majority of the PD criteria sets as being less clear than the MDD criteria, whereas the lay people rated 9 of the 11 PD criteria sets as being more clear than the MDD criteria. C1 HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138. RP Blais, MA (reprint author), MASSACHUSETTS GEN HOSP,INPATIENT PSYCHIAT SERV,DEPT PSYCHIAT,BLAKE 11,32 FRUIT ST,BOSTON,MA 02114, USA. NR 17 TC 7 Z9 7 U1 0 U2 0 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 SN 0885-579X J9 J PERS DISORD JI J. Pers. Disord. PD SPR PY 1996 VL 10 IS 1 BP 16 EP 22 PG 7 WC Psychiatry SC Psychiatry GA UJ380 UT WOS:A1996UJ38000004 ER PT J AU Reid, MS Hsu, K Tolliver, BK Crawford, CA Berger, SP AF Reid, MS Hsu, K Tolliver, BK Crawford, CA Berger, SP TI Evidence for the involvement of phospholipase A(2) mechanisms in the development of stimulant sensitization SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID VENTRAL TEGMENTAL AREA; LONG-TERM POTENTIATION; PLATELET-ACTIVATING-FACTOR; ARACHIDONIC-ACID RELEASE; INDUCED DOPAMINE EFFLUX; FREELY MOVING RATS; NUCLEUS-ACCUMBENS; BEHAVIORAL SENSITIZATION; COCAINE TREATMENT; SUBSTANCE-P AB Evidence suggests that phospholipase A(2) (PLA(2)) activation is involved in numerous neuroplastic phenomena, including long-term potentiation. Considering the pharmacological similarities between long-term potentiation and stimulant sensitization, it seems possible that PLA(2) activity also might have a role in the induction of stimulant sensitization. In this study, we have investigated whether PLA(2) inhibition, by quinacrine, has any effects on stimulant-induced behavioral sensitization. Both locomotor and stereotypic behavioral sensitization were dose-dependently blocked in rats pretreated with quinacrine (8-25 mg/kg i.p.) 15 min before cocaine (30 mg/kg i.p.), when tested with cocaine (15 mg/kg i.p) 72 hr later. Similar results also were found with d-amphetamine (2 mg/kg i.p,) sensitization using a 10-day treatment regimen with testing on day 11. The ability of PLA(2) activation, by melittin, to produce cocaine sensitization also was tested. Local injections of melittin (0.1 mu g/0.4 mu l) into the ventral tegmental area sensitized the subsequent stimulation of locomotor activity, stereotypy and nucleus accumbens dopamine release by cocaine, when tested 72 hr later. Local injections of melittin (0.1-1.0 mu g/0.8 mu l) into the nucleus accumbens had a moderate sensitizing effect on locomotion. Quinacrine (16 mg/kg) pretreatment 45 min before intraventral tegmental area melittin injection significantly decreased melittin-induced sensitization of the locomotor and stereotypy response to cocaine. These results indicate that PLA(2) activation may play a role in the induction of stimulant sensitization. It is proposed that PLA(2) activity in mesolimbic dopamine neurons, at the level of the cell bodies and perhaps the nerve terminals, is involved in the biochemical mechanisms mediating the development of stimulant sensitization. RP Reid, MS (reprint author), UNIV CALIF SAN FRANCISCO,SAN FRANCISCO VET AFFAIRS MED CTR,DEPT PSYCHIAT,PSYCHIAT SERV 116W,SAN FRANCISCO,CA 94121, USA. RI Crawford, cynthia/G-2603-2012 FU NIDA NIH HHS [R29 DA07376] NR 92 TC 27 Z9 28 U1 1 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD MAR PY 1996 VL 276 IS 3 BP 1244 EP 1256 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TZ544 UT WOS:A1996TZ54400049 PM 8786557 ER PT J AU Gillies, R Kollias, N Hasan, T Diddens, H AF Gillies, R Kollias, N Hasan, T Diddens, H TI Spectral characterization of the benzoporphyrin derivative monoacid ring-A photoproduct formed in fetal calf solutions during irradiation with 694 nm continuous-wave radiation SO JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY LA English DT Article DE benzoporphyrin derivative monoacid ring A; photoproduct; spectroscopy; photodynamic therapy; singlet oxygen ID PHOTODYNAMIC THERAPY; PROTOPORPHYRIN-IX; PHOTOSENSITIZER; BIODISTRIBUTION; MODEL AB Benzoporphyrin derivative monoacid ring A (BPD-MA) is a second-generation photosensitizer for photodynamic therapy (PDT) that has shown good results in phase I clinical trials. Similar to other porphyrin derivatives, BPD-MA readily photobleaches during in-vivo PDT treatment. This study investigated the photodegradation of BPD-MA in fetal calf serum (FCS) solutions in vitro. Absorption and fluorescence spectra from dilute solutions of BPD-MA in 10% FCS were recorded before and immediately after irradiation with light at 694 nm. After irradiation, the appearance of a new fluorescence emission band at 650 nm and changes in the fluorescence excitation spectra indicate the formation of a photoproduct. Photoproduct formation was observed only when BPD-MA was bound to FCS and in oxygenated solutions. The spectroscopy of the photoproduct is consistent with the reaction of an oxygen species with the ring B vinyl group, forming a hydroxyaldehyde photoproduct. Monitoring the increase in photoproduct fluorescence during treatment may provide an in-vivo dosimeter to measure PDT efficacy. C1 MASSACHUSETTS GEN HOSP, WELLMAN LABS PHOTOMED, BOSTON, MA 02114 USA. MED LASERZENTRUM LUBECK, LUBECK, GERMANY. NR 17 TC 13 Z9 13 U1 0 U2 1 PU ELSEVIER SCIENCE SA PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 1011-1344 J9 J PHOTOCH PHOTOBIO B JI J. Photochem. Photobiol. B-Biol. PD MAR PY 1996 VL 33 IS 1 BP 87 EP 90 DI 10.1016/1011-1344(95)07222-5 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA UM101 UT WOS:A1996UM10100012 PM 8786464 ER PT J AU Speer, SR Kjelgaard, MM Dobroth, KM AF Speer, SR Kjelgaard, MM Dobroth, KM TI The influence of prosodic structure on the resolution of temporary syntactic closure ambiguities SO JOURNAL OF PSYCHOLINGUISTIC RESEARCH LA English DT Article ID LANGUAGE AB This paper investigates the influence of prosodic structure on the process of sentence comprehension, with a specific focus on the relative contributions of syntactic and prosodic information to the resolution of temporary syntactic closure ambiguities. We argue that prosodic structure provides an initial memory representation for spoken sentences, and that information from this prosodic representation is available to inform syntactic parsing decisions. This view makes three predictions for the processing of temporary syntactic ambiguity: 1. When prosodic and syntactic boundaries coincide, syntactic processing should be facilitated. 2. When prosodic boundaries are placed at misleading points in syntactic structure, syntactic processing should show interference effects. 3. The processing difficulties that have been reliably demonstrated in reading experiments for syntactically complex sentences should disappear when those sentences are presented with a felicitous prosodic structure in listening experiments. These predictions were confirmed by series of experiments measuring end-of-sentence comprehension time and cross-modal naming time for sentences with temporary syntactic closure ambiguities. Sentences with coinciding or conflicting prosodic and syntactic boundaries were compared to a prosodic baseline condition. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NORTHEASTERN UNIV,BOSTON,MA 02115. RP Speer, SR (reprint author), UNIV KANSAS,DEPT PSYCHOL,FRASER HALL,LAWRENCE,KS 66045, USA. FU NIMH NIH HHS [R29 MH51768, T32 MH19729] NR 37 TC 43 Z9 44 U1 0 U2 3 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0090-6905 J9 J PSYCHOLINGUIST RES JI J. Psycholinguist. Res. PD MAR PY 1996 VL 25 IS 2 BP 249 EP 271 DI 10.1007/BF01708573 PG 23 WC Linguistics; Psychology, Experimental SC Linguistics; Psychology GA UQ834 UT WOS:A1996UQ83400004 PM 8667298 ER PT J AU Nagel, HN Shapiro, LP Tuller, B Nawy, R AF Nagel, HN Shapiro, LP Tuller, B Nawy, R TI Prosodic influences on the resolution of temporary ambiguity during on-line sentence processing SO JOURNAL OF PSYCHOLINGUISTIC RESEARCH LA English DT Article ID COMPREHENSION; DURATION; VERBS AB We present three experiments designed to investigate the role of prosody during sentence processing. The first investigated the question of whether an utterance's prosodic contour influences its comprehension on-line. We spliced the beginning and end portions of direct object and embedded clause sentences and observed the consequent effects on comprehension using a dual-task procedure to measure processing load. Our second experiment sought to determine whether the constituent structure of these sentences could be reliably predicted using prosodic information. We found that the duration and F-0 contour associated with the main-clause verb and the following NP reliably distinguished between the direct object and embedded clause constructions. In the final experiment, we manipulated the duration of the main-clause verb and found that subjects used this information to guide their initial pause during on-line sentence comprehension. The need for a model of sentence processing that addresses the use of prosodic information is discussed. C1 SAN DIEGO STATE UNIV,SAN DIEGO,CA 92182. MASSACHUSETTS GEN HOSP,NEUROPSYCHOL LAB,BOSTON,MA 02114. FLORIDA ATLANTIC UNIV,BOCA RATON,FL 33431. FU NIDCD NIH HHS [DC00494] NR 24 TC 31 Z9 31 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0090-6905 J9 J PSYCHOLINGUIST RES JI J. Psycholinguist. Res. PD MAR PY 1996 VL 25 IS 2 BP 319 EP 344 DI 10.1007/BF01708576 PG 26 WC Linguistics; Psychology, Experimental SC Linguistics; Psychology GA UQ834 UT WOS:A1996UQ83400007 PM 8667301 ER PT J AU Segal, AH AF Segal, AH TI Anatomic predilection of the spondyloarthropathies - A case of the nerves? SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE reactive arthritis; neuropeptides; Reiter's syndrome; ankylosing spondylitis; visceral afferents ID GENE-RELATED PEPTIDE; PRIMARY AFFERENT NEURONS; LUMBAR SPINAL OUTFLOW; SUBSTANCE-P; SENSORY INNERVATION; KNEE-JOINT; SERONEGATIVE SPONDYLOARTHROPATHY; INTESTINAL PERMEABILITY; ANKYLOSING-SPONDYLITIS; SYMPATHETIC COMPONENTS AB Gastrointestinal (GI) and genitourinary (GU) inflammation are associated with arthritis of the joints of the lower extremities and lumbosacral spine. Some contemporary models assert that bacterial antigens or immune complexes are released from the viscera and circulate to the joints, inciting inflammation there. Others propose an autoimmune process directed against native joint antigens. However, neither paradigm explains the predilection of such arthritides for specific joints. Recent investigations have shown that peptidergic nerves supplying these joints project to the same spinal segments as those supplying the GI and GU tracts. The peptides released by these nerves act both as neurotransmitters at the nerves' central terminals and as inflammatory mediators at their peripheral terminals. I hypothesize that circuits of peptidergic nerves can transmit signals from abdominal and pelvic viscera to lumbosacrally innervated joints via the spinal cord. predisposing them to arthritis. RP Segal, AH (reprint author), MASSACHUSETTS GEN HOSP, ARTHRIT UNIT, BOSTON, MA 02114 USA. FU NIAID NIH HHS [U01AI26463] NR 60 TC 3 Z9 3 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO ON M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD MAR PY 1996 VL 23 IS 3 BP 491 EP 494 PG 4 WC Rheumatology SC Rheumatology GA TZ328 UT WOS:A1996TZ32800016 PM 8832989 ER PT J AU VanLinthoudt, D Salani, I Zender, R Locatelli, P Ott, H Schumacher, HR AF VanLinthoudt, D Salani, I Zender, R Locatelli, P Ott, H Schumacher, HR TI Citrate in synovial fluid and its relation to inflammation and crystal presence SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE citrate; synovial fluid; calcium pyrophosphate dihydrate crystals; apatite; rheumatoid arthritis; osteoarthritis ID ALIZARIN RED; PHOSPHOCITRATE AB Objective, To investigate the role of citrate in the pathophysiology of arthritides with calcium pyrophosphate dihydrate (CPPD) crystals and/or apatite-like material. Methods, Wt: measured citrate concentrations in the plasma and synovial fluid (SF) of 23 joints whose SF contained these crystals and 33 joints without crystals, The SF originated from 25 joints each of patients with rheumatoid arthritis (RA) and primary osteoarthritis (OA) and 10 patients with various other inflammatory joint diseases. Results, There was significant correlation between citrate concentrations in the SF and plasma with values globally twice as high in the SF as in the plasma. Citrate concentrations in the SF of patients whose SF contained CPPD crystals and/or apatite-like material were not significantly lower than those without crystals. On the other hand, citrate concentrations were significantly lower in the SF of patients with RA and other inflammatory joint diseases versus those with OA, Conclusion, We have no evidence that lower amounts of citrate in SF favor the presence of CPPD crystals or apatite-like material, Our results, however, do suggest a complex regulation of the citrate concentration in SF where cellular metabolic processes and citrates arising from the plasma and neighboring tissues probably interact to produce the levels recorded. C1 COMMUNITY HOSP LAB,CH-2300 LA CHAUX DE FONDS,SWITZERLAND. UNIV PENN,SCH MED,DEPT MED,PHILADELPHIA,PA 19104. VET AFFAIRS MED CTR,ARTHRIT IMMUNOL CTR,PHILADELPHIA,PA. RP VanLinthoudt, D (reprint author), COMMUNITY HOSP,DEPT RHEUMATOL,CH-2300 LA CHAUX DE FONDS,SWITZERLAND. NR 18 TC 6 Z9 6 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO ON M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD MAR PY 1996 VL 23 IS 3 BP 502 EP 505 PG 4 WC Rheumatology SC Rheumatology GA TZ328 UT WOS:A1996TZ32800019 PM 8832992 ER PT J AU Biederman, J Faraone, S Milberger, S Curtis, S Chen, L Marrs, A Ouellete, C Moore, P Spencer, T AF Biederman, J Faraone, S Milberger, S Curtis, S Chen, L Marrs, A Ouellete, C Moore, P Spencer, T TI Predictors of persistence and remission of ADHD into adolescence: Results from a four-year prospective follow-up study SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE attention-deficit hyperactivity disorder; persistence; predictors; remission; longitudinal study ID DEFICIT HYPERACTIVITY DISORDER; PSYCHIATRIC STATUS; CHILDREN; ADULTS; COMORBIDITY; CHILDHOOD; BEHAVIOR; BOYS AB Objective: To evaluate the predictors of persistence and the timing of remission of attention-deficit hyperactivity disorder (ADHD). Method: Subjects were 6- to 17-year old Caucasian, non-Hispanic boys with and without ADHD. DSM-III-R structured diagnostic interviews and blind raters were used to examine psychiatric diagnoses, cognitive achievement, social, school, and family functioning at a 4-year follow-up assessment. Results: At the 4-year follow-up assessment, 85% of children with ADHD continued to have the disorder and 15% remitted. Of those who remitted, half did so in childhood and the other half in adolescence. Predictors of persistence were familiality of ADHD, psychosocial adversity, and comorbidity with conduct, mood, and anxiety disorders. Conclusions: The findings prospectively confirm that the majority of children with ADHD will continue to express the disorder 4 years later. For a minority of children, ADHD was a transient disorder that remits early in development. In addition, we have shown that persistence of ADHD is predictable. Familiality, adversity, and psychiatric comorbidity may be clinically useful predictors of which children with ADHD are at risk for a persistent disorder. RP Biederman, J (reprint author), MASSACHUSETTS GEN HOSP,PEDIAT PSYCHOPHARMACOL UNIT,PSYCHIAT SERV,ACC 725,15 PARKMAN ST,BOSTON,MA 02114, USA. OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [MH41314-08] NR 29 TC 293 Z9 306 U1 1 U2 28 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD MAR PY 1996 VL 35 IS 3 BP 343 EP 351 DI 10.1097/00004583-199603000-00016 PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA TW743 UT WOS:A1996TW74300016 PM 8714323 ER PT J AU Stoddard, FJ AF Stoddard, FJ TI Behavioral aspects of pediatric burns - Tarnowski,KH SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Book Review RP Stoddard, FJ (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,SHRINERS BURNS INST,BOSTON,MA 02114, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD MAR PY 1996 VL 35 IS 3 BP 397 EP 398 PG 2 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA TW743 UT WOS:A1996TW74300029 ER PT J AU Arbiser, JL AF Arbiser, JL TI Angiogenesis and the skin: A primer SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Review ID FIBROBLAST GROWTH-FACTOR; VASCULAR-PERMEABILITY FACTOR; ENDOTHELIAL-CELL GROWTH; ONCOSTATIN-M; DEVELOPMENTAL EXPRESSION; INTRALESIONAL INTERFERON; MALIGNANT-MELANOMA; TUMOR-METASTASIS; WOUND FLUID; BINDING AB Angiogenesis is the development of a blood supply to a given area of tissue, This area of tissue may be part of normal embryonic development, revascularization of a wound bed, or the stimulation of vessel growth by inflammatory or malignant cells. Angiogenesis is of crucial importance to the dermatologist, as it is of key importance in pathologic processes such as psoriasis, warts, and cutaneous malignancy, and it is required for optimal wound healing. Other dermatologic processes wherein angiogenesis is defective or uncontrolled are decubitus ulcers, stasis ulcers, pyogenic granulomas, hemangiomas, Kaposi's sarcoma, and possibly Spitz nevus, hypertrophic scars, and keloids. Recent advances in the understanding of growth factors will likely lead to advances in the treatment of skin cancer and psoriasis, and more rapid healing of wounds. In this review, I hope to summarize the most important growth factors, inhibitors of angiogenesis, and future directions in research and therapeutics involving angiogenesis. C1 MASSACHUSETTS GEN HOSP,DEPT DERMATOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. HOWARD HUGHES MED INST,BOSTON,MA 02115. NR 115 TC 55 Z9 57 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD MAR PY 1996 VL 34 IS 3 BP 486 EP 497 DI 10.1016/S0190-9622(96)90444-2 PG 12 WC Dermatology SC Dermatology GA TZ292 UT WOS:A1996TZ29200015 PM 8609264 ER PT J AU Sager, MA Rudberg, MA Jalaluddin, M Franke, T Inouye, SK Landefeld, CS Siebens, H Winograd, CH AF Sager, MA Rudberg, MA Jalaluddin, M Franke, T Inouye, SK Landefeld, CS Siebens, H Winograd, CH TI Hospital admission risk profile (HARP): Identifying older patients at risk for functional decline following acute medical illness and hospitalization SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID GERIATRIC CONSULTATION; CONTROLLED TRIAL; OUTCOMES; UNIT AB OBJECTIVES: To develop and validate an instrument for stratifying older patients at the time of hospital admission according to their risk of developing new disabilities in activities of daily living (ADL) following acute medical illness and hospitalization. DESIGN: Multi-center prospective cohort study. SETTING: Four university and two private non-federal acute care hospitals. PATIENTS: The development cohort consists of 448 patients and the validation cohort consists of 379 patients who were aged 70 and older and who were hospitalized for acute medical illness between 1989 and 1992. MEASUREMENTS: All patients were evaluated on hospital admission to identify baseline demographic and functional characteristics and were then assessed at discharge and 3 months after discharge to determine decline in ADL functioning. RESULTS: Logistic regression analysis identified three patient characteristics that were independent predictors of functional decline in the development cohort: increasing age, lower admission Mini-Mental Status Exam scores, and lower preadmission IADL function. A scoring system was developed for each predictor variable and patients were assigned to low, intermediate, and high risk categories. The rates of ADL decline at discharge for the low, intermediate, and high risk categories were 17%, 28%, and 56% in the development cohort and 19%, 31%, and 55% in the validation cohort, respectively. Patients in the low risk category were significantly more likely to recover ADL function and to avoid nursing home placement during the 3 months after discharge. CONCLUSION: Hospital Admission Risk Profile (HARP) is a simple instrument that can be used to identify patients at risk of functional decline following hospitalization. HARP can be used to identify patients who might benefit from comprehensive discharge planning, specialized geriatric care, and experimental interventions designed to prevent/reduce the development of disability in hospitalized older populations. C1 UNIV WISCONSIN,MADISON,WI 53706. WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI 53705. UNIV CALIF LOS ANGELES,LOS ANGELES,CA 90024. UNIV CHICAGO,CHICAGO,IL 60637. YALE UNIV,SCH MED,NEW HAVEN,CT 06510. CASE WESTERN RESERVE UNIV,SCH MED,VET AFFAIRS MED CTR,CLEVELAND,OH 44106. UNIV CLEVELAND HOSP,CLEVELAND,OH 44106. CEDARS SINAI MED CTR,LOS ANGELES,CA 90048. VET AFFAIRS MED CTR,PALO ALTO,CA 94304. STANFORD UNIV,PALO ALTO,CA 94304. NR 33 TC 198 Z9 204 U1 3 U2 11 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 1996 VL 44 IS 3 BP 251 EP 257 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA TZ893 UT WOS:A1996TZ89300004 PM 8600192 ER PT J AU Mulrow, CD Chiodo, LK Gerety, MB Lee, S Basu, S Nelson, D AF Mulrow, CD Chiodo, LK Gerety, MB Lee, S Basu, S Nelson, D TI Function and medical comorbidity in south Texas nursing home residents: Variations by ethnic group SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID DISABILITY; DISEASE AB OBJECTIVE: To evaluate differences in functional status and burdens of medical conditions in Mexican American and non-Hispanic white nursing home residents. DESIGN AND SETTING: Cross-sectional survey of 17 nursing homes in south Texas. PARTICIPANTS: A total of 617 older nursing home residents, of whom 366 were Mexican American and 251 were non-Hispanic white. MEASURES: Activities of Daily Living (ADL) status abstracted from standard nurses notes and Burden of Disease abstracted from medical records. RESULTS: Mexican American residents had greater numbers of ADL dependencies and poorer overall ADL scores than non-Hispanic white residents. This poor functioning was not explained by age, gender, or marital or educational status. The average number of medical conditions was greater, and specific conditions, such as cerebrovascular disease, recent acute infections, diabetes, hypertension, and anemia, were more common in Mexican American residents compared with non-Hispanic white residents. In models relating function with medical conditions and ethnic group, ADL scores and dependencies were significantly related to bowel and bladder incontinence, cerebrovascular disease, dementia, recent infections, and skin decubiti, but not to ethnic group. CONCLUSION: Mexican American nursing home residents are more functionally dependent than non-Hispanic white residents. The difference in function is explained by a greater burden of medical conditions in the Mexican American residents. C1 UNIV TEXAS,HLTH SCI CTR,DIV GEN MED,SAN ANTONIO,TX. UNIV TEXAS,HLTH SCI CTR,DIV GERIATR & GERONTOL,SAN ANTONIO,TX. RP Mulrow, CD (reprint author), AUDIE L MURPHY MEM VET ADM MED CTR,CTR GERIATR RES EDUC & CLIN,7400 MERTON MINTER BLVD,SAN ANTONIO,TX 78284, USA. NR 24 TC 18 Z9 18 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 1996 VL 44 IS 3 BP 279 EP 284 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA TZ893 UT WOS:A1996TZ89300008 PM 8600196 ER PT J AU Abrutyn, E Berlin, J Mossey, J Pitsakis, P Levison, M Kaye, D AF Abrutyn, E Berlin, J Mossey, J Pitsakis, P Levison, M Kaye, D TI Does treatment of asymptomatic bacteriuria in older ambulatory women reduce subsequent symptoms of urinary tract infection? SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID NO THERAPY; MORTALITY; ASSOCIATION; SURVIVAL; ADULTS AB OBJECTIVE: To determine whether treatment of asymptomatic bacteriuria in older ambulatory women affects the subsequent development of symptoms of urinary tract infection. DESIGN: A controlled clinical trial. PARTICIPANTS: Older women not having urinary catheters. MEASUREMENTS: Urine cultures every 6 months (the same organism at 10(5) colony-forming units or more per mL on two midstream urine specimens defined asymptomatic bacteriuria) and questionnaire surveys for the new development of symptoms of urinary tract infection (dysuria, frequency, urgency, low back pain with fever) 1, 3, and 6 months after the initial survey. RESULTS: Of the 23 initally culture-positive participants receiving antibiotic treatment for asymptomatic bacteriuria, nine were culture positive at 6 months, which contrasts with 18 of 27 who received no treatment or placebo, P = .05. However, symptoms of urinary tract infection were more common in the antibiotic-treated group. CONCLUSION: Antibiotic therapy effectively reduced the subsequent occurrence of positive urine cultures, but symptoms were not reduced. Based on this study of morbidity, previous studies failing to show any relation to mortality, and the cost and complications of antibiotic therapy in the older population, treatment of asymptomatic bacteriuria in older women is contraindicated. C1 MED COLL PENN,PHILADELPHIA,PA 19129. HAHNEMANN UNIV,PHILADELPHIA,PA 19102. UNIV PENN,SCH MED,CTR CLIN EPIDEMIOL & BIOSTAT,PHILADELPHIA,PA 19104. RP Abrutyn, E (reprint author), VET AFFAIRS MED CTR,38TH & WOODLAND AVE,PHILADELPHIA,PA 19104, USA. NR 19 TC 29 Z9 29 U1 0 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 MAR PY 1996 VL 44 IS 3 BP 293 EP 295 PG 3 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA TZ893 UT WOS:A1996TZ89300011 PM 8600199 ER PT J AU Levine, BS Song, M AF Levine, BS Song, M TI Pharmacokinetics and efficacy of pulse oral versus intravenous calcitriol in hemodialysis patients SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article DE calcitriol; pharmacokinetics; parathyroid hormone; oral; intravenous ID CHRONIC RENAL-FAILURE; SECONDARY HYPERPARATHYROIDISM; PARATHYROID-HORMONE; PERITONEAL-DIALYSIS; INTERMITTENT; THERAPY; 1,25-DIHYDROXYCHOLECALCIFEROL; 1,25-DIHYDROXYVITAMIN-D; 1,25(OH)2D3; SUPPRESSION AB Because intravenous (iv) calcitriol has greater bioavailability than oral calcitriol, it may be more efficacious in suppressing parathyroid hormone (PTH) secretion, In this study, the pharmacokinetics and efficacy of pulse oral and iv calcitriol were compared. Patients were randomized to receive 2 mu g of iv or oral calcitriol after each dialysis, Two pharmacokinetic studies (PK1, PK2) were performed 10 days apart, during which the patients received calcitriol after each dialysis. Calcitriol bioavailability was determined from the area under the curve (AUC(time) (interval) ((hours)) in pg/ml per h), After the PK phase, PTH was lowered to < 200 pg/ml by titrating calcitriol to a maximum of 12 mu g/wk over 4 wk. Calcitriol was then maintained for another 18 wk unless serum calcium exceeded 11.5 mg/dL or Ca x P product exceeded 70; when these limits were reached, calcitriol was held and then restarted at a lower dose. After iv administration, peak serum calcitriol exceeded that achieved orally but by 1 h, calcitriol levels were similar. The AUC(0-0.5) (105 +/- 12, iv; 9 +/- 4, oral) and AUC(0.5-1) (68 +/- 6, iv; 30 +/- 7, oral) were higher with iv (P < 0.05), but cumulative AUC(0-48) did not differ. Individual t(1/2) values ranged from 10 to 129 h for PK1 and from 10 to 50 h for PK2, The t(1/2) for oral calcitriol was 38 +/- 14 h for PK1 and 30 +/- 4 h for PK2 (not significant (NS)), The t(1/2) for iv calcitriol was 26 +/- 5 h for PK1 and 19 +/- 3 h for PK2 (NS, PK1 versus PK2 and oral versus iv), When the PK1 oral and iv data were combined, the mean t(1/2) was 32 +/- 7 h whereas the t(1/2) for PK2 (oral and iv) was 22 +/- 3 h (P < 0.05), Baseline PTH levels were 510 +/- 90 pg/mL and 499 +/- 79 pg/mL, oral and iv, respectively, Serum PTH level at 22 wk was not different between oral and iv groups, 153 +/- 38 pg/mL and 214 +/- 124 pg/mL in iv (NS), The percentage of PTH suppression was 66 +/- 7.4% in the oral group and 69 +/- 12% in the iv group (NS), A major degree of serum iPTH suppression occurred during the initial 4 wk of treatment, concomitant with a rise in serum calcium levels. Adverse effects were similar between groups, as were the average dosages of calcitriol and phosphate binders, In conclusion, the efficacy of intravenous and pulse oral calcitriol were similar in hemodialysis patients with secondary hyperparathyroidism. The early rise in serum calcium levels observed with treatment may have contributed significantly to the suppression of serum iPTH levels, The difference in bioavailability between the different routes does not have a clinically apparent effect, The t(1/2) varied widely among individuals, whereas exposure to calcitriol may decrease the t(1/2). C1 UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA. RP Levine, BS (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,DEPT MED,11301 WILSHIRE BLVD,LOS ANGELES,CA 90073, USA. NR 34 TC 60 Z9 63 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 MAR PY 1996 VL 7 IS 3 BP 488 EP 496 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA UC397 UT WOS:A1996UC39700015 PM 8704116 ER PT J AU Dretler, SP Polykoff, G AF Dretler, SP Polykoff, G TI Calcium oxalate stone morphology: Fine tuning our therapeutic distinctions SO JOURNAL OF UROLOGY LA English DT Article DE calcium oxalate; urinary calculi; kidney calculi; ureteral calculi AB Purpose: We determined specific radiographic morphological patterns of crystallographically analyzed pure and mixed calcium oxalate dihydrate and calcium oxalate monohydrate urinary calculi. Materials and Methods: A total of 86 greater than 1 cm. calculi crystallographically analyzed as pure calcium oxalate monohydrate, calcium oxalate dihydrate or admixtures of the 2 types was studied to determine whether various forms of calcium oxalate differed in radiographic morphology. Results: Four distinct radiographic patterns could be identified by plain film roentgenography: group 1-14 patients with smooth edged, homogeneously dense calculi, some with dentate shapes (12 had pure calcium oxalate monohydrate stones), group 2-33 with multinodular calculi with irregular edges and variegated areas of more and less radiodensity (32 had greater than 60% calcium oxalate monohydrate), group 3-33 with a uniform, stippled pattern, often with identifiable radial striations, and with a larger amount of calcium oxalate dihydrate than groups 1 or 2, and group 4-6 with poorly radiodense, loosely aggregated crystals with a lacy structure. Conclusions: At least 4 patterns of calcium oxalate stones are recognizable by plain film roentgenography. Because the fi agility of calcium oxalate calculi is determined by the relative calcium oxalate monohydrate and dihydrate content, pretreatment recognition of these radiographic patterns may affect the selection of a therapeutic modality. C1 MASSACHUSETTS GEN HOSP,DEPT UROL,BOSTON,MA. HARVARD UNIV,SCH MED,BOSTON,MA. RP Dretler, SP (reprint author), MASSACHUSETTS GEN HOSP,KIDNEY STONE CTR,BOSTON,MA 02114, USA. NR 4 TC 48 Z9 51 U1 1 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-5347 J9 J UROLOGY JI J. Urol. PD MAR PY 1996 VL 155 IS 3 BP 828 EP 833 DI 10.1016/S0022-5347(01)66319-5 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA TU668 UT WOS:A1996TU66800006 PM 8583586 ER PT J AU Zietman, AL Coen, JJ Ferry, JA Scully, RE Kaufman, DS McGovern, FG AF Zietman, AL Coen, JJ Ferry, JA Scully, RE Kaufman, DS McGovern, FG TI The management and outcome of stage IA(E) nonHodgkin's lymphoma of the testis SO JOURNAL OF UROLOGY LA English DT Article DE testis; lymphoma; drug therapy; radiotherapy; testicular neoplasms ID NON-HODGKINS-LYMPHOMA; MALIGNANT-LYMPHOMA; PATTERNS; FAILURE AB Purpose: The initial management of stage I nonHodgkin's lymphoma of the testis is by orchiectomy but the role and efficacy of adjuvant strategies are uncertain. We reviewed cases of lymphoma at our institution to determine whether adjuvant treatment was beneficial. Materials and Methods: A retrospective review of outcome was conducted on 26 patients who presented to our institution. Median followup for the group was 54 months. Kaplan-Meier actuarial analyses were performed on the entire group and subsets. Results: Actuarial 5 and 10-year overall survival rates were 79% and 63%, and relapse-free survival rates were 61% and 46%, respectively. In patients who received adjuvant combination chemotherapy the 5-year relapse-free survival rate improved (75% versus 50%) but effect did not achieve;statistical significance and was lost by 10 years. No relapse-free survival advantage was noted for patients receiving adjuvant irradiation to the pelvic and para-aortic nodes. Patients who did not receive irradiation remained free of isolated relapses in the pelvic or para-aortic regions. Conclusions: These data lend support to the use of adjuvant chemotherapy but do not support a role for adjuvant nodal irradiation. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED ONCOL,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT UROL,BOSTON,MA 02114. RP Zietman, AL (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,BOSTON,MA 02114, USA. NR 21 TC 21 Z9 21 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-5347 J9 J UROLOGY JI J. Urol. PD MAR PY 1996 VL 155 IS 3 BP 943 EP 946 DI 10.1016/S0022-5347(01)66353-5 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA TU668 UT WOS:A1996TU66800040 PM 8583613 ER PT J AU Boland, CW Lee, MJ Sutcliffe, NP Mueller, PR AF Boland, CW Lee, MJ Sutcliffe, NP Mueller, PR TI Loculated pneumothoraces in patients with acute respiratory disease treated with mechanical ventilation preliminary observations after image-guided drainage SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article DE lung, assisted ventilation; pneumothorax; respiratory distress syndrome, adult (ARDS) ID DISTRESS SYNDROME; ADULT AB PURPOSE: To report the clinical impact of image-guided percutaneous drainage of loculated pneumothoraces in patients with acute respiratory disease treated with mechanical ventilation. MATERIALS AND METHODS: Sixteen loculated pneumothoraces were seen in nine patients, Twelve of the 16 lesions were considered suitable for drainage because of their size and location, They were percutaneously drained by means of image-guided placement of catheters that ranged in size from 16 F to 24 F, Gas exchange was assessed clinically, and follow-up chest radiographs and computed tomographic scans were evaluated. RESULTS: Loculated pneumothoraces were reduced in all patients, Improvement in the ratio of arterial oxygen pressure to fraction of inspired oxygen was identified in eight patients, All patients showed an improved arterial oxygen pressure. CONCLUSION: Image-guided catheter placement may play a role in the acute management of loculated pneumothorax and adult respiratory distress syndrome, This type of therapy may reverse the deterioration of gas exchange and reduce the risk of further pulmonary compromise. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIOL,BOSTON,MA 02114. NR 18 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD MAR-APR PY 1996 VL 7 IS 2 BP 247 EP 252 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA UQ438 UT WOS:A1996UQ43800013 ER PT J AU Gao, F Morrison, SG Robertson, DL Thornton, CL Craig, S Karlsson, G Sodroski, J Morgado, M GalvaoCastro, B vonBriesen, H Beddows, S Weber, J Sharp, PM Shaw, GM Hahn, BH Osmanov, S Heyward, WL Esparza, J vandePerre, P Karita, E Sempala, S Tugume, B Biryahwaho, B Wasi, C RubsamenWaigmann, H Holmes, H Newberry, A Ranjbar, S Tomlinson, P Bradac, J Mullins, JI Delwart, EL CheingsongPopov, R Kaleebu, P Myers, G Korber, BTM Chiphangwi, J Taha, T Desormeaux, J Eiumtrakul, S Natpratan, C Khamboonruang, C Miotti, P Halsey, NA Vlahov, D Nelson, KE Phair, J Cao, Y Moore, JP Ho, DD Matocha, M Fowler, A Dilworth, S Sharma, O Brown, R Dusing, S Whitman, J Hoekzema, D Vogel, F AF Gao, F Morrison, SG Robertson, DL Thornton, CL Craig, S Karlsson, G Sodroski, J Morgado, M GalvaoCastro, B vonBriesen, H Beddows, S Weber, J Sharp, PM Shaw, GM Hahn, BH Osmanov, S Heyward, WL Esparza, J vandePerre, P Karita, E Sempala, S Tugume, B Biryahwaho, B Wasi, C RubsamenWaigmann, H Holmes, H Newberry, A Ranjbar, S Tomlinson, P Bradac, J Mullins, JI Delwart, EL CheingsongPopov, R Kaleebu, P Myers, G Korber, BTM Chiphangwi, J Taha, T Desormeaux, J Eiumtrakul, S Natpratan, C Khamboonruang, C Miotti, P Halsey, NA Vlahov, D Nelson, KE Phair, J Cao, Y Moore, JP Ho, DD Matocha, M Fowler, A Dilworth, S Sharma, O Brown, R Dusing, S Whitman, J Hoekzema, D Vogel, F TI Molecular cloning and analysis of functional envelope genes from human immunodeficiency virus type 1 sequence subtypes A through G SO JOURNAL OF VIROLOGY LA English DT Review ID HIGHLY CYTOPATHIC STRAIN; CYTOPLASMIC DOMAIN; NUCLEOTIDE-SEQUENCES; PROTEIN SEQUENCES; AIDS VIRUS; HIV-1; DIVERSITY; ENV; GAG; IDENTIFICATION AB Present knowledge of human immunodeficiency virus type 1 (HIV-1) envelope immunobiology has been derived almost exclusively from analyses of subtype B viruses, yet such viruses represent only a minority of strains currently spreading worldwide. To generate a more representative panel of genetically diverse envelope genes, we PCR amplified, cloned, and sequenced complete gp160 coding regions of 35 primary (peripheral blood mononuclear cell-propagated) HTV-1 isolates collected at major epicenters of the current AIDS pandemic. Analysis of their deduced amino acid sequences revealed several important differences from prototypic subtype B strains, including changes in the number and distribution of cysteine residues, substantial length differences in hypervariable regions, and premature truncations in the gp41 domain. Moreover, transiently expressed glycoprotein precursor molecules varied considerably in both size and carbohydrate content. Phylogenetic analyses of full-length env sequences indicated that the panel included members of all major sequence subtypes of HTV-1 group M (clades A to G), as well as an intersubtype recombinant (FIB) from an infected individual in Brazil. In addition, all subtype E and three subtype G viruses initially classified on the basis of partial env sequences were found to cluster in subtype A in the 3' half of their gp41 coding region, suggesting that they are also recombinant. The biological activity of PCR-derived env genes was examined in a single-round virus infectivity assay, This analysis identified 20 clones, including 1 from each subtype (or recombinant), which expressed fully functional envelope glycoproteins. One of these, derived from a patient with rapid CD4 cell decline, contained an amino acid substitution in a highly conserved endocytosis signal (Y721C), as well as a premature truncation of its gp41 domain, which lacked 17 amino acids. Several other env constructs mediated virus entry with very poor efficiency, although they did not contain sequence changes predicted to alter protein function. These results indicate that the env genes of primary HTV-1 isolates collected worldwide can vary considerably in their genetic, phylogenetic, and biological properties. The panel of env constructs described here should prove valuable for future structure-function studies of naturally occurring envelope glycoproteins as well as AIDS vaccine development efforts targeted against a broader spectrum of viruses. C1 UNIV ALABAMA,DEPT MED,BIRMINGHAM,AL 35294. UNIV ALABAMA,DEPT MICROBIOL,BIRMINGHAM,AL 35294. UNIV NOTTINGHAM,QUEENS MED CTR,DEPT GENET,NOTTINGHAM NG7 2RD,ENGLAND. UNIV LONDON IMPERIAL COLL SCI TECHNOL & MED,ST MARYS HOSP,SCH MED,DEPT COMMUNICABLE DIS,LONDON W2 1PG,ENGLAND. DANA FARBER CANC INST,DEPT PATHOL,BOSTON,MA 02115. FIOCRUZ MS,INST OSWALDO CRUZ,DEPT IMMUNOL,RIO JANEIRO,BRAZIL. FIOCRUZ MS,CTR PESQUISA GONCALO MONIZ,ADV LAB PUBL HLTH,SALVADOR,BA,BRAZIL. GEORG SPEYER HAUS,CHEMOTHERAPEUT FORSCHUNGSINST,FRANKFURT,GERMANY. WHO,GLOBAL PROGRAMME AIDS,GENEVA,SWITZERLAND. NATL AIDS CONTROL PROGRAM,KIGALI,RWANDA. INST TROP MED,B-2000 ANTWERP,BELGIUM. UGANDA VIRUS RES INST,ENTEBBE,UGANDA. MAHIDOL UNIV,SIRIRAJ HOSP,BANGKOK 10700,THAILAND. NATL INST BIOL STAND & CONTROLS,LONDON NW3 6RB,ENGLAND. UNIV WASHINGTON,SEATTLE,WA 98195. LOS ALAMOS NATL LAB,LOS ALAMOS,NM 87545. MALAWI COLL MED,BLANTYRE,MALAWI. CTR DEV & SANTE,PORT AU PRINCE,HAITI. ROYAL THAI ARMY HOSP,CHIANG MAI,THAILAND. ROYAL THAI MINIST PUBL HLTH,CHIANG MAI,THAILAND. CHIANG MAI UNIV,CHIANG MAI 50000,THAILAND. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,BALTIMORE,MD. NORTHWESTERN UNIV,CHICAGO,IL 60611. AARON DIAMOND AIDS RES CTR,NEW YORK,NY. NIAID,AIDS RES & REFERENCE REAGENT PROGRAM,BETHESDA,MD 20892. NIAID,AIDS VACCINE REAGENT PROGRAM,BETHESDA,MD 20892. RI Sharp, Paul/F-5783-2010; Van de Perre, Philippe/B-9692-2008 OI Sharp, Paul/0000-0001-9771-543X; Van de Perre, Philippe/0000-0002-3912-0427 FU NIAID NIH HHS [P30 AI27767, N01AI35170, R01AI25291] NR 104 TC 248 Z9 261 U1 2 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 1996 VL 70 IS 3 BP 1651 EP 1667 PG 17 WC Virology SC Virology GA TV696 UT WOS:A1996TV69600039 PM 8627686 ER PT J AU Moore, JP Sodroski, J AF Moore, JP Sodroski, J TI Antibody cross-competition analysis of the human immunodeficiency virus type 1 gp120 exterior envelope glycoprotein SO JOURNAL OF VIROLOGY LA English DT Article ID NEUTRALIZING MONOCLONAL-ANTIBODIES; CD4 BINDING-SITE; VARIABLE REGIONS; SYNERGISTIC INHIBITION; SURFACE GLYCOPROTEIN; RECEPTOR-BINDING; SOLUBLE CD4; HIV-1; EPITOPES; DOMAIN AB Forty-six monodonal antibodies (MAbs) able to bind to the native, monomeric gp120 glycoprotein of the human immunodeficiency virus type 1 (HIV-1) LAI (HXBc2) strain were used to generate a competition matrix. The data suggest the existence of two faces of the gp120 glycoprotein. The binding sites for the viral receptor, CD4, and neutralizing MAbs appear to cluster on one face, which is presumably exposed on the assembled, oligomeric envelope glycoprotein complex. A second gp120 face, which is presumably inaccessible on the envelope glycoprotein complex, contains a number of epitopes for nonneutralizing antibodies. This analysis should be useful for understanding both the interaction of antibodies with the HIV-1 gp120 glycoprotein and neutralization of HIV-1. C1 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. RP Moore, JP (reprint author), AARON DIAMOND AIDS RES CTR,455 1ST AVE,NEW YORK,NY 10016, USA. FU NIAID NIH HHS [AI 24755, AI 36082, N01 AI 35168] NR 62 TC 278 Z9 284 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 1996 VL 70 IS 3 BP 1863 EP 1872 PG 10 WC Virology SC Virology GA TV696 UT WOS:A1996TV69600064 PM 8627711 ER PT J AU Mader, SL Downing, CL AmosLandgraf, J Swebjka, P AF Mader, SL Downing, CL AmosLandgraf, J Swebjka, P TI Age-related changes in G proteins in rat aorta SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID NUCLEOTIDE-BINDING PROTEINS; VASCULAR SMOOTH-MUSCLE; REGULATORY PROTEIN; ADENYLATE-CYCLASE; INCREASING AGE; BLOOD VESSELS; ALPHA-SUBUNIT; RELAXATION; DESENSITIZATION; DECREASE AB Blood vessels from aged animals and humans have impaired relaxation to beta-adrenergic stimulation. We hypothesized that a loss of stimulatory G protein (Gs) or art increase in inhibitory G proteins (Gi) could explain this impairment Aortic membranes from Fischer 344 rats of 4 age groups (6 week to 24 month) were studied. G-protein levels were initially assessed using cholera and pertussis toxin labeling. There was a marked decline in cholera toxin labeling (which primarily labels Gs alpha) from 6 weeks to 6 months which persisted in 12-month and 24-month animals. Pertussis toxin labeling (which primarily labels Gi alpha) showed only a slight decline with age. Western blotting was performed using specific antibodies for the alpha subunit of Gs, G(1&2), Gi(3), and G beta. There was no significant change in Gs alpha, Gi alpha, or G beta protein levels with age. We conclude there is a loss of cholera toxin-catalyzed ADP ribosylation with age, which does not represent a loss of the stimulatory alpha subunit of G protein. These data suggest that the loss of cholera toxin labeling seen with age may be a marker for loss of Gs alpha function. C1 CASE WESTERN RESERVE UNIV,DEPT MED,CLEVELAND,OH 44106. RP Mader, SL (reprint author), PORTLAND VA MED CTR,POB 1035 11V,PORTLAND,OR 97207, USA. RI Amos-Landgraf, James/K-9288-2013 OI Amos-Landgraf, James/0000-0003-2535-7746 FU NIA NIH HHS [AG-00387]; NIDDK NIH HHS [DK-27651] NR 30 TC 19 Z9 19 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD MAR PY 1996 VL 51 IS 2 BP B111 EP B116 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA UB199 UT WOS:A1996UB19900001 PM 8612094 ER PT J AU Li, KK Cheney, ML AF Li, KK Cheney, ML TI The use of sliding genioplasty for treatment of failed chin implants SO LARYNGOSCOPE LA English DT Article ID RIGID INTERNAL-FIXATION; ADVANCEMENT GENIOPLASTY; MANDIBULAR FRACTURES; HTR POLYMER; INFECTION; BONE; REPLACEMENT C1 HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,DIV FACIAL PLAST & RECONSTRUCT SURG,BOSTON,MA 02114. NR 30 TC 4 Z9 4 U1 0 U2 0 PU LARYNGOSCOPE CO PI ST LOUIS PA 10 S BROADWAY 14TH FLOOR, ST LOUIS, MO 63102-1741 SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD MAR PY 1996 VL 106 IS 3 BP 363 EP 366 DI 10.1097/00005537-199603000-00023 PN 1 PG 4 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA UM977 UT WOS:A1996UM97700023 PM 8614205 ER PT J AU Kang, JX Leaf, A AF Kang, JX Leaf, A TI The cardiac antiarrhythmic effects of polyunsaturated fatty acid SO LIPIDS LA English DT Article; Proceedings Paper CT 2nd Congress of the International-Society-for-the-Study-of-Fatty-Acids-and-Lipids CY JUN 07-10, 1995 CL NIH, NATCHER CONF CTR, BETHESDA, MD SP Int Soc Study Fatty Acids & Lipids HO NIH, NATCHER CONF CTR ID ARRHYTHMIAS; RATS AB Each year in the United States alone some 250,000 persons die within one hour of an acute myocardial infarction. These deaths are largely due to ischemia-induced ventricular arrhythmias, primarily ventricular fibrillation (VF). Thus a safe, simple means of preventing such arrhythmias has considerable public health benefit potential. We have demonstrated that the intravenous infusion of n-3 polyunsaturated fatty acids (PUFA) from fish oils will prevent ischemia-induced VF in prepared, nonanesthetized, exercising dogs, confirming earlier feeding studies in rats. We show that this protective effect is due to an action of the free acidic form of the PUFA to alter the electrophysiology of individual cardiac myocyte so that the cells are electrically more stable. The electrophysiologic effects, in turn, result from direct and specific effects of the PUFA to block the fast voltage-dependent sodium channels. The binding of the free fatty acids is directly to the protein of the sodium channels and results in prolongation of the inactivated state of these channels. Other ion channels are also affected by the PUFA. Two clinical trials with n-3 PUFA are mentioned which inadvertently support the antiarrhythmic potential of PUFA ingestion. C1 MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02129. HARVARD UNIV,SCH MED,VET ADM MED CTR W ROXBURY,DEPT MED,BOSTON,MA 02129. FU NIDDK NIH HHS [R01 DK-38165] NR 16 TC 41 Z9 44 U1 0 U2 1 PU AMER OIL CHEMISTS SOC PI CHAMPAIGN PA 1608 BROADMOOR DRIVE, CHAMPAIGN, IL 61821-0489 SN 0024-4201 J9 LIPIDS JI Lipids PD MAR PY 1996 VL 31 SU S BP S41 EP S44 DI 10.1007/BF02637049 PG 4 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA UB908 UT WOS:A1996UB90800008 PM 8729092 ER PT J AU Laposata, M Muszbek, L AF Laposata, M Muszbek, L TI Thioesterification of platelet proteins with saturated and polyunsaturated fatty acids SO LIPIDS LA English DT Article; Proceedings Paper CT 2nd Congress of the International-Society-for-the-Study-of-Fatty-Acids-and-Lipids CY JUN 07-10, 1995 CL NIH, NATCHER CONF CTR, BETHESDA, MD SP Int Soc Study Fatty Acids & Lipids HO NIH, NATCHER CONF CTR ID GLYCOSYL-PHOSPHATIDYLINOSITOL; PALMITIC ACID; COVALENT MODIFICATION; MEMBRANE-PROTEINS; ATTACHMENT SITE; MYRISTOYL-COA; ACYLATION; PALMITOYLATION; LINKAGES; SUBUNITS AB We have demonstrated that more than 20 platelet proteins can be acylated with fatty acids via thioester linkages. These include the glycoprotein IX beta chain of glycoprotein Ib, components of the von Willebrand factor receptor on the platelet surface, P-selectin, and alpha subunits of G(z), G(q), and G(i). Our studies have shown that platelet proteins can be posttranslationally acylated in thioester linkages not only with palmitate but with myristate and also with the eicosanoid precursor fatty acids arachidonate and eicosapentaenoate. Thioesterification of platelet proteins with fatty acids other than palmitate may have significant functional consequences for reversible binding of proteins to membranes. C1 DEBRECEN UNIV MED,SCH MED,DEPT CLIN CHEM,H-4012 DEBRECEN,HUNGARY. RP Laposata, M (reprint author), HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 32 TC 8 Z9 9 U1 0 U2 2 PU AMER OIL CHEMISTS SOC PI CHAMPAIGN PA 1608 BROADMOOR DRIVE, CHAMPAIGN, IL 61821-0489 SN 0024-4201 J9 LIPIDS JI Lipids PD MAR PY 1996 VL 31 SU S BP S217 EP S221 DI 10.1007/BF02637079 PG 5 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA UB908 UT WOS:A1996UB90800038 PM 8729122 ER PT J AU Robinson, DR Urakaze, M Huang, RY Taki, H Sugiyama, E Knoell, CT Xu, LL Yeh, ETH Auron, PE AF Robinson, DR Urakaze, M Huang, RY Taki, H Sugiyama, E Knoell, CT Xu, LL Yeh, ETH Auron, PE TI Dietary marine lipids suppress continuous expression of interleukin-1 beta gene transcription SO LIPIDS LA English DT Article; Proceedings Paper CT 2nd Congress of the International-Society-for-the-Study-of-Fatty-Acids-and-Lipids CY JUN 07-10, 1995 CL NIH, NATCHER CONF CTR, BETHESDA, MD SP Int Soc Study Fatty Acids & Lipids HO NIH, NATCHER CONF CTR ID TUMOR NECROSIS FACTOR; HUMAN PROINTERLEUKIN-1-BETA GENE; FISH-OIL; RHEUMATOID-ARTHRITIS; FATTY-ACIDS; C-MYC; MICE; SUPPLEMENTATION; CELLS; LUPUS AB n-3 Polyunsaturated fatty acids abundant in marine lipids suppress certain inflammatory and immune reactions, and dietary marine lipid supplements have antiinflammatory effects in experimental and human autoimmune disease. Previous work by other investigators demonstrated that dietary marine lipid supplements suppressed production of cytokines from stimulated human peripheral blood mononuclear cells ex vivo. The present study further documents the ability of n-3 fatty acids to inhibit cytokine formation, and in part defines the mechanism of the inhibition of production of interleukin-1 beta (IL-1 beta) by dietary n-3 fatty acid. Female BALB/c mice were each fed a fat-free balanced diet to which was added either a refined fish oil (FO) preparation as a source of n-3 fatty acid, or beef tallow (BT), which consisted primarily of saturated and monoenoic fatty acids. After ingesting the experimental diets for periods ranging from 3 to 12 wk, spleen cell preparations were stimulated ex vivo with either lipopolysaccharide (LPS) or phorbol 12-myristate 13-acetate (PMA), and proIL-1 beta mRNA (IL-1 beta mRNA) was measured by northern analysis. Levels of IL-1 beta mRNA in both LPS- and PMA-stimulated cells from PT-fed mice were elevated to a greater extent than in cells from FO-fed mice, at most concentrations of LPS and PMA. Stability of LPS-stimulated mRNA levels after actinomycin D was similar for PT and FO groups, indicating that lower levels of IL-l mRNA with FO groups was related to suppressed IL-l gene transcription and not due to accelerated transcript degradation. Nuclear run-on transcription assays revealed a more transient expression of the IL-1 beta gene in LPS-stimulated spleen cells from FO-fed mice compared to cells from PT-fed mice. We conclude that dietary marine lipids reduce transient expression of the IL-1 beta gene in stimulated splenic monocytic cells. Preliminary results from nuclear run-on transcription assays indicate that n-3 fatty acids may not change the initial rate of gene transcription but may promote more rapid shutting down of transcription of this gene after induction than do alternative lipids. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02114. RP Robinson, DR (reprint author), MASSACHUSETTS GEN HOSP,ARTHRIT UNIT,MED SERV,BULLFINCH 165,32 FRUIT ST,BOSTON,MA 02114, USA. RI Taki, Hirofumi/I-6284-2012 FU NCI NIH HHS [CA68544]; NIAMS NIH HHS [AR 43518, AR 03564] NR 50 TC 46 Z9 46 U1 0 U2 3 PU AMER OIL CHEMISTS SOC PI CHAMPAIGN PA 1608 BROADMOOR DRIVE, CHAMPAIGN, IL 61821-0489 SN 0024-4201 J9 LIPIDS JI Lipids PD MAR PY 1996 VL 31 SU S BP S23 EP S31 DI 10.1007/BF02637046 PG 9 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA UB908 UT WOS:A1996UB90800005 PM 8729089 ER PT J AU Horny, C Bernhard, J Coates, A Peterson, HF CastiglioneGertsch, M Gelber, RD Rudenstam, CM Collins, J Lindtner, J Goldhirsch, A Senn, HJ AF Horny, C Bernhard, J Coates, A Peterson, HF CastiglioneGertsch, M Gelber, RD Rudenstam, CM Collins, J Lindtner, J Goldhirsch, A Senn, HJ TI Responsiveness of a single-item indicator versus a multi-item scale: Assessment of emotional well-being in an international adjuvant breast cancer trial. SO MEDICAL CARE LA English DT Article DE breast cancer; quality of life assessment; linear analogue self-assessment scales; responsiveness ID QUALITY-OF-LIFE; HEALTH-STATUS INSTRUMENTS; CLINICAL-TRIALS; RECEIVING END; THERAPY; CHEMOTHERAPY; VALIDATION; ARTHRITIS; ONCOLOGY; PAIN AB A single-item linear analogue self-assessment scale for mood was compared with a 28-item adjective checklist for emotional well-being. To confirm its concurrent validity and responsiveness to treatment and recurrence in patients with breast cancer, emotional well-being was assessed every 3 months for 2 years and at 1 and 6 months after recurrence in 1,169 patients who were premenopausal and 960 patients who were postmenopausal. These patients were enrolled in two International Breast Canter Study Group randomized clinical trials in operable breast cancer conducted from 1986 to 1993. To assess concurrent validity, Pearson's correlations between the linear analogue self-assessment scale and the adjective checklist were calculated for each time-point within each treatment group and for the two assessments after recurrence. Responsiveness to treatment and recurrence were analyzed using paired t tests and the squared ratio of these t tests, an estimate of relative efficiency. Concurrent validity of the mood linear analogue self-assessment was consistently confirmed across four language groups. Both measures were responsive; out of 24 changes over time, 19 were in the expected direction for the linear analogue self-assessment scale (P less than or equal to 0.05 for 9 of 19) and 17 for the adjective checklist (P less than or equal to 0.05 for 10 of 17). The linear analogue self-assessment scale was less but sufficiently efficient for detection of treatment effects, with relative efficiency estimates ranging from 0.16 to 2.45 and a median of 0.66 among the comparisons with relatively stable estimates (ItI greater than or equal to 1.0) and more efficient for recurrence than the adjective checklist. The mood linear analogue self-assessment scale is a valid indicator of emotional well-being in patients with breast cancer in large multicenter, multicultural trials in which comprehensive scales are less feasible. This investigation supports the clinical relevance of linear analogue self-assessment scales as indicators of components of quality of life in cancer clinical trials. C1 IBCSG, COORDINATING CTR, BERN, SWITZERLAND. ROYAL PRINCE ALFRED HOSP, DEPT MED ONCOL, CAMPERDOWN, NSW 2050, AUSTRALIA. DANA FARBER CANC INST, IBCSG, CTR STAT, DIV BIOSTAT & EPIDEMIOL, BOSTON, MA 02115 USA. SAHLGRENS UNIV HOSP, DEPT SURG, GOTHENBURG, SWEDEN. ROYAL MELBOURNE HOSP, MELBOURNE, VIC, AUSTRALIA. INST ONCOL, DEPT SURG, LJUBLJANA, SLOVENIA. OSPED CIVICO, SERV ONCOL, LUGANO, SWITZERLAND. KANTONSSPITAL, MED KLIN C, CH-9007 ST GALLEN, SWITZERLAND. RP Horny, C (reprint author), INSELSPITAL BERN, MED DIV LORY, CH-3010 BERN, SWITZERLAND. NR 44 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD MAR PY 1996 VL 34 IS 3 BP 234 EP 248 PG 15 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA TZ577 UT WOS:A1996TZ57700004 ER PT J AU Halpern, J AF Halpern, J TI The measurement of quality of care in the Veterans Health Administration SO MEDICAL CARE LA English DT Article; Proceedings Paper CT Conference on Database - A Resource for Research and Decision Making CY NOV, 1993 CL WASHINGTON, DC SP Dept Vet Affairs VA, Hlth Serv Res & Dev Ser ID IMPROVEMENT AB The Veterans Health Administration (VHA) is committed to continual refinement of its system of quality measurement. The VHA organizational structure for quality measurement has three levels. At the national level, the Associate Chief Medical Director for Quality Management provides leadership, sets policy, furnishes measurement tools, develops and distributes measures of qualify, and delivers educational programs. At the intermediate level, VHA has four regional offices with staff responsible for reviewing risk management data, investigating quality problems, and ensuring compliance with accreditation requirements. At the hospital level, staff reporting directly to the-chief of staff or the hospital director are responsible for implementing VHA quality management policy. The Veterans Health Administration's philosophy of quality measurement recognizes the agency's moral imperative to provide America's veterans with care that meets accepted standards. Because the repair of faulty systems is more efficient than the identification of poor performers, VHA has integrated the techniques of total quality management into a multifaceted improvement program that also includes the accreditation program and traditional quality assurance activities. VHA monitors its performance by maintaining adverse incident databases, conducting patient satisfaction surveys, contracting for external peer review of 50,000 records per year, and comparing process and outcome rates internally and when possible with external benchmarks. The near-term objectives of VHA include providing medical centers with a quality matrix that will permit local development of quality indicators, construction of a report card for VHA's customers, and implementing the Malcolm W. Baldrige system for quality improvement as the road map for systemwide continuous improvement. Other goals include providing. greater access to data, creating a patient-centered database, providing real-time clinical decision support, and expanding the databases. RP Halpern, J (reprint author), US DEPT VET AFFAIRS,810 VERMONT AVE,WASHINGTON,DC 20420, USA. NR 18 TC 26 Z9 26 U1 1 U2 5 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0025-7079 J9 MED CARE JI Med. Care PD MAR PY 1996 VL 34 IS 3 SU S BP MS55 EP MS68 PG 14 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA TZ837 UT WOS:A1996TZ83700006 PM 8598688 ER PT J AU Janov, AJ Leong, T Nathan, DG Guinan, EC AF Janov, AJ Leong, T Nathan, DG Guinan, EC TI Diamond-Blackfan anemia - Natural history and sequelae of treatment SO MEDICINE LA English DT Article ID CONGENITAL HYPOPLASTIC-ANEMIA; RED-CELL APLASIA; BONE-MARROW TRANSPLANTATION; ERYTHROCYTE ADENOSINE-DEAMINASE; GROWTH; INTERLEUKIN-3; CYCLOSPORINE; CHILDREN; PATIENT; THUMBS C1 DANA FARBER CANC INST,DIV CANC EPIDEMIOL & CONTROL,BOSTON,MA 02115. DANA FARBER CANC INST,DIV BIOSTAT,BOSTON,MA 02115. DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. CHILDRENS HOSP,DIV HEMATOL ONCOL,BOSTON,MA. NR 64 TC 82 Z9 84 U1 0 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0025-7974 J9 MEDICINE JI Medicine (Baltimore) PD MAR PY 1996 VL 75 IS 2 BP 77 EP 87 DI 10.1097/00005792-199603000-00004 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA UD967 UT WOS:A1996UD96700004 PM 8606629 ER PT J AU Blair, SN Horton, E Leon, AS Lee, IM Drinkwater, BL Dishman, RK Mackey, M Kienholz, ML AF Blair, SN Horton, E Leon, AS Lee, IM Drinkwater, BL Dishman, RK Mackey, M Kienholz, ML TI Physical activity, nutrition, and chronic disease SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Review DE exercise; diet; nutrition; coronary heart disease; non-insulin-dependent diabetes mellitus; obesity; osteoporosis; health behavior ID CORONARY HEART-DISEASE; RESTING METABOLIC-RATE; BONE-MINERAL DENSITY; DEPENDENT DIABETES-MELLITUS; CARDIOVASCULAR RISK-FACTORS; LIFE-STYLE CHANGES; IMPAIRED GLUCOSE-TOLERANCE; DIETARY CALCIUM INTAKE; WEIGHT-LOSS PROGRAM; LOW-CALORIE DIET AB Epidemiologic, animal, clinical, and metabolic studies demonstrate the independent roles of physical activity and nutrition in the prevention and treatment of several chronic diseases. Fewer data are available to describe the synergistic effects of exercise and diet, and questions remain as to whether and how these two lifestyle factors work together to promote health and prevent disease. This paper briefly reviews many of the known effects of physical activity and nutrition on the prevention and treatment of coronary heart disease, non-insulin-dependent diabetes mellitus, obesity, and osteoporosis as well as how exercise and diet may work together. A discussion of how to increase physical activity levels and how to improve dietary intake also is included. Finally, current exercise and dietary recommendations are summarized, as are directions for future research. C1 JOSLIN DIABET CTR, BOSTON, MA 02215 USA. UNIV MINNESOTA, MINNEAPOLIS, MN 55455 USA. HARVARD UNIV, SCH MED, BOSTON, MA USA. PACIFIC MED CTR, SEATTLE, WA USA. UNIV GEORGIA, ATHENS, GA 30602 USA. NUTRASWEET CO, DEERFIELD, IL USA. NUTRASWEET CO, MONTROSS, VA USA. RP Blair, SN (reprint author), COOPER INST AEROB RES, 12230 PRESTON RD, DALLAS, TX 75230 USA. NR 201 TC 99 Z9 112 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD MAR PY 1996 VL 28 IS 3 BP 335 EP 349 DI 10.1097/00005768-199603000-00009 PG 15 WC Sport Sciences SC Sport Sciences GA TZ160 UT WOS:A1996TZ16000009 PM 8776222 ER PT J AU Patan, S Munn, LL Jain, RK AF Patan, S Munn, LL Jain, RK TI Intussusceptive microvascular growth in a human colon adenocarcinoma xenograft: A novel mechanism of tumor angiogenesis SO MICROVASCULAR RESEARCH LA English DT Article ID SHEAR-STRESS; ENDOTHELIAL-CELLS; CAPILLARY GROWTH; BLOOD-FLOW; TISSUE; ARCHITECTURE; PERFUSION AB Intussusceptive microvascular growth refers to vascular network formation by insertion of interstitial tissue columns, called tissue pillars or posts, into the vascular lumen and subsequent growth of these columns, resulting in partitioning of the vessel lumen. While intussusception has been reported in normal developing organs, its existence in solid tumors has not been previously documented. By observing the growth of the human colon adenocarcinoma (LS174T) in vivo for a period of 6 weeks, we demonstrate that intussusception is an important mechanism of tumor angiogenesis. At the leading edge of the tumor, vascular growth was found to occur by both intussusception and endothelial sprouting. In the stabilized regions, intussusception led to network remodeling and occlusion of vascular segments. The formation of some tissue pillars appears to depend on intravascular blood-flow patterns or changes in intravascular shear stress. The rapid vascular remodeling by intussusception could possibly contribute to intermittent blood flow in tumors. (C) 1996 Academic Press, Inc. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP Patan, S (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,EDWIN L STEELE LAB,BOSTON,MA 02114, USA. RI Munn, Lance/L-3950-2016 OI Munn, Lance/0000-0003-0698-7232 FU NCI NIH HHS [R35-CA56591, F32 CA61631] NR 27 TC 155 Z9 159 U1 0 U2 4 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0026-2862 J9 MICROVASC RES JI Microvasc. Res. PD MAR PY 1996 VL 51 IS 2 BP 260 EP 272 DI 10.1006/mvre.1996.0025 PG 13 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA UB875 UT WOS:A1996UB87500010 PM 8778579 ER PT J AU Kupryjanczyk, J Thor, AD Beauchamp, R Poremba, C Scully, RE Yandell, DW AF Kupryjanczyk, J Thor, AD Beauchamp, R Poremba, C Scully, RE Yandell, DW TI Ovarian, peritoneal, and endometrial serous carcinoma: Clonal origin of multifocal disease SO MODERN PATHOLOGY LA English DT Article DE p53 gene; clonality; endometrial polyp; mutation; ovary; peritoneum; serous carcinoma ID TUMOR SUPPRESSOR GENES; P53 GENE; CHROMOSOME-ABERRATIONS; CANCER; MUTATIONS; TRANSFORMATION; ADENOCARCINOMA; OVEREXPRESSION; PATHOLOGY AB The clonality of disseminated serous carcinoma involving the ovary, peritoneum, and, occasionally, the endometrium is controversial, Histopathologic examination alone cannot unequivocally distinguish between a monoclonal origin and a multicentric origin, Two patients with peritoneal serous carcinoma with minimal. ovarian involvement (one with endometrial serous carcinoma), nine patients with stage III bilateral ovarian carcinoma, and one patient with stage III bilateral carcinosarcoma were studied for clonality. One patient with ovarian carcinoma that recurred after chemotherapy was also studied, Previous analyses of single frozen tumor specimens from these patients had identified different p53 gene mutations in each patient. To test the hypothesis that the disseminated cancers had a monoclonal origin, we assayed DNA from numerous foci from each patient to determine whether the known p53 mutation was present in each specimen, Identical mutations were detected in the tumor foci from each patient with peritoneal dissemination and minimal ovarian involvement, including one patient with an endometrial serous carcinoma as well, In all the patients with bilateral ovarian cancer, the genetic change in p53 was identical in both ovarian tumors, Genetic progression was observed in two patients, one of whom showed a loss of heterozygosity involving the p53 gene in a recurrent tumor. In the second patient, a p53 mutation not present in either ovarian tumor was detected in a metastatic tumor from the omentum, These results strongly suggest that disseminated serous carcinomas, whether primary in the ovary, endometrium, or peritoneum, are of monoclonal rather than multicentric origin; that bilateral stage III ovarian cancers are typically of monoclonal origin; and that additional genetic events involving p53 might occur during progression of these tumors. C1 UNIV VERMONT,SCH MED,DEPT PATHOL,COLL MED,BURLINGTON,VT 05405. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,JAMES HOMER WRIGHT PATHOL LABS,BOSTON,MA 02114. UNIV MUNSTER,GERHARD DOMAGK INST PATHOL,W-4400 MUNSTER,GERMANY. FU NCI NIH HHS [CA44768] NR 46 TC 56 Z9 58 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD MAR PY 1996 VL 9 IS 3 BP 166 EP 173 PG 8 WC Pathology SC Pathology GA UC335 UT WOS:A1996UC33500002 PM 8685209 ER PT J AU Gilks, CB Young, RH Clement, PB Hart, WR Scully, RE AF Gilks, CB Young, RH Clement, PB Hart, WR Scully, RE TI Benign endocervical adenomyomas and adenoma malignum SO MODERN PATHOLOGY LA English DT Article DE adenoma malignum; adenomyoma; uterine cervix ID UTERUS; ADENOCARCINOMA; ADENOSARCOMA; ENDOMETRIUM AB Ten benign biphasic cervical tumors that we have designated ''adenomyomas of endocervical type'' are reported because they might be confused with adenocarcinoma The patients ranged from 21 to 55 years of age (mean, 40 yr). Two presented with abnormal vaginal bleeding, but, in most patients, the cervical tumors did not cause symptoms. On physical examination or at operation, eight patients were found to have tumors ranging from 1.3 to 8.0 cm in greatest dimension growing into the endocervical canal and, in three cases, prolapsing through the external os. The remaining two patients had mural tumors measuring 11.0 and 23.0 cm in greatest dimension, which projected into the pelvis from the outer aspect of the cervix, without mucosal involvement. The tumors were well circumscribed and grey-white or tawny, and five contained multiple mucin-filled cysts up to 3.0 cm in diameter, One tumor was focally hemorrhagic. On microscopic examination, the tumors were composed of glands and cysts lined by a single layer of endocervical-type mucinous epithelium admired with smooth muscle. The epithelial component tvas typically composed of large irregularly shaped glands with papillary epithelial infolding, surrounded by smaller simple glands, frequently resulting in a lobular arrangement Tubal-type epithelium was present focally in six tumors and endometrial-type glands surrounded by endometrial stroma were present in one case. Both the epithelium and smooth muscle were uniformly bland, without significant mitotic activity, Five patients were treated initially by ''polypectomy.'' Hysterectomy 1 month and 1 year later in two of the cases revealed residual adenomyoma; a ''recurrence'' 3 years after polypectomy in another patient was treated by hysterectomy. In no case has there been evidence of spread beyond the cervix The finding of a cervical tumor composed of bland, irregularly shaped, mucinous glands surrounded by smooth muscle caused significant problems in differential diagnosis and a diagnosis of adenoma malignum was either favored or raised as a possibility by the initial pathologist in five of the cases. The gross circumscription of the adenomyomas, their polypoid appearance, the frequent lobular arrangement of glands, the absence of invasive glands with a desmoplastic stromal reaction, and lack of even focal atypia were the most helpful findings in differentiating these tumors from adenoma malignum. C1 UNIV BRITISH COLUMBIA,DEPT PATHOL,VANCOUVER,BC,CANADA. VANCOUVER HOSP & HLTH SCI CTR,DEPT PATHOL,VANCOUVER,BC,CANADA. CLEVELAND CLIN FDN,DIV PATHOL & LAB MED,CLEVELAND,OH 44195. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA. MASSACHUSETTS GEN HOSP,JAMES HOMER WRIGHT PATHOL LABS,BOSTON,MA 02114. RP Gilks, CB (reprint author), VANCOUVER HOSP,DEPT PATHOL,UBC SITE,2211 WESBROOK MALL,VANCOUVER,BC V6T 2B5,CANADA. NR 14 TC 31 Z9 33 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD MAR PY 1996 VL 9 IS 3 BP 220 EP 224 PG 5 WC Pathology SC Pathology GA UC335 UT WOS:A1996UC33500011 PM 8685218 ER PT J AU Thomason, RW Craig, FE Banks, PM Sears, DL Myerson, GE Gulley, ML AF Thomason, RW Craig, FE Banks, PM Sears, DL Myerson, GE Gulley, ML TI Epstein-Barr virus and lymphoproliferation in methotrexate-treated rheumatoid arthritis SO MODERN PATHOLOGY LA English DT Article DE Epstein-Barr virus; lymphoma; methotrexate; post-transplantation lymphoproliferative disorder; rheumatoid arthritis ID IMMUNOCOMPROMISED HOSTS; TRANSPLANT RECIPIENTS; INSITU HYBRIDIZATION; LYMPHOMAS; DISEASES; DISORDERS; INFECTION; THERAPY; LATENT; IMMUNODEFICIENCY AB Generalized lymphadenopathy developed in a 60-year-old female receiving methotrexate and prednisone for treatment of rheumatoid arthritis, Histologic examination of an enlarged right axillary lymph node revealed effacement of normal architecture by a polymorphic population of lymphocytes. The recognition that the patient was medically immunosuppressed and the similarity of lymph node histology to that of a polymorphic post-transplantation lymphoid proliferation led to suspicion that the adenopathy might represent an immunosuppression-related lymphoid proliferation, This possibility was supported by regression of the adenopathy on discontinuation of methotrexate, despite continued corticosteroid therapy, which is an outcome reminiscent of the remissions observed with reduction of immunosuppressive therapy in post-transplantation lymphoproliferative disorders, Subsequent ancillary laboratory studies of lymph node tissue included genetic probe analysis, which revealed a monoclonal population of B-lymphocytes containing clonal Epstein-Barr virus DNA. In situ hybridization studies performed on lymph node tissue revealed expression of Epstein-Barr virus-encoded RNA 1 transcripts, and immunohistochemical studies revealed expression of Epstein-Barr virus latent membrane protein 1, These ancillary studies confirmed the similarity to post transplantation lymphoproliferative disorder. Although immunosuppression-related lymphoproliferative disorders share features with malignant lymphoma, the possibility of resolution in situations in which immunosuppression can be reversed provides a distinction from true malignancy and is of profound importance in therapeutic decision making. C1 UNIV TEXAS,HLTH SCI CTR,DEPT PATHOL,SAN ANTONIO,TX 78284. WILFORD HALL USAF MED CTR,LACKLAND AFB,TX 78236. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. NORTHSIDE HOSP,ATLANTA,GA. FU NCI NIH HHS [KO8-CA01615] NR 40 TC 35 Z9 35 U1 1 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD MAR PY 1996 VL 9 IS 3 BP 261 EP 266 PG 6 WC Pathology SC Pathology GA UC335 UT WOS:A1996UC33500018 PM 8685225 ER PT J AU Nielsen, GP Rosenberg, AE Young, RH Dickersin, GR Clement, PB Scully, RE AF Nielsen, GP Rosenberg, AE Young, RH Dickersin, GR Clement, PB Scully, RE TI Angiomyofibroblastoma of the vulva and vagina SO MODERN PATHOLOGY LA English DT Article DE angiomyofibroblastoma; vagina; vulva ID DERMATOFIBROSARCOMA PROTUBERANS; EXPRESSION; TUMOR; NEOPLASM; REGION AB Nine vulvar and three vaginal angiomyofibroblastomas from patients 23 to 71 years of age (mean, 46 yr) were analyzed. The tumors were well circumscribed and ranged from 0.9 to 11 cm (average, 4.7 cm) in maximal dimension. On microscopic examination, they had hypercellular and hypocellular areas. The neoplastic cells were spindle-shaped, plasmacytoid, or epithelioid; a variable number were binucleated or multinucleated cells. A focal storiform pattern was present in one tumor, and, in one tumor, the neoplastic cells formed a collar around a central area of dense collagen. There was no significant nuclear atypia, and there was less than one mitotic figure per 10 high-power fields. The tumors contained small- to medium-sized blood vessels, which were characteristically thin-walled and, occasionally, ectatic and branching. The stroma was edematous, separated collagen fibers and contained a Variable number of inflammatory cells, especially lymphocytes and mast cells. Three vulvar tumors contained a variable amount of fat. Ultrastructural study of three tumors showed intracytoplasmic, dilated, rough endoplasmic reticulum, moderate numbers of pinocytotic vesicles, and numerous filaments without dense bodies; rare intercellular rudimentary junctions were identified. Eleven of 11 tumors were immunoreactive for vimentin, 11 of 12 for desmin, three of 11 for muscle actin, one of 12 for smooth muscle actin, and four of 12 for CD34. There was no staining for factor Xllla, keratin, S100 protein, Leu-7, glial fibrillary acidic protein, or CD68. Follow-up revealed no recurrences or metastases. Angiomyofibroblastoma is a distinctive benign tumor that arises most commonly in the vulva and vagina and has a diverse histologic and immunohistochemical profile. C1 VANCOUVER HOSP & HLTH SCI CTR,DEPT PATHOL,VANCOUVER,BC,CANADA. RP Nielsen, GP (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,JAMES HOMER WRIGHT PATHOL LABS,FRUIT ST,BOSTON,MA, USA. NR 25 TC 82 Z9 87 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD MAR PY 1996 VL 9 IS 3 BP 284 EP 291 PG 8 WC Pathology SC Pathology GA UC335 UT WOS:A1996UC33500022 PM 8685229 ER PT J AU Gaffey, MJ Frierson, HF Iezzoni, JC Mills, SE Clement, PB Gersell, DJ Shashi, V vonKapHerr, C Young, RH AF Gaffey, MJ Frierson, HF Iezzoni, JC Mills, SE Clement, PB Gersell, DJ Shashi, V vonKapHerr, C Young, RH TI Ovarian granulosa cell tumors with bizarre nuclei: An immunohistochemical analysis SO MODERN PATHOLOGY LA English DT Article DE fluorescence in situ hybridization; granulosa cell tumor; ovarian sex cord-stromal tumor with bizarre nuclei; trisomy 12 ID CORD-STROMAL TUMORS; CLINICOPATHOLOGIC ANALYSIS; TRISOMY-12; LIPOMA; HYBRIDIZATION; LIPOSARCOMA; CARCINOMA AB Granulosa cell tumors with bizarre nuclei (GCT-BN) are rare lesions with a prognosis apparently similar to that of conventional granulosa cell tumors (GCT-NOS). The immunohistochemical features of GCT-BN have not been described, and the exact nature of the bizarre nuclei (BN) is unclear, Thirteen GCT-BN were studied with antibodies to cytokeratin, vimentin, epithelial membrane antigen, muscle-specific actin, alpha smooth muscle actin, desmin, and S-100 protein. Six cases were also examined by fluorescence in situ hybridization for trisomy 12, a nonrandom chromosomal aberration found in a proportion of ovarian sex-cord stromal tumors. Histologically, 12 tumors (86%) contained BN areas interspersed with large areas of OCT-NOS. The remaining tumor contained only microscopic foci of GCT-NOS. Immunohistochemically, the tumors stained for vimentin (13 tumors), S-100 protein (11 tumors), muscle-specific actin (10 tumors), cytokeratin (eight tumors), alpha smooth muscle actin (eight tumors), and desmin (one tumor), but none stained for epithelial membrane antigen. Immunostaining results for the BN and OCT-NOS areas were concordant in eight (73%) of the 11 tumors in which both areas could be independently assessed. The remaining three tumors (27%) showed discordant results for only one of the eight markers used. In five patients, trisomy 12 was detected by fluorescence in situ hybridization in areas of BN but not in areas of GCT-NOS present in the same tumor. Trisomy 12 was also present in another BN tumor in which the foci of GCT-NOS were too small to be evaluated. We conclude that within GCT-BN, areas with BN are immunohistochemically similar to areas of OCT-NOS present in the same tumor. The finding of trisomy 12 in areas with BN but not GCT-NOS in the same tumor, however, suggests that cells with BN represent a genetically distinct clone of tumor cells arising within OCT-NOS. C1 UNIV VIRGINIA,HLTH SCI CTR,DEPT PEDIAT,CHARLOTTESVILLE,VA 22908. VANCOUVER HOSP & HLTH SCI CTR,DEPT PATHOL,VANCOUVER,BC,CANADA. WASHINGTON UNIV,MED CTR,DEPT PATHOL,ST LOUIS,MO 63130. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,BOSTON,MA. RP Gaffey, MJ (reprint author), UNIV VIRGINIA,HLTH SCI CTR,DEPT PATHOL,BOX 214,CHARLOTTESVILLE,VA 22908, USA. NR 33 TC 14 Z9 14 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD MAR PY 1996 VL 9 IS 3 BP 308 EP 315 PG 8 WC Pathology SC Pathology GA UC335 UT WOS:A1996UC33500026 PM 8685233 ER PT J AU Newton, EM Knauf, U Green, M Kingston, RE AF Newton, EM Knauf, U Green, M Kingston, RE TI The regulatory domain of human heat shock factor 1 is sufficient to sense heat stress SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TRANSCRIPTIONAL ACTIVATION DOMAIN; HUMAN HSP70 PROMOTER; DNA-BINDING; YEAST; PROTEIN; CELLS; LOCALIZATION; INVITRO AB Heat shock factor (HSF) activates transcription in response to cellular stress, Human HSF1 has a central regulatory domain which can repress the activity of its activation domains at the control temperature and render them heat shock inducible. To determine whether the regulatory domain works in tandem with specific features of the HSF1 transcriptional activation domains, we first used deletion and point mutagenesis to define these activation domains. One of the activation domains can be reduced to just 20 amino acids. A GAL4 fusion protein containing the HSF1 regulatory domain and this 20-amino-acid activation domain is repressed at the control temperature but potently activates transcription in response to heat shock. No specific amino acids in this activation domain are required for response to the regulatory domain; in particular, none of the potentially phosphorylated serine and threonine residues are required for heat induction, implying that heat-induced phosphorylation of the transcriptional activation domains is not required for induction. The regulatory domain is able to confer heat responsiveness to an otherwise completely heterologous chimeric activator that contains a portion of the VP16 activation domain, suggesting that the regulatory domain can sense heat in the absence of other portions of HSF1. C1 MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. FU NIGMS NIH HHS [GM43901] NR 36 TC 105 Z9 113 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAR PY 1996 VL 16 IS 3 BP 839 EP 846 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA TW172 UT WOS:A1996TW17200012 PM 8622685 ER PT J AU Ito, T Sasaki, Y Wands, JR AF Ito, T Sasaki, Y Wands, JR TI Overexpression of human insulin receptor substrate 1 induces cellular transformation with activation of mitogen-activated protein kinases SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID SIGNAL-TRANSDUCTION; MAP KINASE; PHOSPHATIDYLINOSITOL 3'-KINASE; PHOSPHORYLATION; EXPRESSION; IRS-1; RAS; REGENERATION; PATHWAYS; CLONING AB The insulin receptor substrate 1 protein (IRS-1) is a specific substrate for insulin receptor tyrosine kinase. Expression and tyrosyl phosphorylation of IRS-1 play an important role during normal hepatocyte growth, and the gene is overexpressed in hepatocellular carcinoma tissue. We determined if IRS-1 overexpression directly contributes to cellular transformation, The human IRS-1 gene was subcloned into a mammalian expression vector driven by the cytomegalovirus early promoter, NIH 3T3 cells transiently transfected with this vector subsequently developed transformed foci. Several stably transfected cell lines were established, and they grew efficiently under low-serum conditions and formed colonies when plated in soft agar. Cell lines overexpressing IRS-1 displayed increased tyrosyl phosphorylation of IRS-1 and association with Grb2 but not with the p85 subunit of phosphatidylinositol 3 '-kinase. Since Grb2 is a component of the son-of-sevenless-Ras pathway and upstream in the mitogen-activated protein kinase (MAPK) cascade, enzymatic activities of the major components of this cascade, such as MAPK kinase and MAPK, were evaluated and found to be substantially increased in three independent cell lines with IRS-1 protein overexpression, Such cells, when injected into nude mice, were highly tumorigenic, and there may be a correlation between the degree of MAPK activation and tumor growth rate, This report describes the generation of a transformed phenotype by overexpression of a molecule without a catalytic domain far upstream in the signal transduction cascade and suggests that prolonged activation of MAPKs by this mechanism may be one of the molecular events related to hepatocellular transformation. C1 MASSACHUSETTS GEN HOSP,MOLEC HEPATOL LAB,MGH CANC CTR,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA. FU NCI NIH HHS [CA-35711]; NIAAA NIH HHS [AA-02666, AA-08169] NR 45 TC 77 Z9 78 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAR PY 1996 VL 16 IS 3 BP 943 EP 951 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA TW172 UT WOS:A1996TW17200024 PM 8622697 ER PT J AU Spiro, DJ Boll, W Kirchhausen, T WesslingResnick, M AF Spiro, DJ Boll, W Kirchhausen, T WesslingResnick, M TI Wortmannin alters the transferrin receptor endocytic pathway in vivo and in vitro SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID CELL-FREE SYSTEM; MEDIATED ENDOCYTOSIS; PHOSPHATIDYLINOSITOL 3-KINASE; K562 CELLS; RAT-LIVER; SEGREGATION; VESICLES; FUSION; GOLGI; VPS34 AB Treatment with the phosphatidylinositol 3-kinase inhibitor wortmannin promotes similar to 30% decrease in the steady-state number of cell-surface transferrin receptors. This effect is rapid and dose dependent, with maximal down-regulation elicited within 30 min of treatment and with an IC50 similar to 25 nM wortmannin. Wortmannin-treated cells display an increased endocytic rate constant for transferrin internalization and decreased exocytic rate constants for transferrin recycling. In addition to these effects in vivo, wortmannin is a potent inhibitor (IC50 similar to 15 nM) of a cell-free assay that detects the delivery of endocytosed probes into a common compartment. Inhibition of the in vitro assay involves the inactivation of a membrane-associated factor that can be recruited onto the surface of vesicles from the cytosol. Its effects on the cell-free assay suggest that wortmannin inhibits receptor sorting and/or vesicle budding required for delivery of endocytosed material to ''mixing'' endosomes. This idea is consistent with morphological changes induced by wortmannin, which include the formation of enlarged transferrin-containing structures and the disruption of the perinuclear endosomal compartment. However, the differential effects of wortmannin, specifically increased transferrin receptor internalization and inhibition of receptor recycling, implicate a role for phosphatidylinositol 3-kinase activity in multiple sorting events in the transferrin receptor's membrane traffic pathway. C1 HARVARD UNIV,SCH MED,DEPT NUTR,PROGRAM BIOL & BIOMED SCI,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. CTR BLOOD RES,BOSTON,MA 02115. NR 50 TC 120 Z9 120 U1 0 U2 3 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD MAR PY 1996 VL 7 IS 3 BP 355 EP 367 PG 13 WC Cell Biology SC Cell Biology GA TZ761 UT WOS:A1996TZ76100002 PM 8868465 ER PT J AU Mackey, SL Heymont, JL Kronenberg, HM Demay, MB AF Mackey, SL Heymont, JL Kronenberg, HM Demay, MB TI Vitamin D receptor binding to the negative human parathyroid hormone vitamin D response element does not require the retinoid X receptor SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID RAT OSTEOCALCIN GENE; THYROID-HORMONE; 1,25-DIHYDROXYVITAMIN-D3 RECEPTOR; 5'-FLANKING REGION; D METABOLITES; DNA ELEMENT; ACID; TRANSCRIPTION; EXPRESSION; SUPPRESSION AB An important physiological control of PTH gene expression is its transcriptional repression by 1,25-dihydroxyvitamin D-3 [1,25-(OH)(2)D-3]. The mechanism of this 1,25-(OH)(2)D-3-mediated transcriptional repression is poorly understood. Previous investigations have identified a DNA sequence in the 5'-regulatory region of the human PTH (hPTH) gene that binds the vitamin D receptor (VDR) and mediates transcription repression in response to 1,25(OH)(2)D-3 in GH4C1 cells. The hPTH gene sequence does not mediate transcriptional repression in ROS 17/2.8 cells, even though up-regulatory vitamin D response elements (VDREs) are active in these cells. The hPTH DNA sequence differs from the upregulatory VDREs in that it contains a single copy of a hexameric motif (AGGTTC) homologous to those repeated in the up-regulatory VDREs. The protein-LNA interactions of this sequence were examined using nuclear extracts from bovine parathyroid, GH4C1, and ROS 17/2.8 cells. In bovine parathyroid nuclear extracts, the VDR binds the down-regulatory hPTH DNA sequence independently of the retinoid X receptor (RXR). In GH4C1 nuclear extracts, two VDR-containing complexes are observed: one lacking RXR and one containing RXR. In ROS 17/2.8 nuclear extracts, a single VDR-dependent complex containing RXR is observed. When the up-regulatory rat osteocalcin VDRE is used as a probe, only VDR-RXR-containing complexes are generated using nuclear extracts from all three cell types. These results demonstrate that the sequence that mediates transcriptional repression in response to 1,25-(OH)(2)D-3 differs from the up-regulatory response elements both in sequence composition and in its ability to bind VDR independently of RXR. C1 HARVARD UNIV,ENDOCRINE UNIT,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114. FU NIDDK NIH HHS [P01-DK-11794, DK-08971] NR 23 TC 70 Z9 71 U1 0 U2 3 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD MAR PY 1996 VL 10 IS 3 BP 298 EP 305 DI 10.1210/me.10.3.298 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TY791 UT WOS:A1996TY79100008 PM 8833658 ER PT J AU Nathan, DG AF Nathan, DG TI Molecular medicine milestones SO MOLECULAR MEDICINE LA English DT Editorial Material C1 DANA FARBER CANC INST,BOSTON,MA 02115. NR 2 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 1076-1551 J9 MOL MED JI Mol. Med. PD MAR PY 1996 VL 2 IS 2 BP 163 EP 164 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA UF240 UT WOS:A1996UF24000001 ER PT J AU Friedman, LS Lynn, RB AF Friedman, LS Lynn, RB TI Irritable bowel syndrome SO MOUNT SINAI JOURNAL OF MEDICINE LA English DT Article ID DISORDERS; MOTILITY; STRESS; COLON C1 MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,BOSTON,MA 02114. THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DIV GASTROENTEROL & HEPATOL,PHILADELPHIA,PA 19107. RP Friedman, LS (reprint author), HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115, USA. NR 32 TC 0 Z9 0 U1 1 U2 2 PU MOUNT SINAI HOSPITAL PI NEW YORK PA BOX 1094 ONE GUSTAVE L LEVY PLACE ATTN: CIRCULATION ASST, NEW YORK, NY 10029-6574 SN 0027-2507 J9 MT SINAI J MED JI Mt. Sinai J. Med. PD MAR PY 1996 VL 63 IS 2 BP 126 EP 133 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA UM396 UT WOS:A1996UM39600015 PM 8775144 ER PT J AU Gasser, T Bove, CM Ozelius, LJ Hallett, M Charness, ME Hochberg, FH Breakefield, XO AF Gasser, T Bove, CM Ozelius, LJ Hallett, M Charness, ME Hochberg, FH Breakefield, XO TI Haplotype analysis at the DYT1 locus in Ashkenazi Jewish patients with occupational hand dystonia SO MOVEMENT DISORDERS LA English DT Article DE hand dystonia; DYT1 locus; musician's cramp; writer's cramp; genetics of dystonia ID AUTOSOMAL DOMINANT INHERITANCE; TORSION DYSTONIA; DNA POLYMORPHISMS; JEWS; GENE; FAMILY; MAP AB Genetic haplotypes at five marker loci that are closely linked to the DYT1 gene on chromosome 99 were determined in 10 Ashkenazi Jewish patients with focal hand dystonia (eight with musician's cramp, two with writer's cramp). The founder haplotype associated with >90% of cases of generalized dystonia in the Ashkenazi Jewish population could not be constructed from any of the twenty chromosomes. Potential haplotypes were determined, and no common haplotype was discerned in these patients. These findings argue against a role for the founder mutation in the DYTI gene in the etiology of occupational hand dystonia in this ethnic group. Further, if the DYTI gene is involved in these later onset dystonias, there is no evidence for a common mutation in the Ashkenazic Jewish population. It appears that excessive, repetitive use, possibly in combination with ulnar neuropathy, may serve as the inciting cause of some focal dystonias. C1 MASSACHUSETTS GEN HOSP EAST,MOLEC NEUROGENET UNIT,BOSTON,MA 02129. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA. HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA. UNIV MUNICH,KLINIKUM GROSSHADERN,DEPT NEUROL,D-81377 MUNICH,GERMANY. NIH,BETHESDA,MD 20892. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT NEUROL,BOSTON,MA 02115. FU NINDS NIH HHS [NS28384] NR 24 TC 19 Z9 19 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD MAR PY 1996 VL 11 IS 2 BP 163 EP 166 DI 10.1002/mds.870110208 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA TY140 UT WOS:A1996TY14000007 PM 8684386 ER PT J AU Giordano, M Sanders, LR Castellino, P Canessa, ML DeFronzo, RA AF Giordano, M Sanders, LR Castellino, P Canessa, ML DeFronzo, RA TI Effect of alpha-adrenergic blockers, ACE inhibitors, and calcium channel antagonists on renal function in hypertensive non-insulin-dependent diabetic patients SO NEPHRON LA English DT Article DE captopril; nifedipine; doxazosin; glomerular filtration rate; proteinuria; NIDDM and hypertension ID CONVERTING-ENZYME-INHIBITION; KIDNEY-FUNCTION; ANTIHYPERTENSIVE TREATMENT; ANGIOTENSIN-II; CONTROLLED TRIAL; NEPHROPATHY; CAPTOPRIL; MELLITUS; DISEASE; THERAPY AB In the present study we investigated the effect of a selective alpha(1)-adrenergic blocker (doxazosin), an angiotensin-converting enzyme (ACE) inhibitor (captopril), and a calcium channel antagonist (nifedipine) on renal function in hypertensive non-insulin-dependent diabetic patients. 30 NIDD hypertensive patients (age = 50 +/- 3 years; BMI = 30 +/- 1 kg/m(2))(mean +/- SEM) were studied before and after a 12-week period of antihypertensive treatment. Ten patients were treated with doxazosin (Cardura) (2-8 mg once daily or 8 mg b.i.d.), 9 with captopril (Capoten) (25-50 mg b.i.d.), and 11 with nifedipine (Procardia-XL) (30-60 mg once daily). Blood pressure, creatinine clearance, 24-hour urinary protein excretion, fasting plasma glucose concentration and glycosylated hemoglobin were measured before and after drug treatment. Easting plasma glucose and glycosylated hemoglobin (HbA(1c)) were similar in all three groups prior to the start of antihypertensive therapy and did not change significantly from baselline in any treatment groups. In the doxazosin group creatinine clearance rose from 99 +/- 8 to 122 +/- 8 ml/1.73 m(2) . min (p < 0.01), while 24-hour urinary protein excretion declined from 2.66 +/- 0.05 to 1.76 +/- 0.02 mg/day/ml/1.73 m(2) . min (p < 0.01). In diabetics treated with captopril creatinine clearance rose from 93 +/- 6 to 109 +/- 9 ml/1.73 m(2) . min (p < 0.05), while the 24-hour urinary protein excretion fell from 2.70 +/- 0.05 to 2.03 +/- 0.04 mg/day/ml/1.73 m(2) . min (p < 0.05). In patients treated with nifedipine creatinine clearance did not change (97 +/- 6 vs. 94 +/- 7 ml/1.73 m(2) . min), while 24-hour urinary protein excretion decreased from 2.84 +/- 0.04 to 1.95 +/- 0.03 mg/day/ml/1.73 m(2) . min. Systolic and diastolic blood pressure were similar in doxazosin (150 +/- 3/95 +/- 2 mm Hg), captopril(153 +/- 3/93 +/- 1), and nifedipine (155 +/- 4/93 +/- 1) groups prior to the start of antihypertensive therapy and declined to 143 +/- 3/84 +/- 3 (doxazosin), 139 +/- 3/82 +/- 3 (captopril), and 141 +/- 3/84 +/- 1 (nifedipine) mm Hg (all p < 0.01 vs. pretreatment). In summary, both doxazosin and captopril treatment were associated with significant rises in GFR, while all three antihypertensive agents caused a significant decline in proteinuria. These results indicate that alpha-adrenergic blockers, ACE inhibitors, and calcium channel antagonists can safely and effectively be used in the clinical management of non-insulin-dependent diabetic patients with hypertension. C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,AUDIE L MURPHY VET MEM HOSP,DIV DIABET,SAN ANTONIO,TX 78284. UNIV NAPLES 2,INST INTERNAL MED & NEPHROL,NAPLES,ITALY. OI CASTELLINO, Pietro/0000-0002-9014-2007 FU NCRR NIH HHS [M01-RR-01346] NR 57 TC 25 Z9 25 U1 1 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-2766 J9 NEPHRON JI Nephron PD MAR PY 1996 VL 72 IS 3 BP 447 EP 453 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA TY499 UT WOS:A1996TY49900013 PM 8852495 ER PT J AU Limmroth, V May, A Diener, HC AF Limmroth, V May, A Diener, HC TI The value of sumatriptan in the acute treatment of migraine and cluster headache SO NERVENHEILKUNDE LA German DT Article DE migraine; cluster headache; sumatriptan; serotonin agonists; 5-HT1D receptors ID BLOOD-FLOW VELOCITY; SUBCUTANEOUS SUMATRIPTAN; ANTIMIGRAINE DRUG; CEREBRAL-ARTERIES; RECEPTORS; EFFICACY; ATTACKS; PAIN; DIHYDROERGOTAMINE; STIMULATION AB Sumatriptan is the first approved migraine medication that mediates receptor selective effects. Its efficacy has been shown in numerous studies worldwide and its safety profile has been extensively investigated. Its mode of action, however, is not yet fully understood. Initially developed as a selective vasoconstrictive drug, sumatriptan demonstrated other effects, which might be important for its clinical efficacy. it blocks the release of vasoactive neuropeptides, suppresses the expression of neurogenic inflammation, and attenuates the nociceptive transmission. Not only does the physician have a new, highly effective migraine medication, but pain researchers have a new tool to investigate the role of the serotonergic system in pain and its treatment. The following article will review current data with regard to sumatriptan's pharmacology, efficacy, and side effects. C1 UNIV ESSEN GESAMTHSCH,NEUROL KLIN,W-4300 ESSEN,GERMANY. RP Limmroth, V (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CTR NEUROSCI,CN4,BLDG 149,13TH ST 6403,BOSTON,MA 02129, USA. NR 61 TC 0 Z9 0 U1 0 U2 0 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 45, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0722-1541 J9 NERVENHEILKUNDE JI Nervenheilkunde PD MAR PY 1996 VL 15 IS 2 BP 101 EP 109 PG 14 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA UF073 UT WOS:A1996UF07300009 ER PT J AU Neve, RL Boyce, FM McPhie, DL Greenan, J OsterGranite, ML AF Neve, RL Boyce, FM McPhie, DL Greenan, J OsterGranite, ML TI Transgenic mice expressing APP-C100 in the brain SO NEUROBIOLOGY OF AGING LA English DT Article DE APP-C100; Alzheimer's disease; mouse brain ID AMYLOID PRECURSOR PROTEIN; CARBOXYL-TERMINAL FRAGMENT; CENTRAL-NERVOUS-SYSTEM; ALZHEIMERS-DISEASE; ALZ-50 IMMUNOREACTIVITY; SYNAPSE LOSS; NEUROTOXICITY; DEPOSITION; NEURONS; RAT AB The classic hallmarks of Alzheimer's disease are the deposition of amyloid in plaques and in the cerebrovasculature, and the emergence of neurofibrillary tangles in neurons. The interplay between these two pathologic processes, on the one hand, and the degeneration of neurons and loss of cognitive functions on the other, remains incompletely understood. We have proposed that one crucial component of this interplay is a fragment of the Alzheimer amyloid protein precursor (APP) comprising the carboxyterminal 100 amino acids of this molecule, which we term APP-C100 (or, more simply, C100). This fragment, which comprises the 42-amino acid amyloid protein (AP) and an additional 58 amino acids carboxyterminal to it, was found to be toxic specifically to nerve cells in vitro. We developed transgenic mouse models to test the hypothesis that APP-C100 causes Alzheimer's disease neuropathology. APP-C100 was delivered to the mouse brain via a transgene expressing C100 under the control of the dystrophin brain promoter. These transgenic animal models for the action of APP-C100 in the brain exhibited some of the neuropathological features characteristic of Alzheimer disease brain. The animal models that we have created can be used to test hypotheses concerning the mechanism by which C100 interacts with a neuronal receptor to kill neurons. C1 MCLEAN HOSP,BELMONT,MA 02178. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,BOSTON,MA 02129. UNIV CALIF RIVERSIDE,DIV BIOMED SCI,RIVERSIDE,CA 92521. RP Neve, RL (reprint author), HARVARD UNIV,SCH MED,DEPT GENET,BELMONT,MA 02178, USA. FU NIA NIH HHS [AG12954]; NICHD NIH HHS [HD19932] NR 44 TC 33 Z9 34 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD MAR-APR PY 1996 VL 17 IS 2 BP 191 EP 203 DI 10.1016/0197-4580(95)02074-8 PG 13 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA UH440 UT WOS:A1996UH44000005 PM 8744400 ER PT J AU Przedborski, S Donaldson, DM Murphy, PL Hirsch, O Lange, D Naini, AB McKennaYasek, D Brown, RH AF Przedborski, S Donaldson, DM Murphy, PL Hirsch, O Lange, D Naini, AB McKennaYasek, D Brown, RH TI Blood superoxide dismutase, catalase and glutathione peroxidase activities in familial and sporadic amyotrophic lateral sclerosis SO NEURODEGENERATION LA English DT Article DE amyotrophic lateral sclerosis; catalase; erythrocyte; enzymatic activity; free radical; glutathione peroxidase; superoxide dismutase ID DISEASE; STRESS AB Recent studies have implicated free radicals in the pathogenesis of amyotrophic lateral sclerosis (ALS), a fatal, paralytic disorder of motor neurons. Herein we report on measurements of erythrocyte activity of the three main free radical scavenging enzymes: copper/zinc superoxide dismutase (Cu/Zn-SOD), catalase, and glutathione peroxidase. We studied 31 patients with sporadic ALS, 18 with familial ALS, and 24 controls, Mean Cu/Zn-SOD activity was reduced in eight familial ALS patients with mutations of Cu/Zn-SOD but was normal in patients with both familial ALS without identified Cu/Zn-SOD mutations and sporadic ALS. Glutathione peroxidase activity was significantly reduced only in sporadic ALS patients treated with insulin-like growth factor I (100 mu g/kg). Catalase activity was normal in sporadic and familial ALS. Neither glutathione peroxidase nor catalase activities correlated significantly with duration of symptoms or age at onset. Vitamin E, vitamin C, and beta-carotene did not affect any of the three enzyme activities. These observations indicate that disturbances of catalase and glutathione peroxidase function are not likely to be central factors in the pathogenesis of ALS. (C) 1996 Academic Press Limited. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CECIL B DAY LAB NEUROMUSCULAR RES,BOSTON,MA. RP Przedborski, S (reprint author), COLUMBIA UNIV COLL PHYS & SURG,DEPT NEUROL,650 W 168TH ST,NEW YORK,NY 10032, USA. FU NINDS NIH HHS [1PO1NS31248-01, 1-KO8-NS01724-02] NR 50 TC 36 Z9 37 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 1055-8330 J9 NEURODEGENERATION JI Neurodegeneration PD MAR PY 1996 VL 5 IS 1 BP 57 EP 64 PG 8 WC Neurosciences SC Neurosciences & Neurology GA UE434 UT WOS:A1996UE43400008 PM 8731383 ER PT J AU Lembo, T Plourde, V Shui, Z Fullerton, S Mertz, H Tache, Y Sytnik, B Munakata, J Mayer, E AF Lembo, T Plourde, V Shui, Z Fullerton, S Mertz, H Tache, Y Sytnik, B Munakata, J Mayer, E TI Effects of the corticotropin-releasing factor (CRF) on rectal afferent nerves in humans SO NEUROGASTROENTEROLOGY AND MOTILITY LA English DT Article DE irritable bowel syndrome; mechanoreceptor; rectal compliance; spinal afferents ID FACTOR RECEPTORS; MOTOR-RESPONSES; NERVOUS-SYSTEM; SPINAL-CORD; STRESS; RAT; ANTINOCICEPTION; HORMONE; NEURONS; INTERLEUKIN-2 AB Corticotropin-releasing-factor (CRF) released in the gastrointestinal mucosa from immune cells or enterochromaffin cells may play a role in the modulation of rectal afferent function. In the current study we evaluated the effects of peripherally administered CRP on afferent mechanisms in the human rectum. We used rectal balloon distention in seven healthy volunteers to evaluate the effect of CRF (1 mu g/ kg) on visceral afferents originating in the rectum which are involved in the following functions: thresholds and intensity of conscious perception, receptive relaxation, reflex inhibition of internal anal sphincter and a viscerosomatic reflex. Rectal mechanoreceptors were stimulated either by distending the rectum using a volume ramp (40 and 400 mL/min), or by intermittent phasic distention. CRF decreased the thresholds and increased the intensity for the sensation of discomfort in response to both ramp and phasic distention. During slow ramp distention, CRF also lowered the stool threshold. CRF increased rectal compliance during slow ramp distention without affecting the rare of receptive relaxation or the inflection point of the compliance curve. CRF had no effect on viscerosomatic referral patterns, or on the rectoanal inhibitory reflex. These findings are consistent with a dual effect of CRF on afferent pathways mediating perception of aversive rectal sensations, and on rectal smooth muscle. C1 W LOS ANGELES VET AFFAIRS MED CTR,DEPT MED,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,BRAIN RES INST,DEPT MED,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,CURE VA,GASTROENTER BIOL CTR,NEUROENTER BIOL GRP,LOS ANGELES,CA 90073. FU NIDDK NIH HHS [DK 40919, DK 17238, DK 33061] NR 49 TC 59 Z9 63 U1 0 U2 3 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 1350-1925 J9 NEUROGASTROENT MOTIL JI Neurogastroenterol. Motil. PD MAR PY 1996 VL 8 IS 1 BP 9 EP 18 DI 10.1111/j.1365-2982.1996.tb00237.x PG 10 WC Gastroenterology & Hepatology; Clinical Neurology; Neurosciences SC Gastroenterology & Hepatology; Neurosciences & Neurology GA TX136 UT WOS:A1996TX13600002 PM 8697187 ER PT J AU Tracey, I Carr, CA Guimaraes, AR Worth, JL Navia, BA Gonzalez, RG AF Tracey, I Carr, CA Guimaraes, AR Worth, JL Navia, BA Gonzalez, RG TI Brain choline-containing compounds are elevated in HIV-positive patients before the onset of AIDS dementia complex: A proton magnetic resonance spectroscopic study SO NEUROLOGY LA English DT Article ID MR SPECTROSCOPY; FRONTAL-CORTEX; NEURONAL LOSS; INFECTION; ENCEPHALOPATHY; CHILDREN AB The CNS is frequently involved in human immunodeficiency virus (HIV) infection. In recent studies using proton magnetic resonance spectroscopy, investigators found a significant reduction in N-acetyl aspartate, a metabolic marker of neurons, in late stages of dementia. To further understand the relationship between proton magnetic resonance spectroscopy changes and clinical disease and dementia, we compared 20 HIV-infected patients presenting at varying stages of acquired immunodeficiency syndrome (AIDS) dementia complex and infection to 10 age-matched controls. We found a significant reduction in N-acetyl aspartate/creatine only in patients who had advanced dementia and CD4 counts less than 200/mu l. By contrast, a significant elevation in compounds containing choline was present in patients in the early stages of HIV infection or who had CD4 counts greater than 200/mu l, in patients with normal MRI scans, and in all AIDS dementia complex groups, including subjects with no or minimal cognitive impairment. An elevated choline level also occurred in later stages of HIV infection (CD4 < 200/mu l). Our results suggest that an increase in choline occurs before N'-acetyl aspartate decrements, MRI abnormalities, and the onset of dementia, and may therefore provide a useful marker for early detection of brain injury associated with HIV infection. C1 MASSACHUSETTS GEN HOSP,NMR CTR,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT NEURORADIOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. FU NIA NIH HHS [AG10679]; NINDS NIH HHS [KO8N-NS01510] NR 49 TC 118 Z9 118 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAR PY 1996 VL 46 IS 3 BP 783 EP 788 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA UB778 UT WOS:A1996UB77800034 PM 8618683 ER PT J AU Menard, MT Kosslyn, SM Thompson, WL Alpert, NM Rauch, SL AF Menard, MT Kosslyn, SM Thompson, WL Alpert, NM Rauch, SL TI Encoding words and pictures: A positron emission tomography study SO NEUROPSYCHOLOGIA LA English DT Article DE neuropsychology; psycholinguistics; language; reading; brain localization; positron emission tomography ID EXTRASTRIATE; APHASIA; ANATOMY; OBJECT; CORTEX AB Subjects viewed words, pictures, crosshairs, or a large X flanked by two smaller xs on either side while their brain activity was monitored using positron emission tomography (PET). When activation from the pictures, crosshairs, or Xs condition was subtracted from activation in the words condition, the left angular gyrus and Broca's area were found to be activated. In the comparison of words and pictures, additional language areas were activated. These results provide support for the classical neurological model of reading. The results also suggest that a ''word form area'' is near the margin of the left angular gyrus. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,DEPT PSYCHOL,CAMBRIDGE,MA 02138. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. NR 38 TC 104 Z9 104 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PD MAR PY 1996 VL 34 IS 3 BP 185 EP 194 DI 10.1016/0028-3932(95)00099-2 PG 10 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA UA322 UT WOS:A1996UA32200003 PM 8868276 ER PT J AU Butler, WE Barker, FG Crowell, RM AF Butler, WE Barker, FG Crowell, RM TI Patients with polycystic kidney disease would benefit from routine magnetic resonance angiographic screening for intracerebral aneurysms: A decision analysis SO NEUROSURGERY LA English DT Article DE cost-effectiveness; decision analysis; intracerebral aneurysm; magnetic resonance imaging; Markov chain; polycystic kidney disease; subarachnoid hemorrhage ID UNRUPTURED INTRACRANIAL ANEURYSMS; SUBARACHNOID HEMORRHAGE; EARLY OPERATION; ARTERIOVENOUS-MALFORMATIONS; CEREBRAL-ANGIOGRAPHY; SACCULAR ANEURYSMS; NATURAL-HISTORY; MANAGEMENT; PROGNOSIS; RISK AB AUTOSOMAL DOMINANT POLYCYSTIC kidney disease (ADPKD) is associated with increased prevalence of cerebral aneurysms and increased risk of subarachnoid hemorrhage. A decision analysis by Levey et al. in 1983 demonstrated that patients with ADPKD would not significantly benefit from routine arteriographic screening for cerebral aneurysms. We reexamined this conclusion in light of new clinical data and the introduction of magnetic resonance imaging (MRI) as a screening method. We compared an MRI screening strategy with a nonscreening strategy. The screening strategy specified MRI screening and then neurosurgical management of detected aneurysms. The nonscreening strategy specified cerebrovascular care only in the event of subarachnoid hemorrhage. The decision tree incorporated estimates derived from the clinical literature for the prevalence of asymptomatic aneurysms in patients with ADPKD (15%), the annual incidence of aneurysmal rupture (1.6%), the morbidity and mortality rates associated with subarachnoid hemorrhage (70 and 56%, respectively), the risk of transfemoral arteriography (0.2%), the sensitivity and specificity of MRI, the morbidity and mortality rates associated with surgical treatment of an unruptured aneurysm (4.1 and 1.0%, respectively), and the life expectancy of patients with ADPKD. The model predicted that the screening strategy would provide 1.0 additional year of life without neurological disability to a 20-year-old patient with ADPKD. A sensitivity analysis showed that the model was most sensitive to estimates of the prevalence of aneurysms in ADPKD, the annual incidence of rupture, and the morbidity and mortality rates associated with rupture. A financial analysis showed that a screening strategy is likely to cost less than a nonscreening strategy. The model predicts that an MRI screening strategy would increase the life expectancy of young patients with ADPKD and reduce the financial impact on society of ADPKD. C1 BERKSHIRE ASSOCIATES,PITTSFIELD,MA. RP Butler, WE (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,NEUROSURG SERV,15 PARKMAN ST,ACC 021,BOSTON,MA 02114, USA. NR 58 TC 40 Z9 40 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD MAR PY 1996 VL 38 IS 3 BP 506 EP 515 PG 10 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA TW572 UT WOS:A1996TW57200042 PM 8837803 ER PT J AU Field, AE Colditz, GA Herzog, DB Heatherton, TF AF Field, AE Colditz, GA Herzog, DB Heatherton, TF TI Disordered eating: Can women accurately recall their binging and purging behaviors 10 years later? SO OBESITY RESEARCH LA English DT Article DE women; eating disorders; recall ID STUDENT POPULATIONS; BULIMIC BEHAVIORS; ADOLESCENT GIRLS; ANOREXIA-NERVOSA; PREVALENCE; INVENTORY; RELIABILITY; ATTITUDES; SAMPLE; AGE AB Objective: To test women's ability to recall their past binging and purging behaviors, Design: Ten-year follow-up study of women who had participated in a cross-sectional survey during college. Subjects: In 1982, a sample of freshman and senior women at a large university in the Boston area were questioned about their weight, dieting history, bulimic symptoms, and eating patterns, attitudes, and concerns, In 1992, all subjects who responded to the 1982 survey were followed up to assess changes in bulimic symptoms and ability to recall past behaviors, Results: Among the 476 women who responded to both surveys, the percentage in 1992 who reported having ever binged and/or purged was less than the percentage in 1982, indicating that the recall of past behaviors was less than perfect, Denial in 1992 of ever having engaged in the behaviors ranged from 22% among the women who were self-inducing vomiting in 1982 to 64% among the women who had reported current fasting or strict dieting in 1982, Recall of past behaviors in 1992 was better among the women who had been current bingers or purgers in 1982, Conclusion: Our results demonstrate that ability to recall past binging and purging is only modest, Therefore to better understand the mental and physical health consequences of these behaviors this information should be collected prospectively. C1 HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA. HARVARD UNIV,SCH MED,BRIGHAM & WOMENS HOSP,DEPT MED,CHANNING LAB,BOSTON,MA. MASSACHUSETTS GEN HOSP,EATING DISORDER UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. HARVARD UNIV,DEPT PSYCHOL,BOSTON,MA 02115. RI Heatherton, Todd/H-5478-2011; Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NIDDK NIH HHS [P30-DK-46200] NR 28 TC 15 Z9 15 U1 3 U2 4 PU NORTH AMER ASSOC STUDY OBESITY PI BATON ROUGE PA 6400 PERKINS RD, BATON ROUGE, LA 70808 SN 1071-7323 J9 OBES RES JI Obes. Res. PD MAR PY 1996 VL 4 IS 2 BP 153 EP 159 PG 7 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA TZ378 UT WOS:A1996TZ37800006 PM 8681048 ER PT J AU Vitale, AT Rodriguez, A Foster, CS AF Vitale, AT Rodriguez, A Foster, CS TI Low-dose cyclosporin A therapy in treating chronic, noninfectious uveitis SO OPHTHALMOLOGY LA English DT Article ID INTRAOCULAR INFLAMMATORY DISEASE; EXPERIMENTAL AUTOIMMUNE UVEITIS; ENDOGENOUS UVEITIS; POSTERIOR UVEITIS; BEHCETS-DISEASE; RISK-FACTORS; NEPHROTOXICITY AB Purpose: To describe the authors' approach to the management of patients with recalcitrant, chronic, endogenous uveitis using low-dose Cyclosporin A (CSA) alone or in combination with other immunosuppressive agents with attention to the anti-inflammatory efficacy, visual outcome, and side effects of therapy. Methods: The authors reviewed the records of 50 patients (92 eyes) with uveitis of various etiologies who had been treated with low-dose CSA (2.5-5.0 mg/kg daily) alone or in combination with prednisone and/or azathioprine (1.5-2.0 mg/kg daily). The median follow-up on low-dose CSA was 16 months (range, 6-64 months). Results: Inflammatory central was achieved in 68 (73.9%) eyes, while persistent inflammatory activity was observed in 14 (15.2%). Thirty-eight (41%) eyes improved two Snellen lines or more, 43 (47.0%) stabilized, and 11 (12.0%) lost two lines or more. The CSA was discontinued because of nephrotoxicity in three patients and in each of two with systemic hypertension and constitutional intolerance to the drug, respectively. Thirteen patients enjoy inflammatory remission with this regimen. Conclusion: Low-dose CSA used alone or in combination with other immunosuppressive agents is effective in achieving inflammatory control with a favorable visual outcome and provides a useful steroid-sparing strategy in the management of chronic endogenous uveitis. The CSA-associated toxicity may be reduced by initiating therapy at very low initial doses, with incremental dosage escalation to the desired target range. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,IMMUNOL & UVEITIS SERV,BOSTON,MA 02114. RETINA SPECIALISTS BOSTON,BOSTON,MA. HOSP SAN JOSE MONTERREY,ITESM,DEPT OFTALMOL,SERV INMUNOL & UVEITIS,MONTERREY,MEXICO. OI de Smet, Marc/0000-0002-9217-5603 NR 35 TC 56 Z9 61 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD MAR PY 1996 VL 103 IS 3 BP 365 EP 373 PG 9 WC Ophthalmology SC Ophthalmology GA UA469 UT WOS:A1996UA46900018 PM 8600411 ER PT J AU TugalTutkun, I Havrlikova, K Power, WJ Foster, CS AF TugalTutkun, I Havrlikova, K Power, WJ Foster, CS TI Changing patterns in uveitis of childhood SO OPHTHALMOLOGY LA English DT Article ID JUVENILE RHEUMATOID-ARTHRITIS; POSTERIOR; DIAGNOSIS; ANTERIOR; DISEASE AB Background: Although uveitis is relatively uncommon in children, its diagnosis and management present a distinct clinical challenge for the physician. An improved knowledge of disease patterns and associated morbidity will help in the care of children with uveitis. Methods: The authors reviewed the records of 130 patients with onset of uveitis at 16 years of age or younger. The etiology of uveitis, complications encountered, treatment administered, and visual results were analyzed. Results: Uveitis associated with juvenile rheumatoid arthritis (JRA) was the largest group (41.5%) followed by idiopathic uveitis (21.5%) and pars planitis (15.3%). Twenty-six percent of the eyes had less than 20/200 visual acuity at the time of first referral. Patients with JRA had the highest rate of complications: cataract (71%), glaucoma (30%), band keratopathy (66%), and hypotony (19%). The most frequent complication of pars planitis was maculopathy (55%). Final visual acuity was less than 20/200 in 26% of eyes with JRA, 10.5% with pars planitis, and 14% with idiopathic uveitis. Conclusion: Uveitis beginning in childhood is a serious disease associated with sight-threatening complications. Juvenile rheumatoid arthritis-associated uveitis remains a leading cause of ocular morbidity in patients with childhood uveitis. Increased awareness by pediatricians, rheumatologists, and ophthalmologists of the seriousness of ocular complications of uveitis in childhood may lead to earlier diagnosis and more effective treatment regimens in the future. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,BOSTON,MA 02114. ISTANBUL UNIV,ISTANBUL FAC MED,DEPT OPHTHALMOL,ISTANBUL,TURKEY. NR 35 TC 115 Z9 122 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD MAR PY 1996 VL 103 IS 3 BP 375 EP 383 PG 9 WC Ophthalmology SC Ophthalmology GA UA469 UT WOS:A1996UA46900020 PM 8600412 ER PT J AU Kramer, M Miller, JW Michaud, N Moulton, RS Hasan, T Flotte, TJ Gragoudas, ES AF Kramer, M Miller, JW Michaud, N Moulton, RS Hasan, T Flotte, TJ Gragoudas, ES TI Liposomal benzoporphyrin derivative verteporfin photodynamic therapy - Selective treatment of choroidal neovascularization in monkeys SO OPHTHALMOLOGY LA English DT Article ID PHOTOCOAGULATION; PERMEABILITY; PHOTOSENSITIZATION; MACULOPATHY; TUMORS; SITES; MODEL AB Purpose: The authors have previously shown that photodynamic therapy (PDT) using lipoprotein-delivered benzoporphyrin derivative mono-acid (BPD) effectively closed experimental choroidal neovascularization (CNV). In the current study, the authors used a clinical preparation, liposomal BPD verteporfin in the same model, with experiments designed to establish optimal dye and light doses, and the timing of laser light irradiation after dye injection, for effective and selective closure of CNV. Methods: Experimental CNV was induced in the maculae of cynomolgus monkeys. Liposomal BPD verteporfin was injected intravenously at doses of 1.0, 0.5, 0.375, and 0.25 mg/kg. Laser light at 692 nm then was applied to CNV, with an irradiance of 600 mW/cm(2) and fluence of 150 J/cm(2), at various times after dye injection, ranging from 5 to 120 minutes. Treatment effect was assessed by fundus photography and fluorescein angiography and confirmed by light and electron microscopy. The PDT of experimental CNV was studied to assess efficacy; PDT performance on normal eyes was studied to investigate selectivity. Results: The CNV closure was demonstrated by fluorescein angiography and histopathologic findings at all tested dye doses. A dye dose of 0.375 mg/kg, with laser light irradiation applied 20 to 50 minutes after dye injection, optimized CNV closure with minimal retinal and choroidal damage. No major local adverse effects were noted, and the drug was well tolerated systematically. Conclusions: Liposomal BPD verteporfin is a potent photosensitizer, and PDT using this dye is a potentially effective and selective treatment for CNV. C1 HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,RETINA SERV,LASER RES LAB,BOSTON,MA. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,WELLMAN LABS PHOTOMED,DEPT DERMATOL,BOSTON,MA. NR 25 TC 148 Z9 158 U1 1 U2 5 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD MAR PY 1996 VL 103 IS 3 BP 427 EP 438 PG 12 WC Ophthalmology SC Ophthalmology GA UA469 UT WOS:A1996UA46900027 PM 8600419 ER PT J AU Craig, WA Andes, D AF Craig, WA Andes, D TI Pharmacokinetics and pharmacodynamics of antibiotics in otitis media SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE otitis media; pharmacodynamics; pharmacokinetics; middle ear fluid ID MIDDLE-EAR FLUID; ANTIMICROBIAL RESISTANCE; STREPTOCOCCUS-PNEUMONIAE; HAEMOPHILUS-INFLUENZAE; MORAXELLA-CATARRHALIS; EFFICACY; ERYTHROMYCIN; AMOXICILLIN; SERUM C1 UNIV WISCONSIN,DEPT MED,MADISON,WI. RP Craig, WA (reprint author), WILLIAM S MIDDLETON MEM VET ADM MED CTR,DEPT MED,2500 OVERLOOK TERRACE,MADISON,WI 53705, USA. NR 30 TC 315 Z9 321 U1 0 U2 8 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD MAR PY 1996 VL 15 IS 3 BP 255 EP 259 DI 10.1097/00006454-199603000-00015 PG 5 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA UA252 UT WOS:A1996UA25200012 PM 8852915 ER PT J AU Linn, WD AF Linn, WD TI Angiotensin-converting enzyme inhibitors in left ventricular dysfunction SO PHARMACOTHERAPY LA English DT Article; Proceedings Paper CT Symposium on Evolving Concepts in the Treatment of Heart Failure, at the 1995 Annual Meeting of the American-College-of-Clinical-Pharmacy CY AUG 06, 1995 CL WASHINGTON, DC SP Amer Coll Clin Pharm ID CONGESTIVE-HEART-FAILURE; PLACEBO-CONTROLLED TRIAL; MYOCARDIAL-INFARCTION; DOUBLE-BLIND; LONG-TERM; EXERCISE PERFORMANCE; ENALAPRIL; CAPTOPRIL; MORTALITY; SURVIVAL AB Angiotensin-converting enzyme (ACE) inhibitors have been used for more than a decade in the treatment of chronic congestive heart failure, In recent years these agents have been used in patients who survived a myocardial infarction. However, primary care providers are often confused as to which patients would benefit the most, and as a result, these life-prolonging drugs are underutilized. The results of randomized controlled trials evaluating ACE inhibitors' effects on morbidity and mortality in patients with chronic congestive heart failure or acute myocardial infarction were evaluated, Angiotensin-converting enzyme inhibitors clearly improve survival in patients with symptomatic congestive heart failure. This survival benefit is approximately 6 months. In patients with asymptomatic systolic dysfunction, these agents also decrease the number of hospital admissions due to heart failure. Angiotensin-converting enzyme inhibitors also improve survival in all patients who experienced an acute myocardial infarction. With the plethora of evidence regarding the positive effects that this class of drugs has on the quality of life and survival of patients with systolic dysfunction, it is still unclear why clinicians are reluctant to use them more often. Primary care providers need to be educated on how to risk stratify patients to make this therapy more cost effective, and when these agents should be started. RP Linn, WD (reprint author), AUDIE L MURPHY MEM VET ADM MED CTR,DEPT MED,7400 MERTON MINTER BLVD,BOX 11-C,SAN ANTONIO,TX 78284, USA. NR 47 TC 5 Z9 5 U1 0 U2 0 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER BOX 806 171 HARRISON AVE, BOSTON, MA 02111 SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD MAR-APR PY 1996 VL 16 IS 2 BP S50 EP S58 PN 2 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA UA857 UT WOS:A1996UA85700005 PM 8668606 ER PT J AU Constantinescu, MA Greenwald, DP Amarante, MTJ Nishioka, NS May, JW AF Constantinescu, MA Greenwald, DP Amarante, MTJ Nishioka, NS May, JW TI Effects of laser versus scalpel tenolysis in the rabbit flexor tendon SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID CARBON-DIOXIDE LASER; ND-YAG LASER; TISSUE ABLATION; PASSIVE MOBILIZATION; PULSED HOLMIUM; VITAMIN-A; CO2-LASER; CLOSURE; REPAIR; DAMAGE AB The use of surgical lasers has been shown to decrease adhesion formation as compared with scalpel control groups in various surgical procedures. The potential benefits of laser technology have not been assessed in the treatment of adherent tendons. The current study was designed to first develop a reliable and reproducible model for consistent adhesion formation following flexor tendon trauma. The second goal was to compare the effects of laser tenolysis procedures on tendon gliding with those of traditional scalpel tenolysis. In phase I, the adhesion-induction model utilized bilateral standardized crush-abrasion injuries to the hind limb digital flexor tendons of New Zealand White rabbits. Following 4 weeks of immobilization, the animals were sacrificed, and peritendoneal adhesions were assessed biomechanically. A significantly higher maximal force was required to extract the adherent tendons from the foot as compared with nontraumatized control tendons. In phase II, six groups of animals underwent the same standardized tendon trauma. Four weeks later the rabbits were randomly assigned to undergo either CO2 laser or holmium:YAG laser tenolysis on one foot. Scalpel lysis was used on the contralateral foot and served as an intraindividual control. Biomechanical assessment was performed at 1, 2, and 4 weeks following tenolysis. Significantly less force was required to extract the treated tendons at 1 and 2 weeks following holmium:YAG laser tenolysis when compared with scalpel or CO2 laser tenolysis. After 4 weeks, differences between holmium: YAG and CO2 laser and scalpel treatment were no longer significant. Extracted tendons were pulled apart to failure, and no difference in breaking strength was noted between groups. We conclude that holmium:YAG laser tenolysis results in easier tendon gliding as compared with scalpel or CO2 laser tenolysis at early time points. Laser tenolysis does not affect intrinsic tendon strength. C1 UNIV S FLORIDA,COLL MED,SECT PLAST SURG,TAMPA,FL 33606. MASSACHUSETTS GEN HOSP,DIV PLAST & RECONSTRUCT SURG,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,WELLMAN LABS PHOTOMED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138. TAMPA GEN HOSP,DIV PLAST & RECONSTRUCT SURG,TAMPA,FL. NR 34 TC 5 Z9 5 U1 1 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD MAR PY 1996 VL 97 IS 3 BP 595 EP 601 DI 10.1097/00006534-199603000-00016 PG 7 WC Surgery SC Surgery GA TX714 UT WOS:A1996TX71400016 PM 8596791 ER PT J AU Beahrs, JO AF Beahrs, JO TI Ritual deception: A window to the hidden determinants of human politics SO POLITICS AND THE LIFE SCIENCES LA English DT Article ID PROSPECT-THEORY AB Political leaders of all persuasions are known to make public statements of affiliative allegiance with more form than substance, and to disavow political motivations obvious to the public. Such ''ritual deceptions'' are better understood in the same light as social etiquette-as partly deceptive behaviors that help to bond individuals with conflicting interests. Those who are more open and honest are often punished, more for breaking unspoken rules and taboos than for the actual content revealed, The functions of ritual deception are explicated by sociobiological theory, and the process, by understanding hypnotic transactions. Political deceptions require the active collaboration of subjects, achieved through the same skills used by experienced hypnotists. Deceptive transactions are more likely to occur in internally traumatized societies, and occur along a continuum from ritual deception to overt disinformation, Examples are taken from recent American history, That the content of ritual deception is so close to full awareness suggests its value as a focal point, both for studying the hidden determinants within human politics, and for policy intervention when appropriate. C1 US DEPT VET AFFAIRS,DEPT VET AFFAIRS MED CTR,PORTLAND,OR 97207. RP Beahrs, JO (reprint author), OREGON HLTH SCI UNIV,PORTLAND,OR 97201, USA. NR 66 TC 3 Z9 4 U1 1 U2 1 PU BEECH TREE PUBLISHING PI GUILDFORD PA 10 WATFORD CLOSE, GUILDFORD, SURREY, ENGLAND GU1 2EP SN 0730-9384 J9 POLIT LIFE SCI JI Polit. Life Sci. PD MAR PY 1996 VL 15 IS 1 BP 3 EP 12 PG 10 WC Biology; History & Philosophy Of Science; Social Issues SC Life Sciences & Biomedicine - Other Topics; History & Philosophy of Science; Social Issues GA UM151 UT WOS:A1996UM15100001 ER PT J AU Glasgow, RE Sorensen, G Giffen, C Shipley, RH Corbett, K Lynn, W AF Glasgow, RE Sorensen, G Giffen, C Shipley, RH Corbett, K Lynn, W TI Promoting worksite smoking control policies and actions: The Community Intervention Trial for Smoking Cessation (COMMIT) Experience SO PREVENTIVE MEDICINE LA English DT Article AB Background. As an important aspect of the COMMIT trial, worksite smoking-control consultations and supports were provided to employers in 11 diverse, moderate-sized communities. After a 4-year intervention period (1989-1992), impacts on worksite policies, support resources for smokers, and employee perceptions were assessed in these communities and in 11 matched Comparison communities. Methods. Data from two surveys are reported here. In each of the 22 COMMIT communities, a sample of worksites within each of four size strata were surveyed to determine worksite policies, activities, and resources regarding smoking. Data from employees were obtained from independent community-wide surveys of community residents. Results. Overall, 44% of the worksites surveyed reported having smokefree policies, with no differences between Intervention and Comparison communities. Thirty-seven percent of Intervention community worksites reported offering smoking cessation resources or assistance for employees during the period of the study, compared to 31% of Comparison community worksites (P = 0.04). Employees in Intervention communities, relative to those in Comparison communities, reported greater awareness of stop-smoking resources, but equivalent increases in worksite smoking bans. Conclusion. Although the level of worksite smoking-cessation activities was higher in Intervention than in Comparison communities, there remains a substantial need to increase the level of such activities and to integrate such activities with restrictive smoking policies. (C) 1996 Academic Press, Inc. C1 HARVARD UNIV,SCH PUBL HLTH,DANA FARBER CANC INST,BOSTON,MA 02138. INFORMAT MANAGEMENT SERV INC,SILVER SPRING,MD. DUKE UNIV,MED CTR,DURHAM,NC 27708. VET AFFAIRS MED CTR,DURHAM,NC 27708. UNIV COLORADO,DEPT ANTHROPOL,DENVER,CO 80217. NCI,NIH,BETHESDA,MD 20892. RP Glasgow, RE (reprint author), OREGON RES INST,1715 FRANKLIN BLVD,EUGENE,OR 97403, USA. FU NCI NIH HHS [CN55513-38] NR 25 TC 18 Z9 18 U1 1 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0091-7435 J9 PREV MED JI Prev. Med. PD MAR-APR PY 1996 VL 25 IS 2 BP 186 EP 194 DI 10.1006/pmed.1996.0045 PG 9 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA UK038 UT WOS:A1996UK03800013 PM 8860284 ER PT J AU Needham, M Barratt, D Cerillo, G Green, I Warburton, H Anderson, M Sturgess, N Rollins, B Reilly, C Hollis, M AF Needham, M Barratt, D Cerillo, G Green, I Warburton, H Anderson, M Sturgess, N Rollins, B Reilly, C Hollis, M TI High level expression of human MCP-1 using the LCR/MEL expression system SO PROTEIN EXPRESSION AND PURIFICATION LA English DT Article ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; SMOOTH-MUSCLE CELLS; GENE-EXPRESSION; OSTEOSARCOMA; SEQUENCE AB We have expressed human monocyte chemoattractant protein-1 (hMCP-1) in preerythroid mouse erythroleukemia (MEL) C88 cells using the locus control region/MEL expression system and studied the biological activity of the purified protein in a range of in vitro experimental systems. The recombinant hMCP-1 is expressed at high levels (similar to 10 mg/liter) in this system and is modified in a manner which is very similar to native hMCP-1. We have developed a simple high-yielding two-step purification route employing dye ligand and ion exchange chromatographies which enables us to separate glycosylated and unglycosylated hMCP-1. The purified glycosylated and unglycosylated forms of hMCP-1 have equivalent biological activities in all of the assay systems tested. (C) 1996 Academic Press, Inc. C1 DANA FARBER CANC INST,BOSTON,MA 02115. RP Needham, M (reprint author), ZENECA PHARMACEUT,VASC INFLAMMATORY & MUSCULOSKELETAL RES DEPT,ALDERLEY PK,MACCLESFIELD SK10 4TG,CHESHIRE,ENGLAND. NR 34 TC 3 Z9 3 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 1046-5928 J9 PROTEIN EXPRES PURIF JI Protein Expr. Purif. PD MAR PY 1996 VL 7 IS 2 BP 173 EP 182 DI 10.1006/prep.1996.0025 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA TY086 UT WOS:A1996TY08600008 PM 8812856 ER PT J AU DieTrill, M AF DieTrill, M TI Navigating through a strange land: A book for brain tumor patients and their families - Roloff,TA SO PSYCHO-ONCOLOGY LA English DT Book Review RP DieTrill, M (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD MAR PY 1996 VL 5 IS 1 BP 71 EP 72 DI 10.1002/(SICI)1099-1611(199603)5:1<71::AID-PON201>3.0.CO;2-X PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA UG155 UT WOS:A1996UG15500013 ER PT J AU Smith, DW Frueh, BC AF Smith, DW Frueh, BC TI Compensation seeking, comorbidity, and apparent exaggeration of PTSD symptoms among Vietnam combat veterans SO PSYCHOLOGICAL ASSESSMENT LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; VALIDITY; SCALE; RELIABILITY AB We evaluated whether veterans who apparently exaggerate their symptoms are more likely to be (a) seeking disability compensation or (b) suffering from more comorbid pathology than nonexaggerating veterans. Fifty-four of 145 (37%) veterans with posttraumatic stress disorder who completed the Minnesota Multiphasic Personality Inventory-2 (J. N. Butcher, W. G. Dahlstrom, J. R. Graham, A. Tellegen, & B. Kaemmer, 1989) were identified as apparent exaggerators, with F (Frequency) - K (Correction) > 13. These participants scored higher than nonexaggerators on self-report measures of various psychological symptoms but were no more likely to be seeking compensation or to have comorbid substance use or other anxiety disorders. Affective disorder was overrepresented among apparent exaggerators, however. Findings support the hypothesis of increased comorbidity among symptom exaggerators as measured by the F - K index but not the commonly held belief that symptom exaggerators are more likely to seek compensation. C1 MED UNIV S CAROLINA,DEPT PSYCHIAT & BEHAV SCI,NATL CRIME VICTIMS RES & TREATMENT CTR,CHARLESTON,SC 29425. RALPH H JOHNSON VET AFFAIRS MED CTR,PSYCHOL SERV,CHARLESTON,SC. NR 21 TC 56 Z9 56 U1 0 U2 0 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 1040-3590 J9 PSYCHOL ASSESSMENT JI Psychol. Assess. PD MAR PY 1996 VL 8 IS 1 BP 3 EP 6 DI 10.1037/1040-3590.8.1.3 PG 4 WC Psychology, Clinical SC Psychology GA UB448 UT WOS:A1996UB44800001 ER PT J AU Faraone, SV Blehar, M Pepple, J Moldin, SO Norton, J Nurnberger, JI Malaspina, D Kaufmann, CA Reich, T Cloninger, CR DePaulo, JR Berg, K Gershon, ES Kirch, DG Tsuang, MT AF Faraone, SV Blehar, M Pepple, J Moldin, SO Norton, J Nurnberger, JI Malaspina, D Kaufmann, CA Reich, T Cloninger, CR DePaulo, JR Berg, K Gershon, ES Kirch, DG Tsuang, MT TI Diagnostic accuracy and confusability analyses: An application to the diagnostic interview for genetic studies SO PSYCHOLOGICAL MEDICINE LA English DT Article ID ATTENTION-DEFICIT DISORDER; EYE TRACKING DYSFUNCTIONS; LATENT STRUCTURE-ANALYSIS; REPEATED SCREENING-TESTS; PSYCHIATRIC-DIAGNOSIS; LINKAGE ANALYSIS; SCHIZOPHRENIA; RELIABILITY; ERROR; SENSITIVITY AB The dominant, contemporary paradigm for developing and refining diagnoses relies heavily on assessing reliability with kappa coefficients and virtually ignores a core component of psychometric practice: the theory of latent structures. This article describes a psychometric approach to psychiatric nosology that emphasizes the diagnostic accuracy and confusability of diagnostic categories. We apply these methods to the Diagnostic Interview for Genetic Studies (DIGS), a structured psychiatric interview designed by the NIMH Genetics Initiative for genetic studies of schizophrenia and bipolar disorder. Our results show that sensitivity and specificity were excellent for both DSM-III-R and RDC diagnoses of major depression, bipolar disorder, and schizophrenia. In contrast, diagnostic accuracy was substantially lower for subtypes of schizoaffective disorder - especially for the DSM-III-R definitions. Both the bipolar and depressed subtypes of DSM-III-R schizoaffective disorder had excellent specificity but poor sensitivity. The RDC definitions also had excellent specificity but were more sensitive than the DSM-III-R schizoaffective diagnoses. The source of low sensitivity for schizoaffective subtypes differed for the two diagnostic systems. For RDC criteria, the schizoaffective subtypes were frequently confused with one another; they were less frequently confused with other diagnoses. In contrast, the DSM-III-R subtypes were often confused with schizophrenia, but not with each other. C1 HARVARD UNIV,SCH MED,MASSACHUSETTS MENTAL HLTH CTR,DEPT PSYCHIAT,INST PSYCHIAT EPIDEMIOL & GENET,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,PSYCHIAT SERV,PEDIAT PSYCHOPHARMACOL UNIT,BOSTON,MA 02114. JOHNS HOPKINS UNIV,DEPT PSYCHIAT,BALTIMORE,MD. NIMH,INTRAMURAL RES PROGRAM,BETHESDA,MD 20892. NIMH,EXTRAMURAL RES PROGRAM,BETHESDA,MD 20892. WASHINGTON UNIV,DEPT PSYCHIAT,ST LOUIS,MO. INDIANA UNIV,DEPT PSYCHIAT,BLOOMINGTON,IN 47405. COLUMBIA UNIV,DEPT PSYCHIAT,NEW YORK,NY. MED COLL GEORGIA,AUGUSTA,GA 30912. RP Faraone, SV (reprint author), VET AFFAIRS MED CTR,PSYCHIAT SERV 116A,940 BELMONT ST,BROCKTON,MA 02401, USA. RI Cloninger, Claude/F-5357-2012; OI Cloninger, Claude/0000-0003-3096-4807; Nurnberger, John/0000-0002-7674-1767; Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [UO1 MH46274, UO1 MH46276, UO1 MH46318] NR 50 TC 70 Z9 71 U1 0 U2 4 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD MAR PY 1996 VL 26 IS 2 BP 401 EP 410 PG 10 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA UA855 UT WOS:A1996UA85500019 PM 8685296 ER PT J AU Ornstein, R AF Ornstein, R TI Dissociative identity disorder: Theoretical and treatment controversies - Cohen,LM, Berzoff,JN, Elin,MR SO PSYCHOSOMATICS LA English DT Book Review C1 HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP Ornstein, R (reprint author), N SUFFOLK MENTAL HLTH ASSOC,BOSTON,MA, USA. NR 1 TC 0 Z9 0 U1 0 U2 2 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD MAR-APR PY 1996 VL 37 IS 2 BP 161 EP 162 PG 2 WC Psychiatry; Psychology SC Psychiatry; Psychology GA TX045 UT WOS:A1996TX04500011 ER PT J AU Hopcia, KL McCarey, YL Sylvester, FC Held, KD AF Hopcia, KL McCarey, YL Sylvester, FC Held, KD TI Radiation-induced apoptosis in HL60 cells: Oxygen effect, relationship between apoptosis and loss of clonogenicity, and dependence of time to apoptosis on radiation dose SO RADIATION RESEARCH LA English DT Article ID IRRADIATED MURINE TUMORS; HL-60 CELLS; THYMOCYTE APOPTOSIS; GAMMA-IRRADIATION; RAT THYMOCYTES; DEATH; INDUCTION; INVITRO; P53; ENDONUCLEASE AB Apoptosis in HL60 human leukemia cells irradiated in vitro was quantified using a DNA fragmentation assay. Dose-response curves for induction of apoptosis in HL60 cells 6 h after irradiation with 280 kVp X rays in air and hypoxia give an oxygen enhancement ratio (OER) of 2.7. This is similar to the OER of 2.8 obtained from survival curves for HL60 cells using a soft agar clonogenic assay. However, HL60 cells are much more sensitive to radiation-induced loss of clonogenicity than to induction of apoptosis at 6 h. For example, 12 Gy in air reduces the surviving fraction to about 0.002 in a clonogenic assay, but 12 Gy does not cause any significant increase in the percentage of apoptosis-like DNA fragmentation 6 h after irradiation compared to unirradiated controls. However, if apoptosis is assayed 2-4 days after irradiation, the HL60 cells show greater sensitivity, with 5 Gy in air causing 45-50% apoptosis at 3 days. When apoptosis is measured 3 days after irradiation, the OER is similar to that obtained for survival and for apoptosis at 6 h. Although the HL60 cells exhibit radiation-induced apoptosis if one waits 2-4 days after low doses of radiation, rather than just 6 h, to conduct the assay, the amount of cells undergoing apoptosis is still not sufficient to account for all the loss of clonogenicity seen when HL60 cells are exposed to ionizing radiation. (C) 1996 by Radiation Research Society C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,BOSTON,MA 02114. FU NCI NIH HHS [CA42167, CA18614] NR 49 TC 50 Z9 52 U1 0 U2 3 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 MAR PY 1996 VL 145 IS 3 BP 315 EP 323 DI 10.2307/3578987 PG 9 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA TY619 UT WOS:A1996TY61900009 PM 8927699 ER PT J AU Huang, PG Taghian, A Allam, A Freeman, J Duffy, M Suit, HD AF Huang, PG Taghian, A Allam, A Freeman, J Duffy, M Suit, HD TI The effect of whole-body irradiation of nude mice on the tumor transplantability and control probability of a human soft tissue sarcoma xenograft SO RADIATION RESEARCH LA English DT Article ID SINGLE-DOSE IRRADIATION; FRACTIONATED-IRRADIATION; XENOTRANSPLANTATION; MURINE; ASSAYS; MOUSE; DELAY AB This study has evaluated the impact of the suppression and recovery of the residual immunity in NCr/Sed nude (nu/nu) mice after whole-body irradiation using xenotransplantability and tumor control probability as the end points. For this investigation the xenograft was a human soft tissue sarcoma (HSTS26T). Two assays, the TD50 (the number of tumor cells required to induce a tumor in 50% of the recipients) and the TCD50 (the radiation dose required to control 50% of tumors) were used. For TD50 assays, tumor cells were injected subcutaneously (sc) into the legs of control and whole-body-irradiated nude mice at 1 day or 4, 8 or 12 weeks after irradiation. For TCD50 assays, tumors were transplanted sc into the legs of nude mice which had not been irradiated or which had been given whole-body irradiation at 1 day or 12 weeks prior to transplantation. The tumors were given single-dose irradiation when they reached 6 mm mean diameter under clamp-hypoxic conditions. The results show that the TD50's of mice receiving the injection 1 day and 4 and 8 weeks after whole-body irradiation were 3.6 to >100 times lower than that of unirradiated mice. Two groups which showed a statistically significant difference in TD50's were those which received the injection 1 day and 8 weeks after whole-body irradiation (P < 0.01 and P < 0.05, respectively). No difference was found in TD50 values between mice that received injection 12 weeks after whole-body irradiation and those which were not irradiated. The TCD50 values of tumors in nonirradiated mice and in mice which had received whole-body irradiation 1 day and 12 weeks prior to transplantation were 26.8, 44.1 and 33.9 Gy, respectively, Significantly lower TCD50 values were found in groups of nonirradiated mice or mice which received whole-body irradiation 12 weeks prior to transplantation in comparison with the group of mice that received whole-body irradiation on day 1 (both P < 0.05). No significant difference was found between the TCD50 values of the group of mice that received whole-body irradiation 12 weeks prior to transplantation and those for nonirradiated controls. Our conclusion is that the whole-body irradiation can enhance the transplantability of the HSTS26T tumor in nude mice significantly; this enhancing effect will decrease to the pre-irradiation level by 12 weeks after whole-body irradiation. Also, the suppression and recovery of residual immunity after whole-body irradiation can influence the TCD50 values of the same tumor xenografts in nude mice significantly. The changes in TD50 and TCD50 values correlate with the depletion and recovery of the total splenic lymphoid cell number, and especially in natural killer cell activity. We recommend that further immunosuppression in nude mice is necessary when using this model system for studies of human tumors. (C) 1996 by Radiation Research Society C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,EDWIN L STEELE LAB RADIAT BIOL,DEPT RADIAT ONCOL,BOSTON,MA 02114. FU NCI NIH HHS [CA13311] NR 25 TC 14 Z9 14 U1 0 U2 3 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 MAR PY 1996 VL 145 IS 3 BP 337 EP 342 DI 10.2307/3578990 PG 6 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA TY619 UT WOS:A1996TY61900012 PM 8927702 ER PT J AU Winalski, CS Palmer, WE Rosenthal, DI Weissman, BN AF Winalski, CS Palmer, WE Rosenthal, DI Weissman, BN TI Magnetic resonance imaging of rheumatoid arthritis SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID CERVICAL-SPINE INVOLVEMENT; SIGNAL INTENSITY; GADOPENTETATE DIMEGLUMINE; CRANIOCERVICAL JUNCTION; GADOLINIUM-DTPA; GD-DTPA; KNEE; STABILIZATION; RADIOGRAPHY; MYELOPATHY AB MR imaging is able to demonstrate both the structural changes that occur in rheumatoid arthritis and the inflammatory changes, including synovial proliferation and joint effusion. MR imaging can demonstrate erosion before it is visible on radiographs. Although MR imaging appears to be very helpful in assessing the severity of rheumatoid arthritis and its response to therapy, the optimal technique for this assessment and the ultimate clinical value of MR imaging have yet to be determined. C1 HARVARD UNIV,SCH MED,DEPT RADIOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. RP Winalski, CS (reprint author), BRIGHAM & WOMENS HOSP,DEPT RADIOL,75 FRANCIS ST,BOSTON,MA 02115, USA. NR 66 TC 27 Z9 29 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0033-8389 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD MAR PY 1996 VL 34 IS 2 BP 243 EP & PG 17 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UD517 UT WOS:A1996UD51700005 PM 8633114 ER PT J AU Fisher, RE Scott, JA Palmer, EL AF Fisher, RE Scott, JA Palmer, EL TI Neural networks in ventilation-perfusion imaging .1. Effects of interpretive criteria and network architecture SO RADIOLOGY LA English DT Article DE computers, diagnostic aid; computers, neural network; embolism, pulmonary; lung, radionuclide studies ID PULMONARY-EMBOLISM AB PURPOSE: To optimize the performance of artificial neural networks in the prediction of pulmonary embolism from ventilation-perfusion (V-P) scans. MATERIALS AND METHODS: Neural networks were constructed with a set of V-P scan criteria that included sharpness and completeness of perfusion defects and involved quantification of abnormalities by using a continuous numeric scale. Several network parameters were systematically varied. Networks were trained with 150 cases and tested with 30 different cases. Findings were compared with those of pulmonary angiography. RESULTS: Networks capable of performing as well as experienced nuclear medicine physicians could be constructed with few V-P scan features. A brief training period was optimal (50-100 iterations). Further training diminished network performance. CONCLUSION: Effective neural networks can be constructed by using a limited number of unconventional V-P scan features. Several parameters can be adjusted to optimize performance. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,DIV NUCL MED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 13 TC 19 Z9 19 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD MAR PY 1996 VL 198 IS 3 BP 699 EP 706 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA TW212 UT WOS:A1996TW21200016 PM 8628857 ER PT J AU Scott, JA Fisher, RE Palmer, EL AF Scott, JA Fisher, RE Palmer, EL TI Neural networks in ventilation-perfusion imaging .2. Effects of interpretive variability SO RADIOLOGY LA English DT Article DE computers, diagnostic aid; computers, neural network; embolism, pulmonary ID ACUTE PULMONARY-EMBOLISM; RADIOLOGIC-DIAGNOSIS AB PURPOSE: To evaluate the usefulness of a neural network developed by one physician and used by another. MATERIALS AND METHODS: Intra- and interobserver variability were analyzed in image categorization of ventilation-perfusion (V-P) scans. This information was used to estimate network performance when it was used by a physician who did not train the network. RESULTS: Network training was optimized by using input parameters that demonstrated both individually high correlations with pulmonary embolism and good reproducibility in multiple interpretations. CONCLUSION: Potential variability exists in the performance of a network when it is supplied with input data by different physicians. The clinical usefulness of a network depends heavily on the similarity of interpretive styles between the network trainer and I-he user. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP Scott, JA (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,DIV NUCL MED,FRUIT ST,BOSTON,MA 02114, USA. NR 15 TC 15 Z9 15 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD MAR PY 1996 VL 198 IS 3 BP 707 EP 713 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA TW212 UT WOS:A1996TW21200017 PM 8628858 ER PT J AU Zuo, CS Jiang, AP Buff, BL Mahon, TG Wong, TZ AF Zuo, CS Jiang, AP Buff, BL Mahon, TG Wong, TZ TI Automatic motion correction for breast MR imaging SO RADIOLOGY LA English DT Article; Proceedings Paper CT 1994 RSNA Scientific Assembly CY NOV 27-DEC 02, 1994 CL CHICAGO, IL SP Radiol Soc N Amer DE breast, MR; breast neoplasms, MR; gadolinium; magnetic resonance (MR), motion correction ID GD-DTPA; ANGIOGENESIS; IMAGES AB In 29 gadolinium-enhanced breast magnetic resonance (MR) examinations, breast motion prevented accurate and efficient image processing. To compensate for global rotations and translations, an automatic motion correction method with a ratio-variance minimization algorithm was used to align images at multiple time points through an iterative process. This method reduced breast motion and improved the accuracy and efficiency of lesion detection. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RP Zuo, CS (reprint author), NEW ENGLAND DEACONESS HOSP,DEPT RADIOL SCI,1 DEACONESS RD,BOSTON,MA 02215, USA. NR 17 TC 29 Z9 29 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD MAR PY 1996 VL 198 IS 3 BP 903 EP 906 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA TW212 UT WOS:A1996TW21200050 PM 8628891 ER PT J AU Bettmann, MA Hartnell, GG Kaufman, JA Lipton, MJ Pieters, PC Rosen, MP AF Bettmann, MA Hartnell, GG Kaufman, JA Lipton, MJ Pieters, PC Rosen, MP TI Cardiac radiology SO RADIOLOGY LA English DT Editorial Material DE embolism, pulmonary; heart, computed tomography (CT); heart, diseases; heart, magnetic resonance (MR); Radiological Society of North America, 81st scientific assembly and annual meeting C1 DEACONESS HOSP,BOSTON,MA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. UNIV CHICAGO,CHICAGO,IL 60637. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,RICHMOND,VA 23298. HARVARD UNIV,BETH ISRAEL HOSP,BOSTON,MA 02215. RP Bettmann, MA (reprint author), DARTMOUTH HITCHCOCK MED CTR,LEBANON,NH 03756, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD MAR PY 1996 VL 198 IS 3 BP 931 EP 933 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA TW212 UT WOS:A1996TW21200061 PM 8628898 ER PT J AU Sadeghi, A Kuisk, H Tran, L StRoyal, L AF Sadeghi, A Kuisk, H Tran, L StRoyal, L TI Urethrography and ischial intertuberosity line in radiation therapy planning for prostate carcinoma SO RADIOTHERAPY AND ONCOLOGY LA English DT Article DE urethrography; radiation therapy planning; prostate cancer ID RETROGRADE URETHROGRAPHY; CANCER; APEX AB We analyzed our urethrography procedure regarding the validity of using the ischial tuberosity line (ITL) as the caudal margin of treatment portals for prostate carcinoma. The distances of the external urethral sphincter and the lowest margin of the opacified urinary bladder were analyzed in one hundred fifteen consecutive urethrograms. None showed the urethral sphincter to be caudal to the ITL. Ten percent of the sphincters were located less than 1.0 cm cephalad to the ITL, yielding inadequate treatment coverage if the ITL was relied on. Arbitrarily considering 2.0 cm or more of the urethral irradiation to be excessive, the use of the ITL would then have resulted in unnecessary normal tissue irradiation of 42.5%. The ITL should not be used as the caudal margin for prostate treatment portals. Variation in sphincter position, as also seen on lateral projections, reveal a need for urethrography as a necessary supplement to computed tomography to plan radiation portals for prostate cancer. C1 UNIV CALIF LOS ANGELES,DEPT RADIAT ONCOL,LOS ANGELES,CA. RP Sadeghi, A (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,RADIAT THERAPY SERV,691-214,LOS ANGELES,CA 90073, USA. NR 21 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD MAR PY 1996 VL 38 IS 3 BP 215 EP 222 DI 10.1016/0167-8140(96)01704-5 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA UB868 UT WOS:A1996UB86800004 PM 8693101 ER PT J AU Webb, RH AF Webb, RH TI Confocal optical microscopy SO REPORTS ON PROGRESS IN PHYSICS LA English DT Review ID SCANNING LASER OPHTHALMOSCOPE; FLUORESCENCE MICROSCOPE; LIGHT-MICROSCOPY; IMAGE-FORMATION; APERTURE; REFLECTION; ABERRATIONS; FIBER AB Confocal optical microscopy is a technique for increasing the contrast of microscope images, particularly in thick specimens. By restricting the observed volume, the technique keeps overlying or nearby scatterers from contributing to the detected signal. The price for this is that the instrument must observe only one point at a time (in the scanning laser version) or a group of separated points with very little light (in the disc version). This paper describes how the confocal advantage comes about and how it is implemented in actual instruments. This review was received in October 1995 (C) 1996 IOP Publishing Ltd C1 MASSACHUSETTS GEN HOSP,WELLMAN LABS PHOTOMED,BOSTON,MA 02114. RP Webb, RH (reprint author), MASSACHUSETTS GEN HOSP,SCHEPENS EYE RES INST,BOSTON,MA 02114, USA. NR 60 TC 327 Z9 332 U1 11 U2 100 PU IOP PUBLISHING LTD PI BRISTOL PA TECHNO HOUSE, REDCLIFFE WAY, BRISTOL, ENGLAND BS1 6NX SN 0034-4885 J9 REP PROG PHYS JI Rep. Prog. Phys. PD MAR PY 1996 VL 59 IS 3 BP 427 EP 471 DI 10.1088/0034-4885/59/3/003 PG 45 WC Physics, Multidisciplinary SC Physics GA UB937 UT WOS:A1996UB93700003 ER PT J AU Hosokawa, Y AF Hosokawa, Y TI Cyclin D1 in oncogenesis SO SEIKAGAKU LA Japanese DT Review ID RETINOBLASTOMA PROTEIN; CELL-CYCLE C1 MASSACHUSETTS GEN HOSP,LAB ENDOCRINE ONCOL,BOSTON,MA 02114. NR 15 TC 2 Z9 2 U1 0 U2 0 PU JAPAN BIOCHEMICAL SOC PI TOKYO PA ISHIKAWA BLDG-3F 25-16 HONGO-5-CHOME, TOKYO TOKYO 113, JAPAN SN 0037-1017 J9 SEIKAGAKU JI Seikagaku PD MAR PY 1996 VL 68 IS 3 BP 201 EP 205 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UC921 UT WOS:A1996UC92100003 PM 8642209 ER PT J AU Boland, GW Mueller, PR AF Boland, GW Mueller, PR TI An update on abscess drainage SO SEMINARS IN INTERVENTIONAL RADIOLOGY LA English DT Article ID DEEP PELVIC ABSCESSES; INTRACAVITARY UROKINASE; TRANSVAGINAL DRAINAGE; TRANSRECTAL DRAINAGE; FLUID COLLECTIONS; ASPIRATION; GUIDANCE C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIOL,BOSTON,MA 02114. NR 20 TC 3 Z9 3 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 381 PARK AVE SOUTH, NEW YORK, NY 10016 SN 0739-9529 J9 SEMIN INTERVENT RAD JI Semin. Interv. Radiol. PD MAR PY 1996 VL 13 IS 1 BP 27 EP 34 DI 10.1055/s-2008-1057889 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UD832 UT WOS:A1996UD83200004 ER PT J AU Gervais, DA Mueller, PR AF Gervais, DA Mueller, PR TI Percutaneous cholecystostomy SO SEMINARS IN INTERVENTIONAL RADIOLOGY LA English DT Article ID ACUTE ACALCULOUS CHOLECYSTITIS; CRITICALLY ILL PATIENTS; TRANSHEPATIC CHOLECYSTOSTOMY; GALLBLADDER PERFORATION; OBSTRUCTIVE-JAUNDICE; DUCT OBSTRUCTION; ELDERLY PATIENTS; CHOLECYSTOLITHOTOMY; COMPLICATIONS; ASPIRATION C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIOL,BOSTON,MA 02114. NR 40 TC 7 Z9 7 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 381 PARK AVE SOUTH, NEW YORK, NY 10016 SN 0739-9529 J9 SEMIN INTERVENT RAD JI Semin. Interv. Radiol. PD MAR PY 1996 VL 13 IS 1 BP 35 EP 43 DI 10.1055/s-2008-1057890 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UD832 UT WOS:A1996UD83200005 ER PT J AU Dawson, SL Zerbey, AL Mueller, PR AF Dawson, SL Zerbey, AL Mueller, PR TI Radiologic management of laparoscopic bile duct injuries SO SEMINARS IN INTERVENTIONAL RADIOLOGY LA English DT Article ID CHOLECYSTECTOMY; COMPLICATIONS RP Dawson, SL (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIOL,32 FRUIT ST,BOSTON,MA 02114, USA. NR 18 TC 3 Z9 3 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 381 PARK AVE SOUTH, NEW YORK, NY 10016 SN 0739-9529 J9 SEMIN INTERVENT RAD JI Semin. Interv. Radiol. PD MAR PY 1996 VL 13 IS 1 BP 45 EP 54 DI 10.1055/s-2008-1057891 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UD832 UT WOS:A1996UD83200006 ER PT J AU Murphy, BL Mueller, PR AF Murphy, BL Mueller, PR TI Metallic biliary stents: Technical points on optimizing results SO SEMINARS IN INTERVENTIONAL RADIOLOGY LA English DT Article ID ENDOPROSTHESIS; OBSTRUCTION C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIOL,BOSTON,MA 02114. NR 10 TC 0 Z9 0 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 381 PARK AVE SOUTH, NEW YORK, NY 10016 SN 0739-9529 J9 SEMIN INTERVENT RAD JI Semin. Interv. Radiol. PD MAR PY 1996 VL 13 IS 1 BP 55 EP 67 DI 10.1055/s-2008-1057892 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UD832 UT WOS:A1996UD83200007 ER PT J AU Dawson, SL AF Dawson, SL TI Image-guided therapies and minimally invasive therapy: One man's perspective SO SEMINARS IN INTERVENTIONAL RADIOLOGY LA English DT Editorial Material RP Dawson, SL (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIOL,32 FRUIT ST,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 381 PARK AVE SOUTH, NEW YORK, NY 10016 SN 0739-9529 J9 SEMIN INTERVENT RAD JI Semin. Interv. Radiol. PD MAR PY 1996 VL 13 IS 1 BP 79 EP 82 DI 10.1055/s-2008-1057894 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UD832 UT WOS:A1996UD83200009 ER PT J AU Adrogue, HJ Wesson, DE AF Adrogue, HJ Wesson, DE TI Role of dietary factors in the hypertension of African Americans SO SEMINARS IN NEPHROLOGY LA English DT Article ID VASCULAR SMOOTH-MUSCLE; BLOOD-PRESSURE; RACIAL-DIFFERENCES; POTASSIUM; SODIUM; ALDOSTERONE; BLACKS; MILD C1 TEXAS TECH UNIV,HLTH SCI CTR,DEPT PHYSIOL & MED,LUBBOCK,TX 79430. RP Adrogue, HJ (reprint author), BAYLOR COLL MED,DEPT VET AFFAIRS MED CTR,HOUSTON,TX 77030, USA. NR 45 TC 15 Z9 16 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9295 J9 SEMIN NEPHROL JI Semin. Nephrol. PD MAR PY 1996 VL 16 IS 2 BP 94 EP 101 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA TZ101 UT WOS:A1996TZ10100005 PM 8668865 ER PT J AU Pardo, FS Su, M Borek, C AF Pardo, FS Su, M Borek, C TI Cyclin D1 induced apoptosis maintains the integrity of the G1/S checkpoint following ionizing radiation irradiation SO SOMATIC CELL AND MOLECULAR GENETICS LA English DT Article ID MUTANT P53 INCREASES; BREAST-CANCER CELLS; WILD-TYPE P53; DNA-DAMAGE; P53-INDEPENDENT MECHANISMS; MOLECULAR MECHANISMS; GENOMIC INSTABILITY; EPITHELIAL-CELLS; MAMMALIAN-CELLS; FIBROBLASTS AB Cell cycle ''checkpoints'' help to ensure the integrity of normal cellular functions prior to replicative DNA synthesis and/or cell division. Cell kinetic abnormalities, particularly arrests at the G1/S and G2/M cell cycle checkpoints, are induced following exposure to ionizing radiation in vitro. Following irradiation, cellular signaling pathways may lead to G1 arrest and/or apoptosis at the G1/S cell cycle transition point. Transfection of cyclin D1, a G1/S cyclin, into a rat embryo cells (REC) results In cellular populations that overexpress cyclin D1, are transformed morphologically: demonstrate an increased incidence of apoptosis, and are tumorigenic in immune-deficient mice, Despite such phenotypic changes, transfected cell populations maintain the integrity of the G1 checkpoint following ionizing radiation. The transfected cells overexpressing Cyclin D1 have a statistically significant increase in the incidence of apoptosis as compared to parental REC strains or mock-transfected REC. The work provides further evidence of Cyclin D1 playing a critical role in maintaining the integrity of the G1/S checkpoint, via the activation of apoptotic pathways following exposure to ionizing radiation in vitro. C1 TUFTS UNIV,DEPT COMMUNITY HLTH,BOSTON,MA 02111. RP Pardo, FS (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,LAB MOL TUMOR RADIAT BIOL,BOSTON,MA 02115, USA. NR 53 TC 38 Z9 38 U1 0 U2 1 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0740-7750 J9 SOMAT CELL MOLEC GEN JI Somat.Cell Mol.Genet. PD MAR PY 1996 VL 22 IS 2 BP 135 EP 144 DI 10.1007/BF02369903 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA VE355 UT WOS:A1996VE35500004 PM 8782492 ER PT J AU SULLIVAN, PR AF SULLIVAN, PR TI PHYSICIANS AND THE PROBLEM OF OTHER CONSCIOUSNESSES SO SOUTHERN JOURNAL OF PHILOSOPHY LA English DT Article C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP SULLIVAN, PR (reprint author), HARVARD UNIV,SCH MED,BOSTON,MA 02115, USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU SOUTHERN J PHILOSOPHY MEMPHIS STATE UNIV PI MEMPHIS PA DEPT PHILOSOPHY, MEMPHIS, TN 38152 SN 0038-4283 J9 SOUTHERN J PHILOS JI South. J. Philos. PD SPR PY 1996 VL 34 IS 1 BP 115 EP 123 PG 9 WC Philosophy SC Philosophy GA TY407 UT WOS:A1996TY40700007 ER PT J AU Lewis, CB AF Lewis, CB TI Exercise programming for older adults - VanNorman,KA SO TOPICS IN GERIATRIC REHABILITATION LA English DT Book Review C1 GEORGE WASHINGTON UNIV,SCH MED & HLTH SCI,WASHINGTON,DC 20052. MASSACHUSETTS GEN HOSP,INST HLTH PROFESS,BOSTON,MA 02114. RP Lewis, CB (reprint author), PHYS THERAPY SERV WASHINGTON DC,WASHINGTON,DC, USA. NR 1 TC 0 Z9 0 U1 1 U2 1 PU ASPEN PUBL INC PI FREDERICK PA 7201 MCKINNEY CIRCLE, FREDERICK, MD 21701 SN 0882-7524 J9 TOP GERIATR REHABIL JI Top. Geriatr. Rehabil. PD MAR PY 1996 VL 11 IS 3 BP 70 EP 71 PG 2 WC Gerontology; Rehabilitation SC Geriatrics & Gerontology; Rehabilitation GA TW600 UT WOS:A1996TW60000015 ER PT J AU Lewis, CB AF Lewis, CB TI Balance and falls SO TOPICS IN GERIATRIC REHABILITATION LA English DT Editorial Material C1 GEORGE WASHINGTON UNIV,SCH MED & HLTH SCI,WASHINGTON,DC 20052. MASSACHUSETTS GEN HOSP,INST HLTH PROFESS,BOSTON,MA 02114. RP Lewis, CB (reprint author), PHYS THERAPY SERV WASHINGTON DC INC,WASHINGTON,DC, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ASPEN PUBL INC PI FREDERICK PA 7201 MCKINNEY CIRCLE, FREDERICK, MD 21701 SN 0882-7524 J9 TOP GERIATR REHABIL JI Top. Geriatr. Rehabil. PD MAR PY 1996 VL 11 IS 3 BP R5 EP R5 PG 1 WC Gerontology; Rehabilitation SC Geriatrics & Gerontology; Rehabilitation GA TW600 UT WOS:A1996TW60000001 ER PT J AU Grossman, SR Laimins, LA AF Grossman, SR Laimins, LA TI EBNA1 and E2: A new paradigm for origin-binding proteins? SO TRENDS IN MICROBIOLOGY LA English DT Article ID EPSTEIN-BARR-VIRUS; REPLICATION; PAPILLOMAVIRUS; DOMAIN; LOOPS; E1 C1 DANA FARBER CANC INST,BOSTON,MA 02115. NORTHWESTERN UNIV,DEPT MICROBIOL IMMUNOL,CHICAGO,IL 60611. NR 16 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0966-842X J9 TRENDS MICROBIOL JI Trends Microbiol. PD MAR PY 1996 VL 4 IS 3 BP 87 EP 89 DI 10.1016/0966-842X(96)81520-4 PG 3 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA UB641 UT WOS:A1996UB64100002 PM 8868083 ER PT J AU Reppert, SM Weaver, DR Godson, C AF Reppert, SM Weaver, DR Godson, C TI Melatonin receptors step into the light: Cloning and classification of subtypes SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Article RP Reppert, SM (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,LAB DEV CHRONOBIOL,JACKSON 1226,BOSTON,MA 02114, USA. OI Weaver, David/0000-0001-7941-6719 NR 20 TC 329 Z9 334 U1 2 U2 9 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0165-6147 J9 TRENDS PHARMACOL SCI JI Trends Pharmacol. Sci. PD MAR PY 1996 VL 17 IS 3 BP 100 EP 102 DI 10.1016/0165-6147(96)10005-5 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA UG757 UT WOS:A1996UG75700004 PM 8936344 ER PT J AU Samore, MH Siber, GR AF Samore, MH Siber, GR TI Pertussis toxin enhanced IgG1 and IgE responses to primary tetanus immunization are mediated by interleukin-4 and persist during secondary responses to tetanus alone SO VACCINE LA English DT Article DE pertussis toxin; immune responses; interleukin-3; anti-tetanus toroid antibodies ID LYMPHOCYTOSIS-PROMOTING FACTOR; DELAYED-TYPE HYPERSENSITIVITY; ISLET-ACTIVATING PROTEIN; BORDETELLA-PERTUSSIS; MONOCLONAL-ANTIBODIES; B-OLIGOMER; CELLS; MICE; IL-4; INHIBITION AB Pertussis toxin (Ptx), the major toxin product of Bordetella pertussis, has potent immunologic effects including adjuvant effects on antibody responses and sensitization for anaphylaxis. In order to further define the effect of Ptx on the class and subclasses and IgE in Balb/c mice after primary and secondary immunization with tetanus toxoid (TT). Low doses of Ptx (100 ng) given intravenously at the time of primary immunization increased primary IgG1 and IgE anti-TT antibodies as well as total IgG1 and IgE concentrations compared to controls. The increase in IgG1 subclass and IgE response when Ptx was present during primary immunization was even more pronounced after secondary immunization with TT alone 3 weeks or 3 months later. Similar effects were noted after diphtheria toxoid immunization in the presence of Ptx. Administration of the anti IL-4 monoclonal antibody (11B11) suppressed the enhanced total and TT-specific IgE responses but not the enhanced IgG1 responses. The presence of low concentrations of Ptx during primary immunization primes for induction of IL-4 producing T-cell help which enhances IgG1 and IgE responses to the primary exposure as well as to subsequent exposures of the antigen in the absence of Ptx. This phenomenon may have significance for the adjuvant activity of vaccines containing Ptx as well as for the immune response to natural pertussis. Copyright (C) 1996 Elsevier Science Ltd. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,INFECT DIS LAB,BOSTON,MA 02115. STATE LAB INST,MASSACHUSETTS PUBL HLTH BIOL LABS,BOSTON,MA. FU NIAID NIH HHS [AI18125, 5T32AI07061-13] NR 46 TC 28 Z9 28 U1 0 U2 0 PU BUTTERWORTH-HEINEMANN LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0264-410X J9 VACCINE JI Vaccine PD MAR PY 1996 VL 14 IS 4 BP 290 EP 297 DI 10.1016/0264-410X(95)00201-B PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA UG716 UT WOS:A1996UG71600008 PM 8744555 ER PT J AU Smith, PL Baukrowitz, T Yellen, G AF Smith, PL Baukrowitz, T Yellen, G TI The inward rectification mechanism of the HERG cardiac potassium channel SO NATURE LA English DT Article ID K+ CHANNELS; INACTIVATION; CELLS AB A human genetic defect associated with 'long Q-T syndrome', an abnormality of cardiac rhythm involving the repolarization of the action potential, was recently found to lie in the HERG gene, which codes for a potassium channel(1). The HERG K+ channel is unusual in that it seems to have the architectural plan of the depolarization-activated K+ channel family (six putative transmembrane segments), yet it exhibits rectification like that of the inward-rectifying K+ channels, a family with different molecular structure (two transmembrane segments)(2-4). We have studied HERG channels expressed in mammalian cells and find that this inward rectification arises from a rapid and voltage-dependent inactivation process that reduces conductance at positive voltages. The inactivation gating mechanism resembles that of C-type inactivation, often considered to be the 'slow inactivation' mechanism of other K+ channels. The characteristics of this gating suggest a specific role for this channel in the normal suppression of arrhythmias. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT NEUROBIOL,BOSTON,MA 02114. OI Yellen, Gary/0000-0003-4228-7866 FU NINDS NIH HHS [R01 NS029693] NR 24 TC 557 Z9 565 U1 6 U2 31 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD FEB 29 PY 1996 VL 379 IS 6568 BP 833 EP 836 DI 10.1038/379833a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TX501 UT WOS:A1996TX50100061 PM 8587608 ER PT J AU Brandt, SA Davis, TL Obrig, H Meyer, BU Belliveau, JW Rosen, BR Villringer, A AF Brandt, SA Davis, TL Obrig, H Meyer, BU Belliveau, JW Rosen, BR Villringer, A TI Functional magnetic resonance imaging shows localized brain activation during serial transcranial stimulation in man SO NEUROREPORT LA English DT Article DE fMRI; brain activation; transcranial stimulation; cerebral blood flow; deoxyhaemoglobin; motor cortex AB AREA and depth penetration of transcranial stimulation methods such as transcranial electrical stimulation (TES) are poorly defined. We investigated the feasibility of a simultaneous TES and fMRI measurement. The aim was to compare the signal intensity changes measured using BOLD fMRI during sequential finger movement with the signal response during artificial transcranial stimulation. TES induced contralateral finger contractions and in T2* weighted images a transient signal increase was observed in the area underlying the electrodes. Compared with the signal obtained during sequential finger movements, the area activated by TES was more localized, signal amplitude was smaller and there was no poststimulus undershoot. These data indicate that TES induces a local blood flow increase associated with a drop in the concentration of deoxyhaemoglobin. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA. RP Brandt, SA (reprint author), HUMBOLDT UNIV BERLIN,FAC MED CHARITE,DEPT NEUROL,D-10098 BERLIN,GERMANY. NR 6 TC 22 Z9 22 U1 1 U2 1 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD FEB 29 PY 1996 VL 7 IS 3 BP 734 EP 736 DI 10.1097/00001756-199602290-00013 PG 3 WC Neurosciences SC Neurosciences & Neurology GA UK478 UT WOS:A1996UK47800013 PM 8733733 ER PT J AU Woodgett, JR Kyriakis, JM Avruch, J Zon, LI Zanke, B Templeton, DJ AF Woodgett, JR Kyriakis, JM Avruch, J Zon, LI Zanke, B Templeton, DJ TI Reconstitution of novel signalling cascades responding to cellular stresses SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY OF LONDON SERIES B-BIOLOGICAL SCIENCES LA English DT Article; Proceedings Paper CT Discussion Meeting on Current Understanding of Intracellular Signalling Pathways CY JUL 04-05, 1995 CL ROYAL SOC, LONDON, ENGLAND SP Royal Soc HO ROYAL SOC ID C-JUN; PROTEIN-2 KINASE; PHOSPHORYLATION; ACTIVATION; REQUIRES; MEMBERS; FAMILY AB Mammalian cells respond to their immediate environment by inducing signal transduction cascades that regulate metabolism, secretion and gene expression. Several of these signalling pathways are structurally and organizationally related insofar as they require activation of a protein-serine kinase via it's phosphorylation on tyrosine and threonine; the archetype being mitogen-activated protein kinase (MAPK) which responds primarily to mitogenic stimuli via Ras. In contrast, two more recently identified cascades are responsive to cellular stresses such as heat, inflammatory cytokines, ischaemia and metabolic poisons. The recent identification of the components of these pathways has allowed manipulation of the stress-responsive pathways and evaluation of their physiological roles. These studies reveal a high degree of independence between the pathways not apparent from in vitro studies. Manipulation of the pathways in vivo will likely result in novel therapies for inflammatory disease and reperfusion injury. C1 MASSACHUSETTS GEN HOSP EAST,BOSTON,MA 02129. HARVARD UNIV,CHILDRENS HOSP,SCH MED,HHMI,BOSTON,MA 02115. CASE WESTERN RESERVE UNIV,SCH MED,INST PATHOL,CLEVELAND,OH 44106. RP Woodgett, JR (reprint author), ONTARIO CANC INST,500 SHERBOURNE ST,TORONTO,ON M4X 1K9,CANADA. RI Templeton, Dennis/F-7695-2011; Woodgett, Jim/F-1087-2010 OI Woodgett, Jim/0000-0003-3731-5797 NR 45 TC 41 Z9 43 U1 0 U2 2 PU ROYAL SOC LONDON PI LONDON PA 6 CARLTON HOUSE TERRACE, LONDON, ENGLAND SW1Y 5AG SN 0962-8436 J9 PHILOS T ROY SOC B JI Philos. Trans. R. Soc. Lond. Ser. B-Biol. Sci. PD FEB 29 PY 1996 VL 351 IS 1336 BP 135 EP 141 DI 10.1098/rstb.1996.0009 PG 7 WC Biology SC Life Sciences & Biomedicine - Other Topics GA UA522 UT WOS:A1996UA52200004 PM 8650259 ER PT J AU White, MF AF White, MF TI The IRS-signalling system in insulin and cytokine action SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY OF LONDON SERIES B-BIOLOGICAL SCIENCES LA English DT Article; Proceedings Paper CT Discussion Meeting on Current Understanding of Intracellular Signalling Pathways CY JUL 04-05, 1995 CL ROYAL SOC, LONDON, ENGLAND SP Royal Soc HO ROYAL SOC ID STIMULATES TYROSINE PHOSPHORYLATION; PHOSPHATIDYLINOSITOL 3'-KINASE; HEMATOPOIETIC-CELLS; SIGNALING PATHWAYS; RECEPTOR; PROTEIN; KINASE; GRB2; SUBSTRATE; TRANSDUCTION AB IRS-signalling proteins are engaged and phosphorylated on tyrosine residues by the receptors for insulin and IGF-1, and various classes of cytokine receptors, including IL-4, IL-9, and IL-13; IFN alpha/beta and IFN gamma; and growth hormone and LIF. IRS-proteins provide an interface between these receptors and signalling proteins which contain Src homology-2 domains (SH2-proteins). The recent identification of IRS-2 provides new insight into the modular structure and function of the IRS-proteins. The IRS-proteins provide a means for signal amplification by eliminating the stoichiometric constraints encountered by most receptors which directly recruit SH2-proteins to their autophosphorylation sites. Moreover, IRS-proteins dissociate the intracellular signalling complex from the endocytic pathways of the activated receptor. The shared use of IRS-proteins by multiple receptors is likely to reveal important connections between various hormones and cytokines that were previously unrecognized, or observed but unexplained. The existence of additional signalling molecules based on the IRS-paradigm is likely. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02215. RP White, MF (reprint author), HARVARD UNIV,SCH MED,DIV RESP,JOSLIN DIABET CTR,BOSTON,MA 02215, USA. FU NIDDK NIH HHS [DK38712, DK43808] NR 69 TC 38 Z9 38 U1 0 U2 0 PU ROYAL SOC LONDON PI LONDON PA 6 CARLTON HOUSE TERRACE, LONDON, ENGLAND SW1Y 5AG SN 0962-8436 J9 PHILOS T ROY SOC B JI Philos. Trans. R. Soc. Lond. Ser. B-Biol. Sci. PD FEB 29 PY 1996 VL 351 IS 1336 BP 181 EP 189 DI 10.1098/rstb.1996.0015 PG 9 WC Biology SC Life Sciences & Biomedicine - Other Topics GA UA522 UT WOS:A1996UA52200016 PM 8650265 ER PT J AU Soll, AH AF Soll, AH TI Medical treatment of peptic ulcer disease - Practice guidelines SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; HELICOBACTER-PYLORI INFECTION; BENIGN GASTRIC-ULCER; GASTRODUODENAL MUCOSAL DAMAGE; RANDOMIZED CONTROLLED TRIAL; RESISTANT DUODENAL-ULCERS; LONG-TERM TREATMENT; DOUBLE-BLIND; CAMPYLOBACTER-PYLORI; MAINTENANCE THERAPY AB Objective. - To integrate the realization that peptic ulcer most commonly reflects infection with Helicobacter pylori or use of aspirin and other nonsteroidal antiinflammatory drugs (NSAIDs) into a disease management approach. Participants. - Guidelines were outlined by the author and presented for review to the American College of Gastroenterology (ACG) Practice Parameters Committee, selected by the president of the ACG, and a panel of experts in peptic ulcer, selected by the committee. Evidence and Consensus Process. - These guidelines were formulated following extensive review of the literature obtained by a MEDLINE search and presented for detailed review and revision to unpublicized committee meetings on three occasions and to experts by mail, These recommendations are an official statement of the ACG and have been approved by the American Gastroenterological Association and the American Society for Gastroenterological Endoscopy. Firm recommendations are discriminated from reasonable suppositions pending definitive data. Conclusions. - Since cure of H pylori infection decreases recurrence rates and facilitates healing, antibiotic therapy is indicated for all H pylori-infected ulcer patients. No optimal, simple antibiotic regimen has yet emerged. Simultaneous conventional ulcer therapy is recommended to facilitate symptom relief and healing. For refractory ulcers, only maximal acid inhibition offers advantage over continued conventional therapy; cure of H pylori infection is likely to facilitate healing of refractory ulcers. Only with complicated or refractory ulcers should conventional maintenance therapy be continued, at least until successful H pylori eradication is confirmed. A search for NSAID use is indicated for all ulcer patients. For NSAID-associated ulcers these drugs should be discontinued if possible and H pylori, if present, should be cured. RP W LOS ANGELES VET AFFAIRS MED CTR, CURE DIGEST DIS RES CTR, BLDG 115, ROOM 215, LOS ANGELES, CA 90073 USA. NR 98 TC 241 Z9 248 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD FEB 28 PY 1996 VL 275 IS 8 BP 622 EP 629 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA TW627 UT WOS:A1996TW62700023 PM 8594244 ER PT J AU Polisson, R AF Polisson, R TI Nonsteroidal anti-inflammatory drugs: Practical and theoretical considerations in their selection SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID PEPTIC-ULCER DISEASE; ANTIINFLAMMATORY DRUGS; GASTROINTESTINAL COMPLICATIONS; ELDERLY PERSONS; RISK; GASTROPATHY; MISOPROSTOL; DAMAGE AB Nonsteroidal anti-inflammatory drugs (NSAIDs) are prescribed frequently for patients with painful musculoskeletal conditions: Each year, physicians write approximately 60 million NSAID prescriptions. Because of the magnitude of patient exposure, gastrointestinal and other side effects of NSAIDs are a significant clinical concern. The mechanism of action of NSAIDs is inhibition of cyclooxygenase with secondary inhibition of proinflammatory prostaglandins. This mechanism also accounts for gastrointestinal toxic side effects of NSAIDs. Two forms of cyclooxygenase, cox-1 and cox-2, appear to be differentially inhibited by NSAIDs. Because cox-1 is responsible for maintaining normal physiologic function in gastric mucosa and other tissues, ''ideal'' NSAIDs would suppress only cox-2. The design of future NSAIDs may be influenced by this concept. NSAID-related peptic ulceration is characterized by its location in the gastric antrum, asymptomatic nature, and ability to develop through both topical and systemic effects of NSAIDs. Major risk factors for patients with rheumatoid arthritis include age >60 years, magnitude of disability, concomitant use of corticosteroids, larger doses/longer duration of NSAID treatment, and a history of peptic ulcer disease. A prophylactic strategy includes the identification of high-risk patients and, if NSAIDs must be used, the addition of misoprostol. C1 HARVARD UNIV, SCH MED, DEPT MED, BOSTON, MA USA. RP Polisson, R (reprint author), MASSACHUSETTS GEN HOSP, ARTHRIT UNIT, BOSTON, MA 02114 USA. NR 29 TC 33 Z9 34 U1 1 U2 2 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 FEB 26 PY 1996 VL 100 SU 2A BP S31 EP S36 DI 10.1016/S0002-9343(97)89544-7 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA TZ929 UT WOS:A1996TZ92900006 PM 8604725 ER PT J AU Chesebro, JH Wiebers, DO Holland, AE Bardsley, WT Litin, SC Meissner, I Zerbe, DM Flaker, GC Webel, R Nolte, B Stevenson, P Byer, J Wright, W Anderson, DC Asinger, RW Newburg, SM Bundlie, SR Farmer, CC Koller, RL Haugland, JM Nance, MA Tarrel, RM Dunbar, DN Jorgensen, CR Sharkey, SW Leonard, AD Kanter, MC Solomon, DH Zabalgoitia, M McAnulty, JH Marchant, C Coull, BM Kelley, RE Chahine, R Palermo, M Teixeiro, P Feldman, G Hayward, A MacMillan, K Gandara, E Anderson, W Blank, N Strauss, R Feinberg, WM Vold, BK Kern, KB Appleton, C Bruck, D Dorr, S Dittrich, HC Rothrock, JF Hagenhoff, C Logan, WR Hamilton, WP Green, BJ Bacon, RS Helgason, CM Kondos, GT Hoff, J Halperin, JL Rothlauf, EB Weinberger, JM Goldman, ME Miller, VT Hockersmith, CJ Cohen, BA Janosik, DL Cadell, DJ Kellerman, L Gomez, CR Labovitz, AJ Rothbart, RM Bailey, GH Burkhardt, C Horwitz, L Blackshear, JL Weaver, L Baker, V Lee, G Lane, G Rubino, F Safford, R Kronmal, RA McBride, R Pearce, L Fletcher, KA Nasco, E Hart, RG Sherman, DG Talbert, RL Heberling, PA Colton, T Levy, DE Marsh, JD Welch, KMA Marler, JR Walker, MD AF Chesebro, JH Wiebers, DO Holland, AE Bardsley, WT Litin, SC Meissner, I Zerbe, DM Flaker, GC Webel, R Nolte, B Stevenson, P Byer, J Wright, W Anderson, DC Asinger, RW Newburg, SM Bundlie, SR Farmer, CC Koller, RL Haugland, JM Nance, MA Tarrel, RM Dunbar, DN Jorgensen, CR Sharkey, SW Leonard, AD Kanter, MC Solomon, DH Zabalgoitia, M McAnulty, JH Marchant, C Coull, BM Kelley, RE Chahine, R Palermo, M Teixeiro, P Feldman, G Hayward, A MacMillan, K Gandara, E Anderson, W Blank, N Strauss, R Feinberg, WM Vold, BK Kern, KB Appleton, C Bruck, D Dorr, S Dittrich, HC Rothrock, JF Hagenhoff, C Logan, WR Hamilton, WP Green, BJ Bacon, RS Helgason, CM Kondos, GT Hoff, J Halperin, JL Rothlauf, EB Weinberger, JM Goldman, ME Miller, VT Hockersmith, CJ Cohen, BA Janosik, DL Cadell, DJ Kellerman, L Gomez, CR Labovitz, AJ Rothbart, RM Bailey, GH Burkhardt, C Horwitz, L Blackshear, JL Weaver, L Baker, V Lee, G Lane, G Rubino, F Safford, R Kronmal, RA McBride, R Pearce, L Fletcher, KA Nasco, E Hart, RG Sherman, DG Talbert, RL Heberling, PA Colton, T Levy, DE Marsh, JD Welch, KMA Marler, JR Walker, MD TI Bleeding during antithrombotic therapy in patients with atrial fibrillation SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID ORAL ANTICOAGULANT-THERAPY; PROSTHETIC HEART-VALVES; PROTHROMBIN-TIME RATIO; INTRACEREBRAL HEMORRHAGE; THROMBOEMBOLIC COMPLICATIONS; DIFFERENT INTENSITIES; RISK-FACTORS; WARFARIN; OUTPATIENTS; TRIAL AB Background: The Stroke Prevention in Atrial Fibrillation II study compared warfarin vs aspirin for stroke prevention in atrial fibrillation. Bleeding complications importantly detracted from warfarin's net effectiveness, particularly among older patients. Objectives: To analyze bleeding complications according to assigned therapy. To identify risk factors for bleeding during anticoagulation. Methods: Eleven hundred patients (mean age, 70 years) were randomized to 325 mg of aspirin daily (enteric coated) vs warfarin (target prothrombin time ratio, 1.3 to 1.8; approximate international normalized ratio, 2.0 to 4.5). Major hemorrhages were defined prospectively. Results: The rate of major bleeding while receiving warfarin was 2.3% per year (95% confidence interval [CI], 1.7 to 3.2) vs 1.1% per year (95% CI, 0.7 to 1.8) while receiving aspirin (relative risk, 2.1; 95% CI, 1.1 to 3.1; P=.02). Intracranial hemorrhage occurred at 0.9% per year (95% CI, 0.5 to 1.5) with warfarin and 0.3% per year (95% CI, 0.1 to 0.8) with aspirin (relative risk, 2.4; P=.08). Age (P=.006), increasing number of prescribed medications (P=.007), and intensity of anticoagulation (P=.02) were independent risks for bleeding at any site during anticoagulation. The rate of major hemorrhage was 1.7% per year in patients aged 75 years or younger who received anticoagulation vs 4.2% per year in older patients (relative risk, 2.6, P=.009); rates by age for intracranial bleeding were 0.6% per year and 1.8% per year, respectively (P=.05). Conclusion: Advancing age and more intense anticoagulation increase the risk of major hemorrhage in patients given warfarin for stroke prevention. C1 HENNEPIN CTY MED CTR,DEPT NEUROL,MINNEAPOLIS,MN 55415. MAYO CLIN & MAYO FDN,ROCHESTER,MN 55905. UNIV MISSOURI,COLUMBIA,MO. ABBOTT NW HOSP,MINNEAPOLIS,MN. PARK NICOLLET MED CTR,MINNEAPOLIS,MN. UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. OREGON HLTH SCI UNIV,PORTLAND,OR 97201. UNIV MIAMI,SCH MED,MIAMI,FL. KAISER PERMANENTE,PORTLAND,OR. UNIV ARIZONA,COLL MED,TUCSON,AZ. UNIV CALIF SAN DIEGO,MED CTR,LA JOLLA,CA 92093. ST JOHNS MERCY MED CTR,ST LOUIS,MO 63141. UNIV ILLINOIS,COLL MED,CHICAGO,IL. UNIV ILLINOIS,COLL MED,PEORIA,IL 61656. MT SINAI MED CTR,NEW YORK,NY 10029. NORTHWESTERN UNIV,SCH MED,CHICAGO,IL. ST LOUIS UNIV,MED CTR,ST LOUIS,MO. UNIV COLORADO,SCH MED,DENVER,CO. MAYO CLIN,JACKSONVILLE,FL 32224. UNIV WASHINGTON,SEATTLE,WA 98195. STAT & EPIDEMIOL RES CORP,SEATTLE,WA. BOSTON UNIV,BOSTON,MA 02215. KNOLL PHARMACEUT,WHIPPANY,NJ. HARVARD UNIV,BOSTON,MA 02115. HENRY FORD HOSP,DETROIT,MI 48202. NINCDS,BETHESDA,MD 20892. NR 67 TC 296 Z9 300 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 FEB 26 PY 1996 VL 156 IS 4 BP 409 EP 416 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA TW328 UT WOS:A1996TW32800007 ER PT J AU Niles, JL Bottinger, EP Saurina, GR Kelly, KJ Pan, GL Collins, AB McCluskey, RT AF Niles, JL Bottinger, EP Saurina, GR Kelly, KJ Pan, GL Collins, AB McCluskey, RT TI The syndrome of lung hemorrhage and nephritis is usually an ANCA-associated condition SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID RAPIDLY PROGRESSIVE GLOMERULONEPHRITIS; ANTINEUTROPHIL-CYTOPLASMIC ANTIBODIES; BASEMENT-MEMBRANE ANTIBODIES; SYSTEMIC VASCULITIS; WEGENERS GRANULOMATOSIS; GOODPASTURES-SYNDROME; PULMONARY HEMORRHAGE; NEUTROPHIL CYTOPLASM; AUTO-ANTIGEN; AUTOANTIBODIES AB Background: In the absence of evidence of arteritis or Wegener's granulomatosis, the syndrome of lung hemorrhage and nephritis has been commonly associated with anti-glomerular basement membrane (GBM) antibodies. However, it has been increasingly recognized that many cases are associated with antineutrophil cytoplasmic antibodies (ANCAs). Objective: To review available clinical and pathologic findings to determine the diseases accounting for lung hemorrhage and nephritis. Methods: We studied the records of 750 patients from whom serum samples were sent to our laboratory for anti-GEM antibody assays between 1981 and 1993 and found 88 patients with evidence of lung hemorrhage and nephritis. Serum samples were retested, using current methods, for anti-GEM antibodies (against noncollagenous 1 domain of the alpha 3 chain of type IV collagen) and for antibodies to proteinase 3 and myeloperoxidase-the two types of ANCA of diagnostic value. Results: Of 88 patients with evidence of lung hemorrhage and nephritis, 48 had ANCAs, six had anti-GBM antibodies, and seven had both. In 48 patients with ANCAs, the pathologic findings that accounted for the pulmonary renal syndrome were pauci-immune necrotizing and crescentic glomerulonephritis and pulmonary capillaritis. Only eight had convincing evidence (during life) of Wegener's granulomatosis and only one other had documented arteritis. In 27 patients without ANCAs or anti-GBM antibodies, a variety of unrelated renal and pulmonary diseases were found. Conclusions: The largest group of patients who present with the syndrome of lung hemorrhage and nephritis have ANCAs and not anti-GBM antibodies. Appropriate tests for antibodies to proteinase 3, antibodies to myeloperoxidase, and anti-GBM antibodies provide reliable guides for making a diagnosis in patients with this pulmonary renal syndrome. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. NCI,BETHESDA,MD 20892. RP Niles, JL (reprint author), MASSACHUSETTS GEN HOSP,DEPT MED,COX 5,BOSTON,MA 02114, USA. NR 41 TC 124 Z9 130 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD FEB 26 PY 1996 VL 156 IS 4 BP 440 EP 445 DI 10.1001/archinte.156.4.440 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA TW328 UT WOS:A1996TW32800011 PM 8607730 ER PT J AU Frenette, PS Mayadas, TN Rayburn, H Hynes, RO Wagner, DD AF Frenette, PS Mayadas, TN Rayburn, H Hynes, RO Wagner, DD TI Susceptibility to infection and altered hematopoiesis in mice deficient in both P- and E-selectins SO CELL LA English DT Article ID LEUKOCYTE ADHESION DEFICIENCY; MOUSE; EXPRESSION; MOLECULE-1; CLONING; INVIVO; RATS AB We describe the phenotype of mice lacking both endothelial selectins after sequential ablation of the genes encoding P- and E-selectins. In contrast with the rather mild phenotypes observed in mice deficient in a single selectin gene, the doubly deficient mice present extreme leukocytosis, elevated cytokine levels, and alterations in hematopoiesis. Granulocytopoiesis is increased both in bone marrow and spleen, while erythropoiesis is partially translocated to the spleen. Virtual lack of leukocyte rolling and low extravasation at sites of inflammation make these animals susceptible to opportunistic bacterial infections, to which they succumb. Our results show that the absence of endothelial selectins severely affects leukocyte homeostasis and indicate that these two selectins are as important for normal leukocyte function as are the leukocyte beta 2 integrins. C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,DEPT PATHOL,BOSTON,MA 02115. MIT,HOWARD HUGHES MED INST,CAMBRIDGE,MA 02139. MIT,CTR CANC RES,DEPT BIOL,CAMBRIDGE,MA 02139. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RI Frenette, Paul/J-8272-2012 FU NHLBI NIH HHS [HL41002, HL53756, P01 HL41484] NR 32 TC 418 Z9 423 U1 2 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD FEB 23 PY 1996 VL 84 IS 4 BP 563 EP 574 DI 10.1016/S0092-8674(00)81032-6 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA TX176 UT WOS:A1996TX17600009 PM 8598043 ER PT J AU Krueger, NX VanVactor, D Wan, HI Gelbart, WM Goodman, CS Saito, H AF Krueger, NX VanVactor, D Wan, HI Gelbart, WM Goodman, CS Saito, H TI The transmembrane tyrosine phosphatase DLAR controls motor axon guidance in Drosophila SO CELL LA English DT Article ID CELL-ADHESION MOLECULE; GROWTH CONE GUIDANCE; NERVOUS-SYSTEM AXONS; IMMUNOGLOBULIN SUPERFAMILY; CYTOPLASMIC REGION; GENETIC-ANALYSIS; FASCICLIN-II; C-ELEGANS; RECEPTOR; PROTEIN AB DLAR is a receptor-like, transmembrane protein-tyrosine phosphatase in Drosophila that is expressed almost exclusively by developing neurons. Analysis of Dlar loss-of-function mutations shows that DLAR plays a key role during motoneuron growth cone guidance. Segmental nerve b (SNb) motor axons normally exit the common motor pathway, enter the ventral target region, and then synapse on specific ventral muscles. In Dlar mutant embryos, SNb axons bypass their normal target region and instead continue to extend along the common pathway. SNd motor axons also make pathfinding errors, while SNa and SNc axons appear normal. Thus, DLAR controls the ability of certain motor axons to navigate specific choice points in the developing Drosophila nervous system. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. UNIV CALIF BERKELEY,HOWARD HUGHES MED INST,DIV NEUROBIOL,DEPT MOLEC & CELL BIOL,BERKELEY,CA 94720. HARVARD UNIV,DEPT MOLEC & CELLULAR BIOL,CAMBRIDGE,MA 02138. FU NIGMS NIH HHS [GM53415]; PHS HHS [AL26598] NR 62 TC 274 Z9 276 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD FEB 23 PY 1996 VL 84 IS 4 BP 611 EP 622 DI 10.1016/S0092-8674(00)81036-3 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA TX176 UT WOS:A1996TX17600013 PM 8598047 ER PT J AU Nitsch, RM Deng, MH Growdon, JH Wurtman, RJ AF Nitsch, RM Deng, MH Growdon, JH Wurtman, RJ TI Serotonin 5-HT2a and 5-HT2e receptors stimulate amyloid precursor protein ectodomain secretion SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BETA-PROTEIN; ALZHEIMERS-DISEASE; GROWTH-FACTOR; KINASE-C; PEPTIDE; ACTIVATION; RELEASE; CLEAVAGE; ALPHA; IDENTIFICATION AB Alzheimer's disease amyloid consists of amyloid beta-peptides (A beta) derived from the larger precursor amyloid precursor protein (APP). Non-amyloidogenic APP processing involves regulated cleavage within the A beta domain followed by secretion of the ectodomain (APPs). APPs secretion can be stimulated by muscarinic acetylcholine receptors coupled to phospholipases and kinases. To determine whether other receptor classes can regulate APP processing, we examined the relation between serotonin receptors and APPs secretion. Serotonin increased APPs release 3-4 fold in 3T3 cells stably overexpressing 5-HT2aR or 5 HT2cR. The increase was dose-dependent and was blocked by serotoninergic antagonists. Phorbol esters also increased APPs secretion, but neither kinase inhibitors nor down-regulation of PKC blocked the serotonin-induced increase in APPs secretion. Thus PKC is not necessary to stimulate APPs secretion. Phospholipase A(2) (PLA(2)) inhibitors blocked the 5-HT2aR-mediated increase in APPs secretion, suggesting a role of PLA(2) in coupling 5-HT2aR to APP processing. In contrast, coupling of 5-HT2cR to APPs secretion involved both PKC and PLA(2). Serotonin also stimulated the release of the APLP2 ectodomain, suggesting that additional members of the APP multigene family are processed via similar regulated pathways. Inasmuch as generation of APPs precludes the formation of amyloidogenic derivatives, serotonin receptors provide a novel pharmacological target to reduce these derivatives in Alzheimer's disease. C1 MIT,DEPT BRAIN & COGNIT SCI,CAMBRIDGE,MA 02139. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROL,BOSTON,MA 02114. NR 52 TC 155 Z9 163 U1 2 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 FEB 23 PY 1996 VL 271 IS 8 BP 4188 EP 4194 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TW960 UT WOS:A1996TW96000039 PM 8626761 ER PT J AU Luo, CM Tang, W Mekeel, KL DeFrank, JS Anne, RP Powell, SN AF Luo, CM Tang, W Mekeel, KL DeFrank, JS Anne, RP Powell, SN TI High frequency and error-prone DNA recombination in ataxia telangiectasia cell lines SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID STRAND BREAK REPAIR; IONIZING-RADIATION; V(D)J RECOMBINATION; HOMOLOGOUS RECOMBINATION; SCID MUTATION; UV; IRRADIATION; DEFECTS; P53; INSTABILITY AB The only specific DNA repair defect found in ataxia telangiectasia (A-T) cells is mis-repair of cleaved DNA In this report we measured DNA recombination, given its role in DNA repair and genetic instability. Using plasmids containing selectable reporter genes, we found a higher frequency of both chromosomal recombination (>100 times) and extra-chromosomal recombination (27 times) in SV40-transformed A-T cell lines compared with in an SV40-transformed normal fibroblast cell line. Southern analysis of single A-T colonies exhibiting postintegration recombination revealed that 24/27 had undergone aberrant rearrangements; recombination in normal fibroblast colonies was achieved by gene conversion in 8/11 clones and 10/11 clones showed unchanged copies of the plasmid. Using co-transfection of two integrating plasmids, each containing a separate deletion in the xgprt reporter gene, the 27 times difference in extrachromosomal recombination was found when the plasmids were cleaved at a distance from the reporter gene. When the plasmids were cleaved within the reporter gene, the co-transfection frequency was reduced in A-T, but was increased in normal cells. We conclude that A-T cell lines have not only a high frequency chromosomal and extra-chromosomal recombination, but also exhibit error-prone recombination of cleaved DNA. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,BOSTON,MA 02114. FU NCI NIH HHS [CA58985] NR 33 TC 66 Z9 66 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 23 PY 1996 VL 271 IS 8 BP 4497 EP 4503 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TW960 UT WOS:A1996TW96000082 PM 8626804 ER PT J AU Girard, JP Springer, TA AF Girard, JP Springer, TA TI Modulation of endothelial cell adhesion by hevin, an acidic protein associated with high endothelial venules SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EXTRACELLULAR-MATRIX; L-SELECTIN; VASCULAR ADDRESSIN; HUMAN TENASCIN; BINDING; THROMBOSPONDIN; SPARC; DIFFERENTIATION; MOLECULE; PEPTIDES AB High endothelial venules (HEV) are specialized plump postcapillary venules in lymphoid tissues that support high levels of lymphocyte extravasation from the blood. We have recently identified a novel human transcript, expressed to high levels in HEV, that encodes a secreted, acidic protein closely related to the anti-adhesive extracellular matrix protein known as BM-40, osteonectin, and SPARC (secreted protein acidic and rich in cysteine). Here, we show that this protein, designated hevin, is associated with basal, lateral, and apical surfaces of HEV cells, and unlike MECA-79 antigen, is not expressed on the underlying basement membrane. In contrast to fibronectin or other adhesive extracellular matrix proteins, purified hevin does not support endothelial cell adhesion in vitro. Moreover, addition of soluble exogenous hevin inhibits attachment and spreading of endothelial cells on fibronectin substrates. Hevin-treated cells do not form focal adhesions and exhibit a rounded morphology. Together, these results suggest that hevin is an abundant extracellular protein that modulates high endothelial cell adhesion to the basement membrane. C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. CNRS,LAB BIOL MOLEC EUCARYOTE,F-31062 TOULOUSE,FRANCE. RI GIRARD, Jean-Philippe/F-5229-2010 FU NCI NIH HHS [CA 31798] NR 37 TC 91 Z9 91 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 FEB 23 PY 1996 VL 271 IS 8 BP 4511 EP 4517 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TW960 UT WOS:A1996TW96000084 PM 8626806 ER PT J AU Jain, RK AF Jain, RK TI Delivery of molecular medicine to solid tumors SO SCIENCE LA English DT Editorial Material C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP Jain, RK (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,EDWIN L STEELE LAB,BOSTON,MA 02114, USA. NR 14 TC 247 Z9 250 U1 0 U2 5 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD FEB 23 PY 1996 VL 271 IS 5252 BP 1079 EP 1080 DI 10.1126/science.271.5252.1079 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TW701 UT WOS:A1996TW70100027 PM 8599082 ER PT J AU Wang, TW Danielson, PD Li, BY Shah, PC Kim, SD Donahoe, PK AF Wang, TW Danielson, PD Li, BY Shah, PC Kim, SD Donahoe, PK TI The p21(RAS) farnesyltransferase alpha subunit in TGF-beta and activin signaling SO SCIENCE LA English DT Article ID GROWTH-FACTOR-BETA; PROTEIN FARNESYLTRANSFERASE; II RECEPTOR; P21RAS; CLONING; RECOGNITION; EXPRESSION; ACTIVATION AB The alpha subunit of p21(RAS) farnesyltransferase (FNTA), which is also shared by geranylgeranyltransferase, was isolated as a specific cytoplasmic interactor of the transforming growth factor-beta (TGF-beta) and activin type I receptors with the use of the yeast two-hybrid system. FNTA interacts specifically with ligand-free TGF-beta type I receptor but is phosphorylated and released upon ligand binding. Furthermore, the release is dependent on the kinase activity of the TGF-beta type II receptor. Thus, the growth inhibitory and differentiative pathways activated by TGF-beta and activin involve novel mechanisms of serine-threonine receptor phosphorylation-dependent release of cytoplasmic interactors and regulation of the activation of small G proteins, such as p21(RAS). RP Wang, TW (reprint author), MASSACHUSETTS GEN HOSP,PEDIAT SURG RES LAB,BOSTON,MA 02114, USA. FU NICHD NIH HHS [HD28138, R01 HD3081, R01 HD32112] NR 34 TC 107 Z9 108 U1 0 U2 2 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD FEB 23 PY 1996 VL 271 IS 5252 BP 1120 EP 1122 DI 10.1126/science.271.5252.1120 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TW701 UT WOS:A1996TW70100039 PM 8599089 ER PT J AU Berenson, JR Lichtenstein, A Porter, L Dimopoulos, MA Bordoni, R George, S Lipton, A Keller, A Ballester, O Kovacs, MJ Blacklock, HA Bell, R Simeone, J Reitsma, DJ Heffernan, M Seaman, J Knight, RD AF Berenson, JR Lichtenstein, A Porter, L Dimopoulos, MA Bordoni, R George, S Lipton, A Keller, A Ballester, O Kovacs, MJ Blacklock, HA Bell, R Simeone, J Reitsma, DJ Heffernan, M Seaman, J Knight, RD TI Efficacy of pamidronate in reducing skeletal events in patients with advanced multiple myeloma SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID PLASMA-CELL MYELOMA; BONE METASTASES; BREAST-CANCER; THERAPY; HYPERCALCEMIA; CHEMOTHERAPY; INHIBITION; ETIDRONATE; ONCOLOGY; CALCIUM AB Background. Skeletal complications are a major clinical manifestation of multiple myeloma. These complications are caused by soluble factors that stimulate osteoclasts to resorb bone, Bisphosphonates such as pamidronate inhibit osteoclastic activity and reduce bone resorption. Methods. Patients with stage III multiple myeloma and at least one lytic lesion received either placebo or pamidronate (90 mg) as a four-hour intravenous infusion given every four weeks for nine cycles in addition to antimyeloma therapy. The patients were stratified according to whether they were receiving first-line (stratum 1) or second-line (stratum 2) antimyeloma chemotherapy at entry into the study. Skeletal events (pathologic fracture, irradiation of or surgery on bone, and spinal cord compression), hypercalcemia (symptoms or a serum calcium concentration greater than or equal to 12 mg per deciliter [3.0 mmol per liter]), bone pain, analgesic-drug use, performance status, and quality of life were assessed monthly. Results. Among 392 treated patients, the efficacy of treatment could be evaluated in 196 who received pamidronate and 181 who received placebo. The proportion of patients who had any skeletal events was significantly lower in the pamidronate group (24 percent) than in the placebo group (41 percent, P<0.001), and the reduction was evident in both stratum 1 (P=0.04) and stratum 2 (P=0.004). The patients who received pamidronate had significant decreases in bone pain and no deterioration in performance status and quality of life. Pamidronate was well tolerated. Conclusions. Monthly infusions of pamidronate provide significant protection against skeletal complications and improve the quality of life of patients with stage III multiple myeloma. (C) 1996, Massachusetts Medical Society. C1 UNIV CALIF LOS ANGELES,JONSSON COMPREHENS CANC CTR,SCH MED,LOS ANGELES,CA 90024. ST THOMAS HOSP,NASHVILLE,TN. UNIV TEXAS,MD ANDERSON CANC CTR,HOUSTON,TX. AMER MED RES INST,ATLANTA,GA. SW INST CLIN RES,RANCHO MIRAGE,CA. MILTON S HERSHEY MED CTR,HERSHEY,PA. CANC CARE ASSOCIATES,TULSA,OK. H LEE MOFFITT CANC CTR,TAMPA,FL. VICTORIA HOSP,LONDON,ON N6A 4G5,CANADA. MIDDLEMORE HOSP,AUCKLAND 6,NEW ZEALAND. SCH MED,AUCKLAND,NEW ZEALAND. ST JOHN GOD HOSP,CENT HIGHLANDS ONCOL PROGRAM,BALLARAT,AUSTRALIA. CIBA PHARMACEUT,SUMMIT,NJ. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP Berenson, JR (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,DIV MED ONCOL,111H,11301 WILSHIRE BLVD,LOS ANGELES,CA 90073, USA. NR 35 TC 701 Z9 722 U1 2 U2 9 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD FEB 22 PY 1996 VL 334 IS 8 BP 488 EP 493 DI 10.1056/NEJM199602223340802 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA TV686 UT WOS:A1996TV68600002 PM 8559201 ER PT J AU Torchilin, VP Narula, J Halpern, E Khaw, BA AF Torchilin, VP Narula, J Halpern, E Khaw, BA TI Poly(ethylene glycol)-coated anti-cardiac myosin immunoliposomes: Factors influencing targeted accumulation in the infarcted myocardium SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES LA English DT Article DE liposome; immunoliposome; long-circulating liposome; antimyosin; antibody; myocardial infarction; drug targeting ID CIRCULATION TIME; LIPOSOMES; LOCALIZATION; FRAGMENTS; DELIVERY; ISCHEMIA; INVIVO AB Biodistribution and infarct accumulation of different liposome preparations in rabbits with experimental myocardial infarction have been investigated. The influence of such parameters as liposome size, and presence or absence of poly(ethylene glycol) (PEG) and infarct-specific antimyosin antibody (AM) on liposome behavior in vivo was studied. All three variables were shown to affect liposome biodistribution, liposome size being the least significant variable. Statistical analysis of the data obtained demonstrated that of all variables, PEG coating expresses the strongest influence on the liposome blood clearance, significantly (P = 0.0001) increasing the mean level of blood radioactivity under all circumstances. Infarct accumulation depended upon the presence of both PEG (P = 0.0013) and AM (P = 0.005). The infarct-to-normal ratio was affected by the presence of AM (P = 0.0002), but the extent of the effect depended also on the presence of PEG (P = 0.01). Two differing mechanisms can be seen in infarct accumulation of PEG-liposomes (slow accumulation via the impaired filtration) and AM-liposomes (specific binding of immunoliposomes with the exposed antigen), Both mechanisms are supplementary in case of liposomes carrying PEG and AM at the same time, An optimization strategy is suggested for using liposomes as carriers for diagnostic (a high target-to-nontarget ratio is required) and therapeutic (a high absolute accumulation in the target is required) agents. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,CARDIAC UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DIV NUCL MED,BOSTON,MA 02114. NORTHEASTERN UNIV,CTR DRUG TARGETING & ANAL,BOSTON,MA 02115. RP Torchilin, VP (reprint author), MASSACHUSETTS GEN HOSP,CTR IMAGING & PHARMACEUT RES,MGH-E,149 13TH ST,BOSTON,MA 02129, USA. NR 32 TC 63 Z9 68 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2736 J9 BBA-BIOMEMBRANES JI Biochim. Biophys. Acta-Biomembr. PD FEB 21 PY 1996 VL 1279 IS 1 BP 75 EP 83 DI 10.1016/0005-2736(95)00248-0 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA TX670 UT WOS:A1996TX67000011 PM 8624365 ER PT J AU LuYao, GL Potosky, AL Albertsen, PC Wasson, JH Barry, MJ Wennberg, JE AF LuYao, GL Potosky, AL Albertsen, PC Wasson, JH Barry, MJ Wennberg, JE TI Follow-up prostate cancer treatments after radical prostatectomy: A population-based study SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID CARCINOMA; MEDICARE; PRESERVATION; MANAGEMENT; MORBIDITY; OUTCOMES AB Background: Radical prostatectomy is one of the most commonly used curative procedures for the treatment of localized prostate cancer. The probability that a patient will undergo additional cancer therapy after this procedure is largely unknown. Purpose: The objective was to determine the likelihood of additional cancer therapy after radical prostatectomy. Methods: Data for this study were derived from a linked dataset that combined information from the Surveillance, Epidemiology, and End Results Program and Medicare hospital and physician claims. Records were included in this study if patient histories met the following criteria: (a) residing in Connecticut, Washington (Seattle-Puget Sound), or Georgia (Metropolitan Atlanta); (b) having been diagnosed with prostate cancer during the period from January 1, 1985, through December 31, 1991; (c) undergoing radical prostatectomy by December 31, 1992; and (d) having no evidence of other types of cancer. Patients were considered to have had additional cancer therapy if they had had radiation therapy, orchiectomy, and/or androgen-deprivation therapy by injection after radical prostatectomy. The interval between the initial treatment and any follow-up treatment was calculated from the date of radical prostatectomy to the Ist day of the follow-up cancer therapy. All presented probabilities are based on Kaplan-Meier estimates. Results: The study population consisted of 3494 Medicare patients, 3173 of whom underwent radical prostatectomy within 3 months of prostate cancer diagnosis. Although radical prostatectomy is often reserved for localized cancer, less than 60% (1934) of patients whose records were included in this study had organ-confined disease, according to final surgical pathology. Overall, the 5-year cumulative incidence of having any additional cancer treatment after radical prostatectomy reached 34.9% (95% confidence interval [CI] = 31.5% -38.5%). For patients with pathologically organ-confined cancer, the 5-year cumulative incidence was 24.3% (95% CI = 20.0%-29.3%) overall and ranged from 15.6% (95% CI = 9.7%-24.5%) for well-differentiated cancer (Gleason scores 2-4) to 41.5% (95% CI = 27.9%-58.4%) for poorly differentiated cancer (Gleason scores 8-10). The corresponding figures for pathologically regional cancer were 22.7% (95% CI = 12.9%-40.5%) and 68.1% (95% CI = 58.7%-77.1%). Conclusion: Further treatment of prostate cancer was done in about one third of patients who had had a radical prostatectomy with curative intent and in about one quarter of patients who were found to have organ-confined disease. Implications: Given the common requirement for follow-up cancer treatments after radical prostatectomy and the uncertainties about the effectiveness of the various follow-up treatment strategies, further investigation of these treatments is warranted. C1 NCI,DIV CANC PREVENT & CONTROL,SURVEILLANCE PROGRAM,BETHESDA,MD 20892. UNIV CONNECTICUT,DIV UROL,DEPT SURG,FARMINGTON,CT. MASSACHUSETTS GEN HOSP,MED PRACTICES EVALUAT CTR,BOSTON,MA 02114. DARTMOUTH COLL,HITCHCOCK MED CTR,DARTMOUTH MED SCH,CTR EVALUAT CLIN SCI,HANOVER,NH 03756. FU AHRQ HHS [HS08397, HS06336] NR 40 TC 146 Z9 150 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD FEB 21 PY 1996 VL 88 IS 3-4 BP 166 EP 173 DI 10.1093/jnci/88.3-4.166 PG 8 WC Oncology SC Oncology GA TV723 UT WOS:A1996TV72300011 PM 8632490 ER PT J AU Tivol, EA Shalish, C Schuback, DE Hsu, YP Breakefield, XO AF Tivol, EA Shalish, C Schuback, DE Hsu, YP Breakefield, XO TI Mutational analysis of the human MAOA gene SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE MAO; polymorphisms; human ID MONOAMINE OXIDASE-A; NORRIE DISEASE; B GENES; PARKINSONS-DISEASE; MOLECULAR-BASIS; CHAIN-REACTION; X-CHROMOSOME; HUMAN-LIVER; PLATELET; DNA AB The monoamine oxidases (MAO-A and MAO-B) are the enzymes primarily responsible for the degradation of amine neurotransmitters, such as dopamine, norepinephrine, and serotonin. Wide variations in activity of these isozymes have been reported in control humans. The MAOA and MAOB genes are located next to each other in the p11.3-11.4 region of the human X chromosome. Our recent documentation of an MAO-A-deficiency state, apparently associated with impulsive aggressive behavior in males, has focused attention on genetic variations in the MAOA gene. In the present study, variations in the coding sequence of the MAOA gene were evaluated by RT-PCR, SSCP, and sequencing of mRNA or genomic DNA in 40 control males with >100-fold variations in MAO-A activity, as measured in cultured skin fibroblasts. Remarkable conservation of the coding sequence was found, with only 5 polymorphisms observed. All but one of these were in the third codon position and thus did not alter the deduced amino acid sequence. The one amino acid alteration observed, lys-->arg, was neutral and should not affect the structure of the protein. This study demonstrates high conservation of coding sequence in the human MAOA gene in control males, and provides primer sets which can be used to search genomic DNA for mutations in this gene in males with neuropsychiatric conditions. (C) 1996 Wiley-Liss, Inc. C1 MASSACHUSETTS GEN HOSP,MOL NEUROGENET UNIT,NEUROL SERV,BOSTON,MA. HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02115. VET ADM MED CTR,BOSTON,MA 02132. FU NIMH NIH HHS [MH52416]; NINDS NIH HHS [NS21921] NR 47 TC 26 Z9 30 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD FEB 16 PY 1996 VL 67 IS 1 BP 92 EP 97 DI 10.1002/(SICI)1096-8628(19960216)67:1<92::AID-AJMG16>3.0.CO;2-K PG 6 WC Genetics & Heredity SC Genetics & Heredity GA TY403 UT WOS:A1996TY40300017 PM 8678123 ER PT J AU Hensold, JO Stratton, CA Barth, D Galson, DL AF Hensold, JO Stratton, CA Barth, D Galson, DL TI Expression of the transcription factor, Spi-1 (PU.1), in differentiating murine erythroleukemia cells is regulated post-transcriptionally - Evidence for differential stability of transcription factor mRNAs following inducer exposure SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MESSENGER-RNA DEGRADATION; PUTATIVE ONCOGENE SPI-1; DNA-BINDING PROTEIN; C-FOS; GENE; ACTIVATION; GLOBIN; CLONING; VIRUS; DEADENYLATION AB Increased expression of the transcription factor Spi-1 (PU.1) results from retroviral insertion in nearly all Friend spleen focus-forming virus-transformed murine erythroleukemia cell lines and exposure of these cells to Me(2)SO, induces their differentiation and decreases Spi-1 mRNA level by 4-5-fold. While these results suggest that alterations in Spi-1 expression have significant effects on erythroblast growth and differentiation, neither the cause nor the effect of the decrease in Spi-1 expression that follows Me(2)SO exposure has been established. The experiments described here demonstrate that the effect of inducers on Spi-1 expression is regulated post-transcriptionally. Nuclear run-off transcriptions demonstrated that Spi-1 transcription was not decreased following Me(2)SO exposure. Additionally, expression of a recombinant Spi-1 mRNA under transcriptional control of a constitutively active Rous sarcoma virus promoter was regulated identically to endogenous Spi-1 mRNA. The ability of Me(2)SO to destabilize Spi-1 mRNA was selective, as the stability of the erythroid transcription factors GATA-1 and NF-E2 were not similarly effected. The effect of Me(2)SO on the stability of Spi-1 mRNA provides a novel means of altering gene expression in these cells and is likely to have significance for the differentiation of these cells. C1 CASE WESTERN RESERVE UNIV,IRELAND CANC CTR,DEPT MED,CLEVELAND,OH 44106. DEPT VET AFFAIRS MED CTR,CLEVELAND,OH 44106. MASSACHUSETTS GEN HOSP,ARTHRIT UNIT,BOSTON,MA 02129. RI Galson, Deborah/E-9370-2010 OI Galson, Deborah/0000-0002-2045-8807 FU NIDDK NIH HHS [DK43414] NR 49 TC 15 Z9 15 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 16 PY 1996 VL 271 IS 7 BP 3385 EP 3391 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TV724 UT WOS:A1996TV72400011 PM 8631937 ER PT J AU Street, JM Evans, JE Natowicz, MR AF Street, JM Evans, JE Natowicz, MR TI Glucuronic acid-conjugated dihydroxy fatty acids in the urine of patients with generalized peroxisomal disorders SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CHROMATOGRAPHY MASS-SPECTROMETRY; GAS-LIQUID-CHROMATOGRAPHY; RAT-LIVER PEROXISOMES; ZELLWEGER SYNDROME; ARACHIDONIC-ACID; BILE-ACIDS; BETA-OXIDATION; INBORN-ERRORS; METABOLISM; HYDROPEROXIDE AB Urine extracts from children diagnosed with generalized peroxisomal disorders were screened by continuous flow-negative ion fast atom bombardment-mass spectrometry. In 45 of 60 children with generalized peroxisomal disorders, we observed one or more intense ions (m/z 489, 505, 461, and others) that are infrequently found in children with cholestatic liver disease or normal children. Compounds giving rise to these ions were isolated using reverse phase and anion exchange chromatography. After appropriate derivatization and/or methanolysis the compounds were analyzed using capillary gas chromatography-mass spectrometry. The major compounds were found to be 12,13-dihydroxy-9-octadecenoic acid and 9,10-dihydroxy-12-octadecenoic acid, with one of the hydroxyl groups in glycosidic linkage with glucuronic acid. Minor compounds were glucuronic acid conjugates of 9,10-dihydroxy-octadecanoic acid, and 12, 13-dihydroxy-6,9-, 15, 16-dihydroxy-9,12-, and 9,10-dihydroxy-12,15-octadecadienoic acids. A series of hexadecanoic, hexadecanoic, and hexadecadienoic acid glucuronides which appear to be beta-oxidation products of the C18 fatty acids were also observed, with the major species being 10,11-dihydroxy-7-hexadecenoic acid glucuronide, In all, 16 C16 and C18 dihydroxy fatty acids were identified by gas chromatography-mass spectrometry, A series of at least 11 trihydroxy fatty acids was also observed but not fully characterized. Measurement of these compounds may prove to be useful in the diagnosis of some peroxisomal disorders. C1 EUNICE KENNEDY SHRIVER CTR MENTAL RETARDAT INC,MASS SPECTROMETRY FACIL,WALTHAM,MA 02254. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RP Street, JM (reprint author), EUNICE KENNEDY SHRIVER CTR MENTAL RETARDAT INC,DIV MED GENET,200 TRAPELO RD,WALTHAM,MA 02254, USA. RI Street, Jackie/A-2016-2011 OI Street, Jackie/0000-0002-1033-4341 FU NICHD NIH HHS [HD05515] NR 49 TC 17 Z9 17 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 FEB 16 PY 1996 VL 271 IS 7 BP 3507 EP 3516 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TV724 UT WOS:A1996TV72400029 PM 8631955 ER PT J AU Tamm, A Kister, A Nolte, KU Gessner, JE Schmidt, RE AF Tamm, A Kister, A Nolte, KU Gessner, JE Schmidt, RE TI The IgG binding site of human Fc gamma RIIIB receptor involves CC' and FG loops of the membrane-proximal domain SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NATURAL-KILLER-CELLS; SINGLE AMINO-ACID; MONOCLONAL-ANTIBODIES; HUMAN-NEUTROPHILS; ALPHA-SUBUNIT; HIGH-AFFINITY; HUMAN IMMUNOGLOBULIN; EPSILON-RI; POLYMORPHISM; EXPRESSION AB Fc gamma receptors for the Fc part of IgG are the mediators for antibody effector functions. Fc gamma RIII and Fc gamma RII are low affinity receptors that, through the interaction with immune complexes, initiate a variety of immunological responses, such as phagocytosis, antibody-dependent cellular cytotoxicity, and release of inflammatory mediators. me set out to define the IgG binding site on human Fc gamma RIII. We assumed that potential beta-turns in Ig-like domains are the most probable determinants for ligand binding, and chimeric Fc gamma RIIIB/Fc epsilon RI receptors as well as single residue mutants were constructed in these regions of Fc gamma RIIIB. Substitution of four amino acids in the membrane-proximal domain (Gln(126), Arg(156), Lys(162), Val(164)) resulted in decreased binding of human IgG1. Lys(162) and Val(164) were found also to be crucial for the interaction with the IgG-binding inhibitory monoclonal antibody 3G8. In a putative three-dimensional model constructed in this study, these residues map on the CC' loop (Gln(126)), on F beta-sheet (Arg(156)), and on the FG loop (Lys(162), Val(164)). Our data are consistent with the study about human Fc gamma RII (Hulett, M. D., Witort, E., Brinkworth, R. I., McKenzie, I. F. C., and Hogarth, P. M. (1994) J. Biol. Chem. 269, 15287-15293), suggesting that common structural determinants, i.e. FG loop or the GFC surface of the membrane-proximal domain, can be involved in interactions with IgG by both low affinity receptor classes Fc gamma RII and Fc gamma RIII. C1 HANNOVER MED SCH,DEPT CLIN IMMUNOL,D-30625 HANNOVER,GERMANY. DANA FARBER CANC INST,IMMUNOBIOL LAB,BOSTON,MA 02115. NR 59 TC 44 Z9 45 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 FEB 16 PY 1996 VL 271 IS 7 BP 3659 EP 3666 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TV724 UT WOS:A1996TV72400051 PM 8631977 ER PT J AU Shima, DT Kuroki, M Deutsch, U Ng, YS Adamis, AP DAmore, PA AF Shima, DT Kuroki, M Deutsch, U Ng, YS Adamis, AP DAmore, PA TI The mouse gene for vascular endothelial growth factor - Genomic structure, definition of the transcriptional unit, and characterization of transcriptional and post-transcriptional regulatory sequences SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MESSENGER-RNA; PERMEABILITY FACTOR; TRANSFERRIN RECEPTOR; FACTOR FAMILY; GM-CSF; EXPRESSION; ANGIOGENESIS; TUMOR; CELLS; VEGF AB We describe the genomic organization and functional characterization of the mouse gene encoding vascular endothelial growth factor (VEGF), a polypeptide implicated in embryonic vascular development and postnatal angiogenesis. The coding region for mouse VEGF is interrupted by seven introns and encompasses approximately 14 kilobases. Organization of exons suggests that, similar to the human VEGF gene, alternative splicing generates the 120-, 164-, and 188-amino acid isoforms, but does not predict a fourth VEGF isoform corresponding to human VEGF(206). Approximately 1.2 kilobases of 5'-flanking region have been sequenced, and primer extension analysis identified a single major transcription initiation site, notably lacking TATA or CCAT consensus sequences. The 5'-flanking region is sufficient to promote a 7-fold induction of basal transcription. The genomic region encoding the 3'-untranslated region was determined by Northern and nuclease mapping analysis. Investigation of mRNA sequences responsible for the rapid turnover of VEGF mRNA (mRNA half-life, <1 h) (Shima, D. T., Deutsch, U., and D'Amore, P. A (1995) FEES Lett. 370, 203-208) revealed that the 3'-untranslated region was sufficient to trigger the rapid turnover of a normally long-lived reporter mRNA in vitro. These data and reagents will allow the molecular and genetic analysis of mechanisms that control the developmental and pathological expression of VEGF. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. CHILDRENS HOSP,SURG RES LAB,BOSTON,MA 02115. HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02115. MAX PLANCK INST PHYSIOL & CLIN RES,W-6350 BAD NAUHEIM,GERMANY. RP Shima, DT (reprint author), HARVARD UNIV,SCH MED,PROGRAM BIOL & BIOMED SCI,BOSTON,MA 02115, USA. FU NEI NIH HHS [EY05985] NR 48 TC 278 Z9 287 U1 3 U2 12 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 16 PY 1996 VL 271 IS 7 BP 3877 EP 3883 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TV724 UT WOS:A1996TV72400081 PM 8632007 ER PT J AU Petty, F Rush, AJ Davis, JM Calabrese, JR Kimmel, SE Kramer, GL Small, JG Miller, MJ Swann, AE Orsulak, PJ Blake, ME Bowden, CL AF Petty, F Rush, AJ Davis, JM Calabrese, JR Kimmel, SE Kramer, GL Small, JG Miller, MJ Swann, AE Orsulak, PJ Blake, ME Bowden, CL TI Plasma GABA predicts acute response to divalproex in mania SO BIOLOGICAL PSYCHIATRY LA English DT Article DE bipolar disorder; mania; GABA; divalproex; valproic acid; lithium; response prediction ID GAMMA-AMINOBUTYRIC-ACID; SODIUM VALPROATE; BIPOLAR DISORDER; AMINO-ACIDS; BRAIN; RAT; DEPRESSION; ILLNESS AB Bipolar I, manic phase inpatients were treated with divalproex sodium, lithium, or placebo in a previously reported parallel group multicenter, double-blind, randomized controlled acute phase treatment trial. Plasma concentrations of gamma aminobutyric acid (GABA) were measured before and after treatment. Higher pretreatment plasma GABA levels were significantly (p = .04) related to a better clinical response to divalproex (n = 19). Pretreatment plasma GABA levels did not correlate with response to either lithium (n = 13) or placebo (n = 31). Following treatment with divalproex sodium, plasma GABA levels decreased significantly (p < .05), compared to placebo. Pretreatment plasma GABA levels were not related to overall severity of manic symptoms. Plasma GABA may predict response to pharmacologic agents acting on the GABA system. C1 UNIV TEXAS,SW MED CTR,DEPT PSYCHIAT,DALLAS,TX. UNIV ILLINOIS,DEPT PSYCHIAT,CHICAGO,IL 60612. ILLINOIS STATE PSYCHIAT INST,CHICAGO,IL 60612. CASE WESTERN RESERVE UNIV,SCH MED,CLEVELAND,OH. INDIANA UNIV,SCH MED,DEPT PSYCHIAT,INDIANAPOLIS,IN 46202. LARUE D CARTER MEM HOSP,INDIANAPOLIS,IN. UNIV TEXAS,SCH MED,DEPT PSYCHIAT,HOUSTON,TX. ABBOTT LABS,ABBOTT PK,IL 60064. UNIV TEXAS,HLTH SCI CTR,DEPT PSYCHIAT,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX. RP Petty, F (reprint author), VET AFFAIRS MED CTR,PSYCHIAT SERV 116A,4500 S LANCASTER RD,DALLAS,TX 75216, USA. OI Rush, Augustus/0000-0003-2004-2382 FU NIMH NIH HHS [MH37899, MH41115] NR 30 TC 40 Z9 42 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD FEB 15 PY 1996 VL 39 IS 4 BP 278 EP 284 DI 10.1016/0006-3223(95)00141-7 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA TW730 UT WOS:A1996TW73000007 PM 8645774 ER PT J AU Compton, PA Anglin, MD KhalsaDenison, ME Paredes, A AF Compton, PA Anglin, MD KhalsaDenison, ME Paredes, A TI The D2 dopamine receptor gene, addiction, and personality: Clinical correlates in cocaine abusers SO BIOLOGICAL PSYCHIATRY LA English DT Article DE cocaine; allele; dopamine; substance abuse; genetic predisposition ID ALLELIC ASSOCIATION C1 W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA. LOS ANGELES ADDICT TREATMENT RES CTR,LOS ANGELES,CA. UNIV CALIF LOS ANGELES,DEPT PSYCHIAT & BIOBEHAV SCI,LOS ANGELES,CA 90024. RP Compton, PA (reprint author), UNIV CALIF LOS ANGELES,INST NEUROPSYCHIAT,DRUG ABUSE RES CTR,1100 GLENDON AVE,SUITE 763,LOS ANGELES,CA 90024, USA. NR 10 TC 30 Z9 31 U1 1 U2 2 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 FEB 15 PY 1996 VL 39 IS 4 BP 302 EP 304 DI 10.1016/0006-3223(95)00476-9 PG 3 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA TW730 UT WOS:A1996TW73000012 PM 8645779 ER PT J AU Subramaniam, M Frenette, PS Saffaripour, S Johnson, RC Hynes, RO Wagner, DD AF Subramaniam, M Frenette, PS Saffaripour, S Johnson, RC Hynes, RO Wagner, DD TI Defects in hemostasis in P-selectin-deficient mice SO BLOOD LA English DT Article ID GRANULE MEMBRANE-PROTEIN; TUMOR NECROSIS FACTOR; WEIBEL-PALADE BODIES; ACTIVATED PLATELETS; MONOCLONAL-ANTIBODY; SHWARTZMAN REACTION; ENDOTHELIAL-CELLS; PLASMA-MEMBRANE; ADHESION; GMP-140 AB Recently, our laboratory showed that platelets, like leukocytes, roll on activated endothelium expressing P-selectin, thus suggesting a role for P-selectin in hemostasis (Frenette et al, Proc Natl Acad Sci USA 92:7450, 1995). We report here that the P-selectin-deficient mice show a 40% prolongation of the bleeding time on amputation of the tip of the tail. Moreover, defective hemostasis was observed in a local Shwartzman-like reaction induced by skin injections of lipopolysaccharide followed by tumor necrosis factor-alpha in the P-selectin-deficient mice. The hemorrhagic lesions, quantitated both macroscopically and microscopically, were twofold larger in the P-selectin-deficient mice. This was also confirmed by measuring the radioactivity in the skin using chromium-labeled red blood cells, Therefore, it is evident that P-selectin plays a role in hemostasis as suggested by its support of platelet rolling. (C) 1996 by The American Society of Hematology. C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. MIT,HOWARD HUGHES MED INST,CAMBRIDGE,MA 02139. MIT,CTR CANC RES,DEPT BIOL,CAMBRIDGE,MA 02139. SCHERING PLOUGH CORP,RES INST,LAFAYETTE,NJ. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RI Frenette, Paul/J-8272-2012 FU NHLBI NIH HHS [P01 HL41484, R01 HL41002, R01 HL53756] NR 41 TC 147 Z9 151 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD FEB 15 PY 1996 VL 87 IS 4 BP 1238 EP 1242 PG 5 WC Hematology SC Hematology GA TV523 UT WOS:A1996TV52300005 PM 8608210 ER PT J AU Alsina, M Boyce, B Devlin, RD Anderson, JL Craig, F Mundy, GR Roodman, GD AF Alsina, M Boyce, B Devlin, RD Anderson, JL Craig, F Mundy, GR Roodman, GD TI Development of an in vivo model of human multiple myeloma bone disease SO BLOOD LA English DT Article ID HUMAN MARROW CULTURES; CELLS; INTERLEUKIN-1; GROWTH; MECHANISMS; RESORPTION; SECRETION; SEVERITY; CYTOKINE; MICE AB Osteolytic bone destruction and its complications, bone pain, pathologic fractures, and hypercalcemia, are a major source of morbidity and mortality in patients with multiple myeloma. The bone destruction in multiple myeloma is due to increased osteoclast (OCL) activity and decreased bone formation in areas of bone adjacent to myeloma cells. The mechanisms underlying osteolysis in multiple myeloma in vivo are unclear. We used a human plasma cell leukemia cell line, ARH-77, that has disseminated growth in mice with severe combined immunodeficiency (SCID) and expresses IgG kappa, as a model for human multiple myeloma. SCID mice were irradiated with 400 rads and mice were injected either with 10(6) ARH-77 cells intravenously (ARH-77 mice) or vehicle 24 hours after irradiation. Development of bone disease was assessed by blood ionized calcium levels, x-rays, and histology. All ARH-77, but none of control mice that survived irradiation, developed hind limb paralysis 28 to 35 days after injection and developed hypercalcemia (1.35 to 1.46 mmol/ L) a mean of 5 days after becoming paraplegic. Lytic bone lesions were detected using x-rays in all the hypercalcemic mice examined. No lytic lesions or hypercalcemia developed in the controls. Controls or ARH-77 mice, after developing hypercalcemia, were then killed and bone marrow plasma from the long bones was obtained, concentrated, and assayed for bone-resorbing activity. Bone marrow plasma from ARH-77 mice induced significant bone resorption in the fetal rat long bone resorption assay when compared with controls (percentage of total Ca-45 released = 35% +/- 4% v 11% +/- 1%). Histologic examination of tissues from the ARH-77 mice showed infiltration of myeloma cells in the liver and spleen and marked infiltration in vertebrae and long bones, with loss of bony trabeculae and increased OCL numbers. Interestingly, cultures of ARH-77 mouse bone marrow for early OCL precursors (colony-forming unit-granulocyte-macrophage [CFU-GM]) showed a threefold increase in CFU-GM from ARH-77 marrow versus controls (185 +/- 32 v 40 +/- 3 per 2 x 10(5) cells plated). Bone-resorbing human and murine cytokines such as interleukin-6 (IL-6), IL-1 alpha or beta, TGF alpha, lymphotoxin, and TNF alpha were not significantly increased in ARH-77 mouse sera or marrow plasma, compared with control mice, although ARH-77 cells produce IL-6 and lymphotoxin in vitro. Conditioned media from ARH-77 cells induced significant bone resorption in the fetal rat long bone resorption assay when compared with untreated media (percentage of total Ca-45 released = 22% +/- 2% v 11% +/- 1%). This effect was not blocked by anti-IL-6 or antilymphotoxin (percentage of total Ca-45 released = 19% +/- 1% and 22% +/- 1%, respectively). Thus, we have developed a model of human multiple myeloma bone disease that should be very useful to dissect the pathogenesis of the bone destruction in multiple myeloma. (C) 1996 by The American Society of Hematology. C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV HEMATOL,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV ENDOCRINOL,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT PATHOL,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. FU NCI NIH HHS [K12 CA01723, CA-40035]; NIADDK NIH HHS [AM35188] NR 24 TC 67 Z9 69 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD FEB 15 PY 1996 VL 87 IS 4 BP 1495 EP 1501 PG 7 WC Hematology SC Hematology GA TV523 UT WOS:A1996TV52300035 PM 8608240 ER PT J AU Wadler, S Yeap, B Vogl, S Carbone, P AF Wadler, S Yeap, B Vogl, S Carbone, P TI Randomized trial of initial therapy with melphalan versus cisplatin-based combination chemotherapy in patients with advanced ovarian carcinoma - Initial and long term results - Eastern cooperative oncology group study E2878 SO CANCER LA English DT Article DE ovarian carcinoma; melphalan; cisplatin; borderline tumor; ovary ID CANCER; CYCLOPHOSPHAMIDE; HEXAMETHYLMELAMINE; REGIMENS; EXPERIENCE; ADRIAMYCIN; CHAP-5 AB BACKGROUND. Following surgical debulking, most patients with International Federations of Gynecology and Obstetrics (FIGO) Stage III or IV carcinoma of the ovary receive treatment with combination chemotherapy. However, the optimal postsurgical therapy for ovarian carcinoma remains to be defined. METHODS. To define better the role of initial therapy with a cisplatin-based chemotherapy regimen, the Eastern Cooperative Oncology Group (ECOG) initiated a randomized, Phase III trial, EST 2878, comparing initial therapy with a single, orally administered alkylating agent, melphalan, versus a complex regimen employing cyclophosphamide, hexamethylmelamine, doxorubicin, and cisplatin (CHAD). Women who failed treatment with melphalan were crossed-over to treatment with CHAD minus the cyclophosphamide (HAD). Study endpoints included response to therapy, time to treatment failure, and overall survival. RESULTS. Between October, 1978, and November, 1980, EST 2878 accrued 253 patients with advanced epithelial carcinoma of the ovary. There were 118 eligible patients initially treated with melphalan and 126 with CHAD. Two patients experienced lethal toxicities, including gastrointestinal hemorrhage (1 patient) and neutropenic sepsis (1 patient), and 22 patients experienced life-threatening toxicities, including hematologic toxicity (21 patients) and anaphylaxis (1 patient). Response to treatment and clinical complete response rates were higher in women receiving CHAD (60% and 38%, respectively) versus melphalan (42% and 21%, respectively) (P = 0.037 and P = 0.024, respectively), but these differences were confined to women older than 50 years of age. Likewise, time to treatment failure was significantly longer in women receiving CHAD (P = 0.014), but the difference was again confined to women older than 50 years of age and to women suboptimally debulked at the time of surgery. Survival did not differ between the two arms (median survivals of 17.5 months with initial melphalan therapy and 19.5 months with CHAD), probably because women treated initially with melphalan received salvage therapy with HAD. Twenty-three patients survived longer than 10 years. Among 18 long term survivors who had retrospective pathologic review, 8 had borderline tumors of the ovary. CONCLUSIONS. In women with advanced ovarian cancer, initial therapy with a cisplatin-based combination chemotherapy regimen resulted in higher clinical complete response rates and longer time to failure compared with initial therapy with a single, oral alkylating agent; however, the benefits of this approach were confined to women older than 50 years of age at diagnosis, and there was no significant difference in survival. (C) 1996 American Cancer Society C1 ALBERT EINSTEIN COLL MED,BRONX,NY 10467. DANA FARBER CANC INST,BOSTON,MA 02115. WISCONSIN CLIN CANC CTR,MADISON,WI. FU NCI NIH HHS [CA21115, CA14958, CA23318] NR 25 TC 17 Z9 17 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 FEB 15 PY 1996 VL 77 IS 4 BP 733 EP 742 DI 10.1002/(SICI)1097-0142(19960215)77:4<733::AID-CNCR20>3.3.CO;2-W PG 10 WC Oncology SC Oncology GA TU581 UT WOS:A1996TU58100020 PM 8616766 ER PT J AU Jacoby, RF Marshall, DJ Newton, MA Novakovic, K Tutsch, K Cole, CE Lubet, RA Kelloff, GJ Verma, A Moser, AR Dove, WF AF Jacoby, RF Marshall, DJ Newton, MA Novakovic, K Tutsch, K Cole, CE Lubet, RA Kelloff, GJ Verma, A Moser, AR Dove, WF TI Chemoprevention of spontaneous intestinal adenomas in the Apc (Min) mouse model by the nonsteroidal anti-inflammatory drug piroxicam SO CANCER RESEARCH LA English DT Article ID COLORECTAL-CANCER; NEOPLASIA; MUTATION; MUCOSA AB C57BL/6J-Min/+ mice (n = 56), heterozygous for a nonsense mutation in the Apc gene, sere randomized at weaning to seven groups, including groups treated with piroxicam at 0, 50, 100, and 200 ppm in the AIN93G diet. After only 6 weeks of treatment, intestinal adenomas and aberrant crypt foci were counted, and serum levels of piroxicam and thromboxane B-2 were quantitated. Tumor multiplicity was decreased in a dose-dependent manner from 17.3 +/- 2.7 in the control to 2.1 +/- 1.1 (12%) in the high-dose piroxicam group (P < 0.001). Thromboxane B-2 levels in plasma also decreased monotonically in parallel to the decrease in tumor multiplicity, consistent with the prostaglandin inhibitory effect of piroxicam. The Min mouse model demonstrates that the nonsteroidal anti-inflammatory drug piroxicam has strong biological and therapeutic effects, potentially useful for prevention of the early adenoma stage of tumor development. C1 UNIV WISCONSIN,DEPT MED,DIV GASTROENTEROL,MADISON,WI 53792. UNIV WISCONSIN,DEPT HUMAN ONCOL,MADISON,WI 53792. CTR COMPREHENS CANC,MADISON,WI 53792. WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI 53705. UNIV WISCONSIN,DEPT BIOSTAT,MADISON,WI 53792. NCI,CHEMOPREVENT LAB,DCPC,BETHESDA,MD 20892. UNIV WISCONSIN,MCARDLE LAB CANC RES,MADISON,WI 53706. FU NCI NIH HHS [CA14520, CA59352, CA50585] NR 20 TC 293 Z9 294 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD FEB 15 PY 1996 VL 56 IS 4 BP 710 EP 714 PG 5 WC Oncology SC Oncology GA TV219 UT WOS:A1996TV21900011 PM 8631000 ER PT J AU Anderson, IC Shipp, MA Docherty, AJP Teicher, BA AF Anderson, IC Shipp, MA Docherty, AJP Teicher, BA TI Combination therapy including a gelatinase inhibitor and cytotoxic agent reduces local invasion and metastasis of murine Lewis lung carcinoma SO CANCER RESEARCH LA English DT Article ID CANCER METASTASIS; ANGIOGENESIS AB The efficacy of combination therapy including an oral gelatinase inhibitor (CT1746) and cytotoxic agent was analyzed using the murine Lewis lung carcinoma model. Primary tumors, pulmonary metastases, and sera from tumor-bearing animals had increased gelatinase B activity that was inhibited by CT1746 levels achievable in vivo. The combination of CT1746 and cyclophosphamide (CTX) was significantly more effective than either single agent in delaying local tumor growth (CT1746/CTX, 30.9 +/- 1.7 days; CT1746, 2.6 +/- 0.3 days; CTX, 19.5 +/- 1.1 days; P < .001) and reducing the number and size of pulmonary metastases [CT1746/CTX, 5 +/- 2 (15% metastases > 3 mm); CT1746, 15 +/- 4 (55% > 3 mm); CTX, 11 +/- 3 (63% > 3 mm); no treatment, 24 +/- 5 (62% > 3 mm); P < .001]. These data support the notion of combining matrix metalloproteinase inhibitors and cytotoxic agents to treat certain epithelial malignancies. C1 DANA FARBER CANC INST,DIV PHARMACOL,BOSTON,MA 02115. DANA FARBER CANC INST,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. CELLTECH THERAPEUT LTD,SLOUGH,BERKS,ENGLAND. RP Anderson, IC (reprint author), DANA FARBER CANC INST,DIV HEMATOL MALIGNANCYIES,44 BINNEY ST,BOSTON,MA 02115, USA. NR 17 TC 89 Z9 90 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD FEB 15 PY 1996 VL 56 IS 4 BP 715 EP 718 PG 4 WC Oncology SC Oncology GA TV219 UT WOS:A1996TV21900012 PM 8631001 ER PT J AU Bae, I Smith, ML Sheikh, MS Zhan, QM Scudiero, DA Friend, SH OConnor, PM Fornace, AJ AF Bae, I Smith, ML Sheikh, MS Zhan, QM Scudiero, DA Friend, SH OConnor, PM Fornace, AJ TI An abnormality in the p53 pathway following gamma-irradiation in many wild-type p53 human melanoma lines SO CANCER RESEARCH LA English DT Article ID TUMOR-SUPPRESSOR GENE; GROWTH-ARREST; GADD45 GENE; DNA-DAMAGE; PROTEIN; ACTIVATION; RADIATION; CELLS; APOPTOSIS AB DNA-damaging agents such as ionizing radiation (IR) activate the tumor suppressor p53, and, in turn, p53 transactivates a number of downstream effector genes such as GADD45, CIP1/WAF1, and MDM2. The induction of these downstream genes following IR appears to be strictly dependent upon the presence of wild-type functional p53 known to evoke G(1) arrest. In this study, we characterized 56 cell lines from 9 different tumor types viith predetermined p53 genotype by measuring the induction of GADD45, CIP1/WAF1, and MDM2 relative mRNA levels after IR. A higher fraction of melanoma lines had wild-type (wt) p53 (5/8, or 63%) compared to the nonmelanoma lines (11/48, or 23%). Most wt p53 (nonmelanoma) cell lines (11/12, or 92%) showed clear induction of both GADD45 and CIP1/WAF1. On the other hand, many wt p53 melanoma lines (4/5, or 80%) showed normal induction of CIP1/WAF1, but little or no induction of GADD45. Despite this defect in GADD45 induction, we found that all wt p53 melanoma lines exhibited strong G(1) arrest and increased levels of p53 protein after IR. The results demonstrated that radiation-induced G(1) arrest could occur by the p53-CIP1/WAF1 pathway without appreciable induction of GADD45 in melanoma lines. Time course experiments demonstrated prolonged induced expression of CIP1/WAF1 mRNA transcripts in melanoma lines in which GADD45 induction was lacking, suggesting some sort of compensatory mechanism involving CIP1/WAF1, in cell lines with defective GADD45 induction. We could reproduce this compensatory effect in RKO colon carcinoma cells in which GADD45 expression was blocked by constitutive antisense vectors. These findings reveal that defective induction of GADD45 following IR is common in human melanoma cell lines. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MOLEC PHARMACOL LAB,NIH,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,FREDERICK,MD 21702. MASSACHUSETTS GEN HOSP,CTR CANC,BOSTON,MA 02129. RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X NR 42 TC 68 Z9 77 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD FEB 15 PY 1996 VL 56 IS 4 BP 840 EP 847 PG 8 WC Oncology SC Oncology GA TV219 UT WOS:A1996TV21900033 PM 8631022 ER PT J AU Salmeron, A Ahmad, TB Carlile, GW Pappin, D Narsimhan, RP Ley, SC AF Salmeron, A Ahmad, TB Carlile, GW Pappin, D Narsimhan, RP Ley, SC TI Activation of MEK-1 and SEK-1 by Tpl-2 proto-oncoprotein, a novel MAP kinase kinase kinase SO EMBO JOURNAL LA English DT Article DE ERK; MAP kinase; oncogene; SAP kinase; Tpl-2 ID T-CELL LYMPHOMAS; SACCHAROMYCES-CEREVISIAE; COT PROTOONCOGENE; GROWTH-FACTORS; C-MYC; EXPRESSION; RAF; GENE; PHOSPHORYLATION; PURIFICATION AB The Tpl-2 protein serine/threonine kinase was originally identified, in a C-terminally deleted form, as the product of an oncogene associated with the progression of Moloney murine leukemia virus-induced T cell lymphomas in rats. The kinase domain of Tpl-2 is homologous to the Saccharomyces cerevisiae gene product, STE11, which encodes a MAP kinase kinase kinase. This suggested that Tpl-2 might have a similar activity. Consistent with this hypothesis, immunoprecipitated Tpl-2 and Tpl-2 Delta C (a C-terminally truncated mutant) phosphorylated and activated recombinant fusion proteins of the mammalian MAP kinase kinases, MEK-1 and SEK-1, in vitro. Furthermore, transfection of Tpl-2 into COS-1 cells or Jurkat T cells, markedly activated the MAP kinases, ERK-1 and SAP kinase (JNK), which are substrates for MEK-1 and SEK-1, respectively, Tpl-2, therefore, is a MAP kinase kinase kinase which can activate two MAP kinase pathways. After Raf and Mos, Tpl-2 is the third serine/threonine oncoprotein kinase that has been shown to function as a direct activator of MEK-1. C1 NATL INST MED RES,DIV CELLULAR IMMUNOL,LONDON NW7 1AA,ENGLAND. IMPERIAL CANC RES FUND,PROT SEQUENCING LAB,LONDON WC2A 3PX,ENGLAND. DANA FARBER CANC INST,BOSTON,MA 02115. OI Pappin, Darryl/0000-0002-8981-8401 NR 61 TC 246 Z9 249 U1 0 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD FEB 15 PY 1996 VL 15 IS 4 BP 817 EP 826 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA TX610 UT WOS:A1996TX61000013 PM 8631303 ER PT J AU Kang, JX Leaf, A AF Kang, JX Leaf, A TI Protective effects of free polyunsaturated fatty acids on arrhythmias induced by lysophosphatidylcholine or palmitoylcarnitine in neonatal rat cardiac myocytes SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE lysophosphatidylcholine; acylcarnitine; fibrillation; fatty acid; excitability; antiarrhythmic ID CANINE PURKINJE-FIBERS; ISCHEMIC-HEART; MEMBRANE DYSFUNCTION; VENTRICULAR MYOCYTES; MYOCARDIUM; LYSOPHOSPHOGLYCERIDES; ACCUMULATION; SARCOLEMMA; CA-2+; LYSOPHOSPHOLIPIDS AB Cultured, spontaneously beating, neonatal rat cardiac myocytes were used to examine the effects of various free fatty acids added to the medium perfusing the cells on lysophosphatidylcholine (LPC)- or acylcarnitine-induced arrhythmias. Perfusion of the cells with LPC or palmitoylcarnitine (2-10 mu M) induced sustained tachyrhythmia with episodes of spasmodic contractures and fibrillation. Free PUFA (10-15 mu M) including eicosapentaenoic acid (EPA, 20:5n-3), docosahexaenoic acid (DHA, 22:6n-3), mu-linolenic acid (18:3n-3), arachidonic acid (AA, 20:4n-6) and linoleic acid (18:2n-6) were able to effectively prevent as well as terminate the LPC or acylcarnitine-induced arrhythmias. In contrast, monounsaturated oleic acid (18:1n-9) and saturated stearic acid (18:0) did not have such effects. The protective effects of the polyunsaturated fatty acids (PUFA) could be reversed by cell perfusion with delipidated bovine serum albumin. To determine the potential primary action by which the PUFA exert the antiarrhythmic effects, measurements of intracellular Ca2+ levels and the response of the cells to electrical pacing in the absence or presence of the PUFA were performed and the effects of verapamil (a L-type Ca2+ channel blocker), tetrodotoxin (a Na+ channel blocker) and Ca2+ ionophore A23187 on the cell contraction and the cytosolic Ca2+ levels were compared with that of the PUFA. Results suggest that an inhibitory effect on the electrical automaticity/excitability of the cardiac myocyte rather than a reduction in cytosolic Ca2+ underlie the protective effects of PUFA. In conclusion, free PUFAs are able to effectively protect the cardiac myocytes against the arrhythmias induced by low concentrations of lysophosphatidylcholine or palmitoylcarnitine. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. VET ADM MED CTR W ROXBURY,BOSTON,MA 02132. FU NIDDK NIH HHS [R01-DK 38165] NR 44 TC 101 Z9 105 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 FEB 15 PY 1996 VL 297 IS 1-2 BP 97 EP 106 DI 10.1016/0014-2999(95)00701-6 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TX428 UT WOS:A1996TX42800015 PM 8851173 ER PT J AU Stanton, TB Trott, DJ Lee, JI McLaren, AJ Hampson, DJ Paster, BJ Jensen, NS AF Stanton, TB Trott, DJ Lee, JI McLaren, AJ Hampson, DJ Paster, BJ Jensen, NS TI Differentiation of intestinal spirochaetes by multilocus enzyme electrophoresis analysis and 16S rRNA sequence comparisons SO FEMS MICROBIOLOGY LETTERS LA English DT Article DE Serpulina; Brachyspira; Treponema; spirochaete; 16S rRNA; multilocus enzyme electrophoresis ID HYODYSENTERIAE COMB-NOV; TREPONEMA-HYODYSENTERIAE; GEN-NOV; SYSTEMATICS; SPIROCHETE; INNOCENS; DYSENTERY; SERPULA AB Multilocus enzyme electrophoresis (MEE) analysis and comparisons of nearly complete 16S rRNA gene sequences (1416 nucleotide positions) were used to evaluate phylogenetic relationships among Serpulina hyodysenteriae strain, B78(T), S. innocens strain B256(T), Brachyspira Aalborgi strain 513A(T), and eight uncharacterised strains of swine, avian, and human intestinal spirochaetes, From MEE analysis, nine strains could be assigned to five groups containing other intestinal spirochaetes (genetic distances between groups = 0.6-0.9). Chicken spirochaete strain C1 and B. aalborgi 513A(T) represented unique electrophoretic types and formed their own MEE groups. Despite MEE differences, the 11 strains had highly similar (96.3-99.9%) 165 rRNA sequences. These findings point out limitations of both MEE analysis and 16S rRNA sequence comparisons when used as solitary techniques for classifying intestinal spirochaetes related to Brachyspira/Serpulina species. C1 MURDOCH UNIV,SCH VET STUDIES,MURDOCH,WA 6150,AUSTRALIA. FORSYTH DENT CTR,BOSTON,MA 02115. RP Stanton, TB (reprint author), USDA,NATL ANIM DIS CTR,ARS,POB 70,AMES,IA 50010, USA. RI Hampson, David/A-9464-2008 OI Hampson, David/0000-0002-7729-0427 NR 25 TC 35 Z9 35 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1097 J9 FEMS MICROBIOL LETT JI FEMS Microbiol. Lett. PD FEB 15 PY 1996 VL 136 IS 2 BP 181 EP 186 PG 6 WC Microbiology SC Microbiology GA TY901 UT WOS:A1996TY90100013 PM 8869502 ER PT J AU Marsischky, GT Filosi, N Kane, MF Kolodner, R AF Marsischky, GT Filosi, N Kane, MF Kolodner, R TI Redundancy of Saccharomyces cerevisiae MSH3 and MSH6 in MSH2-dependent mismatch repair SO GENES & DEVELOPMENT LA Russian DT Article DE Cancer; mutagenesis; mismatch repair; mutS; MSH2; MSH3; MSH6; Saccharomyces cerevisiae ID MEIOTIC GENE CONVERSION; COLORECTAL-CANCER; DNA; MUTATIONS; HOMOLOGS; YEAST; MUTL AB Saccharomyces cerevisiae encodes six genes, MSH1-6, which encode proteins related to the bacterial MutS protein. In this study the role of MSH2, MSH3, and MSH6 in mismatch repair has been examined by measuring the rate of accumulating mutations and mutation spectrum in strains containing different combinations of msh2, msh3, and msh6 mutations and by studying the physical interaction between the MSH2 protein and the MSH3 and MSH6 proteins. The results indicate that S. cerevisiae has two pathways of MSH2-dependent mismatch repair: one that recognizes single-base mispairs and requires MSH2 and MSH6, and a second that recognizes insertion/deletion mispairs and requires a combination of either MSH2 and MSH6 or MSH2 and MSH3. The redundancy of MSH3 and MSH6 explains the greater prevalence of hmsh2 mutations in HNPCC families and suggests how the role of hmsh3 and hmsh6 mutations in cancer susceptibility could be analyzed. C1 DANA FARBER CANC INST,CHARLES A DANA DIV HUMAN CANC GENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. FU NCI NIH HHS [CA06516]; NIAID NIH HHS [AI28691]; NIGMS NIH HHS [GM50006] NR 57 TC 420 Z9 429 U1 1 U2 37 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 FEB 15 PY 1996 VL 10 IS 4 BP 407 EP 420 DI 10.1101/gad.10.4.407 PG 14 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA TY965 UT WOS:A1996TY96500004 PM 8600025 ER PT J AU Graham, KB Berger, JW Patalano, VJ Kunzweiler, TP AF Graham, KB Berger, JW Patalano, VJ Kunzweiler, TP TI Cost of care and severity of conditions in patients presenting to a large, urban ophthalmic emergency department SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,CAMBRIDGE,MA 02138. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 1 EP 1 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39700001 ER PT J AU Bochow, TW Abreu, MM AF Bochow, TW Abreu, MM TI Outcomes and cost associated with the management of exudative age-related macular degeneration. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,BOSTON,MA. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 88 EP 88 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39700088 ER PT J AU AlAswad, LA Chu, JL Shields, SR Lee, D Netland, PA AF AlAswad, LA Chu, JL Shields, SR Lee, D Netland, PA TI Inhibition of fibroblast proliferation and enhancement of glaucoma filtration surgery in the rabbit with cytosine arabinoside SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,BOSTON,MA. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 95 EP 95 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39700095 ER PT J AU Igarashi, S Simmons, RB Igarashi, H Montenegro, MH Kasahara, N Yoshida, A Simmons, RJ AF Igarashi, S Simmons, RB Igarashi, H Montenegro, MH Kasahara, N Yoshida, A Simmons, RJ TI Use of trans-conjunctival mitomycin C for internal revision of glaucoma filtration surgery SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEW ENGLAND EYE RES FDN,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. ASAHIKAWA MED COLL,DEPT OPHTHALMOL,ASAHIKAWA,HOKKAIDO,JAPAN. KUSHIRO RED CROSS HOSP,KUSHIRO,JAPAN. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 109 EP 109 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39700109 ER PT J AU Tsuji, K Yoshida, A Ogasawara, H Kato, Y Murakami, N Cheng, HM AF Tsuji, K Yoshida, A Ogasawara, H Kato, Y Murakami, N Cheng, HM TI MRI of optic nerve blood oxygenation in normal and glaucomatous patients SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,HOWE LAB OPHTHALMOL,BOSTON,MA 02114. MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. ASAHIKAWA MED COLL,DEPT OPHTHALMOL,ASAHIKAWA,HOKKAIDO,JAPAN. ASAHIKAWA MED COLL,DEPT RADIOL,ASAHIKAWA,HOKKAIDO,JAPAN. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 139 EP 139 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39700139 ER PT J AU Merchant, A Zhao, Z Medina, C Foster, CS Cantor, H AF Merchant, A Zhao, Z Medina, C Foster, CS Cantor, H TI Mechanism of genetic resistance to HSV-1 induced retinitis in the von Szily mouse model. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 195 EP 195 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39700195 ER PT J AU Lai, ST Swinger, CA Williams, E Kornmehl, E Davis, R Sutphin, J Kraff, M Zheng, W Lai, M AF Lai, ST Swinger, CA Williams, E Kornmehl, E Davis, R Sutphin, J Kraff, M Zheng, W Lai, M TI Surface photorefractive keratectomy for myopia using the Novatec laser - 6 month results of the phase IIa US FDA study SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NOVATEC LASER SYST INC,CARLSBAD,CA. MT SINAI SCH MED,NEW YORK,NY. SURG CTR DESERT,RANCHO MIRAGE,CA. MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,WINSTON SALEM,NC. UNIV IOWA,IOWA CITY,IA. KRAFF EYE INST,CHICAGO,IL. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 230 EP 230 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39700230 ER PT J AU Abad, JC Lim, JE Pepin, A Talamo, JH AF Abad, JC Lim, JE Pepin, A Talamo, JH TI Evaluation of pentoxifylline in the prevention of haze after photorefractive keratectomy (PRK) in the rabbit SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,CORNEA SERV,BOSTON,MA. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 262 EP 262 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39700262 ER PT J AU Delyargyris, EN Kanellopoulos, AJ Pallikaris, IG Donnenfeld, ED Detorakis, E Koufala, K Lambropoulos, J Perry, HD AF Delyargyris, EN Kanellopoulos, AJ Pallikaris, IG Donnenfeld, ED Detorakis, E Koufala, K Lambropoulos, J Perry, HD TI Comparison of postoperative corneal sensation following photorefractive keratectomy and laser in-situ keratomileusis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 TUFTS UNIV,SCH MED,MEDFORD,MA 02155. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BOSTON,MA. NYU,N SHORE UNIV HOSP,MED CTR,MANHASSET,NY. UNIV CRETE,SCH MED,IRAKLION,GREECE. ORASIS EYE CTR,ATHENS,GREECE. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 263 EP 263 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39700263 ER PT J AU Gaudio, AR Miller, S Sandberg, MA AF Gaudio, AR Miller, S Sandberg, MA TI Identifying high-risk patients with age-related macular degeneration SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,BERMAN GUND LAB STUDY RETINAL DEGENERAT,BOSTON,MA. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 518 EP 518 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39700517 ER PT J AU DelaPaz, MA PericakVance, M Haines, J Seddon, JM AF DelaPaz, MA PericakVance, M Haines, J Seddon, JM TI Phenotypic heterogeneity in families with age-related macular degeneration SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 DUKE UNIV,MED CTR,DEPT OPHTHALMOL,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT NEUROL,DURHAM,NC 27710. HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,BOSTON,MA. HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,DEPT NEUROGENET,BOSTON,MA. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 533 EP 533 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39700532 ER PT J AU Tolentino, MJ Miller, JW Gragoudas, ES Flynn, E Connolly, E Chatzistefanou, K Ferrara, N Adamis, AP AF Tolentino, MJ Miller, JW Gragoudas, ES Flynn, E Connolly, E Chatzistefanou, K Ferrara, N Adamis, AP TI Retinal microangiopathy induced by intravitreal injections of VEGF SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 GENENTECH INC,S SAN FRANCISCO,CA 94080. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BOSTON,MA. HARVARD UNIV,CHILDRENS HOSP,SCH MED,BOSTON,MA. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 568 EP 568 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39700567 ER PT J AU Kim, S Tolentino, M Yoshida, A Kuroki, M Adamis, AP AF Kim, S Tolentino, M Yoshida, A Kuroki, M Adamis, AP TI Iris neovascularization and increased retinal VEGF expression in the hypoxic adult rat SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 HARVARD UNIV,CHILDRENS HOSP,SCH MED,BOSTON,MA 02115. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BOSTON,MA 02115. UNIV CHICAGO,PRITZKER SCH MED,MED CTR,CHICAGO,IL 60637. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 574 EP 574 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39700573 ER PT J AU Duh, E Aiello, LP Takagi, C Clermont, A Mori, F King, GL Bursell, SE AF Duh, E Aiello, LP Takagi, C Clermont, A Mori, F King, GL Bursell, SE TI Vascular endothelial growth factor (VEGF) increases retinal vascular permeability in vivo SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 JOSLIN DIABET CTR,BOSTON,MA 02215. BEETHAM EYE INST,BOSTON,MA. HARVARD UNIV,SCH MED,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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 578 EP 578 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39700577 ER PT J AU SchmidtErfurth, U Miller, J Sickerberg, M Strong, A Hoehne, U Fsachi, M Birngruber, R vandenBerg, H Laqua, H Gragoudas, E Zografos, L Bressler, N AF SchmidtErfurth, U Miller, J Sickerberg, M Strong, A Hoehne, U Fsachi, M Birngruber, R vandenBerg, H Laqua, H Gragoudas, E Zografos, L Bressler, N TI Photodynamic therapy of subfoveal choroidal neovascularization using benzoporphyrin derivative: First results of a multi-center trial SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 UNIV LUBECK,HOSP EYE,LUBECK,GERMANY. MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. WILMER EYE INST,PHILADELPHIA,PA. RI Birngruber, Reginald/Q-2342-2016 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 580 EP 580 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39700579 ER PT J AU Kim, RY Hu, LK Flotte, T Gragoudas, ES Young, LHY AF Kim, RY Hu, LK Flotte, T Gragoudas, ES Young, LHY TI Biodistribution of the photosensitizer BPD in the tumor-bearing rabbit eye using fluorescence photometry and angiography SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BOSTON,MA. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 583 EP 583 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39700582 ER PT J AU Weissgold, DJ Hu, LK Gragoudas, ES Young, LHY AF Weissgold, DJ Hu, LK Gragoudas, ES Young, LHY TI Photodynamic therapy (PDT) of pigmented choroidal melanoma via a trans-scleral approach SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BOSTON,MA. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 584 EP 584 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39700583 ER PT J AU Hu, LK Weissgold, DJ Gragoudas, ES Young, LHY AF Hu, LK Weissgold, DJ Gragoudas, ES Young, LHY TI Photodynamic therapy (PDT) of choroidal vasculature via a transscleral approach SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BOSTON,MA. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 588 EP 588 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39700587 ER PT J AU Kim, SI Ng, EWM Kenney, AG Tolentino, MJ Connolly, EJ Gragoudas, ES Miller, JW AF Kim, SI Ng, EWM Kenney, AG Tolentino, MJ Connolly, EJ Gragoudas, ES Miller, JW TI Rat model of subretinal choroidal neovascular membrane formation: Preliminary results SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BOSTON,MA. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 595 EP 595 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39700594 ER PT J AU Reinke, MH Husain, D Miller, JW Gragoudas, ES AF Reinke, MH Husain, D Miller, JW Gragoudas, ES TI Fluorescein angiographic classification of experimental choroidal neovascularization (CNV) in the cynomolgus monkey SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BOSTON,MA. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 596 EP 596 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39700595 ER PT J AU Ljubimov, AV Burgeson, RE Butkowski, RJ Couchman, JR Huang, Z Nesburn, AB Kenney, MC AF Ljubimov, AV Burgeson, RE Butkowski, RJ Couchman, JR Huang, Z Nesburn, AB Kenney, MC TI Retinal basement membrane alterations in human diabetic retinopathy eyes SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 CEDARS SINAI MED CTR,OPHTHALMOL RES LABS,LOS ANGELES,CA 90048. MASSACHUSETTS GEN HOSP EAST,BOSTON,MA. INCSTAR CORP,STILLWATER,OK. UNIV ALABAMA,BIRMINGHAM,AL 35294. RI Ljubimov, Alexander/E-5883-2013 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 631 EP 631 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39700630 ER PT J AU Guimaraes, FC Rubin, PAD Cruz, AAV AF Guimaraes, FC Rubin, PAD Cruz, AAV TI Quantification of extraocular muscles (EOMs) from coronal CT scans of different subtypes of Graves' orbitopathy. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 UNIV SAO PAULO,SCH MED RIBEIRAO PRETO,DEPT OPHTHALMOL,BR-05508 SAO PAULO,BRAZIL. HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,OCULOPLAST SERV,CAMBRIDGE,MA 02138. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 743 EP 743 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39700741 ER PT J AU Nathanson, JA Scanlon, C McKee, M Ellis, D AF Nathanson, JA Scanlon, C McKee, M Ellis, D TI Hormone modulation of the membrane Na+ pump in mammalian secretory epithelium and retina SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,NEUROPHARMACOL RES LAB,BOSTON,MA 02129. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 880 EP 880 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39700878 ER PT J AU Aiello, LP Pu, X Zhen, ZY Park, DJ Newsome, WP King, GL AF Aiello, LP Pu, X Zhen, ZY Park, DJ Newsome, WP King, GL TI Vascular endothelial growth factor (VEGF) activation of phospholipase C gamma, PI3-kinase & PKC pathways and their effects on endothelial cell proliferation SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,BEETHAM EYE INST,BOSTON,MA. HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,BOSTON,MA. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 946 EP 946 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39700944 ER PT J AU Douros, S Aiello, LM Kopple, A Bursell, SE Smith, F King, BL Chu, J Chin, J King, GL AF Douros, S Aiello, LM Kopple, A Bursell, SE Smith, F King, BL Chu, J Chin, J King, GL TI Characterization of diabetic retinopathy in an Asian-American community clinic. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,BOSTON,MA. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 991 EP 991 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39700989 ER PT J AU Cheng, HM Xiong, J Nakamura, J Arruda, J Kwong, K AF Cheng, HM Xiong, J Nakamura, J Arruda, J Kwong, K TI Acetazolamide-aided MRI of optic nerve blood oxygenation SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,HOWE LAB OPHTHALMOL,BOSTON,MA 02114. MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 1008 EP 1008 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39701006 ER PT J AU Husain, D Miller, JW Michaud, N Flotte, TJ Kramer, M Gragoudas, ES AF Husain, D Miller, JW Michaud, N Flotte, TJ Kramer, M Gragoudas, ES TI Long term effect of photodynamic therapy (PDT) using liposomal benzoporphyrin derivative (BPD) on experimental choroidal neovascularization (CNV) and normal retina and choroid. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 1013 EP 1013 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39701011 ER PT J AU Miller, JW SchmidtErfurth, U Sickenberg, M Gragoudas, ES Bressler, NM Strong, HA Hoehne, U Fsadni, M Lane, AM vandenBergh, H Laqua, H Zografos, L Piquet, B AF Miller, JW SchmidtErfurth, U Sickenberg, M Gragoudas, ES Bressler, NM Strong, HA Hoehne, U Fsadni, M Lane, AM vandenBergh, H Laqua, H Zografos, L Piquet, B TI Selected angiographic findings following photodynamic therapy of subfoveal choroidal neovascularization SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,PDT AMD STUDY GRP,BOSTON,MA. UNIV LUBECK,HOSP EYE,W-2400 LUBECK,GERMANY. HOP JULES GONIN,LAUSANNE,SWITZERLAND. WILMER READING CTR,BALTIMORE,MD. QLT PHOTOTHERAPEUT,VANCOUVER,BC,CANADA. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 1014 EP 1014 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39701012 ER PT J AU Lane, AM Egan, KM Gragoudas, ES AF Lane, AM Egan, KM Gragoudas, ES TI Intraocular melanomas diagnosed before age 30 SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,RETINA SERV,BOSTON,MA. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 1098 EP 1098 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39701096 ER PT J AU Chynn, EW Sibayan, SA Latina, MA Netland, PA Kini, MM AF Chynn, EW Sibayan, SA Latina, MA Netland, PA Kini, MM TI A comparison of intraocular pressure response and complications after Ahmed glaucoma valve implantation, with and without concurrent vitrectomy SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,BOSTON,MA. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 1180 EP 1180 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39701178 ER PT J AU Abreu, MM Sierra, RA Lee, D Netland, PA AF Abreu, MM Sierra, RA Lee, D Netland, PA TI Peripheral iridectomy with frequency doubled Nd:YAG laser versus argon laser in animal eyes SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,BOSTON,MA. FIBEROPT FABRICAT INC,E LONGMEADOW,MA. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 1190 EP 1190 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39701188 ER PT J AU Medina, C Merchant, A Christen, W Power, W Foster, CS AF Medina, C Merchant, A Christen, W Power, W Foster, CS TI Intraocular pressure (IOP) elevation following periorbital triamcinolone injection in patients with intermediate uveitis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,SERV IMMUNOL,BOSTON,MA. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 1694 EP 1694 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39701692 ER PT J AU Coulter, E Rustgi, A Defoe, D Smith, S Kucherlapati, R Marcus, D AF Coulter, E Rustgi, A Defoe, D Smith, S Kucherlapati, R Marcus, D TI Abnormalities of the retinal pigment epithelium in transgenic mice with ACP gene modification SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 MED COLL GEORGIA,DEPT OPHTHALMOL,AUGUSTA,GA 30912. MED COLL GEORGIA,DEPT CELLULAR BIOL & ANAT,AUGUSTA,GA 30912. MASSACHUSETTS GEN HOSP,GI UNIT,BOSTON,MA 02114. E TENNESSEE STATE UNIV,JOHNSON CITY,TN. ALBERT EINSTEIN COLL MED,DEPT MOLEC GENET,BRONX,NY. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 1769 EP 1769 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39701767 ER PT J AU Harris, EW Simon, A Eriksson, U Berson, EL Dryja, TP AF Harris, EW Simon, A Eriksson, U Berson, EL Dryja, TP TI Screen for mutations in the gene encoding 11-cis retinol dehydrogenase in patients with retinitis pigmentosa or an allied disease SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BERMAN GUND LAB,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,OCULAR MOLEC GENET INST,BOSTON,MA. LUDWIG INST CANC RES,S-10401 STOCKHOLM,SWEDEN. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 1774 EP 1774 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39701772 ER PT J AU Krzystolik, MG Miller, JW AF Krzystolik, MG Miller, JW TI Choroidal neovascularization after traumatic choroidal ruptures SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,BOSTON,MA. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 1871 EP 1871 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39701869 ER PT J AU Latina, MA Sibayan, SA AF Latina, MA Sibayan, SA TI In vivo selective targeting of trabecular meshwork cells by laser irradiation - A potential treatment for glaucoma SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,WELLMAN LABS,BOSTON,MA. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 1897 EP 1897 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39701895 ER PT J AU Sibayan, SA Latina, MA White, K Flotte, TJ AF Sibayan, SA Latina, MA White, K Flotte, TJ TI Drug-induced apoptosis of trabecular meshwork cells SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,WELLMAN LABS PHOTOMED,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CUTANEOUS BIOL RES CTR,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT DERMATOL,BOSTON,MA. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 2034 EP 2034 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39702032 ER PT J AU Miller, JW AF Miller, JW TI Laser treatment of macular degeneration including new strategies SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BOSTON,MA. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 2050 EP 2050 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39702048 ER PT J AU Wiggs, JL Allingham, RR DelBono, EA Reardon, M Terminassian, M Damji, KF Youn, J Jones, KH PericakVance, MA Haines, JL AF Wiggs, JL Allingham, RR DelBono, EA Reardon, M Terminassian, M Damji, KF Youn, J Jones, KH PericakVance, MA Haines, JL TI The juvenile glaucoma gene on 1q21-q31 is not associated with primary open angle glaucoma (POAG) SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 TUFTS UNIV,SCH MED,NEW ENGLAND MED CTR,MEDFORD,MA 02155. DUKE UNIV,MED CTR,DURHAM,NC 27706. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,MOLEC NEUROGENET UNIT,CAMBRIDGE,MA 02138. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 2071 EP 2071 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39702069 ER PT J AU Allingham, RR Wiggs, JL Damji, KF Youn, J Tallett, DA Jones, KH DelBono, EA Reardon, M Terminassian, M Hames, JL PericakVance, MA AF Allingham, RR Wiggs, JL Damji, KF Youn, J Tallett, DA Jones, KH DelBono, EA Reardon, M Terminassian, M Hames, JL PericakVance, MA TI Genes linked to systemic hypertension (HTN) and maturity onset diabetes of the young (MODY) are not associated with primary open angle glaucoma (POAG) SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 DUKE UNIV,MED CTR,DURHAM,NC 27706. TUFTS UNIV NEW ENGLAND MED CTR,BOSTON,MA 02111. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 2074 EP 2074 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39702072 ER PT J AU Pralea, AM Phillips, JC DelBono, EA Pralea, C Haines, JL Wiggs, JL AF Pralea, AM Phillips, JC DelBono, EA Pralea, C Haines, JL Wiggs, JL TI Genetic linkage analysis of Rieger's syndrome: Evidence for genetic heterogeneity SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 TUFTS UNIV,NEW ENGLAND MED CTR,SCH MED,DEPT OPHTHALMOL,MEDFORD,MA 02155. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,MOLEC NEUROGENET UNIT,CAMBRIDGE,MA 02138. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 2076 EP 2076 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39702074 ER PT J AU Clermont, AC King, GL Takagi, C Lin, YW Bursell, SE AF Clermont, AC King, GL Takagi, C Lin, YW Bursell, SE TI Enhanced endothelin-1 expression and action is responsible for abnormal retinal, hemodynamics in diabetes SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 JOSLIN DIABET CTR,BOSTON,MA 02215. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 2103 EP 2103 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39702101 ER PT J AU Takagi, H Aiello, LP King, GL AF Takagi, H Aiello, LP King, GL TI Identification & characterization of vascular endothelial growth factor receptors (Flt) in retinal pericytes SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 JOSLIN DIABET CTR,BOSTON,MA 02215. BEETHAM EYE INST,BOSTON,MA. HARVARD UNIV,SCH MED,BOSTON,MA. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 2132 EP 2132 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39702130 ER PT J AU Grosskreutz, CL AnandApte, B Terman, B Quinn, TP DAmore, PA AF Grosskreutz, CL AnandApte, B Terman, B Quinn, TP DAmore, PA TI Vascular endothelial growth factor (VEGF) is a chemoattractant for vascular smooth muscle cells (SMC). SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 HARVARD UNIV,CHILDRENS HOSP,SURG RES LAB,BOSTON,MA 02115. MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. WYETH AYERST RES,ONCOL RES,PEARL RIVER,NY. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 2133 EP 2133 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39702131 ER PT J AU To, KW Adamian, M Berson, EL AF To, KW Adamian, M Berson, EL TI Histopathologic study of X-linked cone degeneration SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BERMAN GUND LAB STUDY RETINAL DEGENERAT,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 2260 EP 2260 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39702258 ER PT J AU Mack, HG Sandberg, MA Berson, EL AF Mack, HG Sandberg, MA Berson, EL TI Clinical features of female patients with generalized choroidal sclerosis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BERMAN GUND LAB STUDY RETINAL DEGENERAT,BOSTON,MA. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 2292 EP 2292 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39702290 ER PT J AU Pawlyk, BS Sandberg, MA Berson, EL AF Pawlyk, BS Sandberg, MA Berson, EL TI Foveal cone pigment regeneration in some RP patients with a rhodopsin mutation SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BERMAN GUND LAB STUDY RETINAL DEGENERATIONS,BOSTON,MA. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 2293 EP 2293 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39702291 ER PT J AU Sandberg, MA Berson, EL AF Sandberg, MA Berson, EL TI Foveal glare recovery in RP patients with a rhodopsin mutation SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BERMAN GUND LAB STUDY RETINAL DEGENERAT,BOSTON,MA. NR 2 TC 1 Z9 1 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 2301 EP 2301 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39702299 ER PT J AU Han, YB GutierrezRamos, J Park, JM ORourke, L Planck, SR Rosenbaum, JT AF Han, YB GutierrezRamos, J Park, JM ORourke, L Planck, SR Rosenbaum, JT TI Importance of beta-2 integrins in endotoxin-induced uveitis as determined in genetically altered mice SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 OREGON HLTH SCI UNIV,CASEY EYE INST,PORTLAND,OR 97201. CTR BLOOD RES,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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 2491 EP 2491 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39702488 ER PT J AU Kanellopoulos, AJ Perry, HD Donnenfeld, ED Deliargyris, EN AF Kanellopoulos, AJ Perry, HD Donnenfeld, ED Deliargyris, EN TI Comparison of tropical timolol gel to oral acetazolamide int he prophylaxis of viscoelastic induced ocular hypertension after penetrating keratoplasty SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA. N SHORE UNIV HOSP,MANHASSET,NY. NYU,MED CTR,NEW YORK,NY 10012. TUFTS UNIV,SCH MED,BOSTON,MA 02111. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 2528 EP 2528 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39702531 ER PT J AU Brazitikos, P Bochow, TW DAmico, DJ Hmelar, M Mathis, M Marcellino, G AF Brazitikos, P Bochow, TW DAmico, DJ Hmelar, M Mathis, M Marcellino, G TI Experimental ocular surgery with a high repetition rate erbium-YAG laser SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 DIMOCRITION UNIV TURAKI,ALEXANDROUPOLIS,GREECE. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,RETINA SERV,BOSTON,MA. COHERENT INC,PALO ALTO,CA. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 2628 EP 2628 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39702624 ER PT J AU Colby, KA Adamis, AP AF Colby, KA Adamis, AP TI Prevalence of corneal neovascularization in a general eye service population SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BOSTON,MA. HARVARD UNIV,CHILDRENS HOSP,SCH MED,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 2734 EP 2734 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39702730 ER PT J AU Rowe, SG Hart, L Capaccioli, K Pineda, R Jakobiec, FA Gragoudas, ES AF Rowe, SG Hart, L Capaccioli, K Pineda, R Jakobiec, FA Gragoudas, ES TI Ultrasound biomicroscopy characterization of primary peripheral iris cysts SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DEPT OPHTHALMOL,MASSACHUSETTS EYE & EAR INFIRM,CAMBRIDGE,MA 02138. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 2785 EP 2785 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39702787 ER PT J AU Choi, JC Bstandig, S Rumelt, S Iwamoto, MA Rubin, PAD Shore, JW AF Choi, JC Bstandig, S Rumelt, S Iwamoto, MA Rubin, PAD Shore, JW TI Porous polyethylene sheet implant with a barrier surface: A rabbit study SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 OPHTHALM CONSULTANTS BOSTON,BOSTON,MA. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 2846 EP 2846 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39702846 ER PT J AU Nicacus, TE Warner, M Remulla, HD Rubin, PAD AF Nicacus, TE Warner, M Remulla, HD Rubin, PAD TI The effect of sucralfate and basic fibroblast growth factor on fibrovascular ingrowth into hydroxyapatite and porous polyethylene alloplastic implants using a novel rabbit model SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. HARVARD UNIV,SCH MED,CHILDRENS HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 2850 EP 2850 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39702852 ER PT J AU Nguyen, QD Vorwerk, CK Dreyer, EB AF Nguyen, QD Vorwerk, CK Dreyer, EB TI Retinal ganglion cells from mice deficient in neuronal nitric oxide synthase exhibit normal calcium fluxes in response to glutamate SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BOSTON,MA. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 2900 EP 2900 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39702896 ER PT J AU Kenney, MC Burgeson, RE Butkowski, RJ Ljubimov, AV AF Kenney, MC Burgeson, RE Butkowski, RJ Ljubimov, AV TI Extracellular matrix of human keratoconus corneas SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 CEDARS SINAI MED CTR,OPHTHALMOL RES LABS,LOS ANGELES,CA 90048. MASSACHUSETTS GEN HOSP,BOSTON,MA. INCSTAR CORP,MINNEAPOLIS,MN. RI Ljubimov, Alexander/E-5883-2013 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 2987 EP 2987 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39702985 ER PT J AU Burk, SE Benson, MD Jakobiec, FA Ceisler, E Mukai, S AF Burk, SE Benson, MD Jakobiec, FA Ceisler, E Mukai, S TI Vitreous amyloidosis without a mutation in the transthyretin gene SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. INDIANA UNIV,MED CTR,INDIANAPOLIS,IN. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 3029 EP 3029 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39703025 ER PT J AU Pounaras, CJ Miller, JW Gragoudas, ES Husain, D Munoz, JL COnnolly, EJ Tolentino, MJ Kaplan, M Kuroki, M Adamis, AP AF Pounaras, CJ Miller, JW Gragoudas, ES Husain, D Munoz, JL COnnolly, EJ Tolentino, MJ Kaplan, M Kuroki, M Adamis, AP TI Upregulation of retinal VEGF expression with ischemic hypoxia and reversal with hyperoxia or scatter photocoagulation in a monkey model. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 UNIV HOSP GENEVA,EYE DEPT,GENEVA,SWITZERLAND. MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. HARVARD UNIV,CHILDRENS HOSP,BOSTON,MA 02115. HARVARD UNIV,SCH MED,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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 3037 EP 3037 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39703033 ER PT J AU Pineda, R Navon, SE AF Pineda, R Navon, SE TI Post-traumatic endophthalmitis: Analysis of injury characteristics and management regimen in a New England population. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,CAMBRIDGE,MA 02138. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 3049 EP 3049 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39703045 ER PT J AU Haimovici, R Mukai, S Haynie, GD Thomas, MA Meredith, TA Gragoudas, ES AF Haimovici, R Mukai, S Haynie, GD Thomas, MA Meredith, TA Gragoudas, ES TI Rhegmatogenous retinal detachment in eyes with uveal melanoma SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 BOSTON UNIV,SCH MED,BOSTON,MA 02215. MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. RETINA CONSULTANTS LTD,FARGO,ND. BARNES RETINA INST,ST LOUIS,MO. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 3106 EP 3106 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39703102 ER PT J AU Regan, S Egan, KM Hart, L Gragoudas, ES AF Regan, S Egan, KM Hart, L Gragoudas, ES TI Color Doppler imaging of untreated and irradiated choroidal melanomas SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 MASSACHUSETTS EYE & EAR INFIRM,RETINA SERV,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 3109 EP 3109 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39703105 ER PT J AU Li, T Snyder, WK Dryja, TP AF Li, T Snyder, WK Dryja, TP TI Transgenic mice carrying dominant rhodopsin mutations T17M or P347S: Evidence that mutant rhodopsin may interfere with disc assembly SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BERMAN GUND LAB STUDY RETINAL DEGENERAT,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,OCULAR MOLEC GENET INST,BOSTON,MA. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 3191 EP 3191 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39703187 ER PT J AU Mukai, S Williams, BO Mulligan, G Mercer, K Jacks, T AF Mukai, S Williams, BO Mulligan, G Mercer, K Jacks, T TI Persistent hyperplastic primary vitreous in mice with targeted disruption of the p53 gene SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 MIT,CTR CANC RES,CAMBRIDGE,MA 02139. HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. RI Williams, Bart/A-3539-2013 OI Williams, Bart/0000-0002-5261-5301 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 3196 EP 3196 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39703192 ER PT J AU Rizzo, JF Miller, S Denison, T Hemdon, T Wyatt, JL AF Rizzo, JF Miller, S Denison, T Hemdon, T Wyatt, JL TI Electrically-evoked cortical potentials from stimulation of rabbit retina with a microfabricated electrode array SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,CAMBRIDGE,MA 02138. MIT,LINCOLN LABS,CAMBRIDGE,MA 02139. NR 0 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 3230 EP 3230 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39703226 ER PT J AU Samiy, N Ng, EWM Ruoff, K Baker, AS DAmico, DJ AF Samiy, N Ng, EWM Ruoff, K Baker, AS DAmico, DJ TI Pneumococcal endophthalmitis in the rat: Clinical and histological characterization SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,RETINA & INFECT DIS SERV,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT OPHTHALMOL,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,CLIN MICROBIOL LAB,BOSTON,MA. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 3556 EP 3556 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39703550 ER PT J AU Ng, EWM Samiy, N Ruoff, K Paton, B Hooper, DC DAmico, DJ Baker, AS AF Ng, EWM Samiy, N Ruoff, K Paton, B Hooper, DC DAmico, DJ Baker, AS TI Ocular pharmacokinetics of oral CP-99,219 in a rabbit model of Staphylococcus epidermidis endophthalmitis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 MASSACHUSETTS EYE & EAR INFIRM,RETINA SERV,BOSTON,MA 02114. MASSACHUSETTS EYE & EAR INFIRM,INFECT DIS SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT OPHTHALMOL,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,CLIN MICROBIOL LAB,BOSTON,MA. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 3566 EP 3566 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39703560 ER PT J AU Bhisitkul, RB Vorwerk, CK Heng, JE Vinals, AF Dreyer, EB AF Bhisitkul, RB Vorwerk, CK Heng, JE Vinals, AF Dreyer, EB TI Ethambutol is selectively toxic to retinal ganglion cells in vivo SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,CAMBRIDGE,MA 02138. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 3575 EP 3575 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39703569 ER PT J AU Berger, JW AF Berger, JW TI Micropulsed diode laser retinal photocoagulation: Thermal considerations SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,LASER RES LAB,BOSTON,MA. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 3586 EP 3586 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39703580 ER PT J AU Kim, I Tolentino, MJ Miller, JW Adamis, AP AF Kim, I Tolentino, MJ Miller, JW Adamis, AP TI Constitutive VEGF mRNA expression in the tissues of normal adult eyes SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,CHILDRENS HOSP,BOSTON,MA. HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 3643 EP 3643 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39703637 ER PT J AU Ghiso, N Punglia, R Kuroki, M Adamis, AP AF Ghiso, N Punglia, R Kuroki, M Adamis, AP TI Oxygen-regulated VEGF gene expression is determined by absolute oxygen concentration SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 HARVARD UNIV,CHILDRENS HOSP,SCH MED,BOSTON,MA 02115. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BOSTON,MA. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 3645 EP 3645 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39703639 ER PT J AU Newsome, WP Takagi, H King, GL Aiello, LP AF Newsome, WP Takagi, H King, GL Aiello, LP TI Hypoxia regulates vascular endothelial growth factor receptor KDR/Flk gene expression through adenosine A2 receptors on retinal capillary endothelial cells. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,BOSTON,MA. HARVARD UNIV,SCH MED,BEETHAM EYE INST,BOSTON,MA. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 3646 EP 3646 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39703640 ER PT J AU Punglia, R Kuroki, M Tolentino, MJ Hsu, J Keough, K DAmato, R Adamis, AP AF Punglia, R Kuroki, M Tolentino, MJ Hsu, J Keough, K DAmato, R Adamis, AP TI IGF-1 increases VEGF mRNA and secreted protein in retinal cells SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,CHILDRENS HOSP,BOSTON,MA. HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 3654 EP 3654 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39703648 ER PT J AU Karatza, EC Tolentino, MJ Delori, FC Kim, SI Ng, EWM Canakis, CS Gragoudas, ES Miller, JW AF Karatza, EC Tolentino, MJ Delori, FC Kim, SI Ng, EWM Canakis, CS Gragoudas, ES Miller, JW TI Comparison study of photosensitizer uptake in vitro using liposomal benzoporphyrin derivative (BPD) SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA. HARVARD UNIV,SCH MED,SCHEPENS EYE RES INST,BOSTON,MA. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 3670 EP 3670 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39703664 ER PT J AU Kuroki, M Adamis, AP AF Kuroki, M Adamis, AP TI Oxygen-regulated VEGF gene expression is independent of gp91(phox) in human monocytes SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 HARVARD UNIV,CHILDRENS HOSP,SCH MED,BOSTON,MA 02115. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BOSTON,MA. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 3675 EP 3675 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39703669 ER PT J AU McKee, M Nathanson, JA AF McKee, M Nathanson, JA TI Innervation of ciliary muscle in glaucoma: Neurofilament protein defines an alteration consistent with the distribution of no synthase. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,NEUROPHARMACOL RES LAB,BOSTON,MA 02129. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 3787 EP 3787 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39703781 ER PT J AU Yoo, SH Vorwerk, CK Miller, JW Husain, D Dreyer, EB AF Yoo, SH Vorwerk, CK Miller, JW Husain, D Dreyer, EB TI Neuronal nitric oxide synthase is necessary for the full expression of excitotoxicity in the retina SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 3817 EP 3817 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39703811 ER PT J AU Siegner, SW Giovanoni, D Erickson, KA Netland, PA AF Siegner, SW Giovanoni, D Erickson, KA Netland, PA TI Distribution of verapamil and norverapamil in the eye and the systemic circulation following topical administration of verapamil in rabbits SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 3849 EP 3849 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39703843 ER PT J AU Ciulla, TA Oberoi, A Pawlyk, BS Miller, JW Sandberg, MA AF Ciulla, TA Oberoi, A Pawlyk, BS Miller, JW Sandberg, MA TI Retinal artery vasospasm and the rabbit electroretinogram SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,RETINA SERV,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BERMAN GUND LAB STUDY RETINAL DEGENERAT,BOSTON,MA. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 3883 EP 3883 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39703877 ER PT J AU Netland, PA Siegner, SW Harris, A AF Netland, PA Siegner, SW Harris, A TI Color doppler ultrasound measurements following topical and retrobulbar epinephrine in the primate SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,BOSTON,MA 02114. INDIANA UNIV,SCH MED,INDIANAPOLIS,IN. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 3884 EP 3884 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39703878 ER PT J AU Dean, JM Clermont, AC Takagi, C Mori, F Bursell, SE AF Dean, JM Clermont, AC Takagi, C Mori, F Bursell, SE TI Effect of an angiotensin converting enzyme inhibitor (Captopril) on retinal hemodynamics in streptozotocin-induced diabetic rats SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 JOSLIN DIABET CTR,BOSTON,MA 02215. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 3890 EP 3890 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39703884 ER PT J AU Igarashi, H Yoshida, A Kanno, H Kato, Y Sakagami, K Cheng, HM AF Igarashi, H Yoshida, A Kanno, H Kato, Y Sakagami, K Cheng, HM TI Stimulatory effects of basic fibroblast growth factor on glycolysis and hexose monophosphate shunt in the rabbit cornea SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 ASAHIKAWA MED COLL,DEPT OPHTHALMOL,ASAHIKAWA,HOKKAIDO,JAPAN. HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA. KUSHIRO RED CROSS HOSP,KUSHIRO,JAPAN. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 4003 EP 4003 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39703997 ER PT J AU Epstein, HF Ma, L Walch, ET Balasubramanyam, A Avruch, J Dunne, PWD AF Epstein, HF Ma, L Walch, ET Balasubramanyam, A Avruch, J Dunne, PWD TI Interactions of the myotonic dystrophy protein kinase. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 BAYLOR COLL MED,DEPT NEUROL,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT OPHTHALMOL,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT MED,HOUSTON,TX 77030. MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 4249 EP 4249 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39704243 ER PT J AU Takagi, C Bursell, SE Clermont, AC Takagi, H Jirousek, MR King, GL AF Takagi, C Bursell, SE Clermont, AC Takagi, H Jirousek, MR King, GL TI Mimicking of abnormal retinal hemodynamics in diabetes by enhancing DAG-PKC levels in the retina of non-diabetic SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 JOSLIN DIABET CTR,BOSTON,MA 02215. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 4291 EP 4291 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39704285 ER PT J AU Alexandrakis, G Filatov, V Talamo, JH Steinert, RF AF Alexandrakis, G Filatov, V Talamo, JH Steinert, RF TI Randomized clinical trial comparing suture in and suture out postkeratoplasty astigmatism with single running suture or interrupted sutures SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,CAMBRIDGE,MA 02138. CTR EYE RES,BOSTON,MA. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 4322 EP 4322 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39704316 ER PT J AU Stinson, WG Miller, JW Husain, D Kenney, AG Lane, AM Gragoudas, ES AF Stinson, WG Miller, JW Husain, D Kenney, AG Lane, AM Gragoudas, ES TI Liposomal BPD quantification in normal and neovascular choroid with fluorescence angiography SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BOSTON,MA. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 4379 EP 4379 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39704373 ER PT J AU Bursell, SE Gardner, WK Aiello, LP Aiello, LM AF Bursell, SE Gardner, WK Aiello, LP Aiello, LM TI A telecommunication based network for retinal imaging and diabetic retinopathy screening SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 JOSLIN DIABET CTR,BOSTON,MA 02215. NR 0 TC 2 Z9 2 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 4390 EP 4390 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39704384 ER PT J AU Shiuey, Y Lucarelli, MJ Pineda, R Navon, S AF Shiuey, Y Lucarelli, MJ Pineda, R Navon, S TI Primary cataract extraction and posterior chamber intraocular lens implantation in penetrating ocular trauma SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,BOSTON,MA. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 4403 EP 4403 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39704397 ER PT J AU Foster, BS March, GA Samiy, N Lucarelli, MJ AF Foster, BS March, GA Samiy, N Lucarelli, MJ TI Clinical, radiographic, and ultrasonographic analysis of optic nerve avulsion SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BOSTON,MA. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 4404 EP 4404 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39704398 ER PT J AU Adamis, AP Kuroki, M Tolentino, MJ Kim, I AF Adamis, AP Kuroki, M Tolentino, MJ Kim, I TI Advanced glycation end products (AGE) increase retinal VEGF gene expression SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 CHILDRENS HOSP,BOSTON,MA 02115. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BOSTON,MA. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 4465 EP 4465 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39704459 ER PT J AU Yamamoto, S Khani, SC McGee, T Berson, EL Dryja, TP AF Yamamoto, S Khani, SC McGee, T Berson, EL Dryja, TP TI Screen for mutations in the human rhodopsin kinase gene in patients with Retinitis pigmentosa SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,OCULAR MOLEC GENET INST,BOSTON,MA. HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,BERMAN GUND LAB,BOSTON,MA. SUNY BUFFALO,DEPT OPHTHALMOL,BUFFALO,NY. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 4551 EP 4551 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39704544 ER PT J AU Parminder, AH Murakami, A Inana, G Berson, EL Dryja, TP AF Parminder, AH Murakami, A Inana, G Berson, EL Dryja, TP TI Screen for mutations in the human Recoverin gene in patients with Retinitis pigmentosa or an allied disease SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,OCULAR MOLEC GENET INST,BOSTON,MA. HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,BERMAN GUND LAB,BOSTON,MA. MIAMI UNIV,SCH MED,BASCOM PALMER EYE INST,MIAMI,FL. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 4552 EP 4552 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39704545 ER PT J AU Sippel, KC DeStefano, JD Berson, EL Dryja, TP AF Sippel, KC DeStefano, JD Berson, EL Dryja, TP TI Screen of the human arrestin gene in patients with Retinitis pigmentosa and Oguchi disease SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,OCULAR MOLEC GENET INST,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BERMAN GUND LAB,BOSTON,MA. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 4553 EP 4553 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39704546 ER PT J AU Seddon, JM PericakVance, M Haines, J Rimmler, J DelaPaz, MA AF Seddon, JM PericakVance, M Haines, J Rimmler, J DelaPaz, MA TI Genetic linkage analysis of the TIMP3 locus in age-related macular degeneration SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT NEUROGENET,BOSTON,MA. DUKE UNIV,MED CTR,DEPT NEUROL,DURHAM,NC. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 4554 EP 4554 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39704547 ER PT J AU Grice, KM DelBono, EA Haines, JL Wiggs, JL Gwiazda, JE AF Grice, KM DelBono, EA Haines, JL Wiggs, JL Gwiazda, JE TI Genetic analysis of pedigrees affected by juvenile onset myopia SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEW ENGLAND COLL OPTOMETRY,MYOPLA RES CTR,BOSTON,MA. TUFTS UNIV,SCH MED,NEW ENGLAND MED CTR,DEPT OPHTHALMOL,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MOLEC NEUROGENET,BOSTON,MA. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 4603 EP 4603 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39704596 ER PT J AU Heiligenhaus, A Schaller, J Mauss, S Dutt, JE Engelbrecht, S Steuhl, KP Foster, CS AF Heiligenhaus, A Schaller, J Mauss, S Dutt, JE Engelbrecht, S Steuhl, KP Foster, CS TI Eosinophil granule proteins expressed in active ocular cicatricial pemphigoid SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 UNIV ESSEN GESAMTHSCH,DEPT OPHTHALMOL,ESSEN,GERMANY. ST BARBARA HOSP,DEPT DERMATOL,DUISBURG,GERMANY. MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 4699 EP 4699 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39704692 ER PT J AU You, TT Hogan, RN Yuhan, KR Foster, CS Dohlman, CH AF You, TT Hogan, RN Yuhan, KR Foster, CS Dohlman, CH TI A histopathologic study of corneal keratopathy in Stevens-Johnson syndrome SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BOSTON,MA. UNIV PENN,SCH MED,PHILADELPHIA,PA 19104. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 4702 EP 4702 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39704695 ER PT J AU MerayoLloves, J Hu, S Zhao, T Foster, CS AF MerayoLloves, J Hu, S Zhao, T Foster, CS TI Treatment comparations in experimental murine ragweed allergic conjunctivitis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,HILLES IMMUNOL LAB,BOSTON,MA. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 4720 EP 4720 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39704713 ER PT J AU Hu, S MerayoLloves, J Zhao, T Foster, CS AF Hu, S MerayoLloves, J Zhao, T Foster, CS TI Potent inhibitory effect of tetrandrine experimental allergic conjunctivitis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,HILLES IMMUNOL LAB,BOSTON,MA. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 4722 EP 4722 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39704715 ER PT J AU Zafirakis, C Hu, S MerayoLloves, J Foster, CS AF Zafirakis, C Hu, S MerayoLloves, J Foster, CS TI A non-radiolabeled in situ hybridization technique for the detection of the inhibitory effect of tetrandrine on experimental allergic conjunctivitis in mice SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,BOSTON,MA. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 4723 EP 4723 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39704716 ER PT J AU Rojas, B Christen, B Markomichelakis, N Foster, CS AF Rojas, B Christen, B Markomichelakis, N Foster, CS TI Medical treatment of CME in patients with uveitis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,CAMBRIDGE,MA 02138. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,CAMBRIDGE,MA 02138. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 4753 EP 4753 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39704746 ER PT J AU Huang, M Vinals, AF Dreyer, EB AF Huang, M Vinals, AF Dreyer, EB TI The ability of Muller cells to detoxify extracellular glutamate is impaired under anoxic conditions SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 4785 EP 4785 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39704778 ER PT J AU Daly, FJ Martin, SC Heinrich, G Rangini, Z Driever, W Sandell, JH AF Daly, FJ Martin, SC Heinrich, G Rangini, Z Driever, W Sandell, JH TI A zebrafish mutant (shrunken head, shr) with retinal degeneration SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 BOSTON UNIV,SCH MED,DEPT ANAT & NEUROBIOL,BOSTON,MA 02118. BOSTON UNIV,SCH MED,SECT BIOMOLEC MED,BOSTON,MA 02118. MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 4786 EP 4786 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39704779 ER PT J AU Kaiser, PK Heng, JE Vorwerk, C Dreyer, EB AF Kaiser, PK Heng, JE Vorwerk, C Dreyer, EB TI Ethambutol mediated optic neuropathy is mediated through perturbation of mitochondrial calcium SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 4805 EP 4805 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39704798 ER PT J AU Vinals, AF Heng, JE Dreyer, EB AF Vinals, AF Heng, JE Dreyer, EB TI Calcium channel control of neurite outgrowth in retinal ganglion cells SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 4824 EP 4824 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39704817 ER PT J AU Chang, EJ Netland, PA AF Chang, EJ Netland, PA TI Retrobulbar chlorpromazine for management of chronic pain in absolute glaucoma SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 5057 EP 5057 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39705050 ER PT J AU Egan, KM Gragoudas, ES AF Egan, KM Gragoudas, ES TI Impact of enucleation on patient survival following proton irradiation for choroidal melanoma SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,RETINA SERV,BOSTON,MA. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 5198 EP 5198 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39705191 ER PT J AU Amano, S Tolentino, MJ Pineda, R Vinals, T Kuroki, M Adamis, AP AF Amano, S Tolentino, MJ Pineda, R Vinals, T Kuroki, M Adamis, AP TI Vascular endothelial growth factor gene expression is increased in hypoxic cornea SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 CHILDRENS HOSP,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BOSTON,MA. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 5214 EP 5214 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39705207 ER PT J AU Hussels, IEM Hahn, LB Reboul, T Arnaud, B Dryja, TP AF Hussels, IEM Hahn, LB Reboul, T Arnaud, B Dryja, TP TI Missense mutation in the gene encoding the alpha subunit of rod transducin cosegregates with Nougaret's congenital night blindness. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 JOHNS HOPKINS MED INST, JOHNS HOPKINS CTR HEREDITARY EYE DIS, WILMER EYE INST, BOSTON, MA USA. MASSACHUSETTS EYE & EAR INFIRM, BOSTON, MA 02114 USA. UNIV MONTPELLIER, SERV OPHTALMOL, F-34059 MONTPELLIER, FRANCE. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB 15 PY 1996 VL 37 IS 3 BP 5240 EP 5240 PG 1 WC Ophthalmology SC Ophthalmology GA TX397 UT WOS:A1996TX39705233 ER PT J AU Kelly, KJ Williams, WW Colvin, RB Meehan, SM Springer, TA GutierrezRamos, JC Bonventre, JV AF Kelly, KJ Williams, WW Colvin, RB Meehan, SM Springer, TA GutierrezRamos, JC Bonventre, JV TI Intercellular adhesion molecule-1-deficient mice are protected against ischemic renal injury SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE cell adhesion molecules; kidney failure, acute; leukocytes; disease models, animal; endothelium, vascular ID REPERFUSION INJURY; SIGNAL TRANSDUCTION; BLOOD-FLOW; RAT; NEUTROPHILS; FAILURE; ICAM-1; MECHANISMS; EXPRESSION; BRAIN AB Studies in the rat have pointed to a role for intercellular adhesion molecule-1 (ICAM-1) in the pathogenesis of acute tubular necrosis. These studies used antibodies, which may have nonspecific effects. We report that renal ICAM-1 mRNA levels and systemic levels of the cytokines IL-1 and TNF-alpha. increase 1 h after ischemia/reperfusion in the mouse. We sought direct proof for a critical role for ICAM-1 in the pathophysiology of ischemic renal. failure using mutant mice genetically deficient in ICAM-1. ICAM-1 is undetectable in mutant mice in contrast with normal mice, in which ICAM-1 is prominent in the endothelium of the vasa recta. Mutant mice are protected from acute renal ischemic injury as judged by serum creatinine, renal histology, and animal survival. Renal leukocyte infiltration, quantitated morphologically and by measuring tissue myeloperoxidase, was markedly less in ICAM-1-deficient than control mice. To evaluate whether prevention of neutrophil infiltration could be responsible for the protection observed in the mutant mice, we treated normal mice with antineutrophil serum to reduce absolute neutrophil counts to < 100 cells/mm(3). These neutrophil-depleted animals were protected against ischemic renal failure. Anti-ICAM-1 antibody protected normal mice against renal ischemic injury but did not provide additional protection to neutrophil-depleted animals. Thus, ICAM-1 is a key mediator of ischemic acute renal failure likely acting via potentiation of neutrophil-endothelial interactions. C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,MED SERV,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,PATHOL SERV,BOSTON,MA 02129. FU NIDDK NIH HHS [DK38773, T32DK07540]; NINDS NIH HHS [NS10828] NR 39 TC 505 Z9 535 U1 0 U2 9 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD FEB 15 PY 1996 VL 97 IS 4 BP 1056 EP 1063 DI 10.1172/JCI118498 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA UD037 UT WOS:A1996UD03700024 PM 8613529 ER PT J AU McMillan, JI Riordan, JW Couser, WG Pollock, AS Lovett, DH AF McMillan, JI Riordan, JW Couser, WG Pollock, AS Lovett, DH TI Characterization of a glomerular epithelial cell metalloproteinase as matrix metalloproteinase-9 with enhanced expression in a model of membranous nephropathy SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE gelatinases; kidney glomerulus; epithelium-enzymology; glomerulonephritis membranous; basement membrane metabolism ID BASEMENT-MEMBRANE; INCREASED PERMEABILITY; FIBROSARCOMA CELLS; HEPARAN-SULFATE; DEGRADATION; PROTEINASES; GLOMERULONEPHRITIS; PURIFICATION; CONTRIBUTES; MACROPHAGES AB The role of the glomerular visceral epithelial cell in the physiologic turnover and pathologic breakdown of the glomerular extracellular matrix has remained largely unexplored. Tn this study a 98-kD neutral proteinase secreted by cultured rat visceral glomerular epithelial cells was shown to be a calcium, zinc-dependent enzyme secreted in latent form. In addition, the protein was heavily glycosylated and demonstrated proteolytic activity against Type I gelatin, Type TV collagen gelatin, and fibronectin. The similarity in molecular mass and substrate specificities to the 92-kD human matrix metalloproteinase-9 (MMP-9, or gelatinase B) suggested the identity of this activity, which was confirmed by immunoprecipitation and Northern blot analysis. The differences in molecular mass (98 vs. 92 kD) were not due to species-specific differences in glycosylation patterns. since cultured rat peritoneal macrophages secreted MMP-9 as a 92-kD enzyme. Furthermore, transfection of the human MMP-9 cDNA into rat glomerular epithelial cells yielded the 98-kD product. Using a specific monoclonal anti-MMP-9 antibody and in situ reverse transcription (ISRT) analysis of MMP-9 mRNA, the expression of this enzyme was evaluated in vivo. Normal rat glomeruli expressed little immunohistochemical or ISRT staining for MMP-9, while in rats with passive Heymann nephritis there was a major increase in MMP-9 protein and mRNA staining within the visceral epithelial cells. The temporal patterns of MMP-9 expression correlated with the period of proteinuria associated with this model, suggesting that a causal relationship may exist between GEC MMP-9 expression and changes in glomerular capillary permeability. C1 UNIV CALIF SAN FRANCISCO,SAN FRANCISCO VAMC,MED SERV 111J,DEPT MED,SAN FRANCISCO,CA 94121. UNIV WASHINGTON,DEPT MED,SEATTLE,WA 98105. FU NIDDK NIH HHS [DK-31398, DK-39766, DK-34198] NR 30 TC 123 Z9 143 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD FEB 15 PY 1996 VL 97 IS 4 BP 1094 EP 1101 DI 10.1172/JCI118502 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA UD037 UT WOS:A1996UD03700028 PM 8613533 ER PT J AU Dong, RP Kameoka, J Hegen, M Tanaka, T Xu, XH Schlossman, SF Morimoto, C AF Dong, RP Kameoka, J Hegen, M Tanaka, T Xu, XH Schlossman, SF Morimoto, C TI Characterization of adenosine deaminase binding to human CD26 on T cells and its biologic role in immune response SO JOURNAL OF IMMUNOLOGY LA English DT Article ID DIPEPTIDYL PEPTIDASE-IV; PERIPHERAL-BLOOD; ACTIVATION ANTIGEN; MONOCLONAL-ANTIBODIES; COMPLEXING PROTEIN; HUMAN-LYMPHOCYTES; SURFACE; EXPRESSION; DEOXYADENOSINE; 1F7 AB CD26, a T cell activation Ag, also known as dipeptidyl peptidase IV, is directly associated with adenosine deaminase (ADA) on the surface of T cells and T cell lines. In the present study, we examined both the binding of ADA to CD26 and the functional consequences of this interaction. We found that ADA was associated with CD26 on T cell lines lacking either ADA or dipeptidyl peptidase IV enzymatic activity, indicating that the association between dipeptidyl peptidase IV and ADA did not require enzymatic activity. Moreover, using immunoelectron microscopy, we demonstrated that CD26 and ADA co-localized on the cell surface, but not inside cells, suggesting that CD26 did not transport ADA to the surface. In keeping with this observation, we showed that human CD26-transfected murine pre-B cell lines lacking human ADA acquired ADA from an extracellular source. More importantly, adenosine in the absence of cell surface ADA inhibited T cell proliferation and IL-2 production induced by various stimuli. On the other hand, cells expressing ADA and CD26 on the surface were much more resistant to the inhibitory effect of adenosine. These data suggest that DA on the cell surface is involved in an important immunoregulatory mechanism by which released ADA binds to cell surface CD26, and this complex is capable of reducing the local concentration of adenosine. C1 DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. DANA FARBER CANC INST,DIV STRUCT MOLEC BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. FU NCI NIH HHS [CA55601]; NIAID NIH HHS [AI12609] NR 59 TC 150 Z9 155 U1 0 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 15 PY 1996 VL 156 IS 4 BP 1349 EP 1355 PG 7 WC Immunology SC Immunology GA TU692 UT WOS:A1996TU69200005 PM 8568233 ER PT J AU Rajan, P Symes, A Fink, JS AF Rajan, P Symes, A Fink, JS TI STAT proteins are activated by ciliary neurotrophic factor in cells of central nervous system origin SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE SN48; primary CNS cultures; cytokine signal transduction; transcription ID LEUKEMIA INHIBITORY FACTOR; TYROSINE-HYDROXYLASE EXPRESSION; FACTOR PREVENTS DEGENERATION; NGF RECEPTOR EXPRESSION; RAT SUBSTANTIA-NIGRA; EMBRYONIC MOTONEURONS; MOTOR NEURONS; CNTF; SURVIVAL; PROMOTES AB Neuropoietic cytokines, including ciliary neurotrophic factor (CNTF) and leukemia inhibitory factor (LIF), have survival effects on cells of the peripheral and central nervous systems (PNS and CNS), CNTF and LIF also produce differentiation in some cells of the PNS, We have shown previously that CNTF activates the signal transducers and activators of transcription (STAT) family of transcription factors, and that this signaling pathway may be one of several employed by CNTF to regulate the expression of the vasoactive intestinal peptide (VIP) gene in cells of the PNS (Symes et al.: Proc Natl Acad Sci USA 90:572-576, 1993; Symes et al,: Mol Endocrinol 8:1750-1763, 1994), To investigate the mechanisms of action of CNTF in the CNS, we have analyzed the activation of STAT proteins in a septal-derived cell line, SN48, and in primary CNS cultures, CNTF treatment of SN48 cells produces a sustained activation of Stat3, CNTF treatment of SN48 cells also activated transcription mediated by the VIP cytokine responsive element (CyRE) which contains a STAT binding site, Mutation of the STAT site in the CyRE attenuated transcriptional activation by CNTF, indicating the importance of STAT proteins to CNTF-dependent transcriptional activation in SN48 cells, In cultures of embryonic rat septum and other brain areas, in addition to Stat3, CNTF also activates Stat1, As in cells of the PNS and non-neuronal cells, the Janus kinase (Jak)-STAT pathway is activated in CNS cells by cytokines, The SN48 cell line may be valuable in further characterization of regulation of the Jak-STAT pathway by neuropoietic cytokines. (C) 1996 Wiley-Liss, Inc. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,MOLEC NEUROBIOL LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. FU NINDS NIH HHS [NS-27514] NR 41 TC 43 Z9 45 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 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD FEB 15 PY 1996 VL 43 IS 4 BP 403 EP 411 DI 10.1002/(SICI)1097-4547(19960215)43:4<403::AID-JNR2>3.0.CO;2-J PG 9 WC Neurosciences SC Neurosciences & Neurology GA TY121 UT WOS:A1996TY12100002 PM 8699527 ER PT J AU Castelli, I Steiner, LA Kaufmann, MA Drop, LJ AF Castelli, I Steiner, LA Kaufmann, MA Drop, LJ TI Renovascular responses to high and low perfusate calcium steady-state experiments in the isolated perfused rat kidney with baseline vascular tone SO JOURNAL OF SURGICAL RESEARCH LA English DT Article ID PLASMA IONIZED CALCIUM; BLOOD-FLOW; HEMODYNAMIC-RESPONSE; HYPERCALCEMIA; HYPOCALCEMIA; NOREPINEPHRINE; AUTOREGULATION; PRESSURE AB Acute hypercalcemia is commonly observed in surgical patients after calcium infusion while acute hypocalcemia is common during rapid citrated blood transfusion. Although high and low ionized calcium ([Ca2+]) within the clinical range produce an increase or decrease in cardiac performance and systemic vessel resistance, respectively, their effects on renal vessels have not been quantified. A possible renal vasoconstriction that might occur with high [Ca2+] is of clinical interest because it is a factor which may contribute to impaired renal circulation and decreased function, In this study we examined the renovascular responses to [Ca2+], which was varied within the clinical range under hemodynamically controlled conditions. We instituted high and low [Ca2+] in the per fusate, which consisted of Krebs-Henseleit buffer containing albumin, 60-65 g/liter. Stable high (n = 10) or low (n = 7) [Ca2+] (1.93 +/- 0.02 and 0.59 +/- 0.01 mM, respectively) was instituted for 10 min and preceded and followed by normal [Ca2+] of the same duration. In a separate protocol (n = 8) verapamil (10(-5) M) was added to the perfusate 10 min before high [Ca2+] was tested. We measured changes in renal flow at a constant perfusion pressure of 110 mm Hg and also characterized the renal vessels over a range of pressures by pressure vs flow plots. High [Ca2+] was associated with a small decrease in how (from 28.8 +/- 2.4 to 26.9 +/- 2.6 ml/min/g, P < 0.02), indicating a small vasopressor effect. This effect was also shown by a leftward shift in the pressure vs flow plots, These changes were prevented by verapamil. GFR decreased (from 0.35 +/- 0.04 to 0.28 +/- 0.06 ml/min/g, P < 0.01) without a significant change in sodium excretion or fractional sodium excretion. Low [Ca2+] was associated with increased renal flow (from 30.8 +/- 2.1 to 35.2 +/- 2.7 ml/min/g, P < 0.02), indicating a vasodilator effect. This effect was also shown by a rightward displacement of the pressure vs how plots. GFR increased from 0.51 +/- 0.03 to 0.56 +/- 0.04 ml/min/g, P < 0.01, as did sodium excretion (from 2.32 +/- 0.22 to 3.87 +/- 0.49 mu Eq/min, P < 0.01) and fractional sodium excretion (from 2.33 +/- 0.26 to 3.61 +/- 0.49%, P < 0.01), We conclude, first, that in the isolated perfused rat kidney, high [Ca2+] is a weak vasopressor while low [Ca2+] has vasodilator action. Second, high [Ca2+] effects are abolished by verapamil pretreatment. These findings illuminate mechanisms of high [Ca2+] effects on renovascular tone. (C) 1996 Academic Press, Inc. C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. BEECHER LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT ANAESTHESIA,BOSTON,MA 02114. RI Steiner, Luzius/C-9836-2011 NR 31 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 FEB 15 PY 1996 VL 61 IS 1 BP 51 EP 57 DI 10.1006/jsre.1996.0080 PG 7 WC Surgery SC Surgery GA TX617 UT WOS:A1996TX61700010 PM 8769942 ER PT J AU OBrien, WA Hartigan, PM Martin, D Esinhart, J Hill, A Benoit, S Rubin, M Lahart, C Wray, N Finegold, SM George, WL Dickinson, GM Klimas, N Diamond, G ZollaPazner, SB Jensen, PC Hawkes, C Oster, C Gordin, F Labriola, AM Spivey, P Matthews, T Weinhold, K Drusano, G Egorin, MJ AF OBrien, WA Hartigan, PM Martin, D Esinhart, J Hill, A Benoit, S Rubin, M Lahart, C Wray, N Finegold, SM George, WL Dickinson, GM Klimas, N Diamond, G ZollaPazner, SB Jensen, PC Hawkes, C Oster, C Gordin, F Labriola, AM Spivey, P Matthews, T Weinhold, K Drusano, G Egorin, MJ TI Changes in plasma HIV-1 RNA and CD4+ lymphocyte counts and the risk of progression to AIDS SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID IMMUNODEFICIENCY-VIRUS-INFECTION; CONTROLLED TRIAL; CLINICAL-TRIALS; END-POINTS; REVERSE-TRANSCRIPTASE; P24 ANTIGEN; ZIDOVUDINE; MARKER; NEOPTERIN; RESISTANCE AB Background. Clinical trials of antiretroviral drugs can take years to complete because the outcomes measured are progression to the acquired immunodeficiency syndrome (AIDS) or death. Trials could be accelerated by the use of end points such as changes in CD4+ lymphocyte counts and plasma levels of human immunodeficiency virus type 1 (HIV-1) RNA and beta(2)-microglobulin, but there is uncertainty about whether these surrogate measures are valid predictors of disease progression. Methods. We analyzed data from the Veterans Affairs Cooperative Study on AIDS, which compared immediate with deferred zidovudine therapy. Patients' plasma levels of HIV-1 RNA and beta(2)-microglobulin were measured in stored plasma. Results. Among the 129 patients in the immediate-treatment group, 34 had disease that progressed to AIDS, as compared with 57 of the 141 patients in the deferred-treatment group (P=0.03). Progression to AIDS correlated strongly with base-line CD4+ lymphocyte counts (P=0.001) and plasma levels of HIV-1 RNA (P<0.001), but not with base-line levels of beta(2)-microglobulin (P=0.14). A decrease of at least 75 percent in the plasma level of HIV-1 RNA over the first six months of zidovudine therapy accounted for 59 percent of the benefit of treatment, defined as the absence of progression to AIDS (95 percent confidence interval, 13 to 112 percent). Plasma beta(2)-microglobulin levels and CD4+ lymphocyte counts explained less of the effect of treatment. A 75 percent decrease in the plasma HIV-1 RNA level plus a 10 percent increase in the CD4+ lymphocyte count could explain 79 percent of the treatment effect (95 percent confidence interval, 27 to 145 percent). Conclusions. Treatment-induced changes in the plasma HIV-1 RNA level and the CD4+ lymphocyte count, taken together, are valid predictors of the clinical progression of HIV-related disease and can be used to assess the efficacy of zidovudine and possibly other antiretroviral drugs as well. (C) 1996, Massachusetts Medical Society. C1 UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA. VET AFFAIRS COOPERAT STUDIES PROGRAM,COORDINATING CTR,W HAVEN,CT. UNIV N CAROLINA,CHAPEL HILL,NC. GLAXO INC,RES TRIANGLE PK,NC 27709. VET AFFAIRS MED CTR,NEW YORK,NY. NYU,SCH MED,NEW YORK,NY. DUKE UNIV,MED CTR,DURHAM,NC. VET AFFAIRS MED CTR,DURHAM,NC 27705. VET AFFAIRS MED CTR,HOUSTON,TX 77030. VET ADM MED CTR,MIAMI,FL 33125. VET ADM MED CTR,SAN FRANCISCO,CA 94121. WALTER REED ARMY MED CTR,WASHINGTON,DC. VET ADM MED CTR,WASHINGTON,DC 20422. DUKE UNIV,VIROL CTR,DURHAM,NC 27706. UNIV MARYLAND,PHARMACOL LAB,COLLEGE PK,MD 20742. RP OBrien, WA (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,DEPT MED,11301 WILSHIRE BLVD,LOS ANGELES,CA 90073, USA. NR 40 TC 605 Z9 610 U1 2 U2 12 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD FEB 15 PY 1996 VL 334 IS 7 BP 426 EP 431 DI 10.1056/NEJM199602153340703 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA TU696 UT WOS:A1996TU69600003 PM 8552144 ER PT J AU Tangir, J Muto, MG Berkowitz, RS Welch, WR Bell, DA Mok, SC AF Tangir, J Muto, MG Berkowitz, RS Welch, WR Bell, DA Mok, SC TI A 400 kb novel deletion unit centromeric to the BRCA1 gene in sporadic epithelial ovarian cancer SO ONCOGENE LA English DT Article DE ovary; cancer; borderline; BRCA1; loss of heterozygosity ID HETEROZYGOSITY; TUMORS AB Allelic deletions on chromosome 17q21 in sporadic ovarian cancer are common, suggesting that inactivation of a tumor suppressor gene(s) in that region may be important for the etiology of these tumors. The recently identified BRCA1 gene on 17q21, involved in the development of familial breast/ovarian cancer, could be a candidate. However, inactivating mutations on BRCA1 in sporadic ovarian cancer has been rarely described. Furthermore, the potential relationship of BRCA1 gene to ovarian tumors of borderline malignancy remains also unclear. We constructed a highly detailed deletion map of chromosome 17q21 based on PCR amplification of eight polymorphic tandem repeat markers in a 650 kb area including three BRCA1 intragenic markers. DNA from 52 sporadic ovarian cancers and 26 borderline tumors, together with their corresponding normal control tissues were used. Only one borderline tumor showed loss of heterozygosity at one marker, whereas 65% of invasive ovarian cancers displayed allelic loss in at least one of the markers studied. A common deletion unit, located approximately 60 kb centromeric to BRCA1, was revealed. These results suggest that inactivation of the BRCA1 gene may not be responsible for the development of borderline ovarian tumors and that another tumor suppressor gene, located centromeric to the BRCA1 gene, may play a role in sporadic ovarian cancer development. C1 BRIGHAM & WOMENS HOSP,DEPT OBSTET GYNECOL & REPROD BIOL,LAB GYNECOL ONCOL,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02115. FU NCI NIH HHS [R01CA63381] NR 27 TC 40 Z9 45 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD FEB 15 PY 1996 VL 12 IS 4 BP 735 EP 740 PG 6 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA TW686 UT WOS:A1996TW68600004 PM 8632895 ER PT J AU Sattler, M Salgia, R Okuda, K Uemura, N Durstin, MA Pisick, E Xu, G Li, JL Prasad, KV Griffin, JD AF Sattler, M Salgia, R Okuda, K Uemura, N Durstin, MA Pisick, E Xu, G Li, JL Prasad, KV Griffin, JD TI The proto-oncogene product p120(CBL) and the adaptor proteins CRKL and c-CRK link c-ABL, p190(BCR/ABL) and p210(BCR/ABL) to the phosphatidylinositol-3' kinase pathway SO ONCOGENE LA English DT Article DE BCR/ABL; c-CBL; c-CRK; CRKL; phosphatidylinositol-3' kinase ID ACUTE LYMPHOBLASTIC-LEUKEMIA; V-CBL; FUSED TRANSCRIPT; 3-KINASE; BINDING; DOMAIN; TRANSFORMATION; FIBROBLASTS; TRUNCATION; CELLS AB Chronic myelogenous leukemia (CML) and some acute lymphoblastic leukemias (ALL) are caused by the t(9;22) chromosome translocation, which produces the constitutively activated BCR/ABL tyrosine kinase. When introduced into factor dependent hematopoietic cell lines, BCR/ABL induces the tyrosine phosphorylation of many cellular proteins. One prominent BCR/ABL substrate is p120(CBL), the cellular homolog of the v-Cbl oncoprotein. In an effort to understand the possible contribution of p120(CBL) to transformation by BCR/ABL, we looked for cellular proteins which associate with p120(CBL) in hematopoietic cell lines transformed by BCR/ABL. In addition to p210(BCR/ABL) and c-ABL, p120(CBL) coprecipitated with an 85 kDa phosphoprotein, which was identified as the p85 subunit of PI3K. Anti-p120(CBL) immunoprecipitates from BCR/ABL-transformed, but not from untransformed, cell lines contained PI3K lipid kinase activity. Interestingly, the adaptor proteins CRKL and c-CRK were also found in these complexes. In vitro binding studies indicated that the SH2 domains of CRKL and c-CRK bound directly to p120(CBL), while the SH3 domains of c-CRK and CRKL bound to BCR/ABL and c-ABL. The N-terminal and the C-terminal SH2 and the SH3 domain of p85(PI3K) bound directly in vitro to p120(CBL). The ABL-SH2, but not ABL-SH3, could also bind to p120(CBL). These data suggest that BCR/ABL may induce the formation of multimeric complexes of signaling proteins which include p120(CBL), PI3K, c-CRK or CRKL, c-ABL and BCR/ABL itself. C1 HARVARD UNIV, SCH MED, DANA FARBER CANC INST, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DANA FARBER CANC INST, DIV TUMOR IMMUNOL, BOSTON, MA 02115 USA. OI Li, Jian-Liang/0000-0002-6487-081X FU NCI NIH HHS [CA60821, CA36167] NR 48 TC 245 Z9 248 U1 2 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD FEB 15 PY 1996 VL 12 IS 4 BP 839 EP 846 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA TW686 UT WOS:A1996TW68600015 PM 8632906 ER PT J AU Gianello, PR Yamada, K Fishbein, JM Lorf, T Nickeleit, V Colvin, RB Arn, JS Sachs, DH AF Gianello, PR Yamada, K Fishbein, JM Lorf, T Nickeleit, V Colvin, RB Arn, JS Sachs, DH TI Long-term acceptance of primarily vascularized renal allografts in miniature swine - Systemic tolerance versus graft adaptation SO TRANSPLANTATION LA English DT Article ID CLASS-I; TRANSPLANTATION AB We have previously demonstrated that tolerance to two-haplotype class I-mismatched renal allografts can be induced uniformly by a short course of cyclosporine. We report here that following transplant nephrectomy, 8 such long-term acceptor animals all accepted a second renal transplant MHC matched to the original donor without additional immunosuppression. These results indicate that the mechanism of tolerance to primarily vascularized renal allografts involves modification of the host's immune system by the first transplant. To assess the possibility that ''graft adaptation'' is also involved in the maintenance of tolerance, we retransplanted class I-disparate kidneys from tolerant animals into naive recipients MHC matched to the original recipient. Three of 4 such transplants were rejected acutely, while one animal demonstrated a markedly prolonged survival, but also eventually rejected. These results, therefore, demonstrate that: (1) graft adaptation is not required in order to maintain tolerance; (2) graft acceptance involves induction of systemic tolerance; and (3) graft adaptation may participate in kidney graft prolongation but is not sufficient to transfer tolerance to a secondary host. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP E,SCH MED,TRANSPLANTAT BIOL RES CTR,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02129. FU NHLBI NIH HHS [HL18646]; NIAID NIH HHS [AI31046] NR 7 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 FEB 15 PY 1996 VL 61 IS 3 BP 503 EP 506 DI 10.1097/00007890-199602150-00032 PG 4 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA TW446 UT WOS:A1996TW44600032 PM 8610368 ER PT J AU Harari, D Gurwitz, JH Avorn, J Bohn, R Minaker, KL AF Harari, D Gurwitz, JH Avorn, J Bohn, R Minaker, KL TI Bowel habit in relation to age and gender - Findings from the National Health Interview Survey and clinical implications SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID UNITED-STATES; TRANSIT-TIME; ANORECTAL MANOMETRY; FECAL IMPACTION; CONSTIPATION; POPULATION; PREVALENCE; PEOPLE; QUESTIONNAIRE; DYSFUNCTION AB Background: Constipation is widely considered to be a common problem among the elderly, as evidenced by the high rate of laxative use in this population. Yet, age-related prevalence studies of constipation generally do not distinguish between actual alteration in bowel movement frequency and subjective self-report of constipation. Objective: To determine the relationship between advancing age and bowel habit. Methods: We employed data collected on 42 375 subjects who participated in the National Health Interview Survey on Digestive Disorders based on interviews with a random nationwide sample of US households. We examined the following characteristics reported by this population according to selected age groupings by decade: constipation, levels of laxative use, and two bowel movements per week or less. Results: Contrary to conventional wisdom, there was no age-related increase in the proportion of subjects reporting infrequent bowel movements. Nonetheless, the prevalence of self-report of constipation increased with advancing age, with a greater proportion of women reporting this symptom than men across all age groups. Laxative use also increased substantially with aging; while women were more likely to use laxatives than men, this effect attenuated with advancing age. A U-shaped relationship was observed between advancing age and bowel habit in men and women; 5.9% of individuals younger than 40 years reported two bowel movements per week or less compared with 3.8% of those aged 60 to 69 years and 6.3% of those aged 80 years or older. This relationship persisted after adjusting for laxative use. Conclusion: These findings suggest that a decline in bowel movement frequency is not an invariable concomitant of aging. In elderly patients who report being constipated, it is essential to take a careful physical, psychological, and bowel history rather than to automatically assume the need for laxative use. C1 MASSACHUSETTS GEN HOSP,GEN MED UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DIV AGING,BOSTON,MA 02115. VET AFFAIRS MED CTR,GERIATR RES EDUC & CLIN CTR,BROCKTON,MA. BRIGHAM & WOMENS HOSP,GERONTOL DIV,PROGRAM ANAL CLIN STRATEGIES,BOSTON,MA 02115. RP Harari, D (reprint author), MASSACHUSETTS GEN HOSP,BEACON HILL GERIATR MED UNIT,100 CHARLES RIVER PLAZA,5TH FLOOR,BOSTON,MA 02114, USA. FU NIA NIH HHS [AG04390, AG94001, AG00599] NR 47 TC 78 Z9 85 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD FEB 12 PY 1996 VL 156 IS 3 BP 315 EP 320 DI 10.1001/archinte.156.3.315 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA TU545 UT WOS:A1996TU54500011 PM 8572842 ER PT J AU Kramm, CM Rainov, NG SenaEsteves, M Chase, M Pechan, PA Chiocca, EA Breakefield, XO AF Kramm, CM Rainov, NG SenaEsteves, M Chase, M Pechan, PA Chiocca, EA Breakefield, XO TI Herpes vector-mediated delivery of marker genes to disseminated central nervous system tumors SO HUMAN GENE THERAPY LA English DT Article ID THYMIDINE KINASE GENE; BRAIN-TUMORS; CELLS; INVIVO; THERAPY AB The present study investigated the ability of a recombinant herpes simplex virus type 1 (HSV) vector to deliver genes into disseminated brain tumor foci through intrathecal injection of the vector. The animal model was designed to simulate brain tumors with cerebrospinal fluid (CSF) metastases, which are found especially in the pediatric population. 9L gliosarcoma cells were injected both into the right frontal lobe and in through the cisterna magna of adult rats. The HSV vector, hrR3, was inoculated intrathecally 5 days later. This vector is defective in the gene for ribonucleotide reductase, and, therefore, replicates preferentially in dividing cells; it retains an intact HSV-thymidine kinase gene (HSV-tk). Two days after injection of the vector, immunohistochemical staining for HSV thymidine kinase (HSV-TK) revealed expression in frontal tumors, as well as in leptomeningeal tumor foci along the entire neuroaxis. HSV-TK-immunopositive cells were most frequent in small tumors contacting the CSF pathways. Frontal lobe tumors showed the highest density of HSV-TK-immunopositive cells around their periphery with little expression in central parts. Some paraventricular neurons temporarily showed HSV-TK-immunolabeling at this early time point. The number of HSV-TK-immunopositive tumor cells markedly decreased 5 days after injection of the HSV vector. In all animals, some toxicity was observed in the first 2-4 days after virus injection with extensive leptomeningeal inflammation. In conclusion, intrathecal application of HSV vectors can mediate widespread transfer of the therapeutic HSV-tk gene into disseminated tumors throughout the brain and CSF pathways. Although there was marked toxicity associated with intrathecal injection of this vector, this mode of gene delivery offers a promising approach for treatment of CSF-metastases in conjunction with development of less toxic vectors. C1 HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02129. UNIV HALLE WITTENBERG,FAC MED,DEPT NEUROSURG,HALLE,GERMANY. MASSACHUSETTS GEN HOSP,NEUROSURG SERV,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,CTR NEUROSCI,MOL NEUROGENET UNIT,BOSTON,MA 02129. UNIV DUSSELDORF,CHILDRENS HOSP,W-4000 DUSSELDORF,GERMANY. FU NINDS NIH HHS [NS24279] NR 28 TC 23 Z9 23 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD FEB 10 PY 1996 VL 7 IS 3 BP 291 EP 300 DI 10.1089/hum.1996.7.3-291 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA UG141 UT WOS:A1996UG14100003 PM 8835217 ER PT J AU Yan, RQ Small, S Desplan, C Dearolf, CR Darnell, JE AF Yan, RQ Small, S Desplan, C Dearolf, CR Darnell, JE TI Identification of a Stat gene that functions in Drosophila development SO CELL LA English DT Article ID REGULATORY ELEMENTS; EXPRESSION; PROTEIN; SEGMENTATION; PHOSPHORYLATION; TRANSCRIPTION; PROMOTER; PATTERN; LETHAL; EMBRYO AB A Drosophila Stat gene (D-Stat) with a zygotic segmental expression pattern was identified. This protein becomes phosphorylated on Tyr-704 when coexpressed in Schneider cells with a Drosophila janus kinase (JAK), Hopscotch (HOP). The phosphorylated protein binds specifically to the consensus sequence TTCCCGGAA. Suppressor mutations of hop(Tum-1), a dominant hyperactive allele of hop whose phenotype is hematocyte overproduction and tumor formation, were selected. One of these mutants, stat(HJ), mapped to the same chromosomal region (92E) as does D-Stat, had an incompletely penetrant pair rule phenotype, and exhibited aberrant expression of the pair rule gene even skipped (eve) at the cellular blastoderm stage. Two D-STAT-binding sites were identified within the eve stripe 3 enhancer region. Mutations in either of the STAT-binding sites greatly decreased the stripe 3 expression in transgenic flies. Clearly, the JAK-STAT pathway is connected to Drosophila early development. C1 NYU,DEPT BIOL,NEW YORK,NY 10003. ROCKEFELLER UNIV,HOWARD HUGHES MED INST,NEW YORK,NY 10021. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEV GENET GRP,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CANC BIOL SECT,JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. RP Yan, RQ (reprint author), ROCKEFELLER UNIV,MOLEC CELL BIOL LAB,NEW YORK,NY 10021, USA. FU NIAID NIH HHS [AI34420, AI32489]; NIGMS NIH HHS [GM1946] NR 50 TC 274 Z9 282 U1 0 U2 11 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD FEB 9 PY 1996 VL 84 IS 3 BP 421 EP 430 DI 10.1016/S0092-8674(00)81287-8 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA TV708 UT WOS:A1996TV70800011 PM 8608596 ER PT J AU Natowicz, MR Wang, Y AF Natowicz, MR Wang, Y TI Human serum hyaluronidase: Characterization of a clinical assay SO CLINICA CHIMICA ACTA LA English DT Article DE hyaluronidase; hyaluronan; hyaluronic acid; hyaluronate ID POLYMORPHISM; PURIFICATION; LIVER AB Hyaluronidase, a lysosomal endoglycosidase mediating hyaluronan (hyaluronic acid) turnover, is thought to be important in many normal developmental and certain pathologic processes. Previous assays of serum hyaluronidase are limited with respect to their applicability for routine clinical chemistry or clinical biochemical genetics applications. We describe a new assay of human serum or plasma hyaluronidase activity based on the determination of released N-acetylglucosamine reducing termini that allows the analysis of the enzyme with small, easily obtained sample volumes. Using 10 mu l of serum or plasma, sodium formate buffer and human umbilical cord hyaluronan as substrate, we found a pH optimum of 3.9 and a K-m and V-max of 114 mg/l and 5102 mU/l, respectively. In addition, the assay has excellent linearity, precision and reproducibility. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PEDIAT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RP Natowicz, MR (reprint author), EUNICE KENNEDY SHRIVER CTR MENTAL RETARDAT INC,DIV MED GENET,200 TRAPELO RD,WALTHAM,MA 02254, USA. NR 22 TC 26 Z9 27 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-8981 J9 CLIN CHIM ACTA JI Clin. Chim. Acta PD FEB 9 PY 1996 VL 245 IS 1 BP 1 EP 6 DI 10.1016/0009-8981(95)06182-7 PG 6 WC Medical Laboratory Technology SC Medical Laboratory Technology GA TZ790 UT WOS:A1996TZ79000001 PM 8646808 ER PT J AU Panchamoorthy, G Fukazawa, T Miyake, S Soltoff, S Reedquist, K Druker, B Shoelson, S Cantley, L Band, H AF Panchamoorthy, G Fukazawa, T Miyake, S Soltoff, S Reedquist, K Druker, B Shoelson, S Cantley, L Band, H TI p120(cbl) is a major substrate of tyrosine phosphorylation upon B cell antigen receptor stimulation and interacts in vivo with Fyn and Syk tyrosine kinases, Grb2 and Shc adaptors, and the p85 subunit of phosphatidylinositol 3-kinase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PERIPHERAL T-CELLS; V-CBL; PROTEIN-KINASE; LYMPHOCYTES-B; MICE LACKING; SRC FAMILY; ZETA-CHAIN; ASSOCIATION; TRUNCATION; ACTIVATION AB We and others have demonstrated that the c-cbl protooncogene product is one of the earliest targets of tyrosine phosphorylation upon T cell receptor stimulation. Given the similarities in the B and T lymphocyte antigen receptors, and the induction of pre-B leukemias in mice by the v-cbl oncogene, we examined the potential involvement of Cbl in B cell receptor signaling. We demonstrate prominent and early tyrosine phosphorylation of Cbl upon stimulation of human B cell lines through surface IgM. Cbl was associated in vivo with Fyn and, to a lesser extent, other Src family kinases. B cell activation also induced a prominent association of Cbl with Syk tyrosine kinase. A substantial fraction of Cbl was constitutively associated with Grb2 and this interaction was mediated by Grb2 SH3 domains. Tyrosine-phosphorylated Shc, which prominently associated with Grb2, was detected in association with Cbl in activated B cells. Thus, Grb2 and Shc adaptors, which associate with immunoreceptor tyrosine based activation motifs, may link Cbl to the B cell receptor. B cell activation also induced a prominent association between Cbl and the p85 subunit of phosphatidylinositol (PI) 3-kinase resulting in the association of a substantial fraction of PI 3-kinase activity with Cbl. Thus, Cbl is likely to play an important role to couple the B cell receptor to the PI 3-kinase pathway. Our results strongly suggest a role for p120(cbl) in signaling downstream of the B cell receptor and support the idea that Cbl participates in a general signal transduction function downstream of the immune cell surface receptors. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DIV RHEUMATOL & IMMUNOL,LYMPHOCYTE BIOL SECT,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT MED,JOSLIN DIABET CTR,RES DIV,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. HARVARD UNIV,BETH ISRAEL HOSP,DIV SIGNAL TRANSDUCT,BOSTON,MA 02115. OREGON HLTH SCI UNIV,DIV HEMATOL & MED ONCOL,PORTLAND,OR 97201. RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 FU NIAMS NIH HHS [AR36308]; NIGMS NIH HHS [GM36624, R01 GM041890] NR 56 TC 172 Z9 172 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 9 PY 1996 VL 271 IS 6 BP 3187 EP 3194 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TU691 UT WOS:A1996TU69100048 PM 8621719 ER PT J AU White, K Tahaoglu, E Steller, H AF White, K Tahaoglu, E Steller, H TI Cell killing by the Drosophila gene reaper SO SCIENCE LA English DT Article ID DEATH AB The reaper gene (rpr) is important for the activation of apoptosis in Drosophila. To investigate whether rpr expression is sufficient to induce apoptosis, transgenic flies were generated that express rpr complementary DNA or the rpr open reading frame in cells that normally live. Transcription of rpr from a heat-inducible promoter rapidly caused widespread ectopic apoptosis and organismal death. Ectopic overexpression of rpr in the developing retina resulted in eye ablation. The occurrence of cell death was highly sensitive to the dosage of the transgene. Because cell death induced by the protein encoded by rpr(RPR)could be blocked by the baculovirus p35 protein, RPR appears to activate a death program mediated by a ced-3/ICE (interleukin-1 converting enzyme)-like protease. C1 MIT,HOWARD HUGHES MED INST,CAMBRIDGE,MA 02139. MIT,DEPT BRAIN & COGNIT SCI,CAMBRIDGE,MA 02139. MIT,DEPT BIOL,CAMBRIDGE,MA 02139. RP White, K (reprint author), MASSACHUSETTS GEN HOSP,CUTANEOUS BIOL RES CTR,BOSTON,MA 02129, USA. RI White, Kristin/D-7936-2013 NR 20 TC 295 Z9 300 U1 1 U2 7 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD FEB 9 PY 1996 VL 271 IS 5250 BP 805 EP 807 DI 10.1126/science.271.5250.805 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TU694 UT WOS:A1996TU69400045 PM 8628996 ER PT J AU Eliasson, L Renstrom, E Ammala, C Berggren, PO Bertorello, AM Bokvist, K Chibalin, A Deeney, JT Flatt, PR Gabel, J Gromada, J Larsson, O Lindstrom, P Rhodes, CJ Rorsman, P AF Eliasson, L Renstrom, E Ammala, C Berggren, PO Bertorello, AM Bokvist, K Chibalin, A Deeney, JT Flatt, PR Gabel, J Gromada, J Larsson, O Lindstrom, P Rhodes, CJ Rorsman, P TI PKC-dependent stimulation of exocytosis by sulfonylureas in pancreatic beta cells SO SCIENCE LA English DT Article ID DIAZOXIDE; GLIBENCLAMIDE; TOLBUTAMIDE; ACTIVATION; CHANNELS; CURRENTS; RELEASE AB Hypoglycemic sulfonylureas represent a group of clinically useful antidiabetic compounds that stimulate insulin secretion from pancreatic beta cells. The molecular mechanisms involved are not fully understood but are believed to involve inhibition of potassium channels sensitive to adenosine triphosphate (K-ATP channels) in the beta cell membrane, causing membrane depolarization, calcium influx, and activation of the secretory machinery. In addition to these effects, sulfonylureas also promoted exocytosis by direct interaction with the secretory machinery not involving closure of the plasma membrane K-ATP channels. This effect was dependent on protein kinase C (PKC) and was observed at therapeutic concentrations of sulfonylureas, which suggests that it contributes to their hypoglycemic action in diabetics. C1 NOVO NORDISK AS,DEPT ISLET CELL PHYSIOL,DK-2100 COPENHAGEN,DENMARK. GOTHENBURG UNIV,DEPT PHYSIOL & PHARMACOL,DIV BIOPHYS,S-41390 GOTHENBURG,SWEDEN. KAROLINSKA INST,ROLF LUFT CTR DIABET RES,DEPT MOLEC MED,S-17176 STOCKHOLM,SWEDEN. BOSTON UNIV,SCH MED,EVANS DEPT MED,DIABET & METAB UNIT,BOSTON,MA 02118. BOSTON UNIV,SCH MED,DEPT BIOCHEM,BOSTON,MA 02118. UNIV ULSTER,DEPT BIOL & BIOMED SCI,COLERAINE BT52 1SA,LONDONDERRY,NORTH IRELAND. UMEA UNIV,DEPT HISTOL & CELL BIOL,S-90187 UMEA,SWEDEN. HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,BOSTON,MA 02215. RI Rorsman, Patrik/A-4331-2016; OI Rorsman, Patrik/0000-0001-7578-0767; Flatt, Peter/0000-0001-8548-7943 NR 28 TC 157 Z9 158 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 FEB 9 PY 1996 VL 271 IS 5250 BP 813 EP 815 DI 10.1126/science.271.5250.813 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TU694 UT WOS:A1996TU69400048 PM 8628999 ER PT J AU Blumenthal, D Causino, N Campbell, E Louis, KS AF Blumenthal, D Causino, N Campbell, E Louis, KS TI Relationships between academic institutions and industry in the life sciences - An industry survey SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID BIOTECHNOLOGY; UNIVERSITY AB Background. Despite growing acceptance of relationships between academia and industry in the life sciences, systematic, up-to-date information about their extent and the consequences for the parties involved remains scarce. We attempted to collect information about the prevalence, magnitude, commercial benefits, and potential risks of such relationships by surveying a representative sample of life-science companies in the United States to determine their relationships with academic institutions. Methods. We collected data by telephone from May through September 1994 from senior executives of 210 life-science companies (of 306 companies surveyed; response rate, 69 percent). The sample contained all Fortune 500 companies in the fields of agriculture, chemicals, and pharmaceuticals; all international pharmaceutical companies with sales volumes similar to those of the Fortune 500 companies; and a random sample of non-fortune 500 companies in the life sciences drawn from multiple commercial and noncommercial directories. Both the survey instrument and the survey methods resembled those of our 1984 study of 106 biotechnology companies, allowing us to assess the evolution of relationships between academia and industry over the past decade. Results. Ninety percent of companies conducting life-science research in the United States had relationships involving the life sciences with an academic institution in 1994. Fifty-nine percent supported research in such institutions, providing an estimated $1.5 billion, or approximately 11.7 percent of all research-and-development funding received that year. The agreements with universities tended to be short-term and to involve small amounts, implying that most such relationships supported applied research or development. Over 60 percent of companies providing support for life-science research in universities had received patents, products, and sales as a result of those relationships. At the same time, the companies reported that their relationships with universities often included agreements to keep the results of research secret beyond the time needed to file a patent. From 1984 to 1994, the involvement of industry with academic institutions has increased, but the characteristics of the relationships have remained remarkably stable. Conclusions. After more than a decade of sustained interaction, universities and industries seem to have formed durable partnerships in the life sciences, although the relationships may pose greater threats to the openness of scientific communication than universities generally acknowledge. However, industrial support for university research is much smaller in amount than federal support, and companies are unlikely to be able to compensate for sizable federal cutbacks. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT HLTH CARE POLICY,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,HLTH POLICY RES & DEV UNIT,BOSTON,MA. UNIV MINNESOTA,COLL EDUC,MINNEAPOLIS,MN 55455. FU NHGRI NIH HHS [HG00724-01] NR 18 TC 191 Z9 193 U1 1 U2 20 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD FEB 8 PY 1996 VL 334 IS 6 BP 368 EP 373 DI 10.1056/NEJM199602083340606 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA TT487 UT WOS:A1996TT48700006 PM 8538709 ER PT J AU vanderGeer, P Wiley, S Gish, GD Lai, VKM Stephens, R White, MF Kaplan, D Pawson, T AF vanderGeer, P Wiley, S Gish, GD Lai, VKM Stephens, R White, MF Kaplan, D Pawson, T TI Identification of residues that control specific binding of the Shc phosphotyrosine-binding domain to phosphotyrosine sites SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE tyrosine phosphorylation; signal transduction ID TYROSINE KINASE-ACTIVITY; INSULIN-RECEPTOR; MONOCLONAL-ANTIBODIES; SIGNAL TRANSDUCTION; NUCLEOTIDE EXCHANGE; EGF RECEPTOR; GRB2; PROTEIN; RAS; PHOSPHORYLATION AB The She adaptor protein contains two phosphotyrosine [Tyr(P)]binding modules-an N-terminal Tyr(P) binding (PTB) domain and a C-terminal Src homology 2 (SH2) domain, We have compared the ability of the She PTB domain to bind the receptors for nerve growth factor and insulin, both of which contain juxtamembrane Asn-Pro-Xaa-Tyr(P) motifs implicated in PTB binding, The She PTB domain binds with high affinity to a phosphopeptide corresponding to the nerve growth factor receptor Tyr-490 autophosphorylation site, Analysis of individual residues within this motif indicates that the Asn at position -3 [with respect to Tyr(P)], in addition to Tyr(P), is critical for PTB binding, while the Pro at position -2 plays a less significant role. A hydrophobic amino acid 5 residues N-terminal to the Tyr(P) is also essential for high-affinity binding, In contrast, the She PTB domain does not bind stably to the Asn-Pro-Xaa-Tyr(P) site at Tyr-960 in the activated insulin receptor, which has a polar residue (Ser) at position -5. Substitution of this Ser at position -5 with Ile markedly increased binding of the insulin receptor Tyr-960 phosphopeptide to the PTB domain, These results suggest that while the She PTB domain recognizes a core sequence of Asn-Pro-Xaa-Tyr(P), its binding affinity is modulated by more N-terminal residues in the ligand, which therefore contribute to the specificity of PTB-receptor interactions, An analysis of residues in the She PTB domain required for binding to Tyr(P) sites identified a specific and evolutionarily conserved Arg (Arg-175) that is uniquely important for ligand binding and is potentially involved in Tyr(P) recognition. C1 MT SINAI HOSP,SAMUEL LUNENFELD RES INST,PROGRAMME MOLEC BIOL & CANC,TORONTO,ON M5G 1X5,CANADA. MT SINAI HOSP,SAMUEL LUNENFELD RES INST,PROT ENGN NETWORK CTR EXCELLENCE,TORONTO,ON M5G 1X5,CANADA. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. JOSLIN DIABET CTR,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RI Pawson, Tony/E-4578-2013; Gish, Gerald/C-7228-2017 NR 49 TC 94 Z9 94 U1 1 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 6 PY 1996 VL 93 IS 3 BP 963 EP 968 DI 10.1073/pnas.93.3.963 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TU640 UT WOS:A1996TU64000001 PM 8577769 ER PT J AU Greenberg, S Chang, P Wang, DC Xavier, R Seed, B AF Greenberg, S Chang, P Wang, DC Xavier, R Seed, B TI Clustered syk tyrosine kinase domains trigger phagocytosis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cytoskeleton; actin; Fe receptors ID RECEPTOR MEDIATED PHAGOCYTOSIS; MACROPHAGE MANNOSE RECEPTOR; ACTIN POLYMERIZATION; MOUSE MACROPHAGES; T-CELLS; ACTIVATION; MEMBRANE AB Phagocytosis is a phylogenetically primitive mechanism adapted by specialized cells of the immune system to ingest particulate pathogens. Recent evidence suggests that the program of specific cytoskeletal rearrangements that underlies phagocytosis may share elements with the antigen receptor signaling pathway in lymphocytes. Tyrosine phosphorylation, necessary for both lymphocyte effector function and phagocytosis, is thought to allow cytoskeletal elements to couple to the intracellular domains of antigen and Fc receptor subunits. We show here that the intracellular domains of the receptors are not inherently required for cytoskeletal coupling. Chimeric transmembrane proteins bearing syk but not src family tyrosine kinase domains are capable of autonomously triggering phagocytosis and redistribution of filamentous actin In COS cells, These responses cannot be initiated by a receptor chimera bearing a point mutation in the syk catalytic domain, and the kinase domain alone is sufficient for initiating cytoskeletal coupling. C1 MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. RP Greenberg, S (reprint author), COLUMBIA UNIV COLL PHYS & SURG,DEPT MED,DIV PULM,NEW YORK,NY 10032, USA. NR 30 TC 105 Z9 105 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 6 PY 1996 VL 93 IS 3 BP 1103 EP 1107 DI 10.1073/pnas.93.3.1103 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TU640 UT WOS:A1996TU64000027 PM 8577722 ER PT J AU Dember, LM Kim, ND Liu, KQ Anderson, P AF Dember, LM Kim, ND Liu, KQ Anderson, P TI Individual RNA recognition motifs of TIA-1 and TIAR have different RNA binding specificities SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SMALL NUCLEAR RIBONUCLEOPROTEIN; U1 RNA; SPLICE SITE; A-PROTEIN; GENE; IDENTIFICATION; DOMAIN; DETERMINANTS; SEGMENT AB TIA-1 and TIAR are two closely related RNA recognition motif (RRM) proteins which possess three RRM-type RNA binding domains (RRMs 1, 2, and 3). Although both proteins have been implicated as effecters of apoptotic cell death, the specific functions of TIA-1 and TIAR are not known, We have performed in vitro selection/amplification from pools of random RNA sequences to identify RNAs to which TIA-1 and TIAR bind with high affinity. Both proteins selected RNAs containing one or several short stretches of uridylate residues suggesting that the two proteins have similar RNA binding specificities. Replacement of the uridylate stretch with an equal number of cytidine residues eliminates the protein-RNA interaction. Mutational analysis indicates that, for both TIA-1 and TIAR, it is the second RNA binding domain (RRM 2) which mediates the specific binding to uridylate-rich RNAs. Although RRM 2 is both necessary and sufficient for this interaction, the affinity for the selected RNA (as determined by filter binding assays) does increase when the second domain of TIAR is expressed together with the first and third domains (K-d = 2 x 10(-8) M) rather than alone (K-d = 5 x 10(-8) M). Although RRM 3 (of either TIA-1 or TIAR) does not interact with the uridylate-rich sequences selected by the full-length proteins, it is a bona fide RNA binding domain capable of affinity-precipitating a population of cellular RNAs ranging in size from 0.5 to 5 kilobases. In contrast, RRM 1 does not affinity-precipitate cellular RNA. The inability of RRM 1 to interact with RNA may be due to the presence of negatively charged amino acids within the RNP 1 octamer. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT RHEUMATOL,BOSTON,MA 02115. RP Dember, LM (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,MAYER 747,44 BINNEY ST,BOSTON,MA 02115, USA. FU NIAID NIH HHS [AI33600] NR 41 TC 137 Z9 139 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 FEB 2 PY 1996 VL 271 IS 5 BP 2783 EP 2788 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TT488 UT WOS:A1996TT48800069 PM 8576255 ER PT J AU Masland, RH AF Masland, RH TI Unscrambling color vision SO SCIENCE LA English DT Editorial Material ID HORIZONTAL CELLS; RECEPTIVE-FIELDS; RETINA RP Masland, RH (reprint author), MASSACHUSETTS GEN HOSP, HOWARD HUGHES MED INST, BOSTON, MA 02114 USA. NR 14 TC 21 Z9 21 U1 1 U2 2 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD FEB 2 PY 1996 VL 271 IS 5249 BP 616 EP 617 DI 10.1126/science.271.5249.616 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TT870 UT WOS:A1996TT87000034 PM 8571123 ER PT J AU Hotamisligil, GS Peraldi, P Budavari, A Ellis, R White, MF Spiegelman, BM AF Hotamisligil, GS Peraldi, P Budavari, A Ellis, R White, MF Spiegelman, BM TI IRS-1-mediated inhibition of insulin receptor tyrosine kinase activity in TNF-alpha- and obesity-induced insulin resistance SO SCIENCE LA English DT Article ID TUMOR-NECROSIS-FACTOR; CELLS; IRS-1 AB Tumor necrosis factor-alpha (TNF-alpha) is an important mediator of insulin resistance in obesity and diabetes through its ability to decrease the tyrosine kinase activity of the insulin receptor (IR). Treatment of cultured murine adipocytes with TNF-alpha was shown to induce serine phosphorylation of insulin receptor substrate 1 (IRS-1) and convert IRS-1 into an inhibitor of the IR tyrosine kinase activity in vitro. Myeloid 32D cells, which lack endogenous IRS-1, were resistant to TNF-alpha-mediated inhibition of IR signaling, whereas transfected 32D cells that express IRS-1 were very sensitive to this effect of TNF-alpha. An inhibitory form of IRS-1 was observed in muscle and fat tissues from obese rats. These results indicate that TNF-alpha induces insulin resistance through an unexpected action of IRS-1 to attenuate insulin receptor signaling. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MOLEC & CELLULAR BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. RI Peraldi, Pascal/O-4592-2016 OI Peraldi, Pascal/0000-0003-0205-9252 FU NIDDK NIH HHS [DK 42539] NR 27 TC 1578 Z9 1640 U1 9 U2 90 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD FEB 2 PY 1996 VL 271 IS 5249 BP 665 EP 668 DI 10.1126/science.271.5249.665 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TT870 UT WOS:A1996TT87000052 PM 8571133 ER PT J AU Stone, CK Thomas, SH Koury, SI Low, RB AF Stone, CK Thomas, SH Koury, SI Low, RB TI Glucagon and phenylephrine combination vs glucagon alone in experimental verapamil overdose SO ACADEMIC EMERGENCY MEDICINE LA English DT Article; Proceedings Paper CT SAEM Annual Meeting CY MAY, 1995 CL SAN ANTONIO, TX SP Soc Acad Emergency Med DE verapamil; overdose; glucagon; phenylephrine; pharmacology; therapy; toxicology; hemodynamics ID TOXICITY; CALCIUM AB Objective: To evaluate glucagon and phenylephrine in combination as a treatment for the hemodynamic effects of verapamil overdose, Methods: Pentobarbital-anesthetized and instrumented dogs were overdosed using a previously developed verapamil overdose model (15 mg/kg IV over 30 minutes), The animals were maintained and observed for 90 minutes or until death. Cardiac output (GO), heart rate (HR), and mean arterial pressure (MAP) were monitored, Following the 30-minute verapamil infusion (toxicity), the control animals received no treatment; the glucagon animals received a 5-mg glucagon bolus and a drip of 5 mg/90 minutes; and the glucagon/phenylephrine animals received the same glucagon therapy plus a phenylephrine drip titrated to 180 mu g/min min over 15 minutes. The groups were compared using analysis of variance: the experimental variables were group and time; the response variables were changes from toxicity for the hemodynamic parameters. Post-hoc comparisons were done with a set at 0.05. Results: A significant change in CO was seen in the glucagon group (Delta = 2.6 L/min) and the glucagon/phenylephrine group (Delta = 1.9 L/min) compared with the control group (Delta = 0.8 L/min). The change in CO was significantly larger for the glucagon animals compared with the glucagon/phenylephrine animals. The change in MAP for the glucagon/phenylephrine group (Delta = 24 mm Hg) was significant compared with the control group (Delta = 14 mm Hg). The MAP change for the glucagon group (Delta = 19 mm Hg) was not significantly different from that of either the control or the glucagon/phenylephrine group. The change in glucagon HR (Delta = 6 beats/min) was significant compared with the control group (Delta = -4 beats/min) and the glucagon/phenylephrine group (Delta = -4 beats/min). Conclusion: The glucagon/phenylephrine therapy improved MAP compared with the control, but reduced CO and HR compared with glucagon alone. Glucagon/phenylephrine therapy is not as effective as glucagon in reversing the hemodynamic effects of experimental verapamil overdose. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT EMERGENCY MED,BOSTON,MA. E CAROLINA UNIV,SCH MED,DEPT EMERGENCY MED,GREENVILLE,NC. SUNY DOWNSTATE MED CTR,DEPT EMERGENCY MED,BROOKLYN,NY. RP Stone, CK (reprint author), UNIV KENTUCKY,MED CTR,DEPT EMERGENCY MED,COLL MED,ROOM M-53,800 ROSE ST,LEXINGTON,KY 40536, USA. NR 13 TC 17 Z9 17 U1 0 U2 1 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD FEB PY 1996 VL 3 IS 2 BP 120 EP 125 DI 10.1111/j.1553-2712.1996.tb03398.x PG 6 WC Emergency Medicine SC Emergency Medicine GA TR781 UT WOS:A1996TR78100007 PM 8808371 ER PT J AU Stone, CK Stapczynski, JS Thomas, SH Koury, SI AF Stone, CK Stapczynski, JS Thomas, SH Koury, SI TI Rate of patient workups by non-emergency medicine residents in an academic emergency department SO ACADEMIC EMERGENCY MEDICINE LA English DT Article; Proceedings Paper CT SAEM Annual Meeting CY MAY, 1995 CL SAN ANTONIO, TX SP Soc Acad Emergency Med DE residency; emergency medicine; education; medical education AB Objective: To quantify the number of patients seen per hour by non-emergency medicine (non-EM) residents in a university hospital ED. Methods: This retrospective observational study was performed in a university hospital ED and level I trauma center. The facility had no EM residency, but was staffed with 24-hour EM faculty coverage. A computerized tracking system was searched for the number of patients seen by each of 93 non-EM residents for 12 nonconsecutive months. The ED schedule for each month was used to calculate the number of hours worked by each resident. From these figures, the number of patients seen per hour by each resident was calculated. Results: The postgraduate years of training of the residents were as follows: 78 (84%) were PGY1, ten (11%) were PGY2, and five (5%) were PGY3. All the residents combined saw a mean 0.95 +/- 0.20 patients/hour, with a range from 0.58 to 1.75 patients/hour. There was no significant difference between the numbers of patients seen when compared by specialty using the Tukey-Kramer test (alpha = 0.05). Conclusion: The rate at which non-EM residents work up patients is consistent with previously reported rates for EM residents. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT EMERGENCY MED,BOSTON,MA. E CAROLINA UNIV,SCH MED,DEPT EMERGENCY MED,GREENVILLE,NC. RP Stone, CK (reprint author), UNIV KENTUCKY,MED CTR,DEPT EMERGENCY MED,ROOM M-53,800 ROSE ST,LEXINGTON,KY 40536, USA. NR 2 TC 3 Z9 3 U1 1 U2 1 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD FEB PY 1996 VL 3 IS 2 BP 153 EP 156 DI 10.1111/j.1553-2712.1996.tb03404.x PG 4 WC Emergency Medicine SC Emergency Medicine GA TR781 UT WOS:A1996TR78100013 PM 8808377 ER PT J AU Spillane, RM Whitman, GJ McCarthy, KA Hulka, CA Hall, DA Kopans, DB AF Spillane, RM Whitman, GJ McCarthy, KA Hulka, CA Hall, DA Kopans, DB TI Computed tomography-guided needle localization of nonpalpable breast lesions: Review of 24 cases SO ACADEMIC RADIOLOGY LA English DT Article DE localization; breast biopsy; breast lesion; needle localization; computed tomography ID PERCUTANEOUS LOCALIZATION; BIOPSY; SONOGRAPHY; EXPERIENCE; VIEW; US AB Rationale and Objectives. We examined the role of computed tomography (CT) in breast imaging, especially in guiding needle localization procedures. Methods. We reviewed our institution's breast imaging database, from 1978 to 1994, for procedures in which CT scanning was used. Twenty-four-CT-guided needle localizations were identified. Medical records, mammograms, CT scans, and patholo,qv reports were reviewed for all patients. Results. Twenty-four needle localizations were performed on 22 female patients. The average size of the lesions localized was 12 mm. The most common reason for CT scanning was the inability to image a suspicious density by conventional mammography on two orthogonal views. Nine malignant and lj benign lesions were localized under CT guidance. One patient developed a postoperative hematoma. No other complications occurred. Conclusion. CT-guided breast localization is a reliable technique that may be used to define selected breast lesions that are difficult to triangulate or localize by conventional two-view mammography. C1 HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,DEPT RADIOL,DIV BREAST IMAGING,BOSTON,MA 02114. NR 25 TC 7 Z9 8 U1 0 U2 0 PU ASSOC UNIV RADIOLOGISTS PI RESTON PA 1891 PRESTON WHITE DR, RESTON, VA 22091 SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD FEB PY 1996 VL 3 IS 2 BP 115 EP 120 DI 10.1016/S1076-6332(05)80376-9 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA TT651 UT WOS:A1996TT65100004 PM 8796651 ER PT J AU Jiang, DY Gazelle, GS Wolf, GL AF Jiang, DY Gazelle, GS Wolf, GL TI A model of focal cancer in rabbit lymph nodes SO ACADEMIC RADIOLOGY LA English DT Article DE cancer; lymph node; computed tomography lymphography; popliteal node AB Rationale and Objectives. We sought to develop a model of focal cancer in the rabbit lymph node. Methods. Under computed tomography (CT) guidance, 4-5 million VX2 cells were directly injected into the popliteal nodes of 14 anesthetized New Zealand White rabbits. Fifteen to 18 days later, percutaneous lymphography was performed with CT scanning using radiopaque nanoparticulates and massage, Histologic correlation also was obtained. Results. In 12 of the 14 animals, focal lesions were successfully created within (n = 6) and adjacent (n = 6) to the node, and all animals appeared to be healthy when euthanized. Within 15 min after massage, CT lymphography showed homo normal node regions and no enhancement of cancer. There was good agreement between histology and lymphography. Conclusion. This method is suitable as a model to test for diagnostic and therapeutic interventions. C1 MASSACHUSETTS GEN HOSP,CTR IMAGING & PHARMACEUT RES,BOSTON,MA 02129. NR 12 TC 7 Z9 7 U1 0 U2 0 PU ASSOC UNIV RADIOLOGISTS PI RESTON PA 1891 PRESTON WHITE DR, RESTON, VA 22091 SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD FEB PY 1996 VL 3 IS 2 BP 159 EP 162 DI 10.1016/S1076-6332(05)80386-1 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA TT651 UT WOS:A1996TT65100010 PM 8796657 ER PT J AU Lorsch, JR Szostak, JW AF Lorsch, JR Szostak, JW TI Chance and necessity in the selection of nucleic acid catalysts SO ACCOUNTS OF CHEMICAL RESEARCH LA English DT Review ID INVITRO SELECTION; RNA; EVOLUTION; TETRAHYMENA; MOLECULES; CLEAVAGE; RIBOZYME; LIGANDS; LIFE; BIND RP Lorsch, JR (reprint author), MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114, USA. OI Lorsch, Jon/0000-0002-4521-4999 NR 57 TC 94 Z9 95 U1 1 U2 13 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0001-4842 J9 ACCOUNTS CHEM RES JI Accounts Chem. Res. PD FEB PY 1996 VL 29 IS 2 BP 103 EP 110 DI 10.1021/ar9501378 PG 8 WC Chemistry, Multidisciplinary SC Chemistry GA TV828 UT WOS:A1996TV82800006 PM 11539421 ER PT J AU Woody, GE AF Woody, GE TI Present difficulties, future possibilities SO ADDICTION LA English DT Article C1 UNIV PENN,DEPT PSYCHIAT,PHILADELPHIA,PA 19104. RP Woody, GE (reprint author), PHILADELPHIA VET AFFAIRS MED CTR,SUBST ABUSE TREATMENT & RES CTR,39TH & WOODLAND AVE,PHILADELPHIA,PA 19104, USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU CARFAX PUBL CO PI ABINGDON PA PO BOX 25, ABINGDON, OXFORDSHIRE, ENGLAND OX14 3UE SN 0965-2140 J9 ADDICTION JI Addiction PD FEB PY 1996 VL 91 IS 2 BP 226 EP 228 DI 10.1111/j.1360-0443.1996.tb03181.x PG 3 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA TT860 UT WOS:A1996TT86000008 ER PT J AU Yousfi, MM ElZimaity, HM Cole, RA Genta, RM Graham, DY AF Yousfi, MM ElZimaity, HM Cole, RA Genta, RM Graham, DY TI Metronidazole, ranitidine and clarithromycin combination for treatment of Helicobacter pylori infection (modified Bazzoli's triple therapy) SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID CAMPYLOBACTER-PYLORI; DUODENAL-ULCERS; SUSCEPTIBILITY; RESISTANCE AB Background: Multi-drug regimens are generally required to reliably cure Helicobacter pylori infection, Metronidazole, clarithromycin and omeprazole has proven to be an effective combination therapy with a cure rate of 90% or greater. Methods: We evaluated a 14-day combination regimen for H, pylori infection consisting of metronidazole 500 mg b.d., clarithromycin 250 mg b.d. and ranitidine 300 mg b.d, (MRC) instead of omeprazole, Ranitidine alone was continued for an additional 4 weeks, H, pylori status was determined by rapid urease testing, histopathology using the Genta stain, and by culture at entry and 4 weeks after completing antimicrobial therapy. Results: Twenty-seven patients with documented peptic ulcer disease and H. pylori infection were treated. Five had previously failed macrolide-based antimicrobial therapy; none had received metronidazole. All ulcers were healed at week 6 except one patient taking naproxen; his H, pylori infection was cured, Overall, H. pylori infection was cured in 78% (95% CI = 58-91%). In patients with clarithromycin-sensitive isolates, the cure rate was 20 of 23 (87%, 95% C.I. = 66-97%); only one of four patients (25%) with clarithromycin-resistant isolates was cured, In contrast, four of five patients with metronidazole-resistant isolates were cured (80%), In patients with isolates sensitive to both antibiotics, the cure rate was 16 of 18 (89%, 95% C.I. = 65-99%), Mild side effects were reported by 27%, including diarrhoea and altered taste. Compliance averaged 98%. Conclusion: These results suggest that the combination of metronidazole, ranitidine and clarithromycin results in high cure rates in patients with clarithromycinsensitive isolates, Omeprazole may not be required for Bazzoli's triple therapy; and large multicentre comparative trials are indicated. C1 VET AFFAIRS MED CTR 111D,DEPT MED,HOUSTON,TX 77030. VET AFFAIRS MED CTR,DEPT PATHOL,HOUSTON,TX 77030. VET AFFAIRS MED CTR,DIV MOLEC VIROL,HOUSTON,TX 77030. BAYLOR COLL MED,HOUSTON,TX 77030. NR 26 TC 26 Z9 26 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0269-2813 J9 ALIMENT PHARM THERAP JI Aliment. Pharmacol. Ther. PD FEB PY 1996 VL 10 IS 1 BP 119 EP 122 PG 4 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA TX821 UT WOS:A1996TX82100013 PM 8871452 ER PT J AU Garcia, GE AF Garcia, GE TI Management of ocular emergencies and urgent eye problems SO AMERICAN FAMILY PHYSICIAN LA English DT Article AB Evaluation of the patient with an acute eye problem begins with documentation of the level of vision in each eye, except in the case of a splash injury. In such cases, immediate copious irrigation is of critical importance. Subconjunctival hemorrhage is common and, typically, completely benign. Herpes simplex infection is painful and can lead to extensive damage. Herpes tester infection is usually accompanied by skin lesions and can be effectively treated with oral acyclovir or famcyclovir. In patients with Bell's palsy, the eye must be carefully protected to prevent secondary injury. Corneal abrasions heal rapidly when antibiotics and patch protection are provided. Acute infections of the eyelids and conjunctivae usually respond well to topical antibiotics and warm compresses. Traumatic injuries require careful evaluation and, frequently, referral to an ophthalmologist. C1 MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. NR 7 TC 4 Z9 4 U1 0 U2 1 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 FEB 1 PY 1996 VL 53 IS 2 BP 565 EP 574 PG 10 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA TU741 UT WOS:A1996TU74100009 PM 8629538 ER PT J AU Nakatani, S Schwammenthal, E Lever, HM Levine, RA Lytle, BW Thomas, JD AF Nakatani, S Schwammenthal, E Lever, HM Levine, RA Lytle, BW Thomas, JD TI New insights into the reduction of mitral valve systolic anterior motion after ventricular septal myectomy in hypertrophic obstructive cardiomyopathy SO AMERICAN HEART JOURNAL LA English DT Article ID SUB-AORTIC STENOSIS; OUTFLOW OBSTRUCTION; ECHOCARDIOGRAPHIC ASSESSMENT; OPERATIVE TREATMENT; SUBAORTIC STENOSIS; MYOTOMY-MYECTOMY; M-MODE; DETERMINANTS; RELIEF AB To determine the mechanism of reduction of mitral valve systolic anterior motion by myectomy, we examined 33 patients with hypertrophic obstructive cardiomyopathy echocardiographically before and after myectomy. Measurements included outflow tract diameter, the direction of ejection streamline (the angle between the ejection flow and the mitral valve), midventricular fractional area change, and papillary muscle inward excursion in the short-axis image. After myectomy, the outflow tract was enlarged (from 1.2 +/- 0.3 cm to 2.1 +/- 0.4 cm; p < 0.001), and the ejection flow became more parallel to mitral leaflets (from 51 +/- 10 degrees to 28 +/- 8 degrees; p < 0.001), whereas hyperdynamic midventricular fractional area change was reduced (81% +/- 14% to 62% +/- 14%; p < 0.001), and papillary muscle excursion decreased (1.3 +/- 0.3 cm to 0.8 +/- 0.3 cm; p < 0.001). Outflow enlargement and reduced ventricular contraction would decrease the Venturi force. Change of ejection streamline and reduced contraction would decrease the drag force onto the mitral leaflets. Blunted papillary motion would increase the mitral leaflet tension and decrease the effect of drag force on both leaflets. Thus myectomy decreases Venturi and drag forces and appears to reduce systolic anterior motion of the mitral valve. C1 CLEVELAND CLIN FDN,DEPT CARDIOL,CARDIOVASC IMAGING CTR,CLEVELAND,OH 44195. CLEVELAND CLIN FDN,DEPT CARDIOTHORAC SURG,CLEVELAND,OH 44195. MASSACHUSETTS GEN HOSP,CARDIAC ULTRASOUND LAB,BOSTON,MA 02114. NR 36 TC 25 Z9 25 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 FEB PY 1996 VL 131 IS 2 BP 294 EP 300 DI 10.1016/S0002-8703(96)90357-9 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA TV307 UT WOS:A1996TV30700015 PM 8579024 ER PT J AU dePrada, JAV Chen, MH Guerrero, JL Padial, LR Jiang, L Schwammenthal, E Sagie, A Weyman, AE Levine, RA Chen, CG AF dePrada, JAV Chen, MH Guerrero, JL Padial, LR Jiang, L Schwammenthal, E Sagie, A Weyman, AE Levine, RA Chen, CG TI Intracardiac echocardiography: In vitro and in vivo validation for right ventricular volume and function SO AMERICAN HEART JOURNAL LA English DT Article ID DIMENSIONAL ECHOCARDIOGRAPHY; DILATED CARDIOMYOPATHY; MYOCARDIAL-INFARCTION; EJECTION FRACTION; DISEASE; SIZE; CINEANGIOGRAMS; PROGNOSIS; HUMANS AB To determine the feasibility and accuracy of intracardiac ultrasonography (ICUS) for the measurement of right ventricular (RV) volumes and function, a 10 MHz ICUS catheter was used in an in vitro and in vivo model. In the in vitro study, 16 sheep hearts were imaged. Sequential cross-sectional images from RV apex to base were recorded during a calibrated pullback. Volumes were calculated by applying Simpson's algorithm. ICUS-obtained volumes correlated well with actual volumes (standard error of estimate [SEE] = 2.3 ml, r = 0.98). For the in vivo study, a beating-heart canine model was used (31 hemodynamic stages in six dogs). Actual volumes were measured by an intracavitary balloon connected to an external column. Sequential cross-sectional images were recorded during the ICUS catheter pullback from apex to base of the RV, and volumes calculated by Simpson's algorithm. Good correlations were observed between ICUS and actual values for diastolic (SEE = 4.1 ml, r = 0.97), systolic (SEE = 3.4 ml, r = 0.96), and ejection fraction (SEE = 3.1%, r = 0.87) values. This new technique can accurately quantitate RV volumes, can function both in vitro and in vivo, and has the potential for increasing applications to questions of clinical and research interest. C1 HARTFORD HOSP, DIV CARDIOL, HARTFORD, CT 06102 USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED, CARDIAC ULTRASOUND LAB, BOSTON, MA USA. UNIV CONNECTICUT, SCH MED, HARTFORD, CT 06112 USA. RI Guerrero, Jorge/I-3666-2015 OI Guerrero, Jorge/0000-0003-4315-7318 NR 29 TC 12 Z9 12 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 EI 1097-5330 J9 AM HEART J JI Am. Heart J. PD FEB PY 1996 VL 131 IS 2 BP 320 EP 328 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA TV307 UT WOS:A1996TV30700019 ER PT J AU Block, KP Mahvi, D Voytovich, M Watkins, JL Mosley, R Reichelderfer, M AF Block, KP Mahvi, D Voytovich, M Watkins, JL Mosley, R Reichelderfer, M TI Mucinous ductal ectasia in an octogenarian: Successful treatment with the Whipple procedure SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID PANCREAS; CYSTADENOCARCINOMA; CYSTADENOMA; RESECTION; TUMORS; AGE AB Mucinous ductal ectasia is a recently defined neoplasm of the pancreas characterized by excessive mucin production, The natural history of this entity is unknown, and only two cases in people over the age of 80 yr have appeared in the literature, In this report, we review the literature on mucinous ductal ectasia and present the first report of an octogenarian who was successfully treated by the Whipple procedure. C1 UNIV WISCONSIN,DEPT SURG,MADISON,WI 53792. UNIV WISCONSIN,DEPT PATHOL,MADISON,WI 53792. WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI. RP Block, KP (reprint author), UNIV WISCONSIN,DEPT MED,GI DIV,DIV GASTROENTEROL,ROOM H6-516,CSC,600 HIGHLAND AVE,MADISON,WI 53792, USA. NR 15 TC 5 Z9 5 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD FEB PY 1996 VL 91 IS 2 BP 388 EP 390 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA TV544 UT WOS:A1996TV54400036 PM 8607515 ER PT J AU EstevaLorenzo, FJ Meehan, KR Spitzer, TR Mazumder, A AF EstevaLorenzo, FJ Meehan, KR Spitzer, TR Mazumder, A TI Allogeneic bone marrow transplantation in a patient with hypereosinophilic syndrome SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article DE hypereosinophilic syndrome; bone marrow transplantation; human; therapy AB We describe a 32-year-old man with idiopathic hypereosinophilic syndrome (HES) who presented with pulmonary dysfunction, thrombocytopenia, lymphadenopathy, and hepatosplenomegaly. The patient developed progressive disease on prednisone and hydroxyurea therapy, and he underwent a successful allogeneic bone marrow transplantation (BMT). The patient is asymptomatic with no evidence of eosinophilia 30 months after transplantation, There is currently no cure for patients with HES, and BMT should be considered in selected patients. (C) 1996 Wiley-Liss, Inc. C1 GEORGETOWN UNIV,MED CTR,VINCENT T LOMBARDI CANC RES CTR,BONE MARROW TRANSPLANT PROGRAM,WASHINGTON,DC 20007. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA. NR 8 TC 25 Z9 26 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD FEB PY 1996 VL 51 IS 2 BP 164 EP 165 DI 10.1002/(SICI)1096-8652(199602)51:2<164::AID-AJH12>3.0.CO;2-I PG 2 WC Hematology SC Hematology GA TT553 UT WOS:A1996TT55300012 PM 8579059 ER PT J AU Wijnen, J Khan, PM Vasen, H Menko, F vanderKlift, H vandenBroek, M vanLeeuwenCornelisse, I Nagengast, F MeijersHeijboer, EJ Lindhout, D Griffioen, G Cats, A Kleibeuker, J Varesco, L Bertario, L Bisgaard, ML Mohr, J Kolodner, R Fodde, R AF Wijnen, J Khan, PM Vasen, H Menko, F vanderKlift, H vandenBroek, M vanLeeuwenCornelisse, I Nagengast, F MeijersHeijboer, EJ Lindhout, D Griffioen, G Cats, A Kleibeuker, J Varesco, L Bertario, L Bisgaard, ML Mohr, J Kolodner, R Fodde, R TI Majority of hMLH1 mutations responsible for hereditary nonpolyposis colorectal cancer cluster at the exonic region 15-16 SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID GRADIENT GEL-ELECTROPHORESIS; SINGLE-BASE CHANGES; GENETIC INSTABILITY; COLON-CANCER; POLYPOSIS; SPECTRUM; HOMOLOG AB Hereditary nonpolyposis colorectal cancer (HNPCC) is a common autosomal dominant cancer susceptibility condition. Inherited mutations in at least four DNA mismatch repair genes, hMSH2, hMLH1, hPMS1, and hPMS2, are known to cause HNPCC. In this study we used denaturing gradient gel electrophoresis (DGGE) to screen for hMLH1 mutations in 34 unrelated HNPCC families (30 Dutch, 3 Italian, and 1 Danish). Ten novel pathogenic germ-line mutations (seven affecting splice sites, two frameshifts, and one in-frame deletion of a single amino acid) have been identified in 12 (35%) of these families. In a previous study, hMSH2 mutations were found in 21% of the same families. While the spectrum of mutations at the hMSH2 gene among HNPCC patients appears heterogeneous, a cluster of hMLH1 mutations has been found in the region encompassing exons 15 and 16, which accounts for 50% of all the independent hMLH1 mutations described to date and for >20% of the unrelated HNPCC kindreds here analyzed. This unexpected finding has a great practical value in the clinical scenario of genetic services. C1 LEIDEN UNIV,SYLVIUS LAB,CTR MED GENET,DEPT HUMAN GENET,2300 RA LEIDEN,NETHERLANDS. LEIDEN UNIV,MED CTR,FDN DETECT HEREDITARY TUMORS,LEIDEN,NETHERLANDS. LEIDEN UNIV,MED CTR,DEPT GASTROENTEROL,LEIDEN,NETHERLANDS. FREE UNIV AMSTERDAM HOSP,DEPT CLIN GENET,AMSTERDAM,NETHERLANDS. UNIV NIJMEGEN HOSP,DEPT GASTROENTEROL,6500 HB NIJMEGEN,NETHERLANDS. ERASMUS UNIV ROTTERDAM,DEPT CLIN GENET,3000 DR ROTTERDAM,NETHERLANDS. UNIV GRONINGEN HOSP,DEPT GASTROENTEROL,GRONINGEN,NETHERLANDS. IST NAZL RIC CANC,I-16132 GENOA,ITALY. UNIV MILAN,REGISTRO ITALIANO POLIPOSI FAMILIARI,MILAN,ITALY. UNIV COPENHAGEN,PANUM INST,INST MED BIOCHEM & GENET,DK-2200 COPENHAGEN,DENMARK. HVIDOVRE UNIV HOSP,DANISH HNPCC REGISTRY,HVIDOVRE,DENMARK. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELLULAR & MOLEC BIOL,BOSTON,MA 02115. OI Fodde, Riccardo/0000-0001-9839-4324; Lindhout, Dick/0000-0001-9580-624X FU NIGMS NIH HHS [GM50006] NR 34 TC 106 Z9 113 U1 0 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 FEB PY 1996 VL 58 IS 2 BP 300 EP 307 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA TR791 UT WOS:A1996TR79100006 PM 8571956 ER PT J AU Nathan, DM McKitrick, C Larkin, M Schaffran, R Singer, DE AF Nathan, DM McKitrick, C Larkin, M Schaffran, R Singer, DE TI Glycemic control in diabetes mellitus: Have changes in therapy made a difference? SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID INSULIN; RETINOPATHY AB PURPOSE: New methods of measuring and controlling glycemia in diabetes mellitus have been developed and implemented in the past 10 years. We examined whether glycemia, as measured by glycosylated hemoglobin, changed in outpatient insulin-dependent diabetes mellitus (IDDM) and noninsulin-dependent diabetes mellitus (NIDDM) populations between 1985 and 1993 and whether contemporaneous changes in therapy could account for observed changes in glycemia. PATIENTS AND METHODS: Outpatients were selected based on having glycated hemoglobin (HbA(1c)) measured in the Massachusetts General Hospital laboratory during March 1985 (IDDM n = 94 and NIDDM n = 137) or during March 1993 (IDDM n = 89 and NIDDM n = 118). Chart reviews established demographic and clinical characteristics, including frequency of blood glucose self-monitoring, insulin injections, office visits, and HbA(1c) measurements during the year prior to the HbA(1c) result. RESULTS: Mean HbA(1c) level was significantly lower in the 1993 IDDM cohort compared with the 1985 cohort (8.77% +/- 1.7% versus 9.47% +/- 2.1%, P = 0.014). In the NIDDM cohorts, the difference in mean HbA(1c) did not achieve statistical significance (8.35% +/- 1.6% in 1993 versus 8.75% +/- 2.1% in 1985, P = 0.09); however, when adjusted for differences in NIDDM duration, HbA(1c) in the 1993 cohort was significantly lower than that in the 1985 cohort. The largest decrease in HbA(1c) in NIDDM was in patients treated with insulin (9.53% +/- 2.0% versus 8.54% +/- 1.5% in 1985 and 1993, respectively, P = 0.004). Multiple linear regression analyses demonstrated that increased frequency of self-monitoring and of insulin injections were associated with lower HbA(1c) in IDDM. CONCLUSIONS: The level of average glycemia has decreased in IDDM patients over the past 8 years, attributable, at least in part, to an increased frequency of monitoring and of insulin injections. Glycemia decreased in NIDDM, especially in the subset of patients treated with insulin. This temporal shift in glycemic control should have a salutary effect on the development of long-term microvascular and neurologic complications. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DIABET RES CTR,GEN MED UNIT,DEPT MED,BOSTON,MA 02114. FU NCRR NIH HHS [RR01166] NR 21 TC 62 Z9 63 U1 0 U2 0 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 FEB PY 1996 VL 100 IS 2 BP 157 EP 163 DI 10.1016/S0002-9343(97)89453-3 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA TV798 UT WOS:A1996TV79800006 PM 8629649 ER PT J AU Christie, RH Freeman, M Hyman, BT AF Christie, RH Freeman, M Hyman, BT TI Expression of the macrophage scavenger receptor, a multifunctional lipoprotein receptor, in microglia associated with senile plaques in Alzheimer's disease SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID LOW-DENSITY LIPOPROTEIN; APOLIPOPROTEIN-E; MEDIATES UPTAKE; PROTEIN; ATHEROSCLEROSIS; ALLELE AB The macrophage scavenger receptor is a multi-functional receptor whose ligands include oxidized low density lipoprotein (LDL), as well as several other polyanionic macromolecules. Although the capacity of the receptor to bind modified LDL has implicated in the process of atherosclerosis, its physiological role remains uncertain. We have examined human brain for expression of macrophage scavenger receptor as part of ongoing studies of lipoprotein receptors in the central nervous system. The receptor is expressed on microglia, but not on astrocytes, neurons, or vessel-associated structures. In Alzheimer disease, there is strong expression of the scavenger receptor in association with senile plaques. C1 MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,MED SERV,BOSTON,MA 02114. FU NIA NIH HHS [AG08487, AG12406]; NIGMS NIH HHS [T32GM07753-16, T32 GM007753] NR 27 TC 109 Z9 111 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 FEB PY 1996 VL 148 IS 2 BP 399 EP 403 PG 5 WC Pathology SC Pathology GA TU542 UT WOS:A1996TU54200008 PM 8579103 ER PT J AU Mosialos, G Birkenbach, M Ayehunie, S Matsumura, F Pinkus, GS Kieff, E Langhoff, E AF Mosialos, G Birkenbach, M Ayehunie, S Matsumura, F Pinkus, GS Kieff, E Langhoff, E TI Circulating human dendritic cells differentially express high levels of a 55-kd actin-bundling protein SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID LANGERHANS CELLS; MONOCLONAL-ANTIBODIES; LYMPHOCYTES; TISSUES AB This study was initiated to examine the differential expression of an evolutionary conserved human 55-kd actin-bundling (p55) protein that is induced in B lymphocytes by Epstein-Barr virus infection. Our study demonstrates that p55 is specifically expressed at constitutively high levels in human peripheral blood dendritic cells and lymph node (interdigitating) dendritic cells. Blood dendritic cells constitute a minority (<2%) of all blood leukocytes but are a distinct population of potent antigen-presenting cells. Immunofluorescence microscopy with a monoclonal antibody specific for p55 showed that 87% of peripheral blood dendritic cells stained brightly in the cytoplasm and in the veiled cytoplasmic extensions. In contrast, monocytes, granulocytes, T cells, and B lymphocytes showed no expression of the p55 protein. Western blot analysis confirmed that only the dendritic cell component of peripheral blood expresses high levels of p55. Staining of human lymph node sections demonstrated selective expression of the p55 antigen by dendritic cells in the T-cell-dependent areas but not in the B cell follicles. p55 is likely to be involved in the organization of a specialized microfilament cytoskeleton in the dendritic cells, and the anti-p55 antibody should be useful for further characterization of this important population of antigen-presenting cells in clinical transplantation, HIV-1 pathogenesis, and autoimmune diseases. C1 MASSACHUSETTS GEN HOSP,RENAL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOLEC GENET & MED,BOSTON,MA. DANA FARBER CANC INST,DEPT HUMAN RETROVIROL,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. UNIV CHICAGO,MARJORIE B KOVLER VIRAL ONCOL LABS,CHICAGO,IL 60637. RUTGERS STATE UNIV,DEPT MOLEC BIOL & BIOCHEM,PISCATAWAY,NJ 08855. OI Matsumura, Fumio/0000-0002-8204-153X FU PHS HHS [A128734] NR 25 TC 132 Z9 133 U1 0 U2 2 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD FEB PY 1996 VL 148 IS 2 BP 593 EP 600 PG 8 WC Pathology SC Pathology GA TU542 UT WOS:A1996TU54200026 PM 8579121 ER PT J AU MacLean, JA Xia, WJ Pinto, CE Zhao, LH Liu, HW Kradin, RL AF MacLean, JA Xia, WJ Pinto, CE Zhao, LH Liu, HW Kradin, RL TI Sequestration of inhaled particulate antigens by lung phagocytes - A mechanism for the effective inhibition of pulmonary cell-mediated immunity SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID DENDRITIC CELLS; ALVEOLAR MACROPHAGES; T-CELLS; RESPIRATORY-TRACT; LANGERHANS CELLS; ACCESSORY CELLS; DOWN-REGULATION; LYMPH-NODES; IN-VITRO; RAT AB Dendritic cells (DCs) have emerged as the dominant antigen-presenting cells (APCs) of the lung, playing a vital role in the induction of cell-mediated immunity to inhaled antigens. We have previously demonstrated that an airway challenge with the soluble antigen hen egg lysozyme yields rapid acquisition of specific antigen-presenting cell activity by purified pulmonary DCs and a cell-mediated immune response in the lung upon secondary challenge. To examine how a particulate antigen leads to a cell-mediated response in vivo, graded concentrations of heat-killed Listeria (HKL) were injected intratracheally into Lewis rats. The bacteria were rapidly ingested by lung macrophages and polymorphonuclear leukocytes. The ability of purified pulmonary DCs pulsed in vivo by an airway challenge with HKL to subsequently stimulate HKL-specific responses ex vivo showed a threshold response, requiring a dose in excess of 10(9) organisms/rat. By contrast, all dosages of HKL yielded specific sensitization of lymphocytes in the draining hilar nodes. Pulmonary DCs purified from rats after a secondary in vivo airway challenge with HKL at day 14 were ineffective antigen-presenting cells except at high dosages of antigen. The generation of cell-mediated pulmonary inflammation paralleled the antigen-presenting cell activity of pulmonary DCs and was observed only at high antigen dosages. Hen egg lysozyme immobilized onto polystyrene beads and injected intratracheally yielded comparable results to those observed with HKL. We suggest that a pulmonary cellular immune response is generated to an inhaled particulate antigen when the protective phagocytic capacities of the lung are exceeded and antigen is able to interact directly with interstitial DCs. The diversion of particulate antigens by pulmonary phagocytes may help to limit undesirable pulmonary inflammation while allowing the generation of antigen-specific immune lymphocytes in vivo. C1 MASSACHUSETTS GEN HOSP,GEN MED SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,IMMUNOPATHOL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. FU NHLBI NIH HHS [HL48385]; NIAID NIH HHS [AI01245] NR 34 TC 53 Z9 54 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 FEB PY 1996 VL 148 IS 2 BP 657 EP 666 PG 10 WC Pathology SC Pathology GA TU542 UT WOS:A1996TU54200033 PM 8579128 ER PT J AU Luzi, L Castellino, P DeFronzo, RA AF Luzi, L Castellino, P DeFronzo, RA TI Insulin and hyperaminoacidemia regulate by a different mechanism leucine turnover and oxidation in obesity SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE insulin resistance; amino acids; protein synthesis; proteolysis ID CHAIN AMINO-ACIDS; PROTEIN-SYNTHESIS; SUBSTRATE AVAILABILITY; INDIRECT CALORIMETRY; METABOLISM; PLASMA; GLUCOSE; CARBOHYDRATE; NIDDM; FAT AB Seven normal glucose-tolerant obese subjects [ideal body weight (IBW) = 161%] and 18 controls (IBW = 102%) were studied with the euglycemic insulin damp (10 and 40 mU . m(-2). min(-1)) technique, [C-14]leucine infusion, and indirect calorimetry to examine if the insulin resistance with respect to glucose metabolism extends to amino acid/protein metabolism. In the basal state, total plasma amino acid and leucine concentrations, endogenous leucine flux (ELF), leucine oxidation (LO), and nonoxidative leucine disposal (NOLD) were similar in obese and control subjects. During both low (10 mU . m(-2). min(-1))- and higher (40 mU . m(-2). min(-1))-dose insulin clamp studies, insulin-mediated glucose uptake was reduced in obese vs. control subjects (P < 0.01). During the last hour of the higher-dose insulin clamp step, the decrease in total plasma amino acids, branched-chain amino acids, and leucine concentration was impaired in obese vs. control subjects (P < 0.01). However, suppression of ELF and NOLD was similar in both groups. During the low-dose insulin clamp, the decrease in plasma leucine concentration, LO, and ELF all were impaired (P < 0.01). A second study was performed in which the total plasma amino acid concentration was increased two- to threefold in both groups. Under these conditions of low plasma insulin/high amino acid levels, LO and NOLD increased similarly in obese and control subjects. In conclusion, insulin resistance is a common feature of both glucose and protein metabolism in obesity. The defect in protein metabolism is characterized by an impairment of the ability of insulin to inhibit proteolysis; the stimulatory effect of hyperaminoacidemia on protein synthesis is intact in obesity. C1 UNIV TEXAS, CTR HLTH SCI, DEPT MED, DIABET DIV, SAN ANTONIO, TX 78284 USA. AUDIE L MURPHY MEM VET ADM MED CTR, SAN ANTONIO, TX 78284 USA. IST SCI SAN RAFFAELE, DEPT INTERNAL MED, RADIOACT & STABLE ISOTOPES LAB, I-20132 MILAN, ITALY. RI Luzi, Livio/M-2696-2016 OI Luzi, Livio/0000-0003-3183-0552 FU NIDDK NIH HHS [DK-24092] NR 35 TC 51 Z9 51 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD FEB PY 1996 VL 270 IS 2 BP E273 EP E281 PG 9 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA TW100 UT WOS:A1996TW10000011 PM 8779949 ER PT J AU Dahlberg, CGW Thompson, BT Joseph, PM Garg, HG Spence, CR Quinn, DA Bonventre, JV Hales, CA AF Dahlberg, CGW Thompson, BT Joseph, PM Garg, HG Spence, CR Quinn, DA Bonventre, JV Hales, CA TI Differential effect of three commercial heparins on Na+/H+ exchange and growth of PASMC SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE vascular remodeling; platelet-derived growth factor; sodium-hydrogen exchange; heparin; pulmonary artery smooth muscle cells ID SMOOTH-MUSCLE CELLS; PORCINE INTESTINAL HEPARIN; STRUCTURAL DETERMINANTS; PH REGULATION; PROLIFERATION; ANTICOAGULANT; INHIBITION; SULFATES; CAPACITY; ABSENCE AB Heparin preparations vary in chemical content and in antiproliferative activity for pulmonary artery smooth muscle cells (PASMC). Intracellular alkalinization via stimulation of the Na+/H+ antiporter appears to be a permissive event for proliferation of PASMC. We wondered whether the variable effect of heparin preparations on PASMC growth might be due to different degrees of inhibition of the Na+/H+ antiporter and whether variations in chemical formulation might correlate with the inhibition. Fluorescent microscopy of bovine PASMC was done using a dye with which fluorescence varies directly with intracellular pH (pH(i)). Bovine PASMC were preincubated with three heparin preparations previously shown to vary in antiproliferative activity at 1.0 mu g/ml for 24 h. Platelet-derived growth factor (PDGF; 60 ng/ml) on PASMC without heparin resulted in a rise in pH(i) of 0.27 +/- 0.02 pH units. The rise in pH units in heparin-treated PASMC was 0.34 +/- 0.03 with Choay, 0.21 +/- 0.02 with Elkins-Sinn, and 0.07 +/- 0.02 with Upjohn (+/- SE; all P < 0.05; n = 5). Upjohn heparin incubation for as little as 15 min still impeded the rise in pH induced by PDGF. Heparin did not block the Na+/H+ exchanger directly, as it still restored pH(i) in response to an acid load. Compared with PASMC proliferation induced by 60 ng/ml PDGF, 1 mu g/ml of Choay, Elkins-Sinn, and Upjohn heparin produced -4 +/- 7.4, 1.4 +/- 4.8, and 48 +/- 2.2% inhibition of PDGF control, respectively (P < 0.05 for Upjohn compared with PDGF and Choay). The heparins varied in protein content and amino acid composition. However, amino acid and glucosamine composition total sulfation, and extent of 3-O-sulfation did not predict their activity. Thus inhibition of PDGF activation of the Na+/H+ antiporter by a given heparin preparation correlated well with its ability to inhibit PASMC proliferation. C1 MASSACHUSETTS GEN HOSP, DEPT MED, PULM CRIT CARE UNIT, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, DEPT MED, RENAL UNIT, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02114 USA. FU NHLBI NIH HHS [R01-HL-39150, 5 T32 HL-07354]; NIDDK NIH HHS [R01 DK-39773] NR 34 TC 18 Z9 18 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD FEB PY 1996 VL 270 IS 2 BP L260 EP L265 PG 6 WC Physiology; Respiratory System SC Physiology; Respiratory System GA TW069 UT WOS:A1996TW06900012 PM 8779995 ER PT J AU Hyman, SE Nestler, EJ AF Hyman, SE Nestler, EJ TI Initiation and adaptation: A paradigm for understanding psychotropic drug action SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID FREELY MOVING RATS; NUCLEUS-ACCUMBENS; CYCLIC-AMP; C-FOS; MOLECULAR MECHANISMS; COCAINE; RECEPTOR; AMPHETAMINE; EXPRESSION; DYNORPHIN AB Objective: This article describes a paradigm-initiation and adaptation-within which to conceptualize the drug-induced neural plasticity that underlies the long-term actions of psychotropic drugs in the brain. Method: Recent advances in neurobiology are reviewed. Results: Recent developments in cellular and molecular neurobiology provide new conceptual and experimental tools for understanding the mechanisms by which psychotropic drugs produce long-lived alterations in brain function. Because of the availability of more robust animal models, the mechanisms by which drugs of abuse produce dependence are better understood than the mechanisms by which antidepressants, antipsychotics, and lithium produce their therapeutic effects. Nonetheless, the fundamental types of mechanisms appear to be similar: chronic drug administration drives the production of adaptations in postreceptor signaling pathways, including regulation of neural gene expression. Whether the results are deleterious or therapeutic depends on the precise neural systems targeted by a particular drug. Conclusions: Biological investigation in psychiatry has often focused too narrowly on synaptic pharmacology, especially on neurotransmitter turnover and neurotransmitter receptors. This review focuses on molecular and cellular changes in neural function that are produced as adaptations to chronic administration of addictive drugs such as psychostimulants and therapeutic drugs such as antidepressants. To understand normal brain function, psychopathology, and the actions of psychiatric treatments, and to exploit the eventual findings of psychiatric genetics, psychiatric research must now extend its efforts beyond the synapse, to an understanding of cellular and molecular neurobiology (in particular, postreceptor signal transduction) as well as to a better understanding of the architecture and function of neural systems. A paradigm is presented to help understand the long-term effects of psychotropic drugs, including the latency in onset of their therapeutic actions. C1 MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138. YALE UNIV,SCH MED,LAB MOLEC PSYCHIAT,NEW HAVEN,CT 06520. NR 49 TC 344 Z9 353 U1 1 U2 14 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 FEB PY 1996 VL 153 IS 2 BP 151 EP 162 PG 12 WC Psychiatry SC Psychiatry GA TT557 UT WOS:A1996TT55700003 PM 8561194 ER PT J AU Aarsland, D Cummings, JL Yenner, G Miller, B AF Aarsland, D Cummings, JL Yenner, G Miller, B TI Relationship of aggressive behavior to other neuropsychiatric symptoms in patients with Alzheimer's disease SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID NURSING-HOME; DEMENTIA; DELUSIONS; DEPRESSION; PSYCHOSIS; AGITATION; SCALE AB Objective: This study explored the relationship between aggressive behavior and other neuropsychiatric symptoms in patients with Alzheimer's disease. Method: Consecutively assessed outpatients with probable or possible Alzheimer's disease (N=75) were assessed with the Behavioral Pathology in Alzheimer's Disease Rating Scale and the Hamilton Depression Rating Scale. Results: Twenty-five patients (33%) had verbal outbursts and 23 patients (17%) engaged in physical aggression in the month prior to assessment. Aggressive patients and nonaggressive patients did not differ regarding age, education, gender, level of depression, or severity of dementia. In she entire group, dysphoria was found in 33%, delusional ideation in 39%, and hallucinations in 16%. Aggressive behavior was more frequent among patients with hallucinations than among those without. Scores on hallucinations and activity disturbance predicted 12% of the variance in total aggressive behavior. When data from patients taking psychotropic medication were excluded from the analysis, hallucination and delusion scores predicted 22% of the variance in the aggression score. Physical aggression was associated with activity disturbance and hallucinations, and verbal aggression was associated with delusional ideation. No other clinical correlates of aggression were identified. Conclusions: Aggressive behavior is a frequent behavioral symptom in Alzheimer's disease. About one-fourth of the variance in aggression could be attributed to psychosis. C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT NEUROL,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT PSYCHIAT & BIOBEHAV SCI,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,PSYCHIAT SERV,BEHAV NEUROSCI SECT,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,HARBOR MED CTR,DEPT NEUROL,LOS ANGELES,CA 90024. OI Aarsland, Dag/0000-0001-6314-216X FU NIA NIH HHS [AG-10123] NR 40 TC 129 Z9 131 U1 2 U2 10 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 FEB PY 1996 VL 153 IS 2 BP 243 EP 247 PG 5 WC Psychiatry SC Psychiatry GA TT557 UT WOS:A1996TT55700015 PM 8561206 ER PT J AU Conhaim, RL McGrath, AM Harms, BA AF Conhaim, RL McGrath, AM Harms, BA TI Does plasma protein depletion increase lung liquid conductance? SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID FLUID FILTRATION; AWAKE SHEEP; HYPOPROTEINEMIA; PRESSURE; BALANCE AB Lung liquid conductance (K-f) is calculated as the quotient of lung lymph flow divided by net filtration pressure (Pnf), where Pnf is the balance of osmotic and hydrostatic pressures in the lung microcirculation. In protein depletion, lymph flow rises with little change in Pnf, suggesting that calculated K-f also rises. However, several previous reports have concluded that protein depletion causes little change in K-f, leaving open the question of how lung lymph flow can rise in protein depletion with little change in Pnf. To address this, we measured K-f in sheep following two kinds of protein depletion: batch plasmapheresis (BP; n = 5) and thoracic duct drainage (TD; n = 5). Both methods lowered plasma protein concentrations by 30%, and raised lung lymph flows by 55%. Lung microvascular hydrostatic pressures and plasma-to-lymph osmotic pressure gradients both changed by 1 to 2 mm Hg. With BP, calculated K-f rose from 0.26 +/- 0.09 at baseline to 0.50 +/- 0.20 on Day 1, and to 0.39 +/- 0.27 ml/mm Hg/30 min on Day 2 (p less than or equal to 0.05). With TD, calculated K-f rose from 0.28 +/- 0.13 at baseline to 0.43 +/- 0.19 on Day 1, and to 0.43 +/- 0.19 ml/mm Hg/30 min on Day 2 (p less than or equal to 0.05). Calculated K-f rose because filtration increased even though the hydrostatic and osmotic driving forces responsible for filtration changed little. This is puzzling because it suggests that lymph flow rose with little or no change in the forces affecting filtration. Our findings contradict several previous reports that concluded that protein depletion produces little or no change in calculated K-f. C1 UNIV WISCONSIN,DEPT SURG,MADISON,WI. RP Conhaim, RL (reprint author), WILLIAM S MIDDLETON MEM VET ADM MED CTR,DEPT SURG,2500 OVERLOOK TERRACE,MADISON,WI 53705, USA. FU NHLBI NIH HHS [HL 46236] NR 22 TC 5 Z9 5 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD FEB PY 1996 VL 153 IS 2 BP 677 EP 683 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA TT884 UT WOS:A1996TT88400032 PM 8564117 ER PT J AU Quinn, DA Dahlberg, CGW Bonventre, JP Scheid, CR Honeyman, T Joseph, PM Thompson, BT Hales, CA AF Quinn, DA Dahlberg, CGW Bonventre, JP Scheid, CR Honeyman, T Joseph, PM Thompson, BT Hales, CA TI The role of Na+/H+ exchange and growth factors in pulmonary artery smooth muscle cell proliferation SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID PROTEIN-KINASE-C; PH REGULATION; ENDOTHELIAL-CELLS; DNA-SYNTHESIS; RAT LUNGS; HYPERTENSION; ANTIPORTER; ACTIVATION; FIBROBLASTS; EXPRESSION AB Chronic hypoxia produces pulmonary hypertension, in part because of hypertrophy and hyperplasia of pulmonary artery smooth muscle cells (PA SMC). Platelet-derived growth factor (PDGF) and epidermal growth factor (EGF) have been shown to stimulate SMC proliferation and may be involved in these vascular changes. Both factors cause a rise in intracellular pH (pH(i)) in systemic vascular SMC through stimulation of the Na+/H+ exchanger, an event that has been thought to be permissive, allowing cell proliferation in response to the growth factor. The present studies examined the possibility that the activation of Na+/H+ exchange is involved in the PA SMC mitogenic response to these growth factors. Na+/H+ exchange activity was assessed by monitoring pH(i) in cultured cells using the pH-sensitive dye, 2'7'-bis(carboxyethyl)-5(6)-carboxyethyl)-5(6)-carboxyfluorescein (BCECF). PDGF (60 ng/ml) exposure led to a marked activation of Na+/H+ exchange, evidenced by a rise in pH(i) (mean +/- SEM) of 0.20 +/- 0.03 pH units (n = 5, P < 0.05). EGF (60 ng/ml) exposure produced a rise in pH(i) of 0.27 +/- 0.03 pH units (n = 5, P < 0.05). Dimethyl amiloride (DMA, 50 mu M), a competitive inhibitor of Na+/H+ exchange, blocked the pH response to PDGF and EGF. PA SMC showed a proliferative response when exposed to PDGF and EGF which was attenuated by 50 mu M DMA (n = 6). Thus, activation of the Na+/H+ exchanger may be important in pulmonary cell signaling in response to growth factors as it has been found to be in systemic vessels. C1 MASSACHUSETTS GEN HOSP,DEPT MED,PULM CRIT CARE UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MED,RENAL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. UNIV MASSACHUSETTS,SCH MED,DEPT PHYSIOL,WORCESTER,MA. FU NHLBI NIH HHS [HL36829, HL39150, HL41188] NR 45 TC 51 Z9 60 U1 1 U2 1 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD FEB PY 1996 VL 14 IS 2 BP 139 EP 145 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA TU365 UT WOS:A1996TU36500005 PM 8630263 ER PT J AU Perkins, SE Fox, JG Walsh, JH AF Perkins, SE Fox, JG Walsh, JH TI Helicobacter mustelae-associated hypergastrinemia in ferrets (Mustela putorius furo) SO AMERICAN JOURNAL OF VETERINARY RESEARCH LA English DT Article ID DUODENAL-ULCER PATIENTS; PYLORI SUBSP-MUSTELAE; CAMPYLOBACTER-PYLORI; GASTRIC-CARCINOMA; ACID-SECRETION; PLASMA GASTRIN; ANIMAL-MODEL; INFECTION; PH; ERADICATION AB Objective-To determine whether ferrets naturally infected with Helicobacter mustelae were hypergastrinemic, compared with ferrets that were specific-pathogen-free (SPF) for H mustelae. Design-Plasma gastrin concentrations in H mustelae infected and SPF ferrets were measured at 3 time points and compared to determine whether H mustelae was associated with hypergastrinemia. Animals-21 H mustelae-infected ferrets and 10 SPF ferrets, Procedure-The H mustelae status of the ferrets was confirmed prior to commencement of the study. Gastric endoscopy was used to obtain gastric mucosal pinch biopsy specimens that were processed for rapid-urease assay, microaerophilic culturing, and histologic evaluation. Plasma gastrin concentrations were determined at 3 time points: baseline after a 12-hour nonfeeding period, and 30 and 60 minutes after oral administration of a standardized meal. Gastrin was measured by radioimmunoassay. Results-The results for the H mustelae-infected group (mean +/- SEM pg/ml) were: baseline, 54.4 +/- 2.56; 30 minutes, 94.5 +/- 6.05; and 60 minutes, 82.6 +/- 5.73. The SPF group results were: baseline, 55.8 +/- 7.35; 30 minutes, 80.8 +/- 5.77; and 60 minutes, 59.7 +/- 4.95. There was a significant (P < 0.01) difference at the 60-minute time point between the 2 groups of animals. The H mustelae group had a 17% higher mean gastrin value al 30 minutes. Conclusions-Helicobacter mustelae is associated with hypergastrinemia in ferrets. Clinical Relevance-Helicobacter-induced hypergastrinemia may be related to the pathogenesis of peptic ulcer disease in ferrets. C1 MIT,DIV COMPARAT MED,CAMBRIDGE,MA 02139. W LOS ANGELES VET AFFAIRS MED CTR,CURE GASTROENTEROL BIOL CTR,LOS ANGELES,CA 90073. FU NCRR NIH HHS [RR01046, RR07036]; NIDDK NIH HHS [DK17294] NR 37 TC 16 Z9 18 U1 0 U2 0 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 SN 0002-9645 J9 AM J VET RES JI Am. J. Vet. Res. PD FEB PY 1996 VL 57 IS 2 BP 147 EP 150 PG 4 WC Veterinary Sciences SC Veterinary Sciences GA TT897 UT WOS:A1996TT89700011 PM 8633798 ER PT J AU Kaufmann, MA Pargger, H Drop, LJ AF Kaufmann, MA Pargger, H Drop, LJ TI Oscillometric blood pressure measurements by different devices are not interchangeable SO ANESTHESIA AND ANALGESIA LA English DT Article ID RANDOM-ZERO; ANESTHESIA AB Blood pressure (BP) is frequently measured in patients by noninvasive blood pressure (NIBP) monitors. Values obtained by oscillometric devices of different brands may appear in one patient's record as if they were interchangeable; their concordance, however, has not been established. In 25 patients with major depression who were treated with electroconvulsive therapy (ECT) BP was measured on either arm by devices manufactured by SpaceLabs (SpL, 12 patients, 182 data points) and Marquette (Marq, 13 patients, 193 data points), respectively, and comparisons were made with simultaneous measurements on the opposite arm by Dinamap 1846SX (DIN), during the awake state and at 1-min intervals up to 5-7 min after ECT. Because ECT is associated with an intense, but short-lasting hyperdynamic state, comparisons of BP values could be made over a wide range of pressures. Bland-Altman plots were constructed to show the distribution of pressure differences at all pressures. Agreements between two instruments were judged according to guide lines by the American Association for Advancement of Medical Instrumentation (AAMI). The standard deviation of the difference (SDD) between two DIN devices was 7 nun Hg for systolic (SEP) and 6.3 mm Hg for diastolic blood pressure (DBP), whereas mean differences were 0.9 and 0.2 nun Hg, respectively (P = not significant [NS]), thus showing reproducibility. Corresponding SDD values SpL versus DIN were 9.1 for SEP and 8.3 nun Hg for DBP, while the mean differences were 1.6 (P = 0.026) and 7.3 (P = 0.0001) mm Hg, respectively. Corresponding SDD values for Marq versus DIN were 11.8 and 9.7 mm Hg with mean differences of 0.8 (P = NS) and 0.3 (P = NS) mm Hg. Whereas SEP differences DIN versus DIN exceeded 10 mm Hg in only 10% of observations, they exceeded that threshold in 31% and 32% of observations for SpL versus DIN and Marq versus DIN, respectively. In view of the variability that exceeds the AAMI guidelines and the one out of three occurrence of individual SEP differences exceeding 10 mm Hg for comparisons of SpL or Marq versus DIN, measurements by these three oscillometric devices are not interchangeable. C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT ANAESTHESIA,BOSTON,MA 02115. NR 17 TC 23 Z9 24 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD FEB PY 1996 VL 82 IS 2 BP 377 EP 381 DI 10.1097/00000539-199602000-00029 PG 5 WC Anesthesiology SC Anesthesiology GA TT440 UT WOS:A1996TT44000029 PM 8561345 ER PT J AU Yanez, P Martyn, JAJ AF Yanez, P Martyn, JAJ TI Prolonged d-tubocurarine infusion and/or immobilization cause upregulation of acetylcholine receptors and hyperkalemia to succinylcholine in rats SO ANESTHESIOLOGY LA English DT Article DE complications, hyperkalemia, immobilization; neuromuscular relaxants, d-tubocurarine, nondepolarizing, succinylcholine receptor, acetylcholine, nicotinic ID SUXAMETHONIUM-INDUCED HYPERKALEMIA; SKELETAL-MUSCLE; UP-REGULATION; GAMMA-SUBUNIT; SENSITIVITY; INJURY; DISUSE; RESISTANCE; PARALYSIS; DIAPHRAGM AB Background: Hyperkalemic cardiac arrest after the administration of succinylcholine (SCh) to critically ill intensive care patients has been attributed to changes in the acetylcholine receptors (AChRs) at the muscle membrane. The current study attempts to characterize the contributory roles of chronic administration of nondepolarizing muscle relaxants typified by d-tubocurarine (dTC) and/or of immobilization on AChR upregulation and the relationship of these AChR changes to SCh-induced hyperkalemia. Methods: Rats received chronic subparalytic infusion of saline or dTC for 28 days via subcutaneous osmotic pumps inserted while they were under anesthesia. Approximately half of the saline- or dTC-treated rats underwent bilateral hind-limb immobilization with plaster casts for the same duration as the infusion. After 4 weeks, the osmotic pumps were removed, and 24-48 h later, the blood potassium concentrations were measured at baseline and at 1, 3, 5, 7, and 10 min after SCh (3 mg/kg). At the end of this period, the gastrocnemius muscle was excised for quantitation of AChR number using I-125-alpha-bungarotoxin. Results: At 28 days, the weight gain in mobile animals receiving saline or dTC infusion did not differ, nor did that in immobilized animals receiving saline or dTC infusion, confirming that infusion of dTC did not unduly affect the ability of the animals to feed. The maximal potassium change after SCh occurred at 5 min. Potassium responses to SCh changed (mean +/- SE): (1) from 3.9 +/- 0.04 to 4.5 +/- 0.1 mEq/l in the mobile saline-treated control group, where the AChR concentration was 18.4 +/- 2 fmol/mg protein; (2) from 3.9 +/- 0.03 to 5.1 +/- 0.1 in the mobile dTC-infused group (AChRs = 48.6 +/- 7); (3) from 3.8 +/- 0.1 to 5.5 +/- 0.3 in the immobilized saline-treated group (AChRs = 107.4 +/- 14); and (4) from 3.8 +/- 0.1 to 6.3 +/- 0.2 in the immobilized-dTC-treated group (AChRs = 183.5 +/- 23). There was a significant positive correlation between maximal change in blood potassium concentration and the respective AChR concentration in the gastrocnemius of the same animal (r = 0.81, P < 0.01). Conclusions: Subtherapeutic (subparalytic) doses of chronic infusion of dTC (with no immobilization) or immobilization alone (with no dTC) independently increased number of AChRs. The infusion of (ITC with immobilization caused the greatest upregulation of AChRs. The magnitude of the increase in blood potassium to SCh was directly dependent on AChR number. This study shows direct evidence and confirms previous speculation that AChR number plays an important role in the magnitude of the hyperkalemic response to SCh. Presuming this represents an appropriate model for patients who are immobilized and/or receiving nondepolarizing muscle relaxants for prolonged periods, exaggerated blood potassium responses to SCh are possible when either or both of these perturbations are present in patients. C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,CLIN & BIOCHEM PHARMACOL LAB,ANESTHESIA SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT ANESTHESIOL,CAMBRIDGE,MA 02138. SHRINERS BURNS INST,BOSTON,MA. NR 42 TC 27 Z9 30 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD FEB PY 1996 VL 84 IS 2 BP 384 EP 391 DI 10.1097/00000542-199602000-00017 PG 8 WC Anesthesiology SC Anesthesiology GA TU976 UT WOS:A1996TU97600018 PM 8602670 ER PT J AU Dewsnup, DH Galgiani, JN Graybill, JR Diaz, M Rendon, A Cloud, GA Stevens, DA AF Dewsnup, DH Galgiani, JN Graybill, JR Diaz, M Rendon, A Cloud, GA Stevens, DA TI Is it ever safe to stop azole therapy for Coccidioides immitis meningitis? SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE coccidioidomycosis; meningitis, fungal; azoles; triazoles; recurrence ID ITRACONAZOLE THERAPY; FLUCONAZOLE THERAPY; KETOCONAZOLE; ANTIFUNGAL; MYCOSES AB Objective: To determine 1) whether patients with coccidioidal meningitis who had achieved remission with oral azole therapy were cured and 2) when oral atole therapy could be discontinued in these patients. Design: Data were gathered on patients with coccidioidal meningitis who had successfully responded to atole therapy in previous clinical trials. Setting: Referral centers, including university, county, and veterans' hospitals and clinics. Patients: 18 patients in whom atole therapy for meningitis had been discontinued, usually because of a presumption of cure. Main Outcome Measures: Clinical and cerebrospinal fluid relapse. Results: 14 of 18 patients (78% [95% CI, 52% to 94%]) had relapse with disseminated disease after discontinuation of therapy, for a total of 1 nonmeningeal and 15 meningeal relapses to date. Relapse occurred both soon and late (range, 0.5 to 30 months) after therapy was discontinued. The characteristics of patients who did not have relapse, including the particular atole used, the duration of therapy, the reason therapy was discontinued, and the cerebrospinal fluid indices before discontinuation, were similar to the characteristics of patients who had relapse. Relapse had serious consequences in some patients; 3 patients died. Conclusion: Our data suggest 1) that disease is only suppressed in patients with meningitis who achieve remission while receiving atole therapy and 2) that discontinuing atole therapy is unsafe. The alternative is lifelong treatment with azoles; this appears to be acceptable, because toxicity is uncommon with triazole therapy, even longterm triazole therapy. C1 SANTA CLARA VALLEY MED CTR,DEPT MED,DIV INFECT DIS,SAN JOSE,CA 95128. VET AFFAIRS MED CTR,DEPT MED,DIV INFECT DIS,TUCSON,AZ 85723. UNIV TEXAS,HLTH SCI CTR,DEPT INFECT DIS,AUDIE MURPHY VET AFFAIRS HOSP,SAN ANTONIO,TX 78284. UNIV ALABAMA,MED CTR,TUMOR INST,BIRMINGHAM,AL 35294. CALIF INST MED RES,SAN JOSE,CA 95128. STANFORD UNIV,SCH MED,STANFORD,CA 94305. NIAID,MYCOSES STUDY GRP,BETHESDA,MD. UNIV ARIZONA,TUCSON,AZ. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. UNIV AUTONOMA NUEVO LEON,MONTERREY,MEXICO. UNIV HOSP,MONTERREY,MEXICO. FU NIAID NIH HHS [N01-AI-15082] NR 23 TC 98 Z9 102 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD FEB 1 PY 1996 VL 124 IS 3 BP 305 EP & PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA TR596 UT WOS:A1996TR59600004 PM 8554225 ER PT J AU Brown, RH AF Brown, RH TI Superoxide dismutase and familial amyotrophic lateral sclerosis: New insights into mechanisms and treatments SO ANNALS OF NEUROLOGY LA English DT Editorial Material ID ENZYME RP Brown, RH (reprint author), MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114, USA. NR 10 TC 25 Z9 25 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD FEB PY 1996 VL 39 IS 2 BP 145 EP 146 DI 10.1002/ana.410390202 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA TY533 UT WOS:A1996TY53300001 PM 8967744 ER PT J AU Gitelman, DR Alpert, NM Kosslyn, S Daffner, K Scinto, L Thompson, W Mesulam, MM AF Gitelman, DR Alpert, NM Kosslyn, S Daffner, K Scinto, L Thompson, W Mesulam, MM TI Functional imaging of human right hemispheric activation for exploratory movements SO ANNALS OF NEUROLOGY LA English DT Article ID CEREBRAL BLOOD-FLOW; PET; ATTENTION; NEGLECT; ASYMMETRIES; DOMINANCE; NETWORK; CORTEX AB We employed positron emission tomography to examine the functional anatomy of the exploratory-motor aspect of spatial attention. Subjects moved their right hand under nonexploratory (control) versus exploratory (active) conditions. Movement architecture and eye movements were matched across conditions. Statistical parametric maps of the exploratory (active) minus nonexploratory (control) tasks in subjects using their right hand in the right hemispace demonstrated activation in right cingulate, premotor and posterior parietal areas. The net activation of multiple right hemisphere cortical areas ipsilateral to the active limb and hemispace strongly supports the predicted, distributed network anatomy and is consistent with possible right hemispheric dominance for exploratory attentional movements. C1 NORTHWESTERN UNIV, DEPT NEUROL, ALZHEIMER PROGRAM, CHICAGO, IL 60611 USA. NORTHWESTERN UNIV, VET ADM LAKESIDE MED CTR, NEUROL SERV 127, CHICAGO, IL 60611 USA. MASSACHUSETTS GEN HOSP, DEPT RADIOL, DIV NUCL MED, BOSTON, MA 02114 USA. BRIGHAM & WOMENS HOSP, DEPT NEUROL, BRAIN BEHAV GRP, BOSTON, MA 02115 USA. HARVARD UNIV, DEPT PSYCHOL, CAMBRIDGE, MA 02138 USA. RP Gitelman, DR (reprint author), NORTHWESTERN UNIV, DEPT NEUROL, CTR BEHAV & COGNIT NEUROL, CHICAGO, IL 60611 USA. NR 18 TC 89 Z9 90 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD FEB PY 1996 VL 39 IS 2 BP 174 EP 179 DI 10.1002/ana.410390206 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA TY533 UT WOS:A1996TY53300005 PM 8967748 ER PT J AU Serratosa, JM DelgadoEscueta, AV Medina, MT Zhang, QW Iranmanesh, R Sparkes, RS AF Serratosa, JM DelgadoEscueta, AV Medina, MT Zhang, QW Iranmanesh, R Sparkes, RS TI Clinical and genetic analysis of a large pedigree with juvenile myoclonic epilepsy SO ANNALS OF NEUROLOGY LA English DT Article ID DINUCLEOTIDE REPEAT POLYMORPHISM; IDIOPATHIC GENERALIZED EPILEPSY; LINKAGE ANALYSIS; HLA REGION; LOCUS; CHROMOSOME-6; FAMILIES; CHILDREN; AGE AB Juvenile myoclonic epilepsy is a common type of idiopathic generalized epilepsy characterized by myoclonic, generalized tonic-clonic, and in 30% of patients, absence seizures. We studied a three-generation pedigree of 33 members, 10 of whom were clinically affected with juvenile myoclonic epilepsy or presented with subclinical electroencephalographic (EEG) 3.5- to 6.0-Hz diffuse polyspike-wave or spike-wave complexes. Juvenile myoclonic epilepsy and the EEG trait segregated as an autosomal dominant trait with 70% penetrance. Linkage analysis using this model showed significant linkage to four microsatellite markers centromeric to human leukocyte antigen (HLA) in chromosome Gp. Maximum lod scores of 3.43 at theta(m=f) = 0.00 for D6S272, D6S466, D6S257, and D6S402 were obtained. Recombinant events in 2 affected members defined the gene region to a 43-cM interval Banked by D6S258 (HLA region) and D6S313 (centro-mere). Our results in this large family provide evidence that a gene responsible for juvenile myoclonic epilepsy and the subclinical, 3.5- to 6.0-Hz, polyspike-wave or spike-wave EEG pattern is located in chromosome 6p. C1 W LOS ANGELES VET AFFAIRS MED CTR,COMPREHENS EPILEPSY PROGRAM 127B,SW REG EPILEPSY CTR,LOS ANGELES,CA 90073. W LOS ANGELES VET AFFAIRS MED CTR,RES SERV,SW REG EPILEPSY CTR,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,CALIF COMPREHENS EPILEPSY PROGRAM,LOS ANGELES,CA. UNIV CALIF LOS ANGELES,DEPT NEUROL,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,DEPT MED,DIV MED GENET,LOS ANGELES,CA 90024. UNIV NACL AUTONOMA HONDURAS,DIRECC INVEST CIENT,TEGUCIGALPA,HONDURAS. NR 31 TC 54 Z9 55 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD FEB PY 1996 VL 39 IS 2 BP 187 EP 195 DI 10.1002/ana.410390208 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA TY533 UT WOS:A1996TY53300007 PM 8967750 ER PT J AU MartinezMartinez, L HernandezAlles, S Alberti, S Tomas, JM Benedi, VJ Jacoby, GA AF MartinezMartinez, L HernandezAlles, S Alberti, S Tomas, JM Benedi, VJ Jacoby, GA TI In vivo selection of porin-deficient mutants of Klebsiella pneumoniae with increased resistance to cefoxitin and expanded-spectrum cephalosporins SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID OUTER-MEMBRANE; ESCHERICHIA-COLI; BETA-LACTAMASES; SALMONELLA-TYPHIMURIUM; POLYACRYLAMIDE GELS; PROTEINS; BACTERIAL; OUTBREAK; INVIVO AB Four Klebsiella pneumoniae isolates (LB1, LB2, LB3, and LB4) with increased antimicrobial resistance were obtained from the same patient, The four isolates were indistinguishable in biotype, plasmid content, lipopolysaccharide, and DNA analysis by pulse-field gel electrophoresis, Isolate LB1 made TEM-1 and SHV-1 beta-lactamases, Isolates LB2, LB3, and LB4 produced SHV-5 in addition to TEM-1 and SHV-1, MICs of cefoxitin, ceftazidime, and cefotaxime against LB1 were 4, 1, and 0.06 mu g/ml, respectively, MICs of ceftazidime against K. pneumoniae LB2, LB3, and LB4 were >256 mu g/ml, and those of cefotaxime were 2, 4, and 64 mu g/ml, respectively, MICs of cefoxitin against K. pneumoniae LB2 and LB3 were 4 mu g/ml, but that against K. pneumoniae LB4 was 128 mu g/ml. K. pneumoniae LB4 could transfer resistance to ceftazidime and cefotaxime, but not that to cefoxitin, to Escherichia coli. Isolate LB4 and cefoxitin-resistant laboratory mutants lacked an outer membrane protein of about 35 kDa whose molecular mass, mode of isolation, resistance to proteases, and reaction with a porin-specific antiserum suggested that it was a porin, MICs of cefoxitin and cefotaxime reverted to 4 and 2 mu g/ml, respectively, when isolate LB4 was transformed with a gene coding for the K. pneumoniae porin OmpK36, We conclude that the increased resistance to cefoxitin and expanded-spectrum cephalosporins of isolate LB4 was due to loss of a porin channel for antibiotic uptake. C1 MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA 02114. UNIV ISLAS BALEARES,DEPT BIOL AMBIENTAL,AREA MICROBIOL,PALMA DE MALLORCA,SPAIN. UNIV BARCELONA,SCH BIOL,DEPT MICROBIOL,BARCELONA,SPAIN. RI Alberti, Sebastian/H-2490-2013; Tomas, Juan/L-1398-2015 OI Alberti, Sebastian/0000-0003-0020-6861; Tomas, Juan/0000-0002-3575-7113 NR 51 TC 155 Z9 169 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 FEB PY 1996 VL 40 IS 2 BP 342 EP 348 PG 7 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA TT556 UT WOS:A1996TT55600011 PM 8834877 ER PT J AU Paster, BJ Dewhirst, FE Cooke, SM Fussing, V Poulsen, LK Breznak, JA AF Paster, BJ Dewhirst, FE Cooke, SM Fussing, V Poulsen, LK Breznak, JA TI Phylogeny of not-yet-cultured spirochetes from termite guts SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID RIBOSOMAL-RNA SEQUENCES; MORPHOLOGY; CELLS AB Comparisons of 16S rDNA sequences were used to determine the phylogeny of not-yet-cultured spirochetes from hindguts of the African higher termite, Nasutitermes lujae (Wasmann). The 16S rRNA genes were amplified directly from spirochete-rich hindguts by using universal primers, and the amplified products were cloned into Escherichia coli, Clones were screened with a spirochete-specific DNA probe, Analysis of 1,410 base positions of the 16S rDNA insert from one spirochete clone, designated NL1, supported its assignment to the genus Treponema, with average interspecies similarities of ca. 85%. The sequence of NL1 was most closely related (ca, 87 to 88% similarity) to sequences of Spirochaeta stenostrepta and Spirochaeta caldaria and to a previously published sequence (ca. 87% similarity) of spirochetal clone MDS1 from the Australian lower termite, Mastotermes darwiniensis (Froggatt), On the basis of 16S rRNA sequence comparisons and individual base signatures, clones NL1 and MDS1 clearly represent two novel species of Treponema, although specific epithets have not yet been proposed. The gross morphology of NL1 was determined from in situ hybridization experiments with an NL1-specific, fluorescently labeled oligonucleotide probe, Cells were approximately 0.3 to 0.4 by 30 mu m in size, with a wavelength and amplitude of about 10 mu m and 0.8 to 1.6 mu m, respectively, Moreover, electron microscopy of various undulate cells present in gut contents confirmed that they possessed ultrastructural features typical of spirochetes, i.e., a wavy protoplasmic cylinder, periplasmic flagella, and an outer sheath. The sequence data suggest that termite gut spirochetes may represent a separate line of descent from other treponemes and that they constitute a significant reservoir of previously unrecognized spirochetal biodiversity. C1 DANISH VET LAB,DK-1790 COPENHAGEN V,DENMARK. TECH UNIV DENMARK,DEPT MICROBIOL,DK-2800 LYNGBY,DENMARK. MICHIGAN STATE UNIV,DEPT MICROBIOL,E LANSING,MI 48824. MICHIGAN STATE UNIV,CTR MICROBIAL ECOL,E LANSING,MI 48824. RP Paster, BJ (reprint author), FORSYTH DENT CTR,DEPT MOLEC GENET,140 FENWAY,BOSTON,MA 02115, USA. FU NIDCR NIH HHS [DE-08303, DE-10374] NR 36 TC 83 Z9 83 U1 1 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD FEB PY 1996 VL 62 IS 2 BP 347 EP 352 PG 6 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA TT690 UT WOS:A1996TT69000007 PM 8593040 ER PT J AU Otley, CC Fewkes, JL Frank, W Olbricht, SM AF Otley, CC Fewkes, JL Frank, W Olbricht, SM TI Complications of cutaneous surgery in patients who are taking warfarin, aspirin, or nonsteroidal anti-inflammatory drugs SO ARCHIVES OF DERMATOLOGY LA English DT Article ID PERIOPERATIVE BLOOD-LOSS; ARTERY BYPASS-SURGERY; ACETYLSALICYLIC-ACID; ANTIPLATELET THERAPY; CATARACT-SURGERY; BLEEDING-TIME; ANTICOAGULANTS; PATENCY; TRIAL; DIPYRIDAMOLE AB Background and Design: No controlled studies exist with regard to the risks of continuing therapy with warfarin sodium or platelet inhibitors or the benefits of briefly discontinuing therapy with these agents in patients who are undergoing cutaneous surgical procedures. Our objective was to determine the frequency of complications of cutaneous surgery in patients who were receiving warfarin or platelet inhibitors and to evaluate whether preoperative discontinuation reduces complications. A retrospective, controlled study was performed of complications of excisional and Mohs micrographic surgery in 653 patients who were being treated with warfarin or platelet inhibitors or with their medications being briefly withheld. Results: Severe complications of cutaneous surgery in patients who are taking warfarin or platelet inhibitors are uncommon, occur in 1.6% of cases, and are not significantly increased compared with complications in control subjects. Furthermore, there was no statistically significant reduction in the rates of severe complications in patients who had their medications preoperatively held. Conclusion: Cutaneous surgery in patients who receive warfarin or platelet inhibitors is associated with a low risk of severe complications, not significantly reduced by brief preoperatively discontinuation. C1 BETH ISRAEL HOSP,BOSTON,MA 02215. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT DERMATOL,BOSTON,MA 02115. NR 45 TC 99 Z9 100 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD FEB PY 1996 VL 132 IS 2 BP 161 EP 166 DI 10.1001/archderm.132.2.161 PG 6 WC Dermatology SC Dermatology GA TV312 UT WOS:A1996TV31200007 PM 8629823 ER PT J AU Sanders, VJ Waddell, AE Felisan, SL Li, XM Conrad, AJ Tourtellotte, WW AF Sanders, VJ Waddell, AE Felisan, SL Li, XM Conrad, AJ Tourtellotte, WW TI Herpes simplex virus in postmortem multiple sclerosis brain tissue SO ARCHIVES OF NEUROLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; INFECTION; TYPE-1; MICE; DEMYELINATION; ENCEPHALITIS; RESPONSES; ANTIGEN; SEARCH; DNA AB Background: Herpes simplex virus (HSV) is a common neurotropic virus that is capable of long latencies. It can cause focal demyelination in animals. Objective: To test for the presence of HSV-1 and -2 in postmortem brain samples from patients with multiple sclerosis (MS) and controls using polymerase chain reaction and Southern blot hybridization. Methods: Dissected plaque tissue classified as active or inactive and unaffected white matter (WM) and gray matter (GM) from 37 cases of MS were screened for HSV using polymerase chain reaction and Southern blot hybridization. White matter and GM from 22 cases of Alzheimer's disease, 17 cases of Parkinson's disease, and 22 cases without neurologic disease served as controls. Results: Forty-six percent (17/37) of the MS cases and 28% (17/61) of the control cases had samples that were positive for HSV (P=.11). Forty-one percent (9/22) of active plaques and 20% (6/30) of inactive plaques were positive for HSV. Twenty-four percent (9/37) and 14% (5/37) of MS cases and 23% (14/61) and 13% (8/61) of non-MS cases had HSV in WM and GM, respectively. No significant differences were found among all subgroups (P=.10). Conclusions: Herpes simplex virus was present in more MS cases than control cases and in more active plaques than inactive plaques. The presence of HSV in WM and GM in cases of MS as well as in control cases makes an etiologic association to the MS disease process uncertain, but cellular localization of HSV and its relationship to oligodendrocytes and latency may reveal such an association in future studies. C1 W LOS ANGELES VET AFFAIRS MED CTR,NEUROL SERV 127A,LOS ANGELES,CA 90073. W LOS ANGELES VET AFFAIRS MED CTR,RES SERV,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,SCH MED,DEPT NEUROL,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,BRAIN RES INST,LOS ANGELES,CA 90024. NR 23 TC 34 Z9 35 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 FEB PY 1996 VL 53 IS 2 BP 125 EP 133 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA TU729 UT WOS:A1996TU72900004 PM 8639061 ER PT J AU Young, LHY Howard, MA Hu, LK Kim, RY Gragoudas, ES AF Young, LHY Howard, MA Hu, LK Kim, RY Gragoudas, ES TI Photodynamic therapy of pigmented choroidal melanomas using a liposomal preparation of benzoporphyrin derivative SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID PROTON-BEAM IRRADIATION; CHLOROALUMINUM SULFONATED PHTHALOCYANINE; HEMATOPORPHYRIN PHOTORADIATION THERAPY; MOUSE-TUMOR MODEL; MALIGNANT-MELANOMA; UVEAL MELANOMAS; CELL CARCINOMA; HYPERTHERMIA; PHOTOSENSITIZER; DESTRUCTION AB Objective: To evaluate the effectiveness of photodynamic therapy of pigmented choroidal melanoma using a liposomal preparation of benzoporphyrin derivative monoacid (BPD), verteporfin. Design: Pigmented choroidal melanomas were established in 25 New Zealand albino rabbit eves. The animals were treated with daily injections of cyclosporine, and tumor growth was monitored with funduscopic examination and ultrasonography. Fifteen minutes after intravenous injection of BPD (2 mg/kg), the rumors were irradiated at 692 nm through an argon-pumped dye laser with the delivered fluence ranging between 40 and 150 J/cm(2). Control animals were treated with light only, photosensitizer only, or observation only. Tumor growth was monitored by indirect ophthalmoscopy, fundus photography, fluorescein angiography, and ultrasonography. Histologic examination was performed. Results: Eighteen tumor-bearing rabbits were treated with light and BPD; 16 were followed up for 1 month, and two were killed immediately for histologic examination. Tumors regressed in all eyes treated with 60 J/cm(2) or more. With fluence of 40 J/cm(2), tumor regrowth was observed in one animal within 10 days of treatment. In the three control groups, all animals showed continuous tumor growth. Histologic examination of the eyes treated with photosensitizer and light immediately after treatment showed prominent vascular occlusion throughout the full thickness of the tumor. One month after treatment, tumor necrosis and infiltration of mononuclear cells and pigment-laden macrophages were the predominant findings. Conclusions: Photodynamic therapy with BPD may have a role in the treatment of pigmented choroidal melanomas. RP Young, LHY (reprint author), HARVARD UNIV, MASSACHUSETTS EYE & EAR INFIRM, SCH MED, DEPT OPHTHALMOL, 243 CHARLES ST, BOSTON, MA 02114 USA. FU NEI NIH HHS [EY10975-01] NR 48 TC 34 Z9 37 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9950 EI 1538-3601 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD FEB PY 1996 VL 114 IS 2 BP 186 EP 192 PG 7 WC Ophthalmology SC Ophthalmology GA TU999 UT WOS:A1996TU99900011 PM 8573023 ER PT J AU Gliklich, RE Eavey, RD Iannuzzi, RA Camacho, AE AF Gliklich, RE Eavey, RD Iannuzzi, RA Camacho, AE TI A contemporary analysis of acute mastoiditis SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID CHILDREN AB Background: Acute mastoiditis persists as a serious infection despite a dramatic decline in incidence coincident with the introduction of antibiotic therapy. Objective: To assist the contemporary practitioner in the recognition and management of acute mastoiditis through the assessment of a large series of patients. Design: Retrospective case series comprising 124 patients with acute mastoiditis. Setting: Pediatric and adult otology referral center. Main Outcome Measures: Selected clinical parameters. Risk factors for necessity of surgical intervention and for increased length of hospitalization were analyzed by a stepwise logistic regression model. Results: A history of antecedent acute otitis media was absent in 45% of patients. Pain (98%) was the most common presenting symptom. Physical signs included an abnormal-appearing tympanic membrane (88%), fever (83%), a narrowed external audit-cry canal (80%), and postauricular edema (76%). Streptococcus pneumoniae was the most commonly isolated organism. Mastoid surgery was required in 62% of the patients. An elevated white blood cell count (relative risk [RR], 7.4; P<.01), proptosis of the auricle (RR, 4.5; P=.03), and fever on admission (RR, 7.3; P=.05) were risk factors for surgical intervention. All 33 patients with complications (27%) proceeded to surgical intervention. The average length of hospital stay was 7.9 days. The strongest predictor for an increased length of hospital stay was whether the patient required surgery (RR, 3.7; P=.002). Conclusions: Acute mastoiditis remains a potentially serious otologic infection. Not all patients present with a classic history or physical examination. Therapeutic mastoidectomy is often required. C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02115. NR 18 TC 60 Z9 61 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD FEB PY 1996 VL 122 IS 2 BP 135 EP 139 PG 5 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA TU726 UT WOS:A1996TU72600005 PM 8630206 ER PT J AU Mironova, M Virella, G LopesVirella, MF AF Mironova, M Virella, G LopesVirella, MF TI Isolation and characterization of human antioxidized LDL autoantibodies SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE autoimmunity; antioxidized LDL autoantibody isolation; arteriosclerosis; affinity constants; isotypes ID LOW-DENSITY-LIPOPROTEIN; FOAM CELL-FORMATION; HERITABLE HYPERLIPIDEMIC RABBIT; IMMUNE-COMPLEXES; OXIDATIVE MODIFICATION; ATHEROSCLEROSIS; DEGRADATION; ANTIBODIES; PROGRESSION; INVIVO AB Autoantibodies to oxidized LDL have been reported in normal subjects and in patients with arteriosclerosis, but their possible pathogenic role is not yet well defined. One important problem is the existence of contradictory data reported by different groups concerning the associations between antioxidized LDL autoantibodies and the presence or progression of arteriosclerotic lesions. Such contradictions led us to decide to isolate and characterize antioxidized LDL antibodies by affinity chromatography with the use of oxidized LDL cross-linked to Sepharose. Antioxidized LDL antibodies were isolated from selected serum samples obtained from eight subjects. Seven of them (six patients and one control subject) had high levels of antioxidized LDL antibody during screening. The other subject, a healthy volunteer, had a low level of antibody. All purified antibodies contained IgG (of subclasses 1 and 3) as the predominant isotype and were primarily specific for oxidized LDL but showed some cross-reactivity with malondialdehyde-modified LDL and native LDL. Two of the purified antibodies cross-reacted with cardiolipin. We determined average dissociation constants for the antioxidized LDL antibodies purified from five individuals, which varied between 2.4x10(-7) and 7.5x10(-7) mol/L, whereas the average dissociation constant of rabbit hyperimmune anti-LDL antibody was determined to be 2.7x10(-8) mol/L. In conclusion, we have purified human autoantibodies reactive with oxidized LDL that appear to be predominantly of moderate-to-low affinity and of variable cross-reactivity, The predominance of IgG1 and IgG3 antibodies is significant from the standpoint of potential pathogenicity, since these two subclasses activate the classic complement pathway system and have the highest binding affinities for Fc gamma receptors on phagocytic cells. C1 RALPH H JOHNSON VA MED CTR,CHARLESTON,SC 29401. MED UNIV S CAROLINA,DEPT MICROBIOL & IMMUNOL,CHARLESTON,SC 29425. MED UNIV S CAROLINA,DIV ENDOCRINOL DIABET & MED GENET,DEPT MED,CHARLESTON,SC 29425. FU NHLBI NIH HHS [HL46815] NR 52 TC 89 Z9 93 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD FEB PY 1996 VL 16 IS 2 BP 222 EP 229 PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA TV417 UT WOS:A1996TV41700006 PM 8620336 ER PT J AU Pujades, C Teixido, J Bazzoni, G Hemler, ME AF Pujades, C Teixido, J Bazzoni, G Hemler, ME TI Integrin alpha 4 cysteines 278 and 717 modulate VLA-4 ligand binding and also contribute to alpha(4/180) formation SO BIOCHEMICAL JOURNAL LA English DT Article ID CELL-ADHESION MOLECULE-1; MONOCLONAL-ANTIBODIES; PLASMA FIBRONECTIN; T-CELLS; EXPRESSION; SUBUNIT; RECEPTOR; DISTINCT; VCAM-1; LINES AB Here we describe experiments in which we mutated four oPthe six integrin alpha(4) subunit cysteine residues that are not present in most other integrin alpha subunits that lack an I domain. In four different types of ligand binding assay we found that optimal integrin alpha(4) beta(1) (VLA-4) binding to vascular cell adhesion molecule 1 (VCAM-1) and/or to CS1 peptide required the presence of both alpha(4) Cys(278) and Cys(717). In addition, optimal ligand binding required divalent cations and reduced cysteines, as evidenced by EDTA and N-ethylmaleimide inhibition results. In a control experiment, an alpha(4) mutation that completely eliminated the alpha(4) 80/70 proteolytic cleavage site had no effect on ligand binding. Notably, although Cys(278) and Cys(717) mutations markedly altered ligand binding, they had no adverse effect on cell adhesion. Thus, compared with cell adhesion, ligand binding is a distinct and apparently more stringent test of VLA-4 integrin-ligand interactions. In addition, we have established that the formation of the previously described alpha(4/180) [Parker, Pujades, Brenner and Hemler (1993) J. Biol. Chem. 268, 7028-7035] also requires Cys(278) and Cys(717), divalent cations and reduced cysteines. Thus alpha(4/180) appears to be more functionally relevant than alpha(4/150). C1 DANA FARBER CANC INST,BOSTON,MA 02115. RI Pujades, Cristina/F-7908-2014; Teixido, Joaquin/J-8543-2014 OI Pujades, Cristina/0000-0001-6423-7451; Teixido, Joaquin/0000-0002-3177-4151 FU NIGMS NIH HHS [GM38903] NR 49 TC 34 Z9 34 U1 0 U2 1 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD FEB 1 PY 1996 VL 313 BP 899 EP 908 PN 3 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TU585 UT WOS:A1996TU58500030 PM 8611173 ER PT J AU Karlsson, JOM Toner, M AF Karlsson, JOM Toner, M TI Long-term storage of tissues by cryopreservation: Critical issues SO BIOMATERIALS LA English DT Article DE cryobiology; cryopreservation; tissue; freezing injury ID INTRACELLULAR ICE FORMATION; DIMETHYL-SULFOXIDE; ADHESIVE INTERACTION; BIOARTIFICIAL LIVER; BIOLOGICAL-SYSTEMS; SALT CONCENTRATION; NONINVASIVE METHOD; MECHANICAL-STRESS; EXTRACELLULAR ICE; FREEZING-INJURY AB The technique of cryopreservation (maintenance of biological samples in a state of 'suspended animation' at cryogenic temperatures), its potential use in tissue engineering applications and current obstacles to the development of effective cryopreservation methods for tissues are reviewed. A didactic overview of the principles of cryobiology and the methodology of cryopreservation is given, with emphasis on the processes of injury to cells during freezing and thawing, and how these are related to the physicochemical and biophysical changes occurring during cryopreservation. Critical issues relevant to the application of cryopreservation methods to tissues are then addressed, including heat and mass transfer limitations in these bulk systems, intrinsic differences between isolated and cultured cells, and mechanisms of freezing injury unique to tissue systems. C1 MASSACHUSETTS GEN HOSP,SURG SERV,BOSTON,MA 02114. SHRINERS BURNS INST,CAMBRIDGE,MA 02139. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02114. FU NIDDK NIH HHS [DK 46270] NR 96 TC 237 Z9 257 U1 8 U2 48 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD FEB PY 1996 VL 17 IS 3 BP 243 EP 256 DI 10.1016/0142-9612(96)85562-1 PG 14 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA TY459 UT WOS:A1996TY45900003 PM 8745321 ER PT J AU Moghe, PV Berthiaume, F Ezzell, RM Toner, M Tompkins, RG Yarmush, ML AF Moghe, PV Berthiaume, F Ezzell, RM Toner, M Tompkins, RG Yarmush, ML TI Culture matrix configuration and composition in the maintenance of hepatocyte polarity and function SO BIOMATERIALS LA English DT Article DE hepatocyte polarity; collagen sandwich; Matrigel; hepatocyte culture ID CELL-ADHESION MOLECULES; EPIDERMAL GROWTH-FACTOR; RAT HEPATOCYTES; PLASMA-MEMBRANE; SANDWICH CONFIGURATION; COLLAGEN SANDWICH; SURFACE POLARITY; MESSENGER-RNA; LIVER; LOCALIZATION AB Several extracellular matrix (ECM) configurations involving type I collagen and Matrigel were examined for their ability to support differentiated function and polarity of cultured adult rat hepatocytes. Collagen sandwich- and Matrigel-based cultures yielded superior and comparable albumin secretion for at least 2 weeks. In collagen sandwich, hepatocytes were polygonal, and formed multicellular arrays. Collagen sandwich was also found to promote in vivo-like polarization of F-actin, cell adhesion molecules (E-cadherin), and lateral (Na+, K+-ATPase, glucose transporter) and apical (dipeptidyl peptidase, aminopeptidase) membrane polarity markers, but not the expression of the gap junction protein connexin 32 and the epidermal growth factor (EGF) receptor. In contrast, hepatocytes cultured in or on Matrigel were more rounded and formed aggregates. Matrigel-based cultures also elicited detectable levels of connexin and EGF receptor and an altered distribution of F-actin, E-cadherin, and apical and lateral membrane proteins. Composite sandwich configurations containing collagen I and Matrigel restored markers lacking in the collagen sandwich, and showed a variable morphology and membrane polarity. Hepatocyte polarity could thus be manipulated by the overall ECM composition. Furthermore, in composite sandwich cultures, these manipulations can be effected largely independent of changes in hepatocyte morphology and albumin secretion. C1 SHRINERS BURNS INST,RES CTR,CAMBRIDGE,MA 02139. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,DEPT SURG,SURG SERV,BOSTON,MA 02114. RUTGERS STATE UNIV,DEPT CHEM & BIOCHEM ENGN,PISCATAWAY,NJ 08854. FU NIDDK NIH HHS [DK 41709, DK 43351, DK 43371] NR 50 TC 143 Z9 146 U1 3 U2 14 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD FEB PY 1996 VL 17 IS 3 BP 373 EP 385 DI 10.1016/0142-9612(96)85576-1 PG 13 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA TY459 UT WOS:A1996TY45900017 PM 8745335 ER PT J AU Kas, J Strey, H Tang, JX Finger, D Ezzell, R Sackmann, E Janmey, PA AF Kas, J Strey, H Tang, JX Finger, D Ezzell, R Sackmann, E Janmey, PA TI F-actin, a model polymer for semiflexible chains in dilute, semidilute, and liquid crystalline solutions SO BIOPHYSICAL JOURNAL LA English DT Article ID QUASIELASTIC LIGHT-SCATTERING; RODLIKE MACROMOLECULES; ISOTROPIC SOLUTION; DYNAMICS; FILAMENTS; NETWORKS; TRANSPORT; DISORDER; TALIN; PHASE AB Single actin filaments were analyzed in solutions ranging from dilute (0.2 mu g/ml), where filaments interact only with solvent, to concentrations (4.0 mg/ml) at which F-actin forms a nematic phase. A persistence length of similar to 1.8 mu m and an average length of similar to 22 mu m (Kaufmann et al., 1992) identify actin as a model for studying the dynamics of semiflexible polymers. In dilute solutions the filaments exhibit thermal bending undulations in addition to diffusive motion. At higher semidilute concentrations (1.4 mg/ml) three-dimensional reconstructions of confocal images of fluorescently labeled filaments in a matrix of unlabeled F-actin reveal steric interactions between filaments, which account for the viscoelastic behavior of these solutions. The restricted undulations of these labeled chains reveal the virtual tube formed around a filament by the surrounding actin. The average tube diameter [a] scales with monomer concentration c as [a] proportional to c-((0.5 +/- 0.15)). The diffusion of filaments in semidilute solutions (c = (0.1-2.0) mg/ml) is dominated by diffusion along the filament contour (reptation), and constraint release by remodeling of the surrounding filaments is rare. The self-diffusion coefficient D-parallel to along the tube decreases linearly with the chain length for semidilute solutions. For concentrations >2.5 mg/ml a transition occurs from an isotropic entangled phase to a coexistence between isotropic and nematic domains. Analysis of the molecular motions of filaments suggests that the filaments in the aligned domains are in thermal equilibrium and that the diffusion coefficient parallel to the director D-parallel to is nearly independent of filament length. We also report the novel direct observation of u-shaped defects, called hairpins, in the nematic domains. C1 TECH UNIV MUNICH, DEPT PHYS, BIOPHYS GRP, D-85748 GARCHING, GERMANY. HARVARD UNIV, SCH MED, MASSACHUSETTS GEN HOSP, SURG RES LAB, BOSTON, MA 02129 USA. RP HARVARD UNIV, BRIGHAM & WOMENS HOSP,SCH MED,DEPT EXPTL MED, DIV EXPTL MED, LMRC 301, BOSTON, MA 02115 USA. RI Strey, Helmut/B-5456-2009 FU NIAMS NIH HHS [AR38910] NR 51 TC 181 Z9 182 U1 3 U2 24 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1996 VL 70 IS 2 BP 609 EP 625 PG 17 WC Biophysics SC Biophysics GA TY684 UT WOS:A1996TY68400004 PM 8789080 ER PT J AU Johnson, EM Berk, DA Jain, RK Deen, WM AF Johnson, EM Berk, DA Jain, RK Deen, WM TI Hindered diffusion in agarose gels: Test of effective medium model SO BIOPHYSICAL JOURNAL LA English DT Article ID TRANSPORT-PROPERTIES; PROTEIN DIFFUSION; FIBROUS MEMBRANES; TRACER DIFFUSION; SIZE; CYLINDERS; FICOLL; ARRAYS AB The diffusivities of uncharged macromolecules in gels (D) are typically lower than in free solution (D-infinity, because of a combination of hydrodynamic and steric factors. To examine these factors, we measured D and D, for dilute solutions of several fluorescein-labeled macromolecules, using an image-based fluorescence recovery after photobleaching technique. Test macromolecules with Stokes-Einstein radii (r(s)) of 2.1-6.2 nm, including three globular proteins (bovine serum albumin, ovalbumin, lactalbumin) and four narrow fractions of Ficoll, were studied in agarose gels with agarose volume fractions (phi) of 0.038-0.073. The gels were characterized by measuring the hydraulic permeability of supported agarose membranes, allowing calculation of the Darcy permeability (K) for each gel sample. It was found that K, which is a measure of the intrinsic hydraulic conductance of the gel, decreased by an order of magnitude as phi was increased over the range indicated. The diffusivity ratio D/D-infinity, which varied from 0.20 to 0.63, decreased with increases in r(s) or phi. Thus as expected, diffusional hindrances were the most severe for large macromolecules and/or relatively concentrated gels. According to a recently proposed theory for hindered diffusion through fibrous media, the diffusivity ratio is given by the product of a hydrodynamic factor (F) and a steric factor (S). The functional form is D/D-infinity = F(r/(s)/K-1/2) S(f), where f = [(r(s) + r(f))/r(f)](2) phi and r(f) is the fiber radius. Values of D/D-infinity calculated from this effective medium theory, without use of adjustable parameters, were in much better agreement with the measured values than were predictions based on other approaches. The strengths and limitations of the effective medium theory for predicting diffusivities in gels are discussed. C1 MIT, DEPT CHEM ENGN, CAMBRIDGE, MA 02139 USA. MASSACHUSETTS GEN HOSP, DEPT RADIAT ONCOL, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02114 USA. RI Berk, David/A-4863-2012 OI Berk, David/0000-0002-3855-6886 FU NCI NIH HHS [R35-CA-J5691]; NIDDK NIH HHS [DK20368] NR 33 TC 200 Z9 203 U1 2 U2 79 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1996 VL 70 IS 2 BP 1017 EP 1023 PG 7 WC Biophysics SC Biophysics GA TY684 UT WOS:A1996TY68400043 PM 8789119 ER PT J AU Corey, DP AF Corey, DP TI Strings and motors: Biophysical approaches to sensory transduction by vertebrate hair cells. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HOWARD HUGHES MED INST,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1996 VL 70 IS 2 BP AWAR1 EP AWAR1 PN 2 PG 1 WC Biophysics SC Biophysics GA TZ682 UT WOS:A1996TZ68200122 ER PT J AU Baukrowitz, T Yellen, G AF Baukrowitz, T Yellen, G TI The dwell time of the last ion in the multi-ion pore of a K+ channel SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DEPT NEUROBIOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1996 VL 70 IS 2 BP MAMA6 EP MAMA6 PN 2 PG 1 WC Biophysics SC Biophysics GA TZ682 UT WOS:A1996TZ68200704 ER PT J AU Bersohn, MM AF Bersohn, MM TI Sarcolemmal sodium-calcium exchange in myocardial ischemia. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,LOS ANGELES,CA 90073. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1996 VL 70 IS 2 BP MP298 EP MP298 PN 2 PG 1 WC Biophysics SC Biophysics GA TZ682 UT WOS:A1996TZ68201181 ER PT J AU Holmgren, M Jurman, ME Yellen, G AF Holmgren, M Jurman, ME Yellen, G TI The internal mouth of the Shaker K+ channel examined through cysteine mutagenesis and chemical modification SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1996 VL 70 IS 2 BP MAMA7 EP MAMA7 PN 2 PG 1 WC Biophysics SC Biophysics GA TZ682 UT WOS:A1996TZ68200702 ER PT J AU Holt, JC Caulfield, JB Umeda, P Slayter, HS Martino, L Melendez, JA Margossian, SS AF Holt, JC Caulfield, JB Umeda, P Slayter, HS Martino, L Melendez, JA Margossian, SS TI Partial cDNA sequence of the neutral protease mekratin and probing human cardiomyopathic heart RNA. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 RHONE POULENC RORER,KING OF PRUSSIA,PA. UNIV ALABAMA,BIRMINGHAM,AL. DANA FARBER CANC INST,BOSTON,MA 02115. ALBANY MED COLL,ALBANY,NY 12208. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1996 VL 70 IS 2 BP MPO41 EP MPO41 PN 2 PG 1 WC Biophysics SC Biophysics GA TZ682 UT WOS:A1996TZ68200924 ER PT J AU Liu, Y Jurman, ME Yellen, G AF Liu, Y Jurman, ME Yellen, G TI Dynamic rearrangement of the outer mouth of a K+ channel during gating SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DEPT NEUROBIOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1996 VL 70 IS 2 BP MAMA3 EP MAMA3 PN 2 PG 1 WC Biophysics SC Biophysics GA TZ682 UT WOS:A1996TZ68200700 ER PT J AU Margossian, SS Anderson, PAW Norton, O Caulfield, JB Chantler, PD Slayter, HS AF Margossian, SS Anderson, PAW Norton, O Caulfield, JB Chantler, PD Slayter, HS TI Ca++-regulation and myofibrillar structure in human cardiomyopathic hearts. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 DUKE UNIV,MED CTR,DURHAM,NC. ALBANY MED COLL,ALBANY,NY 12208. UNIV ALABAMA,BIRMINGHAM,AL. UNIV LONDON ROYAL VET COLL,LONDON SW1,ENGLAND. DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1996 VL 70 IS 2 BP MPO40 EP MPO40 PN 2 PG 1 WC Biophysics SC Biophysics GA TZ682 UT WOS:A1996TZ68200923 ER PT J AU Williamson, P Grobner, G Miller, K Watts, A AF Williamson, P Grobner, G Miller, K Watts, A TI Solid state nuclear magnetic resonance (ss-NMR) of ligand protein interactions in the nicotinic acetylcholine receptor (nAChR) SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 UNIV OXFORD,DEPT BIOCHEM,OXFORD OX1 3QU,ENGLAND. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ANESTHESIA,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1996 VL 70 IS 2 BP MP398 EP MP398 PN 2 PG 1 WC Biophysics SC Biophysics GA TZ682 UT WOS:A1996TZ68201281 ER PT J AU Kas, J Strey, H Tang, JX Finger, D Ezzell, R Sackmann, E Janmey, PA AF Kas, J Strey, H Tang, JX Finger, D Ezzell, R Sackmann, E Janmey, PA TI Molecular motions of single actin fields in dilute, semidilute and liquid crystalline solutions SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DIV EXPTL MED,BOSTON,MA 02115. TECH UNIV MUNICH,DEPT PHYS,BIOPHYS GRP,D-85748 GARCHING,GERMANY. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,SURG RES LAB,DEPT SURG,BOSTON,MA 02129. NR 0 TC 1 Z9 1 U1 0 U2 2 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1996 VL 70 IS 2 BP SUA15 EP SUA15 PN 2 PG 1 WC Biophysics SC Biophysics GA TZ682 UT WOS:A1996TZ68200077 ER PT J AU Rankin, SE Miller, KW AF Rankin, SE Miller, KW TI Threshold cholesterol concentrations required for rapid agonist-induced state transitions in the nicotinic acetylcholine receptor SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1996 VL 70 IS 2 BP SU257 EP SU257 PN 2 PG 1 WC Biophysics SC Biophysics GA TZ682 UT WOS:A1996TZ68200442 ER PT J AU Zviman, MM Hayashi, Z Brand, JG Teeter, JH Restrepo, D AF Zviman, MM Hayashi, Z Brand, JG Teeter, JH Restrepo, D TI Rapid alternate measurement of membrane potential and intracellular calcium in cell ensembles SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 UNIV PENN,MONELL CHEM SENSES CTR,PHILADELPHIA,PA 19104. UNIV PENN,DEPT PHYSIOL,PHILADELPHIA,PA 19104. VET AFFAIRS MED CTR,PHILADELPHIA,PA 19104. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1996 VL 70 IS 2 BP SU471 EP SU471 PN 2 PG 1 WC Biophysics SC Biophysics GA TZ682 UT WOS:A1996TZ68200656 ER PT J AU Fesik, SW Zhou, MM Olejniczak, ET Petros, AM Meadows, RP Sattler, M Harlan, JE Wade, WS Crosby, S Ravichandran, KS Burakoff, SJ AF Fesik, SW Zhou, MM Olejniczak, ET Petros, AM Meadows, RP Sattler, M Harlan, JE Wade, WS Crosby, S Ravichandran, KS Burakoff, SJ TI Structures of protein ligand complexes involved in signal transduction. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 ABBOTT LABS,PPD,ABBOTT PK,IL 60064. DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1996 VL 70 IS 2 BP TUAM2 EP TUAM2 PN 2 PG 1 WC Biophysics SC Biophysics GA TZ682 UT WOS:A1996TZ68201342 ER PT J AU Shangguan, T Siegel, DP Lear, JD Axelsen, P Alford, D Bentz, J AF Shangguan, T Siegel, DP Lear, JD Axelsen, P Alford, D Bentz, J TI Correlation of influenza virus fusion and inactivation with conformational changes in hemagglutinin. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 LIPOSOME CO INC,PRINCETON,NJ 08540. PROCTER & GAMBLE CO,CINCINNATI,OH 45253. UNIV PENN,DEPT BIOCHEM & BIOPHYS,PHILADELPHIA,PA 19104. UNIV PENN,DEPT PHARMACOL,PHILADELPHIA,PA 19104. CTR BLOOD RES,BOSTON,MA 02115. DREXEL UNIV,DEPT BIOSCI BIOTECH,PHILADELPHIA,PA 19104. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1996 VL 70 IS 2 BP WP351 EP WP351 PN 2 PG 1 WC Biophysics SC Biophysics GA TZ682 UT WOS:A1996TZ68202538 ER PT J AU Smith, PL Baukrowitz, T Yellen, G AF Smith, PL Baukrowitz, T Yellen, G TI Mechanism of inward rectification in the HERG potassium channel SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DEPT NEUROBIOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1996 VL 70 IS 2 BP WAMA3 EP WAMA3 PN 2 PG 1 WC Biophysics SC Biophysics GA TZ682 UT WOS:A1996TZ68202084 ER PT J AU Chauhan, D Uchiyama, H Akbarali, Y Urashima, M Yamamoto, K Libermann, TA Anderson, KC AF Chauhan, D Uchiyama, H Akbarali, Y Urashima, M Yamamoto, K Libermann, TA Anderson, KC TI Multiple myeloma cell adhesion-induced interleukin-6 expression in bone marrow stromal cells involves activation of NF-kappa B SO BLOOD LA English DT Article ID STIMULATORY FACTOR-II; TUMOR-NECROSIS-FACTOR; TRANSCRIPTION FACTOR; GENE-EXPRESSION; GROWTH-FACTOR; PLASMA-CELLS; RESPONSE PATTERNS; HUMAN-FIBROBLASTS; AUTOCRINE GROWTH; DISEASE SEVERITY AB Adhesion of multiple myeloma (MM) cells to bone marrow stromal cells (BMSCs) not only localizes MM cells in the marrow microenvironment, but also triggers interleukin-6 (IL-6) secretion by BMSCs and related MM cell proliferation. In the present study, we characterized the regulation of IL-6 gene expression in BMSCs during MM cell adhesion. Adhesion of ARH-77, Hs-Sultan, IM-9, and U266 MM cell lines to BMSCs and BMSC lines (LP 101 and AA 101) triggered 5-through 15-fold and 2-through 4-fold increases in IL-6 secretion, respectively. IL-6 mRNA transcripts were undetectable by Northern blotting in IM-9 MM cells or LP 101 BMSCs cultured alone; however, adherence of IM-9 cells to LP 101 cells induced a transient increase in IL-6 transcripts at 6 hours, followed by peak IL-6 secretion at 24 hours. To confirm increased IL-6 transcription and characterize its regulation, LP101 BMSCs were transiently transfected with full length and deletion fragments of the IL-6 promoter linked to the chloramphenicol acetyltransferase (CAT) reporter gene. Transient transfection of LP101 BMSCs with plasmid containing an intact NF-kappa B site showed a 6.8 +/- 0.4-fold increase in CAT activity triggered by IM-9 MM cell adhesion (n = 3, P < .05). Transfection of LP 101 cells with plasmid containing a single base pair deletion from the NF-kappa B binding motif abolished the MM adhesion-induced increase in CAT activity, whereas transfection with plasmid containing three copies of synthetic NF-kappa B sequence resulted in an 8.1 +/- 0.7-fold increase in CAT activity related to MM adhesion (n = 3, P < .05). These data suggest that the NF-kappa B site is one of the essential regulatory elements for MM cell adhesion-induced IL-6 transcription in BMSCs. Electrophoretic mobility shift assays confirmed the involvement of NF-kappa B activation in regulating MM adhesion-induced IL-6 transcription in BMSCs. Further characterization of the upstream events in the signalling cascade regulating IL-6 may not only delineate mechanisms of IL-6 regulation during paracrine MM cell growth, but also provide new therapeutic strategies based on interruption of IL-6 mediated tumor cell growth. (C) 1996 by The American Society of Hematology. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. BETH ISRAEL HOSP,DEPT MED,BOSTON,MA 02215. KANAZAWA UNIV,CANC RES INST,DEPT MOLEC PATHOL,KANAZAWA,ISHIKAWA 920,JAPAN. RI Libermann, Towia/F-9866-2010 FU NCI NIH HHS [CA 50947] NR 64 TC 402 Z9 412 U1 2 U2 7 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD FEB 1 PY 1996 VL 87 IS 3 BP 1104 EP 1112 PG 9 WC Hematology SC Hematology GA TT484 UT WOS:A1996TT48400034 PM 8562936 ER PT J AU Gow, DW Caplan, D AF Gow, DW Caplan, D TI An examination of impaired acoustic-phonetic processing in aphasia SO BRAIN AND LANGUAGE LA English DT Article ID AUDITORY COMPREHENSION; SPEECH-PERCEPTION; VOICE; PLACE AB This research examines the nature of acoustic-phonetic impairments found in aphasia, and the reliability of patient performance on phoneme discrimination and identification tasks. Aphasic patients were tested on three phoneme discrimination tasks examining their ability to discriminate items on the basis of contrasts in sonorance, manner, place, or voicing using both spoken and synthetic stimuli. One of these tests involving the discrimination of spoken, one-syllable items was given to patients on three occasions over the course of 1 year to examine short- and long-term test reliability. In addition to these measures, patients were tested on three phoneme identification tasks using stimulus items drawn from the discrimination tests. The results of these tests how that aphasic patients may display stable patterns of performance on these measures over time and between tests. Furthermore, these findings suggest that discriminations of synthetic speech do not necessarily reflect patients' ability to discriminate spoken speech tokens. These results are interpreted as evidence that aphasics display stable, discrete impairments in acoustic-phonetic processing, and that these deficits may be measured reliably using phoneme discrimination and identification tasks using natural speech. (C) 1996 Academic Press, Inc. C1 MASSACHUSETTS GEN HOSP,NEUROPSYCHOL LAB,DEPT NEUROL,BOSTON,MA 02114. FU NIDCD NIH HHS [DC00776]; NINDS NIH HHS [P01-NS27950-2] NR 32 TC 29 Z9 29 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0093-934X J9 BRAIN LANG JI Brain Lang. PD FEB PY 1996 VL 52 IS 2 BP 386 EP 407 PG 22 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA TY765 UT WOS:A1996TY76500007 PM 8811970 ER PT J AU Baxter, LT Jain, RK AF Baxter, LT Jain, RK TI Pharmacokinetic analysis of the microscopic distribution of enzyme-conjugated antibodies and prodrugs: Comparison with experimental data SO BRITISH JOURNAL OF CANCER LA English DT Article DE enzyme-conjugated antibody; mathematical model; prodrug; two-step therapy ID BINDING-SITE BARRIER; G AMIDASE CONJUGATE; MONOCLONAL-ANTIBODY; MICROVASCULAR PERMEABILITY; PERIVASCULAR DISTRIBUTION; INTERSTITIAL PRESSURE; NEOPLASTIC TISSUES; MODELING ANALYSIS; DELIVERY SYSTEM; CANCER-THERAPY AB A mathematical model was developed to improve understanding of the biodistribution and microscopic profiles of drugs and prodrugs in a system using enzyme-conjugated antibodies as part of a two-step method for cancer treatment. The use of monoclonal antibodies alone may lead to heterogeneous uptake within tumour tissue; the use of a second, low molecular weight agent may provide greater penetration into tumour tissue. This mathematical model was used to describe concentration profiles surrounding individual blood vessels within a tumour. From these profiles the area under the curve and specificity ratios were determined. By integrating these results spatially, average tissue concentrations were determined and compared with experimental results from three different systems in the literature: two using murine antibodies and one using humanised fusion proteins. The maximum enzyme conversion rate (V-max) and the residual antibody concentration in the plasma and normal tissue were seen to be key determinants of drug concentration and drug-prodrug ratios in the tumour and other organs. Thus, longer time delays between the two injections, clearing the antibody from the bloodstream and the use of 'weaker' enzymes (lower V-max) will be important factors in improving this prodrug approach. Of these, the model found the effective clearance of antibody outside of the tumour to be the most effective. The use of enzyme-conjugated antibodies may offer the following advantages over the bifunctional antibody-hapten system: (i) more uniform distribution of the active agent; (ii) higher concentrations possible for the active agent; and (iii) greater specificity (therapeutic index). C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP Baxter, LT (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,STEELE LAB TUMOR BIOL,BOSTON,MA 02114, USA. FU NCI NIH HHS [R35-CA-56591] NR 57 TC 34 Z9 34 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD FEB PY 1996 VL 73 IS 4 BP 447 EP 456 DI 10.1038/bjc.1996.80 PG 10 WC Oncology SC Oncology GA TV410 UT WOS:A1996TV41000008 PM 8595158 ER PT J AU Movassaghi, K Goodman, ML Keith, D AF Movassaghi, K Goodman, ML Keith, D TI Ulcerative eosinophilic granuloma: A report of five new cases SO BRITISH JOURNAL OF ORAL & MAXILLOFACIAL SURGERY LA English DT Article ID ORAL-MUCOSA; TONGUE AB Five new cases of ulcerative eosinophilic granuloma were diagnosed at the Massachusetts General Hospital between 1982 and 1993. In all cases the site was the tongue. They were unifocal, did not recur, and had a benign course. This report illustrates their benign nature despite the occasional aggressive presentation, and outlines possible aetiology. C1 HARVARD COMMUN HLTH PLAN,BOSTON,MA. HARVARD SCH DENT MED,BOSTON,MA. MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA. HARVARD SCH MED,BOSTON,MA. RP Movassaghi, K (reprint author), MASSACHUSETTS GEN HOSP,DEPT ORAL & MAXILLOFACIAL SURG,BOSTON,MA 02114, USA. NR 12 TC 10 Z9 10 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH, MIDLOTHIAN, SCOTLAND EH1 3AF SN 0266-4356 J9 BRIT J ORAL MAX SURG JI Br. J. Oral Maxillofac. Surg. PD FEB PY 1996 VL 34 IS 1 BP 115 EP 117 DI 10.1016/S0266-4356(96)90148-5 PG 3 WC Dentistry, Oral Surgery & Medicine; Surgery SC Dentistry, Oral Surgery & Medicine; Surgery GA TW230 UT WOS:A1996TW23000022 PM 8645663 ER PT J AU Cobau, CD Declercq, K Neuberg, D Ingle, JN Tormey, DC AF Cobau, CD Declercq, K Neuberg, D Ingle, JN Tormey, DC TI A randomized trial of megestrol acetate with or without premarin in the treatment of potentially responsive metastatic breast cancer - A study of the Eastern Cooperative Oncology Group (E2185) SO CANCER LA English DT Article DE breast cancer; metastatic; treatment; hormone responsive; megace; premarin; randomized trial ID TAMOXIFEN; THERAPY AB BACKGROUND. Human breast cancer cells in vitro exhibit increased levels of progestin receptors (PgR) after brief exposure to physiologic concentrations of estrogens. Prior clinical studies have positively correlated the responsiveness of metastatic breast cancer to progestin therapy with the level of PgR in the tumor cells. METHODS. These observations were used as the scientific basis for a randomized clinical trial by the Eastern Cooperative Oncology Group (ECOG) to compare the effectiveness of megestrol acetate (MEG) alone in a daily dose of 160 mg with MEG alternated with premarin in a dose of 1.25 mg/day on the first 3 days of a 14 day cycle (PRE/MEG). From 1985 through 1989, 266 eligible and fully evaluable patients were randomized to 1 of the treatment arms and accrued to this trial. All patients were postmenopausal with biochemical estrogen cytosol protein receptor (ER) positive (greater than or equal to 10 fm/mg) tumors. The treatment groups were balanced with respect to performance status, number of involved organ systems, and PgR levels. RESULTS. Forty-five of 135 (33%) (95% confidence interval [CI], 25-42%) patients receiving MEG experienced a partial (PR) or complete (CR) response. Thirty-one of 131 (23%) (95% CI, 17-32%) patients receiving PRE/MEG achieved a PR or CR. Survival was not influenced by treatment selection. However, median time to progression was seven months for patients receiving MEG and four months for the group receiving PRE/MEG (P = 0.03). The treatment failure hazard rate was higher for patients with a short disease free interval after primary treatment of the breast cancer, poor performance status, non-white race, and visceral disease. Survival was negatively impacted by short disease free interval, administration of prior radiation therapy, prior treatment for metastatic disease, and hepatic involvement. CONCLUSIONS. Sequential treatment with premarin and megestrol acetate is not superior to treatment with megace alone in potentially hormone responsive patients with advanced breast cancer. (C) 1996 American Cancer Society. C1 DANA FARBER CANC INST,BOSTON,MA 02115. MAYO CLIN,ROCHESTER,MN. AMC CANC RES CTR,DENVER,CO. RP Cobau, CD (reprint author), FLOWER HOSP,5200 HARROUN RD,SYLVANIA,OH 43560, USA. FU NCI NIH HHS [CA37403, CA23318, CA35415] NR 18 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD FEB 1 PY 1996 VL 77 IS 3 BP 483 EP 489 PG 7 WC Oncology SC Oncology GA TR916 UT WOS:A1996TR91600009 PM 8630955 ER PT J AU Koya, K Li, Y Wang, H Ukai, T Tatsuta, N Kawakami, M Shishido, T Chen, LB AF Koya, K Li, Y Wang, H Ukai, T Tatsuta, N Kawakami, M Shishido, T Chen, LB TI MKT-077, a novel rhodacyanine dye in clinical trials, exhibits anticarcinoma activity in preclinical studies based on selective mitochondrial accumulation SO CANCER RESEARCH LA English DT Article ID CARCINOMA-CELLS INVITRO; LIVING CELLS; MEMBRANE-POTENTIALS; RHODAMINE-123; RETENTION; TOXICITY; GROWTH; PLASMA AB MKT-077 (formerly known as FJ-776) is a newly synthesized, highly water-soluble (>200 mg/ml) rhodacyanine dye that exhibits significant antitumor activity in a variety of model systems, In culture, MKT-077 inhibits the growth of five human cancer cell lines (colon carcinoma CX-1, breast carcinoma MCF-7, pancreatic carcinoma CRL1420, bladder transitional cell carcinoma EJ, and melanoma LOX) but not monkey kidney CV-1, an indicator cell line for normal epithelial cells. In nude mice, MKT-077 inhibits the growth of s.c. implanted human renal carcinoma A498 and human prostate carcinoma DU145 and prolongs the survival of mice bearing i.p. implanted human melanoma LOX (tumor:control = 344%). Subcellular localization indicates that MKT-077 is taken up and retained by mitochondria, and flow cytometric analysis suggests that CX-1 cells take up MKT-077 to a much greater extent than CV-1 cells, Quantitation of MKT-077 uptake by ethanol extraction shows that CX-1 cells accumulate 65-fold more MKT-077 than do CV-1 cells, MKT-077 is the first delocalized lipophilic cation with a favorable pharmacological and toxicological profile in preclinical studies, MKT-077 is now being investigated in Phase I clinical trials. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. FUJI PHOTO FILM CO LTD,ASHIGARA RES LABS,MINAMIASHIGARA,KANAGAWA 25001,JAPAN. NR 34 TC 134 Z9 136 U1 1 U2 10 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD FEB 1 PY 1996 VL 56 IS 3 BP 538 EP 543 PG 6 WC Oncology SC Oncology GA TR324 UT WOS:A1996TR32400024 PM 8564968 ER PT J AU ModicaNapolitano, JS Koya, K Weisberg, E Brunelli, BT Li, Y Chen, LB AF ModicaNapolitano, JS Koya, K Weisberg, E Brunelli, BT Li, Y Chen, LB TI Selective damage to carcinoma mitochondria by the rhodacyanine MKT-077 SO CANCER RESEARCH LA English DT Article ID RAT-LIVER MITOCHONDRIA; NUCLEAR-DNA; RHODAMINE-123; CELLS; PROBE; ACCUMULATION; RETENTION; SAFRANINE; TOXICITY; DYE AB We investigated the mitochondrial toxicity of the lipophilic cation, MKT-077, and the role of mitochondria in selective malignant cell killing by this compound by examining the effect of MKT-077 on mitochondrial structure and function in treated cells and in isolated organelles, Results of this study demonstrate changes in mitochondrial ultrastructure that are induced by MKT-077 treatment in carcinoma cells but not in similarly treated normal epithelial cells, In addition, MKT-077 was found to inhibit respiratory activity in isolated intact mitochondria and electron transport activity in freeze-thawed mitochondrial membrane fragments in a dose-dependent manner, The concentration of MKT-077 necessary to obtain half-maximal inhibition of ADP-stimulated respiration was approximately 4-fold greater in mitochondria isolated from cells of the normal epithelial cell line, CV-1 (15 mu g MKT-077/mg protein), as compared to the human colon carcinoma cell line, CX-1 (4 mu g MKT-077/mg protein), Further, the data show a selective loss of mitochondrial DNA in CX-1 and CRL1420 cells (carcinoma) but not CV-1 cells (normal epithelial) treated with 3 mu g/ml MKT-077 for up to 3 days, Under the same conditions, nuclear DNA was unaffected in all three cell lines, The sensitivity of the cell lines tested to mitochondrial damage by MKT-077 correlates well with their sensitivity to cytotoxicity by MKT-077, These results demonstrate selective mitochondrial damage by MKT-077 at the cellular, biochemical, and molecular levels and suggest that selective effects on mitochondrial structure and function may provide a basis for the selective malignant cell killing exhibited by this compound. C1 TUFTS UNIV,DEPT BIOL,MEDFORD,MA 02155. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELLULAR & MOLEC BIOL,BOSTON,MA 02115. NR 27 TC 107 Z9 110 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD FEB 1 PY 1996 VL 56 IS 3 BP 544 EP 550 PG 7 WC Oncology SC Oncology GA TR324 UT WOS:A1996TR32400025 PM 8564969 ER PT J AU Weisberg, EL Koya, K ModicaNapolitano, J Li, Y Chen, LB AF Weisberg, EL Koya, K ModicaNapolitano, J Li, Y Chen, LB TI In vivo administration of MKT-077 causes partial yet reversible impairment of mitochondrial function SO CANCER RESEARCH LA English DT Article ID RAT-LIVER MITOCHONDRIA; CARCINOMA-CELLS; RHODAMINE-123; ACCUMULATION; DEQUALINIUM; SEQUENCES AB The effects of in vivo administration of a pharmacologically toxic dose of the lipophilic cationic compound, MKT-077, mere investigated in selected vital organs of the rat, MKT-077 (15 mg/kg body weight), administered by bolus i.v. injection every day for 5 days, did not detectably influence rat heart and kidney mitochondrial respiration, Although the same dosage of MKT-077 significantly decreased respiratory rates in rat Liver mitochondria relative to untreated controls, complete recovery was evident within 3 days following drug withdrawal, Whereas the mitochondrial DNA of rat kidney and liver appeared to be unaffected by MKT-077 treatment, levels of heart mtDNA were noticeably less than control levels in the immediate interval following drug administration, However, this latter effect was partially reversed as early as 10 days following treatment and completely reversed within a 30-day posttreatment period, These results strongly suggest that a pharmacologically toxic dose of MKT-077 minimally affects the overall functional integrity of mitochondria in such critical, although highly vulnerable, tissues as the heart, liver, and kidney. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELLULAR & MOLEC BIOL,BOSTON,MA 02115. TUFTS UNIV,DEPT BIOL,MEDFORD,MA 02155. NR 18 TC 42 Z9 44 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 FEB 1 PY 1996 VL 56 IS 3 BP 551 EP 555 PG 5 WC Oncology SC Oncology GA TR324 UT WOS:A1996TR32400026 PM 8564970 ER PT J AU Tahara, H Smith, AP Gaz, RD Cryns, VL Arnold, A AF Tahara, H Smith, AP Gaz, RD Cryns, VL Arnold, A TI Genomic localization of novel candidate tumor suppressor gene loci in human parathyroid adenomas SO CANCER RESEARCH LA English DT Article ID ENDOCRINE NEOPLASIA TYPE-1; CHROMOSOME 11Q13; OVARIAN-CANCER; ALLELIC LOSS; LINKAGE MAP; LONG ARM; ALLELOTYPE; ONCOGENE; CELL; OVEREXPRESSION AB Only one oncogene, cyclin D1/PRAD1, has an established role in parathyroid tumorigenesis, and parathyroid tumor suppressor genes on chromosome arms 1p and 11q, which still have not been identified, have also been implicated by loss of heterozygosity analysis, To investigate whether other putative tumor suppressor genes are involved in the pathogenesis of parathyroid adenomas, we performed a more comprehensive analysis of allelic losses in these tumors. Using 39 polymorphic markers, we examined each chromosome arm, excluding the short arms of the acrocentric chromosomes, In 25 parathyroid adenomas, frequent loss of heterozygosity, in >25% of the informative cases, was observed on chromosome arms 6q (30%), 11p (27%), and 15q (35%), in addition to previously reported 1p (30%) and 11q (38%) allelic losses, To more specifically localize the smallest shared regions of molecular genetic deletion, we examined the following chromosomes in greater detail: chromosome 6 (9 additional markers), chromosome 11 (8 additional markers), and chromosome 15 (15 additional markers), The regions most commonly deleted in these tumors were 6q22-23, 6q26-27, 11q13, 15q11-21, and 15q26-qter. All tumors with 11p loss had patterns consistent with monosomy for chromosome 11, These findings provide novel evidence for the existence of tumor suppressor genes on chromosome arms 6q and 15q that contribute commonly to the pathogenesis of parathyroid adenomas. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,ENDOCRINE ONCOL LAB,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,BOSTON,MA 02114. FU NCI NIH HHS [K01-CA-01752-01A1]; NIDDK NIH HHS [DK-11794] NR 48 TC 126 Z9 126 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 FEB 1 PY 1996 VL 56 IS 3 BP 599 EP 605 PG 7 WC Oncology SC Oncology GA TR324 UT WOS:A1996TR32400034 PM 8564978 ER PT J AU Harrison, L Galanopoulos, T Ascione, AG Antoniades, HN Demple, B AF Harrison, L Galanopoulos, T Ascione, AG Antoniades, HN Demple, B TI Regulated expression of APE apurinic endonuclease mRNA during wound healing in porcine epidermis SO CARCINOGENESIS LA English DT Article ID DNA-REPAIR; MESSENGER-RNA; CELLS; CDNA; MUTAGENESIS; HOMOLOG; CANCER AB Abasic (AP) sites in DNA are cytotoxic and mutagenic and their repair is initiated by AP endonucleases. The major AP endonuclease of mammalian cells is encoded by the APE gene. Ape protein has also been proposed to modulate the activity of some transcription factors independently of its AP endonuclease activity. We investigated whether APE expression is coordinated with cell division, which could diminish mutagenesis. The level of APE mRNA was followed during wound healing in porcine epidermis, in which surgical wounding prompts rapid cell proliferation followed by a differentiation program to regenerate normal skin. In situ hybridization with a probe from human APE cDNA revealed strongly decreased expression in rapidly proliferating migrating cells during the first 1-3 days following wounding, succeeded by sharply increased APE expression that exceeded the pre-wounding levels by days 9-17. These changes were not observed in the surrounding undamaged tissue. In contrast to the foregoing in vivo results, APE expression in cultured primary human fibroblasts (IMR90) or myeloid leukemia cells (K562) was not coordinated with cell division. This biphasic APE expression during wound healing could relate to transcription factor regulation or it could allow unhindered DNA synthesis or prepare the developing epidermis to handle DNA damage. However, if transient under-expression of APE-encoded repair enzyme does occur, it might render regenerating skin especially vulnerable to mutagenesis during the cell proliferation phase. C1 HARVARD UNIV,SCH PUBL HLTH,DEPT MOLEC & CELLULAR TOXICOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. FU NIGMS NIH HHS [GM40000] NR 39 TC 21 Z9 21 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD FEB PY 1996 VL 17 IS 2 BP 377 EP 381 DI 10.1093/carcin/17.2.377 PG 5 WC Oncology SC Oncology GA UC149 UT WOS:A1996UC14900033 PM 8625467 ER PT J AU Weinstein, BM Fishman, MC AF Weinstein, BM Fishman, MC TI Cardiovascular morphogenesis in zebrafish SO CARDIOVASCULAR RESEARCH LA English DT Review DE development; zebrafish ID MYOSIN HEAVY-CHAINS; CAENORHABDITIS-ELEGANS; SPT-1 MUTATION; HEART TUBE; GERM-CELLS; FATE MAP; EMBRYO; SPECIFICATION; GASTRULATION; POLARITY C1 MASSACHUSETTS GEN HOSP EAST,CARDIOVASC RES CTR,CHARLESTOWN,MA 02129. NR 39 TC 21 Z9 22 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD FEB PY 1996 VL 31 SI SI BP E17 EP E24 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA UL027 UT WOS:A1996UL02700003 PM 8681341 ER PT J AU Hayashi, Y Zviman, MM Brand, JG Restrepo, D Teeter, JH AF Hayashi, Y Zviman, MM Brand, JG Restrepo, D Teeter, JH TI Optical and electrophysiological recordings of monosodium glutamate-induced responses in mouse taste cells SO CHEMICAL SENSES LA English DT Meeting Abstract C1 KYOTO UNIV,FOOD SCI RES INST,UJI,KYOTO 611,JAPAN. MONELL CHEM SENSES CTR,PHILADELPHIA,PA 19104. UNIV PENN,SCH DENT MED,DEPT BIOCHEM,PHILADELPHIA,PA 19104. VET AFFAIRS MED CTR,PHILADELPHIA,PA 19104. UNIV PENN,DEPT PHYSIOL,PHILADELPHIA,PA 19104. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0379-864X J9 CHEM SENSES JI Chem. Senses PD FEB PY 1996 VL 21 IS 1 BP 53 EP 53 PG 2 WC Behavioral Sciences; Food Science & Technology; Neurosciences; Physiology SC Behavioral Sciences; Food Science & Technology; Neurosciences & Neurology; Physiology GA TW943 UT WOS:A1996TW94300063 ER PT J AU Mittleman, MA Meigs, JB Waxman, S Singer, DE Sutherland, P Matheney, T Lipinska, I Stec, JJ Muller, JE Nathan, DM Wilson, PWF Tofler, GH AF Mittleman, MA Meigs, JB Waxman, S Singer, DE Sutherland, P Matheney, T Lipinska, I Stec, JJ Muller, JE Nathan, DM Wilson, PWF Tofler, GH TI Impaired glucose tolerance and hemostasis: The framingham offspring study. SO CIRCULATION LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEACONESS HOSP,INST PREVENT CARDIOVASC DIS,BOSTON,MA. 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 FEB 1 PY 1996 VL 93 IS 3 BP P4 EP P4 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA TR330 UT WOS:A1996TR33000076 ER PT J AU Stafford, RS Singer, D AF Stafford, RS Singer, D TI Low rates of warfarin use in atrial fibrillation among US physicians 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 FEB 1 PY 1996 VL 93 IS 3 BP P61 EP P61 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA TR330 UT WOS:A1996TR33000133 ER PT J AU Lee, JS Adrie, C Jacob, HJ Roberts, JD Zapol, WM Bloch, KD AF Lee, JS Adrie, C Jacob, HJ Roberts, JD Zapol, WM Bloch, KD TI Chronic inhalation of nitric oxide inhibits neointimal formation after balloon-induced arterial injury SO CIRCULATION RESEARCH LA English DT Article DE nitric oxide; neointimal formation angioplasty; inhalation therapy ID SMOOTH-MUSCLE CELLS; PLATELET THROMBUS FORMATION; BLEEDING-TIME; PULMONARY VASOCONSTRICTION; CORONARY ANGIOPLASTY; INTIMAL HYPERPLASIA; S-NITROSOTHIOLS; RELAXING FACTOR; PROLIFERATION; ADHESION AB Systemic and local intravascular NO administration inhibits neointimal formation after vascular injury in animal models. NO appears to attenuate smooth muscle proliferation both directly and indirectly by preventing the release of growth factors. Inhalation of low concentrations of NO dilates pulmonary vascular smooth muscle but does not cause systemic vasodilatation. Recently, NO inhalation was found to inhibit platelet function in vivo. We studied the effects of NO inhalation on neointimal formation after balloon-induced injury of the adult rat carotid artery. Beginning 60 minutes before carotid injury, rats breathed either air with 0 or 80 ppm NO for 14 days. Rats were killed, carotid arteries were fixed and paraffin-embedded, and neointimal formation was measured by analyzing the ratio of intimal to medial areas (I/M ratio) in carotid artery cross sections. Intimal hyperplasia was evident in both groups of animals, but I/M ratios were 43% less in animals breathing 80 ppm NO for 2 weeks than in animals breathing air alone (0.78+/-0.12 and 1.37+/-0.11 [mean+/-SE], respectively; P<.02). Similarly, 1 week after carotid injury, neointimal formation was less in rats breathing 80 ppm NO than in rats breathing air alone (I/M ratio, 0.39+/-0.11 versus 0.76+/-0.06; P<.02). Breathing 20 ppm NO for 2 weeks or 80 ppm NO for 1 week followed by air alone for 1 week did not attenuate neointimal formation measured al 14 days. In anesthetized rats breathing 80 ppm NO or air alone for 1 hour, neither systemic blood pressure nor bleeding time differed. These observations demonstrate that inhaling 80 ppm NO inhibits neointimal formation after balloon-induced carotid artery injury in rats. NO inhalation may represent a safe and novel method of preventing restenosis after percutaneous angioplasty. C1 MASSACHUSETTS GEN HOSP,DEPT ANAESTHESIA,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,GEN MED SERV,CARDIAC UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,BOSTON,MA 02114. FU NHLBI NIH HHS [K08 HL004237, HL-42397, HL-45895, T32 HL-07208] NR 53 TC 94 Z9 97 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7330 J9 CIRC RES JI Circ.Res. PD FEB PY 1996 VL 78 IS 2 BP 337 EP 342 PG 6 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA TU871 UT WOS:A1996TU87100020 PM 8575078 ER PT J AU Howard, SP Park, SJ HughesDavies, L Coleman, CN Price, BD AF Howard, SP Park, SJ HughesDavies, L Coleman, CN Price, BD TI Suramin increases p53 protein levels but does not activate the p53-dependent G(1) checkpoint SO CLINICAL CANCER RESEARCH LA English DT Article ID PROSTATE-CANCER CELLS; GROWTH-FACTOR; DNA-BINDING; INHIBITS GROWTH; HELA-CELLS; KINASE-C; APOPTOSIS; DAMAGE; AGENTS; IRRADIATION AB Suramin is an antineoplastic agent which has a cytostatic effect on both normal and tumor-derived cells, We have investigated whether the induction of growth arrest by suramin requires the p53 protein, a tumor suppressor gene product involved in the initiation of growth arrest following DNA damage, Activation of the p53 protein by genotoxic agents causes increased p53 protein levels and p53-dependent transcription of the p21 gene. The p21 protein then inhibits cyclin-dependent kinases, initiating G(1) arrest. Exposure of NIH-3T3 cells to suramin caused a rapid (1-2 h) increase in the level of p53-DNA-binding activity, Flow cytometric analysis indicated that suramin arrested NIH-3T3 cells in G(0)-G(1). However, suramin did not increase the p53-dependent transcription of the p21 gene or inhibit cyclin-dependent kinase 2 kinase activity, If NIH-3T3 cells were exposed to radiation or suramin plus radiation, p21 mRNA levels were increased and cyclin-dependent kinase 2 kinase activity was inhibited, indicating that suramin does not block the cells' ability to increase p21 levels, To determine whether the G(0)-G(1) arrest induced by suramin required p53, NIH-3T3 cells transfected with a dominant negative mutant p53 gene to eliminate wild-type p53 function (NMP cells) were exposed to suramin, NMP cells still exhibited G(0)-G(1) arrest after suramin treatment. Suramin increases p53 protein levels, but fails to increase p21 mRNA levels or to activate the G(1) checkpoint, These data suggest that suramin induces growth arrest in NIH-3T3 cells by a mechanism that is independent of cellular p53 status. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,JOINT CTR RADIAT THERAPY,STRESS PROT GRP,BOSTON,MA 02115. FU NCI NIH HHS [CA64585] NR 56 TC 15 Z9 15 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD FEB PY 1996 VL 2 IS 2 BP 269 EP 276 PG 8 WC Oncology SC Oncology GA TU875 UT WOS:A1996TU87500005 PM 9816169 ER PT J AU Kristjansen, PEG Brown, TJ Shipley, LA Jain, RK AF Kristjansen, PEG Brown, TJ Shipley, LA Jain, RK TI Intratumor pharmacokinetics, flow resistance, and metabolism during gemcitabine infusion in ex vivo perfused human small cell lung cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID TUMOR BLOOD-FLOW; MAGNETIC-RESONANCE; SOLID TUMORS; 2',2'-DIFLUORODEOXYCYTIDINE GEMCITABINE; ENERGY-METABOLISM; MAMMARY-CARCINOMA; LACTIC-ACID; RAT-TUMORS; NUDE RATS; XENOGRAFTS AB The relationship between tumor physiology and the pharmacokinetics of 2',2' difluorodeoxycytidine [gemcitabine (dFdC)] in ex vivo perfused human small cell lung cancer was examined, Two small cell lung cancer sublines, 54A and 54B, with known in vivo sensitivity to dFdC, were grown as tissue-isolated tumors in athymic mice and perfused ex vivo with or without 20-40 mu M dFdC. Arteriovenous differences in gases, pH, and metabolites were determined before and during drug infusion, The geometric flow resistance (FR) of individual tumors was calculated, and dFdC and its inactive metabolite 2',2' difluorodeoxyuridine were determined by high-performance liquid chromatography of consecutive samples from the output line, Both tumors had prominent lactate production concurrent with a significant O-2 consumption. The arteriovenous pH drop was similar to 0.3 in both tumor lines, Significant metabolic differences between 54A and 54B tumors were found that elucidated previously described differences further, Pharmacokinetic analysis showed that the initial tumor uptake of dFdC was flow limited, and a significant inverse correlation between the geometric FR and initial drug uptake was found, The rate constant for recovery of the drug in the tumor outflow was greater in 54B tumors (P < 0.05), and the geometric FR was greater in 54A tumors (P < 0.01). The drug conversion rate was independent of physiological parameters, Attempts to modify the delivery of dFdC should be directed at the tumor blood flow distribution, More generally, our experimental model provides useful new insight into metabolism and intratumor pharmacokinetics of chemotherapeutic agents in solid tumors. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,EDWIN L STEELE LAB,BOSTON,MA 02114. ELI LILLY & CO,LILLY RES LABS,INDIANAPOLIS,IN 46285. FU NCI NIH HHS [R35-CA-56591] NR 42 TC 26 Z9 26 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 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD FEB PY 1996 VL 2 IS 2 BP 359 EP 367 PG 9 WC Oncology SC Oncology GA TU875 UT WOS:A1996TU87500015 PM 9816179 ER PT J AU Natowicz, MR Prence, EM Chaturvedi, P Newburg, DS AF Natowicz, MR Prence, EM Chaturvedi, P Newburg, DS TI Urine sulfatides and the diagnosis of metachromatic leukodystrophy SO CLINICAL CHEMISTRY LA English DT Article DE arylsulfatase A; sulfatidase; lysosomal storage disease; chromatography, liquid; heritable disorders ID PERFORMANCE LIQUID-CHROMATOGRAPHY; ARYLSULFATASE-A; PSEUDODEFICIENCY ALLELES; CEREBROSIDE SULFATE; FIBROBLASTS; DEFICIENCY; EXCRETION; DISEASE; BRAIN; ASSAY AB A deficiency of the lysosomal enzyme arylsulfatase A (ASA) causes the lysosomal storage disorder metachromatic leukodystrophy (MLD), The diagnosis of MLD is straightforward in cases with deficient leukocyte or fibroblast ASA activity and a typical clinical history, However, several atypical and late-onset forms of MLD have been described, The diagnosis is also complicated by the high frequency of presumably benign polymorphisms at the ASA gene locus that are associated with markedly diminished in vitro ASA activity, Additional diagnostic tools are needed in the clinically and (or) enzymatically atypical cases. Although analyses of urinary sulfatides have been reported to be helpful in the diagnosis of MLD, previously described methods are complex and incompletely characterized and validated. We developed an improved method for determining urinary sulfatides and applied it to a cohort of individuals with MLD. The sulfatides are extracted from urine, separated from glycerol-based lipids by alkaline hydrolysis, isolated by ion-exchange chromatography, and hydrolyzed to galactosylceramide, which is then perbenzoylated and quantified by HPLC, This assay provides excellent resolution of sulfatides from other lipids and good analytical precision. In addition, the urinary sulfatide concentrations of healthy controls (mean +/- SD: 0.16 +/- 0.07 nmol/mg creatinine; range: 0.07-0.34; n = 18) are clearly distinguished from those of individuals with MLD (7.6 +/- 6.1 nmol/mg creatinine; 1.2-24.2; n = 20). C1 EUNICE KENNEDY SHRIVER CTR MENTAL RETARDAT INC,DIV BIOMED SCI,WALTHAM,MA 02254. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PEDIAT,BOSTON,MA 02114. RP Natowicz, MR (reprint author), EUNICE KENNEDY SHRIVER CTR MENTAL RETARDAT INC,DIV MED GENET,200 TRAPELO RD,WALTHAM,MA 02254, USA. FU NICHD NIH HHS [HD29272, HD13021] NR 28 TC 18 Z9 18 U1 0 U2 1 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD FEB PY 1996 VL 42 IS 2 BP 232 EP 238 PG 7 WC Medical Laboratory Technology SC Medical Laboratory Technology GA TV950 UT WOS:A1996TV95000006 PM 8595716 ER PT J AU Sharkey, PK Graybill, JR Johnson, ES Hausrath, SG Pollard, RB Kolokathis, A Mildvan, D FanHavard, P Eng, RHK Patterson, TF Pottage, JC Simberkoff, MS Wolf, J Meyer, RD Gupta, R Lee, LW Gordon, DS AF Sharkey, PK Graybill, JR Johnson, ES Hausrath, SG Pollard, RB Kolokathis, A Mildvan, D FanHavard, P Eng, RHK Patterson, TF Pottage, JC Simberkoff, MS Wolf, J Meyer, RD Gupta, R Lee, LW Gordon, DS TI Amphotericin B lipid complex compared with amphotericin B in the treatment of cryptococcal meningitis in patients with AIDS SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID SYSTEMIC FUNGAL-INFECTIONS; FLUCONAZOLE; TOXICITY AB The study objective was to obtain preliminary information regarding the safety and efficacy of amphotericin B (AmB) lipid complex (ABLC) in the treatment of AIDS-associated cryptococcal meningitis. Of 55 patients randomly assigned to 6 weeks of therapy with ABLC (1.2-5.0 mg/[kg . d], with ascending doses for three sequential cohorts) or AmB (0.7-1.2 mg/[kg . d]), 46 received greater than or equal to 12 doses. Transfusion requirements, mean decreases in hemoglobin level, and mean increases in creatinine level were significantly greater with AmB than with ABLC. The total number of adverse events, infusion-related events, and occurrences of hypomagnesemia and hypokalemia associated with each form of therapy were similar, Among 21 recipients of ABLC at a dosage of 5 mg/kg (daily for 2 weeks and then thrice weekly for 4 weeks), symptoms and signs resolved for 18 (86%), Of those receiving greater than or equal to 12 doses of ABLC, cultures converted to negative for 8 (42%), were undeterminable for 3 (16%), and remained positive for 8 (42%) despite resolution of symptoms, Although preliminary, these data suggest ABLC has significant activity in patients with AIDS-associated cryptococcal meningitis, Because this formulation has less hematologic and renal toxicity than does AmB, further evaluation of ABLC is warranted. C1 AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. ST MICHAELS HOSP,NEWARK,NJ. UNIV TEXAS,MED BRANCH,GALVESTON,TX 77550. BETH ISRAEL MED CTR,NEW YORK,NY 10003. VET AFFAIRS MED CTR,NEW YORK,NY. DEPT VET AFFAIRS MED CTR,E ORANGE,NJ. YALE UNIV,SCH MED,NEW HAVEN,CT. RUSH UNIV,RUSH PRESBYTERIAN ST LUKES MED CTR,CHICAGO,IL 60612. THOMAS JEFFERSON UNIV,PHILADELPHIA,PA 19107. UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA. LIPSOME CO INC,PRINCETON,NJ. BRISTOL MYERS SQUIBB PHARMACEUT RES INST,PRINCETON,NJ 08543. RP Sharkey, PK (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT MED,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. NR 14 TC 151 Z9 157 U1 0 U2 2 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 FEB PY 1996 VL 22 IS 2 BP 315 EP 321 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA TU876 UT WOS:A1996TU87600017 PM 8838189 ER PT J AU Fudala, PJ Yu, E Macfadden, W Kampman, K Cornish, J AF Fudala, PJ Yu, E Macfadden, W Kampman, K Cornish, J TI Evaluation of the effects of naloxone and buprenorphine in morphine-stabilized opiate addicts SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 DEPT VET AFFAIRS MED CTR,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,PHILADELPHIA,PA 19104. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1996 VL 59 IS 2 BP PII90 EP PII90 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TX001 UT WOS:A1996TX00100325 ER PT J AU Wolfe, GR Stewart, JE Maeder, LA Hartz, GW AF Wolfe, GR Stewart, JE Maeder, LA Hartz, GW TI Use of Dental Coping Beliefs Scale to measure cognitive changes following oral hygiene interventions SO COMMUNITY DENTISTRY AND ORAL EPIDEMIOLOGY LA English DT Article DE dental beliefs; locus of control; oral health; self-efficacy ID MULTIDIMENSIONAL HEALTH LOCUS; SELF-EFFICACY; PERFORMANCE; BEHAVIORS; RELAPSE; PROGRAM AB This study employed a recently developed questionnaire, the Dental Coping Beliefs Scale (DCBS), to evaluate the effect of oral hygiene interventions on dental beliefs. The DCBS was administered to 100 subjects. Compared to an untreated control group, there was an increase in the ability to improve oral health through self-effort for the three experimental interventions: Attention (AI), Education (El) and Cognitive Behavioral (CBI). When the Dental Coping Beliefs Scale was divided into scales of Internal Locus of Control, External Locus of Control, Self-Efficacy, and Oral Health Beliefs, additional changes were evident. For the CBI Group, all four scales changed significantly between baseline measurement and post-intervention toward beliefs favoring control and prevention of dental disease using brushing and flossing. For the A and E groups, three scales paralleled the results of the CBI: Internal Locus of Control and Self-Efficacy increased and External Locus of Control decreased after the intervention. However, unlike the CBI, Oral Health Beliefs did not significantly change. Overall, for all experimental groups, there was a shift from external locus of control beliefs to internal beliefs. The untreated Control Group showed no changes across the five weeks. This study was supported by a VA Medical Research Service Merit Review Award. C1 UNIV CALIF LOS ANGELES,SECT PREVENT DENT,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SECT PERIODONTOL,LOS ANGELES,CA 90024. US DEPT VET AFFAIRS,OUTPATIENT CLIN,PALO ALTO,CA. RP Wolfe, GR (reprint author), US DEPT VET AFFAIRS,OUTPATIENT CLIN,PSYCHOL SERV 116B,351 E TEMPLE ST,LOS ANGELES,CA 90012, USA. NR 32 TC 28 Z9 28 U1 1 U2 6 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0301-5661 J9 COMMUNITY DENT ORAL JI Community Dentist. Oral Epidemiol. PD FEB PY 1996 VL 24 IS 1 BP 37 EP 41 DI 10.1111/j.1600-0528.1996.tb00810.x PG 5 WC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health SC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health GA TZ710 UT WOS:A1996TZ71000009 PM 8833513 ER PT J AU Ezekowitz, RAB Hoffmann, JA AF Ezekowitz, RAB Hoffmann, JA TI Editorial overview SO CURRENT OPINION IN IMMUNOLOGY LA English DT Editorial Material C1 INST BIOL MOLEC & CELLULAIRE,CNRS,F-67084 STRASBOURG,FRANCE. RP Ezekowitz, RAB (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,DEPT PEDIAT,FRUIT ST,BOSTON,MA 02114, USA. NR 2 TC 8 Z9 8 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 FEB PY 1996 VL 8 IS 1 BP 1 EP 2 DI 10.1016/S0952-7915(96)80096-3 PG 2 WC Immunology SC Immunology GA UC436 UT WOS:A1996UC43600001 ER PT J AU Epstein, J Eichbaum, Q Sheriff, S Ezekowitz, RAB AF Epstein, J Eichbaum, Q Sheriff, S Ezekowitz, RAB TI The collectins in innate immunity SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID MANNOSE-BINDING-PROTEIN; COMPLEMENT PATHWAY; CLASSICAL PATHWAY; GENE; ASSOCIATION; FREQUENCY; CHILDREN; LECTIN; DEFECT; FORMS AB The collectins are proteins with collagen tails and globular lectin domains that appear to play an important role in mammalian first line host defense. Recent insights have clarified the structural basis of ligand recognition, the interactions of collectins with complement cascades, and the association with disease susceptibility. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. BRISTOL MYERS SQUIBB PHARMACEUT RES INST,MACROMOLEC CRYSTALLOG,PRINCETON,NJ 08543. HARVARD UNIV,MASSACHUSETTS GEN HOSP,DEPT PEDIAT,BOSTON,MA 02114. RP Epstein, J (reprint author), HARVARD UNIV,CHILDRENS HOSP,DEPT PEDIAT,300 LONGWOOD AVE,ENDERS BLDG 610,BOSTON,MA 02115, USA. NR 58 TC 203 Z9 208 U1 0 U2 5 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 FEB PY 1996 VL 8 IS 1 BP 29 EP 35 DI 10.1016/S0952-7915(96)80101-4 PG 7 WC Immunology SC Immunology GA UC436 UT WOS:A1996UC43600006 PM 8729443 ER PT J AU Raab, G Kover, K Paria, BC Dey, SK Ezzell, RM Klagsbrun, M AF Raab, G Kover, K Paria, BC Dey, SK Ezzell, RM Klagsbrun, M TI Mouse preimplantation blastocysts adhere to cells expressing the transmembrane form of heparin-binding EGF-like growth factor SO DEVELOPMENT LA English DT Article DE juxtacrine growth factor; EGF receptor; heparan sulfate proteoglycan; TGF-alpha; mouse ID LEUKEMIA INHIBITORY FACTOR; FACTOR RECEPTOR FAMILY; FACTOR-ALPHA; PERIIMPLANTATION PERIOD; DELAYED IMPLANTATION; SIGNAL TRANSDUCTION; ESTROGEN-RECEPTOR; SURFACE; EMBRYOS; UTERUS AB Previous studies have shown that heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) mRNA is synthesized in the mouse uterine luminal epithelium, temporally, just prior to implantation, and spatially, only at the site of blastocyst apposition (Das, S. K., Wang, X. N., Paria, B. C., Damm, D., Abraham, J. A., Klagsbrun, M., Andrews, G. K. and Dey, S. K. (1994) Development 120, 1071-1083). HB-EGF is synthesized as a transmembrane protein (HB-EGF(TM)) that can be processed to release the soluble growth factor. An antibody that cross-reacts only with the transmembrane form detected HB-EGF(TM) in uterine luminal epithelium in a spatial manner similar to that of HB-EGF mRNA. HB-EGF(TM) is a juxtacrine growth factor that mediates cell-cell contact. To ascertain if HB-EGF(TM) could be an adhesion factor for blastocysts, a mouse cell line synthesizing human HB-EGF(TM) was co-cultured with mouse blastocysts. Cells synthesizing HB-EGF(TM) adhered to day-4 mouse blastocysts more extensively than parental cells or cells synthesizing a constituitively secreted form of HB-EGF. Adhesion of cells synthesizing HB-EGF(TM) to blastocysts was inhibited by excess recombinant HB-EGF but less so by TGF-alpha. adhesion was also inhibited by the synthetic peptide P21 corresponding to the HB-EGF heparin binding domain, and by incubating the blastocysts with heparinase. In addition, adhesion to delayed implanting dormant blastocysts, which lack EGF receptor (EGFR), was diminished relative to normal blastocysts. These results suggested that adhesion between blastocysts and cells synthesizing HB-EGF(TM) was mediated via interactions with both blastocyst EGFR and heparan sulfate proteoglycan (HSPG). It was concluded that HB-EGF(TM), which is synthesized exclusively in the luminal epithelium at the site of blastocyst apposition, and which is a juxtacrine adhesion factor for blastocysts, could be one of the mediators of blastocyst adhesion to the uterus in the process of implantation. C1 CHILDRENS HOSP,DEPT SURG,BOSTON,MA 02115. CHILDRENS HOSP,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,SURG RES LABS,BOSTON,MA 02129. UNIV KANSAS,MED CTR,DEPT PHYSIOL,KANSAS CITY,KS 66160. FU NCI NIH HHS [CA 37392]; NICHD NIH HHS [HD 29968]; NIGMS NIH HHS [GM 47397] NR 67 TC 157 Z9 166 U1 1 U2 6 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0950-1991 J9 DEVELOPMENT JI Development PD FEB PY 1996 VL 122 IS 2 BP 637 EP 645 PG 9 WC Developmental Biology SC Developmental Biology GA TY517 UT WOS:A1996TY51700024 PM 8625815 ER PT J AU Reynet, C Kahn, CR Loeken, MR AF Reynet, C Kahn, CR Loeken, MR TI Expression of the gene encoding glycogen phosphorylase is elevated in diabetic rat skeletal muscle and is regulated by insulin and cyclic AMP SO DIABETOLOGIA LA English DT Article DE glycogen phosphorylase; muscle; gene expression; insulin ID SYNTHASE PHOSPHATASE-ACTIVITY; PROTEIN-KINASE; SEQUENCE; IDENTIFICATION; ACTIVATION; RESISTANCE; DECREASES; MELLITUS; RECEPTOR; ELEMENT AB Glycogen phosphorylase regulates the breakdown of glycogen into glucose, but as previous studies have demonstrated, the control of glycogen metabolism becomes deregulated in diabetes mellitus. Messenger RNA levels encoding several different proteins are altered in skeletal muscle biopsies of patients with insulin-dependent and non-insulin-dependent diabetes. The possible alteration of expression of the gene encoding the skeletal muscle isoform of glycogen phosphorylase during diabetes has not previously been investigated. We examined the effect of streptozotocin-induced diabetes and insulin treatment on glycogen phosphorylase mRNA in rat skeletal muscle; glycogen phosphorylase mRNA levels were elevated in diabetic rat muscle tissue, but were partially suppressed in diabetic rat muscle following insulin treatment. To distinguish between the effects of insulin and counter-regulatory hormones on glycogen phosphorylase mRNA levels, we employed differentiating rat L6 myoblasts in culture. Insulin stimulated the accumulation of glycogen phosphorylase mRNA as determined by Northern blot analysis. Moreover, insulin and dibutyryl cAMP stimulated expression of a transiently transfected chloramphenicol acetyl transferase reporter gene under the control of the muscle glycogen phosphorylase promoter in differentiating myotubes in culture, suggesting that the effects of insulin and counter-regulatory hormones on glycogen phosphorylase mRNA are at the level of transcription. These results suggest that insulin and epinephrine may participate in the induction of the glycogen phosphorylase gene during myogenesis; moreover, activation of this gene in muscle tissue may be a contributing factor in impaired glycogen storage during uncontrolled diabetes. C1 JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02215. FU NCI NIH HHS [CA 50599]; NIDDK NIH HHS [DK 45935] NR 38 TC 10 Z9 10 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD FEB PY 1996 VL 39 IS 2 BP 183 EP 189 DI 10.1007/BF00403961 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TR711 UT WOS:A1996TR71100008 PM 8635670 ER PT J AU Yao, ZH Gross, GJ AF Yao, ZH Gross, GJ TI Role of K-ATP channels in memory associated with myocardial preconditioning SO DRUG NEWS & PERSPECTIVES LA English DT Article ID SENSITIVE POTASSIUM CHANNELS; T-WAVE CHANGES; CARDIAC MEMORY; INFARCT SIZE; RABBIT HEARTS; DOGS; ADENOSINE; ISCHEMIA; RECEPTORS; BLOCKADE C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ANESTHESIA,BOSTON,MA 02114. MED COLL WISCONSIN,DEPT PHARMACOL & TOXICOL,MILWAUKEE,WI 53226. NR 39 TC 3 Z9 3 U1 0 U2 1 PU J R PROUS SA PI BARCELONA PA APARTADO DE CORREOS 540, PROVENZA 388, 08025 BARCELONA, SPAIN SN 0214-0934 J9 DRUG NEWS PERSPECT JI Drug News Perspect. PD FEB PY 1996 VL 9 IS 1 BP 13 EP 18 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA UU780 UT WOS:A1996UU78000002 ER PT J AU Yamatsuji, T Okamoto, T Takeda, S Murayama, Y Tanaka, N Nishimoto, I AF Yamatsuji, T Okamoto, T Takeda, S Murayama, Y Tanaka, N Nishimoto, I TI Expression of V642 APP mutant causes cellular apoptosis as Alzheimer trait-linked phenotype SO EMBO JOURNAL LA English DT Article DE amyloid precursor protein; apoptosis; bcl-2; familial Alzheimer's disease; G proteins ID AMYLOID PRECURSOR PROTEIN; CULTURED SKIN FIBROBLASTS; LONG-TERM POTENTIATION; ALPHA-SUBUNIT; MISSENSE MUTATION; BINDING PROTEIN; BETA-PROTEIN; CELLS; DISEASE; CALCIUM AB APP is a transmembrane precursor of beta-amyloid. In dominantly inherited familial Alzheimer's disease (FAD), point mutations V642I, V642F and V642G have been discovered in APP(695). Here we show that expression of these mutants (FAD-APPs) causes a clone of COS cells to undergo apoptosis associated with DNA fragmentation, Apoptosis by the three FAD-APPs was the highest among all possible V642 mutants; normal APP(695) had no effect on apoptosis, suggesting that apoptosis by APP mutants in this system is phenotypically linked to the FAD trait. FAD-APP-induced apoptosis was sensitive to bcl-2 and most probably mediated by heteromeric G proteins. This study presents a model system allowing analysis of the mechanism for FAD-APP-induced cytotoxicity. C1 HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,BOSTON,MA 02129. UNIV TOKYO,SCH MED,DEPT MED 4,BUNKYO KU,TOKYO 112,JAPAN. OKAYAMA UNIV,SCH MED,DEPT SURG 1,OKAYAMA 700,JAPAN. NR 58 TC 102 Z9 105 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD FEB 1 PY 1996 VL 15 IS 3 BP 498 EP 509 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA TU925 UT WOS:A1996TU92500006 PM 8599933 ER PT J AU DiSimone, N Crowley, WF Wang, QF Sluss, PM Schneyer, AL AF DiSimone, N Crowley, WF Wang, QF Sluss, PM Schneyer, AL TI Characterization of inhibin activin subunit, follistatin, and activin type II receptors in human ovarian cancer cell lines: A potential role in autocrine growth regulation SO ENDOCRINOLOGY LA English DT Article ID FACTOR-BETA; GRANULOSA-CELLS; ALPHA-SUBUNIT; HUMAN-SERUM; PROTEIN; RAT; FOLLICULOGENESIS; RADIOIMMUNOASSAY; SECRETION; PRECURSOR AB Although ovarian cancer is the most common gynecological malignancy with a relatively poor 5-yr survival record, the mechanism(s) by which these tumors arise is not well understood. A role for inhibins and activins in regulating this transformation is suggested by the detection of circulating alpha or dimeric inhibin in some patients with ovarian cancer and by the alpha inhibin knockout mouse, in which development of gonadal tumors in 100% of hornozygotes is associated with greatly elevated activin levels. To develop diagnostic tools with greater specificity for ovarian cancers, the present study was targeted at characterizing the biosynthetic capacity of the epithelial ovarian cancer cell lines from the American Type Culture Collection with respect to inhibin, activin, the related activin-binding protein follistatin (FS), and activin receptor type II. In addition, the functional capacity of this system was investigated by examining the ability of activin and FS to modulate cellular proliferation. All six cell lines contained abundant messenger RNA (mRNA) for activin receptor type II, but no inhibin alpha-subunit mRNA was detected in any cell line. Two cell lines contained mRNA for activin beta B-subunit (CaOV4 and SKOV3), one cell Line contained beta A-subunit mRNA (SW626), and one cell line contained both (ES2); the latter also contained FS mRNA. FS mRNA was detected in another cell line (PA-1) that contained no detectable activin beta-subunit mRNA. Finally, one cell line (CaOV3) contained neither beta-subunit nor FS mRNA. C1 MASSACHUSETTS GEN HOSP,REPROD ENDOCRINE UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,NATL CTR INFERTIL RES,BOSTON,MA 02114. FU NICHD NIH HHS [P30 HD028138, R01-HD-31894, T32 HD007396, U54 HD029164, U54-HD-29164] NR 45 TC 92 Z9 94 U1 0 U2 1 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD FEB PY 1996 VL 137 IS 2 BP 486 EP 494 DI 10.1210/en.137.2.486 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TR826 UT WOS:A1996TR82600014 PM 8593793 ER PT J AU Meier, CA AF Meier, CA TI Co-activators and co-repressors: Mediators of gene activation by nuclear hormone receptors SO EUROPEAN JOURNAL OF ENDOCRINOLOGY LA English DT Article RP Meier, CA (reprint author), MASSACHUSETTS GEN HOSP,DIV ENDOCRINE,BOSTON,MA 02114, USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0804-4643 J9 EUR J ENDOCRINOL JI Eur. J. Endocrinol. PD FEB PY 1996 VL 134 IS 2 BP 158 EP 159 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TV898 UT WOS:A1996TV89800005 PM 8630512 ER PT J AU Fujimoto, K Lyman, SD Hirayama, F Ogawa, M AF Fujimoto, K Lyman, SD Hirayama, F Ogawa, M TI Isolation and characterization of primitive hematopoietic progenitors of murine fetal liver SO EXPERIMENTAL HEMATOLOGY LA English DT Article; Proceedings Paper CT 1995 Annual Meeting of the ISEH CY 1995 CL DUSSELDORF, GERMANY SP Int Soc Exptl Hematol DE fetal liver; hematopoietic stem cells; clonal cell culture; hematopoietic cytokines ID COLONY-STIMULATING FACTOR; TYROSINE KINASE RECEPTOR; STEM-CELLS; C-KIT; INTERLEUKIN-3-DEPENDENT PROLIFERATION; SYNERGISTIC INTERACTIONS; MONOCLONAL-ANTIBODY; CULTURE; DIFFERENTIATION; GENE AB We have isolated hematopoietic progenitors from mouse fetal liver using a sequential protocol of density gradient centrifugation, panning, and cell sorting. Isolated AA4.1(+)Ly6A/E(+)CD43(++) cells with density ranging from 1.0631 to 1.0710 g/cm(3) were 480- to 600-fold enriched for multipotential progenitors relative to unfractionated cells and showed 40 to 60% colony-forming efficiency. We then examined the effects of various cytokines on the colony formation from enriched fetal liver cells. Steel factor (SF), interleukin-3 (IL-3), IL-4, IL-6, IL-11, and granulocyte colony-stimulating factor (G-CSF) as single agents supported formation of significant numbers of colonies, but flt3/flk-2 ligand (FL) and IL-12 did not. When the cytokines were combined, FL, SF, IL-3, and IL-4 each synergized individually with IL-6, IL-11, IL-12, or G-CSF to support formation of various types of colonies. Next we analyzed the growth factor requirements for proliferation and differentiation of lymphohematopoietic progenitors by using the two-step methylcellulose culture assay we established recently. None of the early-acting factors were effective as a single agent, but combinations of SF or FL with IL-6, IL-11, or G-CSF were effective in supporting B cell potential of the primary colonies. Of these, the combination of FL plus IL-11 appeared to be the most effective. C1 IMMUNEX CORP,SEATTLE,WA. RALPH H JOHNSON DEPT VET AFFAIRS MED CTR,CHARLESTON,SC. MED UNIV S CAROLINA,DEPT MED,CHARLESTON,SC 29425. FU NIDDK NIH HHS [DK32294] NR 41 TC 13 Z9 13 U1 0 U2 1 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 FEB PY 1996 VL 24 IS 2 BP 285 EP 290 PG 6 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA TX753 UT WOS:A1996TX75300028 PM 8641354 ER PT J AU Salgia, R Sattler, M Pisick, E Li, JL Griffin, JD AF Salgia, R Sattler, M Pisick, E Li, JL Griffin, JD TI p210(BCR/ABL) induces formation of complexes containing focal adhesion proteins and the protooncogene product p120(c-Cbl) SO EXPERIMENTAL HEMATOLOGY LA English DT Article; Proceedings Paper CT 1995 Annual Meeting of the ISEH CY 1995 CL DUSSELDORF, GERMANY SP Int Soc Exptl Hematol DE p120(c-Cbl); paxinin; talin; p210(BCR/ABL); focal adhesion proteins ID V-CBL; BINDING; BCR; ABL; TRANSFORMATION; TRUNCATION; SEQUENCES; ONCOGENE; DOMAIN AB Chronic myelogenous leukemia (CML) is a myeloproliferative disorder caused by the t(9;22) translocation. This translocation creates a unique tyrosine kinase oncogene, bcr/abl, whose product, p210(BCR/ABL), is localized to the actin cytoskeleton. One of the major tyrosine phosphoproteins in cells transformed by p210(BCR/ABL) is the protooncoprotein p120(c-Cbl). We have previously shown that p210(BCR/ABL) induces formation of a multimeric complex of proteins which include p120(c-Cbl), phosphotidylinositol-3' kinase, and p210(BCR/ABL) itself. Here we show that certain focal adhesion proteins are also part of this complex, including paxillin and talin. The sites in paxillin required to bind to p120(c-Cbl) in this complex have been partially mapped. The interaction of p120(c-Cbl) with paxillin is specific, since other focal adhesion proteins, such as p125(FAK), vinculin, and alpha-actinin, are not in this complex. The binding of p120(c-Cbl) to the focal adhesion protein paxillin could contribute to the known adhesive defects of CML cells. C1 DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA. OI Li, Jian-Liang/0000-0002-6487-081X FU NCI NIH HHS [CA60821, CA36167] NR 26 TC 52 Z9 53 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 FEB PY 1996 VL 24 IS 2 BP 310 EP 313 PG 4 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA TX753 UT WOS:A1996TX75300032 PM 8641358 ER PT J AU Robertson, MJ Cochran, KJ Cameron, C Le, JM Tantravahi, R Ritz, J AF Robertson, MJ Cochran, KJ Cameron, C Le, JM Tantravahi, R Ritz, J TI Characterization of a cell line, NKL, derived from an aggressive human natural killer cell leukemia SO EXPERIMENTAL HEMATOLOGY LA English DT Article DE natural killer cell; large granular lymphocyte leukemia; natural killing; IL-2 ID LARGE GRANULAR LYMPHOCYTES; HUMAN PERIPHERAL-BLOOD; RECEPTOR GAMMA-CHAIN; FUNCTIONAL COMPONENT; SURFACE-MOLECULE; IL-2 RECEPTOR; ANTIGEN; INTERLEUKIN-2; PROLIFERATION; ACTIVATION AB Cell line NKL was established from the peripheral blood of a patient with CD3(-)CD16(+)CD56(+) large granular lymphocyte (LGL) leukemia. The neoplastic LGL of this patient mediated natural killing and antibody-dependent cellular cytotoxicity (ADCC) and exhibited proliferative responses similar to normal CD16(+)CD56(dim) natural killer (NK) cells. The morphology of NKL cells resembles that of normal activated NK cells. The karyotype of NKL is 47, XY, add (1) (q42), +6, del (6) (q15 q23), del (17) (p11). NKL cells express CD2, CD6, CD11a, CD26, CD27, CD29, CD38, CD43, CD58, CD81, CD94, CD95, class II MHC, and the C1.7.1 antigen, but do not express detectable levels of CD3, CD4, CD5, CD8, CD14, CD19, CD20, CD28, alpha/beta or gamma/delta T cell receptors on the cell surface. The density of the CD16, CD56, and CD57 antigens declined markedly on NKL cells during prolonged in vitro culture. Nevertheless, NKL cells can mediate ADCC as well as natural killing. NKL cells are strictly dependent on interleukin-2 (IL-2) for sustained growth and die if deprived of IL-2 for more than 7 days. NKL cells proliferate in response to concentrations of IL-2 as low as 1 pM, but an optimal proliferative response requires similar to 100 pM IL-2. NKL cells growing in the presence of IL-2 express abundant IL-2R alpha with little or no detectable IL-2 beta or gamma chain on the cell surface; NKL cells deprived of IL-2 express high levels of both IL-2R alpha, and beta. IL-4, IL-7, and IL-12, unlike IL-2, do not maintain the viability of NKL cells. Furthermore, IL-1, IL-4, IL-6, IL-7, IL-12, tumor necrosis factor-alpha (TNF-alpha), interferon-alpha (IFN-alpha), and IFN-gamma do not support the growth of NKL cells. The NKL cell Line may prove useful for studies of human NK cell biology. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. RP Robertson, MJ (reprint author), DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,44 BINNEY ST,BOSTON,MA 02115, USA. RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NCI NIH HHS [CA-01730, CA-41619] NR 48 TC 269 Z9 271 U1 0 U2 4 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 FEB PY 1996 VL 24 IS 3 BP 406 EP 415 PG 10 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA UA024 UT WOS:A1996UA02400002 PM 8599969 ER PT J AU Walters, M Andrews, NC Magis, W Martin, DIK AF Walters, M Andrews, NC Magis, W Martin, DIK TI Erythroid AP-1/NF-E2 elements vary in their response to NF-E2 SO EXPERIMENTAL HEMATOLOGY LA English DT Article DE NF-E2; AP-1; globin; transcription ID LOCUS-CONTROL REGION; PROTEIN DNA INTERACTIONS; DOMINANT CONTROL REGION; TRANSCRIPTION FACTOR NF-E2; LEUCINE ZIPPER PROTEIN; GAMMA-GLOBIN GENE; HYPERSENSITIVE SITE-4; NUCLEAR PROTEINS; CACCC ELEMENT; BINDING AB AP-1/NF-E2 motifs found in erythroid transcriptional control elements are associated with powerful transcriptional activation and thought to be regulated by the erythroid transcription factor NF-E2 We have studied AP-1/NF-E2 motifs from three different erythroid control elements (5'HS2 of the human beta-globin locus control region [LCR], the porphobilinogen deaminase [PBGD] promoter, and the mouse Band 3 promoter). We find that these AP-1/NF-E2 elements differ both in their ability to bind NF-E2 and their activity in transient assays. Each of the elements is bound by AP-1, but only the 5'HS2 and PBGD sites are bound by NF-E2. We examined the activity of these sites in minimal promoter constructs in transient assays. In erythroid cells, activity of duplicated NF-E2 motifs is positively correlated with binding by NF-E2; however, the Band 3 element not bound by NF-E2 is also active in some contexts. In HeLa cells, all sites were active and duplicated sites were most active. In F9 mouse teratocarcinoma cells, which express neither NF-E2 nor AP-1, the elements' activity parallels that in erythroid cells. While these findings are consistent with other evidence that NF-E2 is an important regulator of erythroid transcription, they suggest that some sites that resemble NF-E2 elements are actually regulated by other factors; we speculate that other tissue-specific and/or generally expressed factors may act on these sites. C1 FRED HUTCHINSON CANC RES CTR,DIV CLIN RES,SEATTLE,WA 98109. UNIV WASHINGTON,SCH MED,DEPT PEDIAT,SEATTLE,WA 98195. CHILDRENS HOSP,DIV HEMATOL ONCOL,BOSTON,MA. DANA FARBER CANC CTR,BOSTON,MA. HARVARD UNIV,HOWARD HUGHES MED INST,DEPT PEDIAT,SCH MED,BOSTON,MA. OI Andrews, Nancy/0000-0003-0243-4462 FU NHLBI NIH HHS [R01 HL48790] NR 41 TC 4 Z9 4 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 FEB PY 1996 VL 24 IS 3 BP 445 EP 452 PG 8 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA UA024 UT WOS:A1996UA02400007 PM 8599974 ER PT J AU Caviness, VS Takahashi, T Miyama, S Nowakowski, RS Delalle, I AF Caviness, VS Takahashi, T Miyama, S Nowakowski, RS Delalle, I TI Regulation of normal proliferation in the developing cerebrum potential actions of trophic factors SO EXPERIMENTAL NEUROLOGY LA English DT Article; Proceedings Paper CT Satellite Symposium on Trophic Factors, Neural Growth and Transplantation in the CNS, at the 2nd Joint Meeting of the Physiological Societies of Japan/UK/Eire CY APR 01-02, 1995 CL NAGOYA, JAPAN ID VISUAL-CORTEX; CELL-CYCLE; SOMATOSENSORY CORTEX; RHESUS-MONKEY; MESSENGER-RNA; HUMAN BRAIN; MOUSE; EXPRESSION; SYSTEM; PHASE AB We review here a computational model of neocortical histogenesis based upon experiments in the developing cerebral wall of the mouse. Though based upon experiments in mouse, commonalities of developmental history and structure of neocortex across mammalian species suggest that the principles which support this model will be generally applicable to neocortical evolution and development across species, In its scope the model spans the successive histogenetic events: cell proliferation, cell migration, and the positioning of cell somata in neocortical layers following migration. Neurons are produced in a pseudostratified epithelium (PVE) which lines the ventricular cavities of the embryonic cerebrum. The parameters which determine the rate and total number of neurons produced in the PVE are (1) the size of the founder population, (2) the number of integer cell cycles executed by the founder population and its progeny in the course of the neuronogenetic interval, (3) the growth fraction, and (4) the fraction of cells which exits the cycle (Q fraction) with each integer cycle. There is a systematic relationship between the integer cycle of origin and the sequence of cell migration, position in the cortex, and the extent to which a set of postmigratory neurons will be diluted in the cortex by the combined effects of tissue growth and cell death. Variation across species in the number of integer cell cycles as a function of the rate of progression of Q may be expected to modulate profoundly the total numbers of neurons that are produced but not the relative proportions of neurons assigned to the major neocortical layers. (C) 1996 Academic Press, Inc. C1 KEIO UNIV, SCH MED, DEPT PEDIAT, TOKYO 160, JAPAN. UNIV MED & DENT NEW JERSEY, ROBERT WOOD JOHNSON MED SCH, DEPT NEUROSCI & CELL BIOL, PISCATAWAY, NJ 08854 USA. RP Caviness, VS (reprint author), HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, DEPT NEUROL, BOSTON, MA 02114 USA. RI Nowakowski, Richard/C-3217-2016; OI Nowakowski, Richard/0000-0002-5006-3670 FU NINDS NIH HHS [NS28061, NS12005] NR 79 TC 8 Z9 8 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD FEB PY 1996 VL 137 IS 2 BP 357 EP 366 PG 10 WC Neurosciences SC Neurosciences & Neurology GA TW727 UT WOS:A1996TW72700021 PM 8635552 ER PT J AU Babyatsky, MW deBeaumont, M Thim, L Podolsky, DK AF Babyatsky, MW deBeaumont, M Thim, L Podolsky, DK TI Oral trefoil peptides protect against ethanol- and indomethacin-induced gastric injury in rats SO GASTROENTEROLOGY LA English DT Article ID PANCREATIC SPASMOLYTIC POLYPEPTIDE; XENOPUS-LAEVIS; CAMPYLOBACTER-PYLORI; INTEGUMENTARY MUCIN; STOMACH MUCOSA; MUCUS; EXPRESSION; DOMAIN; DAMAGE; SECRETION AB Background & Aims: The trefoil factors, a family of proteins abundantly expressed in gastrointestinal mucous cells, protect the epithelium in vitro. This study determines the effects of exogenously administered trefoil peptides on experimental injury in rats in vivo, Methods: Gastric injury was induced by either intragastric absolute ethanol (1.0 mt) or subcutaneous indomethacin (20 mg/kg). Recombinant human spasmolytic polypeptide (rHSP) or rat intestinal trefoil factor (ITF) were administered at different doses and time points before or after injury. Vehicle or bovine serum albumin was used as control. The pH of the stomach contents was assessed when the rats were killed, Gastric injury was blindly evaluated macroscopically and histologically. Serum levels of rHSP and ITF were determined by an enzyme-linked immunosorbent assay, Results: Oral rHSP and ITF markedly protected against both ethanol- and indomethacin-induced gastric injury (P < 0.005 at doses of 1-15 mg/rat) when given up to 2 hours before injury; no protection was noted by intraperitoneal rHSP against ethanol injury, Intraperitoneal rHSP protected against indomethacin-induced injury only at the maximal dose given (15 mg). Neither rHSP nor ITF altered gastric pH, Protection was not associated with systemic absorption of trefoil peptides, Conclusions: Topical trefoil peptides protect the gastric mucosa against ethanol- and indomethacin-induced gastric injuries. These peptides contribute to surface mucosal defense. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,GASTROINTESTINAL UNIT,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CTR STUDY INFLAMMATORY BOWEL DIS,DEPT MED,BOSTON,MA 02114. BIOSCI,DK-2880 BAGSVAERD,DENMARK. MT SINAI MED CTR,GASTROINTESTINAL DIV,NEW YORK,NY 10029. FU NIDDK NIH HHS [DK 41557, DK 43351] NR 48 TC 230 Z9 243 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 FEB PY 1996 VL 110 IS 2 BP 489 EP 497 DI 10.1053/gast.1996.v110.pm8566596 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA TT975 UT WOS:A1996TT97500020 PM 8566596 ER PT J AU Brugge, WR Lee, MJ Warshaw, AL AF Brugge, WR Lee, MJ Warshaw, AL TI EUS methods for the staging of pancreatic cancer SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD FEB PY 1996 VL 43 IS 2 SU S BP P5 EP P5 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA TX115 UT WOS:A1996TX11500047 ER PT J AU Wright, DA Ke, N Smalle, J Hauge, BM Goodman, HM Voytas, DF AF Wright, DA Ke, N Smalle, J Hauge, BM Goodman, HM Voytas, DF TI Multiple non-LTR retrotransposons in the genome of Arabidopsis thaliana SO GENETICS LA English DT Article ID TY1-COPIA GROUP RETROTRANSPOSONS; REVERSE-TRANSCRIPTASE SEQUENCES; ELEMENT FAMILY; PLANT GENOMES; EVOLUTION; GENE; DNA; RETROVIRUSES; DROSOPHILA; NUCLEAR AB DNA sequence analysis near the Arabidopsis thaliana ABI3 gene revealed the presence of a non-LTR retrotransposon insertion that we have designated Ta11-1. This insertion is 6.2 kb in length and encodes two overlapping reading frames with similarity to non-LTR retrotransposon proteins, including reverse transcriptase. A polymerase chain reaction assay was developed based on conserved amino acid sequences shared between the Ta11-1 reverse transcriptase and those of non-LTR retrotransposons from other species. Seventeen additional A. thaliana reverse transcriptases were identified that range in nucleotide similarity from 48-88% (Ta12-Ta28). Phylogenetic analyses indicated that the A. thaliana sequences are more closely related to each other than to elements from other organisms, consistent with the vertical evolution of these sequences over most of their evolutionary history. One sequence, Ta17, is located in the mitochondrial genome. The remaining are nuclear and of low copy number among 17 diverse A. thaliana ecotypes tested, suggesting that they are not highly active in transposition. The paucity of retrotransposons and the small genome size of A. thaliana support the hypothesis that most repetitive sequences have been lost from the genome and that mechanisms may exist to prevent amplification of extant element families. C1 IOWA STATE UNIV SCI & TECHNOL, DEPT ZOOL & GENET, AMES, IA 50011 USA. HARVARD UNIV, SCH MED, DEPT GENET, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, DEPT MOLEC BIOL, BOSTON, MA 02114 USA. NR 45 TC 68 Z9 74 U1 0 U2 1 PU GENETICS SOCIETY AMERICA PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 0016-6731 EI 1943-2631 J9 GENETICS JI Genetics PD FEB PY 1996 VL 142 IS 2 BP 569 EP 578 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA TR639 UT WOS:A1996TR63900022 PM 8852854 ER PT J AU Hogan, K Gregg, RG Powers, PA AF Hogan, K Gregg, RG Powers, PA TI The structure of the gene encoding the human skeletal muscle alpha(1) subunit of the dihydropyridine-sensitive L-type calcium channel (CACNL1A3) SO GENOMICS LA English DT Article AB The structure of the gene encoding the human skeletal muscle alpha(1) subunit (CACNL1A3) of the dihydropyridine-sensitive voltage-dependent calcium channel was determined by isolation of overlapping genomic DNA clones from human cosmid, phage, and P1 libraries. Genomic fragments containing exons were subcloned, and the sequences of the exons and flanking introns were defined. Knowledge of the genomic structure of the CACNL1A3 gene, which spans 90 kb and consists of 44 exons, will facilitate the search for additional mutations in CACNL1A3 that cause neuromuscular disease. (C) 1996 Academic Press, Inc. C1 UNIV WISCONSIN,DEPT ANESTHESIOL,MADISON,WI 53705. UNIV WISCONSIN,WAISMAN CTR MENTAL RETARDAT & HUMAN DEV,MADISON,WI 53705. WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI 53705. NR 12 TC 26 Z9 30 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD FEB 1 PY 1996 VL 31 IS 3 BP 392 EP 394 DI 10.1006/geno.1996.0066 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA TU592 UT WOS:A1996TU59200019 PM 8838325 ER PT J AU DelaCuesta, RS Eichhorn, JH Rice, LW Fuller, AF Nikrui, N Goff, BA AF DelaCuesta, RS Eichhorn, JH Rice, LW Fuller, AF Nikrui, N Goff, BA TI Histologic transformation of benign endometriosis to early epithelial ovarian cancer SO GYNECOLOGIC ONCOLOGY LA English DT Article ID ATYPICAL ENDOMETRIOSIS; CARCINOMA AB Between 1975 and 1990, 79 patients with Stage I epithelial ovarian cancer were treated at Massachusetts General Hospital. Patients were identified from the tumor registry and medical records were retrospectively reviewed. Pathological slides were evaluated for the presence of endometriosis, specifically looking for malignancy arising in endometriosis. Evidence of endometriosis was found in 22 of the 79 cases (28%). In the 23 cases of endometrioid histology, 9 cases (39%) were associated with endometriosis and, in the 17 cases of clear cell tumors, 7 (41%) were associated with endometriosis. All 8 cases of mixed histology had clear cell and/or endometrioid components and 4 cases (50%) were associated with endometriosis. Endometrioid adenocarcinoma accounted for 41% of the tumors associated with endometriosis, clear cell carcinoma 31%, mixed (endometrioid and/or clear cell types) 18%, and other types 9%. Among the 22 patients with associated endometriosis, we found 7 carcinomas (32%) arising in endometriosis. In these 7 cases a spectrum of benign and atypical endometriosis with a transition to clear cell or endometrioid adenocarcinoma were identified. These premalignant changes were characterized by cytologic atypia and architectural proliferation. Endometriosis was frequently encountered among patients with Stage I epithelial ovarian cancer of endometrioid and clear cell histologies. Endometriosis may play a role in the pathogenesis of some early stage malignant ovarian epithelial neoplasms. (C) 1996 Academic Press, Inc. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,VINCENT MEM GYNECOL ONCOL SERV,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02114. NR 27 TC 115 Z9 118 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD FEB PY 1996 VL 60 IS 2 BP 238 EP 244 PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA TV676 UT WOS:A1996TV67600012 ER PT J AU AbuJawdeh, GM Jacobs, TW Niloff, J Cannistra, SA AF AbuJawdeh, GM Jacobs, TW Niloff, J Cannistra, SA TI Estrogen receptor expression is a common feature of ovarian borderline tumors SO GYNECOLOGIC ONCOLOGY LA English DT Article ID TERM FOLLOW-UP; STEROID-RECEPTORS; PROGESTERONE RECEPTORS; PERITONEAL IMPLANTS; CARCINOMA; GROWTH; CANCER; MALIGNANCY; SURVIVAL AB Purpose. The presence of estrogen receptor (ER) and its therapeutic significance in ovarian borderline tumors (OBT) have not been established, We recently observed a response to tamoxifen therapy given empirically to a patient with unresectable, recurrent serous borderline tumor (SET). In view of this observation the present study was undertaken to assess ER expression in 51 cases of OBT, Materials and methods. ER expression was determined retrospectively, using an immunohistochemical method on formalin-fixed, paraffin-embedded specimens, from 35 cases of SBTs, 6 cases of mucinous mullerian (MMBT), and 10 cases of mucinous intestinal borderline tumors (MIBT). ER was considered positive if >5% of tumor epithelial cell nuclei were immunostained, Both SBTs and mucinous borderline tumors (MBTs) were included to determine the influence of histologic type on ER expression. Results. The patients ranged in age from 25 to 77 years (median 43 years for SBTs, 36 years for MMBTs, and 37 years for MIBTs). The stage distribution for the SBTs was stage I in 27 patients (77%), stage II in 4 patients (11.5%), and stage III in 4 patients (11.5%). All patients with MBTs were stage I, ER expression was observed in the majority of cases and correlated with histologic type: 94% (33/35) of SBTs and 100% (6/6) of MMBTs were ER positive compared to 0% (0/10) of MIBTs (P ( 0.01). In the SET category the presence of ER did not correlate significantly with stage or age. In addition, ER was positive in all four SET implants (including one involved lymph node) and two recurrent SBTs analyzed. Conclusion. ER expression is a common feature of SET and MMBT, but not MIBT. The relevance of ER expression in the pathogenesis and treatment of OBTs requires further investigation. (C) 1996 Academic Press, Inc. C1 BETH ISRAEL HOSP,DANA FARBER CANC INST,DEPT OBSTET,BOSTON,MA 02215. BETH ISRAEL HOSP,DANA FARBER CANC INST,DEPT GYNECOL,BOSTON,MA 02215. BETH ISRAEL HOSP,DANA FARBER CANC INST,DEPT MED ONCOL,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA 02215. RP AbuJawdeh, GM (reprint author), BETH ISRAEL HOSP,DANA FARBER CANC INST,DEPT PATHOL,330 BROOKLINE AVE,BOSTON,MA 02215, USA. NR 35 TC 48 Z9 49 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD FEB PY 1996 VL 60 IS 2 BP 301 EP 307 DI 10.1006/gyno.1996.0043 PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA TV676 UT WOS:A1996TV67600023 PM 8631556 ER PT J AU Emanuel, EJ AF Emanuel, EJ TI Pain and symptom Control - Patient rights and physician responsibilities SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID PHASE-I; INFORMED CONSENT; CANCER PAIN; EUTHANASIA; ATTITUDES; TRIALS; CARE AB Patients with advanced cancer have a fundamental right to adequate symptom control. In order to secure this right, the treating clinicians take on a set of responsibilities. This article explores this right with specific reference to palliative care, experimental therapies, and physician-assisted suicide or euthanasia. C1 HARVARD UNIV,SCH MED,DIV MED ETH,BOSTON,MA. RP Emanuel, EJ (reprint author), DANA FARBER CANC INST,DIV CANC EPIDEMIOL & CONTROL,CTR OUTCOMES & POLICY RES,44 BINNEY ST,BOSTON,MA 02115, USA. NR 30 TC 10 Z9 10 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD FEB PY 1996 VL 10 IS 1 BP 41 EP & DI 10.1016/S0889-8588(05)70326-9 PG 18 WC Oncology; Hematology SC Oncology; Hematology GA TV140 UT WOS:A1996TV14000004 PM 8821559 ER PT J AU Li, XP Rawn, J DeCamp, MM Mentzer, SJ AF Li, XP Rawn, J DeCamp, MM Mentzer, SJ TI Hybridoma screening for cell adhesion molecules using multiple parallel comparisons in conditions of flow SO HYBRIDOMA LA English DT Article ID DETACHMENT ASSAY; MODEL; SURFACES; ANTIBODY; CALCEIN; CULTURE AB Cell adhesion is a complex biophysical process that plays a central role in immunophysiology. Because of the complex force-energy relationships involved, insights into the mechanism of cell adhesion largely depend on comparative measurements, In this report, we describe a comparative approach to the measurement of cell adhesion under conditions of flow, The assay system perfuses fluorescently labeled lymphocytes over a cell monolayer in commercially available multiwell culture plates. The fluorescently labeled cells demonstrate a reproducible flow pattern within the well, Videomicroscopic recordings of cell movement have demonstrated rolling behavior over a wide range of cell velocities, This technique permits the measurement of cell adhesion over a variety of flow velocities, time courses, and treatment conditions, The ability to vary treatment conditions and provide multiple parallel conditions suggests the utility of this approach in the development of monoclonal antibodies (MAb) recognizing cell adhesion molecules. C1 BRIGHAM & WOMENS HOSP,DIV THORAC SURG,IMMUNOPHYSIOL LAB,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. FU NHLBI NIH HHS [HL47078] NR 29 TC 3 Z9 4 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 FEB PY 1996 VL 15 IS 1 BP 43 EP 47 DI 10.1089/hyb.1996.15.43 PG 5 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Immunology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology GA TY436 UT WOS:A1996TY43600006 PM 9064285 ER PT J AU Carr, MW Alon, R Springer, TA AF Carr, MW Alon, R Springer, TA TI The C-C chemokine MCP-1 differentially modulates the avidity of beta 1 and beta 2 integrins on T lymphocytes SO IMMUNITY LA English DT Article ID INTERCELLULAR-ADHESION MOLECULE-1; CELL-ADHESION; TRANSENDOTHELIAL MIGRATION; ENDOTHELIAL-CELLS; CYTOKINE; LEUKOCYTES; MIP-1-BETA; MONOCYTES; RECEPTOR; ICAM-1 AB The ability of chemokines, particularly MCP-1, to induce integrin-dependent binding of T lymphocytes to endothelial adhesion molecules or extracellular matrix (ECM) components was examined. MCP-1 induced significant adhesion to fibronectin (FN) and to endothelial-secreted ECM but not to purified ICAM-1 or VCAM-1, or to activated endothelium. The MCP-1-induced binding of T lymphocytes to FN was rapid, dose dependent, and resulted from activation of both VLA-4 and VLA-5. Like MCP-1, the chemokines RANTES and MIP-1 beta induced T lymphocyte binding to FN, but not to ICAM-1. We suggest, therefore, that these T lymphocyte chemokines may be most important, not in initiating integrin-dependent firm adhesion of T lymphocytes to the vascular wall, but rather, in subsequent adhesive interactions during migration into tissue. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RP Carr, MW (reprint author), HARVARD UNIV,CTR BLOOD RES,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA31798]; NHLBI NIH HHS [HL48675] NR 45 TC 172 Z9 173 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 1074-7613 J9 IMMUNITY JI Immunity PD FEB PY 1996 VL 4 IS 2 BP 179 EP 187 DI 10.1016/S1074-7613(00)80682-2 PG 9 WC Immunology SC Immunology GA TX225 UT WOS:A1996TX22500008 PM 8624808 ER PT J AU Granholm, E Asarnow, RF Marder, SR AF Granholm, E Asarnow, RF Marder, SR TI Display visual angle and attentional scanpaths on the span of apprehension task in schizophrenia SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Article; Proceedings Paper CT 4th International Congress on Schizophrenia CY APR 17-21, 1993 CL COLORADO SPRINGS, CO ID PSYCHOPATHOLOGY; SELECTIVITY; DISORDERS; CHILDREN; PARALLEL; SERIAL AB The effect of display visual angle on span of apprehension (SOA) task performance was investigated in patients with schizophrenia and nonpsychiatric individuals. Narrow and wide visual-angle presentations of 3- and 10-letter arrays were compared. Detection rates were significantly higher with narrow than wide visual angle for nonpsychiatric individuals; the performance of those with schizophrenia was stable across visual-angle conditions. Patients with schizophrenia were best discriminated from nonpsychiatric individuals in the narrow-angle, 10-letter condition. Scanpath analyses, which were based on the pattern of detection rates across different target quadrant locations, suggested that the patients with schizophrenia used a similar number and path of covert scan moves as did the controls. Hypotheses are discussed regarding which of the multiple cognitive processes tapped by the SOA task may be impaired in schizophrenia. C1 UNIV CALIF SAN DIEGO,DEPT PSYCHIAT,SAN DIEGO,CA 92103. UNIV CALIF LOS ANGELES,DEPT PSYCHIAT & BIOBEHAV SCI,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. RP Granholm, E (reprint author), VET AFFAIRS MED CTR,PSYCHOL SERV 116B,3350 LA JOLLA VILLAGE DR,SAN DIEGO,CA 92161, USA. RI Granholm, Eric/P-7680-2014 FU NIMH NIH HHS [MH14584, MH30911] NR 40 TC 13 Z9 13 U1 0 U2 1 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0021-843X J9 J ABNORM PSYCHOL JI J. Abnorm. Psychol. PD FEB PY 1996 VL 105 IS 1 BP 17 EP 24 PG 8 WC Psychology, Clinical; Psychology, Multidisciplinary SC Psychology GA TR921 UT WOS:A1996TR92100002 PM 8666706 ER PT J AU Licht, EA Sankar, R Tanaka, D Gee, M AF Licht, EA Sankar, R Tanaka, D Gee, M TI Epilepsy and teenage pregnancies: Results of a nationwide survey SO JOURNAL OF ADOLESCENT HEALTH LA English DT Meeting Abstract C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT PEDIAT,DIV PEDIAT NEUROL,LOS ANGELES,CA 90024. CHILDRENS HOSP LOS ANGELES,DEPT ADOLESCENT MED,LOS ANGELES,CA 90027. W LOS ANGELES VET AFFAIRS MED CTR,DEPT NEUROL,LOS ANGELES,CA 90073. NR 0 TC 0 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1054-139X J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD FEB PY 1996 VL 18 IS 2 BP 128 EP 128 PG 1 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA TX086 UT WOS:A1996TX08600033 ER PT J AU Ring, D Jupiter, JB Labropoulos, PK Guggenheim, JJ Stanitsky, DF Spencer, DM AF Ring, D Jupiter, JB Labropoulos, PK Guggenheim, JJ Stanitsky, DF Spencer, DM TI Treatment of deformity of the lower limb in adults who have osteogenesis imperfecta SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article AB The Ilizarov method of lengthening was used to correct deformities of the lower extremity in six patients who had type-I osteogenesis imperfecta, as categorized by Sillence et al, The average age was thirty-one years (range, fourteen to fifty-one years), The deformities included shortening of four tibiae and three femora as well as an angular malalignment (average, 28 degrees; range, 20 to 40 degrees) of all four tibiae and one femur, One patient also had a non-union of the right femur. The average angular correction was 23 degrees (range, 20 to 30 degrees), The seven limb segments gained an average of 6.6 centimeters (range, two to eleven centimeters) in length, All limb-length discrepancies were corrected to within two centimeters of the length of the contralateral limb, At an average of three years and four months (range, one year and seven months to six years), the roentgenographic appearance of the fully matured bone was comparable ,vith that of the original bone. There were no fractures or increases in the angulation of the segment of new bone, Two patients had pain when walking: it was related to a chronic pin-track infection in one and to osteoarthrosis of the ankle in the other, The functional status of four patients was improved and that of the other two patients was unchanged, All six patients were pleased with the outcome of the procedure. There were eighteen complications: stiffness of the knee in two patients; a peroneal nerve palsy in two; a superficial pin-track infection in three; and a deep pin-track infection, greater-than-normal loss of blood intraoperatively, loosening of two pins, worsening of the instability of the knee, and an infection in the knee in one patient each, In another patient, a Rush rod that had been placed before correction of the deformity migrated proximally and had to be removed after completion of the correction, There were five fractures. RP Ring, D (reprint author), MASSACHUSETTS GEN HOSP,DEPT ORTHOPAED SURG,ACC 529A,15 PARKMAN ST,BOSTON,MA 02114, USA. NR 13 TC 14 Z9 16 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 FEB PY 1996 VL 78A IS 2 BP 220 EP 225 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA TV538 UT WOS:A1996TV53800008 PM 8609112 ER PT J AU Mitlak, BH Finkelman, RD Hill, EL Li, J Martin, B Smith, T DAndrea, M Antoniades, HN Lynch, SE AF Mitlak, BH Finkelman, RD Hill, EL Li, J Martin, B Smith, T DAndrea, M Antoniades, HN Lynch, SE TI The effect of systemically administered PDGF-BB on the rodent skeleton SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID GROWTH-FACTOR; BONE; CELLS; REGENERATION; COMBINATION; EXPRESSION; CULTURES; INVITRO; GENE; AA AB Platelet-derived growth factor (PDGF), an osteoblast mitogen, has been demonstrated to accelerate fracture healing and periodontal bone repair when applied locally in vivo. To explore whether PDGF could stimulate bone formation in intact bone, we administered it systemically to rats rendered acutely estrogen-deficient, Because PDGF map stimulate bone resorption in vitro, PDGF was administered with and without an antiresorptive agent (alendronate). All treatments were given by intravenous injection 3 times a week for 6 weeks, Spinal bone mineral density (BMD) decreased by 5% in the vehicle-treated ovariectomized (OVX) rats by the end of the study as determined by DXA. Treatment with PDGF prevented this bone loss and significantly (p < 0.05) increased the bone density in the spine (9%) and whole skeleton (5.8%), Combined treatment with PDGF and alendronate resulted in a greater increase at the spine (18%) and whole skeleton (12.8%) than either agent alone, Histomorphometric analysis demonstrated that treatment with PDGF increased the osteoblast number and osteoblast perimeter without consistent changes in osteoclast estimates, Biomechanical testing demonstrated that PDGF administration increased the vertebral body compressive strength and femoral shaft torsional stiffness and resulted in a trend for enhanced femoral head shearing strength, Coadministration of alendronate further increased these indices of bone strength, PDGF administration also caused premature closure of the growth plate, decreased body fat, and resulted in extraskeletal collagen deposition, We therefore demonstrate, for the first time, that systemic administration of PDGF can increase bone density and strength throughout the skeleton. C1 MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. INST MOLEC BIOL INC,WORCESTER,MA. UNIV CALIF DAVIS,MED CTR,SACRAMENTO,CA 95817. NR 31 TC 83 Z9 84 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 1996 VL 11 IS 2 BP 238 EP 247 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TT568 UT WOS:A1996TT56800012 PM 8822348 ER PT J AU Eckhardt, WF Laconetti, DJ Kwon, JS Brown, E Troianos, CA AF Eckhardt, WF Laconetti, DJ Kwon, JS Brown, E Troianos, CA TI CASE 1--1996 - Inadvertent carotid artery cannulation during pulmonary artery catheter insertion SO JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA LA English DT Article ID INTERNAL JUGULAR-VEIN; CENTRAL VENOUS CANNULATION; ATTEMPTED CENTRAL VENIPUNCTURE; COMPLETE HEART-BLOCK; BUNDLE-BRANCH BLOCK; CARDIAC-TAMPONADE; PERCUTANEOUS CANNULATION; TENSION PNEUMOTHORAX; SUBCLAVIAN VEIN; ATRIAL THROMBUS C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. FAIRFAX HOSP,FAIRFAX,VA. MERCY HOSP,DEPT ANESTHESIOL,PITTSBURGH,PA 15219. NR 83 TC 25 Z9 25 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 1053-0770 J9 J CARDIOTHOR VASC AN JI J. Cardiothorac. Vasc. Anesth. PD FEB PY 1996 VL 10 IS 2 BP 283 EP 290 DI 10.1016/S1053-0770(96)80252-7 PG 8 WC Anesthesiology; Cardiac & Cardiovascular Systems; Respiratory System; Peripheral Vascular Disease SC Anesthesiology; Cardiovascular System & Cardiology; Respiratory System GA TX806 UT WOS:A1996TX80600021 PM 8850412 ER PT J AU Sager, PT Behboodikhah, M AF Sager, PT Behboodikhah, M TI Frequency-dependent electrophysiologic effects of d,l-sotalol and quinidine and modulation by beta-adrenergic stimulation SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Article DE autonomic nervous system; action potential; quinidine; sotalol ID ACTION-POTENTIAL DURATION; CARDIAC PURKINJE-FIBERS; RECTIFIER K+-CURRENT; III ANTIARRHYTHMIC AGENT; VENTRICULAR-TACHYCARDIA; CYCLE LENGTH; REFRACTORY PERIOD; OUTWARD CURRENT; PROLONGATION; HUMANS AB Introduction: Frequency-dependent electrophysiologic actions of oral quinidine and oral sotalol may be clinically important, but these properties and their modulation by beta-adrenergic sympathetic stimulation have not been determined. Methods and Results: The frequency-dependent effects of oral quinidine (n = 17) and oral d,l-sotalol (n = 17) were determined at: (1) drug-free baseline; (2) during steady-state drug dosing; and (3) during isoproterenol infusion to patients receiving quinidine or d,l-sotalol. The monophasic APD(90) and RVERP were prolonged 12% to 17% (P < 0.001) during pharmacologic therapy, and frequency-dependent effects were only observed for the RVERP during sotalol. In both drug groups, isoproterenol significantly reduced the sinus cycle length and reduced the RVERP to a greater extent at longer than at shorter paced cycle lengths. While isoproterenol fully reversed quinidine's effects on the APD(90) and RVERP, sotalol-induced APD(90) prolongation was reduced by only 2% to 4%, and the RVERP was unaffected. Isoproterenol attenuated the frequency-dependent effects of quinidine on QRS duration by a relatively fixed amount of 7% to 10%. Isoproterenol fully reversed quinidine-induced, but did not affect sotalol-induced, prolongation in the sustained VT cycle length. Conclusions: (1) Over the range of examined cycle lengths, oral quinidine and d,l-sotalol did not exert frequency-dependent effects on ventricular repolarization. (2) Isoproterenol fully reversed quinidine's effects on refractoriness, repolarization, and prolongation of VT cycle length, whereas d,l-sotalol's effects were largely preserved, despite significant reductions in sinus cycle length. (3) These results suggest that beta-blockade is important in preventing reversal of antiarrhythmic drug effects by augmented sympathetic nervous system tone. C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT MED,LOS ANGELES,CA. RP Sager, PT (reprint author), W LOS ANGELES VAMC,DIV CARDIOL 691 W111E,11301 WILSHIRE BLVD,LOS ANGELES,CA 90073, USA. NR 55 TC 9 Z9 10 U1 0 U2 1 PU FUTURA PUBL CO PI ARMONK PA 135 BEDFORD RD, PO BOX 418, ARMONK, NY 10504-0418 SN 1045-3873 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD FEB PY 1996 VL 7 IS 2 BP 102 EP 112 DI 10.1111/j.1540-8167.1996.tb00505.x PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA TV761 UT WOS:A1996TV76100002 PM 8853020 ER PT J AU Dustin, ML Ferguson, LM Chan, PY Springer, TA Golan, DE AF Dustin, ML Ferguson, LM Chan, PY Springer, TA Golan, DE TI Visualization of CD2 interaction with LFA-3 and determination of the two-dimensional dissociation constant for adhesion receptors in a contact area SO JOURNAL OF CELL BIOLOGY LA English DT Article ID FUNCTION-ASSOCIATED ANTIGEN-3; SUPPORTED PLANAR MEMBRANES; T-CELL; HISTOCOMPATIBILITY ANTIGEN; PHOTOBLEACHING RECOVERY; IMMUNE-SYSTEM; BINDING-SITE; PROTEIN; FLUORESCENCE; RECOGNITION AB Many adhesion receptors have high three-dimensional dissociation constants (K-d) for counterreceptors compared to the K(d)s of receptors for soluble extracellular ligands such as cytokines and hormones. Interaction of the T lymphocyte adhesion receptor CD2 with its counter-receptor, LFA-3, has a high solution-phase K-d (16 mu M at 37 degrees C), yet the CD2/LFA-3 interaction serves as an effective adhesion mechanism. We have studied the interaction of CD2 with LFA-3 in the contact area between Jurkat T lymphoblasts and planar phospholipid bilayers containing purified, fluorescently labeled LFA-3. Redistribution and lateral mobility of LFA-3 were measured in contact areas as functions of the initial LFA-3 surface density and of time after contact of the cells with the bilayers. LFA-3 accumulated at sites of contact with a half-time of similar to 15 min, consistent with the previously determined kinetics of adhesion strengthening. The two-dimensional K-d for the CD2/LFA-3 interaction was 21 molecules/mu m(2), which is lower than the surface densities of CD2 on T cells and LFA-3 on most target or stimulator cells. Thus, formation of CD2/LFA-3 complexes should be highly favored in physiological interactions. Comparison of the two-dimensional (membrane-bound) and three-dimensional (solution-phase) K(d)s suggest that cell-cell contact favors CD2/LFA-3 interaction to a greater extent than that predicted by the three-dimensional K-d and the intermembrane distance at the site of contact. LFA-3 molecules in the contact site were capable of lateral diffusion in the plane of the phospholipid bilayer and did not appear to be irreversibly trapped in the contact area, consistent with a rapid off-rate. These data provide insights into the function of low affinity interactions in adhesion. C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. WASHINGTON UNIV,SCH MED,CTR IMMUNOL,ST LOUIS,MO 63110. WASHINGTON UNIV,SCH MED,DEPT PATHOL,ST LOUIS,MO 63110. BRIGHAM & WOMENS HOSP,CTR BLOOD RES,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DIV HEMATOL ONCOL,BOSTON,MA 02115. FU NCI NIH HHS [CA31798]; NHLBI NIH HHS [HL15157, HL32854] NR 50 TC 179 Z9 180 U1 0 U2 7 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD FEB PY 1996 VL 132 IS 3 BP 465 EP 474 DI 10.1083/jcb.132.3.465 PG 10 WC Cell Biology SC Cell Biology GA TU636 UT WOS:A1996TU63600018 PM 8636222 ER PT J AU VanRemmen, H Williams, MD Heydari, AR Takahashi, R Chung, HY Yu, BY Richardson, A AF VanRemmen, H Williams, MD Heydari, AR Takahashi, R Chung, HY Yu, BY Richardson, A TI Expression of genes coding for antioxidant enzymes and heat shock proteins is altered in primary cultures of rat hepatocytes SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID TRANSCRIPTIONAL REGULATION; MONOLAYER-CULTURE; FOOD RESTRICTION; CELLS; STRESS; LIVER; AGE; CHAPERONES; DISMUTASE; ACID AB The expression of genes for heat shock proteins in the HSP70 family and genes for antioxidant enzymes was studied in rat hepatocytes cultured in either L-15 or Williams E media an a collagen matrix for up to 48 hours. The mRNA transcripts for the heat shock proteins hsp70, hsc70, and grp78 were induced dramatically when hepatocytes were cultured in L-15, and to a lesser extent when cultured in Williams E. The increase in hsp70 and hsc70 mRNA levels in the cultured hepatocytes was correlated with an increase in the nuclear transcription of these two genes and the binding activity of the heat shock transcription factor to the heat shock element. Culturing rat hepatocytes in either L-15 or Williams E resulted in a decrease in the levels of the mRNA transcripts for catalase and glutathione peroxidase and the activities of these two enzymes. However, the expression of Cu/Zn-superoxide dismutase, i.e., the level of the mRNA transcript or the enzymatic activity, did not change appreciably when hepatocytes were cultured for up to 48 hours. The decline in catalase and glutathione peroxidase expression in the cultured hepatocytes was correlated with a decrease in the GSH/GSSG ratio and an increase in lipid peroxidation. These data show that the expression of several genes involved in cellular protection change when hepatocytes are placed in primary cultures. Therefore, one must be careful in extrapolating from primary cultures to the liver in vivo, especially when studying processes that might be affected by heat shock proteins or antioxidant enzymes. (C) 1996 Wiley-Liss, Inc. C1 UNIV TEXAS,HLTH SCI CTR,AUDIE L MURPHY MEM VET HOSP,CTR GERIATR RES EDUC & CLIN,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT PHYSIOL,SAN ANTONIO,TX 78284. FU NIA NIH HHS [AG01548, AG01188] NR 40 TC 27 Z9 27 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD FEB PY 1996 VL 166 IS 2 BP 453 EP 460 PG 8 WC Cell Biology; Physiology SC Cell Biology; Physiology GA TR613 UT WOS:A1996TR61300024 PM 8592006 ER PT J AU Lee, MM Donahoe, PK Hasegawa, T Silverman, B Crist, GB Best, S Hasegawa, Y Noto, RA Schoenfeld, D MacLaughlin, DT AF Lee, MM Donahoe, PK Hasegawa, T Silverman, B Crist, GB Best, S Hasegawa, Y Noto, RA Schoenfeld, D MacLaughlin, DT TI Mullerian inhibiting substance in humans: Normal levels from infancy to adulthood SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PITUITARY-GONADAL RELATIONS; MESSENGER-RIBONUCLEIC-ACID; GRANULOSA-CELLS; SERUM LEVELS; HORMONE; IMMUNOASSAY; BIRTH; EXPRESSION; ONTOGENY; FOLLICLE AB Mullerian inhibiting substance (MIS) is a gonadal hormone synthesized by Sertoli cells of the testis and granulosa cells of the ovary. To facilitate the use of MIS for the evaluation of intersex disorders and as a tumor marker in women with MIS-expressing ovarian tumors, we measured MIS in 600 serum samples from males and females. These data show that mean MIS values for males rise rapidly during the first year of life and are highest during late infancy, then gradually decline until puberty. In contrast, MIS values in females are lowest at birth and exhibit a minimal increase throughout the prepubertal years. Whereas MIS is uniformly measurable in all prepubertal boys studied, it is undetectable in most prepubertal female subjects. These data reveal an easily discernible sexually dimorphic pattern of expression and confirm that MIS can be used as a testis-specific marker during infancy and early childhood. MIS values that are above the upper limits for females are discriminatory for the presence of testicular tissue or ovarian tumor, and those below the lower limits for males are consistent with dysgenetic or absent testes or the presence of ovarian tissue. These data will enable normal and abnormal levels of MIS to be differentiated with higher precision and will facilitate the use of MIS in the management of gonadal disorders. C1 MASSACHUSETTS GEN HOSP, PEDIAT ENDOCRINE UNIT, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, CTR BIOSTAT, BOSTON, MA 02114 USA. TOKYO METROPOLITAN KIYOSE CHILDRENS HOSP, DIV ENDOCRINOL & METAB, TOKYO, JAPAN. CHILDRENS MEM HOSP, DEPT PEDIAT ENDOCRINOL & DIABET, CHICAGO, IL 60614 USA. NEW YORK MED COLL, DEPT PEDIAT ENDOCRINOL, VALHALLA, NY 10595 USA. RP Lee, MM (reprint author), MASSACHUSETTS GEN HOSP, PEDIAT SURG RES LAB, WARREN 11, BOSTON, MA 02114 USA. RI Hasegawa, Tomonobu/L-3331-2013; OI Lee, Mary/0000-0002-7204-4884 FU FDA HHS [FD-R-000669]; NCRR NIH HHS [MO1-RR-01066]; NIDDK NIH HHS [DK-02129] NR 24 TC 259 Z9 269 U1 1 U2 6 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD FEB PY 1996 VL 81 IS 2 BP 571 EP 576 DI 10.1210/jc.81.2.571 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TU981 UT WOS:A1996TU98100026 PM 8636269 ER PT J AU Kinsley, BT Simonson, DC AF Kinsley, BT Simonson, DC TI Evidence for a hypothalamic-pituitary versus adrenal cortical effect of glycemic control on counterregulatory hormone responses to hypoglycemia in insulin-dependent diabetes mellitus SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID DEFECTIVE GLUCOSE COUNTERREGULATION; CORTICOTROPIN-RELEASING FACTOR; AUTONOMIC NEUROPATHY; SUBSEQUENT HYPOGLYCEMIA; RECURRENT HYPOGLYCEMIA; VASOPRESSIN SECRETION; UNAWARENESS; SYMPTOMS; PLASMA; THRESHOLDS AB The epinephrine and cortisol responses to hypoglycemia are reduced in insulin-dependent diabetes mellitus (IDDM) patients in strict glycemic control. However, it is not known whether these abnormalities are mediated at a central (hypothalamic-pituitary) or peripheral (adrenal) level. To examine this question, we measured counterregulatory hormone secretion during a 3-h hypoglycemic hyperinsulinemic clamp (12 pmol/kg . min) that lowered glucose from 5.0 to 2.2 mmol/L in steps of 0.55 mmol/L every 30 min in 13 well controlled IDDM subjects (hemoglobin A(1), 7.8 +/- 0.2%), 14 poorly controlled IDDM subjects (hemoglobin A(1), 12.3 +/- 1.5%), and 20 healthy volunteers. Basal levels of ACTH, cortisol, and epinephrine were similar in all 3 groups before hypoglycemia. At the nadir glucose level (2.2 mmol/L), ACTH, cortisol, and epinephrine levels were significantly lower in well controlled IDDM compared to healthy controls, and the glucose levels required for significant secretion of ACTH, cortisol, and epinephrine also were lower in well controlled IDDM compared to those in both poorly controlled IDDM and healthy volunteers (P < 0.05). During hypoglycemia, ACTH levels were significantly correlated with cortisol levels (r = 0.43; P < 0.05). Because adrenomedullary epinephrine synthesis is partially dependent on adequate adrenocortical function, we also determined whether the blunted epinephrine response might result from the reduced cortisol secretion. Eleven of the control subjects underwent a second identical insulin clamp study during which metyrapone was administered to produce adrenal cortical blockade. Despite higher basal ACTH levels after metyrapone and sustained elevations in ACTH during hypoglycemia, the cortisol response was abolished during metyrapone treatment, indicating effective blockade. However, epinephrine responses did not differ during hypoglycemia with or without metyrapone treatment. We conclude that 1) ACTH, cortisol, and epinephrine responses during hypoglycemia are reduced in IDDM patients in strict glycemic control; 2) the lower cortisol response is correlated with reduced ACTH levels; and 3) in healthy subjects, the cortisol response to hypoglycemia is abolished by adrenocortical blockade with metyrapone, whereas the epinephrine response to hypoglycemia remains intact. These data suggest that central adaptations in hypothalamic-pituitary responses to hypoglycemia rather than alterations in adrenal gland function per se underlie the reduced counterregulatory responses seen in IDDM subjects in strict glycemic control. C1 NEW ENGLAND DEACONESS HOSP, JOSLIN DIABET CTR, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02115 USA. RP Kinsley, BT (reprint author), BRIGHAM & WOMENS HOSP, SECT DIABET & METAB, 221 LONGWOOD AVE, BOSTON, MA 02115 USA. FU NIDDK NIH HHS [DK-36836] NR 67 TC 17 Z9 17 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD FEB PY 1996 VL 81 IS 2 BP 684 EP 691 DI 10.1210/jc.81.2.684 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TU981 UT WOS:A1996TU98100046 PM 8636289 ER PT J AU Seifer, DB Gardiner, AC LambertMesserlian, G Schneyer, AL AF Seifer, DB Gardiner, AC LambertMesserlian, G Schneyer, AL TI Differential secretion of dimeric inhibin in cultured luteinized granulosa cells as a function of ovarian reserve SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID FOLLICLE-STIMULATING-HORMONE; AGE; WOMEN; HYPERSTIMULATION; GONADOTROPIN; ESTRADIOL; PROTEINS; LEVEL; CYCLE; FLUID AB Day 3 serum FSH is an indirect assessment of ovarian reserve and has been shown to be prognostic of outcome in ovulation induction and assisted reproductive technology programs. The precise physiologic basis for day 3 serum FSH screening is unknown. We tested the hypothesis that dimeric inhibin is differentially secreted from luteinized granulosa cells collected from women in preparation for in vitro fertilization with low vs. high day 3 serum FSH levels. This prospective study consisted of luteinized granulosa cells harvested from 7 women with low day 3 serum FSH levels (less than or equal to 6 IU/L) and from 8 women with high FSH levels (greater than or equal to 10 IU/L) in preparation for in vitro fertilization-embryo transfer. Following retrieval, cells were isolated and then pooled within each individual patient and plated at 50,000 cells per well. Media was removed at 24 and 48 h and analyzed for dimeric and total inhibin concentrations by immunoassay as well as estradiol and progesterone concentrations by RIA. Dimeric inhibin was secreted at 2-fold higher concentrations in the low FSH group 43.2 pg/ml (30.8-60.6) (geometric mean and 95% confidence interval) compared with the high FSH group, 21.0 pg/ml (15.0-29.6), P < 0.004. Total inhibin was secreted at 1.8-fold higher concentrations in the low FSH group, 1148.2 pg/ml (931.1-1415.8) compared with the high FSH group, 639.7 pg/ml (428.5-955.0), P < 0.013. No significant differences in either estradiol or progesterone concentrations were noted. These data suggest that day 3 serum FSH is an indirect bioassay of dimeric inhibin production at the granulosa cell level. Thus, these data provide a potential physiological basis for day 3 serum FSH screening in ovulation induction and ART programs. C1 MASSACHUSETTS GEN HOSP, NATL CTR INFERTIL RES, BOSTON, MA 02114 USA. RP Seifer, DB (reprint author), BROWN UNIV, SCH MED, WOMEN & INFANTS HOSP, DEPT OBSTET & GYNECOL, DIV REPROD ENDOCRINOL, PROVIDENCE, RI 02905 USA. OI Seifer, David/0000-0003-3950-9341; Messerlian, Geralyn/0000-0002-9440-3411 FU NIA NIH HHS [AG00566]; NICHD NIH HHS [R01-HD-31894]; PHS HHS [U54-29164] NR 17 TC 56 Z9 59 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD FEB PY 1996 VL 81 IS 2 BP 736 EP 739 DI 10.1210/jc.81.2.736 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TU981 UT WOS:A1996TU98100053 PM 8636296 ER PT J AU Alexander, JM Bikkal, HA Zervas, NT Laws, ER Klibanski, A AF Alexander, JM Bikkal, HA Zervas, NT Laws, ER Klibanski, A TI Tumor-specific expression and alternate splicing of messenger ribonucleic acid encoding activin transforming growth factor-beta receptors in human pituitary adenomas SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID SERINE THREONINE KINASE; ACTIVIN RECEPTOR; II RECEPTORS; DOMAINS; BIOSYNTHESIS; INHIBITION; SECRETION; CLONING; ORIGIN AB Activin, a member of the transforming growth factor-beta (TGF beta) cytokine family, acts as a pituitary cell mitogen via a novel family of receptor-linked serine/threonine (Ser/Thr) kinases. Pituitary tumors synthesize activin subunits, and the autocrine action of these growth factors may modulate tumor proliferation. We, therefore, investigated the expression of activin/TGF beta type I receptor messenger ribonucleic acids (mRNAs), designated ALK1 through ALK5, (ALK = activin receptor-like kinase), and type II receptor mRNAs using RT-PCR in 34 human pituitary adenomas of all phenotypes and normal pituitary tissue. ALK2 and ALK5, specific mediators of activin and TGF beta signals, respectively, were found to be expressed only in tumor and not in normal pituitary cells, and ALK2 expression was found only in tumors of a mammosomatotroph cell lineage. ALK1, ALK3, and ALK4 mRNAs were found in both normal and neoplastic pituitary cells. The alternatively spliced cytoplasmic domain of ALK4 consists of 11 kinase subdomains, that are critical for modulating receptor function and intracellular signaling. Truncated forms of the ALK4 cytoplasmic domain lacking these subdomains may attenuate activin signal transduction and affect both tumor phenotype and proliferation via the of inactive type I/type II complexes. Three truncated ALK4 mRNAs generated by alternate splicing of the cytoplasmic kinase domain were found to be tumor specific. One of these truncated receptor mRNAs, ALK4-5, is a novel splice variant that has not been previously described. Expression of the ActRII and T beta RII type II receptor mRNAs, which specifically bind activin and TGF beta, respectively, was highly prevalent among all tumor subtypes and normal pituitary tissue. However, ActRIIB, an activin-specific type II receptor that displays a 3- to 4-fold higher affinity for ligand than ActRII, was expressed in 94% of tumors, but was not prevalent in normal tissue. These data are the first to demonstrate tumor-specific expression of Ser/Thr kinase receptors mRNAs and their splice variants in human pituitary adenomas. C1 MASSACHUSETTS GEN HOSP, NEUROSURG SERV, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02114 USA. UNIV VIRGINIA, HLTH SCI CTR, DEPT NEUROSURG, CHARLOTTESVILLE, VA 22908 USA. RP Alexander, JM (reprint author), MASSACHUSETTS GEN HOSP, DEPT MED, NEUROENDOCRINE UNIT, JACKSON 1021, FRUIT ST, BOSTON, MA 02114 USA. FU NIDDK NIH HHS [DK-40947] NR 40 TC 55 Z9 57 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD FEB PY 1996 VL 81 IS 2 BP 783 EP 790 DI 10.1210/jc.81.2.783 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TU981 UT WOS:A1996TU98100061 PM 8636304 ER PT J AU Weiss, MJ Orkin, SH AF Weiss, MJ Orkin, SH TI In vitro differentiation of murine embryonic stem cells - New approaches to old problems SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID BONE MORPHOGENETIC PROTEIN-4; GENE-EXPRESSION; MOUSE EMBRYOS; ES CELLS; HEMATOPOIETIC DEVELOPMENT; HOMOLOGOUS RECOMBINATION; INVITRO DEVELOPMENT; VENTRALIZING FACTOR; YOLK-SAC; VASCULOGENESIS C1 HARVARD UNIV,CHILDRENS HOSP,SCH MED,HOWARD HUGHES MED INST,DIV HEMATOL ONCOL,RES LABS,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PEDIAT,BOSTON,MA 02115. HOWARD HUGHES MED INST,BOSTON,MA 02115. RI Weiss, Mitchell/A-1245-2013 NR 60 TC 96 Z9 102 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD FEB 1 PY 1996 VL 97 IS 3 BP 591 EP 595 DI 10.1172/JCI118454 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA UB656 UT WOS:A1996UB65600004 PM 8609212 ER PT J AU Ponath, PD Qin, SX Ringler, DJ ClarkLewis, I Wang, J Kassam, N Smith, H Shi, XJ Gonzalo, JA Newman, W GutierrezRamos, JC Mackay, CR AF Ponath, PD Qin, SX Ringler, DJ ClarkLewis, I Wang, J Kassam, N Smith, H Shi, XJ Gonzalo, JA Newman, W GutierrezRamos, JC Mackay, CR TI Cloning of the human eosinophil chemoattractant, eotaxin - Expression, receptor binding, and functional properties suggest a mechanism for the selective recruitment of eosinophils SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE chemokines; cytokines; inflammation; eosinophils; chemotaxis ID INFLAMMATORY PROTEIN 1-ALPHA; NEUTROPHIL-ACTIVATING PEPTIDE-2; COUPLED RECEPTORS; LANGERHANS CELLS; HUMAN RANTES; INTERLEUKIN-8; MIGRATION; GRANULOCYTES; PURIFICATION; CHEMOKINES AB The CC chemokine eotaxin, identified in guinea pigs and also recently in mice, may be a key element for the selective recruitment of eosinophils to certain inflamed tissues. Using a partial mouse eotaxin cDNA probe, the human eotaxin gene was cloned and found to be 61.8 and 63.2% identical at the amino acid level ro guinea pig and mouse eotaxin. Human eotaxin protein was a strong and specific eosinophil chemoattractant in vitro and was an effective eosinophil chemoattractant when injected into the skin of a rhesus monkey. Radiolabeled eotaxin was used to identify a high affinity receptor on eosinophils (0.52 nM K-d), expressed at 4.8 x 10(4) sites per cell. This receptor also bound RANTES and monocyte chemotactic protein-3 with lower affinity, but not macrophage inflammatory protein-1 alpha. Eotaxin could desensitize calcium responses of eosinophils to RANTES and monocyte chemotactic protein-3, although RANTES was able to only partially desensitize eosinophil calcium responses to eotaxin. Immunohistochemistry on human nasal polyp with antieotaxin mAbs showed that certain leukocytes as well as respiratory epithelium were intensely immunoreactive, and eosinophil infiltration occurred at sites of eotaxin upregulation. Thus eotaxin in humans is a potent and selective eosinophil chemoattractant that is expressed by a variety cell types in certain inflammatory conditions. C1 LEUKOSITE INC,CAMBRIDGE,MA 02142. UNIV BRITISH COLUMBIA,BIOMED RES CTR,VANCOUVER,BC,CANADA. UNIV BRITISH COLUMBIA,DEPT BIOCHEM & MOLEC BIOL,VANCOUVER,BC,CANADA. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. RI Mackay, Charles/A-9673-2008 OI Mackay, Charles/0000-0002-6338-7340 FU NIGMS NIH HHS [R01 GM-50969-01] NR 55 TC 591 Z9 603 U1 0 U2 4 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD FEB 1 PY 1996 VL 97 IS 3 BP 604 EP 612 DI 10.1172/JCI118456 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA UB656 UT WOS:A1996UB65600006 PM 8609214 ER PT J AU Huffman, JA Hull, WM Dranoff, G Mulligan, RC Whitsett, JA AF Huffman, JA Hull, WM Dranoff, G Mulligan, RC Whitsett, JA TI Pulmonary epithelial cell expression of GM-CSF corrects the alveolar proteinosis in GM-CSF-deficient mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE alveolar proteinosis; transgenic mice; granulocyte-macrophage colony-stimulating factor (GM-CSF); surfactant homeostasis; gene correction ID COLONY-STIMULATING FACTOR; SURFACTANT-ASSOCIATED PROTEINS; TRANSGENIC MICE; LUNG; HEMATOPOIESIS; LINES; RNA AB Mutation of the granulocyte-macrophage colony-stimulating factor (GM-CSF) gene by homologous recombination caused alveolar proteinosis in mice. To further discern the role of GM-CSF in surfactant homeostasis, the synthesis of GRM-CSF was directed to the respiratory epithelium of GM-CSF-null mutant mice (GM-/-)with a chimeric gene expressing GM-CSF under the control of the promoter from the human surfactant protein-C (SP-C) gene. Transgenic mice bearing the SP-C-GM-CSF construct (SP-C-GM+) were bred to GM-/- mice resulting in complete correction of alveolar proteinosis in bitransgenic GM-/-, SP-C-GM+ mice. No effects of the transgene were found outside the lung. GM-CSF was increased in bronchoalveolar lavage fluid of the bitransgenic mice. Surfactant proteins-A and -B and phospholipid in bronchoalveolar lavage fluid were normalized in the GM-/-, SP-C-GM+ mice, SP-A, -B, and -C mRNAs were unaltered in lungs from GM-CSF-deficient and -replete mice. Expression of GM-CSF in respiratory epithelial cells of transgenic mice restores surfactant homeostasis in GM-/- mice. From these findings, we conclude that GM-CSF regulates the clearance or catabolism rather than synthesis of surfactant proteins and lipids. C1 CHILDRENS HOSP,MED CTR,DIV PULM BIOL,CINCINNATI,OH 45229. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. MIT,WHITEHEAD INST,CAMBRIDGE,MA 02142. FU NHLBI NIH HHS [HL41496, HL49004] NR 32 TC 174 Z9 177 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD FEB 1 PY 1996 VL 97 IS 3 BP 649 EP 655 DI 10.1172/JCI118461 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA UB656 UT WOS:A1996UB65600011 PM 8609219 ER PT J AU Maiden, MFJ Tanner, A Macuch, PJ AF Maiden, MFJ Tanner, A Macuch, PJ TI Rapid characterization of periodontal bacterial isolates by using fluorogenic substrate tests SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID POLYACRYLAMIDE-GEL-ELECTROPHORESIS; SIALIDASE NEURAMINIDASE ACTIVITY; STREPTOCOCCUS-MILLERI GROUP; API-ZYM SYSTEM; SP-NOV; VIRIDANS STREPTOCOCCI; ANAEROBIC-BACTERIA; SDS-PAGE; PRESUMPTIVE IDENTIFICATION; ENZYMATIC CHARACTERIZATION AB Eighty-nine species of subgingival bacteria, represented by 121 reference strains and 892 patient isolates, including gram-negative, gram-positive, aerobic, facultatively anaerobic, microaerophilic, and anaerobic species, were characterized with a panel of fluorogenic, 4-methylumbelliferyl-linked substrate tests. Identifications of all patient isolates were confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of whole-cell proteins relative to reference strains. Characteristic profiles of positive fluorogenic reactions differentiated most of the species, including five Porphyromonas species, six pigmenting and five nonpigmenting Prevotella species, Bacteroides forsythus, three Capnocytophaga species, six Actinomyces species, four Propionibacterium species, and eight Streptococcus species. Two mannoside isomers differentiated Actinomyces israelii and Actinomyces gerencseriae. In addition to Porphyromonas gingivalis, B. forsythus, and Capnocytophaga species, Fusobacterium alocis, Actinomyces odontolyticus, Actinomyces meyeri, and Bifidobacterium dentium were all positive for so-called trypsin-like activity. Fusobacterium nucleatum, Eikenella corrodens, Actinobacillus actinomycetemcomitans, and Campylobacter species were nonreactive with the carbohydrate-based substrates tested. Fluorogenic substrate tests provided a sensitive and simple method for biochemical characterization that could presumptively identify to species level most subgingival isolates within 4 h. The method was ideal for rapidly obtaining presumptive identifications of isolates prior to confirming identifications by definitive methods, such as SDS-PAGE. RP Maiden, MFJ (reprint author), FORSYTH DENT CTR,DEPT PERIODONTOL MICROBIOL,140 FENWAY,BOSTON,MA 02115, USA. FU NIDCR NIH HHS [DE 10160, DE 09513] NR 51 TC 37 Z9 38 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD FEB PY 1996 VL 34 IS 2 BP 376 EP 384 PG 9 WC Microbiology SC Microbiology GA TQ538 UT WOS:A1996TQ53800027 PM 8789019 ER PT J AU Patenaude, AF Basili, L Fairclough, DL Li, FP AF Patenaude, AF Basili, L Fairclough, DL Li, FP TI Attitudes of 47 mothers of pediatric oncology patients toward genetic testing for cancer predisposition SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID HUNTINGTONS-DISEASE; MUTATIONS AB Purpose: To assess attitudes toward testing for cancer susceptibility genes, we interviewed mothers of pediatric oncology patients about their cancer causation theories, interest in hypothetical predisposition testing for themselves and their healthy children, and anticipated impact of testing. Patients and Methods: The subjects were 47 mothers of two or more living children, one of whom was 6 to 24 months postdiagnosis of cancer. Potential risks and benefits of hypothetical generic predisposition testing for cancer susceptibility were described. A semistructured interview assessed the following: (1) recall of discussions with the pediatric oncologist about the possible role of heredity in causing the child's cancer; (2) mothers' personal theories of the etiology of their child's cancer; (3) family cancer history; (4) interest in genetic predisposition testing for themselves and unaffected (cancer-free) children; and (5) expected sequelae of testing. Results: If genetic cancer predisposition tests were available, 51% of mothers would test themselves and 42% would test healthy children, even with no medical benefit. With established medical benefit, an additional 36% of mothers would seek testing for themselves and another 49% would test their healthy children. Interest in cancer predisposition testing among mothers extended far beyond those with significant family histories of cancer. Most mothers would consider minor children's wishes in the decision about testing and would tell children under age 18 their test results. Conclusion: As increasing numbers of cancer susceptibility are identified, parents of pediatric oncology patients may be receptive to opportunities to test themselves and their healthy children. Counseling will be important to aid in decisions about testing. Research is essential to evaluate the long-term impact of predisposition testing. (C) 1996 by American Society of Clinical Oncology. C1 CHILDRENS HOSP,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. RP Patenaude, AF (reprint author), DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. NR 17 TC 35 Z9 35 U1 0 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 FEB PY 1996 VL 14 IS 2 BP 415 EP 421 PG 7 WC Oncology SC Oncology GA TU998 UT WOS:A1996TU99800014 PM 8636751 ER PT J AU Travis, LB Weeks, J Curtis, RE Chaffey, JT Stovall, M Banks, PM Boice, JD AF Travis, LB Weeks, J Curtis, RE Chaffey, JT Stovall, M Banks, PM Boice, JD TI Leukemia following low-dose total body irradiation and chemotherapy for non-Hodgkin's lymphoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ACUTE NONLYMPHOCYTIC LEUKEMIA; COMBINATION CHEMOTHERAPY; ADVANCED LYMPHOSARCOMA; LYMPHOCYTIC LYMPHOMA; CYCLOPHOSPHAMIDE; VINCRISTINE; PREDNISONE; ADRIAMYCIN; THERAPY; RISK AB Purpose: Low-dose total body irradiation (TBI) is used to treat non-Hodgkin's lymphoma (NHL) and several other malignancies. Large volumes of bone marrow and other tissue receive considerable exposure, but few studies have quantified late carcinogenic sequelae. Patients and Methods: A cohort of 61 2-year survivors of NHL treated with low-dose TBI was monitored for second cancer occurrence, Data on primary and subsequent therapy were collected, and cumulative dose of radiation to active bone marrow (ABM) (median, 5.2 Gy) was reconstructed. Results: Thirteen second primary cancers occurred, Four patients developed acute nonlymphocytic leukemia (ANLL), which represents a relative risk (90) of 117(95% confidence interval [Cl], 31.5 to 300) compared with population rates. A fifth patient was diagnosed with myelodysplastic syndrome (MDS). All five patients with secondory hematologic malignancies subsequently received salvage treatment, with either alkylating agents alone (n = 1) or combined modality therapy (CMT) (n = 4). Overall, eight solid tumors were observed (RR = 2.0; 95% Cl, 0.9 to 4.0). The 15-year cumulative risks of all second cancers and secondary ANLL were 37% and 17%, respectively. Conclusions: Despite the small number of subjects, a considerable risk of leukemia was observed among patients treated with low-dose TBI in combination with CMT including alkylating agents. Based on these results, approximately eight to nine excess ANLLs might be expected to occur among 100 NHL patients treated with low-dose TBI and salvage treatment and followed-up for 15 years. C1 DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD JOINT CTR RADIOTHERAPY,BOSTON,MA. UNIV TEXAS,MD ANDERSON CANC CTR,HOUSTON,TX. UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX. RP Travis, LB (reprint author), NCI,RADIAT EPIDEMIOL BRANCH,NIH,UNITED STATES DEPT HLTH & HUMAN SERV,EXECUT PLAZA N,SUITE 408,BETHESDA,MD 20892, USA. NR 46 TC 69 Z9 78 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 FEB PY 1996 VL 14 IS 2 BP 565 EP 571 PG 7 WC Oncology SC Oncology GA TU998 UT WOS:A1996TU99800035 PM 8636772 ER PT J AU Soriano, JL OSullivan, RL Bear, L Phillips, KA McNally, RJ Jenike, MA AF Soriano, JL OSullivan, RL Bear, L Phillips, KA McNally, RJ Jenike, MA TI Trichotillomania and self-esteem: A survey of 62 female hair pullers SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID CLINICAL CHARACTERISTICS; STABILITY; PERSONALITY; ADOLESCENT; ANXIETY; RATINGS; SCALE AB Background: The psychological features of trichotillomania have received little empirical attention, despite the fact that sufferers commonly report negative self-image to be one of the most disturbing aspects of the disorder. We conducted the current study to identify specific factors that predict self-esteem problems in hair pullers. Method: Sixty-two women with trichotillomania or repetitive hair pulling completed self-report forms assessing factors possibly related to self-esteem in hair pullers. The survey included questions related to demographics, hair-pulling symptoms, mood and anxiety symptoms, and body image concerns. Results: Self-esteem did not appear to be directly related to age at onset of hair pulling or severity of hair loss. However, self-esteem was related to level of depression, frequency of hair pulling, level of anxiety, and body dissatisfaction unrelated to hair pulling. Conclusion: Several factors, including the frequency of hair pulling, are associated with low self-esteem in patients with trichotillomania. Specific efforts should be made to address these issues in treatment. C1 HARVARD UNIV,DEPT PSYCHOL,CAMBRIDGE,MA 02138. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,OCD CLIN & RES UNIT,BOSTON,MA. BROWN UNIV,SCH MED,BUTLER HOSP,DEPT PSYCHIAT,PROVIDENCE,RI 02912. NR 49 TC 51 Z9 52 U1 1 U2 6 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD FEB PY 1996 VL 57 IS 2 BP 77 EP 82 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA TV771 UT WOS:A1996TV77100004 PM 8591973 ER PT J AU McCusker, J Willis, G McDonald, M Sereti, SM Lewis, BF Sullivan, JL AF McCusker, J Willis, G McDonald, M Sereti, SM Lewis, BF Sullivan, JL TI Community-wide HIV counselling and testing in central Massachusetts: Who is retested and does their behavior change? SO JOURNAL OF COMMUNITY HEALTH LA English DT Article; Proceedings Paper CT IX International Conference on AIDS/HIV STD World Congress CY JUN 06-11, 1993 CL BERLIN, GERMANY ID INTRAVENOUS-DRUG-USERS; IMMUNODEFICIENCY VIRUS-INFECTION; RISK BEHAVIORS; SEROPREVALENCE; ANTIBODY AB HIV counselling and testing was provided to 4267 individuals between September 1987 and June 1992 at a multi-site program, including community clinics, drug treatment programs, and a men's prison in central Massachusetts. Half of those tested reported the risk behaviors targeted by the programs: injection drug use (38.1%) and sexual contact with a drug injector (12.6%). The objectives of this study were to examine 1) factors associated with repeat HN testing among these initially seronegative, and 2) behavior change following counselling and testing. Initially 7.4% were HIV positive, and 12.4% of those testing negative were retested within one year. Risk behavior was the only strong independent predictor of retesting (odds ratios of 3.8 and 4.2 for men reporting sex with men and recent drug injectors, respectively). Changes in risk behaviors between the time of the initial test and the second test were assessed (n = 207). Among those who continued to inject drugs at follow-up there was a reduction in the percent visiting shooting galleries (p = 0.05); no other significant behavior changes were reported. While selection bias may be responsible in part for the minimal behavior change observed, continued monitoring of risk behavior and counselling are warranted. C1 ST MARYS HOSP,DEPT CLIN EPIDEMIOL & COMMUNITY STUDIES,MONTREAL,PQ H3T 1M5,CANADA. MCGILL UNIV,DEPT EPIDEMIOL & BIOSTAT,MONTREAL,PQ,CANADA. MASSACHUSETTS GEN HOSP,HLTH POLICY RES & DEV UNIT,BOSTON,MA 02114. DEPT PUBL HLTH,HIV COUNSELLING TESTING & SUPPORT SERV,WORCESTER,MA. UNIV MASSACHUSETTS,SCH PUBL HLTH,AMHERST,MA 01003. RES CTR ADDICT BEHAV,SALEM,MA. UNIV MASSACHUSETTS,MED CTR,SCH MED,WORCESTER,MA 01655. FU NIDA NIH HHS [R01-DA-05615] NR 18 TC 22 Z9 22 U1 0 U2 1 PU HUMAN SCI PRESS INC PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 SN 0094-5145 J9 J COMMUN HEALTH JI J. Community Health PD FEB PY 1996 VL 21 IS 1 BP 11 EP 22 DI 10.1007/BF01682760 PG 12 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA TQ186 UT WOS:A1996TQ18600002 PM 8903580 ER PT J AU Fletcher, MA Kloczewiak, M Loiselle, PM Amato, SF Black, KM Warren, HS AF Fletcher, MA Kloczewiak, M Loiselle, PM Amato, SF Black, KM Warren, HS TI TALF peptide-immunoglobulin G conjugates that bind lipopolysaccharide SO JOURNAL OF ENDOTOXIN RESEARCH LA English DT Article ID LIMULUS ANTILIPOPOLYSACCHARIDE FACTOR; PERMEABILITY-INCREASING PROTEIN; AMINO-TERMINAL FRAGMENT; POLYMYXIN-B SULFATE; ANTI-LPS FACTOR; MONOCLONAL-ANTIBODIES; ENDOTOXIN AB Several peptides mimicking the amino acid sequence of Tachypleus anti-LPS factor (TALF) bind LPS with high affinity and some neutralize LPS in vitro and in vivo (Kloczewiak M., Black K.M., Loiselle P., Cavaillon J-M., Wainwright N., Warren H.S. Synthetic peptides that mimic the binding site of horseshoe crab anti-lipopolysaccharide factor. J Infect Dis 1994; 170: 1490-1497). Two such peptides, TALF29-59 and TALF41-53, were covalently coupled to human IgG via a disulfide bond using the heterobifunctional linker, N-succinimidyl-3-(2-pyridyldithio)propionate (SPDP). The resulting peptide-IgG conjugates contained 4-8 moles peptide per mole IgG and were evaluated for the ability to bind and neutralize LPS. Both conjugates bound LPS in a LPS capture Western blot assay. In a fluid-phase radioimmunoassay, half-maximal binding of 5 mu g/ml LPS by many different Escherichia coli strains occurred at 50-100 mu g/ml for both conjugates. Coagulation of Limulus amoebocyte lysate was only minimally inhibited by 5 mu g/ml of each conjugate. Our data suggest that TALF peptide-IgG conjugates bind LPS with high affinity, but only weakly neutralize LPS. These studies provide an initial step towards the development of peptide-IgG preparations that might be useful for the treatment of Gram-negative sepsis by binding and clearing LPS. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA. SHRINERS BURNS INST,CHILDRENS SERV,BOSTON,MA. SHRINERS BURNS INST,DEPT MED,BOSTON,MA. CREAT BIOMOL,HOPKINTON,MA. NR 23 TC 7 Z9 8 U1 0 U2 2 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH, MIDLOTHIAN, SCOTLAND EH1 3AF SN 0968-0519 J9 J ENDOTOXIN RES JI J. Endoxtin Res. PD FEB PY 1996 VL 3 IS 1 BP 49 EP 55 PG 7 WC Biochemistry & Molecular Biology; Immunology; Medicine, Research & Experimental; Microbiology SC Biochemistry & Molecular Biology; Immunology; Research & Experimental Medicine; Microbiology GA UE602 UT WOS:A1996UE60200006 ER PT J AU Zhang, W Zimmer, G Chen, JZ Ladd, D Li, E Alt, FW Wiederrecht, G Cryan, J ONeill, EA Seidman, CE Abbas, AK Seidman, JG AF Zhang, W Zimmer, G Chen, JZ Ladd, D Li, E Alt, FW Wiederrecht, G Cryan, J ONeill, EA Seidman, CE Abbas, AK Seidman, JG TI T cell responses in calcineurin A alpha-deficient mice SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID CYCLOSPORINE-A; CATALYTIC SUBUNIT; STEM-CELLS; RAT-BRAIN; CYCLOPHILIN; EXPRESSION; IDENTIFICATION; MECHANISMS; INHIBITION; ACTIVATION AB We have created embryonic stem (ES) cells and mice lacking the predominant isoform (alpha) of the calcineurin A subunit (CNA alpha) to study the role of this serine/threonine phosphatase in the immune system. T and B cell maturation appeared to be normal in CNA alpha(-/-) mice. CNA alpha(-/-) cells responded normally to mitogenic stimulation (i.e., PMA plus ionomycin, concanavalin A, and anti-CD3 epsilon antibody). However, CNA alpha(-/-) mice generated defective antigen-specific T cell responses in vivo. Mice produced from CNA alpha(-/-) ES cells injected into RAG-2-deficient blastocysts had a similar defective T cell response, indicating that CNA alpha is required for T cell function per se, rather than for an activity of other cell types involved in the immune response. CNA alpha(-/-) T cells remained sensitive to both cyclosporin A and FK506, suggesting that CNA beta or another CNA-like molecule can mediate the action of these immunosuppressive drugs. CNA alpha(-/-) mice provide an animal model for dissecting the physiologic functions of calcineurin as well as the effects of FK506 and CsA. C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT PATHOL,DIV IMMUNOL RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,LMRC,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP E,CARDIOVASC RES CTR,BOSTON,MA 02129. BRIGHAM & WOMENS HOSP,DEPT MED,DIV CARDIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,HOWARD HUGHES MED INST,BOSTON,MA 02115. CHILDRENS HOSP,BOSTON,MA 02115. CTR BLOOD RES,BOSTON,MA 02115. MERCK & CO INC,RES LABS,DEPT MOLEC IMMUNOL,RAHWAY,NJ 07065. NR 38 TC 28 Z9 29 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD FEB 1 PY 1996 VL 183 IS 2 BP 413 EP 420 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA TW109 UT WOS:A1996TW10900008 ER PT J AU Biancone, L Araki, M Araki, K Vassalli, P Stamenkovic, I AF Biancone, L Araki, M Araki, K Vassalli, P Stamenkovic, I TI Redirection of tumor metastasis by expression of E-selectin in vivo SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID LEUKOCYTE ADHESION MOLECULE-1; CELL-ADHESION; SIALYL-LEX; MELANOMAS; SURFACE; LINES; CDNA AB The selectin class of adhesion molecules plays a critical role in facilitating leukocyte adhesion to and subsequent transmigration of endothelium. On this basis, selectins have been suggested to promote tumor cell attachment to endothelium, thereby facilitating metastasis of certain types of tumors, although direct evidence for such a role is lacking. To explore this hypothesis, two sets of transgenic mice were developed: TgnES, which constitutively expresses cell surface E-selectin in all tissues, under the control of the beta-actin promoter; and TgnEsol, which expresses truncated, soluble E-selectin in the liver, under the control of the alpha 1 antitrypsin promoter. B16F10 melanoma cells were stably transfected with alpha(1,3/1,4) fucosyltransferase-specific cDNA (B16F10ft), allowing them to express E-selectin Ligands or with hygromycin resistance selection vector only (B16F10hygro). Normal mice injected with B16F10ft and B16F10hygro and transgenic mice injected with B16F10hygro developed lung tumors exclusively. In contrast, TgnES mice injected with B16F10ft cells developed massive infiltrating liver tumors. B16F10ft cells injected into TgnEsol mice also formed liver tumors, but these grew more slowly, with a well-delineated, noninfiltrating distinct histologic pattern. These observations provide direct evidence that expression of E-selectin can redirect metastasis of tumor cells expressing appropriate ligands in vivo. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,BOSTON,MA 02129. UNIV GENEVA,CTR MED UNIV,DEPT PATHOL,CH-1211 GENEVA 4,SWITZERLAND. FU NCI NIH HHS [CA55735] NR 20 TC 136 Z9 141 U1 1 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD FEB 1 PY 1996 VL 183 IS 2 BP 581 EP 587 DI 10.1084/jem.183.2.581 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA TW109 UT WOS:A1996TW10900023 PM 8627169 ER PT J AU Steele, DJR Laufer, TM Smiley, ST Ando, Y Grusby, MJ Glimcher, LH Auchincloss, H AF Steele, DJR Laufer, TM Smiley, ST Ando, Y Grusby, MJ Glimcher, LH Auchincloss, H TI Two levels of help for B cell alloantibody production SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID II-DEFICIENT MICE; T-CELL; ANTIGEN PRESENTATION; CYTOPLASMIC DOMAIN; ACTIVATION; EXPRESSION; REJECTION; INVIVO AB We have examined whether T cell, stimulation by direct or indirect pathways contributes to alloantibody production by B cells after major histocompatibility complex (MHC)-disparate skin graft rejection in mice. Experiments were performed using normal mice, MHC class II-deficient mice, MHC class II-deficient mice with an intact peripheral CD4(+) cell population (due to expression of class II antigens only on thymic epithelium), mice lacking the cytoplasmic tail of their MHC class II antigens, and mice depleted of CD4(+) cells by anti-CD4 monoclonal antibody treatment. Depletion of recipient CD4(+) cells reduced alloantibody production to barely detectable levels. Absence of donor MHC class II antigens did not affect the production of either immunoglobulin (Ig)M or IgG antibodies directed at class I alloantigens. Absence of recipient MHC class II antigens, however, led to production of only IgM but not IgG antibodies, even if the recipients had an intact CD4(+) cell population. Absence of the cytoplasmic tail of the recipient's MHC class II antigens led to the production of slightly reduced amounts of IgG antibody. These findings indicate that (a) CD4(+) cells are essential helper cells for B cell alloantibody production; (b) production of IgM alloantibody can occur with help from CD4(+) cells, which recognize either donor class II antigens or modified recipient class II antigens; (c) isotype switching from IgM. to IgG alloantibody requires help from CD4(+) cells activated by antigens presented by recipient MHC class II molecules; and (d) the cytoplasmic domain of the recipient MHC class II molecules may be involved in the mechanism that leads to isotype switching by B cells. Thus, there are two levels of CD4-mediated help available for B cells responding to alloantigens: one (involving a noncognate interaction) can produce B cell activation, and a second (involving a cognate interaction) is required for differentiation and IgG alloantibody production. C1 MASSACHUSETTS GEN HOSP,TRANSPLANT UNIT,SURG SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,RENAL UNIT,MED SERV,BOSTON,MA 02114. HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT RHEUMATOL & IMMUNOL,BOSTON,MA 02114. FU NHLBI NIH HHS [HL-18646, HL-36372]; NIAID NIH HHS [AI21569] NR 16 TC 142 Z9 143 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD FEB 1 PY 1996 VL 183 IS 2 BP 699 EP 703 DI 10.1084/jem.183.2.699 PG 5 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA TW109 UT WOS:A1996TW10900039 PM 8627185 ER PT J AU Mort, EA AF Mort, EA TI Clinical decision-making in the face of scientific uncertainty: Hormone replacement therapy as an example SO JOURNAL OF FAMILY PRACTICE LA English DT Article; Proceedings Paper CT Invitational Workshop on the Scientific Base of Primary Care CY JAN 24-25, 1995 CL WASHINGTON, DC SP Inst Med DE clinical decision-making; primary health care; hormone replacement therapy; patient satisfaction; physician's practice patterns ID EARLY BREAST-CANCER; POSTMENOPAUSAL WOMEN; PATIENT; OSTEOPOROSIS; ESTROGEN; OUTCOMES; LIFE; PARTICIPATION; INFORMATION; PREFERENCES AB There is widespread variation in the prescribing patterns of postmenopausal hormone replacement therapy. While some degree of variation is expected, the systematic variation according to geographic region, physician gender, and medical specialty raises questions about how clinical decisions are made. This paper explores the determinants of these practice patterns, specifically the contribution of patients' preferences, scientific uncertainty, and physicians' recommendations. A role for col laborative decision-making is described and the use of decision-support tools is discussed. The primary care setting is proposed as the ideal context in which to study collaborative decision-malting. Additional research is needed to more fully elucidate the value of collaborative decision-making with respect to clinical and quality of-life outcomes, patient satisfaction with decision making, and costs. C1 MASSACHUSETTS GEN HOSP,MED SERV,GEN INTERNAL MED UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT HLTH CARE POLICY,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. NR 39 TC 25 Z9 25 U1 2 U2 3 PU APPLETON & LANGE PI E NORWALK PA 25 VAN ZANT ST, E NORWALK, CT 06855 SN 0094-3509 J9 J FAM PRACTICE JI J. Fam. Pract. PD FEB PY 1996 VL 42 IS 2 BP 147 EP 151 PG 5 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA TV376 UT WOS:A1996TV37600009 PM 8606304 ER PT J AU Ribalet, B Mirell, CJ Johnson, DG Levin, SR AF Ribalet, B Mirell, CJ Johnson, DG Levin, SR TI Sulfonylurea binding to a low-affinity site inhibits the Na/K-ATPase and the K-ATP channel in insulin-secreting cells SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Article ID PANCREATIC BETA-CELLS; B-CELLS; PUMP INHIBITION; ISLETS; RECEPTOR; RELEASE; GLUCOSE; GLIBENCLAMIDE; NA+,K+-ATPASE; NA,K-ATPASE AB We have used hamster insulinoma tumor (HIT) cells, an insulin-secreting tumor cell line, to investigate modulation of the Na/K-ATPase and of the ATP-sensitive K channel (K-ATP) by the sulfonylurea glyburide. Membrane proteins from cells cultured in RPMI with 11 mM glucose have at least two glyburide receptor populations, as evidenced by high and low binding affinity constants, (K-d = 0.90 and 91 nM, respectively). In these cells K-ATP channel activity was blocked by low glyburide concentrations, IC50 = 5.4 nM. At 12.5 nM glyburide the inhibition developed slowly, tau = 380 s, and caused reduction of channel activity by 75%. At higher concentrations, however, inhibition occur-red at a fast rate, tau = 42 s at 100 nM, and was almost complete. Na/K-ATPase activity measured enzymatically and electrophsiologically was also suppressed by glyburide, but higher concentrations were needed, IC50 = 20-40 nM. Inhibition occurred rapidly, tau = 30 s at 50 nM, when maximum, activity was reduced by 40%. By contrast, cells cultured in RPMI supplemented with 25 mM glucose exhibit a single receptor population binding glyburide with low affinity, K-d = 68 nM. In these cells inhibition of the Na/K-ATPase by the sulfonylurea was similar to that observed in cells cultured in 11 mM glucose, but K-ATP channel inhibition was markedly altered. Inhibition occurred only at high concentrations of glyburide and at a fast rate; maximum inhibition was observed at similar to 100 nM. Based on these data, we propose that glyburide binding to the high affinity site affects primarily K-ATP channel activity, while inter action with the low affinity site inhibits both Na/K-ATPase and K-ATP channel activities. The latter observation suggests possible functional interactions between the Na/K-ATPase and the K-ATP channel. C1 W LOS ANGELES VET AFFAIRS MED CTR,MED SERV,DIABET RES LAB,LOS ANGELES,CA 90073. RP Ribalet, B (reprint author), UNIV CALIF LOS ANGELES,SCH MED,DEPT PHYSIOL,LOS ANGELES,CA 90024, USA. FU NIDDK NIH HHS [R01-DK-46616] NR 37 TC 26 Z9 26 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD FEB PY 1996 VL 107 IS 2 BP 231 EP 241 DI 10.1085/jgp.107.2.231 PG 11 WC Physiology SC Physiology GA TY125 UT WOS:A1996TY12500006 PM 8833343 ER PT J AU Matulonis, U Dosiou, C Freeman, G Lamont, C Mauch, P Nadler, LM Griffin, LD AF Matulonis, U Dosiou, C Freeman, G Lamont, C Mauch, P Nadler, LM Griffin, LD TI B7-1 is superior to B7-2 costimulation in the induction and maintenance of T cell-mediated antileukemia immunity - Further evidence that B7-1 and B7-2 are functionally distinct SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ACTIVATION ANTIGEN-B7; COUNTER-RECEPTOR; TUMOR REJECTION; EXPRESSION; CTLA-4; IDENTIFICATION; PROLIFERATION; MOLECULES; RNA AB Although intact, viable tumor cells rarely induce a clinically significant immune response in vivo, immunogenicity can be elicited by irradiated tumor cells that protect against subsequent challenge with wild-type intact viable tumor cells. Genetic modification of murine tumor cells, by transfection of cDNAs encoding either cytokines, MHC molecules, or costimulatory molecules, has been capable of inducing antitumor immunity, We and others have previously demonstrated that expression of the B7-1 costimulatory molecule, in either immunogenic or nonimmunogenic tumors, can protect against subsequent challenge with wild-type tumor cells. In this work, using a murine model of acute myeloid leukemia, we demonstrate that the B7-1 costimulatory molecule is superior to the B7-2 molecule in its capacity to protect against wild-type tumor challenge and eradicate minimal residual disease. These results provide compelling evidence that the B7-1 and B7-2 costimulatory signals are functionally distinct, thus resulting in clinically significant differences in the induction of antitumor immunity in vivo. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP Matulonis, U (reprint author), DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA66996, CA34183, CA47843] NR 23 TC 144 Z9 146 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 1 PY 1996 VL 156 IS 3 BP 1126 EP 1131 PG 6 WC Immunology SC Immunology GA TR327 UT WOS:A1996TR32700031 PM 8557988 ER PT J AU Merrill, DP Moonis, M Chou, TC Hirsch, MS AF Merrill, DP Moonis, M Chou, TC Hirsch, MS TI Lamivudine or stavudine in two- and three-drug combinations against human immunodeficiency virus type 1 replication in vitro SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID RECOMBINANT INTERFERON-ALPHA; REVERSE-TRANSCRIPTASE; SYNERGISTIC INHIBITION; IN-VITRO; PHASE-I; INVITRO; ZIDOVUDINE; RESISTANCE; POTENT; HIV AB Two- and three-drug combinations of lamivudine or stavudine with other antiretroviral drugs were evaluated for activity against human immunodeficiency virus type 1 (HIV-1) activity in peripheral blood mononuclear cells, Other agents included zidovudine, didanosine, nevirapine, and saquinavir. Paired zidovudine-sensitive and -resistant clinical HIV-1 isolates were used, Additive or synergistic interactions were observed against the zidovudine-sensitive isolate with the following combinations: lamivudine-zidovudine, lamivudine-stavudine, lamivudine-saquinavir, lamivudine-nevirapine, stavudine-zidovudine, stavudine-didanosine, stavudine-saquinavir, stavudine-nevirapine, lamivudine-zidovudine-saquinavir, lamivudine-zidovudine-stavudine, stavudine-zidovudine-nevirapine, lamivudine-zidovudine-nevirapine, and stavudine-zidovudine-saquinavir. Against the zidovudine-resistant isolate, additive or synergistic interactions were seen with most two- and three-drug combinations, but the combination of stavudine-zidovudine was antagonistic, The clinical implications of these in vitro observations should be explored. C1 HARVARD UNIV,INFECT DIS UNIT,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114. MEM SLOAN KETTERING CANC CTR,BIOCHEM PHARMACOL LAB,NEW YORK,NY 10021. RI Chou, Ting-Chao/B-4111-2009 OI Chou, Ting-Chao/0000-0002-3340-1594 FU FIC NIH HHS [TW-00004]; NCI NIH HHS [CA-12464]; NIAID NIH HHS [AI-32350] NR 54 TC 84 Z9 84 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 FEB PY 1996 VL 173 IS 2 BP 355 EP 364 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA TT665 UT WOS:A1996TT66500011 PM 8568296 ER PT J AU Harrer, E Harrer, T Barbosa, P Feinberg, M Johnson, RP Buchbinder, S Walker, BD AF Harrer, E Harrer, T Barbosa, P Feinberg, M Johnson, RP Buchbinder, S Walker, BD TI Recognition of the highly conserved YMDD region in the human immunodeficiency virus type 1 reverse transcriptase by HLA-A2-restricted cytotoxic T lymphocytes from an asymptomatic long-term nonprogressor SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID INHIBITORS; RESISTANT; THERAPY; CELLS AB The human immunodeficiency virus (HIV) type 1 reverse transcriptase (RT) is an important target for therapeutic intervention and for HIV-1-specific cytotoxic T lymphocytes (CTL), An HLA-A2-restricted CTL epitope containing the sequence YMDD, which is highly conserved among human and animal retroviruses and essential for function of the RNA-dependent DNA polymerase, is identified, The drug resistance mutation at RT amino acid 184 (M184V), associated with (-)-2'-deoxy-3'-thiacytidine (lamivudine), (-)-2'-deoxy-5-fluoro-3'-thiacytidine (FTC), and dideoxyinosine resistance, is located within this epitope and abolishes recognition by an established CTL response, This study demonstrates that the CTL response may target functionally relevant regions of the RT protein and suggests drug therapy may select for viral variants with altered susceptibility to established cellular immune responses. C1 MASSACHUSETTS GEN HOSP,AIDS RES CTR & INFECT DIS UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. UNIV CALIF SAN FRANCISCO,GLADSTONE INST,SAN FRANCISCO,CA. UNIV CALIF SAN FRANCISCO,CTR AIDS RES,SAN FRANCISCO,CA. DEPT PUBL HLTH,AIDS OFF,SAN FRANCISCO,CA. FU NIAID NIH HHS [AI-28568] NR 16 TC 64 Z9 64 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 FEB PY 1996 VL 173 IS 2 BP 476 EP 479 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA TT665 UT WOS:A1996TT66500031 PM 8568316 ER PT J AU Goldmann, WH Ezzell, RM Adamson, ED Niggli, V Isenberg, G AF Goldmann, WH Ezzell, RM Adamson, ED Niggli, V Isenberg, G TI Vinculin, talin and focal adhesions SO JOURNAL OF MUSCLE RESEARCH AND CELL MOTILITY LA English DT Article ID ROUS-SARCOMA VIRUS; EMBRYO FIBROBLASTS; ALPHA-ACTININ; CHICKEN VINCULIN; PLASMA-MEMBRANE; CELL-ADHESION; PHOSPHORYLATION; BINDING; PROTEIN; EXPRESSION C1 UNIV BERN,DEPT PATHOL,CH-3010 BERN,SWITZERLAND. TECH UNIV MUNICH,D-85747 GARCHING,GERMANY. BURNHAM FDN,LA JOLLA,CA 92037. RP Goldmann, WH (reprint author), HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,SURG RES LAB,BOSTON,MA 02129, USA. RI Goldmann, Wolfgang/H-5572-2013 NR 51 TC 30 Z9 30 U1 0 U2 1 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0142-4319 J9 J MUSCLE RES CELL M JI J. Muscle Res. Cell Motil. PD FEB PY 1996 VL 17 IS 1 BP 1 EP 5 DI 10.1007/BF00140319 PG 5 WC Cell Biology SC Cell Biology GA UJ188 UT WOS:A1996UJ18800001 PM 8740427 ER PT J AU Phillips, KA Nierenberg, AA Brendel, G Fava, M AF Phillips, KA Nierenberg, AA Brendel, G Fava, M TI Prevalence and clinical features of body dysmorphic disorder in atypical major depression SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article ID IMAGINED UGLINESS C1 BROWN UNIV,SCH MED,DEPT PSYCHIAT & HUMAN BEHAV,PROVIDENCE,RI 02912. MASSACHUSETTS GEN HOSP,DEPRESS RES PROGRAM,BOSTON,MA 02114. HARVARD UNIV,SCH MED,CONSOLIDATED DEPT PSYCHIAT,BOSTON,MA. RP Phillips, KA (reprint author), BUTLER HOSP,345 BLACKSTONE BLVD,PROVIDENCE,RI 02906, USA. NR 23 TC 70 Z9 71 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 FEB PY 1996 VL 184 IS 2 BP 125 EP 129 DI 10.1097/00005053-199602000-00012 PG 5 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA TZ002 UT WOS:A1996TZ00200012 PM 8596110 ER PT J AU Prence, EM Chaturvedi, P Newburg, DS AF Prence, EM Chaturvedi, P Newburg, DS TI In vitro accumulation of glucocerebroside in neuroblastoma cells: A model for study of Gaucher disease pathobiology SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE glycosphingolipids; beta-glucosidase; SH-SY5Y cells; neuronal cells ID INHIBITION; MACROPHAGES; MOUSE; GENE AB Gaucher disease is the most common lysosomal glycosphingolipid storage disease; decreased activity of glucosylceramide beta-glucosidase (GCase) results in the accumulation of glucocerebroside (GlcCer) in macrophage-derived cells, The most devastating types of Gaucher disease also involve neuronopathology, thought to be mediated by intracellular GlcCer accumulation in the brain, In this study, we developed an in vitro neuronal cell model for accumulation of endogenous GlcCer to enable studies on the cellular basis for the neuronopathology of this disease. A human neuroblastoma cell line (SH-SY5Y) was selected because it produced appreciable GCase, When these cells were treated with conduritol B epoxide (CBE), a competitive, irreversible inhibitor of this enzyme, GCase levels fell precipitously, while other lysosomal hydrolase levels were unaffected. Relative to untreated control cells, the CBE-treated cells accumulated higher levels of GlcCer, but not other related glycolipids, over time. Thus, this in vitro system displayed many essential biological parameters relevant for studies on cellular events responsible for the neurologic damage that occurs in some types of Gaucher disease, This model should also be useful in investigations of the normal role of sphingolipids in neuronal cell function. (C) 1996 Wiley-Liss, Inc. C1 EUNICE KENNEDY SHRIVER CTR MENTAL RETARDAT INC,DEPT BIOCHEM,WALTHAM,MA 02254. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RP Prence, EM (reprint author), EUNICE KENNEDY SHRIVER CTR MENTAL RETARDAT INC,DIV MED GENET,200 TRAPELO RD,WALTHAM,MA 02254, USA. FU NICHD NIH HHS [HD13021] NR 32 TC 10 Z9 10 U1 0 U2 7 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD FEB 1 PY 1996 VL 43 IS 3 BP 365 EP 371 DI 10.1002/(SICI)1097-4547(19960201)43:3<365::AID-JNR11>3.0.CO;2-4 PG 7 WC Neurosciences SC Neurosciences & Neurology GA TT530 UT WOS:A1996TT53000011 PM 8714525 ER PT J AU Tanaka, M Lee, K MartinezAugustin, O He, Y Sanderson, IR Walker, WA AF Tanaka, M Lee, K MartinezAugustin, O He, Y Sanderson, IR Walker, WA TI Exogenous nucleotides alter the proliferation, differentiation and apoptosis of human small intestinal epithelium SO JOURNAL OF NUTRITION LA English DT Article DE apoptosis; AMP; proliferation; TUNEL assay; humans ID PROGRAMMED CELL-DEATH; DIETARY NUCLEOTIDES; CHLORIDE SECRETION; HISTONE GENE; TRANSPORT; NUCLEOSIDES AB The turnover of intestinal epithelial cells is a finely regulated process extending from undifferentiated crypt stem cells to terminally differentiated villus cells. The final phase of this maturation process is apoptosis and extrusion. Recent studies have shown that programmed cell death (PCD) occurs not only in senescent cells and in rapidly developing tissues but also in response to cellular stress preventing damaged cells from entering uncontrolled proliferation without repair. This study examined the role of exogenous nucleotides on cell proliferation, differentiation and apoptosis in organ cultures of human fetal small intestine. The addition of adenosine monophosphate (AMP), a putative stress reactant, to the culture media resulted in the suppression of crypt cell proliferation followed by the restoration of differentiation and the induction of apoptosis across a broad range of villus epithelium when compared with controls without added nucleotide. In contrast, the addition to cytidine monophosphate (CMP) to the culture media did not increase apoptosis, despite the nucleotide being taken up by the fetal small intestine in a similar dose- and time-dependent manner to AMP. Furthermore, Bar mRNA, an Apoptosis-inducer gene, was increased with addition of AMP, suggesting that the induction of apoptosis may be channeled through the p53 pathway. These results suggest that a specific exogenous nucleotide, AMP, may have an important role in controlling the dynamic balance of cellular turnover in the developing human small intestine. C1 HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,COMBINED PROGRAM PEDIAT GASTROENTEROL & NUTR,BOSTON,MA 02114. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. RI Martinez Augustin, Olga/K-6720-2014 OI Martinez Augustin, Olga/0000-0001-8291-3468 FU NICHD NIH HHS [HD-12437, HD-31852]; NIDDK NIH HHS [DK-40561] NR 47 TC 33 Z9 40 U1 0 U2 1 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3166 J9 J NUTR JI J. Nutr. PD FEB PY 1996 VL 126 IS 2 BP 424 EP 433 PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA TU525 UT WOS:A1996TU52500008 PM 8632215 ER PT J AU LaMontagne, AD Mangione, TW Christiani, DC Kelsey, KT AF LaMontagne, AD Mangione, TW Christiani, DC Kelsey, KT TI Medical surveillance for ethylene oxide exposure: Practices and clinical findings in Massachusetts hospitals SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID ADMINISTRATIONS 1990-1991 SURVEY; COGNITIVE DYSFUNCTION; SAFETY; WORKPLACE; POLYNEUROPATHY; NEUROTOXICITY; PREVALENCE; MORTALITY; INDUSTRY; DISEASE AB The medical surveillance requirements of the Occupational Safety and Health Administration's (OSHA) ethylene oxide (EtO) standard became effective in 1985. However, little is known about the nature of the response of EtO users to this regulatory requirement. In an effort to begin to understand this, we conducted a survey of EtO health and safety in Massachusetts hospitals (n = 92). We determined the cumulative incidence of provision of EtO medical surveillance, the characteristics of the surveillance interventions provided, and the clinical findings of EtO medical surveillance efforts in Massachusetts hospitals. From 1985 to 1993 medical surveillance for EtO exposure was provided one or more times in 62% of EtO-using hospitals. Sixty-five percent of EtO medical surveillance providers reported performance of all five medical surveillance procedures required by OSHA's EtO standard. Medical surveillance provider certification in occupational medicine or nursing, and a greater extent of coverage of written medical surveillance policies, were related to higher likelihoods of fulfillment of OSHA-required procedures. Twenty-seven percent of medical surveillance providers reported detection of EtO-related symptoms or conditions, ranging from mucous membrane irritation to peripheral neuropathy. These findings reveal widespread implementation of OSHA-mandated EtO medical surveillance, with concomitant incomplete fulfillment of OSHA-specified procedures. From the provider-based survey, we estimate that one or more workers at 19% of EtO-using Massachusetts hospitals have experienced EtO-related health effects. C1 JOHN SNOW INC,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,PULM & CRIT CARE UNIT,DEPT MED,BOSTON,MA. HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,BOSTON,MA 02115. RP LaMontagne, AD (reprint author), HARVARD UNIV,SCH PUBL HLTH,OCCUPAT HLTH PROGRAM,665 HUNTINGTON AVE,BOSTON,MA 02115, USA. RI Kelsey, Karl/I-1252-2014 FU NIEHS NIH HHS [T32 ES 07069, ES00002]; NIOSH CDC HHS [R03OH03088-01] NR 52 TC 12 Z9 12 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1076-2752 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD FEB PY 1996 VL 38 IS 2 BP 144 EP 154 DI 10.1097/00043764-199602000-00012 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA TY108 UT WOS:A1996TY10800008 PM 8673519 ER PT J AU Kravitz, RL Delafield, JP Hays, RD Drazin, R Conolly, M AF Kravitz, RL Delafield, JP Hays, RD Drazin, R Conolly, M TI Bedside charting of pain levels in hospitalized patients with cancer: A randomized controlled trial SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE cancer pain; pain measurement; physician behavior quality of care; randomized controlled trial ID INSTRUMENT AB Despite advances in the technology of cancer pain assessment and control, cancer pain often remains undertreated even in hospital settings. To determine whether a graphical display of cancer patients' pain levels might improve their treatment, the investigators conducted a randomized controlled trial. Patients assigned to the intervention group (N = 40) had periodic pain assessments by study staff who graphically recorded their reported pain-intensity levels on bedside wall charts. Control group patients (N = 38) had periodic pain assessments by study staff but did not have this information displayed. The resulted failed to show a significant beneficial effect of the intervention on pain control, sleep, cancer-related symptoms, or analgesic dosing, but confidence intervals were broad. More research is needed to improve the quality of care for inpatients with cancer-related pain. C1 W LOS ANGELES VET AFFAIRS MED CTR,DIV GEN INTERNAL MED,LOS ANGELES,CA 90073. DEPT SOCIAL POLICY,SANTA MONICA,CA. UNIV CALIF LOS ANGELES,DEPT HLTH SERV,LOS ANGELES,CA. SCI CONSULTANTS IND,LOS ANGELES,CA. UNIV CALIF LOS ANGELES,DEPT MED,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,DEPT ANESTHESIOL,LOS ANGELES,CA 90024. RP Kravitz, RL (reprint author), UNIV CALIF DAVIS,DEPT MED,SACRAMENTO,CA 95817, USA. RI Hays, Ronald/D-5629-2013; OI Kravitz, Richard/0000-0001-5575-529X NR 16 TC 25 Z9 25 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 1996 VL 11 IS 2 BP 81 EP 87 DI 10.1016/0885-3924(95)00155-7 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA TY118 UT WOS:A1996TY11800003 PM 8907138 ER PT J AU Frueh, BC Smith, DW Libet, JM AF Frueh, BC Smith, DW Libet, JM TI Racial differences on psychological measures in combat veterans seeking treatment for PTSD SO JOURNAL OF PERSONALITY ASSESSMENT LA English DT Article; Proceedings Paper CT 9th Annual Meeting of the International-Society-for-Traumatic-Stress-Studies CY OCT 24-27, 1993 CL SAN ANTONIO, TX SP Int Soc Traumat Stress Studies ID POSTTRAUMATIC-STRESS-DISORDER; VIETNAM VETERANS; PSYCHOPHYSIOLOGICAL RESPONSES; MMPI; VALIDITY; SYMPTOMS; RELIABILITY; DIAGNOSIS; EXPOSURE; BLACK AB In this article, we examined racial differences in psychometric data on 4 commonly used self-report inventories administered to a group of 206 combat veterans evaluated at a Veterans Affairs Medical Center outpatient posttraumatic stress disorder (PTSD) treatment program. Patients completed the Beck Depression Inventory, Mississippi Scale for Combat-Related PTSD, Dissociative Experiences Scale (DES), and Minnesota Multiphasic Personality Inventory-2 (MMPI-2). Black veterans showed greater elevations than White veterans on the DES, and the F-K index and Scales 6 and 8 of the MMPI-2. In addition, normative data are presented for the entire sample on each measure. Results suggest that, consistent with studies using the original MMPI, these patients endorse severe levels of psychopathology across a broad range of symptoms, including depression and disturbed thinking. Implications for clinical practice and future research are addressed. C1 MED UNIV S CAROLINA,DEPT PSYCHIAT & BEHAV SCI,CHARLESTON,SC 29425. UNIV ARKANSAS,FAYETTEVILLE,AR 72701. RP Frueh, BC (reprint author), RALPH H JOHNSON VET AFFAIRS MED CTR,PSYCHOL SERV 116B,109 BEE ST,CHARLESTON,SC 29401, USA. NR 42 TC 30 Z9 30 U1 1 U2 1 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 SN 0022-3891 J9 J PERS ASSESS JI J. Pers. Assess. PD FEB PY 1996 VL 66 IS 1 BP 41 EP 53 DI 10.1207/s15327752jpa6601_3 PG 13 WC Psychology, Clinical; Psychology, Social SC Psychology GA TQ293 UT WOS:A1996TQ29300003 PM 8576834 ER PT J AU Gogas, KR Levine, JD Basbaum, AI AF Gogas, KR Levine, JD Basbaum, AI TI Differential contribution of descending controls to the antinociceptive actions of kappa and mu opioids, an analysis of formalin-evoked c-fos expression SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID RAT SPINAL-CORD; PROTEIN-LIKE IMMUNOREACTIVITY; DORSAL HORN; NOR-BINALTORPHIMINE; SELECTIVE AGONIST; RECEPTOR SUBTYPES; ELECTRICAL-STIMULATION; OPIATE RECEPTORS; CROSS-TOLERANCE; MORPHINE AB In this study, the effect of intracerebroventricular (icv) administration of (5R)-(5 alpha,7 alpha,8 beta)-N-methyl-N-[7-(1-pyrrolindinyl)-1-oxaspiro[4,5]dec-8-yl]-4-benzofurnacetamide monohydrochloride (Cl-977) on pain behaviors and on spinal cord fos-like immunoreactivity (FLl) evoked by unilateral formalin injection into the hindpaw of rats was examined. Intracerebroventricular administration of Cl-977 (0.13-13.00 nmol) produced a dose-dependent inhibition of formalin-evoked pain behaviors, with significant inhibition after 1.30, 4.40 and 13.00 nmol. The estimated ED(50) for icv Cl-977 inhibition of formalin-evoked behaviors was 0.95 nmol and the E(max) was 53%. The inhibitory effect of 4.40 nmol of icv Cl-977 on formalin-evoked behaviors was prevented by either pretreatment with the kappa selective antagonist nor-binaltorphimine (10 or 100 nmol) or coadministration of the opiate receptor antagonist, naloxone (30 nmol). The lowest dose of icv Cl-977 tested (0.13 nmol) produced a 50% reduction in FLl in the superficial laminae but did not inhibit the expression of FLl in any other regions of the spinal cord. The fos-inhibitory effect of low-dose icy Cl-977 in the superficial cord was reversed by coadministration of naloxone (30 nmol). Higher doses of icy Cl-977 that suppressed formalin-evoked behaviors did not inhibit the expression of FLl in any region of the spinal cord. Finally, neither the inhibitory effect of 4.40 nmol Cl-977 on formalin-evoked behaviors nor the formalin-evoked pattern of FLl expression in the spinal cord of rats treated with this dose of Cl-977 was affected by lesions of the dorsolateral funiculus. These results provide the first evidence that supraspinal kappa receptor-mediated antinociception is not dependent on the integrity of the dorsolateral funiculus and may be mediated exclusively at the supraspinal level, suggesting that there are multiple mechanisms through which opioids can evoke antinociceptive effects. C1 UNIV CALIF SAN FRANCISCO,DEPT ANAT,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,DEPT PHYSIOL,SAN FRANCISCO,CA. UNIV CALIF SAN FRANCISCO,DEPT MED,SAN FRANCISCO,CA. UNIV CALIF SAN FRANCISCO,W M KECK FDN CTR INTEGRAT NEUROSCI,SAN FRANCISCO,CA. MASSACHUSETTS GEN HOSP,DEPT MOLEC & DEV NEUROSCI,BOSTON,MA. FU NIDA NIH HHS [DA 08377]; NINDS NIH HHS [NS21445] NR 61 TC 31 Z9 33 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD FEB PY 1996 VL 276 IS 2 BP 801 EP 809 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TV378 UT WOS:A1996TV37800058 PM 8632353 ER PT J AU Lee, WPA Idler, RS AF Lee, WPA Idler, RS TI Functional transfer of pronator quadratus free flap for thenar muscle loss SO JOURNAL OF RECONSTRUCTIVE MICROSURGERY LA English DT Article ID TRANSPLANTATION AB A case of functional replacement for traumatic thenar muscle loss using an innervated pronator quadratus free flap is reported. The pronator quadratus matched the damaged thenar muscle in size and excursion and provided satisfactory thumb opposition in long-term follow-up. RP Lee, WPA (reprint author), HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,DIV PLAST SURG,AMBULATORY CARE CTR 453,BOSTON,MA 02114, USA. NR 12 TC 3 Z9 3 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 381 PARK AVE SOUTH, NEW YORK, NY 10016 SN 0743-684X J9 J RECONSTR MICROSURG JI J. Reconstr. Microsurg. PD FEB PY 1996 VL 12 IS 2 BP 77 EP 80 DI 10.1055/s-2007-1006457 PG 4 WC Surgery SC Surgery GA TY918 UT WOS:A1996TY91800003 PM 8656404 ER PT J AU Lapidus, CS Sutula, FC Stadecker, MJ Vine, JE Grande, DJ AF Lapidus, CS Sutula, FC Stadecker, MJ Vine, JE Grande, DJ TI Angiosarcoma of the eyelid: Yellow plaques causing ptosis SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID SOFT-TISSUE; CUTANEOUS ANGIOSARCOMA; HEPATIC ANGIOSARCOMA; FACE; LYMPHANGIOSARCOMA; SARCOMAS; SCALP; HEAD; NECK C1 TUFTS UNIV,SCH MED,DEPT DERMATOL,BOSTON,MA 02111. MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,BOSTON,MA 02114. TUFTS UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02111. UNIV TEXAS,HLTH SCI CTR,DEPT DERMATOL,HOUSTON,TX. LAHEY CLIN FDN,DEPT DERMATOL,BURLINGTON,MA. RP Lapidus, CS (reprint author), BOSTON UNIV,SCH MED,DEPT DERMATOL,609 ALBANY ST,BOSTON,MA 02118, USA. NR 23 TC 11 Z9 11 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD FEB PY 1996 VL 34 IS 2 BP 308 EP 310 DI 10.1016/S0190-9622(96)80145-9 PN 1 PG 3 WC Dermatology SC Dermatology GA TV697 UT WOS:A1996TV69700025 PM 8642103 ER PT J AU DiSalvo, TG Paul, SD LloydJones, D Smith, AJC VillarrealLevy, G Bamezai, V Hussain, SI Eagle, KA OGara, PT AF DiSalvo, TG Paul, SD LloydJones, D Smith, AJC VillarrealLevy, G Bamezai, V Hussain, SI Eagle, KA OGara, PT TI Care of acute myocardial infarction by noninvasive and invasive cardiologists: Procedure use, cost and outcome SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID NEW-YORK-STATE; CORONARY ANGIOPLASTY; IMMEDIATE; SPECIALTY; DISEASE; ASTHMA AB Objectives. This study sought to determine how noninvasive and invasive cardiologists may differ in the hospital care of patients with acute myocardial infarction. Background. Scant information exists regarding the effect of noninvasive and invasive cardiology subspecialization on invasive cardiac procedural use, cost and outcome in the care of patients with acute myocardial infarction. Methods. This study analyzed a prospective cohort of 292 patients admitted to an urban tertiary care hospital from the emergency room under the care of noninvasive or invasive cardiologists. Clinical characteristics; hospital course, including management, utilization of diagnostic coronary angiography and percutaneous transluminal coronary angioplasty; direct hospital costs; length of hospital stay; and post hospital discharge follow-up data were collected by a prospective data base instrument. Conclusions. Noninvasive and invasive cardiologists differ in their rate of utilization of coronary angioplasty in similar patients with acute myocardial infarction. C1 BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. UNIV MICHIGAN,MED CTR,ANN ARBOR,MI. RP DiSalvo, TG (reprint author), MASSACHUSETTS GEN HOSP,MGH HEART FAILURE CTR,BULFINCH 211,32 FRUIT ST,BOSTON,MA 02114, USA. RI Lloyd-Jones, Donald/C-5899-2009 NR 33 TC 20 Z9 20 U1 3 U2 3 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 FEB PY 1996 VL 27 IS 2 BP 262 EP 269 DI 10.1016/0735-1097(95)00488-2 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA TR890 UT WOS:A1996TR89000002 PM 8557892 ER PT J AU Foster, GP Weissman, NJ Picard, MH Fitzpatrick, PJ Shubrooks, SJ Zarich, SW AF Foster, GP Weissman, NJ Picard, MH Fitzpatrick, PJ Shubrooks, SJ Zarich, SW TI Determination of aortic valve area in valvular aortic stenosis by direct measurement using intracardiac echocardiography: A comparison with the gorlin and continuity equations SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID ORIFICE AREA; DOPPLER ECHOCARDIOGRAPHY; ULTRASOUND; CATHETER; ADULTS; QUANTIFICATION; EXPERIENCE; MORPHOLOGY; DISEASE; SIZE AB Objectives. This study sought to 1) show that intracardiac echocardiography can allow direct measurement of the aortic valve area, and 2) compare the directly measured aortic valve area from intracardiac echocardiography with the calculated aortic valve area from the Gorlin and continuity equations. Background. Intracardiac echocardiography has been used in the descriptive evaluation of the aortic valve; however, direct measurement of the aortic valve area using this technique in a clinical setting has not been documented. Despite their theoretical and practical limitations, the Gorlin and continuity equations remain the current standard methods for determining the aortic valve orifice area. Methods. Seventeen patients underwent intracardiac echocardiography for direct measurement of the aortic valve area, including four patients studied both before and after valvuloplasty, for a total of 21 studies. Immediately after intracardiac echocardiography, hemodynamic data were obtained from transthoracic echocardiography and cardiac catheterization. Results. Adequate intracardiac echocardiographic images were obtained in 17 (81%) of 21 studies. The average aortic valve area (mean +/- SD) determined by intracardiac echocardiography for the 13 studies in the Gorlin analysis group was 0.59 +/- 0.18 cm(2) (range 0.37 to 1.01), and the average aortic valve area determined by the Gorlin equation was 0.62 +/- 0.18 cm(2) (range 0.31 to 0.88). The average aortic valve area determined by intracardiac echo cardiography for the 17 studies in the continuity analysis group was 0.66 +/- 0.23 cm(2) (range 0.37 to 1.01), and that for the continuity equation was 0.62 +/- 0.22 cm(2) (range 0.34 to 1.06). There was a significant correlation between the aortic valve area determined by intracardiac echocardiography and the aortic valve area calculated by the Gorlin (r = 0.78, p = 0.002) and continuity equations (r = 0.82, p < 0.0001). Conclusions. In the clinical setting, intracardiac echocardiography can directly measure the aortic valve area with an accuracy similar to the invasive and noninvasive methods currently used. This study demonstrates a new, quantitative use for intracardiac echocardiographic imaging with many potential clinical applications. C1 DEACONESS HOSP,DIV CARDIOVASC,BOSTON,MA. RP Foster, GP (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CARDIAC ULTRASOUND LAB,VBK508,32 FRUIT ST,BOSTON,MA 02114, USA. OI Picard, Michael/0000-0002-9264-3243 NR 29 TC 23 Z9 23 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 FEB PY 1996 VL 27 IS 2 BP 392 EP 398 DI 10.1016/0735-1097(95)00462-9 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA TR890 UT WOS:A1996TR89000021 PM 8557911 ER PT J AU Norling, LL TufroMcReddie, A Gomez, RA Moore, LC Kaskel, FJ AF Norling, LL TufroMcReddie, A Gomez, RA Moore, LC Kaskel, FJ TI Accumulation of acidic renin isoforms in kidneys of cyclosporine-A-treated rats SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article DE prorenin; arteriolopathy; renin processing; nephrotoxicity ID ISOELECTRIC HETEROGENEITY; PROTEINS; SECRETION; FORMS AB Chronic cyclosporin A (CsA) treatment results in major hemodynamic changes in the renal microvasculature and in expression of the intrarenal renin angiotensin system. Changes in renin expression in kidneys of CsA-treated rats include the recruitment of immunoreactive renin in afferent arterioles and in the juxtaglomerular apparatus. This study presents evidence that an acidic isoform of renin is increased in kidneys of CsA-treated rats. Immunoblots of rat kidney homogenate separated by polyacrylamide-gel electrophoresis and also by isoelectric focusing demonstrate the presence of an acidic isoform (pi 5.5 and estimated molecular weight of approximately 32 to 36 kd) seen in increased amounts in kidney homogenate from CsA-treated rats. Silver- stained two-dimensional gels of renin separated from kidney homogenate with pepstatin agarose confirm the presence of an acidic renin isoform in CsA-treated rats. In rats that received CsA for varied intervals of 1, 3, 5, and 8 wk, this acidic isoform is shown to significantly accumulate relative to duration of treatment with CsA when immunoreactive bands are analyzed by densitometric scanning (r(2) = 0.90, P < 0.001). Renin enzymatic activity also increased in kidney homogenate of CsA-treated rats relative to duration of treatment with CsA (r(2) = 0.486, P < 0.001). Prorenin in these same samples was significantly decreased compared with controls. The acidic renin isoform identified in kidney homogenate of CsA-treated rats may be involved in the vascular changes that are seen in this model. C1 SUNY STONY BROOK,HLTH SCI CTR,DEPT PEDIAT,STONY BROOK,NY 11794. MASSACHUSETTS GEN HOSP,PEDIAT NEPHROL UNIT,BOSTON,MA 02114. UNIV VIRGINIA,HLTH SCI CTR,DEPT PEDIAT,CHARLOTTESVILLE,VA. SUNY STONY BROOK,HLTH SCI CTR,DEPT PHYSIOL & BIOPHYS,STONY BROOK,NY 11794. SUNY STONY BROOK,HLTH SCI CTR,DEPT PHYSIOL,STONY BROOK,NY 11794. SUNY STONY BROOK,HLTH SCI CTR,DEPT BIOPHYS,STONY BROOK,NY 11794. FU NICHD NIH HHS [HD28810]; NIDDK NIH HHS [KO8DK02048, DK26341] NR 31 TC 8 Z9 8 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD FEB PY 1996 VL 7 IS 2 BP 331 EP 337 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA TZ306 UT WOS:A1996TZ30600021 PM 8785405 ER PT J AU Rich, JA Holmes, MD Hodges, DM AF Rich, JA Holmes, MD Hodges, DM TI Preferred sources of AIDS information, risk perceptions, and risk behaviors among inner-city community college students SO JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION LA English DT Article DE acquired immunodeficiency syndrome (AIDS); inner-city college students; AIDS risk perceptions ID SEXUAL-BEHAVIOR; PERCEIVED RISK; KNOWLEDGE; ADOLESCENTS; ATTITUDES; DETERMINANTS; PREVENTION; PROGRAM; BELIEFS AB To understand preferred sources of acquired immunodeficiency syndrome (AIDS) information and level of worry about human immunodeficiency virus (HIV) among community college students, a survey of 102 students in an inner-city community college was conducted. The survey requested information on preferred sources of information about AIDS, risk behaviors, and level of worry about HIV infection compared with other life risks. Forty-six per cent of respondents had engaged in risk behaviors for AIDS. Of those who were sexually active, 81% acknowledged not always using a condom. Students noted that they were more likely to believe AIDS information from a health professional than from a friend, relative, teacher, clergy, or celebrity. Overall, getting AIDS ranked third on a list of life worries, ranking only behind getting bad grades and the death of a family member. For students who identified themselves as black or Latino, however, getting AIDS ranked first on a list of life risks. For those students who reported highrisk behavior for getting HIV, getting AIDS also ranked first on a list of life worries. We conclude that those students at whom messages about risk status have been targeted are most likely to report being more worried about getting AIDS than about other adverse life events. It remains unclear, however, whether heightened levels of worry about HIV actually translate into changes in risk behavior. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,BOSTON,MA. RI Rich, John/I-2002-2013 NR 18 TC 7 Z9 7 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0027-9684 J9 J NATL MED ASSOC JI J. Natl. Med. Assoc. PD FEB PY 1996 VL 88 IS 2 BP 87 EP 93 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA TV066 UT WOS:A1996TV06600007 PM 8776063 ER PT J AU delaMonte, SM Xu, YY Hutchins, GM Wands, JR AF delaMonte, SM Xu, YY Hutchins, GM Wands, JR TI Developmental patterns of neuronal thread protein gene expression in Down syndrome SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article DE neuronal thread protein; Down syndrome; Alzheimer's disease; central nervous system; neurofilament protein ID ALZHEIMERS-DISEASE; SECRETORY PROTEIN; DEMENTIA; BRAIN AB Neuronal thread proteins (NTP) are a group of immunologically related molecules expressed in brain and neuroectodermal tumor cell lines, NTP gene expression is up-regulated and NTP molecules accumulate in Alzheimer's disease (AD) brains, pathological states associated with regenerative neuritic sprouting, and during brain development. To investigate the role of NTP over-expression in AD, we examined NTP immunoreactivity in brains from differently aged individuals with Down syndrome, since patients with Down syndrome nearly always develop AD neuropathology and dementia, using SMI monoclonal antibodies to neurofilament protein, we detected age-associated increases in neurofilament immunoreactive (SMI-positive) neurites in Layers I and II of the cerebral cortex beginning at 1. year of age, followed by SMI-positive neurofibrillary tangles beginning at age 5 years, and then SMI-positive plaques beginning in the third decade. Increased NTP immunoreactivity in Down syndrome brains began in the second decade, prior to establishment of widespread AD neurodegeneration (Down syndrome + AD), and at an age when low-level or absent NTP expression was observed in control brains. Analysis of SDS and Triton X-100-treated histological sections and tissue extracts demonstrated that a largely insoluble, denaturation-resistant form of NTP accumulates in both Down syndrome + AD and AD brains, The findings provide further evidence that abnormal NTP expression and accumulation in brain may be an early marker of AD neurodegeneration in Down syndrome. C1 HARVARD UNIV,SCH MED,DEPT MED,ALZHEIMERS DIS RES CTR,DIV NEUROPATHOL,BOSTON,MA 02129. JOHNS HOPKINS MED INST,DEPT PATHOL,BALTIMORE,MD 21205. RP delaMonte, SM (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,MGH E CANC CTR,ROOM 7308,149 13TH ST,BOSTON,MA 02129, USA. NR 29 TC 17 Z9 17 U1 2 U2 2 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 FEB PY 1996 VL 135 IS 2 BP 118 EP 125 DI 10.1016/0022-510X(95)00257-3 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA TY109 UT WOS:A1996TY10900004 PM 8867067 ER PT J AU Shipp, TD Shamberger, RC Benacerraf, BR AF Shipp, TD Shamberger, RC Benacerraf, BR TI Prenatal diagnosis of a grade IV sacrococcygeal teratoma SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article ID MANAGEMENT AB Sacrococcygeal teratomas occur in approximately one per 40,000 births and are the most common congenital tumors in the newborn.(1) Most sacrococcygeal teratomas are external and extend outward from the lower part of the sacrum and buttock. While the majority of these tumors are external, a small number of internal sacrococcygeal teratomas are almost completely presacral with no external presentation. Although most of these tumors are solid or mixed solid and cystic, a small number are cystic. We present the prenatal diagnosis of a mixed solid and cystic presacral teratoma and describe its sonographic appearance, differential diagnosis, management, and outcome. C1 MASSACHUSETTS GEN HOSP,DEPT OBSTET & GYNECOL,BOSTON,MA 02114. BRIGHAM & WOMENS HOSP,DEPT OBSTET & GYNECOL,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT RADIOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,CHILDRENS HOSP,SCH MED,DEPT SURG,BOSTON,MA 02115. NR 9 TC 6 Z9 6 U1 0 U2 0 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD FEB PY 1996 VL 15 IS 2 BP 175 EP 177 PG 3 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA TR356 UT WOS:A1996TR35600015 PM 8622198 ER PT J AU Gallay, P Stitt, V Mundy, C Oettinger, M Trono, D AF Gallay, P Stitt, V Mundy, C Oettinger, M Trono, D TI Role of the karyopherin pathway in human immunodeficiency virus type 1 nuclear import SO JOURNAL OF VIROLOGY LA English DT Article ID INFECTED-CELLS; PROTEIN; VIRIONS; LOCALIZATION; HIV-1; DNA AB The interaction of the human immunodeficiency virus type 1 (HIV-1) nucleoprotein complex with the cell nuclear import machinery is necessary for viral replication in macrophages and for the establishment of infection in quiescent T lymphocytes. The karyophilic properties of two viral proteins, matrix (MA) and Vpr, are keys to this process. Here, we show that an early step of HIV-1 nuclear import is the recognition of the MA nuclear localization signal (NLS) by Rch1, a member of the karyopherin-alpha family. Furthermore, we demonstrate that an N-terminally truncated form of Rch1 which binds MA but fails to localize to the nucleus efficiently blocks MA- but not Vpr-mediated HIV-1 nuclear import. Correspondingly, NLS peptide inhibits the nuclear migration of MA but not that of Vpr and prevents the infection of terminally differentiated macrophages by vpr-defective virus but not wild-type virus. These results are consistent with a model in which Rch1 or another member of the karyopherin-alpha family, through the recognition of the MA NLS, participates in docking the HIV-1 nucleoprotein complex at the nuclear pore, In addition, our data suggest that Vpr governs HIV-1 nuclear import through a distinct pathway. C1 SALK INST BIOL STUDIES,INFECT DIS LAB,LA JOLLA,CA 92037. MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. FU NIAID NIH HHS [AI37510]; NIGMS NIH HHS [GM48026] NR 47 TC 216 Z9 219 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 FEB PY 1996 VL 70 IS 2 BP 1027 EP 1032 PG 6 WC Virology SC Virology GA TP526 UT WOS:A1996TP52600042 PM 8551560 ER PT J AU Trkola, A Purtscher, M Muster, T Ballaun, C Buchacher, A Sullivan, N Srinivasan, K Sodroski, J Moore, JP Katinger, H AF Trkola, A Purtscher, M Muster, T Ballaun, C Buchacher, A Sullivan, N Srinivasan, K Sodroski, J Moore, JP Katinger, H TI Human monoclonal antibody 2G12 defines a distinctive neutralization epitope on the gp120 glycoprotein of human immunodeficiency virus type 1 SO JOURNAL OF VIROLOGY LA English DT Article ID DEPENDENT CELLULAR CYTOTOXICITY; HTLV-III LAV; ENVELOPE GLYCOPROTEIN; T-CELL; MEDIATED CYTOTOXICITY; INFECTED-CELLS; CD4 BINDING; HIV-1; SERA; SITE AB We have isolated and characterized human monoclonal antibody 2G12 to the gp120 surface glycoprotein of human immunodeficiency virus type 1 (HIV-1). This antibody patently and broadly neutralizes primary and T-cell line-adapted clade B strains of HIV-1 in a peripheral blood mononuclear cell-based assay and inhibits syncytium formation in the AA-2 cell line. Furthermore, 2G12 possesses neutralizing activity against strains from clade A but not from clade E. Complement- and antibody-dependent cellular cytotoxicity-activating functions of 2G12 were also defined. The gp120 epitope recognized by 2G12 was found to be distinctive; binding of 2G12 to LAI recombinant gp120 was abolished by amino acid substitutions removing N-linked carbohydrates in the C2, C3, V4, and C4 regions of gp120. This gp120 mutant recognition pattern has not previously been observed, indicating that the 2G12 epitope is unusual. Consistent with this, antibodies able to block 2G12 binding to recombinant gp120 mere not detected in significant quantities in 16 HIV-positive human serum samples. C1 AGR UNIV VIENNA,INST APPL MICROBIOL,A-1190 VIENNA,AUSTRIA. HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HUMAN RETROVIROL,DEPT PATHOL,BOSTON,MA 02115. RP Trkola, A (reprint author), NYU,SCH MED,AARON DIAMOND AIDS RES CTR,455 1ST AVE,NEW YORK,NY 10016, USA. RI Trkola, Alexandra/K-2115-2012 OI Trkola, Alexandra/0000-0003-1013-876X FU NIAID NIH HHS [N01 AI35168, R01 AI25541, R01 AI36082] NR 66 TC 821 Z9 840 U1 2 U2 20 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 1996 VL 70 IS 2 BP 1100 EP 1108 PG 9 WC Virology SC Virology GA TP526 UT WOS:A1996TP52600051 PM 8551569 ER PT J AU Pascual, M TolkoffRubin, N Schifferli, JA AF Pascual, M TolkoffRubin, N Schifferli, JA TI Is adsorption an important characteristic of dialysis membranes? SO KIDNEY INTERNATIONAL LA English DT Editorial Material RP Pascual, M (reprint author), MASSACHUSETTS GEN HOSP,RENAL UNIT,JACKSON 825,BOSTON,MA 02114, USA. NR 0 TC 43 Z9 45 U1 2 U2 2 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD FEB PY 1996 VL 49 IS 2 BP 309 EP 313 DI 10.1038/ki.1996.47 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA TR103 UT WOS:A1996TR10300002 PM 8821812 ER PT J AU Lewandowski, ED Doumen, C White, LT LaNoue, KF Damico, LA Yu, X AF Lewandowski, ED Doumen, C White, LT LaNoue, KF Damico, LA Yu, X TI Multiplet structure of (13)G NMR signal from glutamate and direct detection of tricarboxylic acid (TCA) cycle intermediates SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE carbon-13; isotopomers; NMR spectroscopy; tricarboxylic acid cycle ID NUCLEAR-MAGNETIC-RESONANCE; INTACT HEARTS; C-13; FLUX; SPECTROSCOPY AB For the first time,C-13 NMR signals are shown from C-13-enriched, low-level tricarboxylic acid (TCA) cycle intermediates from extracts of normal cardiac tissue, As the low tissue content of the key intermediates alpha-ketoglutarate (alpha-KG) and succinate (SUC) in normal, well perfused tissues has until now precluded direct NMR detection from intact tissues and tissue extracts, C-13 NMR Signal from glutamate has generally been used to infer the isotopomer patterns of intermediates that are in chemical exchange with glutamate, However, the required assumptions regarding intracellular compartmentation for such indirect analysis have not been previously tested, as glutamate is largely cytosolic while the TCA cycle enzymes are located in the mitochondria. Chromatographic isolation of alpha-KG and SUC from heart tissue extracts allowed isotopomer analysis to be performed for comparison with that of glutamate, At steady state, a direct relationship between glutamate and alpha-ketoglutarate isotopomers was found, but succinate isotopomers matched those of glutamate only in hearts that displayed negligible contributions from the oxidation of unlabeled endogenous carbon sources. C1 PENN STATE UNIV,HERSHEY MED CTR,DEPT PHYSIOL,HERSHEY,PA. RP Lewandowski, ED (reprint author), HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,NMR CTR,DEPT RADIOL,BLDG 149,13TH ST,BOSTON,MA 02129, USA. FU NHLBI NIH HHS [R01HL49244] NR 15 TC 28 Z9 28 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0740-3194 J9 MAGNET RESON MED JI Magn.Reson.Med. PD FEB PY 1996 VL 35 IS 2 BP 149 EP 154 DI 10.1002/mrm.1910350203 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA TT422 UT WOS:A1996TT42200002 PM 8622576 ER PT J AU Hamberg, LM Boccalini, P Stranjalis, G Hunter, GJ Huang, ZH Halpern, E Weisskoff, RM Moskowitz, MA Rosen, BR AF Hamberg, LM Boccalini, P Stranjalis, G Hunter, GJ Huang, ZH Halpern, E Weisskoff, RM Moskowitz, MA Rosen, BR TI Continuous assessment of relative cerebral blood volume in transient ischemia using steady state susceptibility-contrast MRI SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE cerebral blood volume; magnetic resonance imaging; contrast agent; cerebral ischemia ID MAGNETIC-SUSCEPTIBILITY; COMPUTED-TOMOGRAPHY; BRAIN; HYPEREMIA; AGENT; SCAN; FLOW; CATS; NMR AB The utility of a noninvasive steady state susceptibility-contrast MRI technique for continuous measurement of relative cerebral blood volume (rCBV) during global transient ischemia and subsequent hyperemia in a feline ischemia model is demonstrated, The measurements were obtained during a 10-min period of occlusion and l-h period of reperfusion, Maximal hyperemic responses in gray matter, basal ganglia, and white matter (observed at 7, 7, and 5 min, respectively) were 1.9 +/- 0.5, 1.8 +/- 0.3, and 1.7 +/- 0.6 times greater than baseline CBV (mean +/- SEM), Thirty to forty minutes after onset of reperfusion, CBV returned to normal, Thereafter, it decreased below baseline, nearing the control level by 1 h after onset of reperfusion, Steady state susceptibility-contrast MRI permits continuous, in vivo mapping of alterations in CBV. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,MHG,NMR CTR,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,DEPT NEUROL,STROKE RES LAB,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,NEUROSURG SERV,BOSTON,MA. RP Hamberg, LM (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,CIPR,BOSTON,MA 02129, USA. RI Moskowitz, Michael/D-9916-2011 NR 26 TC 64 Z9 65 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0740-3194 J9 MAGNET RESON MED JI Magn.Reson.Med. PD FEB PY 1996 VL 35 IS 2 BP 168 EP 173 DI 10.1002/mrm.1910350207 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA TT422 UT WOS:A1996TT42200006 PM 8622580 ER PT J AU Asch, DA Christakis, NA AF Asch, DA Christakis, NA TI Why do physicians prefer to withdraw some forms of life support over others? Intrinsic attributes of life-sustaining treatments are associated with physicians' preferences SO MEDICAL CARE LA English DT Article DE critical care; decision making; life support care; ethics; euthanasia; methodology ID DECISION-MAKING; EUTHANASIA; ATTITUDES; MODELS; ILL AB Some physicians caring for critically ill patients have preferences for withdrawing some forms of life support over others, even after the decision to withdraw life support has already been made. Past research has attempted to explain these preferences by variations in clinical circumstances. The authors wondered whether differences in the forms of life support themselves might be important, and whether these differences would reveal implicit goals that physicians attempt to achieve. Four hundred fifty-six university-affiliated internists were surveyed and their rank-ordered preferences for withdrawing eight different forms of life support were assessed. The authors then sought to explain these preferences on the basis of intrinsic characteristics of the eight forms of life support determined by an expert panel of critical care physicians. In general, the physicians studied prefer to withdraw forms of life support that are scarce, expensive, invasive, artificial, unnatural, emotionally taxing, high technology, and rapidly fatal when withdrawn. They prefer not to withdraw forms of therapy that require continuous rather than intermittent administration, and forms of therapy that cause pain when withdrawn. Even when a decision has been made to withdraw life-sustaining treatment from a patient, many physicians have preferences for the manner in which this is accomplished. These preferences may reflect perceived intrinsic characteristics of different forms of life support that are consistent across physicians. C1 VET AFFAIRS MED CTR,GEN INTERNAL MED SECT,PHILADELPHIA,PA. UNIV PENN,LEONARD DAVIS INST HLTH ECON,PHILADELPHIA,PA 19104. UNIV CHICAGO,DEPT SOCIOL,CHICAGO,IL 60637. UNIV CHICAGO,GEN INTERNAL MED SECT,CHICAGO,IL 60637. RP Asch, DA (reprint author), UNIV PENN,SCH MED,DIV GEN INTERNAL MED,317 RALSTONPENN CTR,3615 CHESTNUT ST,PHILADELPHIA,PA 19104, USA. RI Christakis, Nicholas/B-6690-2008; Christakis, Nicholas/C-3205-2009 NR 25 TC 54 Z9 55 U1 1 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0025-7079 J9 MED CARE JI Med. Care PD FEB PY 1996 VL 34 IS 2 BP 103 EP 111 DI 10.1097/00005650-199602000-00002 PG 9 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA TU795 UT WOS:A1996TU79500002 PM 8632684 ER PT J AU Maggard, MA Catlin, EA Hudson, PL Donahoe, PK MacLaughlin, DT AF Maggard, MA Catlin, EA Hudson, PL Donahoe, PK MacLaughlin, DT TI Reduction of epidermal growth factor receptor phosphorylation by activated mullerian inhibiting substance is vanadate-sensitive SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID DUCT REGRESSION; A431 CELLS; GRANULOSA-CELLS; TERMINAL DOMAIN; OOCYTE MEIOSIS; TUMOR-GROWTH; INVITRO; FETAL; HORMONE; SERTOLI AB The carboxy-terminal domain of recombinant human Mullerian inhibiting substance (MIS) inhibits cellular proliferation in vitro and decreases epidermal growth factor (EGF)-dependent phosphorylation of the EGF receptor. Proteolytically cleaved and undissociated MIS is more potent than carboxy-terminal MIS alone, supporting a functional role for the amino-terminal region of the molecule. MIS does not block EGF binding to the EGF receptor, thus, MIS reduction of EGF receptor phosphorylation must occur distal to receptor ligand binding, The effect of proteolytically cleaved MIS on reduction of EGF receptor phosphorylation in membrane preparations is decreased by a specific phosphatase inhibitor, vanadate, thus implicating a membrane phosphatase in this MIS action at the EGF receptor. (C) 1996 by W.B. Saunders Company C1 MASSACHUSETTS GEN HOSP,PEDIAT SURG RES LAB,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,PEDIAT SURG SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,NEONATOL UNIT,CHILDRENS SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. FU FDA HHS [FD-R-000669]; NCI NIH HHS [CA-17393]; NHLBI NIH HHS [R29-HL46198] NR 36 TC 5 Z9 5 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD FEB PY 1996 VL 45 IS 2 BP 190 EP 195 DI 10.1016/S0026-0495(96)90052-9 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TV615 UT WOS:A1996TV61500010 PM 8596488 ER PT J AU Tsai, EY Jain, J Pesavento, PA Rao, A Goldfeld, AE AF Tsai, EY Jain, J Pesavento, PA Rao, A Goldfeld, AE TI Tumor necrosis factor alpha gene regulation in activated T cells involves ATF-2/Jun and NFATp SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ELEMENT-BINDING PROTEIN; NUCLEAR FACTOR; NF-AT; TRANSCRIPTION FACTORS; CYCLOSPORINE-A; LYMPHOCYTES-T; PROMOTER; JUN; IDENTIFICATION; FAMILY AB The human tumor necrosis fatter alpha (TNF-alpha) gene is one of the earliest genes expressed upon the activation of a T or B cell through its antigen receptor. Previous experiments have demonstrated that in stimulated T cells, a TNF-alpha promoter element, k3, which binds NFATp, is required for the cyclosporin A-sensitive transcriptional activation of the gene. Here, we demonstrate that a cyclic AMP response element (CRE), which lies immediately upstream of the k3 site, is also required for induction of TNF-alpha gene transcription in T cells stimulated by calcium ionophore or T-cell receptor ligands. The CRE binds ATF-2 and Jun proteins in association with NFATp bound to k3. These proteins bind noncooperatively in vitro; however, the transcriptional activity of the CRE/k3 composite site is dramatically higher than the activity of the k3 site alone, indicating that the two sites cooperate in vivo. This study is the first demonstration of a role for ATF-2 in TNF-alpha gene transcription and of a functional interaction between ATF-2/Jun and NFATp. This novel pairing of NFATp with ATF-2/Jun may account for the specific and immediate pattern of TNF-alpha gene transcription in stimulated T cells. C1 DANA FARBER CANC INST,DEPT MED,INFECT DIS LAB,BOSTON,MA 02115. DANA FARBER CANC INST,DIV CELLULAR & MOLEC BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. FU NCI NIH HHS [CA-58735, CA42471]; NIGMS NIH HHS [GM46227] NR 46 TC 214 Z9 217 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD FEB PY 1996 VL 16 IS 2 BP 459 EP 467 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA TQ233 UT WOS:A1996TQ23300001 PM 8552071 ER PT J AU Berditchevski, F Zutter, MM Hemler, ME AF Berditchevski, F Zutter, MM Hemler, ME TI Characterization of novel complexes on the cell surface between integrins and proteins with 4 transmembrane domains (TM4 proteins) SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID MEMBRANE-SPANNING DOMAINS; LEUKEMIA-VIRUS TYPE-1; MONOCLONAL-ANTIBODIES; SYNCYTIUM FORMATION; MOLECULAR-CLONING; T-CELLS; ENDOTHELIAL-CELLS; INCLUDING CD9; C33 ANTIGEN; ADHESION AB Here we identified several new integrin/TM4 protein complexes on the cell surface. By immunoprecipitation using nonstringent conditions, and by reciprocal immunoprecipitation, we found that alpha(3) beta(1) and alpha(6) beta(1) integrins but not alpha(2) beta(1), alpha(5) beta(1) or alpha(6) beta(4) integrins associated with CD9 and CD81 in alpha(3) beta(1)/CD81, alpha(3) beta(1)/CD9, alpha(6) beta(1)/CD81, and alpha(6) beta(1)/CD9 complexes. Also, cross-linking experiments established that alpha(3) beta(1)/CD81, alpha(3) beta(1)/CD9, and alpha(3) beta(1)/CD63 associations occur on the surface of intact cells and suggested that a critical interaction site is located within extracellular domains. Cross-linking in conjunction with reimmunoprecipitation indicated that larger multi-component alpha(3) beta(1)/TM4/TM4 complexes (alpha(3) beta(1)/CD9/CD63, alpha(3) beta(1)/CD81/CD63, and alpha(3) beta(1)/CD9/CD81) also could be detected on the cell surface. Immunofluorescent staining showed redistribution of alpha(3) beta(1)/TM4 complexes toward the periphery of cells plated on various extracellular matrix substrates and also showed that these complexes were localized in cell footprints. Staining of human tissues yielded additional results consistent with co-localization of alpha(3) beta(1) and CD9, CD63, and CD81 proteins. In conclusion we suggest that the prevalence of integrin/TM4 complexes in diverse cellular environments is indicative of their general physiological importance. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. WASHINGTON UNIV,SCH MED,ST LOUIS,MO 63110. FU NIGMS NIH HHS [GM-38903] NR 49 TC 237 Z9 239 U1 1 U2 4 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD FEB PY 1996 VL 7 IS 2 BP 193 EP 207 PG 15 WC Cell Biology SC Cell Biology GA TV789 UT WOS:A1996TV78900001 PM 8688552 ER PT J AU Kovacs, DM Fausett, HJ Page, KJ Kim, TW Moir, RD Merriam, DE Hollister, RD Hallmark, OG Mancini, R Felsenstein, KM Hyman, BT Tanzi, RE Wasco, W AF Kovacs, DM Fausett, HJ Page, KJ Kim, TW Moir, RD Merriam, DE Hollister, RD Hallmark, OG Mancini, R Felsenstein, KM Hyman, BT Tanzi, RE Wasco, W TI Alzheimer-associated presenilins 1 and 2: Neuronal expression in brain and localization to intracellular membranes in mammalian cells SO NATURE MEDICINE LA English DT Article ID BETA-PROTEIN PRECURSOR; DISEASE AB Mutations in two recently identified genes appear to cause the majority of early-onset familial Alzheimer's disease (FAD). These two novel genes, presenilin 1 (PS1) and presenilin 2 (PS2) are members of an evolutionarily conserved gene family. The normal biological role(s) of the presenilins and the mechanism(s) by which the FAD-associated mutations exert their effect remain unknown. Employing in situ hybridization, we demonstrate that the expression patterns of PS1 and PS2 in the brain are extremely similar to each other and that messages for both are primarily detectable in neuronal populations. Immunochemical analyses indicate that PS1 and PS2 are similar in size and localized to similar intracellular compartments (endoplasmic reticulum and Golgi complex). FAD-associated mutations in PS1 and PS2 do not significantly modify either their migration patterns on SDS-polyacrylamide gel electrophoresis or their overall subcellular localization, although subtle differences in perinuclear staining were noted for mutant PS1. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP EAST,SCH MED,GENET & AGING UNIT,BOSTON,MA 02129. HARVARD UNIV,MASSACHUSETTS GEN HOSP EAST,SCH MED,DEPT NEUROL,BOSTON,MA 02129. BRISTOL MYERS SQUIBB CO,DEPT 405,WALLINGFORD,CT 06492. NR 24 TC 486 Z9 497 U1 1 U2 14 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1078-8956 J9 NAT MED JI Nat. Med. PD FEB PY 1996 VL 2 IS 2 BP 224 EP 229 DI 10.1038/nm0296-224 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA TU060 UT WOS:A1996TU06000044 PM 8574969 ER PT J AU Alpert, NM Berdichevsky, D Levin, Z Morris, ED Fischman, AJ AF Alpert, NM Berdichevsky, D Levin, Z Morris, ED Fischman, AJ TI Improved methods for image registration SO NEUROIMAGE LA English DT Article ID AUTOMATED ALGORITHM; PET AB We report a system for PET-MRI registration that is improved or optimized in several areas: (1) Automatic scalp/brain segmentation replaces manual drawing operations, (2) a new fast and accurate method of image registration, (3) visual assessment of registration quality is enhanced by composite imaging methods (i.e., fusion) and (4) the entire procedure is embedded in a commercially available scientific visualization package, thereby providing a consistent graphical user interface. The segmentation algorithm was tested on 17 MRI data sets and was successful in all cases. Accuracy of image registration was equal to that of the Woods algorithm, but 10 times faster for PET-PET and 4 times faster for PET-MRI. The image fusion method allows detection of misalignments on the order of 2-3 mm. These results demonstrate an integrated system for intermodality image registration, which is important because the procedure can be performed by technicians with no anatomic knowledge and reduces the required time from hours to about 15 min on a modern computer workstation. (C) 1996 Academic Press, Inc. RP Alpert, NM (reprint author), MASSACHUSETTS GEN HOSP,DIV NUCL MED,PET IMAGING LAB,FRUIT ST,BOSTON,MA 02114, USA. FU NCI NIH HHS [2T32CA09362] NR 16 TC 77 Z9 77 U1 0 U2 7 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD FEB PY 1996 VL 3 IS 1 BP 10 EP 18 DI 10.1006/nimg.1996.0002 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA TY638 UT WOS:A1996TY63800002 PM 9345471 ER PT J AU Weber, AL Dallow, RL Sabates, NR AF Weber, AL Dallow, RL Sabates, NR TI Graves' disease of the orbit SO NEUROIMAGING CLINICS OF NORTH AMERICA LA English DT Article ID COMPUTED-TOMOGRAPHY; OPHTHALMOPATHY; DIAGNOSIS; FEATURES AB Graves' disease, the most common orbital disorder, affects approximately 0.5% of the population of the United States. It is the underlying cause in 15% to 28% of cases of unilateral exophthalmos and in 80% of cases with bilateral exophthalmos. Also called ''thyroid-associated ophthalmopathy,'' ''autoimmune thyroid disease,'' ''endocrine exophthalmos,'' and ''thyroid eye disease,'' Graves' disease presents with enlargement of the extraocular muscles, increased orbital fat volume, and venous stasis caused by increased orbital pressure. This article discusses the clinical evaluation and radiologic findings of this common orbital disorder. C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT RADIOL,BOSTON,MA 02114. UNIV MISSOURI,SCH MED,EYE FDN KANSAS CITY,KANSAS CITY,MO. NR 34 TC 11 Z9 13 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 1052-5149 J9 NEUROIMAG CLIN N AM JI Neuroimaging Clin. N. Am. PD FEB PY 1996 VL 6 IS 1 BP 61 EP & PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA UN741 UT WOS:A1996UN74100005 PM 8919134 ER PT J AU Weber, AL Jakobiec, FA Sabates, NR AF Weber, AL Jakobiec, FA Sabates, NR TI Pseudotumor of the orbit SO NEUROIMAGING CLINICS OF NORTH AMERICA LA English DT Article ID TOLOSA-HUNT SYNDROME; WEGENERS GRANULOMATOSIS; INTRACRANIAL EXTENSION; PAINFUL OPHTHALMOPLEGIA; BONE DESTRUCTION; SARCOIDOSIS; MYOSITIS; INVOLVEMENT; DISEASE; MANIFESTATIONS AB Pseudotumor of the third most common ophthalmologic disease after Graves' disease and lymphoproliferative disease. It is usually a continuous illness, although recurrent forms do occur, especially in the pediatric age group. The radiologic evaluation consists of computed tomography and magnetic resonance imaging. The imaging findings, correlated with the clinical findings, allow a diagnosis in most cases and, hence, obviate the need for a biopsy. C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT RADIOL,BOSTON,MA 02114. UNIV MISSOURI,EYE FDN KANSAS CITY,KANSAS CITY,MO 64110. NR 71 TC 12 Z9 13 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 1052-5149 J9 NEUROIMAG CLIN N AM JI Neuroimaging Clin. N. Am. PD FEB PY 1996 VL 6 IS 1 BP 73 EP & PG 21 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA UN741 UT WOS:A1996UN74100006 PM 8919135 ER PT J AU Weber, AL Jakobiec, FA Sabates, NR AF Weber, AL Jakobiec, FA Sabates, NR TI Lymphoproliferative disease of the orbit SO NEUROIMAGING CLINICS OF NORTH AMERICA LA English DT Article ID LYMPHOMATOID GRANULOMATOSIS; LYMPHOID NEOPLASMS; OCULAR ADNEXA; MANIFESTATIONS; INVOLVEMENT; PLASMACYTOMAS; HYPERPLASIA; CONJUNCTIVA; LEUKEMIA; SOLITARY AB Lymphoproliferative disease of the orbit represents a diverse group of lesions affecting various soft tissue structures within the orbital cavity. They are one of the most common disease entities encountered in orbital pathology and frequently present with proptosis or anterior tumefactive swelling in the lids, conjunctiva, and lacrimal glands. For elucidation of the underlying cause, computed tomography and magnetic resonance imaging are the optimal imaging modalities. C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT RADIOL,BOSTON,MA 02114. UNIV MISSOURI,EYE FDN KANSAS CITY,KANSAS CITY,MO 64110. NR 51 TC 20 Z9 20 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 1052-5149 J9 NEUROIMAG CLIN N AM JI Neuroimaging Clin. N. Am. PD FEB PY 1996 VL 6 IS 1 BP 93 EP & PG 20 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA UN741 UT WOS:A1996UN74100007 PM 8919136 ER PT J AU Warner, MA Weber, AL Jakobiec, FA AF Warner, MA Weber, AL Jakobiec, FA TI Benign and malignant tumors of the orbital cavity including the lacrimal gland SO NEUROIMAGING CLINICS OF NORTH AMERICA LA English DT Review ID NERVE SHEATH TUMORS; GRANULAR-CELL MYOBLASTOMA; FIBROUS HISTIOCYTOMA; COMPUTED-TOMOGRAPHY; NEURO-BLASTOMA; RHABDOID TUMOR; MESENCHYMAL CHONDROSARCOMA; CLINICAL CHARACTERISTICS; RADIOLOGICAL FINDINGS; MELANOMA AB Computed tomography and magnetic resonance imaging are of utmost importance and utility in the diagnosis and surgical approach to orbital neoplasia. Computed tomography delineates bony structures and areas of calcification, whereas magnetic resonance imaging provides information regarding lesion composition and extent of disease. The clinical presentation, general histology, and imaging characteristics of common and uncommon orbital tumors are discussed. C1 HARVARD UNIV,SCH MED,DEPT OPHTHALMOL,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT RADIOL,BOSTON,MA 02115. MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,BOSTON,MA 02114. MASSACHUSETTS EYE & EAR INFIRM,DEPT RADIOL,BOSTON,MA 02114. NR 106 TC 14 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 1052-5149 J9 NEUROIMAG CLIN N AM JI Neuroimaging Clin. N. Am. PD FEB PY 1996 VL 6 IS 1 BP 123 EP & PG 22 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA UN741 UT WOS:A1996UN74100009 PM 8919138 ER PT J AU Weber, AL Klufas, R Pless, M AF Weber, AL Klufas, R Pless, M TI Imaging evaluation of the optic nerve and visual pathway - Including cranial nerves affecting the visual pathway SO NEUROIMAGING CLINICS OF NORTH AMERICA LA English DT Review ID NEUROFIBROMATOSIS TYPE-1; CHIASMAL SYNDROME; ORBITAL MENINGIOMA; MR FINDINGS; LONG-TERM; GLIOMA; LESIONS; SUPRASELLAR; NEURITIS; TUMORS AB The radiologic investigation of the optic pathways has an integral part in the diagnostic evaluation of diverse lesions, such as inflammatory disease, vascular disorders, and benign and malignant tumors that afflict the optic pathways. These radiologic methods consist principally of computed tomography and magnetic resonance imaging, and, in vascular lesions, magnetic resonance angiography and conventional angiography. C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT RADIOL,BOSTON,MA 02114. BRIGHAM & WOMENS HOSP,DEPT NEURORADIOL,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT NEUROOPHTHALMOL,BOSTON,MA 02115. NR 161 TC 13 Z9 17 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 1052-5149 J9 NEUROIMAG CLIN N AM JI Neuroimaging Clin. N. Am. PD FEB PY 1996 VL 6 IS 1 BP 143 EP & PG 36 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA UN741 UT WOS:A1996UN74100010 PM 8919139 ER PT J AU Weber, AL RodriguezDeVelasquez, A Lucarelli, MJ Cheng, HM AF Weber, AL RodriguezDeVelasquez, A Lucarelli, MJ Cheng, HM TI Normal anatomy and lesions of the lacrimal sac and duct - Evaluated by dacryocystography, computed tomography, and MR imaging SO NEUROIMAGING CLINICS OF NORTH AMERICA LA English DT Review ID SQUAMOUS-CELL CARCINOMA; DRAINAGE; TUMORS; SCINTILLOGRAPHY; MELANOMA; EPIPHORA; SYSTEM; SINUS AB Abnormalities of the lacrimal drainage system are common ophthalmologic problems. Patients usually present with epiphora, swelling, or a mass in the lacrimal sac area. This article provides a survey of the anatomic and pathologic findings of the lacrimal drainage system, with an emphasis on radiologic indications, methods, and findings. C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT RADIOL,BOSTON,MA 02114. NR 121 TC 29 Z9 33 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 1052-5149 J9 NEUROIMAG CLIN N AM JI Neuroimaging Clin. N. Am. PD FEB PY 1996 VL 6 IS 1 BP 199 EP & PG 20 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA UN741 UT WOS:A1996UN74100012 PM 8919141 ER PT J AU Lustrin, ES Brown, JH Novelline, R Weber, AL AF Lustrin, ES Brown, JH Novelline, R Weber, AL TI Radiologic assessment of trauma and foreign bodies of the eye and orbit SO NEUROIMAGING CLINICS OF NORTH AMERICA LA English DT Article ID BLOW-IN FRACTURES; COMPUTED-TOMOGRAPHY; INTRAORBITAL WOOD; OPTIC NEUROPATHY; CT; DIAGNOSIS AB The detection and definition of orbital trauma is a frequent clinical problem. Therefore, the radiologic assessment is crucial. This article discusses the radiologic techniques and types of injuries that occur to the orbit. C1 LONG ISL JEWISH MED CTR,ALBERT EINSTEIN COLL MED,DEPT RADIOL,NEW HYDE PK,NY 10467. NYU,HOSP JOINT DIS,SCH MED,DEPT RADIOL,NEW YORK,NY 10003. HARVARD UNIV,SCH MED,DEPT RADIOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. NR 43 TC 11 Z9 12 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 1052-5149 J9 NEUROIMAG CLIN N AM JI Neuroimaging Clin. N. Am. PD FEB PY 1996 VL 6 IS 1 BP 219 EP & PG 20 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA UN741 UT WOS:A1996UN74100013 PM 8919142 ER PT J AU Rubin, PAD Remulla, HD AF Rubin, PAD Remulla, HD TI Surgical methods and approaches in the treatment of orbital disease SO NEUROIMAGING CLINICS OF NORTH AMERICA LA English DT Article ID NEEDLE ASPIRATION BIOPSY; GRAVES-DISEASE; CORALLINE HYDROXYAPATITE; OPTIC NEUROPATHY; DECOMPRESSION; OPHTHALMOPATHY; IMPLANT; TUMORS; FAT; REMOVAL AB Many orbital disorders require surgical intervention to establish the diagnosis or to provide the basis for planning the appropriate surgical procedure in these selected cases. The indications for biopsy versus complete surgical excision of orbital lesions are outlined. The nature of the specific techniques, including fine-needle aspiration biopsy, endoscopic biopsy, anterior orbitotemy, lateral orbitotomy, and multidisciplinary combined approaches to the orbit is discussed. Separate sections, with an emphasis on clinical radiographic correlates, are devoted to the commonly encountered surgical disorders: thyroid orbital decompression and acquired anophthalmia (evisceration, enucleation, and exenteration). C1 MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT OPHTHALMOL,BOSTON,MA. NR 68 TC 8 Z9 8 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 1052-5149 J9 NEUROIMAG CLIN N AM JI Neuroimaging Clin. N. Am. PD FEB PY 1996 VL 6 IS 1 BP 239 EP & PG 19 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA UN741 UT WOS:A1996UN74100014 PM 8919143 ER PT J AU Weber, AL AF Weber, AL TI Imaging of the globe, orbit, and visual pathway - Preface SO NEUROIMAGING CLINICS OF NORTH AMERICA LA English DT Editorial Material C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT RADIOL,BOSTON,MA 02114. 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 1052-5149 J9 NEUROIMAG CLIN N AM JI Neuroimaging Clin. N. Am. PD FEB PY 1996 VL 6 IS 1 BP R15 EP R16 PG 2 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA UN741 UT WOS:A1996UN74100001 ER PT J AU Sandson, TA Price, BH AF Sandson, TA Price, BH TI Diagnostic testing and dementia SO NEUROLOGIC CLINICS LA English DT Review ID POSITRON EMISSION TOMOGRAPHY; NORMAL-PRESSURE HYDROCEPHALUS; PROGRESSIVE SUPRANUCLEAR PALSY; PROBABLE ALZHEIMERS-DISEASE; WHITE-MATTER LESIONS; MAGNETIC-RESONANCE SPECTROSCOPY; MULTI-INFARCT DEMENTIA; TEMPORAL-LOBE ATROPHY; IMAGING PROCEDURE CT; CEREBRAL BLOOD-FLOW AB The prevalence of dementia is expected to increase markedly as our population ages. Although only a minority of cases currently are found to have treatable causes, the personal and financial costs of misdiagnosis are great. Furthermore, progress in developing effective therapy hinges on accurate diagnosis. This article reviews the current state of diagnostic testing in the diagnosis of dementia. C1 HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. MCLEAN HOSP,BELMONT,MA 02178. RP Sandson, TA (reprint author), BETH ISRAEL HOSP,BEHAV NEUROL UNIT,330 BROOKLINE AVE,BOSTON,MA 02215, USA. NR 146 TC 9 Z9 9 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0733-8619 J9 NEUROL CLIN JI Neurol. Clin. PD FEB PY 1996 VL 14 IS 1 BP 45 EP & DI 10.1016/S0733-8619(05)70242-5 PG 16 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA TW877 UT WOS:A1996TW87700004 PM 8676848 ER PT J AU Lippa, CF Saunders, AM Smith, TW Swearer, JM Drachman, DA Ghetti, B Nee, L PulaskiSalo, D Dickson, D Robitaille, Y Bergeron, C Crain, B Benson, MD Farlow, M Hyman, BT StGeorgeHyslop, P Roses, AD Pollen, DA AF Lippa, CF Saunders, AM Smith, TW Swearer, JM Drachman, DA Ghetti, B Nee, L PulaskiSalo, D Dickson, D Robitaille, Y Bergeron, C Crain, B Benson, MD Farlow, M Hyman, BT StGeorgeHyslop, P Roses, AD Pollen, DA TI Familial and sporadic Alzheimer's disease: Neuropathology cannot exclude a final common pathway SO NEUROLOGY LA English DT Article ID PRECURSOR PROTEIN GENE; MIS-SENSE MUTATION; APOLIPOPROTEIN-E; SENILE DEMENTIA; MISSENSE MUTATION; CEREBRAL-CORTEX; TYPE-4 ALLELE; APP GENE; LOCUS; CHROMOSOME-14 AB Whether all etiologic forms of Alzheimer's disease (AD) share a final common pathway is a major issue, We determined the severity and regional distribution of neuronal loss, amyloid plaques, neuritic plaques (NPs), and neurofibrillary tangles (NFTs), and calculated the ratio of neuronal loss to NPs and NFTs in brains of 19 familial AD (FAD) patients with linkage to chromosome 14, six AD patients with mutations of chromosome 21 (codon 717 of the beta-amyloid precursor protein gene), and 11 sporadic AD (SAD) patients, There was no difference in the pattern of distribution of the various pathologic features or in the ratio of neuronal loss to NPs or NFTs in any AD group, However, FAD groups could be distinguished from SAD by the greater severity and the lack of influence of apolipoprotein E genotype on pathology, These differences may reflect differences in age at onset rather than different etiopathologic mechanisms, The similarity of pathologic findings in the different AD groups provides evidence for a final common pathophysiologic pathway in AD. C1 UNIV MASSACHUSETTS,MED CTR,DEPT NEUROL,WORCESTER,MA 01655. UNIV MASSACHUSETTS,MED CTR,DEPT PATHOL,WORCESTER,MA. INDIANA UNIV,MED CTR,DEPT PATHOL,INDIANAPOLIS,IN. INDIANA UNIV,MED CTR,DEPT MED & MOLEC GENET,INDIANAPOLIS,IN. INDIANA UNIV,MED CTR,DEPT MED,INDIANAPOLIS,IN. INDIANA UNIV,MED CTR,DEPT NEUROL,INDIANAPOLIS,IN. RICHARD L ROUDEBUSH VET AFFAIRS MED CTR,INDIANAPOLIS,IN 46202. NIH,DEPT NEUROL,BETHESDA,MD 20892. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. UNIV MONTREAL,DEPT PATHOL,MONTREAL,PQ H3C 3J7,CANADA. UNIV TORONTO,TORONTO,ON,CANADA. DUKE UNIV,DEPT NEUROL,DURHAM,NC. ALBERT EINSTEIN COLL MED,DEPT PATHOL,BRONX,NY 10467. JOHNS HOPKINS UNIV,DEPT PATHOL,BALTIMORE,MD 21205. OI Dickson, Dennis W/0000-0001-7189-7917 FU NIA NIH HHS [AG-10133, AG-05134, AG-70922] NR 70 TC 75 Z9 77 U1 1 U2 3 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD FEB PY 1996 VL 46 IS 2 BP 406 EP 412 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA TZ712 UT WOS:A1996TZ71200019 PM 8614503 ER PT J AU Bashir, R Chamberlain, M Ruby, E Hochberg, FH AF Bashir, R Chamberlain, M Ruby, E Hochberg, FH TI T-cell infiltration of primary CNS lymphoma SO NEUROLOGY LA English DT Article; Proceedings Paper CT 47th Annual Meeting of the American-Academy-of-Neurology CY MAY, 1995 CL SEATTLE, WA SP Amer Acad Neurol ID NERVOUS-SYSTEM LYMPHOMA; EPSTEIN-BARR-VIRUS; IMMUNE-DEFICIENCY-SYNDROME; INSITU HYBRIDIZATION; ADHESION MOLECULE-1; BRAIN; EXPRESSION; AIDS; BINDING; DOMAIN AB We stained 13 primary CNS lymphomas (PCNSLs) (six from patients with AIDS, seven from immunocompetent patients) with a panel of antibodies to T cells (pan T cell [CD3], T helper cell [CD4], T suppressor cell [CD8], delta/Delta cell [CD4(-)8(-)]), B cells (CD20), hematopoietic cells (T200), and NK cell (CD56). We estimated the percentage of tumor cells staining with each antibody. All tumors were B-cell lymphomas. The non-AIDS tumors showed a significant infiltration with CD3(+) cells (mean of 10.82% of total cells). The AIDS patients' tumors showed a smaller percentage of CD3(+) infiltrating cells (mean, 4.88% of total cells) (p < 0.01). CD4(+) cells were 9.11% of the total hematopoietic cells in the non-AIDS patients and 3.13% in AIDS patients (p 0.01). AIDS patients showed some CD8(+) cells (0.3%), which was significantly higher than in immunocompetent patients (0%) (p < 0.05). Very few tumor cells stained with the NK cell and delta Delta cell markers. Both immunocompetent and AIDS patients with PCNSL exhibit significant CD3(+) and CD4(+) cell infiltration of their tumors; this infiltration is significantly lower in AIDS patients. AIDS patients show a minor CD8(+) cell infiltration of their tumors. These results on PCNSL are different from systemic lymphomas, which show a higher CD4 and CD8 cell infiltration, and may offer insights into the more aggressive nature of AIDS-related PCNSL. C1 UNIV CALIF SAN DIEGO,MED CTR,SAN DIEGO,CA 92103. UNIV NEBRASKA,MED CTR,DEPT PREVENT & SOCIETAL MED,OMAHA,NE. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. RP Bashir, R (reprint author), UNIV NEBRASKA,MED CTR,DIV NEUROL,DEPT INTERNAL MED,600 S 42ND ST,OMAHA,NE 68198, USA. NR 31 TC 22 Z9 23 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD FEB PY 1996 VL 46 IS 2 BP 440 EP 444 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA TZ712 UT WOS:A1996TZ71200025 PM 8614509 ER PT J AU Olanow, CW Good, PF Shinotoh, H Hewitt, KA Vingerhoets, F Snow, BJ Beal, MF Calne, DB Perl, DP AF Olanow, CW Good, PF Shinotoh, H Hewitt, KA Vingerhoets, F Snow, BJ Beal, MF Calne, DB Perl, DP TI Manganese intoxication in the rhesus monkey: A clinical, imaging, pathologic, and biochemical study SO NEUROLOGY LA English DT Article ID BLOOD-BRAIN-BARRIER; PARKINSONS-DISEASE; RAT STRIATUM; DOPAMINE; IRON; METABOLISM; PRIMATE; VULNERABILITY; NEUROTOXICITY; TRANSFERRIN AB We gave three adult rhesus monkeys seven IV injections of manganese chloride at similar to 1-week intervals, We evaluated neurologic status by serial clinical examinations and performed a levodopa test if the animal developed features of basal ganglia dysfunction. After the animals were killed, we performed neuropathologic, neurochemical, and laser microprobe mass analysis (LAMMA) studies. Two of three animals developed a parkinsonian syndrome characterized by bradykinesia, rigidity, and facial grimacing suggestive of dystonia but not tremor. Neither animal responded to levodopa. Autopsy demonstrated gliosis primarily confined to the globus pallidus (GP) and the substantia nigra pars reticularis (SNr), We detected focal mineral deposits throughout the GP and SNr, particularly in a perivascular distribution. LAMMA studies noted that mineral deposits were primarily comprised of iron and aluminum. The severity of pathologic change correlated with the degree of clinical dysfunction. These studies demonstrate that, in contrast to Parkinson's disease (PD) and MPTP-induced parkinsonism, manganese primarily damages the GP and SNr and relatively spares the nigrostriatal dopaminergic system. Further, the results suggest that Mn-induced parkinsonism can be differentiated from PD and MPTP-induced parkinsonism by the clinical syndrome and response to levodopa. The accumulation of iron and aluminum suggests that iron/aluminum-induced oxidant stress may contribute to the damage associated with Mn toxicity. C1 MT SINAI MED CTR,DIV NEUROPATHOL,NEW YORK,NY 10029. UNIV BRITISH COLUMBIA,DIV NEUROL,CTR NEURODEGENERAT DISORDERS,VANCOUVER,BC V5Z 1M9,CANADA. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. RP Olanow, CW (reprint author), MT SINAI MED CTR,DEPT NEUROL,1 GUSTAVE LEVY PL,BOX 1137,NEW YORK,NY 10029, USA. NR 61 TC 202 Z9 208 U1 2 U2 5 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD FEB PY 1996 VL 46 IS 2 BP 492 EP 498 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA TZ712 UT WOS:A1996TZ71200036 PM 8614520 ER PT J AU Blumenfeld, H Cha, JH Cudkowicz, ME AF Blumenfeld, H Cha, JH Cudkowicz, ME TI Trimethoprim and sulfonamide-associated meningoencephalitis with MRI correlates SO NEUROLOGY LA English DT Article ID ASEPTIC-MENINGITIS; SULFAMETHOXAZOLE AB Early recognition of trimethoprim and sulfonamide-induced aseptic meningitis is important because drug cessation leads to rapid clinical improvement. We present clinical and laboratory findings in two typical cases. In both cases, MRI revealed previously undescribed diffuse white matter abnormalities that resolved within a few months. These MRI findings are important because they may aid in early diagnosis of this condition in the appropriate clinical setting. In addition, the white matter abnormalities suggest an encephalitic component in addition to the meningitis. RP Blumenfeld, H (reprint author), MASSACHUSETTS GEN HOSP,DEPT NEUROL,ACC 835,BOSTON,MA 02114, USA. NR 10 TC 10 Z9 10 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD FEB PY 1996 VL 46 IS 2 BP 556 EP 558 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA TZ712 UT WOS:A1996TZ71200049 PM 8614533 ER PT J AU Pless, M Ronthal, M AF Pless, M Ronthal, M TI Treatment of opsoclonus-myoclonus with high-dose intravenous immunoglobulin SO NEUROLOGY LA English DT Article C1 HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DEPT NEUROL,BOSTON,MA 02215. RP Pless, M (reprint author), HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,NEUROOPHTHALMOL DIV,243 CHARLES ST,BOSTON,MA 02116, USA. NR 6 TC 32 Z9 33 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD FEB PY 1996 VL 46 IS 2 BP 583 EP 584 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA TZ712 UT WOS:A1996TZ71200059 PM 8614543 ER PT J AU Lytton, WW Destexhe, A Sejnowski, TJ AF Lytton, WW Destexhe, A Sejnowski, TJ TI Control of slow oscillations in the thalamocortical neuron: A computer model SO NEUROSCIENCE LA English DT Article DE thalamus; inhibition; bursting; spindles; epilepsy ID LATERAL GENICULATE-NUCLEUS; THALAMIC RELAY NEURONS; ELECTROPHYSIOLOGICAL PROPERTIES; LOW-FREQUENCY; INTRINSIC OSCILLATION; RETICULARIS THALAMI; CALCIUM CURRENTS; CAT; RAT; CELLS AB We investigated computer models of a single thalamocortical neuron to assess the interaction of intrinsic voltage-sensitive channels and cortical synaptic input in producing the range of oscillation frequencies observed in these cells in vivo. A morphologically detailed model with Hodgkin-Huxley-like ion channels demonstrated that intrinsic properties would be sufficient to readily produce 3 to 6 Hz oscillations. Hyperpolarization of the model cell reduced its oscillation frequency monotonically whether through current injection or modulation of a potassium conductance, simulating the response to a neuromodulatory input. We performed detailed analysis of highly reduced models to determine the mechanism of this frequency control. The interburst interval was controlled by two different mechanisms depending on whether or not the pacemaker current, I-H, was present. In the absence of I-H, depolarization during the interburst interval occurred at the same rate with different current injections. The voltage difference from the nadir to threshold for the low-threshold calcium current, I-H, determined the interburst interval. In contrast, with I-H present, the rate of depolarization depended on injected current. With the full model, simulated repetitive cortical synaptic input entrained oscillations up to approximately double the natural frequency. Cortical input readily produced phase resetting as well. Our findings suggest that neither ascending brainstem control altering underlying hyperpolarization, nor descending drive by repetitive cortical inputs, would alone be sufficient to produce the range of oscillation frequencies seen in thalamocortical neurons. Instead, intrinsic neuronal mechanisms would dominate for generating the delta range (0.5-4 Hz) oscillations seen during slow wave sleep, whereas synaptic interactions with cortex and the thalamic reticular nucleus would be required for faster oscillations in the frequency range of spindling (7-14 Hz). C1 SALK INST BIOL STUDIES,HOWARD HUGHES MED INST,LA JOLLA,CA 92037. UNIV CALIF SAN DIEGO,DEPT BIOL,LA JOLLA,CA 92093. RP Lytton, WW (reprint author), UNIV WISCONSIN,WILLIAM S MIDDLETON MEM VET HOSP,DEPT NEUROL,1300 UNIV AVE,MSC 1720,MADISON,WI 53706, USA. NR 50 TC 30 Z9 30 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD FEB PY 1996 VL 70 IS 3 BP 673 EP 684 DI 10.1016/S0306-4522(96)83006-5 PG 12 WC Neurosciences SC Neurosciences & Neurology GA TN528 UT WOS:A1996TN52800006 PM 9045080 ER PT J AU Carroll, RS Schrell, UMH Zhang, JP Dashner, K Nomikos, P Fahlbusch, R Black, PM AF Carroll, RS Schrell, UMH Zhang, JP Dashner, K Nomikos, P Fahlbusch, R Black, PM TI Dopamine D-1, dopamine D-2, and prolactin receptor messenger ribonucleic acid expression by the polymerase chain reaction in human meningiomas SO NEUROSURGERY LA English DT Article DE dopamine receptors; meningiomas; polymerase chain reaction; prolactin receptors ID BREAST-CANCER; CEREBRAL MENINGIOMAS; HORMONAL DEPENDENCY; GROWTH; CELLS; CULTURE; BROMOCRIPTINE; ASSOCIATION; FRAGMENTS; NEOPLASMS AB PREVIOUS STUDIES HAVE suggested the presence of high-affinity dopamine D-1 receptors and prolactin receptors in human cerebral meningiomas. In this study, using the polymerase chain reaction, we report the presence of the messenger ribonucleic acid (mRNA) for the dopamine D-1 and D-2 receptors and the prolactin receptor in meningioma tissue specimens and cell cultures derived from meningioma tissue. Dopamine D-1 receptor mRNA was present in a majority of female tissue specimens and in all male tissue specimens. D-2 receptor mRNA was detected in all specimens examined. Prolactin receptor mRNA was present in a little more than half of the female and male meningioma tumor specimens. The polymerase chain reaction products were directly sequenced to confirm the identity of these receptors in meningiomas and cell cultures. Ligand binding studies confirmed the presence of the dopamine D-1 receptor in meningioma tissue specimens. In contrast, receptor studies with the dopamine D-2 ligand [I-125]4-iodospiperone failed to detect D-2 binding in meningioma membrane preparations. These results suggest the existence of active dopamine D-2 receptors in cerebral meningiomas. C1 BRIGHAM & WOMENS HOSP,BRAIN TUMOR CTR,BOSTON,MA 02115. CHILDRENS HOSP,BOSTON,MA. DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. UNIV ERLANGEN NURNBERG,DEPT NEUROSURG,W-8520 ERLANGEN,GERMANY. RP Carroll, RS (reprint author), BRIGHAM & WOMENS HOSP,NEUROSURG LABS,221 LONGWOOD AVE,ROOM 121,BOSTON,MA 02115, USA. NR 39 TC 13 Z9 13 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD FEB PY 1996 VL 38 IS 2 BP 367 EP 374 DI 10.1097/00006123-199602000-00027 PG 8 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA TQ420 UT WOS:A1996TQ42000069 PM 8869066 ER PT J AU Cunningham, JJ Lydon, MK Emerson, R Harmatz, PR AF Cunningham, JJ Lydon, MK Emerson, R Harmatz, PR TI Low ceruloplasmin levels during recovery from major burn injury: Influence of open wound size and copper supplementation SO NUTRITION LA English DT Article DE copper supplementation; ceruloplasmin; plasma concentrations; major burn injury; vitamin C ID TOTAL PARENTERAL-NUTRITION; SERUM COPPER; YOUNG MEN; ABSORPTION; CHILDREN; GUIDELINES; PLASMA; RAT AB Copper (Cu) status is often judged by the plasma level of its chief transport protein, ceruloplasmin (Cp). Only copper deficiency and heredity are known to decrease circulating Cp. Cp is an acute-phase responsive protein in trauma and it is also induced by Cu supplementation. Despite this, plasma concentrations of Cp remain low during the acute recovery from major burn injury. The high provision of vitamin C typically used in burn patients may influence these observations when an indirect oxidase activity assay is used. We employed a radial immunodiffusion (RID) assay specific for the Cp protein as well as an indirect oxidase assay for Cp in a series of 11 burned children who were supplemented with both Cu and vitamin C, either enterally or parenterally. Our findings confirm that low Cp is a characteristic of the acute recovery from major burns. The oxidase assay is shown to be valid for very low Cp levels even during high vitamin C provision. When these data are combined with our previously reported series, a strong relationship between the size of the open wound area and the amount of circulating Cp is demonstrated. Copper supplementation by either the enteral or parenteral routes is only marginally successful in restoring Cp toward normal levels. C1 MASSACHUSETTS GEN HOSP,SHRINERS BURNS INST,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,SURG SERV,BOSTON,MA 02114. CHILDRENS HOSP,OAKLAND RES INST,OAKLAND,CA 94609. RP Cunningham, JJ (reprint author), UNIV MASSACHUSETTS,DEPT NUTR,CHENOWETH LAB 201,BOX 31420,AMHERST,MA 01003, USA. NR 20 TC 11 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0899-9007 J9 NUTRITION JI Nutrition PD FEB PY 1996 VL 12 IS 2 BP 83 EP 88 DI 10.1016/0899-9007(96)90704-2 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA UN298 UT WOS:A1996UN29800003 PM 8724377 ER PT J AU Rubin, PAD Chen, VN Acquadro, MA AF Rubin, PAD Chen, VN Acquadro, MA TI Cluster headache presenting with orbital inflammation SO OPHTHALMIC SURGERY AND LASERS LA English DT Article ID REFLEX SYMPATHETIC DYSTROPHY; PAIN; CAUSALGIA RP Rubin, PAD (reprint author), HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,EYE PLAST & ORBIT SERV,243 CHARLES ST,BOSTON,MA 02114, USA. NR 22 TC 5 Z9 5 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0022-023X J9 OPHTHALMIC SURG LAS JI Ophthalmic Surg. Lasers PD FEB PY 1996 VL 27 IS 2 BP 143 EP 146 PG 4 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA TV835 UT WOS:A1996TV83500009 PM 8640439 ER PT J AU Black, P Carroll, R Glowacka, D AF Black, P Carroll, R Glowacka, D TI Expression of platelet-derived growth factor transcripts in medulloblastomas and ependymomas SO PEDIATRIC NEUROSURGERY LA English DT Article DE medulloblastomas; ependymomas; platelet-derived growth factor; growth factors; central nervous system neoplasia ID PDGF-RECEPTOR GENES; RIBONUCLEIC-ACID; HUMAN MENINGIOMAS; MESSENGER-RNA; CELL-LINE; COEXPRESSION; STIMULATION; RAT AB We used Northern blot analysis to measure the expression of mRNA for platelet-derived growth factor subunit A (PDGF-B), PDGF-B and the PDGF-alpha receptor (PDGFR-alpha) and PDGF-beta receptor (PDGFR-beta) in ependymomas and medulloblastomas. We analyzed tissue from 5 patients for each tumor type, looking specifically for components of an autocrine or paracrine system in these tumors. PDGF-A was expressed in all tumors, PDGFR-alpha, which binds all 3 PDGF isoforms, was only found in ependymomas, Thus only ependymomas appeared to have a potential for using PDGFR-alpha autocrine loops. PDGF-B was expressed only in ependymomas, although the PDGFR-beta was expressed in both medulloblastomas and ependymomas. Again, therefore, only ependymomas appear to have a potential autocrine loop with PDGFR-beta. These data suggest that ependymomas have the biochemical prerequisites for autocrine and/or paracrine loops using PDGFR-alpha or PDGFR-beta systems, In this they resemble other glial tumors such as anaplastic astrocytomas and glioblastomas. Medulloblastomas do not appear to have the ligand and/or receptor for either the PDGFR-alpha or PDGFR-beta autocrine loop. C1 BRIGHAM & WOMENS HOSP,CHILDRENS HOSP,NEUROSURG LABS,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,CHILDRENS HOSP,BRAIN TUMOR CTR,BOSTON,MA 02115. DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. NR 19 TC 29 Z9 29 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1016-2291 J9 PEDIATR NEUROSURG JI Pediatr. Neurosurg. PD FEB PY 1996 VL 24 IS 2 BP 74 EP 78 DI 10.1159/000121020 PG 5 WC Clinical Neurology; Pediatrics; Surgery SC Neurosciences & Neurology; Pediatrics; Surgery GA UX505 UT WOS:A1996UX50500005 PM 8841077 ER PT J AU Shapiro, NL Cunningham, MJ Parikh, SR Eavey, RD Cheney, ML AF Shapiro, NL Cunningham, MJ Parikh, SR Eavey, RD Cheney, ML TI Congenital unilateral facial paralysis SO PEDIATRICS LA English DT Article ID NEWBORN C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT OTORHINOLARYNGOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02114. NR 13 TC 15 Z9 15 U1 0 U2 4 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD FEB PY 1996 VL 97 IS 2 BP 261 EP 265 PG 5 WC Pediatrics SC Pediatrics GA TU284 UT WOS:A1996TU28400022 PM 8584391 ER PT J AU Lambert, CR Stiel, H Leupold, D Lynch, MC Kochevar, IE AF Lambert, CR Stiel, H Leupold, D Lynch, MC Kochevar, IE TI Intensity-dependent enzyme photosensitization using 532 nm nanosecond laser pulses SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID ROSE-BENGAL; CELL ACETYLCHOLINESTERASE; PICOSECOND FLUORESCENCE; PHOTODYNAMIC THERAPY; SINGLET OXYGEN; HEMATOPORPHYRIN; INACTIVATION; MECHANISM; TUMOR; DYES AB The intensity dependence of the rose bengal (RB)-photosensitized inhibition of red blood cell acetylcholinesterase has been studied experimentally and the results compared to a quantitative excitation/deactivation model of RE photochemistry. Red blood cell membrane suspensions containing 5 mu M RB were irradiated with 532 mm, 8 ns laser pulses with energies between 1 and 98.5 mJ. A constant dose (7 J) was delivered to all samples by varying the total number of pulses. At incident energies greater than similar to 4.5 mJ/pulse, the efficiency for photosensitized enzyme inhibition decreased as the energy/pulse increased. The generation of RB triplet state was monitored as a function of laser energy and the triplet-triplet absorption coefficient was determined to be 1.9 x 10(4) M(-1) cm(-1) at 530 mn. The number of singlet oxygen molecules produced at each intensity was calculated from both the physico-mathematical model and from laser flash photolysis results. The results indicated that the photosensitized inhibition of acetylcholinesterase was exclusively mediated by singlet oxygen, even at the highest laser intensities employed. C1 HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, WELLMAN LABS PHOTOMED, BOSTON, MA 02114 USA. MAX BORN INST NICHTLINEARE OPT & KURZZEITSPEKTROS, BERLIN, GERMANY. FU NIGMS NIH HHS [GM30755] NR 33 TC 29 Z9 30 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0031-8655 EI 1751-1097 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD FEB PY 1996 VL 63 IS 2 BP 154 EP 160 DI 10.1111/j.1751-1097.1996.tb03007.x PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA TV096 UT WOS:A1996TV09600002 PM 8657729 ER PT J AU Cincotta, L Szeto, D Lampros, E Hasan, T Cincotta, AH AF Cincotta, L Szeto, D Lampros, E Hasan, T Cincotta, AH TI Benzophenothiazine and benzoporphyrin derivative combination phototherapy effectively eradicates large murine sarcomas SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID MOUSE-TUMOR MODEL; PHOTODYNAMIC THERAPY; CELLS; PHOTOSENSITIZERS; HEMATOPORPHYRIN; MACROPHAGES; LIMITATION; ACTIVATION; ANALOGS; INVIVO AB The tumoricidal effects of photochemotherapy with two photosensitizers, 5-ethylamino-9-diethylaminobenzo[a] phenothiazinium chloride (EtNBS) and benzoporphyrin derivative monoacid ring A (BPD-MA), were evaluated separately and in combination against the EMT-6 fibrosarcoma implanted subcutaneously in BALB/c mice. Animals carrying tumors 8-10 mm in diameter were divided into eight different groups (similar to 20/group) and subjected to various photoirradiation and drug conditions. The tumor response to photodynamic therapy (PDT) was measured as the mean tumor wet weight 2 weeks post-PDT. The combination treatment with 5.25 mg/kg EtNBS and 2.5 mg/kg BPD-MA followed by photoirradiation with 100 J/cm(2) at 652 mn and then by 100 J/cm(2) at 690 nm resulted in a 95% reduction in the average tumor weights compared to controls (no light, no drugs) with 76% of the mice being tumor free 2 weeks post-PDT. Because treatment with EtNBS or BPD-MA at twice the light dose and drug concentration resulted in either no significant reduction in tumor weights or increased the lethality of treatment, respectively, the data suggest that the enhanced PDT effect observed with the combination of drugs is synergistic rather than additive. Histology of tumors 24 h post-PDT with the combination of drugs showed nearly complete destruction of the tumor mass with little or no damage to the vasculature and no extravasation of red blood cells. There was no damage to the normal skin adjacent to the tumor. Fluorescence microscopy of EMT-6 cells incubated in vitro with the two photosensitizers revealed that they were localized to different intracellular compartments, The fluorescence pattern from frozen tumor tissue slices following the in vivo administration of the photosensitizers indicated a greater intracellular localization for EtNBS vs BPD-MA. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,WELLMAN LABS PHOTOMED,DEPT DERMATOL,BOSTON,MA. ERGO SCI INC,BOSTON,MA. RP Cincotta, L (reprint author), ROWLAND INST SCI INC,100 EDWIN H LAND BLVD,CAMBRIDGE,MA 02142, USA. NR 44 TC 46 Z9 46 U1 0 U2 1 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD FEB PY 1996 VL 63 IS 2 BP 229 EP 237 DI 10.1111/j.1751-1097.1996.tb03019.x PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA TV096 UT WOS:A1996TV09600014 PM 8657737 ER PT J AU Jette, DU Downing, J AF Jette, DU Downing, J TI The relationship of cardiovascular and psychological impairments to the health status of patients enrolled in cardiac rehabilitation programs SO PHYSICAL THERAPY LA English DT Article DE cardiovascular disease; health status; psychology; rehabilitation ID MOS SHORT-FORM; MEDICAL OUTCOMES; FUNCTIONAL STATUS; SURVEY SF-36; VALIDITY; DISEASE; DISABILITY; SURGERY; IMPACT AB Background and Purpose. Understanding the causes of differences in disability among individuals is an important research focus for rehabilitation professionals. The purpose of this study was to examine the relationship between health status and the impairments commonly associated with cardiovascular pathophysiology. Subjects. The subjects were patients (N=789) enrolled in 13 cardiac rehabilitation programs in Massachusetts. Methods. Data were collected on psychological and physiological impairments, demographic characteristics, and health status. Multivariate analyses were used to determine which measures of impairment and patient characteristics were related to health status. Results. Psychological impairment was related to all scales of the MOS 36-item Short-Form Health Survey (SF-36). Very few measures of physiological impairment and individual characteristics were related to SF-36 scores. The models accounted for 16% to 57% of the variability of the instrument's scales. Conclusion and Discussion. In patients entering cardiac rehabilitation, psychological distress is related to poor health in both the physical and psychological dimensions. Variability in health status is not well explained by traditional measures of impairment or demographic characteristics. Physical therapists working to address their patients' health needs must consider collecting data, setting goals, and devising interventions that address psychological impairment. C1 MASSACHUSETTS GEN HOSP,DEPT PREVENT CARDIOL,BOSTON,MA 02114. RP Jette, DU (reprint author), SIMMONS COLL,GRAD PROGRAM PHYS THERAPY,300 FENWAY,BOSTON,MA 02115, USA. NR 29 TC 14 Z9 16 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 FEB PY 1996 VL 76 IS 2 BP 130 EP 139 PG 10 WC Orthopedics; Rehabilitation SC Orthopedics; Rehabilitation GA TX850 UT WOS:A1996TX85000002 PM 8592717 ER PT J AU Reuber, TL Ausubel, FM AF Reuber, TL Ausubel, FM TI Isolation of arabidopsis genes that differentiate between resistance responses mediated by the RPS2 and RPM1 disease resistance genes SO PLANT CELL LA English DT Article ID LOCUS; IDENTIFICATION; AVIRULENCE; RECOGNITION; THALIANA; AVRRPT2; RNA AB The Arabidopsis disease resistance gene RPS2 is involved in recognition of bacterial pathogens carrying the avirulence gene avrRpt2, and the RPM1 resistance gene is involved in recognition of pathogens carrying avrRpm1 or avrB. We identified and cloned two Arabidopsis genes, AIG1 and AIG2 (for avrRpt2-induced gene), that exhibit RPS2- and avrRpt2-dependent induction early after infection with Pseodomonas syringae pv maculicola strain ES4326 carrying avrRpt2. However, ES4326 carrying avrRpm1 or avrB did not induce early expression of AIG1 and AIG2. Conversely, ES4326 carrying avrRpm1 or avrB induced early expression of the previously isolated defense-related gene ELI3, whereas ES4326 carrying avrRpt2 did not, The induction patterns of the AIG genes and ELI3 demonstrate that different resistance gene-avr gene combinations can elicit distinct defense responses. Furthermore, by examining the expression of AIG1 and ELI3 in plants infiltrated with a mixed inoculum of ES4326 carrying avrRpt2 and ES4326 carrying avrRpm1, we found that there is interference between the RPS2- and RPM1-mediated resistance responses. C1 HARVARD UNIV, SCH MED, DEPT GENET, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, DEPT MOLEC BIOL, BOSTON, MA 02114 USA. OI Reuber, Lynne/0000-0001-7806-2437 FU NIGMS NIH HHS [GM48707] NR 36 TC 175 Z9 182 U1 0 U2 6 PU AMER SOC PLANT BIOLOGISTS PI ROCKVILLE PA 15501 MONONA DRIVE, ROCKVILLE, MD 20855 USA SN 1040-4651 EI 1532-298X J9 PLANT CELL JI Plant Cell PD FEB PY 1996 VL 8 IS 2 BP 241 EP 249 DI 10.1105/tpc.8.2.241 PG 9 WC Biochemistry & Molecular Biology; Plant Sciences; Cell Biology SC Biochemistry & Molecular Biology; Plant Sciences; Cell Biology GA TY089 UT WOS:A1996TY08900009 PM 8742710 ER EF