FN Thomson Reuters Web of Science™ VR 1.0 PT J AU VIVIER, E MUNROE, M ARINIELLO, P ANDERSON, P AF VIVIER, E MUNROE, M ARINIELLO, P ANDERSON, P TI IDENTIFICATION OF TISSUE-INFILTRATING LYMPHOCYTES EXPRESSING PEN5, A MUCIN-LIKE GLYCOPROTEIN SELECTIVELY EXPRESSED ON NATURAL-KILLER-CELLS SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID THYMOCYTES; PRECURSORS; INDUCTION; MARKER; TARGET AB PEN5 is a carbohydrate epitope selectively expressed on peripheral blood natural killer cells. We have used a monoclonal antibody reactive with PEN5 to survey the expression of PEN5(+) large granule lymphocytes in a variety of human tissues. PEN5(+) cells are scattered throughout lymphoid (eg, lymph none, tonsil, thymus, spleen, and intestine) and nonlymphoid (eg, liver, esophagus, lung, and uterus) organs. Due to their relatively abundant cytoplasm, these cells are somewhat larger than resting tissue lymphocytes. The majority of splenic (87 +/- 13%, n = 5) and hepatic (92 +/- 6%, n = 53 PEN(5)+ lymphocytes coexpress TLA-1, a cytotoxic granule protein found in natural killer cells. In some tissues leg, tonsil and Peyer's patch), however, relatively few PEN5(+) lymphocytes coexpress TIA-1, possibly reflecting different stages of activation or differentiation. Our results indicate that PEN5 may be a useful marker of tissue-infiltrating natural killer cells and reveal these cells to be surprisingly abundant in lymphoid tissues. C1 DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. CNRS,INSERM,CTR IMMUNOL,MARSEILLE,FRANCE. UNIV LONDON,DEPT PATHOL,LONDON,ENGLAND. IMMUNOGEN INC,BOSTON,MA. FU NCI NIH HHS [CA53595] NR 19 TC 11 Z9 11 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 1995 VL 146 IS 2 BP 409 EP 418 PG 10 WC Pathology SC Pathology GA QF427 UT WOS:A1995QF42700013 PM 7531954 ER PT J AU SCHOFIELD, D WEST, DC ANTHONY, DC MARSHAL, R SKLAR, J AF SCHOFIELD, D WEST, DC ANTHONY, DC MARSHAL, R SKLAR, J TI CORRELATION OF LOSS OF HETEROZYGOSITY AT CHROMOSOME 9Q WITH HISTOLOGICAL SUBTYPE IN MEDULLOBLASTOMAS SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; PRIMITIVE NEUROECTODERMAL TUMORS; CEREBELLAR NEURO-BLASTOMA; CELL CARCINOMA SYNDROME; LINKAGE MAP; DNA CONTENT; POLYMORPHISM; GENE AB Patients with the nevoid basal cell carcinoma syndrome (NBCCS) are at increased risk for medulloblastomas as well as for basal cell carcinomas. The gene for NBCCS has been mapped to chromosome 9q2.3-q31 by linkage analysis, and loss of heterozygosity (LOH) in this region has been demonstrated in approximately one-half of sporadic basal cell carcinomas. In the present study, LOH for chromosome 9q22.3-q31 microsatellite markers was investigated in medulloblastomas occurring among children with NBCCS and in sporadic medulloblastomas. Histologically, all 3 NBCCS medulloblastomas were noted to have a desmoplastic phenotype, and LOH was detected in both of the 2 cases for which microsatellite markers were heterozygous in normal tissues. LOH was also detected in a subset of sporadic medulloblastomas, each of which were found on display the desmoplastic phenotype. In all, 3 of the 6 sporadic desmoplastic tumors showed LOH, whereas LOH was not seen in any of the 11 sporadic, non-desmoplastic tumors lacking detectable LOH each showed histological features of so-called cerebellar neuroblastoma, a subgroup of desmoplastic medulloblastoma with extensive neuroblastomatous differentiation. The data are consistent with a role for inactivation of a tumor suppressor gene at chromosome 9q in the development of medulloblastomas in patients with NBCCS and of sporadic medulloblastomas characterized by a desmoplastic phenotype similar to that found in patients with NBCCS. Restriction of chromosome 9q loss to non-neuroblastomatous desmoplastic tumors suggests that this variant of medulloblastoma maybe pathogenetically distinct from tumors having other histological phenotypes. C1 BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PEDIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. RP SCHOFIELD, D (reprint author), CHILDRENS HOSP,DEPT PATHOL,300 LONGWOOD AVE,BOSTON,MA 02115, USA. OI Anthony, Douglas/0000-0002-3815-2240 NR 40 TC 76 Z9 77 U1 0 U2 3 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD FEB PY 1995 VL 146 IS 2 BP 472 EP 480 PG 9 WC Pathology SC Pathology GA QF427 UT WOS:A1995QF42700019 PM 7856756 ER PT J AU MUTTER, GL CHAPONOT, ML FLETCHER, JA AF MUTTER, GL CHAPONOT, ML FLETCHER, JA TI A POLYMERASE CHAIN-REACTION ASSAY FOR NONRANDOM X-CHROMOSOME INACTIVATION IDENTIFIES MONOCLONAL ENDOMETRIAL CANCERS AND PRECANCERS SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID SEVERE COMBINED IMMUNODEFICIENCY; CARCINOMA; HYPERPLASIA; GENE; METHYLATION; CARRIERS; LESIONS; REPEAT AB We hypothesize that endometrial carcinoma and their precursors share a monoclonal growth pattern and tested this thesis with archival paraffin-embedded tissues using a polymerase chain reaction-based assay for non-random X chromosome inactivation. Of the 10 well-differentiated endometrial adenocarcinoma cases with heterozygous markers (HUMARA, X-linked androgen receptor gene), 9 had skewed X inactivation consistent with a monoclonal process, and one contained a structurally altered HUMARA gene. X inactivation skewing similar to that of the tumor was seen in matched control polyclonal tissues of 4 (of 9) cases, caused by the small number of endometrial stem cells at the time of embryonic X inactivation. When the polymerase chain reaction assay was applied to four potential endometrial precancers (atypical endometrial hyperplasia) and matched control tissues, two were inconclusive, and two were found to be monoclonal. We conclude that 1) it is essential to include polyclonal control tissues in X inactivation analyses to determine whether skewing is a specific indicator of monoclonality; and 2) endometrial adenocarcinomas and some putative precancers, atypical endometrial hyperplasia, are monoclonal. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. RP MUTTER, GL (reprint author), BRIGHAM & WOMENS HOSP,DEPT PATHOL,75 FRANCIS ST,BOSTON,MA 02115, USA. RI Mutter, George/C-5819-2009 FU NCI NIH HHS [R29-CA49859] NR 34 TC 107 Z9 108 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 1995 VL 146 IS 2 BP 501 EP 508 PG 8 WC Pathology SC Pathology GA QF427 UT WOS:A1995QF42700022 PM 7856759 ER PT J AU CASTILLO, L SANCHEZ, M VOGT, J CHAPMAN, TE DEROJASWALKER, TC TANNENBAUM, SR AJAMI, AM YOUNG, VR AF CASTILLO, L SANCHEZ, M VOGT, J CHAPMAN, TE DEROJASWALKER, TC TANNENBAUM, SR AJAMI, AM YOUNG, VR TI PLASMA ARGININE, CITRULLINE, AND ORNITHINE KINETICS IN ADULTS, WITH OBSERVATIONS ON NITRIC-OXIDE SYNTHESIS SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE NITRATE; N-15-LABELING; FLUX; HOMEOSTASIS; METABOLISM; AVAILABILITY ID DIETARY ARGININE; GAS-CHROMATOGRAPHY; AMINO-ACIDS; COMPARTMENTAL-MODELS; ALPHA-KETOGLUTARATE; HEALTHY-SUBJECTS; WHOLE-BODY; METABOLISM; RATS; ARGININE AB The plasma fluxes of ornithine (Orn), arginine (Arg), and citrulline (Cit) and rate of conversion of labeled ornithine-to-citrulline (Q(Orn-->Cit)) were estimated in six healthy adult men receiving an arginine-rich or arginine-free L-amino acid-based diet, each for 6 days. On day 7 an 8-h (3-h fast, 5-h fed) primed continuous intravenous infusion of L-[guanido-N-15,N-15] arginine, L-[ureido-C-13]citrulline, L-[5,5,H-2(2)]ornithine, and L-[5,5,5-H-2(3)]leucine was conducted. Mean citrulline fluxes (mu mol.kg(-1).h(-1)) were 10.4-13.6 for the various conditions and/or diets and remained unchanged (P > 0.05). Arginine flux was lowered (P < 0.01) by 38% for fed state during arginine-free period. Ornithine fluxes for arginine-rich were (P < 0.01) reduced with the arginine-free diet. Rates of Q(Orn-->Cit) declined by 30% (P < .05) during the fed arginine-free period. Short-term restriction in the dietary supply of arginine did not alter the rate of whole body nitric oxide synthesis. One subject showed a very high output of nitrate on arginine-free diet (6 times average for remaining subjects). C1 MIT, SCH SCI, HUMAN NUTR LAB, CAMBRIDGE, MA 02139 USA. MASSACHUSETTS GEN HOSP, SHRINERS BURNS INST, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, DEPT SURG, BOSTON, MA 02114 USA. UNIV ULM, W-7900 ULM, GERMANY. TRACER TECHNOL, SOMERVILLE, MA 02145 USA. RP CASTILLO, L (reprint author), MIT, DIV TOXICOL, RM E18-613, CAMBRIDGE, MA 02142 USA. FU NCI NIH HHS [CA-26731]; NCRR NIH HHS [RR-88]; NIDDK NIH HHS [DK-15856] NR 56 TC 92 Z9 93 U1 1 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 EI 1522-1555 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD FEB PY 1995 VL 268 IS 2 BP E360 EP E367 PG 8 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA QF545 UT WOS:A1995QF54500023 PM 7864114 ER PT J AU SALZMAN, AL MENCONI, MJ UNNO, N EZZELL, RM CASEY, DM GONZALEZ, PK FINK, MP AF SALZMAN, AL MENCONI, MJ UNNO, N EZZELL, RM CASEY, DM GONZALEZ, PK FINK, MP TI NITRIC-OXIDE DILATES TIGHT JUNCTIONS AND DEPLETES ATP IN CULTURED CACO-2BBE INTESTINAL EPITHELIAL MONOLAYERS SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE PERMEABILITY; SODIUM NITROPRUSSIDE; S-NITROSO-N-ACETYLPENICILLAMINE; GUANOSINE 3',5'-CYCLIC MONOPHOSPHATE ID SMOOTH-MUSCLE CELLS; AUTO-ADP-RIBOSYLATION; GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE; PARACELLULAR PERMEABILITY; INTERFERON-GAMMA; RAT INTESTINE; VASODILATORS; MACROPHAGES; INHIBITION; INTEGRITY AB We tested the hypothesis that nitric oxide (NO) modulates the permeability of tight junctions in a model intestinal epithelium (Caco-2BBe monolayers). Incubation with sodium nitroprusside (SNP) resulted in time- and concentration-dependent decreases in transepithelial resistance. Permeability to fluorescein sulfonic acid increased during incubation for 24 h in the presence of 1.25 mM SNP, 5 mM S-nitroso-N-acetylpenicillamine (SNAP), or 1% NO gas. SNP-induced hyperpermeability was not due to loss of cell viability, as confirmed by intact ultrastructure, unaltered lactate dehydrogenase release, and ability to recover baseline permeability. Incubation with SNP increased permeability but only minimally increased intracellular levels of guanosine 3',5'-cyclic monophosphate (cGMP). Incubation with Escherichia coli heat-stable enterotoxin greatly increased cGMP levels with only a minimal effect on permeability. Cellular ATP levels decreased after incubation with SNP, SNAP, or gaseous NO. Incubation with SNP led to diminished fluorescein-phalloidin staining of junctional actin (confocal microscopy) and widened tight junctions (electron microscopy). We conclude that NO reduces ATP levels and reversibly increases the permeability of tight junctions in cultured Caco-2BBe cells. C1 HARVARD UNIV, BETH ISRAEL HOSP, SCH MED, DEPT SURG, BOSTON, MA 02215 USA. HARVARD UNIV, BETH ISRAEL HOSP, SCH MED, DEPT ANESTHESIOL, BOSTON, MA 02215 USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG, SURG RES LAB, BOSTON, MA 02129 USA. FU NIDDK NIH HHS [DK-43351]; NIGMS NIH HHS [2 R01 GM-37631-07, 5T32GM-07035] NR 49 TC 208 Z9 215 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD FEB PY 1995 VL 268 IS 2 BP G361 EP G373 PG 13 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA QF544 UT WOS:A1995QF54400021 PM 7864133 ER PT J AU ZHANG, RS GUTH, PH SCREMIN, OU CHAUDHURI, G AF ZHANG, RS GUTH, PH SCREMIN, OU CHAUDHURI, G TI H-2 GAS CLEARANCE TECHNIQUE FOR SEPARATING RAT UTERINE BLOOD-FLOW INTO ENDOMETRIAL AND MYOMETRIAL COMPONENTS SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE OVARIECTOMIZED RAT; IODO[C-14]ANTIPYRINE AUTORADIOGRAPHY; ENDOMETRIAL BLOOD FLOW; MYOMETRIAL BLOOD FLOW; GASTRIC MUCOSAL BLOOD FLOW; 17-BETA-ESTRADIOL; PENTAGASTRIN; PHENYLEPHRINE ID OOPHORECTOMIZED EWES; ESTRADIOL AB The H-2 gas clearance technique was employed to measure uterine blood flow (UBF) in ovariectomized rats. A needle-type platinum electrode (125 mu m diam) was inserted into the rat uterine wall to measure the tissue blood flow surrounding the electrode. The electrode can be placed in individual layers of the uterus to measure the endometrial blood flow (EBF) or the myometrial blood flow (MBF). By use of this technique, baseline EBF and MBF were 37.8 +/- 3.53 (n = 21) and 47.2 +/- 4.56 (n = 5) ml.min(-1).100 g(-1), respectively, with an EBF/MBF ratio of 0.8. Intravenous bolus injection of 17 beta-estradiol (1 mu g/kg) induced a significant increase in UBF. Phenylephrine, an alpha-adrenergic receptor agonist, reduced UBF. In some animals, a second platinum electrode was used to measure gastric mucosal blood flow simultaneously with UBF. While 17 beta-estradiol selectively increased UBF, pentagastrin selectively increased gastric mucosal blood flow. To further validate the baseline UBF distribution between endometrial and myometrial layers, iodo[C-14]antipyrine autoradiography was employed. With the iodo[C-14]antipyrine technique, the EBF/MBF ratio was 0.91 +/- 0.07 (n = 5), which is similar to that obtained with the H-2 gas clearance technique. C1 UNIV CALIF LOS ANGELES, SCH MED, DEPT OBSTET & GYNECOL MOLEC & MED PHARMACOL, LOS ANGELES, CA 90024 USA. UNIV CALIF LOS ANGELES, SCH MED, DEPT PHYSIOL, LOS ANGELES, CA 90024 USA. W LOS ANGELES VET AFFAIRS MED CTR, CTR ULCER RES & EDUC, LOS ANGELES, CA 90024 USA. FU NHLBI NIH HHS [HL-46843] NR 40 TC 7 Z9 7 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regulat. Integr. Compar. Physiol. PD FEB PY 1995 VL 268 IS 2 BP R569 EP R575 PG 7 WC Physiology SC Physiology GA QF753 UT WOS:A1995QF75300034 PM 7864254 ER PT J AU ASCH, DA HANSENFLASCHEN, J LANKEN, PN AF ASCH, DA HANSENFLASCHEN, J LANKEN, PN TI DECISIONS TO LIMIT OR CONTINUE LIFE-SUSTAINING TREATMENT BY CRITICAL CARE PHYSICIANS IN THE UNITED-STATES - CONFLICTS BETWEEN PHYSICIANS PRACTICES AND PATIENTS WISHES SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID ILL PATIENTS; FUTILITY; ATTITUDES; SUPPORT; EUTHANASIA; WITHDRAWAL; POLICY AB We surveyed a national sample of 879 physicians practicing in adult intensive care units in the United States, in order to determine their practices with regard to limiting life-sustaining medical treatment, and particularly their decisions to continue or forgo life support without the consent or against the wishes of patients or surrogates. Virtually all of the respondents (96%) have withheld and withdrawn life-sustaining medical treatment on the expectation of a patient's death, and most do so frequently in the course of a year. Many physicians continue life-sustaining treatment despite patient or surrogate wishes that it be discontinued (34%), and many unilaterally withhold (83%) or withdraw (82%) life-sustaining treatment that they judge to be futile. Some of these decisions are made without the knowledge or consent of patients or their surrogates, and some are made over their objections. We conclude that physicians do not reflexively accept requests by patients or surrogates to limit or continue life-sustaining treatment, but place these requests alongside a collection of other factors, including assessments of prognosis and perceptions of other ethical, legal, and policy guidelines. While debate continues about the ethical and legal foundations of medical futility, our results suggest that most critical care physicians are incorporating some concept of medical futility into decision making at the bedside. C1 UNIV PENN, LEONARD DAVIS INST HLTH ECON, PHILADELPHIA, PA 19104 USA. UNIV PENN, SCH MED, DIV PULM & CRIT CARE MED, PHILADELPHIA, PA 19104 USA. RP ASCH, DA (reprint author), UNIV PENN, SCH MED,VET AFFAIRS MED CTR,DIV GEN INTERNAL MED, 317 RALSTON PENN CTR, 3615 CHESTNUT ST, PHILADELPHIA, PA 19104 USA. OI Hansen-Flaschen, John/0000-0003-1989-7244 NR 33 TC 177 Z9 180 U1 0 U2 3 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD FEB PY 1995 VL 151 IS 2 BP 288 EP 292 PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA QF547 UT WOS:A1995QF54700008 PM 7842181 ER PT J AU SLANETZ, PA WHITMAN, GJ CHEW, FS AF SLANETZ, PA WHITMAN, GJ CHEW, FS TI EPIDIDYMAL ABSCESS SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Note C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP SLANETZ, PA (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,32 FRUIT ST,BOSTON,MA 02114, USA. NR 4 TC 8 Z9 8 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD FEB PY 1995 VL 164 IS 2 BP 376 EP 376 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA QC794 UT WOS:A1995QC79400019 PM 7839972 ER PT J AU RIVITZ, SM KAUFMAN, JA CAMBRIA, RP GELLER, SC AF RIVITZ, SM KAUFMAN, JA CAMBRIA, RP GELLER, SC TI PERCUTANEOUS ASPIRATION THROMBECTOMY OF AN ACUTELY OCCLUDED AORTORENAL BYPASS GRAFT SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Discussion ID MR ANGIOGRAPHY; EMBOLECTOMY; ARTERIES C1 MASSACHUSETTS GEN HOSP,DIV VASC SURG,BOSTON,MA 02114. RP RIVITZ, SM (reprint author), MASSACHUSETTS GEN HOSP,DIV VASC RADIOL,32 FRUIT ST,BOSTON,MA 02114, USA. NR 14 TC 2 Z9 2 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD FEB PY 1995 VL 164 IS 2 BP 455 EP 458 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA QC794 UT WOS:A1995QC79400037 PM 7839988 ER PT J AU KAUFMAN, JA CRENSHAW, WB KUTER, I GELLER, SC AF KAUFMAN, JA CRENSHAW, WB KUTER, I GELLER, SC TI PERCUTANEOUS PLACEMENT OF A CENTRAL VENOUS ACCESS DEVICE VIA AN INTERCOSTAL VEIN SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Note ID PARENTERAL-NUTRITION; CATHETERS C1 MASSACHUSETTS GEN HOSP,DEPT HEMATOL ONCOL,BOSTON,MA 02114. RP KAUFMAN, JA (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,VASC RADIOL SECT,GRAY 2,32 FRUIT ST,BOSTON,MA 02114, USA. NR 7 TC 13 Z9 13 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD FEB PY 1995 VL 164 IS 2 BP 459 EP 460 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA QC794 UT WOS:A1995QC79400038 PM 7839989 ER PT J AU ORTEGA, AE HUNTER, JG PETERS, JH SWANSTROM, LL SCHIRMER, B SANGSTER, W RATTNER, DW FERGUSON, C SOPER, N PETELIN, J UNGER, SW APELGREN, KN ARREGUI, ME AF ORTEGA, AE HUNTER, JG PETERS, JH SWANSTROM, LL SCHIRMER, B SANGSTER, W RATTNER, DW FERGUSON, C SOPER, N PETELIN, J UNGER, SW APELGREN, KN ARREGUI, ME TI A PROSPECTIVE, RANDOMIZED COMPARISON OF LAPAROSCOPIC APPENDECTOMY WITH OPEN APPENDECTOMY SO AMERICAN JOURNAL OF SURGERY LA English DT Article ID TRIAL AB BACKGROUND: While the advantages of laparoscopic cholecystectomy are clear, the benefits of laparoscopic appendectomy (LA) are more subtle. We conducted a randomized clinical trial to evaluate whether LA is deserving of more widespread clinical application than it has yet received. MATERIALS AND METHODS: Two hundred fifty-three patients with a preoperative diagnosis of acute appendicitis were randomized into three groups. LA with an endoscopic linear stapler (LAS) (U.S. Surgical Corp., Norwalk, Connecticut) was performed on 78 patients, LA with catgut ligatures (LAL) on 89, and open appendectomy (OA) on 86. LA was performed with a three-trocar technique. OA was accomplished through a right lower-quadrant transverse incision. Data with normal distributions were analyzed by analysis of variance. Nonparametric data were analyzed with either the Kruskal-Wallis H test or Fisher's exact test. RESULTS: The mean operative times for the procedures were 66 +/- 24 minutes (LAS), 68 +/- 25 minutes (LAL), and 58 +/- 27 minutes (OA). The relative brevity of OA compared to LAS and LAL was statistically significant (P <0.01). Conversion to open procedures was approximately as frequent in the LAS group (n = 5) and the LAL (n = 6). One OA, 2 LAS, and 11 LAL patients experienced vomiting Postoperatively (P <0.05). Two intra-abdominal abscesses occurred in LAS, 4 in LAL, and 0 in OA patients (P = NS). Wound infections were more common following OA (n = 11) than LAL (n = 4) or LAS (n = 0) (P <0.05, <0.001). The mean length of postoperative hospital stay was 2.16 +/- 3.2 days (LAS), 2.98 +/- 2.7 days (LAL), and 2.83 +/- 1.6 (OA) (P <0.05 OA versus LAS). The number of clays patients required pain medications overall was not different between groups, but a subgroup analysis of 134 patients who rated their postoperative pain on a visual analogue scale revealed a significantly lower mean level among patients undergoing LA (LAS and LAL) versus OA (P <0.001). Patients undergoing LA resumed regular activities sooner than those undergoing OA (9 +/- 9 days versus 14 +/- 11 days, P <0.001). Rates of readmission to the hospital were similar for all procedures. CONCLUSIONS: Laparoscopic appendectomy appears to have distinct advantages over open appendectomy. The laparoscopic procedures produced less pain and. allowed more rapid return to full activities, and LAS required shorter hospital stays. The only disadvantages to the laparoscopic approach were slightly increased operative time for both procedures, and increased emesis following LAL. C1 EMORY UNIV,SCH MED,DEPT SURG,ATLANTA,GA 30322. UNIV SO CALIF,DEPT SURG,LOS ANGELES,CA. OREGON HLTH SCI UNIV,DEPT SURG,PORTLAND,OR 97201. UNIV VIRGINIA,DEPT SURG,CHARLOTTESVILLE,VA. MASSACHUSETTS GEN HOSP,BOSTON,MA. WASHINGTON UNIV,SCH MED,ST LOUIS,MO. SHAWNEE MISSION,SHAWNEE MISSION MED CTR,SHAWNEE,KS. MICHIGAN STATE UNIV,E LANSING,MI. NR 8 TC 243 Z9 248 U1 0 U2 8 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD FEB PY 1995 VL 169 IS 2 BP 208 EP 213 DI 10.1016/S0002-9610(99)80138-X PG 6 WC Surgery SC Surgery GA QE637 UT WOS:A1995QE63700004 PM 7840381 ER PT J AU ZITTEL, TT VONELM, B TEICHMANN, RK RABOULD, HE BECKER, HD AF ZITTEL, TT VONELM, B TEICHMANN, RK RABOULD, HE BECKER, HD TI CHOLECYSTOKININ IS PARTLY RESPONSIBLE FOR REDUCED FOOD-INTAKE AND BODY-WEIGHT LOSS AFTER TOTAL GASTRECTOMY IN RATS SO AMERICAN JOURNAL OF SURGERY LA English DT Article ID ROUX-Y ESOPHAGOJEJUNOSTOMY; RECEPTOR-BINDING SITES; CCK-A RECEPTORS; NUTRITIONAL-STATUS; BRAIN; RECONSTRUCTION; ANTAGONIST; L-365,260; MALABSORPTION; CONSEQUENCES AB PURPOSE: To determine the cause of body weight loss after total gastrectomy. METHODS: We evaluated the acute effect of exogenous cholecystokinin (CCK) on food intake and the chronic effect of CCK receptor blockade on food intake and body weight after total gastrectomy in rats. RESULTS: Exogenous CCK significantly reduced food intake in gastrectomized rats; this was blocked by administration of a CCK-A but not a CCK-B receptor antagonist. Chronic treatment with a CCK-A or CCK-B receptor antagonist after total gastrectomy in rats significantly increased postoperative food intake and body weight. CONCLUSION: Our data indicate that endogenous CCK is partly responsible for reduced food intake and body weight loss after total gastrectomy in rats. C1 UNIV TUBINGEN HOSP,DEPT ABDOMINAL & TRANSPLANTAT SURG,TUBINGEN,GERMANY. W LOS ANGELES VET AFFAIRS MED CTR,CTR GASTROENTER BIOL,CURE,LOS ANGELES,CA. UNIV CALIF LOS ANGELES,LOS ANGELES,CA. NR 50 TC 15 Z9 15 U1 0 U2 0 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD FEB PY 1995 VL 169 IS 2 BP 265 EP 270 DI 10.1016/S0002-9610(99)80148-2 PG 6 WC Surgery SC Surgery GA QE637 UT WOS:A1995QE63700014 PM 7840391 ER PT J AU FERRY, JA HARRIS, NL PAPANICOLAOU, N YOUNG, RH AF FERRY, JA HARRIS, NL PAPANICOLAOU, N YOUNG, RH TI LYMPHOMA OF THE KIDNEY - A REPORT OF 11 CASES SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE LYMPHOMA; KIDNEY; B CELL; MALT ID PRIMARY RENAL LYMPHOMA; B-CELL LYMPHOMA; NON-HODGKINS-LYMPHOMA; MALIGNANT-LYMPHOMA; ACQUIRED-IMMUNODEFICIENCY; FAILURE; DISEASE; INFILTRATION; INVOLVEMENT; DIAGNOSIS AB We describe 11 patients first seen with symptoms or signs related to lymphoma predominantly or exclusively involving one or both kidneys. The patients were seven men and four women, aged 40-77 years (median, 67). Seven of them had one or more other prior (four), subsequent (two) or both simultaneous and subsequent (one) primary malignant or premalignant lesions. The presenting symptoms of the patients with lymphoma included local pain (five cases), loss of appetite or nausea (four cases), hematuria (two cases), weight loss (two cases) or malaise (two cases). One patient had renal failure at presentation. One lymphoma was an incidental finding at the time of aneurysm resection. Nine patients had unilateral disease; two patients had bilateral disease. Six unilateral cases were initially considered on clinical (five) or clinical and pathological (one) evaluation to be primary carcinomas of the kidney. Gross examination of nephrectomy specimens revealed fleshy or firm, yellow, tan, or gray tumors from 5.7 to 22 cm (median, 7.5) in greatest dimensions that frequently invaded perinephric fat and adjacent structures. The lymphomas were subclassified as diffuse large cell (seven cases), follicular and diffuse large cell (one case), small lymphocytic plasmacytoid (two cases), and small noncleaved cell lymphoma (non-Burkitt's type) (one case). Immunophenotyping in nine cases revealed that all were B-lineage tumors. Three patients had Ann Arbor stage I disease, three had stage II, and five had stage IV. On follow-up, ranging from 1 week to 169 months (median, 15 months), 5 patients were alive and free of lymphoma. Four patients died of progressive disease 1 week to 23 months after diagnosis. One patient is alive at 4 months but has not completed chemotherapy. One asymptomatic patient has not been treated. Renal lymphomas are predominantly large-cell lymphomas of B-lineage affecting middle-aged and older adults and often can be treated successfully. Both clinically and pathologically, they can be mistaken for carcinomas of the kidney. A high proportion of patients in this series had malignant tumors of other types. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT RADIOL,BOSTON,MA 02115. RP FERRY, JA (reprint author), MASSACHUSETTS GEN HOSP,DEPT PATHOL,JAMES HOMER WRIGHT PATHOL LABS,BOSTON,MA 02114, USA. NR 71 TC 51 Z9 55 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD FEB PY 1995 VL 19 IS 2 BP 134 EP 144 DI 10.1097/00000478-199502000-00002 PG 11 WC Pathology; Surgery SC Pathology; Surgery GA QC789 UT WOS:A1995QC78900002 PM 7832273 ER PT J AU GOULART, RA MARK, EJ ROSEN, S AF GOULART, RA MARK, EJ ROSEN, S TI TUMEFACTIONS AS AN EXTRAVASCULAR MANIFESTATION OF WEGENERS GRANULOMATOSIS SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE WEGENERS GRANULOMATOSIS; VASCULITIS; RETROPERITONEAL FIBROSIS; ANTINEUTROPHIL CYTOPLASMIC ANTIBODY; STRAWBERRY GUMS; ORBITAL PSEUDOTUMOR; BREAST; MEDIASTINUM ID POLYARTERITIS NODOSA; STRAWBERRY GUMS; LIMITED FORM; BREAST; INVOLVEMENT; ADENOPATHY; DIAGNOSIS; STENOSIS; FEATURES; BIOPSY AB Wegener's granulomatosis appeared as localized or infiltrative tumefactions in six patients. The tissue swellings affected the retroperitoneum, mediastinum (two), breast, retroorbital tissue (two), and gingiva. There was extensive fibroblastic proliferation in each case with a predominantly granulocytic inflammatory component, microabscess formation, and collagen necrobiosis. In one of the mediastinal lesions and in the gingiva, there was a granulomatous component as well. In the breast were scattered multinucleated histiocytes. Necrotizing vasculitis was absent or limited in all cases. All patients responded dramatically to cyclophosphamide and/or prednisone after the diagnosis was established. These observations indicate a role for tissue destruction in Wegener's granulomatosis mediated by granulocytes without a vasculitic component. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. RP GOULART, RA (reprint author), BETH ISRAEL HOSP,DEPT PATHOL,330 BROOKLINE AVE,BOSTON,MA 02215, USA. NR 51 TC 29 Z9 29 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD FEB PY 1995 VL 19 IS 2 BP 145 EP 153 DI 10.1097/00000478-199502000-00003 PG 9 WC Pathology; Surgery SC Pathology; Surgery GA QC789 UT WOS:A1995QC78900003 PM 7832274 ER PT J AU NORMAN, J GAHTAN, V FRANZ, M BRAMSON, R AF NORMAN, J GAHTAN, V FRANZ, M BRAMSON, R TI OCCULT VASCULAR INJURIES FOLLOWING GUNSHOT WOUNDS RESULTING IN LONG-BONE FRACTURES OF THE EXTREMITIES SO AMERICAN SURGEON LA English DT Article; Proceedings Paper CT 62nd Annual Scientific Meeting and Post Graduate Course Program of the Southeastern-Surgical-Congress CY FEB 06-10, 1994 CL LAKE BUENA VISTA, FL SP SE SURG CONGRESS ID TRAUMA ANGIOGRAPHY; ARTERIOGRAPHY; PROXIMITY AB The routine use of arteriography following penetrating injuries to the extremities has declined in popularity in recent years. A careful physical examination coupled with Doppler-derived blood pressure has been shown to be sufficient to determine the presence of significant vascular injuries in most circumstances. Evaluating for occult vascular injuries in the presence of a complex wound involving the fracture of a long bone, however, seems to be an exception to this trend in management. This study was undertaken to ascertain the incidence of occult versus clinically apparent vascular injuries in patients suffering gun shot wounds (GSW) to the extremities that were associated with a long bone fracture. To address the value of invasive arteriographic evaluation, physical examination (pulse palpation, Doppler-derived limb blood pressure) was compared to arteriography in 75 consecutive patients following a GSW that resulted in fracture of the tibia/fibula (n = 28), femur (n = 19), humerus (n = 17), or radius/ulna (n = 11). Fourteen patients (19%) had an abnormal physical examination, with 13 (93%) of these also having an abnormal arteriogram. Of the 61 (81%) patients with a normal physical examination, an occult vascular injury was found on subsequent arteriography in 17 (28%). These occult injuries were classified as minor (intimal flap less than one-fourth the diameter of the vessel, segmental narrowing, noncritical branch vessel injury) or major (large intimal flap, occlusion, pseudoaneurysm, A-V fistula). The majority (83%) of occult injuries were minor and did not require operative intervention. Seventeen per cent of the occult injuries were classified as major, but required repair or ligation in only one (1.6% of all patients with normal vascular physical examination). There were no amputations or complications resulting from the nonoperated occult injuries after a mean follow up period of 5.4 months. We conclude that clinically occult arterial injuries-although present in nearly one-third of patients following GSW and fracture-typically demonstrate an uneventful, self-limited natural history. Although the sensitivity of physical examination alone is relatively modest (77%) in detecting occult vascular injuries, the benign natural course for the vast majority of these injuries and the infrequent need for surgical repair suggest that the routine use of arteriography is not justified even when the GSW is associated with a long bone fracture. C1 HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02115. RP NORMAN, J (reprint author), UNIV S FLORIDA,SCH MED,DEPT SURG,ROOM 112,13000 BRUCE B DOWNS BLVD,TAMPA,FL 33612, USA. NR 10 TC 16 Z9 16 U1 0 U2 1 PU SOUTHEASTERN SURGICAL CONGRESS PI ATLANTA PA 1776 PEACHTREE RD, NW., SUITE 410N, ATLANTA, GA 30309-2352 SN 0003-1348 J9 AM SURGEON JI Am. Surg. PD FEB PY 1995 VL 61 IS 2 BP 146 EP 150 PG 5 WC Surgery SC Surgery GA QH858 UT WOS:A1995QH85800012 PM 7856975 ER PT J AU KIKUCHI, T KIMURA, RS PAUL, DL ADAMS, JC AF KIKUCHI, T KIMURA, RS PAUL, DL ADAMS, JC TI GAP-JUNCTIONS IN THE RAT COCHLEA - IMMUNOHISTOCHEMICAL AND ULTRASTRUCTURAL ANALYSIS SO ANATOMY AND EMBRYOLOGY LA English DT Article DE GAP JUNCTION; CONNEXIN26; RAT; COCHLEA ID INTER-CELLULAR JUNCTIONS; GUINEA-PIG COCHLEA; STRIA VASCULARIS; SUPPORTING CELLS; INTERCELLULAR-JUNCTIONS; MOLECULAR-CLONING; INNER-EAR; INTRACELLULAR-RECORDINGS; DC POTENTIALS; ORGAN AB Gap junctions in the rat cochlea were investigated using immunostaining for connexin26 and transmission electron microscopy. Electron microscopy of normal and pre-embedded immunostained material showed that there were gap junctions between and among all cells that light microscopy showed to have immunostained appositions. Light microscopy showed immunostaining between and among all cell types that electron microscopy showed to be joined by gap junctions. Immunostaining for connexin26 was therefore taken as providing a reasonable approximation of the locations of gap junctions throughout the cochlea and was used to provide an overview of the extent of those locations. Cells interconnected via gap junctions fell into one of two groups. The first group consists of nonsensory epithelial cells and includes interdental cells of the spiral limbus, inner sulcus cells, organ of Corti supporting cells, outer sulcus cells, and cells within the root processes of the spiral ligament. The second group consists of connective tissue cells and includes various fibrocyte types of the spiral limbus and spiral ligament, basal and intermediate cells of the stria vascularis, and mesenchymal cells which line the scala vestibuli. The present work represents a first attempt towards a description of how serial gap junctions among cochlear cells reflect a level of organization of the tissue. The organization described here, together with a great deal of information from previous investigators, suggest that serially arranged gap junctions of both epithelial and connective tissue cells serve as the strucural basis for recycling endolymphatic potassium ions that pass through the sensory cells during the transduction process. C1 HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02114. MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. FU NIDCD NIH HHS [R01 DC00073] NR 53 TC 403 Z9 430 U1 0 U2 10 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-2061 J9 ANAT EMBRYOL JI Anat. Embryol. PD FEB PY 1995 VL 191 IS 2 BP 101 EP 118 DI 10.1007/BF00186783 PG 18 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA QC068 UT WOS:A1995QC06800003 PM 7726389 ER PT J AU EISENBERG, E CARR, DB CHALMERS, TC AF EISENBERG, E CARR, DB CHALMERS, TC TI NEUROLYTIC CELIAC PLEXUS BLOCK FOR TREATMENT OF CANCER PAIN - A METAANALYSIS SO ANESTHESIA AND ANALGESIA LA English DT Article ID PANCREATIC-CANCER; ABDOMINAL-PAIN; RELIEF; ALCOHOL; TRIALS AB We performed a meta-analysis of the efficacy and safety of neurolytic celiac plexus block (NCPB) for cancer pain. A literature search yielded 59 papers, but data on NCPB in two or more patients was available in only 24 papers. Twenty-one studies were retrospective, one was prospective, and two were randomized and controlled. Cancer type was stated in 1117 of 1145 patients reported (63% pancreatic, 37% nonpancreatic). A bilateral posterior approach with 150-50 mt of 50%-100% alcohol was the most common technique. Nonradiologically guided NCPB was performed in 246 patients (32%); guidance was by computed tomography (CT) in 214 (28%), radiograph in 271 (34%), fluoroscopy in 36 (5%), or ultrasound in 7 (<1%). Good to excellent pain relief was reported in 878/989 patients (89%) during the first 2 wk after NCPB. Long-term followup beyond 3 mo revealed persistent benefit. Partial to complete pain relief continued in approximately 90% of patients alive at 3 mo post-NCPB and in 70%-90% until death even if beyond 3 mo post-NCPB, Patients with pancreatic cancer responded similarly to those with other intraabdominal malignancies. Common adverse effects were transient, including local pain (96%), diarrhea (44%), and hypotension (38%); complications occurred in 2%. This analysis suggests that: 1) NCPB has long-lasting benefit for 70%-90% of patients with pancreatic and other intraabdominal cancers, regardless of the technique used; 2) adverse effects are common but transient and mild; and 3) severe adverse effects are uncommon. C1 TUFTS UNIV NEW ENGLAND MED CTR,DEPT ANESTHESIA,BOSTON,MA 02111. TUFTS UNIV NEW ENGLAND MED CTR,DEPT MED,DIV CLIN CARE RES,BOSTON,MA 02111. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA. HARVARD UNIV,SCH MED,BOSTON,MA. RAMBAM MED CTR,PAIN RELIEF CLIN,HAIFA,ISRAEL. NR 32 TC 220 Z9 232 U1 0 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD FEB PY 1995 VL 80 IS 2 BP 290 EP 295 DI 10.1097/00000539-199502000-00015 PG 6 WC Anesthesiology SC Anesthesiology GA QD734 UT WOS:A1995QD73400015 PM 7818115 ER PT J AU REBECK, GW HARR, SD STRICKLAND, DK HYMAN, BT AF REBECK, GW HARR, SD STRICKLAND, DK HYMAN, BT TI MULTIPLE, DIVERSE SENILE PLAQUE-ASSOCIATED PROTEINS ARE LIGANDS OF AN APOLIPOPROTEIN-E RECEPTOR, THE ALPHA(2)-MACROGLOBULIN RECEPTOR LOW-DENSITY-LIPOPROTEIN RECEPTOR-RELATED PROTEIN SO ANNALS OF NEUROLOGY LA English DT Article ID AMYLOID-BETA-PROTEIN; SPORADIC ALZHEIMERS-DISEASE; ACTIVATOR INHIBITOR TYPE-1; ALPHA-2-MACROGLOBULIN RECEPTOR; PLASMINOGEN-ACTIVATOR; HUMAN BRAIN; NERVOUS-SYSTEM; MESSENGER-RNA; HIGH-AFFINITY; PEPTIDE AB Both apolipoprotein E and its receptor, the low-density-lipoprotein receptor-related protein (LRP), are associated with senile plaques in Alzheimer's disease. We examined the relationship of other LRP-related molecules to senile plaques. LRP is a multifunctional receptor that binds and rapidly internalizes at least seven ligands: apolipoprotein E, activated alpha(2)-macroglobulin, tissue and urokinase-type plasminogen activators, plasminogen activator inhibitor-1, lipoprotein lipase, and lactoferrin. Using immunohistochemistry, we showed that all of these ligands, representing a diverse group of otherwise apparently unrelated proteins, accumulate on senile plaques. We also studied expression of the receptor-associated protein, a physiological inhibitor of LRP, in the hippocampal formation from normal subjects and Alzheimer's disease patients. Receptor-associated protein colocalizes with LRP on neuronal soma, but not on neuronal processes or reactive astrocytes. It is not present on senile plaques. These results suggest that senile plaque-associated LRP can bind its ligands, but clearance of these compounds may be impaired in the vicinity of senile plaques. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. AMER RED CROSS,DEPT BIOCHEM,ROCKVILLE,MD. FU NIA NIH HHS [AG08487, AG05598]; NIGMS NIH HHS [GM42581] NR 52 TC 252 Z9 253 U1 0 U2 4 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 1995 VL 37 IS 2 BP 211 EP 217 DI 10.1002/ana.410370212 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA QG846 UT WOS:A1995QG84600011 PM 7531418 ER PT J AU LANDWEHRMEYER, GB MCNEIL, SM DURE, LS GE, P AIZAWA, H HUANG, Q AMBROSE, CM DUYAO, MP BIRD, ED BONILLA, E DEYOUNG, M AVILAGONZALES, AJ WEXLER, NS DIFIGLIA, M GUSELLA, JF MACDONALD, ME PENNEY, JB YOUNG, AB VONSATTEL, JP AF LANDWEHRMEYER, GB MCNEIL, SM DURE, LS GE, P AIZAWA, H HUANG, Q AMBROSE, CM DUYAO, MP BIRD, ED BONILLA, E DEYOUNG, M AVILAGONZALES, AJ WEXLER, NS DIFIGLIA, M GUSELLA, JF MACDONALD, ME PENNEY, JB YOUNG, AB VONSATTEL, JP TI HUNTINGTONS-DISEASE GENE - REGIONAL AND CELLULAR EXPRESSION IN BRAIN OF NORMAL AND AFFECTED INDIVIDUALS SO ANNALS OF NEUROLOGY LA English DT Article ID STRIATAL PROJECTION NEURONS; TRINUCLEOTIDE CAG REPEAT; BULBAR MUSCULAR-ATROPHY; MESSENGER-RNA; INSITU HYBRIDIZATION; MYOTONIC-DYSTROPHY; ANDROGEN RECEPTOR; FRAGILE-X; INSTABILITY; NUCLEUS AB Huntington's disease (HD) is an autosomal dominant disorder characterized by involuntary movements, dementia, and progressive, global, but regionally accentuated, brain atrophy. The disease affects the striatum most severely. An expansion of a trinucleotide repeat on chromosome 4p16.3 within the coding region of a gene termed IT15 has been identified as the mutation causing HD. The normal function of IT15 and the mechanisms by which the presence of the mutation causes HD are unknown. Although IT15 expression has been detected in the brain, as well as in other organ tissues,. by Northern blot and in situ hybridization, it is not known whether a preferential regional or cellular expression of IT15 exists within the central nervous system of normal, affected, and presymptomatic individuals. Using quantitative in situ hybridization methods, we examined extensively the regional and cellular expression of IT15. In controls, IT15 expression was observed in all brain regions examined with the highest levels seen in cerebellum, hippocampus, cerebral cortex, substantia nigra pars compacta. and pontine nuclei. Expression in the striatum was intermediate and expression in the globus pallidus was low. IT15 was expressed predominantly in neurons; a low but significant level of expression was seen in glial cells. Analysis of grain counts per square micrometer in neurons showed that the regional differences in the level of mRNA expression were related to density and size of neurons in a given region and not primarily to differences in levels of mRNA expression in individual cells after correction for cell size. Neurons susceptible to degeneration in HD did not selectively express high levels of IT15 mRNA. In HD brains (grades 2-4), the distribution and levels of IT15 mRNA were comparable with controls in all areas except in neostriatum where the intensity of labeling was significantly reduced. Presymptomatic HD brains had a striatal expression similar to controls and surviving striatal neurons in more advanced HD had an expression of IT15 within normal limits. It is apparent from these results that the presence of expanded trinucleotide repeats in IIB does not result in the absence of IT15 mRNA expression or in altered patterns or levels of expression. The lack of correlation between the levels of IT15 mRNA expression and susceptibility to degeneration in HD strongly suggests that the mutant gene acts in concert with other factors to cause the distinctive pattern of neurodegeneration in HD. C1 MASSACHUSETTS GEN HOSP E,CTR NEUROSCI,MOLEC NEUROGENET UNIT,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA. MCLEAN HOSP,CTR BRAIN TISSUE RESOURCE,BELMONT,MA 02178. HARVARD UNIV,SCH MED,DEPT NEUROPATHOL,BELMONT,MA 02178. UNIV ZULIA,MARACAIBO,VENEZUELA. COLUMBIA UNIV,COLL PHYS & SURG,DEPT NEUROL,NEW YORK,NY 10032. COLUMBIA UNIV,COLL PHYS & SURG,DEPT PSYCHIAT,NEW YORK,NY 10032. HEREDITARY DIS FDN,SANTA MONICA,CA. RI Dure, Leon/B-3243-2008 FU NIA NIH HHS [AG08856]; NIMH NIH HHS [MH 31862]; NINDS NIH HHS [NS 16367] NR 59 TC 140 Z9 142 U1 0 U2 6 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 1995 VL 37 IS 2 BP 218 EP 230 DI 10.1002/ana.410370213 PG 13 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA QG846 UT WOS:A1995QG84600012 PM 7847863 ER PT J AU KIMURA, RS TREHEY, JA HUTTA, J AF KIMURA, RS TREHEY, JA HUTTA, J TI DEGENERATION OF VESTIBULAR SENSORY CELLS CAUSED BY ABLATION OF THE VESTIBULAR AQUEDUCT IN THE GERBIL EAR SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE ENDOLYMPHATIC HYDROPS; VESTIBULAR AQUEDUCT VEIN; VESTIBULAR SENSORY CELL DEGENERATION ID MENIERES-DISEASE; ENDOLYMPHATIC HYDROPS; SAC AB The vestibular aqueduct of the gerbil has a unique anatomic feature that makes it possible to selectively obliterate the endolymphatic sac with or without interfering with its venous drainage. In animals in which only the endolymphatic sac was ablated, endolymphatic hydrops was slight in the cochlea and was al,sent in the vestibular labyrinth. The cochlear and vestibular sensory cells were normal. In animals in which both the endolymphatic duct and the vein were obliterated, hydrops was slight, with the exception of a few cochleas that showed moderate hydrops. The sensory cells of the posterior canal cristae had degenerated in all specimens, while varied pathologic changes in cochlear and vestibular sensory cells were present in some specimens. These results suggest that hydrops is primarily due to blockage of the endolymphatic duct and sac and that degeneration of sensory cells occurs when blood flow in the vestibular aqueduct is impeded. Pathologic changes in the endolymphatic sac, including the vascular plexus at the endolymphatic sac, may play an important role in the production of endolymphatic hydrops and vestibular symptoms in Meniere's disease. C1 HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02115. RP KIMURA, RS (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,243 CHARLES ST,BOSTON,MA 02114, USA. FU NIDCD NIH HHS [R01 DC00073] NR 23 TC 6 Z9 6 U1 0 U2 0 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD FEB PY 1995 VL 104 IS 2 BP 155 EP 160 PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA QG227 UT WOS:A1995QG22700013 PM 7857019 ER PT J AU SINGER, S CORSON, JM DEMETRI, GD HEALEY, EA MARCUS, K EBERLEIN, TJ AF SINGER, S CORSON, JM DEMETRI, GD HEALEY, EA MARCUS, K EBERLEIN, TJ TI PROGNOSTIC FACTORS PREDICTIVE OF SURVIVAL FOR TRUNCAL AND RETROPERITONEAL SOFT-TISSUE SARCOMA SO ANNALS OF SURGERY LA English DT Article ID RANDOMIZED TRIAL; POSTOPERATIVE RADIOTHERAPY; ADJUVANT CHEMOTHERAPY; EXTREMITY; SURGERY; DOXORUBICIN; THERAPY; ADULTS AB Objective The authors identified prognostic factors relevant to clinical outcomes (especially survival) in truncal and retroperitoneal soft-tissue sarcoma. Summary Background Data These results can be used to optimize surgical management and select patients most likely to benefit from novel therapeutic strategies in future trials. Methods A retrospective analysis was performed of a prospectively compiled database of 183 consecutive patients with truncal and retroperitoneal sarcomas seen at the Brigham and Women's Hospital and the Dana Farber Cancer Institute between 1970 to 1994. Results For truncal sarcoma, multivariate analysis showed that high-grade histology was associated with an eightfold increased risk of death compared with low-grade histology (p = 0.001). In addition to grade, gross positive margin of resection (p = 0.001), microscopic positive margin (p = 0.023), and tumors greater than 5 cm in size (p = 0.018) were important independent prognostic factors for survival. In this series, postoperative radiation therapy for truncal sarcoma was associated with a 2.4-fold decreased risk of death compared with truncal sarcoma patients receiving no adjuvant radiation therapy, having adjusted for the other prognostic factors (p = 0.030). In contrast, for retroperitoneal sarcoma, multivariate analysis showed that high-grade and intermediate-grade histology were associated with a five- to sixfold increased risk of death compared with low-grade histology (p = 0.009). In addition to grade, gross positive margin of resection (p = 0.001) and microscopic positive margin (p = 0.004) were important independent prognostic factors for survival in retroperitoneal sarcoma. Patients who received either preoperative or postoperative chemotherapy for retroperitoneal sarcoma had a 4.6-fold (p = 0.002) and 3-fold (p = 0.010) increased risk of death, respectively, compared with patients receiving no adjuvant chemotherapy, having adjusted for the other prognostic factors. Conclusions The histologic grade and the margin of resection are prognostic for survival in both truncal and retroperitoneal soft tissue sarcoma. Tumor size was an independent prognostic factor for truncal sarcoma, but not for retroperitoneal sarcoma. Postoperative adjuvant radiation was beneficial to overall survival for truncal sarcoma. In this series of patients receiving a heterogeneous mixture of chemotherapeutic regimens-either as preoperative ''neoadjuvant'' therapy or as postoperative ''adjuvant'' therapy, there were no beneficial effects on survival compared with nonrandomized patients not receiving chemotherapy. C1 BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. RP SINGER, S (reprint author), HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT SURG,DIV SURG ONCOL,75 FRANCIS ST,BOSTON,MA 02115, USA. NR 20 TC 166 Z9 175 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD FEB PY 1995 VL 221 IS 2 BP 185 EP 195 DI 10.1097/00000658-199502000-00009 PG 11 WC Surgery SC Surgery GA QF808 UT WOS:A1995QF80800009 PM 7857146 ER PT J AU CANVER, CC ARMSTRONG, VM NICHOLS, RD MENTZER, RM AF CANVER, CC ARMSTRONG, VM NICHOLS, RD MENTZER, RM TI COLOR-FLOW DUPLEX ULTRASOUND ASSESSMENT OF INTERNAL THORACIC ARTERY GRAFT AFTER CORONARY-BYPASS SO ANNALS OF THORACIC SURGERY LA English DT Article ID MAMMARY ARTERY; REACTIVE HYPEREMIA AB In an effort to develop a noninvasive method to evaluate now characteristics of the internal thoracic artery (ITA) graft after coronary artery bypass grafting, we performed color-now duplex ultrasound studies of the right and left ITAs of 42 patients before and 5 weeks after bypass grafting. The ITA was visualized with a duplex scanner (5.0-MHz probe) through the first or second intercostal space. We recorded the diameter, peak systolic velocity, and end-diastolic velocity for each patient. Preoperative measurements of the native ITAs were obtained easily in all patients. Postoperatively, the unused right ITA was seen in all patients. Postoperative visualization of the left ITA graft was adequate to make reliable measurements in 40 patients (95%). Postoperative end-diastolic velocities of the unused right ITA and the left ITA graft were markedly higher than the preoperative end-diastolic velocities of the native ITAs (p < 0.001). Whereas there was a marked increase in the peak systolic velocity of the postoperative unused right ITA (p < 0.05), the postoperative peak systolic velocity of the left ITA graft was significantly lower than the preoperative value (p < 0.001). We conclude that postoperative visualization of the left ITA graft is possible with the use of color-flow duplex ultrasound. Ultrasonic surveillance of postoperative ITAs may reveal ITA graft velocity abnormalities before overt graft failure is manifested in the patient who has undergone coronary artery bypass grafting. C1 UNIV WISCONSIN,WILLIAM S MIDDLETON MEM VET HOSP,SCH MED,CARDIOTHORAC SURG SECT,MADISON,WI. NR 11 TC 15 Z9 16 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD FEB PY 1995 VL 59 IS 2 BP 389 EP 392 DI 10.1016/0003-4975(94)00842-U PG 4 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA QF299 UT WOS:A1995QF29900021 PM 7847953 ER PT J AU KAPLAN, DK ATSUMI, N DAMBRA, MN VLAHAKES, GJ AF KAPLAN, DK ATSUMI, N DAMBRA, MN VLAHAKES, GJ TI DISTAL CIRCULATORY SUPPORT FOR THORACIC AORTIC OPERATIONS - EFFECTS ON INTRACRANIAL-PRESSURE SO ANNALS OF THORACIC SURGERY LA English DT Article ID ANEURYSMS; BYPASS; SHUNT; PARAPLEGIA; OCCLUSION AB Spinal cord ischemia can result from aortic clamping during thoracic aortic operations. The perfusion gradient for spinal cord perfusion is positively influenced by distal aortic pressure and negatively influenced by intracranial pressure (ICP). Hemodynamic and ICP changes were examined in a swine model of descending thoracic aortic surgery where distal aortic perfusion was achieved under one of three conditions: (1) clamping without support, (2) a passive aortofemoral shunt, or (3) a left atrium-femoral artery bypass system. With aortic clamping alone, ICP increased from 9.8 +/- 2.2 mm Hg to 15.2 +/- 2.8 mm Hg (p < 0.05). With passive shunting, ICP was decreased to 13.8 +/- 3.0 mm Hg, which was still significantly elevated above baseline. However, with active bypass, ICP remained at control level (9.8 +/- 2.2 mm Hg). Mean distal aortic pressure, which was 82 +/- 10 mm Hg in the control state, decreased to 20 +/- 0.5 mm Hg with clamping alone and to 39 +/- 9 mm Hg with passive shunting, whereas with active support, a distal pressure of 64 +/- 8 mm Hg was achieved. In contrast to passive shunting, active distal bypass results in maintenance of ICP at baseline levels and results in distal aortic pressure significantly greater than that achieved with either aortic clamping alone or passive shunting. Thus, active distal circulatory support produces the greatest salutary effect on the two determinants of the spinal cord perfusion pressure gradient: ICP and distal aortic pressure. This support modality may be the best adjunctive technique to maintain the spinal cord perfusion gradient and hence minimize the risk of ischemic injury. C1 MASSACHUSETTS GEN HOSP,DEPT SURG,CARDIAC SURG UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MED,CARDIAC ANESTHESIA GRP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 26 TC 14 Z9 14 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD FEB PY 1995 VL 59 IS 2 BP 448 EP 452 DI 10.1016/0003-4975(94)00849-3 PG 5 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA QF299 UT WOS:A1995QF29900033 PM 7847964 ER PT J AU MARDER, K RICHARDS, M BELLO, J BELL, K SANO, M MILLER, L FOLSTEIN, M ALBERT, M STERN, Y AF MARDER, K RICHARDS, M BELLO, J BELL, K SANO, M MILLER, L FOLSTEIN, M ALBERT, M STERN, Y TI CLINICAL CORRELATES OF ALZHEIMERS-DISEASE WITH AND WITHOUT SILENT RADIOGRAPHIC ABNORMALITIES SO ARCHIVES OF NEUROLOGY LA English DT Article ID WHITE MATTER LUCENCIES; CEREBROVASCULAR RISK-FACTORS; CEREBRAL BLOOD-FLOW; SCAN LEUKO-ARAIOSIS; COGNITIVE IMPAIRMENT; SIGNAL ABNORMALITIES; NEUROLOGIC FINDINGS; BRAIN MR; DEMENTIA; INDIVIDUALS AB Objective: To determine whether patients with Alzheimer's disease (AD) who do not have historical or clinical evidence of stroke but who do have computed tomographic or magnetic resonance imaging evidence of noncortical lesions smaller than 2 cm or periventricular ''caps'' differ from other patients with AD. Methods: The computed tomographic or magnetic resonance imaging scans of 158 patients meeting criteria of the National Institute of Neurological Disorders and Stroke-Alzheimer's Disease and Related Disorders Association for probable AD were reviewed by one neuroradiologist. Two measures of disease severity-the Modified Mini-Mental State examination and the Blessed Dementia Rating Scale (Part I)-were subjected to two-way analysis of variance with scan type (computed tomography or magnetic resonance imaging) and lesion number as between-group factors and age and disease duration as covariates. Results: No relationship was seen between lesion number or periventricular caps and disease severity, Conclusion: In this cross-sectional analysis using these clinical measures, patients with AD who have well-defined radiographic abnormalities cannot be differentiated from patients with AD who do not have them. C1 COLUMBIA UNIV,COLL PHYS & SURG,DEPT PSYCHIAT,NEW YORK,NY 10032. COLUMBIA UNIV,COLL PHYS & SURG,GERTRUDE H SERGIEVSKY CTR,NEW YORK,NY 10032. COLUMBIA UNIV,COLL PHYS & SURG,CTR ALZHEIMERS DIS RES,NEW YORK,NY 10032. ALBERT EINSTEIN COLL MED,DIV NEURORADIOL,BRONX,NY. JOHNS HOPKINS UNIV,SCH MED,DEPT PSYCHIAT & BEHAV SCI,BALTIMORE,MD 21205. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PSYCHIAT,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROL,BOSTON,MA. RP MARDER, K (reprint author), COLUMBIA UNIV,COLL PHYS & SURG,INST NEUROL,DEPT NEUROL,710 W 168TH ST,BOX 5,NEW YORK,NY 10032, USA. FU NCRR NIH HHS [MO1 RR00645]; NIA NIH HHS [AG07232, AG07370] NR 31 TC 32 Z9 32 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 1995 VL 52 IS 2 BP 146 EP 151 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA QF548 UT WOS:A1995QF54800008 PM 7848122 ER PT J AU GOLDEN, JA NIELSEN, GP POBER, BR HYMAN, BT AF GOLDEN, JA NIELSEN, GP POBER, BR HYMAN, BT TI THE NEUROPATHOLOGY OF WILLIAMS-SYNDROME - REPORT OF A 35-YEAR-OLD MAN WITH PRESENILE BETA/A4 AMYLOID PLAQUES AND NEUROFIBRILLARY TANGLES SO ARCHIVES OF NEUROLOGY LA English DT Note ID IDIOPATHIC INFANTILE HYPERCALCEMIA; ALZHEIMERS-DISEASE; LONG ARM; PHENOTYPIC FEATURES; DOWNS-SYNDROME; MORPHOLOGY; DEMENTIA; DELETION; SENILE AB Objective: To study neuropathologically Williams syndrome in a 35-year-old patient. Methods: Sections from multiple regions of the brain were examined with luxol fast blue and hematoxylineosin staining, and selected sections were stained with the silver impregnation technique (Bielschowsky technique) and Congo red. In addition, immunohistochemistry with monoclonal antibodies against glial fibrillary acidic protein, beta/A4 amyloid, paired helical filaments, and phosphorylated tau protein was performed on cortical, hippocampal, amygdaloid, and basal ganglian sections. Results: No specific macroscopic or microscopic abnormalities were recognized that are specific for Williams syndrome. The histopathologic examination did, however, demonstrate the presence of Alzheimer-type changes, including beta/A4 amyloid-containing senile plaques and scattered neurofibrillary tangles in neocortex and medial temporal lobe structures (entorhinal cortex, CA1 area of the hippocampus, and amygdala). Plaques were most numerous in the amygdala (7/mm(2)) and in the entorhinal cortex (4/mm(2)). Neurofibrillary tangles were less numerous (<1/mm(2)), except in the hippocampus, where approximately 2/mm(2) were found. Conclusions: To our knowledge, ours represents the first neuropathologic description of a patient with Williams syndrome. Although Williams syndrome is usually sporadic, familial cases have been reported along with candidate chromosomal loci. If our findings are confirmed in additional patients with Williams syndrome, they map provide clues to other factors that are important in the pathogenesis of senile plaques (with beta/A4 amyloid deposition) and neurofibrillary tangles. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,PATHOL SERV NEUROPATHOL,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,NEUROL SERV,BOSTON,MA 02114. HARVARD UNIV,CHILDRENS HOSP,SCH MED,DIV GENET,BOSTON,MA 02114. YALE UNIV,SCH MED,DEPT GENET,NEW HAVEN,CT 06510. RP GOLDEN, JA (reprint author), HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT PATHOL NEUROPATHOL,75 FRANCIS ST,BOSTON,MA 02115, USA. FU NIA NIH HHS [P50-AG05134, AG08487] NR 35 TC 13 Z9 13 U1 1 U2 5 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 1995 VL 52 IS 2 BP 209 EP 212 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA QF548 UT WOS:A1995QF54800023 PM 7848137 ER PT J AU BHOL, K UDELL, I HAIDER, N YUNIS, JJ MOHIMEN, A NEUMAN, R GRASSO, C AHMED, AR FOSTER, S AF BHOL, K UDELL, I HAIDER, N YUNIS, JJ MOHIMEN, A NEUMAN, R GRASSO, C AHMED, AR FOSTER, S TI OCULAR CICATRICIAL PEMPHIGOID - A CASE-REPORT OF MONOZYGOTIC TWINS DISCORDANT FOR THE DISEASE SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; SYSTEMIC LUPUS-ERYTHEMATOSUS; DEPENDENT DIABETES-MELLITUS; DQ-BETA-CHAIN; MULTIPLE-SCLEROSIS; IDENTICAL-TWINS; RHEUMATOID-ARTHRITIS; NATIONWIDE SERIES; JEWISH PATIENTS; CONCORDANCE AB Objective: To identify the major histocompatibility complex markers and the autoantibody associated with ocular cicatricial pemphigoid (OCP) in a proband, her unaffected cotwin, and the children of the cotwin. Ocular cicatricial pemphigoid is a chronic autoimmune disorder that affects the conjunctiva and other squamous epithelium. It is associated with the major histocompatibility complex class II alleles that are presumed to provide enhanced susceptibility to the disease. We encountered a pair of monozygotic female twins, one of whom has OCP. In addition to totally identical physical appearances since birth, the two sisters have identical blood groups. Methods: The following studies were performed on the patient, her unaffected cotwin sister, and her children: (1) polymorphism of major histocompatibility complex class II genes by DNA typing, (2) sequence analysis of DQ beta gene second and third exons, and (3) serologic evaluation for the presence of anti-basement membrane zone autoantibodies specific for OCP by Western immunoblot with the use of skin and conjunctiva lysates as substrates. Result: Both monozygotic twins had the same HLA. haplotypes. The sequence analysis of the second and third exons of DQ beta genes revealed no significant differences between the proband and her unaffected cotwin. Autoantibodies specific to OCP were detected only in the patient's serum. The serum of the unaffected cotwin and the other relatives did not demonstrate the presence of the OCP autoantibody. Conclusion: This isolated family study does not support a single-gene theory for the development of OCP. It is most likely due to a multigene effect and associated with environmental factors. C1 BOSTON UNIV,SCH MED,DEPT DERMATOL,BOSTON,MA 02118. LONG ISL JEWISH MED CTR,ALBERT EINSTEIN COLL MED,DEPT OPHTHALMOL,NEW HYDE PK,NY 11042. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PATHOL,DIV IMMUNOGENET,BOSTON,MA 02115. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,BOSTON,MA. CATHOLIC MED CTR BROOKLYN QUEENS,BROOKLYN,NY. FU NEI NIH HHS [2RO1EY08379]; NIDCR NIH HHS [1RO1DE09978] NR 39 TC 11 Z9 12 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD FEB PY 1995 VL 113 IS 2 BP 202 EP 207 PG 6 WC Ophthalmology SC Ophthalmology GA QH042 UT WOS:A1995QH04200027 PM 7864752 ER PT J AU MANN, D SCHUMACHER, HR AF MANN, D SCHUMACHER, HR TI PSEUDOSEPTIC INFLAMMATORY KNEE EFFUSION CAUSED BY PHAGOCYTOSIS OF SICKLED ERYTHROCYTES AFTER FRACTURE INTO THE KNEE-JOINT SO ARTHRITIS AND RHEUMATISM LA English DT Note ID CELL DISEASE; ARTHRITIS AB A 57-year-old black man with sickle cell disease was admitted to the hospital because of a painful crisis. After a fall with a fracture into the right knee joint, he developed an acutely painful, swollen knee. Synovial fluid from the right knee showed leukocyte counts of up to 154,000/mm(3) and was negative for urate and calcium pyrophosphate dihydrate crystals. Gram stains and cultures were negative, Some sickled red cells were seen by light microscopy; electron microscopy revealed crystallike arrays of sickled hemoglobin tactoids in erythrocytes which were enfolded and phagocytized by the cells of the synovial fluid. We suggest that this phagocytosis of sickled red cells is the likely cause for the otherwise unexplained inflammation, C1 DEPT VET AFFAIRS MED CTR,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,PHILADELPHIA,PA 19104. OI Mann, Douglas /0000-0002-2516-0145 NR 10 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD FEB PY 1995 VL 38 IS 2 BP 284 EP 287 DI 10.1002/art.1780380219 PG 4 WC Rheumatology SC Rheumatology GA QF433 UT WOS:A1995QF43300018 PM 7848320 ER PT J AU MAHER, BA MANSCHRECK, TC WOODS, BT YURGELUNTODD, DA TSUANG, MT AF MAHER, BA MANSCHRECK, TC WOODS, BT YURGELUNTODD, DA TSUANG, MT TI FRONTAL BRAIN VOLUME AND CONTEXT EFFECTS IN SHORT-TERM RECALL IN SCHIZOPHRENIA SO BIOLOGICAL PSYCHIATRY LA English DT Article DE FRONTAL BRAIN VOLUME; SCHIZOPHRENIA; CONTEXT-AIDED RECALL; WORD LISTS ID THOUGHT-DISORDER; PREDICTABILITY; TOMOGRAPHY; CONSTRAINT AB In a group of schizophrenic patients, magnetic resonance imaging (MRI) measures of relative frontal brain volume (total frontal volume/total cerebral volume) correlated highly with the capacity to use context as an aid to recall in a verbal memory task. The dorsolateral area of the prefrontal cortex appears to have contributed most to this effect. Recall of simple word lists without contextual features revealed no correlation with relative frontal volume. With increasing contextual organization of the material, correlations between frontal volume and recall scores increased significantly. These findings are consistent with the general proposition that impairment in the use of informational redundancy is a significant component of schizophrenic pathology. C1 MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02114. DARTMOUTH COLL,SCH MED,DEPT PSYCHIAT,CONCORD,NH. NEW HAMPSHIRE HOSP,CONCORD,NH. VET AFFAIRS MED CTR,DEPT MED,TEMPLE,TX. HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BELMONT,MA 02178. MCLEAN HOSP,BELMONT,MA 02178. HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS MENTAL HLTH CTR,BOSTON,MA 02115. RP MAHER, BA (reprint author), HARVARD UNIV,DEPT PSYCHOL,1120 WILLIAM JAMES HALL,CAMBRIDGE,MA 02138, USA. FU NIMH NIH HHS [MH44277] NR 37 TC 58 Z9 58 U1 1 U2 1 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiat. PD FEB 1 PY 1995 VL 37 IS 3 BP 144 EP 150 DI 10.1016/0006-3223(94)00203-F PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA QD270 UT WOS:A1995QD27000002 PM 7727622 ER PT J AU LIU, SJ HAHN, WC BIERER, BE GOLAN, DE AF LIU, SJ HAHN, WC BIERER, BE GOLAN, DE TI INTRACELLULAR MEDIATORS REGULATE CD2 LATERAL DIFFUSION AND CYTOPLASMIC CA2+ MOBILIZATION UPON CD2-MEDIATED T-CELL ACTIVATION SO BIOPHYSICAL JOURNAL LA English DT Article ID HUMAN LYMPHOCYTE-T; E-ROSETTE FORMATION; FUNCTION-ASSOCIATED ANTIGEN-3; CYCLIC-AMP; MONOCLONAL-ANTIBODY; BINDING-SITES; MONOMERIC ACTIN; CYTOCHALASIN-D; CROSS-LINKING; 2ND LIGAND AB CD2 is a T cell surface glycoprotein that participates in T cell adhesion and activation. These processes are dynamically interrelated, in that T cell activation regulates the strength of CD2-mediated T cell adhesion. The lateral redistribution of CD2 and its ligand CD58 (LFA-3) in T cell and target membranes, respectively, has also been shown to affect cellular adhesion strength. We have used the fluorescence photobleaching recovery technique to measure the lateral mobility of CD2 in plasma membranes of resting and activated Jurkat T leukemia cells. CD2-mediated T cell activation caused lateral immobilization of 90% of cell surface CD2 molecules. Depleting cells of cytoplasmic Ca2+, loading cells with dibutyric cAMP, and disrupting cellular microfilaments each partially reversed the effect of CD2-mediated activation on the lateral mobility of CD2. These intracellular mediators apparently influence the same signal transduction pathways, because the effects of the mediators on CD2 lateral mobility were not additive. in separate experiments, activation-associated cytoplasmic Ca2+ mobilization was found to require microfilament integrity and to be negatively regulated by cAMP. By directly or indirectly controlling CD2 lateral diffusion and cell surface distribution, cytoplasmic Ca2+ mobilization may have an important regulatory role in CD2 mediated T cell adhesion. C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DIV HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. FU NHLBI NIH HHS [HL-15157, HL-32854]; NIAID NIH HHS [AI-28554] NR 68 TC 17 Z9 17 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 1995 VL 68 IS 2 BP 459 EP 470 PG 12 WC Biophysics SC Biophysics GA QC121 UT WOS:A1995QC12100007 PM 7696499 ER PT J AU WRAY, SH MIJOVICPRELEC, D KOSSLYN, SM AF WRAY, SH MIJOVICPRELEC, D KOSSLYN, SM TI VISUAL PROCESSING IN MIGRAINEURS SO BRAIN LA English DT Article DE MIGRAINE; LOW-LEVEL VISUAL PROCESSING ID MONKEY STRIATE CORTEX; CEREBRAL BLOOD-FLOW; CLASSICAL MIGRAINE; SPATIAL-FREQUENCY; AURA; SEARCH; ORIENTATION; DISCOMFORT; ACTIVATION; ATTENTION AB Twelve migraine subjects with aura and 12 matched control subjects performed four computerized visual tasks, Because chronic electroencephalographic and regional cerebral blood flow abnormalities in posterior brain functions have been documented during interictal periods, migraine subjects were tested between migraine attacks. Two tasks, orientation detection and temporal order judgement, were devised to examine 'low-level' visual processes. The results were compared with results from two tasks, picture naming and word priming, that were devised to examine 'high-level' visual processes. Regarding the response time data across all four tasks, the migraine group was faster in the two low-level tasks. There were no differences in error rate in any of the four tasks. The migraineur's apparent response time advantage in the low-level tasks provides a psychophysical corroboration of their assumed oversensitivity to visual stimuli The remaining two tasks, picture naming and word priming, which involve the use of previously stored information, do not distinguish migraineurs from matched control subjects. These results suggest that migraineurs are better in low-level visual processing, in that the signals to the primary visual cortex (Area V1) are processed more rapidly, but this hypersensitivity does not carry over to the subsequent processing stages (beyond V1 to superior parietal and inferior temporal cortices), as evidenced by the absence of a response time advantage in the two higher-level vision tasks. C1 HARVARD UNIV, DEPT PSYCHOL, CAMBRIDGE, MA 02138 USA. RP WRAY, SH (reprint author), MASSACHUSETTS GEN HOSP, DEPT NEUROL, NEUROVISUAL DISORDERS UNIT, ACC 837, 15 PARKMAN ST, BOSTON, MA 02114 USA. FU PHS HHS [P01-17778-09] NR 57 TC 96 Z9 97 U1 3 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 EI 1460-2156 J9 BRAIN JI Brain PD FEB PY 1995 VL 118 BP 25 EP 35 DI 10.1093/brain/118.1.25 PN 1 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA QP972 UT WOS:A1995QP97200003 PM 7895008 ER PT J AU CAPLAN, D WATERS, GS AF CAPLAN, D WATERS, GS TI ON THE NATURE OF THE PHONOLOGICAL OUTPUT PLANNING PROCESSES INVOLVED IN VERBAL REHEARSAL - EVIDENCE FROM APHASIA SO BRAIN AND LANGUAGE LA English DT Article ID SHORT-TERM-MEMORY; WORKING MEMORY; WORD-LENGTH; SPEECH; ARTICULATION; LEXICON; SPAN AB This paper describes the performance of an aphasic patient, R.W., in producing the sounds of words and in verbal rehearsal. R.W. showed evidence of retained abilities to access aspects of the forms of spoken words but made numerous phonemic paraphasias in single word production tasks. He did not show features of dysarthria or apraxia of speech. This pattern indicates that his deficit affected a process that plans the phonological forms of spoken words. R.W.'s performances in short-term memory and metalinguistic tasks involving single words were consistent with impaired rehearsal functions. The pattern of results indicates that rehearsal requires planning of the phonological forms of spoken items and suggests that activating entries in the phonological output lexicon is not adequate to permit rehearsal to proceed normally. (C) 1995 Academic Press, Inc. RP CAPLAN, D (reprint author), MASSACHUSETTS GEN HOSP,NEUROPSYCHOL LAB,VINCENT BURNHAM 827,FRUIT ST,BOSTON,MA 02114, USA. FU NIDCD NIH HHS [DC00942]; NINDS NIH HHS [NS29101] NR 37 TC 21 Z9 21 U1 1 U2 7 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0093-934X J9 BRAIN LANG JI Brain Lang. PD FEB PY 1995 VL 48 IS 2 BP 191 EP 220 DI 10.1006/brln.1995.1009 PG 30 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA QG258 UT WOS:A1995QG25800003 PM 7728516 ER PT J AU SHERIDAN, RL RYAN, CM QUINBY, WC BLAIR, J TOMPKINS, RG BURKE, JF AF SHERIDAN, RL RYAN, CM QUINBY, WC BLAIR, J TOMPKINS, RG BURKE, JF TI EMERGENCY MANAGEMENT OF MAJOR HYDROFLUORIC-ACID EXPOSURES SO BURNS LA English DT Note AB Exposures of as little as 2.5 per cent of the body surface to concentrated hydrofluoric acid (HF) may be fatal. Survival after major HF exposures is facilitated by aggressive emergency management which, we feel, includes wound irrigation, subeschar injection of calcium gluconate, monitored supplementation of serum calcium, and prompt wound excision carried out as an emergency procedure. The following case reports and literature review illustrate the important differences between exposures to concentrated HF of as little as 2 per cent of the body surface and smaller exposures to concentrated HF or exposure to dilute HF. RP SHERIDAN, RL (reprint author), MASSACHUSETTS GEN HOSP,SHRINERS BURNS INST,51 BLOSSOM ST,BOSTON,MA 02114, USA. NR 0 TC 44 Z9 49 U1 0 U2 1 PU BUTTERWORTH-HEINEMANN LTD PI OXFORD PA LINACRE HOUSE JORDAN HILL, OXFORD, OXON, ENGLAND OX2 8DP SN 0305-4179 J9 BURNS JI Burns PD FEB PY 1995 VL 21 IS 1 BP 62 EP 64 DI 10.1016/0305-4179(95)90785-X PG 3 WC Critical Care Medicine; Dermatology; Surgery SC General & Internal Medicine; Dermatology; Surgery GA QD696 UT WOS:A1995QD69600014 PM 7718123 ER PT J AU SILVA, JA LEONG, GB AF SILVA, JA LEONG, GB TI VISUAL-PERCEPTUAL ABNORMALITIES IN DELUSIONAL MISIDENTIFICATION SO CANADIAN JOURNAL OF PSYCHIATRY-REVUE CANADIENNE DE PSYCHIATRIE LA English DT Note ID CAPGRAS DELUSION; FACE AB Delusional misidentification syndromes are often found in conjunction with visual-perceptual abnormalities. These abnormalities appear to be independent of visual hallucinations and are illusory in nature. A case of delusional misidentification with visual-perceptual abnormalities is presented. Cognitive and visual phenomenology suggests that careful recording of visual abnormalities may shed light on the relation between delusional misidentification and abnormal visual cognition. C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX. UNIV CALIF LOS ANGELES,LOS ANGELES,CA. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA. RP SILVA, JA (reprint author), AUDIE L MURPHY MEM VET ADM MED CTR,PSYCHIAT SERV 116A,7400 MERTON MINTER BLVD,SAN ANTONIO,TX 78284, USA. NR 24 TC 11 Z9 11 U1 0 U2 0 PU CANADIAN PSYCHIATRIC ASSOC PI OTTAWA PA SUITE 200, 237 ARGYLE AVE, OTTAWA ON K2P 1B8, CANADA SN 0706-7437 J9 CAN J PSYCHIAT JI Can. J. Psychiat.-Rev. Can. Psychiat. PD FEB PY 1995 VL 40 IS 1 BP 6 EP 8 PG 3 WC Psychiatry SC Psychiatry GA QX508 UT WOS:A1995QX50800004 PM 7874682 ER PT J AU KIANG, DT KENNEDY, BJ YOUNGER, J PERRY, MC SCHILLING, A KORZUN, AH NOWAK, BS WOOD, W AF KIANG, DT KENNEDY, BJ YOUNGER, J PERRY, MC SCHILLING, A KORZUN, AH NOWAK, BS WOOD, W TI ALTERNATING CHEMOTHERAPY REGIMENS FOR PATIENTS WITH METASTATIC BREAST-CANCER - A PILOT-STUDY BASED ON TUMOR-MARKER KINETICS SO CANCER LA English DT Article DE BREAST CANCER; CHEMOTHERAPY; TUMOR MARKER; LIVER METASTASIS ID 5-FLUOROURACIL; METHOTREXATE; EFFICACY; ONCOLOGY AB Background. Chemotherapy is most effective when applied during the biologically active stage of tumor cells. According to the authors' previous tumor marker kinetic study, methotrexate plus 5-fluorouracil (MF) was found to yield either a cytolytic effect in an MF-sensitive tumor cell population or a cytostatic effect in an MF-resistant population. In the latter, the suppressive effect was transient and the biologic activity resumed in one week after MF administration. Methods. Based on this marker kinetic study, an alternating chemotherapy program was designed to study its antitumor and side effects. Methotrexate (M) (200 mg/m(2)) and 5-fluorouracil (F) (500 mg/m(2)) were administered intravenously on day 1 followed 24 hours later by leucovorin (L) (10 mg/m(2) orally every 6 hours for 6 doses). Cyclophosphamide (C) 300 (mg/m(2)), doxorubicin (A) (50 mg/m(2)), and vincristine (V) (1 mg/m(2)) were given on day 8. The MFL/CAV was given every 4 weeks. Results. Forty-nine patients with metastatic breast cancer were enrolled; 41 were eligible. There were 5 complete and 23 partial remissions, producing a total response rate of 68%. In 15 patients with liver metastases, the response rate was 73% and the median survival 13.7 months, results superior to those previously reported for this subgroup of patients. Side effects were manageable. Conclusions. This regimen, which can be given safely in an outpatient setting, yielded encouraging response and survival rates in patients with visceral-dominant disease with poor prognoses. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA. UNIV MISSOURI,DEPT MED,COLUMBIA,MO. RHODE ISL HOSP,PROVIDENCE,RI. HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,BOSTON,MA. CANC & LEUKEMIA GRP B,OFF DATA MANAGER,AMHERST,MA. RP KIANG, DT (reprint author), UNIV MINNESOTA,SCH MED,DEPT MED,BOX 168,MINNEAPOLIS,MN 55455, USA. FU NCI NIH HHS [CA-12046, CA-12449, CA-16450] NR 17 TC 7 Z9 8 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD FEB 1 PY 1995 VL 75 IS 3 BP 826 EP 830 DI 10.1002/1097-0142(19950201)75:3<826::AID-CNCR2820750313>3.0.CO;2-H PG 5 WC Oncology SC Oncology GA QC449 UT WOS:A1995QC44900012 PM 7828133 ER PT J AU GORDON, LI ANDERSEN, J COLGAN, J GLICK, J RESNICK, GD OCONNELL, M CASSILETH, PA AF GORDON, LI ANDERSEN, J COLGAN, J GLICK, J RESNICK, GD OCONNELL, M CASSILETH, PA TI ADVANCED DIFFUSE NON-HODGKINS-LYMPHOMA - ANALYSIS OF PROGNOSTIC FACTORS BY THE INTERNATIONAL INDEX AND BY LACTIC-DEHYDROGENASE IN AN INTERGROUP STUDY SO CANCER LA English DT Article DE LYMPHOMAS; PROGNOSTIC FACTORS; LACTIC DEHYDROGENASE; INTERNATIONAL INDEX; CHEMOTHERAPY ID LARGE-CELL LYMPHOMA; COOPERATIVE-ONCOLOGY-GROUP; STANDARD REGIMEN CHOP; PHASE-II TRIAL; M-BACOD; COMBINATION CHEMOTHERAPY; HISTIOCYTIC LYMPHOMA; INTERMEDIATE-GRADE; REGRESSION; DISEASE AB Background. Recent data have suggested that there are no differences among various anthracycline-based chemotherapy regimens [including cyclophosphamide, vincristine, methotrexate, and prednisone (CHOP), methotrexate, calcium leucovorin, bleomycin, doxorubicin, cyclophosphamide, and dexamethasone (m-BACOD), methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B), and cyclophosphamide, doxorubicin, etoposide, prednisone, cytosine arabinoside, bleomycin, vincristine, methotrexate, and calcium leucovorin (PROMACE-cyta-BOM)] in patients with diffuse aggressive lymphomas. Because outcome appears to depend on certain prognostic factors, risk groups can be identified. Therefore, these prognostic factors were examined for their correlations with survival, time-to-treatment failure (TTF), and disease free survival (DFS) in a group of patients with diffuse aggressive non-Hodgkin's lymphoma who were treated on a single randomized trial with either CHOP or m-BACOD. Methods. From July 1984 to January 1988, 392 patients with diffuse large cell or diffuse mixed non-Hodgkin's lymphoma were enrolled in an Intergroup study and were randomly assigned to treatment with CHOP or m-BACOD chemotherapy. Of these, 325 were eligible for response, toxicity, and survival analysis, and the results were reported. The survival and TTF results now have been updated. The 286 patients who had lactic dehydrogenase (LDH) data available at study entry were analyzed for prognostic features according to the International Index criteria and using Martingale Residuals for proportional hazards regression. Results. There were no differences in survival, TTF, and disease free survival between groups of patients treated with either CHOP or m-BACOD. In addition, analysis using the International Index criteria confirmed that patients in the lower risk groups had better outcome than patients in the higher risk groups (5-year survival was 56 and 58% for low and low/intermediate risk groups, respectively, and 37% and 31% for high/intermediate and high risk groups, respectively). There were, however, no differences in survival, disease free survival, or TTF within any risk group when treatment with CHOP or m-BACOD were compared. In addition, analysis using Martingale residuals for proportional hazards regression identified LDH level (> 3 X normal) as an important prognostic factor that was not captured by the International Index. Thus, 5-year survival was 57% if LDH was normal or below, 42% if LDH was 1-3 X normal, and 21% if LDH was > 3 X normal. Conclusion. In patients with advanced diffuse large cell or diffuse mixed non-Hodgkin's lymphoma, there are no differences in outcome that can be attributed to treatment with CHOP vs. m-BACOD; this holds for any prognostic group identified by the International Index. However, the level of LDH at time of study entry is an important prognostic factor that is predictive of survival and may help to identify candidates for future clinical trials. C1 ROBERT H LURIE CANC CTR,CHICAGO,IL. DANA FARBER CANC INST,BOSTON,MA. MAYO CLIN & MAYO FDN,ROCHESTER,MN. UNIV PENN,CTR CANC,PHILADELPHIA,PA. NEW YORK HOSP,CORNELL MED CTR,NEW YORK,NY. UNIV MIAMI,SYLVESTER CANC CTR,MIAMI,FL. RP GORDON, LI (reprint author), NORTHWESTERN UNIV,SCH MED,DEPT MED,DIV HEMATOL ONCOL,303 E CHICAGO AVE,CHICAGO,IL 60611, USA. OI Gordon, Leo/0000-0003-1666-7064 FU NCI NIH HHS [CA 13650, CA 17145, CA 23318] NR 27 TC 18 Z9 21 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD FEB 1 PY 1995 VL 75 IS 3 BP 865 EP 873 DI 10.1002/1097-0142(19950201)75:3<865::AID-CNCR2820750319>3.0.CO;2-Z PG 9 WC Oncology SC Oncology GA QC449 UT WOS:A1995QC44900018 PM 7530168 ER PT J AU FLETCHER, JA NAEEM, R XIAO, S CORSON, JM AF FLETCHER, JA NAEEM, R XIAO, S CORSON, JM TI CHROMOSOME-ABERRATIONS IN DESMOID TUMORS - TRISOMY-8 MAY BE A PREDICTOR OF RECURRENCE SO CANCER GENETICS AND CYTOGENETICS LA English DT Article ID DERMATOFIBROSARCOMA PROTUBERANS; CYTOGENETIC ANALYSIS; ABNORMALITIES; HYBRIDIZATION; DISEASE AB Cytogenetic analyses of short-term cultures revealed clonal chromosome aberrations in 6 of 13 desmoid tumors. These aberrations included two consistent events, trisomy 8 (n = 4) and trisomy 20 (n = 3), which have not been reported previously in desmoid tumors. Because trisomy 8 was found in two recurrent desmoid tumors, we used fluorescent in situ hybridization (FISH) methodology to evaluate chromosome 8 in 25 paraffin-embedded and frozen desmoid specimens. The FISH studies demonstrated that both patients with cytogenetic trisomy 8 at the time of recurrence also had had trisomy 8 in primary tumors 4 years earlier. The proportion of trisomy 8 cells in these cases did not change substantially between original diagnosis and recurrence. The FISH studies also revealed trisomy 8 in one recurrent desmoid tumor which had been cytogenetically unremarkable and revealed trisomy 8 in one recurrent desmoid that had not been karyotyped. Four of six patients with trisomy 8 had been followed for more than 1 year, and the desmoid tumors in each of these 4 patients recurred. By contrast, recurrence was noted in only 2 of 17 patients whose desmoid tumors lacked trisomy 8. Our findings demonstrate that trisomy 8 and trisomy 20 are nonrandom aberrations in desmoid tumors. Trisomy 8 appears to be associated with an increased risk of recurrence. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. CHILDRENS HOSP,DIV HEMATOL ONCOL,BOSTON,MA 02115. RP FLETCHER, JA (reprint author), BRIGHAM & WOMENS HOSP,DEPT PATHOL,75 FRANCIS ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [1K11CAO1498-03] NR 19 TC 73 Z9 82 U1 1 U2 1 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0165-4608 J9 CANCER GENET CYTOGEN JI Cancer Genet. Cytogenet. PD FEB PY 1995 VL 79 IS 2 BP 139 EP 143 DI 10.1016/0165-4608(94)00134-W PG 5 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA QM858 UT WOS:A1995QM85800011 PM 7889507 ER PT J AU SHAPIRO, GI EDWARDS, CD KOBZIK, L GODLESKI, J RICHARDS, W SUGARBAKER, DJ ROLLINS, BJ AF SHAPIRO, GI EDWARDS, CD KOBZIK, L GODLESKI, J RICHARDS, W SUGARBAKER, DJ ROLLINS, BJ TI RECIPROCAL RB INACTIVATION AND P16(INK4) EXPRESSION IN PRIMARY LUNG CANCERS AND CELL-LINES SO CANCER RESEARCH LA English DT Note ID D-TYPE CYCLINS; RETINOBLASTOMA PROTEIN; GENE; PHOSPHORYLATION; BINDING AB cdk4-mediated phosphorylation of the retinoblastoma susceptibility protein (Rb) is stimulated by cyclin D1, an oncogene, and inhibited hg p16, a candidate tumor suppressor. We examined these proteins in non-small cell lung cancer (NSCLC), which is predominantly Rb positive, and small cell lung cancer (SCLC), which is Rh negative. Most NSCLC and SCLC resection specimens and cell lines overexpress cyclin D1 (indicating that cyclin D1 overexpression and Rb inactivation can coexist in SCLC). However, 9 of 9 Rb-positive NSCLC cell lines have absent or low p16, while an Rb-negative NSCLC line and 5 of 5 SCLC cell lines have high levels of p16. In primary resection specimens, p16 was undetectable in 18 of 27 NSCLC samples and abundant in 4 of 5 SCLC samples. Our data confirm the predicted reciprocity between Rh inactivation and p16 expression in a common human malignancy and define differential p16 expression as a fundamental distinction between NSCLC and SCLC. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DANA FARBER CANC INST,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DIV THORAC SURG,BOSTON,MA 02115. FU NCI NIH HHS [CA19589, CA59594] NR 27 TC 325 Z9 335 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD FEB 1 PY 1995 VL 55 IS 3 BP 505 EP 509 PG 5 WC Oncology SC Oncology GA QD717 UT WOS:A1995QD71700013 PM 7834618 ER PT J AU GARG, HG SIEBERT, JW GARG, A NEAME, PJ AF GARG, HG SIEBERT, JW GARG, A NEAME, PJ TI IDURONIC ACID-RICH PROTEOGLYCANS (PG(IDOA)) AND HUMAN POSTBURN SCAR MATURATION - ISOLATION AND CHARACTERIZATION SO CARBOHYDRATE RESEARCH LA English DT Article DE IDURONIC ACID; PROTEOGLYCAN; BURN SCAR; COLLAGEN FORMATION ID CHONDROITIN SULFATE PROTEOGLYCAN; PROTEODERMATAN SULFATE; HYPERTROPHIC SCAR; HUMAN SKIN; COLLAGEN; GLYCOSAMINOGLYCANS; PURIFICATION; FIBRONECTIN; TENDON; BONE AB Proteoglycans (PGs) were extracted from human hypertrophic and normal scar tissues from two different stages of maturation after burn injury, under dissociative conditions (4 M guanidinium chloride containing proteinase inhibitors). The extracts were fractionated by ion-exchange chromatography, followed by ethanol precipitation, to give PG-containing iduronic acid (PG(IdoA)). The size of the PG(IdoA) decreased with the maturation of scars. Glycosaminoglycan (GAG) chains from PG(IdoA) were released by alkaline borohydride treatment, and their M(r) values were evaluated by polyacrylamide gel electrophoresis. The M(r) values for PG(IdoA) protein cores of the hypertrophic scars (5+ years and 2-5 years) and normal scar (5+ years and 2-5 years) were 22.6, 25, 19 and 21 KDa, respectively. The iduronic acid content of PG(IdoA) from both types of scar increased in their maturation phase. The M(r) values of PG(IdoA) decreased with maturation. PG(IdoA) carried the sulfate group mainly attached al C-4 of the 2-amino-2-deoxy-D-galactose residue. The NH2-terminal amino acid sequences of all the PG(IdoA) were similar to those of normal human skin or bone PG II (decorin) (i.e., Asp-Glu-Ala-B-Gly-Ile-Gly-Pro-Glu-Val-Pro-Asp-Asp-Arg). C1 HARVARD UNIV, SCH MED, SHRINERS BURNS INST, DEPT BIOL CHEM & MOLEC PHARMACOL, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, BOSTON, MA 02114 USA. NYU, MED CTR, INST RECONSTRUCT PLAST SURG, NEW YORK, NY 10016 USA. SHRINERS HOSP CRIPPLED CHILDREN, TAMPA UNIT, ORTHOPED RES LABS, TAMPA, FL 33612 USA. NR 44 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD FEB 1 PY 1995 VL 267 IS 1 BP 105 EP 113 DI 10.1016/0008-6215(94)00284-M PG 9 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA QG633 UT WOS:A1995QG63300008 PM 7697662 ER PT J AU RAWSON, NE BRANS, JG LOWRY, LD TEETER, JH RESTREPO, D AF RAWSON, NE BRANS, JG LOWRY, LD TEETER, JH RESTREPO, D TI 2ND MESSENGER DEPENDENCE OF CALCIUM RESPONSES IN ISOLATED MAMMALIAN OLFACTORY NEURONS - ONE PATHWAY OR 2 SO CHEMICAL SENSES LA English DT Meeting Abstract ID ODORANTS; CA2+ C1 MONELL CHEM SENSES CTR,PHILADELPHIA,PA 19104. THOMAS JEFFERSON UNIV,PHILADELPHIA,PA 19107. VET AFFAIRS MED CTR,PHILADELPHIA,PA. UNIV PENN,PHILADELPHIA,PA 19104. NR 4 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 1995 VL 20 IS 1 BP 157 EP 158 PG 2 WC Behavioral Sciences; Food Science & Technology; Neurosciences; Physiology SC Behavioral Sciences; Food Science & Technology; Neurosciences & Neurology; Physiology GA QQ130 UT WOS:A1995QQ13000178 ER PT J AU PALACIOS, IF TUZCU, ME WEYMAN, AE NEWELL, JB BLOCK, PC AF PALACIOS, IF TUZCU, ME WEYMAN, AE NEWELL, JB BLOCK, PC TI CLINICAL FOLLOW-UP OF PATIENTS UNDERGOING PERCUTANEOUS MITRAL BALLOON VALVOTOMY SO CIRCULATION LA English DT Article DE STENOSIS; MITRAL VALVE; FOLLOW-UP STUDIES ID SURGICAL CLOSED COMMISSUROTOMY; SHORT-TERM; STENOSIS; VALVULOPLASTY; VALVE AB Background This study is the clinical follow-up (20+/-12 months; range, 6 to 49 months) of 327 patients who had percutaneous mitral balloon valvotomy (PMV) at the Massachusetts General Hospital. Methods and Results There were seven in-hospital deaths. Patients were divided into two groups according to their echocardiographic score; 211 patients had echocardiographic scores less than or equal to 8 and 116, echocardiographic scores >8. Patients with echocardiographic scores >8 were older (64+/-11 versus 48+/-14 years, P<.01), and more had atrial fibrillation (65% versus 40%, P<.01), calcium under fluoroscopy (81% versus 29%, P<.01), and previous surgical commissurotomy (30% versus 16%, P<.01) than patients with echocardiographic scores less than or equal to 8. With PMV, mitral valve area increased from 1.0+/-0.3 to 2.2+/-0.8 cm(2) in patients with echocardiographic scores less than or equal to 8 and from 0.8+/-1 to 1.7+/-0.7 cm(2) in those with echocardiographic scores >8. Rates of survival (98+/-2% versus 72+/-11%), survival with freedom from mitral valve replacement (91+/-4% versus 55+/-13%), and survival with freedom from combined events (79+/-10% versus 39+/-18%) at follow-up were greater in patients with echocardiographic scores less than or equal to 8 (P<.00005). Cox regression analysis identified the echocardiographic score as the most important unfavorable intermediate long-term follow-up prediction factor after PMV. Conclusions The excellent intermediate long-term clinical follow-up of patients with echocardiographic score less than or equal to 8 and no calcified mitral valves suggests that PMV may be the treatment of choice in this group of patients. RP PALACIOS, IF (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,CARDIAC UNIT,BOSTON,MA 02114, USA. NR 37 TC 107 Z9 114 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 1 PY 1995 VL 91 IS 3 BP 671 EP 676 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA QD434 UT WOS:A1995QD43400010 PM 7828292 ER PT J AU MELE, D VANDERVOORT, P PALACIOS, I RIVERA, JM DINSMORE, RE SCHWAMMENTHAL, E MARSHALL, JE WEYMAN, AE LEVINE, RA AF MELE, D VANDERVOORT, P PALACIOS, I RIVERA, JM DINSMORE, RE SCHWAMMENTHAL, E MARSHALL, JE WEYMAN, AE LEVINE, RA TI PROXIMAL JET SIZE BY DOPPLER COLOR-FLOW MAPPING PREDICTS SEVERITY OF MITRAL REGURGITATION - CLINICAL-STUDIES SO CIRCULATION LA English DT Article DE ECHOCARDIOGRAPHY; REGURGITATION; MITRAL VALVE; MAPPING ID CARDIAC-OUTPUT; ECHOCARDIOGRAPHIC MEASUREMENT; VALVULAR REGURGITATION; AORTIC-INSUFFICIENCY; ORIFICE METHOD; STROKE VOLUME; VALVE REPAIR; INVITRO; AREA; QUANTIFICATION AB Background Recent studies have shown that many instrument and physiological factors limit the ability of color Doppler total jet area within the receiving chamber to predict the severity of valvular regurgitation. In contrast, the proximal or initial dimensions of the jet as it emerges from the orifice have been shown to increase directly with orifice size and to correlate well with the severity of aortic insufficiency. Only limited data, however, are available regarding the value of proximal jet size in mitral regurgitation, and it has not been examined in short-axis or transthoracic views. The purpose of the present study, therefore, was to evaluate the relation between proximal jet size and other measures of the severity of mitral regurgitation. Methods and Results In 49 patients, the anteroposterior height of the proximal jet as it emerges from the mitral valve was measured in the parasternal long-axis view; proximal jet width and area were measured in the short-axis view at the same level. Results were compared with regurgitant volume and fraction by pulsed Doppler subtraction of aortic and mitral flows in 47 patients without more than trace aortic insufficiency; with angiographic grade determined within 24 hours in 33 catheterized patients; and with angiographic regurgitant fraction in 13 patients who were in normal sinus rhythm and had no significant aortic and tricuspid insufficiency. Proximal jet height, width, and area correlated well with Doppler regurgitant volume and fraction (r=.86 to .95; SEE=7.7 to 9.0 mL; 5.9% to 7.3%). Proximal jet size could also be used to distinguish angiographic grades of mitral regurgitation with minimal overlap (P<.0001) and correlated well with angiographic regurgitant fraction (r=.85 to .91; SEE=4.1% to 5.1%). Conclusions Proximal jet size correlates well with established measures of the severity of, mitral regurgitation. It is conveniently available with transthoracic clinical scanning and should be useful in the routine evaluation of patients with mitral regurgitation. C1 MASSACHUSETTS GEN HOSP,NONINVAS CARDIAC LAB,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,INVAS CARDIAC LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RI rivera, miguel/D-5026-2014 NR 74 TC 102 Z9 103 U1 0 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 1 PY 1995 VL 91 IS 3 BP 746 EP 754 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA QD434 UT WOS:A1995QD43400021 PM 7828303 ER PT J AU LEE, RT BERDITCHEVSKI, F CHENG, GC HEMLER, ME AF LEE, RT BERDITCHEVSKI, F CHENG, GC HEMLER, ME TI INTEGRIN-MEDIATED COLLAGEN MATRIX REORGANIZATION BY CULTURED HUMAN VASCULAR SMOOTH-MUSCLE CELLS SO CIRCULATION RESEARCH LA English DT Article DE INTEGRINS; ATHEROSCLEROSIS; COLLAGEN; VASCULAR SMOOTH MUSCLE; ADHESION ID MONOCLONAL-ANTIBODY; ADHESION; GROWTH; VLA-2; MIGRATION; FIBROBLASTS; FIBRONECTIN; EXPRESSION; RECEPTOR; LAMININ AB Vascular smooth muscle cells perform the important function of modulation of vascular extracellular matrix. Because integrins mediate many cell-matrix interactions, the role of integrins in reorganization of collagen by cultured human vascular smooth muscle cells was studied. Immunoprecipitation demonstrated that human vascular smooth muscle cells express multiple beta(1) integrins. Monoclonal antibody A2-IIE10 (a blocking anti-alpha(2) antibody) inhibited adhesion of smooth muscle cells to collagen by 31%. The blocking anti-alpha(1) antibody 1B3.1 inhibited adhesion by 40%, whereas a blocking anti-alpha(3) antibody had no effect on adhesion. When 1B3.1 and A2-IIE10 were both used, a 79% reduction in adhesion was observed, indicating that active alpha(1) and alpha(2) integrins cooperatively mediate adhesion. The blocking anti-beta(1) antibody Mab13 abolished smooth muscle cell-mediated gel contraction, and the alpha(2)-blocking antibody A2-IIE10 had a dose-dependent partial inhibitory effect (37%). In contrast, blocking antibodies to alpha(1) and alpha(3) had no effect. When anti-alpha(1) (1B3.1) and anti-alpha(2) (A2-IIE10) monoclonal antibodies were combined, no synergistic effect on inhibition of gel contraction was observed. Surprisingly, collagen gel contraction was inhibited by 46% by an anti-beta(1) antibody (TS2/16) known for its stimulatory effect on cell adhesion. Thus, whereas alpha(1) beta(1) and alpha(2) beta(1) integrins both participate in adhesion of vascular smooth muscle cells to collagen, only alpha(2) beta(1) integrins mediate collagen reorganization. In addition, collagen reorganization appears to be a dynamic process, adversely affected by excessive adhesion strengthening. C1 DANA FARBER CANC INST,BOSTON,MA. RP LEE, RT (reprint author), HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT MED,DIV CARDIOVASC,75 FRANCIS ST,BOSTON,MA 02115, USA. FU NIGMS NIH HHS [GM-38903] NR 44 TC 112 Z9 115 U1 1 U2 2 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 1995 VL 76 IS 2 BP 209 EP 214 PG 6 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA QP858 UT WOS:A1995QP85800007 PM 7834831 ER PT J AU ROBERTS, JD ROBERTS, CT JONES, RC ZAPOL, WM BLOCH, KD AF ROBERTS, JD ROBERTS, CT JONES, RC ZAPOL, WM BLOCH, KD TI CONTINUOUS NITRIC-OXIDE INHALATION REDUCES PULMONARY ARTERIAL STRUCTURAL-CHANGES, RIGHT-VENTRICULAR HYPERTROPHY, AND GROWTH-RETARDATION IN THE HYPOXIC NEWBORN RAT SO CIRCULATION RESEARCH LA English DT Article DE PULMONARY ARTERY HYPERTENSION; CONGENITAL HEART DISEASE; NITRIC OXIDE; NEWBORN RATS ID SMOOTH-MUSCLE CELLS; ATRIAL NATRIURETIC FACTOR; CONGENITAL HEART-DISEASE; FACTOR GENE-EXPRESSION; RELAXING FACTOR; ENDOTHELIUM; HYPERTENSION; PROLIFERATION; VASOCONSTRICTION; CIRCULATION AB Breathing low oxygen levels for several weeks produces progressive pulmonary artery hypertension and smooth muscle hypertrophy and hyperplasia in many species. Because nitric oxide (NO) is an important regulator of pulmonary vascular tone, we examined whether the continuous inhalation of low levels of NO gas would attenuate pulmonary arterial structural changes in hypoxic rat pups. Nine-day-old rat pups and their mothers continuously breathed at FIO2 0.21 or 0.10 with or without adding 20 ppm (by volume) NO far 2 weeks. Lung tissue was obtained for vascular morphometric analysis, and the hearts were dissected to measure right ventricular weight and levels of mRNA encoding rat atrial natriuretic factor (rANF). In addition, femur and skull length were radiographically determined. Breathing at FIO2 0.10 for 14 days increased pulmonary arterial wall thickness and the proportion of muscular arteries in the lung periphery. Right ventricular weight and right ventricular rANF gene expression increased, whereas body weight and skeletal growth were reduced (all P<.05). Continuous inhalation of 20 ppm NO at FIO2 0.10 for 2 weeks decreased hypoxic pulmonary vascular structural changes and somatic growth retardation and prevented the increase of right ventricular weight and right ventricular rANF mRNA levels. These observations suggest that chronically breathing NO attenuates pulmonary vascular smooth muscle hypertrophy and/or hyperplasia and extension into distal arterial walls, right ventricular hypertrophy, and growth retardation of newborns breathing at a low oxygen level. C1 MASSACHUSETTS GEN HOSP,HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,HARVARD UNIV,SCH MED,CARDIOVASC RES CTR,BOSTON,MA 02114. RP ROBERTS, JD (reprint author), MASSACHUSETTS GEN HOSP,HARVARD UNIV,SCH MED,DEPT ANESTHESIA,BOSTON,MA 02114, USA. FU NHLBI NIH HHS [HL-42397] NR 53 TC 92 Z9 94 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 1995 VL 76 IS 2 BP 215 EP 222 PG 8 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA QP858 UT WOS:A1995QP85800008 PM 7834832 ER PT J AU HASEGAWA, H KANNER, AM AF HASEGAWA, H KANNER, AM TI SEIZURE CONTROL AFTER CHRONIC PHARMACOTHERAPY IN EPILEPTIC DISORDERS BEGINNING AFTER 40 YEARS OF AGE SO CLINICAL NEUROPHARMACOLOGY LA English DT Review DE ADULT ONSET EPILEPSY; MONOTHERAPY; POLYTHERAPY; CARBAMAZEPINE; PHENOBARBITAL; PRIMIDONE; PHENYTOIN ID STROKE AB Few studies have been published on the pharmacologic response to treatment of patients whose seizures begin after 40 years of age. The purpose of this study was to assess the impact of chronic pharmacotherapy on the seizure control of such patients. We retrospectively studied the seizure frequency recorded during a 12-month period in a group of 94 outpatients whose seizure disorders began after 40 years of age (median age of seizure onset 56.5 years) and who had been treated with anticonvulsant medication for a median period of 6 years (range 18 months to 12 years). We assessed the relationship between the patients' seizure frequency during the last 12 months of treatment using (a) the present and previously prescribed pharmacologic regimens, (b) anticonvulsant blood levels of present regimen, (c) etiology and duration of seizure disorder, (d) age at onset of seizures, and (e) presence of electrographic (EEG) and neuroradiologic abnormalities. We only identified side effects occurring at blood levels within or below the drug's therapeutic range. Seventy-eight patients (83%) were seizure free during the last 12 months of treatment, 11 (11%) had rare seizures, and five (6%) had more than four seizures per year. Seizure frequency was not affected by duration and etiology of seizure disorder, age at onset of seizures, seizure type, neuroradiologic or electroencephalographic abnormalities, and present or previously prescribed pharmacologic regimens, Persistent side effects were reported in seven of 76 (9%) monotherapy regimens and in two of 12 (17%) polytherapy regimens. Our data suggest that seizures beginning after the age of 40 have a favorable prognosis after chronic pharmacotherapy. C1 RUSH PRESBYTERIAN ST LUKES MED CTR,RUSH EPILEPSY CTR,CHICAGO,IL 60612. RUSH PRESBYTERIAN ST LUKES MED CTR,DEPT NEUROL SCI,CHICAGO,IL 60612. WILLIAM S MIDDLETON MEM VET ADM MED CTR,NEUROL SERV,MADISON,WI. WILLIAM S MIDDLETON MEM VET ADM MED CTR,FRANCIS M FORESTER EPILEPSY CTR,MADISON,WI. UNIV WISCONSIN,DEPT NEUROL,MADISON,WI. NR 23 TC 3 Z9 3 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0362-5664 J9 CLIN NEUROPHARMACOL JI Clin. Neuropharmacol. PD FEB PY 1995 VL 18 IS 1 BP 13 EP 22 DI 10.1097/00002826-199502000-00002 PG 10 WC Clinical Neurology; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA QF316 UT WOS:A1995QF31600002 PM 8665530 ER PT J AU JASTY, M ANDERSON, MJ HARRIS, WH AF JASTY, M ANDERSON, MJ HARRIS, WH TI TOTAL HIP-REPLACEMENT FOR DEVELOPMENTAL DYSPLASIA OF THE HIP SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article; Proceedings Paper CT 22nd Open Scientific Meeting of the Hip-Society CY 1994 CL NEW ORLEANS, LA SP HIP SOC ID FEMORAL-HEAD ALLOGRAFTS; RECONSTRUCTION AB Total hip arthroplasty relieves pain and improves function for many patients with endstage arthritis secondary to developmental dysplasia of the hip. Acetabular dysplasia, however, presents a special problem for total hip reconstruction in these patients, Structural bone grafting with femoral head autografting to the dysplastic acetabulum and cementing acetabular components into the graft provides satisfactory short-term results, but longer-term followup data show high acetabular component failure rates. At a mean followup period of 7 years, 20% of components were loose, and at a mean followup period of 12 years, 46% were loose, Noncemented porous-coated hemispherical acetabular components have considerably expanded the success of total hip replacement without the need for structural bone grafting in such patients, At a mean followup period of almost 7 years, none of the acetabular components were reported to be loose in 1 series, For most patients, the acetabular dysplasia can be managed by techniques such as reaming deeper, using small-diameter porous-coated acetabular components, using screws to provide rigid initial stability for the components, increasing the height of the prosthetic hip center, and covering small portions of the components with bone graft chips if necessary. 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 19 TC 65 Z9 72 U1 0 U2 4 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD FEB PY 1995 IS 311 BP 40 EP 45 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA QF554 UT WOS:A1995QF55400004 PM 7634589 ER PT J AU HARRIS, WH AF HARRIS, WH TI THE PROBLEM IS OSTEOLYSIS SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article; Proceedings Paper CT 22nd Open Scientific Meeting of the Hip-Society CY 1994 CL NEW ORLEANS, LA SP HIP SOC ID TOTAL HIP-REPLACEMENT; IMPROVED CEMENTING TECHNIQUES; 10-YEAR FOLLOW-UP; ULTRACLEAN AIR; BONE INGROWTH; ARTHROPLASTY; OPERATIONS; COMPONENTS; SEPSIS; JOINT AB Recent studies have generated considerable information that reveals substantial support for major change in the understanding of total hip arthroplasty and its current state, Although some of these observations appear unrelated at first glance, they can be drawn together to support the thesis that osteolysis is the dominant problem in total hip arthroplasty, These observations are as follows: (1) Five-year followup data are required for a minimum assessment of a new concept in total hip design and material because osteolysis is uncommon before that time, (2) Excellent fixation can be achieved on the femoral side with, good cementing and good cementless techniques, Thus, femoral component loosening is less of an issue currently, (3) Many acetabular components become loose because of the ingress of particulate debris that leads to linear bone loss at the interface with the pelvis, a process that is biologically akin to the more florid forms of osteolysis, Thus, much acetabular component loosening represents a form of osteolysis, (4) Many cementless femoral reconstructions have developed a high incidence of femoral osteolysis, (5) Many cementless sockets have developed a high incidence of pelvic osteolysis, Taken in conjunction, these observations suggest that periprosthetic osteolysis is the leading problem in contemporary total hip replacement. 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 53 TC 513 Z9 528 U1 4 U2 21 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD FEB PY 1995 IS 311 BP 46 EP 53 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA QF554 UT WOS:A1995QF55400005 PM 7634590 ER PT J AU HOKE, JF MUIR, KT GLASS, PSA SHLUGMAN, D ROSOW, CE DERSHWITZ, M MICHALOWSKI, P AF HOKE, JF MUIR, KT GLASS, PSA SHLUGMAN, D ROSOW, CE DERSHWITZ, M MICHALOWSKI, P TI PHARMACOKINETICS (PK) OF REMIFENTANIL (R) AND ITS METABOLITE (GR90291) IN SUBJECTS WITH RENAL-DISEASE SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 GLAXO INC,RES TRIANGLE PK,NC 27709. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. DUKE UNIV,MED CTR,DURHAM,NC. NR 0 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 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1995 VL 57 IS 2 BP 148 EP 148 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QJ312 UT WOS:A1995QJ31200054 ER PT J AU SKINNER, MH KOSHSUBER, J VAN, B AF SKINNER, MH KOSHSUBER, J VAN, B TI USE OF A COMPUTER-PROVIDED ALERT MESSAGE TO IMPROVE THERAPEUTIC DRUG-MONITORING SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 UNIV TEXAS,HLTH SCI CTR,DIV CLIN PHARM,SAN ANTONIO,TX. AUDIE L MURPHY MEM VET ADM MED CTR,QUAL IMPROVEMENT SERV,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SERV PHARM,SAN ANTONIO,TX 78284. 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 1995 VL 57 IS 2 BP 192 EP 192 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QJ312 UT WOS:A1995QJ31200227 ER PT J AU KIM, KM AF KIM, KM TI SEQPWR AND SEQOPR - COMPUTER-PROGRAMS FOR DESIGN OF MAXIMUM INFORMATION TRIALS BASED ON GROUP SEQUENTIAL LOGRANK TESTS SO COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE LA English DT Article DE CLINICAL TRIALS; INTERIM ANALYSIS; PROPORTIONAL HAZARDS MODEL; SURVIVAL ANALYSIS; TYPE I ERROR SPENDING FUNCTION ID CLINICAL-TRIALS AB The maximum information trial paradigm for clinical trials with failure time data was recognized and has been investigated. With the maximum information trial paradigm, a study is concluded when a prespecified maximum number of events of interest, thus maximum information, has been accrued if there was no early stopping due to treatment difference or lack thereof. We present two interactive FORTRAN programs for use in designing maximum information trials based on group sequential logrank tests. The program SEQPWR computes the attainable power of group sequential logrank tests given the combinations of the accrual and follow-up durations. The program SEQOPR allows the users to investigate the operating characteristics of the maximum information trial given the information fractions of interim analyses. A clinical trial from the Eastern Cooperative Oncology Group is provided to illustrate the usage and features of the programs. RP KIM, KM (reprint author), HARVARD UNIV,SCH PUBL HLTH,DANA FARBER CANC INST,DEPT BIOSTAT,DIV BIOSTAT,44 BINNEY ST,MAYER 4,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA52733] NR 14 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCI PUBL IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0169-2607 J9 COMPUT METH PROG BIO JI Comput. Meth. Programs Biomed. PD FEB PY 1995 VL 46 IS 2 BP 143 EP 153 DI 10.1016/0169-2607(94)01615-M PG 11 WC Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods; Engineering, Biomedical; Medical Informatics SC Computer Science; Engineering; Medical Informatics GA QQ567 UT WOS:A1995QQ56700006 PM 7796583 ER PT J AU ROCK, KL UNANUE, ER AF ROCK, KL UNANUE, ER TI ANTIGEN RECOGNITION SO CURRENT OPINION IN IMMUNOLOGY LA English DT Editorial Material C1 WASHINGTON UNIV,SCH MED,ST LOUIS,MO. RP ROCK, KL (reprint author), HARVARD UNIV,DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. NR 7 TC 3 Z9 3 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 1995 VL 7 IS 1 BP 65 EP 68 DI 10.1016/0952-7915(95)80030-1 PG 4 WC Immunology SC Immunology GA QM154 UT WOS:A1995QM15400010 ER PT J AU WRAY, SH AF WRAY, SH TI OPTIC NEURITIS - GUIDELINES SO CURRENT OPINION IN NEUROLOGY LA English DT Article ID MULTIPLE-SCLEROSIS; FOLLOW-UP; CORTICOSTEROIDS; TRIAL; RISK AB A major breakthrough in the therapy of demyelinating disease has recently been disclosed by the Optic Neuritis Treatment Trial. Over the past 6 years the trial has accumulated evidence that a high dose of corticosteroids taken to treat patients with an isolated acute attack of optic neuritis reduces the rate at which multiple sclerosis develops over a 2-year period of follow-up. The findings of the trial have had an immediate impact on the neuro-ophthalmic and neurologic community in the USA; therefore, I have focused my review on this important topic. RP WRAY, SH (reprint author), MASSACHUSETTS GEN HOSP,DEPT NEUROL,NEUROVISUAL DISORDERS UNIT,CTR AMBULATORY CARE,LEVEL 8,BOSTON,MA 02114, USA. NR 17 TC 8 Z9 8 U1 0 U2 0 PU CURRENT SCIENCE PI PHILADELPHIA PA 400 MARKET STREET,SUITE 750 ATTN:SARAH WHEALEN/SUB MGR, PHILADELPHIA, PA 19106 SN 1350-7540 J9 CURR OPIN NEUROL JI Curr. Opin. Neurol. PD FEB PY 1995 VL 8 IS 1 BP 72 EP 76 DI 10.1097/00019052-199502000-00012 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA QK527 UT WOS:A1995QK52700012 PM 7749521 ER PT J AU ARBISER, JL KATZ, J AF ARBISER, JL KATZ, J TI HAEMOPHILUS-INFLUENZAE BACTEREMIA IN ELDERLY MEN WITH KAPOSIS-SARCOMA - 2 CASE-REPORTS AND A REVIEW OF THE LITERATURE SO CUTIS LA English DT Review ID B CELLULITIS; PATIENT; ADULTS AB Hemophilus influenzae is a common pathogen responsible for respiratory infections, meningitis, and bacteremia in children, and a rare cause of bacteremia in adults. We report two cases of H. influenzae bacteremia in elderly men with Kaposi's sarcoma. Both of the patients described are elderly men with no other stigmata of the acquired immune deficiency syndrome. Both Kaposi's sarcoma of the elderly and adult H. influenzae bacteremia are relatively uncommon, and the coappearance of these syndromes may suggest a common immune defect predisposing to these syndromes, or Kaposi's sarcoma may provide a portal of entry for this organism. We suggest that patients with Kaposi's sarcoma who may have bacteremia receive appropriate antibiotic treatment for H. influenzae until a causative agent is isolated. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. BRIGHAM & WOMENS HOSP,BOSTON,MA. RP ARBISER, JL (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT DERMATOL,ACC 489,FRUIT ST,BOSTON,MA 02114, USA. NR 13 TC 3 Z9 3 U1 0 U2 0 PU EXCERPTA MEDICA INC PI BELLE MEAD PA 105 RAIDER BLVD, BELLE MEAD, NJ 08502 SN 0011-4162 J9 CUTIS JI Cutis PD FEB PY 1995 VL 55 IS 2 BP 101 EP 103 PG 3 WC Dermatology SC Dermatology GA QG100 UT WOS:A1995QG10000008 PM 7729153 ER PT J AU JAFFA, AA RUST, PF MAYFIELD, RK AF JAFFA, AA RUST, PF MAYFIELD, RK TI KININ, A MEDIATOR OF DIABETES-INDUCED GLOMERULAR HYPERFILTRATION SO DIABETES LA English DT Article ID MELLITUS; KALLIKREIN; RATS; INSULIN; PROSTAGLANDIN; RENIN; HYPERTENSION; LOCALIZATION; EXPRESSION; HORMONES AB Renal kallikrein is increased in diabetic patients and streptozotocin (STZ)-induced diabetic rats with hyperfiltration. Chronic inhibition of renal kallikrein reduces glomerular filtration rate (GFR) and renal plasma flow (RPF) in hyperfiltering Sn-induced diabetic rats, To investigate whether these actions of kallikrein and its inhibition are kinin-mediated, we used a B-2-kinin receptor antagonist (BKA). In STZ-induced diabetic rats with hyperfiltration, renal kallikrein excretion rate was significantly increased (P less than or equal to 0.01), and kinin excretion rate was increased 57%, as compared with control rats. Left kidney GFR and RPF were measured before and during a 40-min infusion of BKA (0.5 mu g kg(-1).min(-1)) or vehicle. Infusion of the kinin receptor antagonist reduced the GFR and RPF significantly. GFR was reduced by 18%, hom an average baseline value of 2.07 +/- 0.11 to 1.70 +/- 0.06 ml/min, P less than or equal to 0.001 (means +/- SE). RPF was reduced by 25%, hom 6.74 +/- 0.38 to 5.06 +/- 0.17 ml/min, P less than or equal to 0.001. Total renal vascular resistance was significantly increased during BKA infusion, P less than or equal to 0.001. Vehicle infusion for the same period had no significant effect on GFR, RPF, or renal vascular resistance. These findings further support the hypothesis that increased renal production of kinins contributes to the renal vasodilation of diabetes. C1 MED UNIV S CAROLINA,DEPT PHARMACOL,CHARLESTON,SC 29425. MED UNIV S CAROLINA,DEPT BIOMETRY,CHARLESTON,SC 29425. RALPH H JOHNSON DEPT VET AFFAIRS MED CTR,CHARLESTON,SC. RP JAFFA, AA (reprint author), MED UNIV S CAROLINA,DEPT MED,DIV ENDOCRINOL DIABET & METAB,171 ASHLEY AVE,CHARLESTON,SC 29425, USA. NR 28 TC 50 Z9 51 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD FEB PY 1995 VL 44 IS 2 BP 156 EP 160 DI 10.2337/diabetes.44.2.156 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QD999 UT WOS:A1995QD99900005 PM 7859934 ER PT J AU DORIA, A CALDWELL, JS JI, LN REYNET, C RICH, SS WEREMOWICZ, S MORTON, CC WARRAM, JH KAHN, CR KROLEWSKI, AS AF DORIA, A CALDWELL, JS JI, LN REYNET, C RICH, SS WEREMOWICZ, S MORTON, CC WARRAM, JH KAHN, CR KROLEWSKI, AS TI TRINUCLEOTIDE REPEATS AT THE RAD LOCUS - ALLELE DISTRIBUTIONS IN NIDDM AND MAPPING TO A 3-CM REGION ON CHROMOSOME 16Q SO DIABETES LA English DT Note ID DIABETES-MELLITUS; INSULIN; LINKAGE; GENE; MUTATIONS; DEAFNESS; HUMANS AB A 10-allele polymorphism was identified in rad (ras associated with diabetes), a gene that is overexpressed in non-insulin-dependent diabetes mellitus (NIDDM) muscle. The polymorphism, designated RAD1, consists of a variable number of trinucleotide repeats (GTT and ATT) located in the poly(A) region of an intronic Alu sequence. Based on the number of GTT and ATT repetitions, the alleles can be grouped into four classes (III). RAD1 allele frequencies were determined in 210 NIDDM patients and 133 nondiabetic control subjects, all Caucasians, One allele (number 8, class III) accounted for >80% of the chromosomes in both groups. However, an excess of minor alleles, all belonging to class I, II, or TV, was observed among NIDDM chromosomes (P < 0.025), suggesting a possible association between RAD1 and NIDDM predisposition. To promote further studies to test the hypothesis that genetic variability at the rad locus contributes to NIDDM, we mapped rad on the human genome. Using the fluorescence in situ chromosomal hybridization technique, rad was unequivocally assigned to chromosomal band 16q22. In families that were informative for RAD1, the rad locus was mapped within a 3-cM region defined by the markers D16S265, D16S186, and D16S397 (logarithm of odds scores = 10.08, 10.9, and 10.84 at recombination fractions of 0.024, 0.001, and 0.03, respectively). The high degree of heterozygosity of these markers mill allow large-scale family studies to be performed to test the presence of linkage between rad and NIDDM. C1 JOSLIN DIABET CTR,DIV RES,EPIDEMIOL & GENET SECT,BOSTON,MA 02215. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02115. UNIV MINNESOTA,DEPT LAB MED & PATHOL,MINNEAPOLIS,MN 55455. UNIV MINNESOTA,INST HUMAN GENET,MINNEAPOLIS,MN 55455. FU NIDDK NIH HHS [DK-45935, P30-DK-36836] NR 24 TC 31 Z9 31 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD FEB PY 1995 VL 44 IS 2 BP 243 EP 247 DI 10.2337/diabetes.44.2.243 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QD999 UT WOS:A1995QD99900019 PM 7859947 ER PT J AU GREENE, MF ALLRED, EN LEVITON, A AF GREENE, MF ALLRED, EN LEVITON, A TI MATERNAL METABOLIC CONTROL AND RISK OF MICROCEPHALY AMONG INFANTS OF DIABETIC MOTHERS SO DIABETES CARE LA English DT Article ID HEAD CIRCUMFERENCE; FETAL MACROSOMIA; PREGNANCIES; GROWTH; INSULIN; WOMEN AB OBJECTIVE- To measure the incidence of microcephaly among infants of diabetic mothers (IDM) and assess its relationship to metabolic control during pregnancy. RESEARCH DESIGN AND METHODS- Head circumference data for 556 consecutive live-born singleton infants of women with insulin-requiring diabetes antedating pregnancy delivered between 28 and 40 weeks of gestation and the results of 3,242 HbA(1) determinations collected during their pregnancies were examined. RESULTS- There were fewer head circumferences al or below the 3rd percentile and more at or above the 97th percentile than expected. Head circumference was not related to maternal metabolic control as documented by the HbA(1) values. CONCLUSIONS- The less-than-expected incidence of microcephaly observed in this patient population probably reflects the well-known tendency of IDM toward macrosomia. C1 MASSACHUSETTS GEN HOSP,DEPT OBSTET GYNECOL & REPROD BIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,BOSTON,MA 02114. CHILDRENS HOSP,NEUROEPIDEMIOL UNIT,BOSTON,MA 02115. FU NINDS NIH HHS [NS-2609 3] NR 20 TC 6 Z9 6 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD FEB PY 1995 VL 18 IS 2 BP 166 EP 169 DI 10.2337/diacare.18.2.166 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QE300 UT WOS:A1995QE30000002 PM 7729292 ER PT J AU NATHAN, DM AF NATHAN, DM TI INFERENCES AND IMPLICATIONS - DO RESULTS FROM THE DIABETES CONTROL AND COMPLICATIONS TRIAL APPLY IN NIDDM SO DIABETES CARE LA English DT Review ID CONVENTIONAL INSULIN THERAPY; CORONARY HEART-DISEASE; METABOLIC CONTROL; GLYCEMIC CONTROL; RISK-FACTORS; MELLITUS; RETINOPATHY; GLUCOSE; SECRETION; PREVALENCE C1 HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, DIABET RES CTR, BOSTON, MA 02114 USA. RP NATHAN, DM (reprint author), HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, DIABET UNIT, BOSTON, MA 02114 USA. NR 55 TC 46 Z9 46 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD FEB PY 1995 VL 18 IS 2 BP 251 EP 257 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QE300 UT WOS:A1995QE30000018 PM 7729307 ER PT J AU JONES, RN SADER, HS ERWIN, ME ANDERSON, SC ALDRIDGE, KA ALLEN, S ANHALT, J APPELBAUM, P ARRINGTON, KL AYERS, L BAKER, C BEAVIS, K BERGER, J BERTHOLD, G BIRNBAUM, M BOYLE, J BRECHER, S BRECKENRIDGE, R BROWN, W BRUCKNER, D CARROLL, K CHAUDHARY, S CLEARY, T COCKERILL, F COYLE, M CRAWFORD, V DALTON, H DOERN, G EDBERG, S GELFAND, M GERLACH, EH GOODMAN, N GORZYNSKI, E GREEN, P GROSCHEL, D HANFF, P HANNA, B HARRELL, L HAUGEN, T HEAGREY, M HUMPHRIES, J ISENBERG, H JENKINS, S JONES, E JORGENSEN, J KAUFFMAN, C KEISER, J KOCKA, F KOMINOS, S LEVISON, M LOCKWOOD, W MANOS, J MARTIN, W MCLAUGHLIN, J METCHOCK, B MICKELSEN, P MOODY, J MORELLO, J MOSTOW, S MOTYL, M MURRAY, B MURRAY, PR NOLTE, F PARK, C PEZZLO, M PRICE, M PUSCSH, A REED, K REIMER, L RINALDI, M RISTUCCIA, A ROBINSON, A ROSATI, L SAUBOLLE, M SCHALHAB, J SCHULTZ, G SCHWALBE, R SEWELL, D SHALES, D SIERRA, M SINNOTT, J SLIFKIN, M SMITH, L SPIEGEL, C STANECK, J STEELEMOORE, L STEIN, G STEVENS, D STRATTON, C TAN, J THOMAS, J WAITES, K WEINSTEIN, M WELCH, W WIN, W WOODS, G WRIGHT, L YUNGBLUTH, M ZWADYK, P AF JONES, RN SADER, HS ERWIN, ME ANDERSON, SC ALDRIDGE, KA ALLEN, S ANHALT, J APPELBAUM, P ARRINGTON, KL AYERS, L BAKER, C BEAVIS, K BERGER, J BERTHOLD, G BIRNBAUM, M BOYLE, J BRECHER, S BRECKENRIDGE, R BROWN, W BRUCKNER, D CARROLL, K CHAUDHARY, S CLEARY, T COCKERILL, F COYLE, M CRAWFORD, V DALTON, H DOERN, G EDBERG, S GELFAND, M GERLACH, EH GOODMAN, N GORZYNSKI, E GREEN, P GROSCHEL, D HANFF, P HANNA, B HARRELL, L HAUGEN, T HEAGREY, M HUMPHRIES, J ISENBERG, H JENKINS, S JONES, E JORGENSEN, J KAUFFMAN, C KEISER, J KOCKA, F KOMINOS, S LEVISON, M LOCKWOOD, W MANOS, J MARTIN, W MCLAUGHLIN, J METCHOCK, B MICKELSEN, P MOODY, J MORELLO, J MOSTOW, S MOTYL, M MURRAY, B MURRAY, PR NOLTE, F PARK, C PEZZLO, M PRICE, M PUSCSH, A REED, K REIMER, L RINALDI, M RISTUCCIA, A ROBINSON, A ROSATI, L SAUBOLLE, M SCHALHAB, J SCHULTZ, G SCHWALBE, R SEWELL, D SHALES, D SIERRA, M SINNOTT, J SLIFKIN, M SMITH, L SPIEGEL, C STANECK, J STEELEMOORE, L STEIN, G STEVENS, D STRATTON, C TAN, J THOMAS, J WAITES, K WEINSTEIN, M WELCH, W WIN, W WOODS, G WRIGHT, L YUNGBLUTH, M ZWADYK, P TI EMERGING MULTIPLY RESISTANT ENTEROCOCCI AMONG CLINICAL ISOLATES .1. PREVALENCE DATA FROM 97 MEDICAL-CENTER SURVEILLANCE STUDY IN THE UNITED-STATES SO DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE LA English DT Article ID LACTAMASE-PRODUCING ENTEROCOCCI; VANCOMYCIN RESISTANCE; ANTIMICROBIAL SUSCEPTIBILITIES; GLYCOPEPTIDE RESISTANCE; FAECIUM D366; AMPICILLIN; FAECALIS; PENICILLIN; INFECTIONS; ANTIBIOTICS AB To assess the evolving problem of therapeutic drug resistances among enterococci, we organized a comprehensive national (United States) surveillance trial using 99 recruited microbiology laboratories in 48 of the 49 contiguous stares or districts. AIL but two sites completed the protocol that generated information from nearly 2000 enterococci, usually isolated from blood cultures. All strains were speciated by the same method (API 20S) and were susceptibility tested by three methods (broth microdilution, disk diffusion, and Etest) against ampicillin, penicillin, vancomycin, teicoplanin, gentamicin, and streptomycin. Strains resistant to a glycopeptide or penicillin, or possessing high-level aminoglycoside resistance were referred to the monitor's laboratory for validation and additional susceptibility testing against other alternative antimicrobial agents. The most common species were Enterococcus faecalis and Enterococcus faecium. However, antimicrobial resistance occurred most often among the E. faecium isolates. Twenty-three percent of participant centers (22 sites) reported 87 vancomycin-resistant isolates, which accounts for 4.4% of the isolates evaluated. A recent audit (March 1994) of the laboratories not reporting vancomycin resistance during the study interval (October-December 1992) revealed that 61% of sites have now recognized these strains, a threefold increase in 12-15 months. Teicoplanin remained active against 28% (Van B phenotype) of vancomycin-resistant enterococci (10 E. faecalis, 13 E. faecium, and one Enterococcus spp.). Ampicillin-resistant beta-lactamase-positive strains were found only at one medical center (two strains, 0.2% of referred or validated strains); however, ampicillin-resistant strains represented 12% of all enterococcal, bur nearly 60% of E. faecium strains. Aminoglycoside resistance was: gentamicin 27% and streptomycin 36% of strains. The susceptibility to alternative drugs was: ciprofloxacin 25%, erythromycin 3%, trimethoprim/sulfamethoxazole 22%, and spectinomycin 97%. All National Committee for Clinical Laboratory Standards tests and interpretive criteria performed well. Other drugs worthy of therapeutic consideration include chloramphenicol, tetracyclines (especially doxycycline), novobiocin, trospectomycin or kanamycin as a co-drug, and some newer fluoroquinolones (sparfloxacin and clinafloxacin). Because of this rapidly evolving problem of drug-resistant invasive enterococcal infections, new alternative combination regimens require immediate consideration for structured clinical trials. C1 MILTON S HERSHEY MED CTR, HERSHEY, PA USA. OHIO STATE UNIV HOSP, COLUMBUS, OH USA. CTR DIS CONTROL, ATLANTA, GA USA. THOMAS JEFFERSON UNIV, PHILADELPHIA, PA USA. ST BARNABAS HOSP, BRONX, NY USA. NEBRASKA METHODIST HOSP, OMAHA, NE USA. BROOKLYN HOSP CTR, BROOKLYN, NY USA. CABRINI MED CTR, MALVERN, VIC, AUSTRALIA. VET ADM MED CTR, BOSTON, MA USA. NICHOLS INST, LOMA LINDA, CA USA. WSU, CTR HLTH, DETROIT, MI USA. UNIV CALIF LOS ANGELES, LOS ANGELES, CA USA. UNIV UTAH, MED CTR, SALT LAKE CITY, UT 84112 USA. ST JOHNS HOSP, LONDON, ENGLAND. JACKSON MEM HOSP, MIAMI, FL USA. MAYO CLIN & MAYO FDN, ROCHESTER, MN USA. HARBORVIEW MED CTR, SEATTLE, WA USA. VIRGINIA COMMONWEALTH UNIV MED COLL VIRGINIA, RICHMOND, VA USA. UNIV MASSACHUSETTS, MED CTR, AMHERST, MA 01003 USA. YALE NEW HAVEN MED CTR, NEW HAVEN, CT USA. ST FRANCIS REG MED CTR, WICHITA, KS USA. UNIV KENTUCKY, COLL MED, LEXINGTON, KY 40506 USA. VET ADM MED CTR, BUFFALO, NY USA. HITCHCOCK MED CTR, HANOVER, NH USA. UNIV VIRGINIA, HLTH SCI CTR, CHARLOTTESVILLE, VA 22903 USA. BETH ISRAEL HOSP, BOSTON, MA USA. BELLEVUE HOSP, NEW YORK, NY USA. DUKE UNIV, MED CTR, DURHAM, NC 27706 USA. VET ADM MED CTR, IOWA CITY, IA USA. BOZEMAN DEACONESS HOSP, BOZEMAN, MT USA. UNIV MISSISSIPPI, MED CTR, UNIVERSITY, MS 38677 USA. LONG ISL JEWISH MED CTR, NEW HYDE PK, NY USA. ASSOCIATED PATHOL LABS, LAS VEGAS, NV USA. UNIV TEXAS, HLTH SCI CTR, SAN ANTONIO, TX USA. VET ADM MED CTR, ANN ARBOR, MI USA. GEORGE WASHINGTON UNIV HOSP, WASHINGTON, DC 20052 USA. COOK CTY HOSP, CHICAGO, IL USA. PITTSBURGH MERCY HOSP, PITTSBURGH, PA USA. MED COLL PENN, PHILADELPHIA, PA USA. MED UNIV S CAROLINA, CHARLESTON, SC USA. UNIV HOSP ALBUQUERQUE, ALBUQUERQUE, NM USA. GRADY MEM HOSP, ATLANTA, GA USA. STANFORD UNIV, STANFORD, CA USA. ST PAUL RAMSEY HOSP, ST PAUL, MN USA. UNIV CHICAGO HOSP, CHICAGO, IL USA. ROSE MED CTR, DENVER, CO USA. BETH ISRAEL MED CTR, NEW YORK, NY USA. UNIV TEXAS, SCH MED, AUSTIN, TX USA. UNIV WASHINGTON, SCH MED, SEATTLE, WA USA. EMORY UNIV HOSP, ATLANTA, GA USA. FAIRFAX HOSP, FALLS CHURCH, VA USA. UNIV CALIF IRVINE, IRVINE, CA USA. ST LUKES EPISCOPAL HOSP, HOUSTON, TX USA. MAINE MED CTR, PORTLAND, ME USA. MARSHFIELD CLIN FDN MED RES & EDUC, MARSHFIELD, WI USA. VET ADM MED CTR, SALT LAKE CITY, UT USA. AUDIE L MURPHY MEM VET ADM MED CTR, SAN ANTONIO, TX USA. THERAPEUT RES INST, SARASOTA, FL USA. HARTFORD HOSP, HARTFORD, CT USA. SONORA LAB SCI, MESA, AZ USA. GOOD SAMARITAN HOSP, PHOENIX, AZ USA. BROOKE ARMY MED CTR, FT SAM HOUSTON, TX USA. ARKANSAS CHILDRENS HOSP, LITTLE ROCK, AR USA. UNIV MARYLAND HOSP, BALTIMORE, MD USA. VET ADM MED CTR, PORTLAND, OR USA. VET ADM MED CTR, CLEVELAND, OH USA. SUNY HLTH SCI CTR, BROOKLYN, NY USA. TAMPA GEN HOSP, TAMPA, FL USA. ALLEGHENY GEN HOSP, PITTSBURGH, PA USA. ST MICHAELS HOSP, NEWARK, NJ USA. UNIV WISCONSIN HOSP, MADISON, WI USA. UNIV HOSP CINCINNATI, CINCINNATI, OH USA. MED CTR DELAWARE, NEWARK, DE USA. MICHIGAN STATE UNIV, E LANSING, MI USA. VET ADM MED CTR, BOISE, ID USA. VANDERBILT UNIV SCH MED, NASHVILLE, TN USA. AKRON INFECT DIS, AKRON, OH USA. W VIRGINIA UNIV HOSP, MORGANTOWN, WV USA. UNIV ALABAMA HOSP & CLIN, BIRMINGHAM, AL USA. UNIV MED & DENT NEW JERSEY, NEW BRUNSWICK, NJ USA. MED CTR HOSP VERMONT, BURLINGTON, VT USA. MED COLL PENN, PHILADELPHIA, PA USA. LATTER DAY ST HOSP, SALT LAKE CITY, UT USA. LAKESIDE VET ADM MED CTR, CHICAGO, IL USA. VET ADM MED CTR, DURHAM, NC 27705 USA. RP JONES, RN (reprint author), UNIV IOWA, COLL MED, DEPT PATHOL, DIV MED MICROBIOL, 5232 RCP, IOWA CITY, IA 52242 USA. NR 42 TC 110 Z9 113 U1 0 U2 1 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0732-8893 J9 DIAGN MICR INFEC DIS JI Diagn. Microbiol. Infect. Dis. PD FEB PY 1995 VL 21 IS 2 BP 85 EP 93 DI 10.1016/0732-8893(94)00147-O PG 9 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA QX796 UT WOS:A1995QX79600006 PM 7628198 ER PT J AU FRESTON, JW BORCH, K BRAND, SJ CARLSSON, E CREUTZFELDT, W HAKANSON, R OLBE, L SOLCIA, E WALSH, JH WOLFE, MM AF FRESTON, JW BORCH, K BRAND, SJ CARLSSON, E CREUTZFELDT, W HAKANSON, R OLBE, L SOLCIA, E WALSH, JH WOLFE, MM TI EFFECTS OF HYPOCHLORHYDRIA AND HYPERGASTRINEMIA ON STRUCTURE AND FUNCTION OF GASTROINTESTINAL CELLS - A REVIEW AND ANALYSIS SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE OMEPRAZOLE; HYPOCHLORHYDRIA; HYPERGASTRINEMIA; ENTEROCHROMAFFIN-LIKE CELL CARCINOIDS; PEPTIC ULCER ID GASTRIC-ACID SECRETION; GROWTH-FACTOR-ALPHA; PERFUSED RAT STOMACH; ZOLLINGER-ELLISON SYNDROME; DUODENAL-ULCER PATIENTS; CANINE PARIETAL-CELLS; MULTIPLE ENDOCRINE NEOPLASIA; 24-HOUR INTRAGASTRIC ACIDITY; LONG-TERM TREATMENT; PLASMA-GASTRIN AB Since hypochlorhydria can induce hypergastrinemia, and gastrin has a trophic effect on some gastrointestinal cells, states that cause elevated plasma gastrin levels are of interest in terms of effects on cell growth and function. This article reviews the relationship between gastric mucosal cells during periods of acid stimulation and inhibition and analyses the effects of hypochlorhydria and hypergastrinemia on gastric and colonic cells and tumors. Hypochlorhydria releases the inhibitory effect of antral gastrin cells, inducing them to release gastrin in the presence of peptides or amino acids in the gastric lumen or in response to antral distension. Gastrin stimulates the oxyntic mucosa, which may lead to hyperplasia of enterochromaffin-like cells, resulting in enterochromaffin-like carcinoid tumors in aged rats and, rarely, in patients with chronic atrophic gastritis or gastrinomas. In addition to hypergastrinemia, other factors appear to be required for the progression of enterochromaffin-like hyperplasia to carcinoids; genetic factors may be involved. Gastrin elevations due to anti-secretory drug therapy are indirectly proportional to the degree of acid inhibition and are reversible upon cessation of therapy. The gastrin levels during omeprazole therapy are similar to those caused by gastric vagotomy. Available evidence does not support a relationship between hypergastrinemia and the occurrence or growth of gastric carcinoma or colonic tumors. C1 LINKOPING UNIV HOSP,DEPT SURG,S-58185 LINKOPING,SWEDEN. MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,BOSTON,MA 02114. ASTRA HASSLE AB,MOLNDAL,SWEDEN. UNIV GOTTINGEN,DIV GASTROENTEROL & ENDOCRINOL,W-3400 GOTTINGEN,GERMANY. LUND UNIV,DEPT PHARMACOL,LUND,SWEDEN. SAHLGRENS UNIV HOSP,DEPT SURG 2,GOTHENBURG,SWEDEN. UNIV PAVIA,DEPT HUMAN PATHOL,I-27100 PAVIA,ITALY. UNIV CALIF LOS ANGELES,VET ADM WADSWORTH MED CTR,SCH MED,LOS ANGELES,CA 90073. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DIV GASTROENTEROL,BOSTON,MA 02115. RP FRESTON, JW (reprint author), UNIV CONNECTICUT,CTR HLTH,DEPT MED,FARMINGTON,CT 06030, USA. NR 154 TC 38 Z9 38 U1 0 U2 1 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD FEB PY 1995 VL 40 IS 2 SU S BP S50 EP S62 DI 10.1007/BF02214871 PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QK829 UT WOS:A1995QK82900004 PM 7859584 ER PT J AU TEICHER, BA DUPUIS, NP LIU, F ROBINSON, MF MENON, K AF TEICHER, BA DUPUIS, NP LIU, F ROBINSON, MF MENON, K TI ADMINISTRATION OF A HEMOGLOBIN SOLUTION DECREASES HYPOXIA AND INCREASES RADIATION RESPONSE IN A RAT MAMMARY-CARCINOMA SO DRUG DEVELOPMENT RESEARCH LA English DT Article DE HEMOGLOBIN SOLUTION; TUMOR HYPOXIA; RADIATION SENSITIZATION ID CHEMOTHERAPEUTIC ALKYLATING-AGENTS; O2 TENSION MEASUREMENTS; TUMOR BLOOD-FLOW; BOVINE HEMOGLOBIN; OXYGEN DISTRIBUTION; TISSUE OXYGENATION; SOLID TUMORS; NECK TUMORS; RADIOSENSITIVITY; HEMATOCRIT AB Administration of an ultrapurified bovine hemoglobin solution (8 ml/kg, iv) to female Fisher 344 rats bearing the 13672 mammary carcinoma implanted subcutaneously in the hind leg reduced the hypoxic fraction of the tumor from 49 to 36% with normal air breathing and to 28% with carbogen (95% oxygen/5% carbon dioxide) breathing. When administration of the hemoglobin solution was followed by single dose (10, 20, or 30 Gray) local radiation therapy, the dose modifying factor was 1.5 with air breathing and 2.7 with carbogen breathing. For fractionated radiation therapy, 2, 3, or 4 Gray was delivered locally daily for 5 days. When the hemoglobin solution was administered prior to each radiation fraction and air breathing maintained, there was a 1.8-fold increase in tumor growth delay. When daily hemoglobin solution administration was accompanied by carbogen breathing, there was a 2.6-fold increase in tumor growth delay. Less frequent administration of the hemoglobin solution (alternate days, twice weekly or once weekly) resulted in 1.5- to 1.7-fold increases in tumor growth delay. The greatest increases in tumor oxygenation occurred shortly after administration of the hemoglobin solution; in fact at 12 h post administration of the hemoglobin solution, the tumors appeared to be more hypoxic than prior to administration of the hemoglobin solution. by 24 h post administration of the hemoglobin solution, the oxygen tension profile of the tumors were returning to pretreatment levels. further investigation of this ultrapurified hemoglobin solution in cancer is warranted. (C) 1995 Wiiey-Liss, Inc. C1 JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. RP TEICHER, BA (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. NR 72 TC 8 Z9 8 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0272-4391 J9 DRUG DEVELOP RES JI Drug Dev. Res. PD FEB PY 1995 VL 34 IS 2 BP 231 EP 240 DI 10.1002/ddr.430340212 PG 10 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QK041 UT WOS:A1995QK04100011 ER PT J AU LEE, KC DEEDS, JD SEGRE, GV AF LEE, KC DEEDS, JD SEGRE, GV TI EXPRESSION OF PARATHYROID HORMONE-RELATED PEPTIDE AND ITS RECEPTOR MESSENGER RIBONUCLEIC-ACIDS DURING FETAL DEVELOPMENT OF RATS SO ENDOCRINOLOGY LA English DT Article ID GENE; CLONING; HYPERCALCEMIA; COLLAGEN; TISSUES; CHAIN AB PTH-related peptide (PTHrP) is a causative agent of hypercalcemia associated with malignancy. PTHrP binds to and activates the same receptor as does PTH. Because PTHrP has been suggested to regulate the growth and differentiation of cells as a paracrine/autocrine factor, we examined the expression of bath PTHrP and its receptor genes during fetal development of rats (15-20 days gestation) by in situ hybridization with riboprobes. Both PTHrP and its receptor messenger RNAs (mRNAs) were expressed not only in the skeleton, but also in many fetal extraskeletal tissues, such as choroid plexus, ears, lungs, tooth buds, heart, and skin. In these extraskeletal tissues, PTHrP mRNA was expressed mainly in surface-lining cells, whereas its receptor mRNA was expressed mainly in adjacent mesenchymal cells. In endochondral bones, these two genes were expressed in largely discrete, but mostly neighboring, areas, although the localizations of these two mRNAs changed over developmental stages. The expression patterns of PTHrP and its receptor mRNAs during fetal development suggest PTHrP's roles as a paracrine factor and its involvement in epithelial-mesenchymal(-like) interactions. C1 HARVARD UNIV, MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED, ENDOCRINE UNIT, BOSTON, MA 02114 USA. FU NIDDK NIH HHS [DK-11794, DK-47237] NR 23 TC 288 Z9 290 U1 0 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD FEB PY 1995 VL 136 IS 2 BP 453 EP 463 DI 10.1210/en.136.2.453 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QD586 UT WOS:A1995QD58600011 PM 7835276 ER PT J AU BISSETTE, G GRIFF, D CARNES, M GOODMAN, B LAVINE, M LEVANT, B AF BISSETTE, G GRIFF, D CARNES, M GOODMAN, B LAVINE, M LEVANT, B TI APPARENT SEASONAL RHYTHMS IN HYPOTHALAMIC NEUROPEPTIDES IN RATS WITHOUT PHOTOPERIOD CHANGES SO ENDOCRINOLOGY LA English DT Article ID FACTOR-LIKE IMMUNOREACTIVITY; MANTLED GROUND-SQUIRRELS; CIRCANNUAL RHYTHMS; AFFECTIVE-DISORDER; SUPRACHIASMATIC NUCLEUS; OLFACTORY BULBECTOMY; DEPRESSED-PATIENTS; PERIOD; LESIONS; RESPONSES AB An apparent seasonal or circannual rhythm in the hypothalamic content of CRF, TRH, neurotensin, and neuromedin N has been observed in 12 separate monthly coherts (n = 10@ or 130 total) adult, male Sprague-Dawley rats obtained at the same time each month from a single commercial supplier and held under constant (12:12) photoperiod conditions since birth. Both annual and 4-month (terannual) harmonics can be statistically discerned in these apparent rhythms, which exhibit cycles containing concentration changes up to 3-fold the lowest levels across the year (CRF up arrow 390%, TRH up arrow 173%, neurotensin up arrow 136%, and neuromedin N up arrow 150%). Hypothalamic somatostatin did not exhibit these statistically significant robust rhythms nor did any peptide in regions outside the hypothalamus. These data indicate that a mechanism allowing enhanced or diminished physiological availability of these regulatory neuropeptides at different times of the year may exist and may display distinct cycles even in the absence of normal photoperiod cues. Possible regulatory responses of pituitary receptor populations for these hypothalamic peptides must be considered. As certain of these neuropeptides also appear to be altered in the cerebrospinal fluid of patients with major depression or schizophrenia, similar hypothalamic cyclic changes may underly psychiatric symptoms with seasonal periodicity. C1 UNIV WISCONSIN, MIDDLETON VET ADM HOSP, DEPT MED, MADISON, WI 53705 USA. DUKE UNIV, INST STAT & DECIS SCI, DURHAM, NC 27705 USA. UNIV KANSAS, MED CTR, DEPT PHARMACOL TOXICOL & THERAPEUT, KANSAS CITY, KS 66160 USA. RP BISSETTE, G (reprint author), DUKE UNIV, MED CTR, DEPT PHARMACOL & PSYCHIAT, BOX 3859, DURHAM, NC 27710 USA. FU NIMH NIH HHS [MH-45975] NR 44 TC 18 Z9 18 U1 1 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD FEB PY 1995 VL 136 IS 2 BP 622 EP 628 DI 10.1210/en.136.2.622 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QD586 UT WOS:A1995QD58600034 PM 7835296 ER PT J AU KRISHNAN, AV CRAMER, SD BRINGHURST, FR FELDMAN, D AF KRISHNAN, AV CRAMER, SD BRINGHURST, FR FELDMAN, D TI REGULATION OF 1,25-DIHYDROXYVITAMIN-D-3 RECEPTORS BY PARATHYROID-HORMONE IN OSTEOBLASTIC CELLS - ROLE OF 2ND-MESSENGER PATHWAYS SO ENDOCRINOLOGY LA English DT Article ID PROTEIN-KINASE-C; GENE-EXPRESSION; UP-REGULATION; BONE-CELLS; RAT; STIMULATION; TRANSCRIPTION; MOUSE; QUANTITATION; INHIBITION AB The regulation of vitamin D receptor (VDR) abundance in MC3T3-E1 mouse osteoblasts and UMR 106-01 rat osteosarcoma cells by rat PTH 1-34, human PTH-related protein 1-34, and agents that activate specific signal transduction pathways was studied. Treatment of these cells with forskolin (FSK) caused up-regulation of VDR, whereas treatment with phorbol esters suppressed VDR levels. PTH or PTH-related protein treatment induced a 2- to 3-fold increase in VDR, which was equivalent to that elicited by FSK in UMR 106-01 cells but less than the FSK-induced increase (similar to 8-fold) in MC3T3-E1 cells. PTH treatment of MC3T3-E1 cells resulted in an approximately 3-fold increase in VDR levels with maximum stimulation occurring at 10(-9) M PTH after 4 h of treatment. In UMR 4-7 cells, a subclone of UMR 106-01 cells that express cAMP resistance due to regulated expression of a mutant form of the type 1 regulatory subunit of the cAMP-dependent protein kinase A (PKA), the up-regulation of VDR abundance due to FSK and PTH treatment was mostly prevented. Pretreatment of MC3T3-E1 cells with staurosporine, an inhibitor of PKC, resulted in an approximately S-fold increase in basal VDR levels but did not enhance the PTH-mediated up-regulation of VDR. Collectively, these data suggest that the increase in VDR abundance observed in these target cells is mainly due to the activation of the PKA. signal transduction pathway. Treatment of UMR 106-01 cells with PTH for 4 h before exposure of the cells to 1,25-dihydroxyvitamin D-3 resulted in a 2-fold increase in the induction of 25-hydroxyvitamin D-3-24 hydroxylase messenger RNA. Thus, exposure of target cells to PTH augments their response to 1,25-dihydroxyvitamin D-3 due to up-regulation of VDR abundance. C1 STANFORD UNIV, SCH MED, DEPT MED, DIV ENDOCRINOL, STANFORD, CA 94305 USA. MASSACHUSETTS GEN HOSP, BOSTON, MA 02114 USA. FU NCI NIH HHS [1-F32-CA-59086]; NIDDK NIH HHS [DK-42482] NR 42 TC 57 Z9 57 U1 0 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD FEB PY 1995 VL 136 IS 2 BP 705 EP 712 DI 10.1210/en.136.2.705 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QD586 UT WOS:A1995QD58600043 PM 7835303 ER PT J AU WALTON, NY RUBINSTEIN, BK TREIMAN, DM AF WALTON, NY RUBINSTEIN, BK TREIMAN, DM TI CARDIAC-HYPERTROPHY SECONDARY TO STATUS EPILEPTICUS IN THE RAT SO EPILEPSY RESEARCH LA English DT Article DE STATUS EPILEPTICUS; CARDIAC HYPERTROPHY; RATS ID EPILEPTOGENIC ACTIVITY; NEURAL DISCHARGE; DEATH; DYSFUNCTION; PILOCARPINE; EPILEPSY; SEIZURES; DIAZEPAM; LITHIUM AB Status epilepticus was induced in rats by sequential injections of lithium and pilocarpine. Seizure activity was aborted by a combination of MK-801 and diazepam, with status duration ranging from 3 to 180 min. When the hearts were examined 8-12 days later, rats that had experienced an episode of status epilepticus had significantly heavier hearts than did controls. The nature of the cardiac tissue changes was not examined, and deserves further study. C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT NEUROL,LOS ANGELES,CA 90024. RP WALTON, NY (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,NEUROL & RES SERV,BLDG 304,E3-112,LOS ANGELES,CA 90073, USA. NR 17 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-1211 J9 EPILEPSY RES JI Epilepsy Res. PD FEB PY 1995 VL 20 IS 2 BP 121 EP 124 DI 10.1016/0920-1211(94)00074-7 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA QH610 UT WOS:A1995QH61000004 PM 7750508 ER PT J AU RUTECKI, PA AF RUTECKI, PA TI NORADRENERGIC MODULATION OF EPILEPTIFORM ACTIVITY IN THE HIPPOCAMPUS SO EPILEPSY RESEARCH LA English DT Article DE NOREPINEPHRINE; CA3 SUBFIELD; AFTERHYPERPOLARIZATION; PAROXYSMAL DEPOLARIZING SHIFT (PDS); PICROTOXIN; ELEVATED EXTRACELLULAR POTASSIUM ID RAT HIPPOCAMPUS; NETWORK EXCITABILITY; PYRAMIDAL CELLS; HIGH POTASSIUM; NORADRENALINE; NEURONS; EPILEPSY; INVITRO; AFTERHYPERPOLARIZATION; INITIATION AB Norepinephrine has been proposed to have both pro- and anticonvulsant properties. In the CA3 region of rat hippocampal slices, we studied the effects of norepinephrine and selective adrenergic agonists and antagonists on spontaneously occurring epileptiform discharges produced by either picrotoxin, a convulsant that impairs GABA(A)-mediated inhibition, or by elevated extracellular potassium ([K+](0)). Bath application of 5 mu M norepinephrine (NE) increased the rate of discharges produced by 7.5 mM [K+](0) but not the rate of picrotoxin-induced discharges. At higher concentrations (greater than or equal to 10 mu M), NE slowed the rate of spontaneous epileptiform discharges produced by picrotoxin. Spontaneous discharges produced by either picrotoxin or 7.5 mM [K+](0) were slowed or stopped by alpha-adrenergic receptor activation, the alpha(1) receptor being most responsible for this slowing effect. The alpha(2) agonist clonidine had minimal effects on the discharge rate; however, the alpha(2) antagonists yohimbine and idazoxan slowed the rate. In contrast, beta receptor or adenylate cyclase activation increased the rate of spontaneous discharges. This acceleration in rate was accompanied by a decrease in the amplitude and duration of the afterhyperpolarization (AHP) that follows the intracellularly recorded paroxysmal depolarizing shift (PDS). These results confirm that beta-adrenergic receptor activation increases the rate of epileptiform discharges and suggest that the acceleration is a result of a decrease in the AHP duration and amplitude. Activation of alpha-adrenergic receptors slowed the rate of epileptiform discharges without an associated change in the AHP. The AHP that follows the PDS helps define the maximal rate of epileptiform discharges in the hippocampal slice and a decrease in the duration of the AHP may contribute to the transition from an interictal to ictal pattern of epileptiform activity. C1 WILLIAM S MIDDLETON MEM VET ADM MED CTR,FRANCIS M FORSTER EPILEPSY CTR,MADISON,WI 53705. RP RUTECKI, PA (reprint author), UNIV WISCONSIN,DEPT NEUROL,2500 OVERLOOK TR,MADISON,WI 53705, USA. FU NINDS NIH HHS [R29-NS28580] NR 40 TC 34 Z9 35 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-1211 J9 EPILEPSY RES JI Epilepsy Res. PD FEB PY 1995 VL 20 IS 2 BP 125 EP 136 DI 10.1016/0920-1211(94)00078-B PG 12 WC Clinical Neurology SC Neurosciences & Neurology GA QH610 UT WOS:A1995QH61000005 PM 7750509 ER PT J AU FRUMAN, DA WOOD, MA GJERTSON, CK KATZ, HR BURAKOFF, SJ BIERER, BE AF FRUMAN, DA WOOD, MA GJERTSON, CK KATZ, HR BURAKOFF, SJ BIERER, BE TI FK506 BINDING-PROTEIN-12 MEDIATES SENSITIVITY TO BOTH PK506 AND RAPAMYCIN IN MURINE MAST-CELLS SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article ID CALCINEURIN PHOSPHATASE-ACTIVITY; P70 S6 KINASE; HUMAN FK506-BINDING PROTEIN; CYCLOSPORINE-A; IMMUNOSUPPRESSANT FK506; SIGNAL-TRANSDUCTION; IMMUNOPHILIN LIGAND; MOLECULAR-CLONING; LYMPHOCYTES-T; ACTIVATION AB The immunosuppressive drugs FK506 and rapamycin bind to a family of intracellular proteins termed FK506-binding proteins (FKBP). FK506 and rapamycin inhibit lymphocyte-activation pathways by forming complexes with an FKBP; subsequently, the drug/FKBP complexes interact with target molecules involved in signal transduction. A key target of FK506/FKBP12 complexes is calcineurin, a calcium- and calmodulin-dependent serine/threonine phosphatase. In mammalian cells, rapamycin treatment is associated with inhibition of the activity of several cellular serine/threonine kinases, including p70 S6 kinase. These kinases may function in signaling pathways involving TOR gene producs, which have been shown to interact with rapamycin/FKBP12 complexess in vitro. To determine if FKBP12 mediates the effects of both FK506 and rapamycin in mammalian cells, we overexpressed FKBP12 in a murine mast cell line. Increased expression of FKBP12 resulted in increased sensitivity to FK506 and rapamycin, as measured by inhibition of calcineurin activity and p70 S6 kinase activity, respectively. In contrast, overexpression of FKBP25 had no effect on sensitivity to either drug. Two distinct point mutations in FKBP12, one altering a hydrophobic residue within the drug-binding pocket and the other changing a charged surface residue of FKBP12, abrogated its ability to mediate sensitivity to FK506 and rapamycin. These results establish that FKBP12 can mediate sensitivity to both FK506 and rapamycin in mammalian cells. C1 DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DIV MED SCI,COMM IMMUNOL,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. CHILDRENS HOSP,DIV PEDIAT ENDOCRINOL,BOSTON,MA. BRIGHAM & WOMENS HOSP,DEPT RHEUMATOL & IMMUNOL,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DIV HEMATOL ONCOL,BOSTON,MA 02115. FU NHLBI NIH HHS [HL36110]; NIAID NIH HHS [AI32514, AI32101] NR 55 TC 54 Z9 55 U1 0 U2 0 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD FEB PY 1995 VL 25 IS 2 BP 563 EP 571 DI 10.1002/eji.1830250239 PG 9 WC Immunology SC Immunology GA QY506 UT WOS:A1995QY50600038 PM 7533090 ER PT J AU WEISS, MJ ORKIN, SH AF WEISS, MJ ORKIN, SH TI GATA TRANSCRIPTION FACTORS - KEY REGULATORS OF HEMATOPOIESIS SO EXPERIMENTAL HEMATOLOGY LA English DT Review ID C-KIT LIGAND; MAST-CELLS; DNA-BINDING; ERYTHROID-DIFFERENTIATION; DEVELOPING MOUSE; HOMOLOGOUS RECOMBINATION; POSITIVE REGULATOR; ENDOTHELIAL-CELLS; PROMOTER ACTIVITY; STEM-CELLS C1 HARVARD UNIV,CHILDRENS HOSP,SCH MED,DANA FARBER CANC INST,DEPT PEDIAT,DIV HEMATOL ONCOL,BOSTON,MA 02115. HOWARD HUGHES MED INST,BOSTON,MA 02115. RI Weiss, Mitchell/A-1245-2013 NR 96 TC 357 Z9 365 U1 2 U2 7 PU CARDEN JENNINGS PUBL COLTD 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 1995 VL 23 IS 2 BP 99 EP 107 PG 9 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA QF191 UT WOS:A1995QF19100004 PM 7828675 ER PT J AU SZCZEPIORKOWSKI, ZM DICKERSIN, GR LAPOSATA, M AF SZCZEPIORKOWSKI, ZM DICKERSIN, GR LAPOSATA, M TI FATTY-ACID ETHYL-ESTERS DECREASE HUMAN HEPATOBLASTOMA CELL-PROLIFERATION AND PROTEIN-SYNTHESIS SO GASTROENTEROLOGY LA English DT Article ID GLUTATHIONE-S-TRANSFERASE; NONOXIDATIVE ETHANOL-METABOLISM; HUMAN HEPATOCYTES; SYNTHASE; IDENTIFICATION; MYOCARDIUM; PANCREAS; TISSUES; CULTURE; RAT AB Background/Aims: Fatty acid ethyl esters (FAEEs) are nonoxidative products of ethanol metabolism. They have been implicated as mediators of ethanol-induced organ damage because FAEE and FAEE synthase have been found specifically in the organs damaged by ethanol abuse. This study showed toxicity specifically related to FAEE or their metabolites for intact human hepatoblastoma-derived cells (HepG2). Methods: The lipid core of human low-density lipoprotein (LDL) was extracted and the LDL particle reconstituted with either ethyl oleate or ethyl arachidonate. Cultured HepG2 cells were incubated with LDL containing FAEE. Cell proliferation was measured by [methyl-H-3]thymidine incorporation. Protein synthesis was determined using L-[S-35]methionine. Results: Incubation of cells with 600 mu mol/L ethyl oleate or 800 mu mol/L ethyl arachidonate decreased [methyl-H-3]thymidine incorporation into HepG2 cells by 31% and 37%, respectively. LDL reconstituted with 400 mu mol/L ethyl oleate decreased protein synthesis in intact HepG2 cells by 41%. Electron microscopy revealed significant changes in cell morphology, particularly involving the cell nucleus. FAEE delivered in reconstituted LDL were rapidly hydrolyzed and the fatty acids re-esterified into phospholipids, triglycerides, and cholesterol esters, with preference for triglycerides. Conclusions: These findings provide evidence that FAEE are toxic for intact human hepatoblastoma cells and that they or their metabolites may be an important causative agent in ethanol-induced liver damage. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RI Szczepiorkowski, Zbigniew/A-1359-2007 OI Szczepiorkowski, Zbigniew/0000-0003-2357-9564 FU NIDDK NIH HHS [R01 DK37454] NR 34 TC 74 Z9 75 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD FEB PY 1995 VL 108 IS 2 BP 515 EP 522 DI 10.1016/0016-5085(95)90081-0 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QE148 UT WOS:A1995QE14800027 PM 7835594 ER PT J AU RICHTER, JM CHRISTENSEN, MR KAPLAN, LM NISHIOKA, NS AF RICHTER, JM CHRISTENSEN, MR KAPLAN, LM NISHIOKA, NS TI EFFECTIVENESS OF CURRENT TECHNOLOGY IN THE DIAGNOSIS AND MANAGEMENT OF LOWER GASTROINTESTINAL HEMORRHAGE SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID COLONOSCOPY; ANGIOGRAPHY; ANGIODYSPLASIA AB Lower gastrointestinal hemorrhage is a common clinical problem for which multiple diagnostic tests and therapeutic interventions have been developed but no optimal approach has been established. We reviewed 107 consecutive patients admitted to the Massachusetts General Hospital for management of acute lower gastrointestinal hemorrhage to determine the effectiveness of diagnostic and management technologies, with particular attention to urgent colonoscopy. Colonoscopy yielded a diagnosis in 90% of patients, provided the opportunity for successful therapy in 9 of 13 patients (69%), and shortened hospital stay. Angiography performed after a scan positive for bleeding was often diagnostic, and angiography provided the means for successful therapy in 5 of 10 patients (50%). Barium enema and sigmoidoscopy had lower clinical yields. Although roles exist for other technologies, colonoscopy is the most convenient and effective first test in the evaluation of patients with significant lower gastrointestinal hemorrhage. Diagnostic yield, therapeutic opportunity, and cost effectiveness are maximized in early studies. C1 MASSACHUSETTS GEN HOSP,WELLMAN LAB PHOTOMED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. RP RICHTER, JM (reprint author), MASSACHUSETTS GEN HOSP,GEN INTERNAL MED UNIT,GASTROINTESTINAL UNIT,JACKSON 7,BOSTON,MA 02114, USA. NR 16 TC 93 Z9 94 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 1995 VL 41 IS 2 BP 93 EP 98 DI 10.1016/S0016-5107(05)80588-7 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QH094 UT WOS:A1995QH09400001 PM 7721024 ER PT J AU TISHKOFF, DX ROCKMILL, B ROEDER, GS KOLODNER, RD AF TISHKOFF, DX ROCKMILL, B ROEDER, GS KOLODNER, RD TI THE SEP1 MUTANT OF SACCHAROMYCES-CEREVISIAE ARRESTS IN PACHYTENE AND IS DEFICIENT IN MEIOTIC RECOMBINATION SO GENETICS LA English DT Article ID DOUBLE-STRAND BREAKS; SYNAPTONEMAL COMPLEX-FORMATION; TRANSFER PROTEIN-BETA; ESCHERICHIA-COLI; CHROMOSOME SYNAPSIS; YEAST-CELLS; DNA; EXCHANGE; MEIOSIS; GENE AB Strand exchange protein 1 (Sep1) from Saccharomyces cerevisiae promotes homologous pairing of DNA in vitro and sep1 mutants display pleiotropic phenotypes in both vegetative and meiotic cells. In this study, we examined in detail the ability of the sep1 mutant to progress through meiosis I prophase and to undergo meiotic recombination. In meiotic return-to-growth experiments, commitment to meiotic recombination began at the same time in wild type and mutant; however, recombinants accumulated at decreased rates in the mutant. Gene conversion eventually reached nearly wild-type levels, whereas crossing over reached 15-50% of wild type. In an assay of intrachromosomal pop-out recombination, the sep1, dmc1 and rad51 single mutations had only small effects; however, pop-out recombination was virtually eliminated in the sep1 dmc1 and sep1 rad51 double mutants, providing evidence for multiple recombination pathways. Analysis of meiotic recombination intermediates indicates that the sep1 mutant is deficient in meiotic double-strand break repair. In a physical assay, the formation of mature reciprocal recombinants in the sep1 mutant was delayed relative to wild type and ultimately reached only 50% of the wild-type level. Electron microscopic analysis of meiotic nuclear spreads indicates that the sep1 Delta mutant arrests in pachytene, with apparently normal synaptonemal complex. This arrest is RAD9-independent. We hypothesize that the Sep1 protein participates directly in meiotic recombination and that other strand exchange enzymes, acting in parallel recombination pathways, are able to substitute partially for the absence of the Sep1 protein. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. YALE UNIV,DEPT BIOL,NEW HAVEN,CT 06520. FU NIGMS NIH HHS [GM-29383] NR 52 TC 42 Z9 44 U1 0 U2 0 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 SN 0016-6731 J9 GENETICS JI Genetics PD FEB PY 1995 VL 139 IS 2 BP 495 EP 509 PG 15 WC Genetics & Heredity SC Genetics & Heredity GA QE145 UT WOS:A1995QE14500002 PM 7713413 ER PT J AU BODE, BP KAMINSKI, DL SOUBA, WW LI, AP AF BODE, BP KAMINSKI, DL SOUBA, WW LI, AP TI GLUTAMINE TRANSPORT IN ISOLATED HUMAN HEPATOCYTES AND TRANSFORMED LIVER-CELLS SO HEPATOLOGY LA English DT Article ID AMINO-ACID-TRANSPORT; PERFUSED-RAT-LIVER; SYSTEM-N; PRIMARY CULTURES; NITROGEN-METABOLISM; HORMONAL-REGULATION; MEMBRANE-VESICLES; HUMAN FIBROBLASTS; SKELETAL-MUSCLE; EXPRESSION AB The transport of L-glutamine was examined in isolated adult and fetal human hepatocytes as well as in the human hepatoma cell lines HepG2 and SK-Hep. In all cells studied, glutamine uptake was at least 85% Na+-dependent. Kinetic analysis of the Na+-dependent component indicated mediation by a single transporter in three human hepatocyte preparations and in SK-Hep cells, whereas two transporters appeared to be responsible for glutamine uptake in HepG2 cells and in hepatocytes from the liver of one male patient. Amino acid inhibition analysis showed primary mediation by System N in fetal and adult hepatocytes, whereas System ASC was principally responsible for glutamine uptake in transformed cells. Similar to the rat transporter, human System N was pH-sensitive, stereospecific, and responsive to treatment with steroid hormones. Although the human carrier was less tolerant of Li+- for Na+ substitution, glutamine transport in primary human hepatocytes was stimulated by treatment with hypotonic buffer (cell swelling), as reported in rat parenchymal cells. In contrast, glutamine transport in hepatoma cells was relatively insensitive to changes in extracellular pH and failed to show enhanced activity in response to hypoosmotic challenge. Collectively, the data suggest that markedly distinct plasma membrane transporters mediate the concentrative uptake of glutamine in normal and transformed human hepatocytes, and that the salient properties of System N have been largely conserved from rat to man. C1 MONSANTO CO, LIVER BIOL LAB, ST LOUIS, MO USA. ST LOUIS UNIV, SCH MED, DEPT SURG, ST LOUIS, MO USA. HARVARD UNIV, SCH MED, BOSTON, MA USA. RP BODE, BP (reprint author), MASSACHUSETTS GEN HOSP, DIV SURG ONCOL, COX BLDG, 6TH FLOOR, BOSTON, MA 02114 USA. OI Li, Albert/0000-0001-5772-6265 NR 31 TC 60 Z9 65 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD FEB PY 1995 VL 21 IS 2 BP 511 EP 520 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RB789 UT WOS:A1995RB78900035 PM 7843725 ER PT J AU TAYLOR, E AF TAYLOR, E TI RADICAL EMPIRICISM AND THE NEW SCIENCE OF CONSCIOUSNESS SO HISTORY OF THE HUMAN SCIENCES LA English DT Article C1 MASSACHUSETTS GEN HOSP,BOSTON,MA. RP TAYLOR, E (reprint author), HARVARD UNIV,SCH MED,BOSTON,MA 02115, USA. NR 47 TC 3 Z9 3 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 6 BONHILL STREET, LONDON, ENGLAND EC2A 4PU SN 0952-6951 J9 HIST HUM SCI JI Hist. Hum. Sci. PD FEB PY 1995 VL 8 IS 1 BP 47 EP 60 DI 10.1177/095269519500800104 PG 14 WC History & Philosophy Of Science; History Of Social Sciences SC History & Philosophy of Science; Social Sciences - Other Topics GA QN059 UT WOS:A1995QN05900004 ER PT J AU WONG, TY SUSTER, S DUNCAN, LM MIHM, MC AF WONG, TY SUSTER, S DUNCAN, LM MIHM, MC TI NEVOID MELANOMA - A CLINICOPATHOLOGICAL STUDY OF 7 CASES OF MALIGNANT-MELANOMA MIMICKING SPINDLE AND EPITHELIOID CELL NEVUS AND VERRUCOUS DERMAL NEVUS SO HUMAN PATHOLOGY LA English DT Article DE NEVOID MELANOMA; VERRUCOID PATTERN; DOME-SHAPED PATTERN; VERRUCOUS DERMAL NEVUS; SPINDLE AND EPITHELIOID CELL NEVUS ID SPITZS NEVUS; DIAGNOSIS; PROGNOSIS AB We report seven cases of a distinctive type of malignant melanoma characterized by a deceptively benign histological appearance with an architecture resembling that of benign melanocytic nevi on scanning magnification. Two predominant architectural patterns were observed: a dome-shaped pattern (two specimens) and a verrucoid pattern (five specimens). The specimens with a dome-shaped pattern of growth were characterized by a smooth epidermal surface and a proliferation of epithelioid melanoma cells with an inconspicuous intraepidermal component resembling spindle and epithelioid cell nevi (Spitz nevi). Gradual diminution in the size of dermal nests toward the bases of the lesions simulating the maturation phenomenon of benign nevi was observed; however, the dermal organization in cords and strands of melanoma cells and the persistence of cellular atypia extending to the bases of the tumors allowed their recognition as malignant melanomas. On the other hand, the specimens with a verrucoid growth pattern consisted of broad, exophytic tumors with a verrucous epidermal surface resembling that of papillomatous dermal nevi but distinguished from them by the presence of a continuous proliferation of melanocytes along the dermal-epidermal junction and by confluent sheets of melanoma cells in the dermis without evidence of true maturation. Clinical follow-up showed local recurrence in three patients after intervals ranging from 5 months to 5 years and regional metastasis in one patient after 2 years. The lesions described here may constitute a serious pitfall for diagnosis because of their innocent silhouette on scanning magnification and their superficial resemblance to spindle and/or epithelioid cell nevi and benign verrucous melanocytic nevi. Proper attention to cytological detail and subtle architectural features will aid in recognizing this unusual variant of malignant melanoma. Copyright (C) 1995 by W.B. Saunders Company C1 BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA. MT SINAI MED CTR,DEPT PATHOL,MIAMI BEACH,FL 33140. UNIV MIAMI,SCH MED,MIAMI BEACH,FL. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. ALBANY MED COLL,DEPT DERMATOL,ALBANY,NY. RI Duncan, Lyn/E-9878-2013 NR 36 TC 52 Z9 52 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD FEB PY 1995 VL 26 IS 2 BP 171 EP 179 DI 10.1016/0046-8177(95)90034-9 PG 9 WC Pathology SC Pathology GA QH464 UT WOS:A1995QH46400008 PM 7860047 ER PT J AU LI, XP ABDI, K MENTZER, SJ AF LI, XP ABDI, K MENTZER, SJ TI HYBRIDOMA SCREENING USING AN AMPLIFIED FLUORESCENCE MICROASSAY TO QUANTIFY IMMUNOGLOBULIN CONCENTRATION SO HYBRIDOMA LA English DT Article ID MONOCLONAL-ANTIBODIES; CULTURE; CELLS AB The early identification of antibody-secreting hybridomas significantly reduces the time and resources devoted to unproductive colonies, To quantify the immunoglobulin concentration in hybridoma supernatants within 2 weeks of fusion, we used immunomagnetic microspheres to capture immunoglobulin in the hybridoma culture supernatant, The captured immunoglobulin was detected using a goat anti-mouse second antibody liked to beta-galactosidase. With data transformation to correct for the nonlinear accumulation of the fluorescent reaction product, the enzymatic hydrolysis of fluorescein digalactoside permitted the reliable detection of less than 10 pg of immunoglobulin per milliliter, To determine the value of quantifying immunoglobulin concentration within 2 weeks of fusion, the amplified fluorescence microassay was applied to the evaluation of 3 consecutive fusions and more than 1200 growing hybridoma colonies, Using antibody concentrations greater than 10 ng/ml as a threshold for routine subculture, the selection of hybridoma colonies based on antibody secretion was threefold more efficient than selection based on colony growth alone, These results suggest the utility of the early determination of immunoglobulin concentration in the selection of hybridoma colonies. C1 BRIGHAM & WOMENS HOSP,DANA FARBER CANC INST,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA 02215. FU NHLBI NIH HHS [HL47078] NR 12 TC 9 Z9 9 U1 0 U2 1 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 1995 VL 14 IS 1 BP 75 EP 78 DI 10.1089/hyb.1995.14.75 PG 4 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Immunology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology GA QK340 UT WOS:A1995QK34000010 PM 7768535 ER PT J AU PASCUAL, M FRENCH, LE AF PASCUAL, M FRENCH, LE TI COMPLEMENT IN HUMAN-DISEASES - LOOKING TOWARDS THE 21ST-CENTURY SO IMMUNOLOGY TODAY LA English DT Article AB The complement system has evolved to fulfil crucial functions, including opsonization of microorganisms, enhancement of inflammatory responses, clearance of immune complexes and cell lysis. Deficiencies or dysregulations of this system are associated with major health burdens, such as infectious and autoimmune diseases. A recent meeting* addressed the function and role of complement, and its regulators, in human disease. C1 UNIV HOSP GENEVA,DEPT DERMATOL,GENEVA,SWITZERLAND. RP PASCUAL, M (reprint author), MASSACHUSETTS GEN HOSP,RENAL UNIT,BOSTON,MA 02114, USA. NR 0 TC 22 Z9 22 U1 0 U2 0 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 FEB PY 1995 VL 16 IS 2 BP 58 EP 61 DI 10.1016/0167-5699(95)80088-3 PG 4 WC Immunology SC Immunology GA QE596 UT WOS:A1995QE59600003 PM 7888067 ER PT J AU KIRIKAE, F KIRIKAE, T QURESHI, N TAKAYAMA, K MORRISON, DC NAKANO, M AF KIRIKAE, F KIRIKAE, T QURESHI, N TAKAYAMA, K MORRISON, DC NAKANO, M TI CD14 IS NOT INVOLVED IN RHODOBACTER-SPHAEROIDES DIPHOSPHORYL LIPID A INHIBITION OF TUMOR-NECROSIS-FACTOR-ALPHA AND NITRIC-OXIDE INDUCTION BY TAXOL IN MURINE MACROPHAGES SO INFECTION AND IMMUNITY LA English DT Article ID LIPOPOLYSACCHARIDE-BINDING PROTEINS; RHODOPSEUDOMONAS-SPHAEROIDES; LPS BINDING; BACTERIAL LIPOPOLYSACCHARIDE; NONTOXIC LIPOPOLYSACCHARIDE; BEARING PARTICLES; SOLUBLE CD14; FATTY-ACIDS; ENDOTOXIN; RECEPTORS AB Taxol, a microtubule stabilizer with anticancer activity, mimics the actions of lipopolysaccharide (LPS) on murine macrophages in vitro. Recently, it was shown that taxol-induced macrophage activation was inhibited by the LPS antagonist Rhodobacter sphaeroides diphosphoryl lipid A (RsDPLA). To investigate the mechanisms of taxol-induced macrophage activation, the present study focused on the interaction of LPS, RsDPLA, and taxol in the activation of and binding to macrophages. Taxol alone induced murine C3H/He macrophages to secrete tumor necrosis factor alpha (TNF) and to produce nitric oxide (NO) with kinetics similar to that of LPS. Macrophages from LPS-hyporesponsive C3H/HeJ mice, in contrast, did not yield any detectable TNF and NO production in response to LPS or taxol. RsDPLA inhibited taxol-induced TNF and NO production from C3H/He macrophages in a dose-dependent manner. The inhibition by RsDPLA was specific for LPS and taxol in that RsDPLA did not inhibit heat-killed Listeria monocytogenes- or zymosan-induced TNF production. Polymyxin B blocked the inhibitory effect of RsDPLA on taxol-induced TNF production. The inhibitory activity of RsDPLA appeared to be reversible since macrophages still responded to taxol in inducing TNF production after the RsDPLA was washed out with phosphate-buffered saline prior to the addition of taxol. Taxol-induced TNF production was not inhibited by colchicine, vinblastine, or 10-deacetylbaccatine III. A mutant cell line, J7.DEF3, defective in expression of a CD14 antigen, responded equally well to taxol by producing TNF as did the parent J774.1 cells. This suggested that the activation of macrophages by taxol does not require CD14. Taxol-induced TNF production by the mutant cells was also inhibited by RsDPLA. I-125-labeled LPS and H-3-labeled taxol was reported to bind to J774.1 cells predominantly via CD14 and microtubules, respectively. The binding of I-125-labeled LPS to J7.DEF3 cells was about 30 to 40% of that to J774.1 cells, The binding of I-125-LPS to J774.1 cells was inhibited by unlabeled LPS and RsDPLA but not by taxol. On the other hand, H-3-labeled taxol bound to both J774.1 cells and J7.DEF3 cells in similar time- and dose-dependent manners, The binding of [H-3] taxol to these cells was inhibited by taxol but not by LPS or RsDPLA. Although the binding studies failed to examine cross competition for binding to macrophages, a possible explanation of these results is that LPS, RsDPLA, and taxol share the same molecule(s) on murine macrophages for their functional receptor(s), which is neither CD14 nor tubulin. C1 JICHI MED SCH,DEPT MICROBIOL,MINAMI KAWACHI,TOCHIGI 32904,JAPAN. UNIV WISCONSIN,COLL AGR & LIFE SCI,DEPT BACTERIOL,MADISON,WI 53706. WILLIAM S MIDDLETON MEM VET ADM MED CTR,MYCOBACTERIOL RES LAB,MADISON,WI 53706. UNIV KANSAS,MED CTR,CTR CANC,KANSAS CITY,KS 66160. FU NCI NIH HHS [P01 CA54474]; NIAID NIH HHS [R37 AI23447]; NIGMS NIH HHS [GM36054] NR 59 TC 52 Z9 52 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD FEB PY 1995 VL 63 IS 2 BP 486 EP 497 PG 12 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA QC603 UT WOS:A1995QC60300017 PM 7529746 ER PT J AU MAGEE, DM WILLIAMS, DM SMITH, JG BLEICKER, CA GRUBBS, BG SCHACHTER, J RANK, RG AF MAGEE, DM WILLIAMS, DM SMITH, JG BLEICKER, CA GRUBBS, BG SCHACHTER, J RANK, RG TI ROLE OF CD8 T-CELLS IN PRIMARY CHLAMYDIA INFECTION SO INFECTION AND IMMUNITY LA English DT Article ID MOUSE PNEUMONITIS AGENT; NECROSIS-FACTOR-ALPHA; IFN-GAMMA; BETA-2-MICROGLOBULIN-DEFICIENT MICE; LISTERIA-MONOCYTOGENES; DEFICIENT MICE; HOST DEFENSE; CRYPTOCOCCUS-NEOFORMANS; TRACHOMATIS INFECTION; TOXOPLASMA-GONDII AB The role of CD4 and CD8 T cells in primary Chlamydia trachomatis pneumonia was investigated by using in vivo depletion techniques to eliminate T cell populations. Reduction of either CD4 T cells or CD8 T cells caused a significant increase in organism burden in the lungs, as measured by both quantitative culture and detection of chlamydial antigen on day 14 postinfection. Chlamydia-specific antibody levels in plasma or antigen-induced gamma interferon (IFN-gamma) production by spleen cells was dramatically reduced by depletion of CD4 cells. The reduction in IFN-gamma achieved by depletion of CD8 cells did not reach statistical significance. In the survival studies, depletion of CD4 cells led to a significant increase in mortality. Although there was a trend toward higher mortality, depletion of CD8 cells did not significantly increase mortality. The role of CD8 T cells in host defense was clarified in studies using beta 2-microglobulin-deficient (major histocompatibility class I antigen-deficient, C1D) mice which are defective in CD8 T-cell function. In this model, a significant increase in organism burden was seen during infection in C1D mice compared with that in C57BL/6 controls and a significant increase in mortality was observed as well. However, surviving C1D mice were able to clear the infection by day 34. C1D mice had increased numbers of CD4 T cells in both the spleen and the lungs during infection compared,vith those of C57BL/6 controls. IFN-gamma in C57BL/6 mice was produced by both CD4 and CD8 cells. Thus, there is a protective role for both CD4 and CD8 cells in host defense against Chlamydia infection, but the former appear to be dominant. C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,DIV INFECT DIS,SAN ANTONIO,TX 78284. UNIV CALIF SAN FRANCISCO,DEPT LAB MED,SAN FRANCISCO,CA 94132. UNIV ARKANSAS MED SCI HOSP,DEPT MICROBIOL & IMMUNOL,LITTLE ROCK,AR 72205. RP MAGEE, DM (reprint author), TEXAS CTR INFECT DIS,DEPT IMMUNOL RES,SAN ANTONIO,TX 78223, USA. FU NIAID NIH HHS [AI 22380, AI 26328] NR 46 TC 76 Z9 78 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD FEB PY 1995 VL 63 IS 2 BP 516 EP 521 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA QC603 UT WOS:A1995QC60300021 PM 7822016 ER PT J AU SIMPSON, S HOLLANDER, G SHE, J LEVELT, C HUANG, M TERHORST, C AF SIMPSON, S HOLLANDER, G SHE, J LEVELT, C HUANG, M TERHORST, C TI SELECTION OF PERIPHERAL AND INTESTINAL T-LYMPHOCYTES LACKING CD3-ZETA SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE INTRAEPITHELIAL LYMPHOCYTE; MHC; SIGNAL TRANSDUCTION; TCR ID CELL RECEPTOR/CD3 COMPLEX; GAMMA-CHAIN; INTRAEPITHELIAL LYMPHOCYTES; NEGATIVE SELECTION; DEFICIENT MICE; ANTIGEN; GUT; CD3-EPSILON; ACTIVATION; EPITHELIUM AB The CD3 zeta chain of the TCR plays a pivotal role in the activation of T cell responses toward foreign antigen and in the selection of the T cell repertoire. T lymphocytes from mice deficient in CD3 zeta (CD3 zeta/eta(-/-) mice) express very few cell surface TCR-CD3 complexes, and these animals have poorly developed thymuses which lack single-positive CD8 and CD4 thymocytes. Nevertheless, a substantial number of single-positive CD4(+) and CD8(+) T lymphocytes are found in peripheral lymphoid organs of CD3 zeta/eta(-/-) animals. Using double-mutant mice, generated by breeding CD3 zeta/eta(-/-) mice with others deficient in the expression of either class I or class II MHC molecules, we demonstrate here that positive selection of peripheral CD4(+) and CD8(+) T lymphocytes can occur in the absence of CD3 zeta/eta molecules. Analysis of the intestinal intra-epithelial lymphocytes from CD3 zeta/eta(-/-) mice revealed a novel T cell population expressing high levels of an alternative TCR alpha beta, due to the replacement of CD3 zeta by Fc epsilon Rl gamma. Developmentally, these cells also depend on class I MHC expression, In contrast, TCR gamma delta/Fc epsilon Rl gamma(+) T cells develop independently of MHC class I or class II molecules. These experiments demonstrate that the unique subset of intestinal TCR alpha beta/Fc epsilon Rl gamma(+) lymphocytes is developmentally dependent on MHC expression. The restricted expression of TCR alpha beta/Fc epsilon Rl gamma(+) cells in the intestinal mucosa (rather than the thymus or lymph nodes) supports the hypothesis that selection of these T cells occurs extrathymically. C1 HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DEPT MED,DIV IMMUNOL,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. GENPHARM INT,MT VIEW,CA 94043. MAX PLANCK INST IMMUNOL,D-79106 FREIBURG,GERMANY. FU NIAID NIH HHS [AI-28046] NR 33 TC 21 Z9 21 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 FEB PY 1995 VL 7 IS 2 BP 287 EP 293 DI 10.1093/intimm/7.2.287 PG 7 WC Immunology SC Immunology GA QH585 UT WOS:A1995QH58500016 PM 7734423 ER PT J AU SHIPP, TD BROMLEY, B BENACERRAF, BR AF SHIPP, TD BROMLEY, B BENACERRAF, BR TI SONOGRAPHICALLY DETECTED ABNORMALITIES OF THE UMBILICAL-CORD SO INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS LA English DT Article DE UMBILICAL CORD; PRENATAL ULTRASONOGRAPHY; ABNORMALITIES ID NECROTIZING FUNISITIS; DIAGNOSIS; PSEUDOCYST; HEMANGIOMA AB Objectives: This study was undertaken as a retrospective chart review to evaluate the range of umbilical cord abnormalities detected by prenatal sonography, as well as the outcome and pathologic correlation. Methods: We identified 13 cases of umbilical cord abnormalities detected sonographically over a 46-month period. We evaluated the ultrasound appearance, size, location, and color Doppler characteristic in each case. Results: There were 4 instances of clear cysts on the umbilical cord, 8 with complex masses, and 1 with complete, cystic encasement of the cord throughout its length, The pathology included vascular abnormalities (hemangioma, hematoma, varicosity), edema of the umbilical cord with pseudocysts, and syncytial knots. There was 1 known karyotypic abnormality (trisomy 13). Twelve of the 13 newborns survived; the neonatal death occurred in the fetus with trisomy 13. Conclusion: The presence of umbilical cord abnormalities may represent a variety of pathologic entities. Clinical outcome is usually favorable. C1 MASSACHUSETTS GEN HOSP,DEPT OBSTET & GYNECOL,BOSTON,MA 02114. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT OBSTET & GYNECOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. NR 20 TC 17 Z9 18 U1 0 U2 0 PU ELSEVIER SCI PUBL IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0020-7292 J9 INT J GYNECOL OBSTET JI Int. J. Gynecol. Obstet. PD FEB PY 1995 VL 48 IS 2 BP 179 EP 185 DI 10.1016/0020-7292(94)02297-C PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA QH100 UT WOS:A1995QH10000006 PM 7789592 ER PT J AU HUG, EB FITZEK, MM LIEBSCH, NJ MUNZENRIDER, JE AF HUG, EB FITZEK, MM LIEBSCH, NJ MUNZENRIDER, JE TI LOCALLY CHALLENGING OSTEOGENIC AND CHONDROGENIC TUMORS OF THE AXIAL SKELETON - RESULTS OF COMBINED PROTON AND PHOTON RADIATION-THERAPY USING 3-DIMENSIONAL TREATMENT PLANNING SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 35th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 11-15, 1993 CL NEW ORLEANS, LA SP Amer Soc Therapeut Radiol & Oncol DE CHORDOMA; CHONDROSARCOMA; OSTEOGENIC SARCOMA; GIANT CELL TUMOR; CHARGED PARTICLE THERAPY; RADIATION THERAPY ID GIANT-CELL TUMOR; CHORDOMA; BONE; CHONDROSARCOMA; CHONDROBLASTOMA; RADIOTHERAPY; SARCOMA; SKULL AB Purpose: Tumors of the axial skeleton are at high risk for local failure. Total surgical resection is rarely possible. Critical normal tissues limit the efficacy of conventional photon therapy. This study reviews our experience of using combined high dose proton and photon radiation therapy following three-dimensional (3D) treatment planning. Methods and Materials: Between December 1980 and September 1992, 47 patients were treated at the Massachusetts General Hospital and Harvard Cyclotron Laboratory for primary or recurrent chordomas and chondrosarcomas (group 1, 20 patients), osteogenic sarcomas (group 2, 15 patients) and giant cell tumors, osteo- or chondroblastomas (group 3, 12 patients). Radiation treatment was given postoperatively in 23 patients, pre- and postoperatively in 17 patients, and 7 patients received radiation therapy as definitive treatment modality following biopsy only. The proton radiation component was delivered using a 160 MeV proton beam and the photon component using megavoltage photons up to 23 MV energy with 1.8-2.0 Cobalt Gray Equivalent (CGE) per fraction, once a day. Total external beam target dose ranged from 55.3 CGE to 82.0 CGE with mean target doses of 73.9 CGE (group 1), 69.8 CGE (group 2), and 61.8 CGE (group 3). Results: Group 1 (chordoma and chondrosarcoma): Five of 14 patients (36%) with chordoma recurred locally, and 2 out of 5 patients developed distant metastasis, resulting in 1 death from disease. A trend for improved local control was noted for primary vs. recurrent tumors, target doses > 77 CGE and gross total resection. All patients with chondrosarcoma achieved and maintained local control and disease-free status. Five-year actuarial local control and overall survival rates were 53% and 50% for chordomas and 100% and 100% for chondrosarcomas, respectively. Group 2 (osteogenic sarcoma): Three of 15 patients (20%) never achieved local control and died within 6 months of completion of radiation treatment. Only 1 out of 12 patients who were controlled for more than 6 months failed locally, yielding a 5-year local control rate of 59% for 15 patients. Overall, 4 patients (27%) developed distant metastasis (two in patients with uncontrolled primary); 4 patients succumbed to their disease, 3 patients died of intercurrent disease, resulting in overall survival of 44% at 5 years. Group 3 (giant cell tumors, osteo- and chondroblastoma): One of 8 patients with giant cell tumor failed locally, 1 patient distantly, and all patients are alive. Three of 4 patients with osteo- or chondroblastoma are alive and well. One patient suffered local recurrence and died of disease. Local control rate and overall survival for this group of 12 patients was 76% and 87% and local control for patients with giant cell tumors 83% at 5 years. In the majority of cases radiotherapy was well tolerated. However, one patient with a large base of skull tumor developed retinopathy, one patient required enucleation of a previously blind eye, and another patient with sacral tumor developed chronic diarrhea. Conclusion: Combined proton and photon radiation therapy optimized by 3D treatment planning, allows the delivery of higher radiation doses to tumors of the axial skeleton, while respecting normal tissue constraints. High radiation doses can result in improved long-term local control. C1 HARVARD UNIV, HARVARD CYCLOTRON LAB, CAMBRIDGE, MA 02138 USA. RP HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, DEPT RADIAT ONCOL, BOSTON, MA 02114 USA. FU NCI NIH HHS [CA 2139] NR 40 TC 99 Z9 102 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD FEB 1 PY 1995 VL 31 IS 3 BP 467 EP 476 DI 10.1016/0360-3016(94)00390-7 PG 10 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA QG401 UT WOS:A1995QG40100004 PM 7852108 ER PT J AU BENK, V LIEBSCH, NJ MUNZENRIDER, JE EFIRD, J MCMANUS, P SUIT, H AF BENK, V LIEBSCH, NJ MUNZENRIDER, JE EFIRD, J MCMANUS, P SUIT, H TI BASE OF SKULL AND CERVICAL-SPINE CHORDOMAS IN CHILDREN TREATED BY HIGH-DOSE IRRADIATION SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Note DE CHORDOMA; SKULL NEOPLASM; TREATMENT; RADIOTHERAPY; PROTON THERAPY ID RADIATION-THERAPY; CHONDROSARCOMA AB Purpose: To evaluate the outcome of children with base of skull or cervical spine chordomas treated by high dose irradiation. Methods and Materials: Eighteen children, 4 to 18 years of age, with base of skull or cervical spine chordomas, received fractionated high-dose postoperative radiation using mixed photon and 160 MeV proton beams, The median tumor dose was 69 Cobalt Gray-equivalent (CGE) with a 1.8 CGE daily fraction. Results: The median follow-up was 72 months, The 5-year actuarial survival was 68% and the 5-year disease-free survival (DFS) was 63%. The only significant prognostic factor was the location: patients with cervical spine chordomas had a worse survival than those with base of skull lesions (p = 0.008). The incidence of treatment-related morbidity was acceptable: two patients developed a growth hormone deficit corrected by hormone replacement, one temporal lobe necrosis, and one fibrosis of the temporalis muscle, improved by surgery. Conclusion: Chordomas in children behave similarly to those in adults: children can receive the same high-dose irradiation as adults with acceptable morbidity. C1 MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. HARVARD UNIV,CYCLOTRON LAB,CAMBRIDGE,ENGLAND. NR 27 TC 88 Z9 90 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD FEB 1 PY 1995 VL 31 IS 3 BP 577 EP 581 DI 10.1016/0360-3016(94)00395-2 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA QG401 UT WOS:A1995QG40100019 PM 7852123 ER PT J AU GILSTRAP, LC CHRISTENSEN, R CLEWELL, WH DALTON, ME DAVIDSON, EC ESCOBEDO, MB GJERDINGEN, DK GODDARDFINEGOLD, J GOLDENBERG, RK GRIMES, DA HANSEN, TN KAUFFMAN, RE KEELER, EB OH, W SUSMAN, EJ VOGEL, MG AVERY, ME BALLARD, PL BALLARD, RA CROWLEY, P GARITE, T GOLDENBERG, RL HANKINS, GDV JOBE, AH KOPPE, JG MAHER, JE MERKATZ, IR SHANKARAN, S SIMPSON, KN SINCLAIR, JC SLOTKIN, TA TAEUSCH, HW WRIGHT, LL ALEXANDER, D BERBERICH, MA BRACKEN, M COOPER, L CULPEPPER, L ELLIOTT, JM FERGUSON, JH FRIGOLETTO, F GAIL, DB HALL, WH JONES, MD MEDOFFCOOPER, B MERENSTEIN, GB WHALEN, JM AF GILSTRAP, LC CHRISTENSEN, R CLEWELL, WH DALTON, ME DAVIDSON, EC ESCOBEDO, MB GJERDINGEN, DK GODDARDFINEGOLD, J GOLDENBERG, RK GRIMES, DA HANSEN, TN KAUFFMAN, RE KEELER, EB OH, W SUSMAN, EJ VOGEL, MG AVERY, ME BALLARD, PL BALLARD, RA CROWLEY, P GARITE, T GOLDENBERG, RL HANKINS, GDV JOBE, AH KOPPE, JG MAHER, JE MERKATZ, IR SHANKARAN, S SIMPSON, KN SINCLAIR, JC SLOTKIN, TA TAEUSCH, HW WRIGHT, LL ALEXANDER, D BERBERICH, MA BRACKEN, M COOPER, L CULPEPPER, L ELLIOTT, JM FERGUSON, JH FRIGOLETTO, F GAIL, DB HALL, WH JONES, MD MEDOFFCOOPER, B MERENSTEIN, GB WHALEN, JM TI EFFECT OF CORTICOSTEROIDS FOR FETAL MATURATION ON PERINATAL OUTCOMES SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article AB Objective.-To develop a consensus on the use of antenatal corticosteroids for fetal maturation in preterm infants. Participants.-A nonfederal, nonadvocate, 16-member consensus panel including representatives from neonatology, obstetrics, family medicine, behavioral medicine, psychology, biostatistics, and the public; 19 experts in neonatology, obstetrics, and pharmacology presented data to the consensus panel and a conference audience of approximately 500. Evidence.-An extensive bibliography of references was produced for the consensus panel and the conference audience using a variety of on-line databases including MEDLINE. The consensus panel met several times prior to the conference to review the literature. It also commissioned an updated meta-analysis, a neonatal registry review, and an economic analysis that were presented at the conference. The experts prepared abstracts for distribution at the conference, presented data, and answered questions from the panel and audience. The panel evaluated the strength of the scientific evidence using the grading system developed by the Canadian Task Force on the Periodic Health Examination and adapted by the US Preventive Services Task Force, Consensus.-The consensus panel, answering predefined consensus questions, developed their conclusions based on the scientific evidence presented in open forum and the scientific literature. Consensus Statement.-The consensus panel composed a draft statement that was read in its entirety at the conference for comment. The panel released a revised statement at the end of the conference and finalized the revisions a few weeks after the conference. Conclusions.-Antenatal corticosteroid therapy is indicated for women at risk of premature delivery with few exceptions and will result in a substantial decrease in neonatal morbidity and mortality, as well as substantial savings in health care costs, The use of antenatal corticosteroids for fetal maturation is a rare example of a technology that yields substantial cost savings in addition to improving health. C1 UNIV FLORIDA,COLL MED,GAINESVILLE,FL. PHOENIX PERINATAL ASSOCIATES,DEPT MATERNAL FETAL MED,PHOENIX,AZ. TUFTS UNIV,NEW ENGLAND MED CTR,DEPT OBSTET & GYNECOL,BOSTON,MA 02111. MARTIN LUTHER KING JR CHARLES R DREW UNIV,LOS ANGELES,CA. UNIV TEXAS,HLTH SCI CTR,DIV NEONATOL,SAN ANTONIO,TX. UNIV MINNESOTA,DEPT FAMILY PRACTICE & COMMUNITY HLTH,ST PAUL,MN 55108. BAYLOR COLL MED,DEPT PEDIAT & PATHOL,DIV PEDIAT NEUROL,HOUSTON,TX 77030. UNIV ALABAMA,SCH MED,CTR OBSTET RES,BIRMINGHAM,AL. UNIV ALABAMA,SCH MED,DEPT OBSTET & GYNECOL,BIRMINGHAM,AL. BAYLOR COLL MED,DEPT PEDIAT,HOUSTON,TX 77030. WAYNE STATE UNIV,CHILDRENS HOSP MICHIGAN,DEPT PEDIAT & PHARMACOL,DETROIT,MI. RAND CORP,DEPT SOCIAL POLICY,SANTA MONICA,CA 90406. BROWN UNIV,WOMEN & INFANTS HOSP,SCH MED,DEPT PEDIAT,PROVIDENCE,RI. PENN STATE UNIV,BIOBEHAV HLTH PROGRAM,UNIVERSITY PK,PA 16802. SCH DIST HATBORO HORSHAM,ELKINS PK,PA. NICHHD,BETHESDA,MD 20892. UNIV PENN,SCH MED,DEPT PEDIAT,DIV NEONATOL,PHILADELPHIA,PA 19104. CHILDRENS HOSP PHILADELPHIA,PHILADELPHIA,PA 19104. NHLBI,DIV LUNG DIS,CELL & DEV BIOL BRANCH,BETHESDA,MD 20892. YALE UNIV,DEPT EPIDEMIOL & PUBL HLTH,NEW HAVEN,CT 06520. NINR,DIV EXTRAMURAL PROGRAMS,BETHESDA,MD. BROWN UNIV,MEM HOSP RHODE ISL,DEPT FAMILY MED,PAWTUCKET,RI 02860. NIH,OFF MED APPLICAT RES,BETHESDA,MD 20892. MASSACHUSETTS GEN HOSP,VINCENT MEM HOSP,DIV OBSTET,BOSTON,MA 02114. UNIV TEXAS,SW MED CTR,DEPT OBSTET & GYNECOL,DALLAS,TX 75235. UNIV CALIF LOS ANGELES,HARBOR MED CTR,SCH MED,WALTER P MARTIN RES CTR,TORRANCE,CA 90509. UNIV COLORADO,SCH MED,DEPT PEDIAT,DENVER,CO. CHILDRENS HOSP,DENVER,CO 80218. UNIV PENN,SCH NURSING,PHILADELPHIA,PA 19104. UNIV COLORADO,CHILDRENS HOSP,SCH MED,DEPT PEDIAT,DENVER,CO 80202. NICHHD,OFF SCI POLICY & ANAL,BETHESDA,MD 20892. NICHHD,CTR RES MOTHERS & CHILDREN,BETHESDA,MD 20892. RP GILSTRAP, LC (reprint author), UNIV TEXAS,SW MED CTR,DEPT OBSTET & GYNECOL,DALLAS,TX 75235, USA. NR 0 TC 490 Z9 504 U1 1 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD FEB 1 PY 1995 VL 273 IS 5 BP 413 EP 418 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA QD203 UT WOS:A1995QD20300027 ER PT J AU FLEMING, K GREEN, MF AF FLEMING, K GREEN, MF TI BACKWARD-MASKING PERFORMANCE DURING AND AFTER MANIC EPISODES SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Article ID SCHIZOPHRENIA SPECTRUM DISORDERS AB In a longitudinal design, 16 inpatients with bipolar mood disorder and 16 normal control participants were administered measures of backward masking. Bipolar inpatients were assessed while actively manic and again following manic episode. Clinical state was determined from ratings on an expanded version of the Brief Psychiatric Rating Scale. Two backward masking paradigms were used: (a) a staircase method, which yielded a critical interstimulus interval, and (b) set interstimulus intervals, which provided a masking function. Bipolar patients performed significantly worse than the normal controls at both sessions, but the Group X Session interaction was nonsignificant with both masking procedures. The masking performance deficit for the manic patients was not related to the presence of psychotic symptoms but seemed to be partially associated with lithium treatment. The results indicate that the impaired masking performance of manic patients is not strictly limited to the period of the manic episode. C1 UNIV CALIF LOS ANGELES, RES CTR, DEPT PSYCHIAT & BIOBEHAV SCI, POB 6022, CAMARILLO, CA 93011 USA. W LOS ANGELES VET AFFAIRS MED CTR, LOS ANGELES, CA USA. ST ELIZABETH HOSP, WASHINGTON, DC 20032 USA. NIMH, BETHESDA, MD 20892 USA. FU NIMH NIH HHS [MH-43292, MH-30911] NR 32 TC 26 Z9 26 U1 0 U2 2 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0021-843X J9 J ABNORM PSYCHOL JI J. Abnorm. Psychol. PD FEB PY 1995 VL 104 IS 1 BP 63 EP 68 PG 6 WC Psychology, Clinical; Psychology, Multidisciplinary SC Psychology GA QD428 UT WOS:A1995QD42800007 PM 7897054 ER PT J AU SIMON, BA TSUZAKI, K VENEGAS, JG AF SIMON, BA TSUZAKI, K VENEGAS, JG TI VENTILATION DISTRIBUTION AND REGIONAL LUNG IMPEDANCE DURING PARTIAL UNILATERAL BRONCHIAL OBSTRUCTION SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE POSITRON IMAGING; LUNG IMAGING; REGIONAL VENTILATION; DOGS; LUNG MECHANICS ID HIGH-FREQUENCY VENTILATION; GAS-TRANSPORT; CHEST-WALL; DOGS AB Significant degrees of mainstem bronchial obstruction may not have a detectable effect on ventilation distribution at normal breathing frequencies. We determined the effect of graded left main-stem bronchial obstruction (area reduction of 50 and 70%) on the distribution of tidal volume (VT) and mean lung volume (VL) using radioactive (NN)-N-13 and two-dimensional planar positron imaging in six supine anesthetized tracheotomized dogs. Measurements were made during eucapnic high-frequency oscillatory ventilation at frequencies (f) of 0.2, 1, 5, and 10 Hz. Right and left lung respiratory system complex impedance (Z) values were assessed by simultaneous measurements of dynamic regional lung volume by positron imaging and carinal pressure. The results show a progressive shift of VT away from the obstruction at f > 1 Hz, with VT left-to-right (L/R) ratios of 0.9, 0.9, 0.58, and 0.46 at f of 0.2, 1, 5, and 10 Hz, respectively, for 70% obstruction. VT shifts with f for 50% obstruction were similar but of lesser magnitude. VL Lm, ratio was 0.88 and did not change with f or obstruction. The real part of Z was frequency dependent and increased at low f independent of obstruction. The real part of Z L/R ratio increased with obstruction at 5 and 10 Hz. At low f there was a difference between left and right imaginary parts of Z due to the difference in VL. There was no significant change in the imaginary part of Z as a result of obstruction. We conclude that up to a 70% unilateral bronchial obstruction is not detectable by distribution of ventilation at f less than or equal to 1 Hz. At higher f, unilateral obstruction produces a redistribution of VT, reflecting the high contribution of resistance to regional Z. These results suggest that high-frequency ventilation is potentially disadvantageous in patients with airway obstruction because it may make the distribution of ventilation less uniform and impair gas exchange. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT BIOMED ENGN,CLIN 2,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ANESTHESIA,BOSTON,MA 02114. FU NHLBI NIH HHS [HL-38267] NR 24 TC 4 Z9 4 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD FEB PY 1995 VL 78 IS 2 BP 663 EP 669 PG 7 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA QG477 UT WOS:A1995QG47700038 PM 7759437 ER PT J AU OGAWA, N DANG, H TALAL, N AF OGAWA, N DANG, H TALAL, N TI APOPTOSIS AND AUTOIMMUNITY SO JOURNAL OF AUTOIMMUNITY LA English DT Review ID TRANSFORMING GROWTH FACTOR-BETA-1; PROGRAMMED CELL-DEATH; ACTIVATED HUMAN-LYMPHOCYTES; FAS ANTIGEN; T-CELLS; LPR MICE; B-CELLS; DNA FRAGMENTATION; BCL-2 EXPRESSION; CROSS-LINKING C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV CLIN IMMUNOL,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. FU NIDCR NIH HHS [DE 10863, DE 09311] NR 109 TC 34 Z9 36 U1 0 U2 0 PU ACADEMIC PRESS (LONDON) LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0896-8411 J9 J AUTOIMMUN JI J. Autoimmun. PD FEB PY 1995 VL 8 IS 1 BP 1 EP 19 DI 10.1006/jaut.1995.0001 PG 19 WC Immunology SC Immunology GA QF809 UT WOS:A1995QF80900001 PM 7734031 ER PT J AU NORD, KD DORE, DD DEENEY, VF ARMSTRONG, AL CUNDY, PJ COLE, BF EHRLICH, MG AF NORD, KD DORE, DD DEENEY, VF ARMSTRONG, AL CUNDY, PJ COLE, BF EHRLICH, MG TI EVALUATION OF TREATMENT MODALITIES FOR SEPTIC ARTHRITIS WITH HISTOLOGICAL GRADING AND ANALYSIS OF LEVELS OF URONIC-ACID, NEUTRAL PROTEASE, AND INTERLEUKIN-1 SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID HUMAN ARTICULAR-CARTILAGE; ANTIGEN-INDUCED ARTHRITIS; PROTEOGLYCAN DEGRADATION; STAPHYLOCOCCUS-AUREUS; BACTERIAL ARTHRITIS; PYOGENIC ARTHRITIS; SYNOVIAL-FLUIDS; JOINT; ARTHROSCOPY; COLLAGENASE AB We compared the effectiveness of antibiotics alone and in combination with arthroscopy, arthroscopy with debridement, arthrotomy, or needle aspiration for the treatment of septic arthritis. Each modality has its proponents, but, to our knowledge, no comparative studies have been conducted in animals. We used biochemical and histological analysis to compare these methods of treatment in an experimental model. The right hind knee of thirty goats was injected with 1 x 10(5) Staphylococcus aureus bacilli. The left hind knee mas not inoculated and served as the normal control. Seventy-two hours after inoculation, a two-week course of treatment with intramuscular administration of cefuroxime sodium, either alone or in combination with another mode of treatment, was initiated in each of five groups. The cartilage was evaluated histologically with biochemical, enzymatic, and interleukin-1 analyses. Despite the early therapeutic intervention, on the average, there was a 25 per cent loss of uronic acid (t test, p < 0.001) and a 43 per cent increase in neutral protease activity (signed-rank test, p = 0.003) in the treatment groups. There were no significant intergroup differences with regard to the histochemical-histological rating or the levels of uronic acid, neutral protease, or interleukin-1. CLINICAL RELEVANCE: The treatment of septic arthritis, excluding that in the hip joint, is changing, with an emphasis on less invasive operative techniques. In the present study, early treatment with an appropriate antibiotic and such treatment with arthrotomy, arthroscopy, arthroscopy with debridement, or needle aspiration produced indistinguishable results. Our findings suggest that, if an infected knee joint is diagnosed early and appropriate antibiotic therapy is initiated immediately after the diagnosis, any of the standard treatment modalities can effectively eradicate the infection, with minimum damage to the cartilage. C1 WILFORD HALL USAF MED CTR,CLIN INVEST FACIL,LACKLAND AFB,TX 78236. MASSACHUSETTS GEN HOSP,ORTHOPAED RES LAB,BOSTON,MA 02114. BROWN UNIV,SCH MED,PROVIDENCE,RI 02903. RI Cole, Bernard/I-3775-2012 NR 73 TC 21 Z9 21 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 1995 VL 77A IS 2 BP 258 EP 265 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA QJ302 UT WOS:A1995QJ30200013 PM 7844133 ER PT J AU UY, HL DALLAS, M CALLAND, JW BOYCE, BF MUNDY, GR ROODMAN, GD AF UY, HL DALLAS, M CALLAND, JW BOYCE, BF MUNDY, GR ROODMAN, GD TI USE OF AN IN-VIVO MODEL TO DETERMINE THE EFFECTS OF INTERLEUKIN-1 ON CELLS AT DIFFERENT STAGES IN THE OSTEOCLAST LINEAGE SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID COLONY-STIMULATING FACTOR; BONE-RESORPTION INVITRO; HUMAN MARROW CULTURES; PAGETS-DISEASE; PROGENITOR CELLS; STROMAL CELLS; FACTOR-ALPHA; NORMAL MICE; INVIVO; BISPHOSPHONATES AB In vitro model systems have been used extensively to study factors that affect osteoclast formation and to identify osteoclast precursors. However, in vitro systems do not examine the entire process of osteoclast differentiation simultaneously and lack accessory cells normally present in vivo. Additionally, the role that metabolism of the factor may play on its osteotropic activity in vivo is not addressed by these culture systems. Therefore, we have developed an in vivo model that permits us to examine simultaneously the effects of osteotropic factors on three distinct stages of osteoclast differentiation: (1) multipotent osteoclast precursors, the granulocyte-macrophage colony-forming unit (CFU-GM); (2) more differentiated marrow mononuclear osteoclast precursors; and (3) mature osteoclasts already present on bone surfaces. In the current study, we used interleukin-1 (IL-1) as a prototypic osteotropic factor to test the utility of this system to delineate the cellular mechanisms responsible for enhanced osteoclast activity stimulated by this cytokine. IL-1 induced hypercalcemia and enhanced the growth and differentiation of CFU-GM, increased the number of more committed mononuclear osteoclast precursors, and stimulated mature osteoclasts to resorb bone. These data demonstrate that this simple in vivo model permits the easy delineation of the stages of osteoclast development, in which osteotropic factors act to enhance bone turnover, and may be useful in understanding the mechanism of action of antiresorptive agents. C1 AUDIE L MURPHY MEM VET ADM MED CTR,RES SERV 151,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT ENDODONT,SAN ANTONIO,TX. UNIV TEXAS,HLTH SCI CTR,DEPT PATHOL,SAN ANTONIO,TX 78284. FU NIADDK NIH HHS [AM 35188]; NIAMS NIH HHS [AR 41336, AR 39539] NR 29 TC 42 Z9 44 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 1995 VL 10 IS 2 BP 295 EP 301 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QF460 UT WOS:A1995QF46000016 PM 7754810 ER PT J AU BENNETT, KL JACKSON, DG SIMON, JC TANCZOS, E PEACH, R MODRELL, B STAMENKOVIC, I PLOWMAN, G ARUFFO, A AF BENNETT, KL JACKSON, DG SIMON, JC TANCZOS, E PEACH, R MODRELL, B STAMENKOVIC, I PLOWMAN, G ARUFFO, A TI CD44 ISOFORMS CONTAINING EXON V3 ARE RESPONSIBLE FOR THE PRESENTATION OF HEPARIN-BINDING GROWTH-FACTOR SO JOURNAL OF CELL BIOLOGY LA English DT Article ID T-CELL ACTIVATION; METASTASIS-ASSOCIATED VARIANT; FIBROBLAST GROWTH; ENDOTHELIAL-CELLS; CORE PROTEIN; SULFATE PROTEOGLYCANS; BIOLOGICAL-ACTIVITIES; EXTRACELLULAR-MATRIX; HYALURONATE RECEPTOR; HIGH-AFFINITY AB Glycosaminoglycan-modified isoforms of CD44 have been implicated in growth factor presentation at sites of inflammation, In the present study we show that COS cell transfectants expressing CD44 isoforms containing the alternatively spliced exon V3 are modified with heparan sulfate (HS), Binding studies with three HS-binding growth factors, basic-fibroblast growth factor (b-FGF), heparin binding-epidermal growth factor (HB-EGF), and amphiregulin, showed that the HS-modified CD44 isoforms are able to bind to b-FGF and HB-EGF, but not AR, b-FGF and HB-EGF binding to HS-modified CD44 was eliminated by pretreating the protein with heparitinase or by blocking with free heparin. HS-modified CD44 immunoprecipitated from keratinocytes, which express a CD44 isoform containing V3, also bound to b-FGF, We examined whether HS-modified CD44 isoforms were expressed by activated endothelial cells where they might present HS-binding growth factors to leukocytes during an inflammatory response. PCR and antibody-binding studies showed that activated cultured endothelial cells only express the CD44H isoform which does not contain any of the variably spliced exons including V3. Immunohistological studies with antibodies directed to CD44 extracellular domains encoded by the variably spliced exons showed that vascular endothelial cells in inflamed skin tissue sections do not express CD44 spliced variants. Keratinocytes, monocytes, and dendritic cells in the same specimens were found to express variably spliced CD44. (SO4-2)-S-35-labeling experiments demonstrated that activated cultured endothelial cells do not express detectable levels of chondroitin sulfate or HS-modified CD44, Our results suggest that one of the functions of CD44 isoforms expressing V3 is to bind and present a subset of HS-binding proteins. Furthermore, it is probable that HS-modified CD44 is involved in the presentation of HS-binding proteins by keratinocytes in inflamed skin, However, our data suggests that CD44 is not likely to be the proteoglycan principally involved in presenting HS-binding growth factors to leukocytes on the vascular cell wall. C1 JOHN RADCLIFFE HOSP,INST MOLEC MED,MOLEC IMMUNOL GRP,OXFORD OX3 9DU,ENGLAND. UNIV FREIBURG,DEPT DERMATOL,W-7800 FREIBURG,GERMANY. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. RP BENNETT, KL (reprint author), BRISTOL MYERS SQUIBB PHARMACEUT RES INST,3005 1SST AVE,SEATTLE,WA 98121, USA. RI PLOWMAN, Greg/E-2012-2011 NR 65 TC 321 Z9 325 U1 1 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 FEB PY 1995 VL 128 IS 4 BP 687 EP 698 DI 10.1083/jcb.128.4.687 PG 12 WC Cell Biology SC Cell Biology GA QH005 UT WOS:A1995QH00500020 PM 7532176 ER PT J AU LARUE, A OHARA, R MATSUYAMA, SS JARVIK, LF AF LARUE, A OHARA, R MATSUYAMA, SS JARVIK, LF TI COGNITIVE CHANGES IN YOUNG-OLD ADULTS - EFFECT OF FAMILY HISTORY OF DEMENTIA SO JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY LA English DT Article ID ALZHEIMERS-DISEASE; AGE; PERFORMANCE; HEALTH; RISK AB Cognitive performance of 40 first-degree relatives of patients with probable Alzheimer disease was compared to that of 24 matched controls without a family history of dementia. Across a test-retest interval ranging from 1 to 6 years, relatives more often showed evidence of cognitive decline, and in multivariate analyses of memory and intelligence measures, relatives of patients with early-onset dementia (< 67 years) showed greater decline than controls or relatives of patients with late-onset dementia. All changes observed to date are in the subclinical range, and further follow-up will be needed to determine the reliability of change trajectories. However, the findings suggest that family history of dementia may be worthy of monitoring in research on normal cognitive aging. C1 UNIV CALIF LOS ANGELES,DEPT PSYCHIAT & BIOBEHAV SCI,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,BRENTWOOD DIV,LOS ANGELES,CA. FU NIMH NIH HHS [MH36205] NR 21 TC 23 Z9 23 U1 0 U2 1 PU SWETS ZEITLINGER BV PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 1380-3395 J9 J CLIN EXP NEUROPSYC JI J. Clin. Exp. Neuropsychol. PD FEB PY 1995 VL 17 IS 1 BP 65 EP 70 DI 10.1080/13803399508406582 PG 6 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA QJ150 UT WOS:A1995QJ15000008 PM 7608303 ER PT J AU SHORTEN, GD ALI, HH ROBERTS, JT AF SHORTEN, GD ALI, HH ROBERTS, JT TI ASSESSMENT OF PATIENT POSITION FOR FIBEROPTIC INTUBATION USING VIDEOLARYNGOSCOPY SO JOURNAL OF CLINICAL ANESTHESIA LA English DT Article DE FIBEROPTICS; INTUBATION, INTRATRACHEAL; LARYNGOSCOPY AB Study Objective: To compare laryngoscopic appearance obtained during flexible fiberoptic laryngoscopy with the patient's atlanto-occipital joint in the neutral and extended positions. Design: Controlled clinical trial with each patient (in the neutral position) acting as his or her own control. Setting: University teaching hospital. Patients: 20 adult ASA physical status I and II patients, without anatomical airway abnormalities, undergoing elective surgical procedures. Interventions: Fiberoptic laryngoscopy was performed on each patient with his or her atlanto-occipital joint in the neutral and extended positions. Measurements and Main Results: Photographs of the laryngoscopic appearances were graded on a scale of 1 to 4 by a blinded observer according to the proportion of the laryngeal inlet visible. Atlanto-occipital extension improved laryngoscopic appearance in 14 cases and produced no change in the remaining 6. Conclusion: Atlanto-occipital extension is a useful maneuver during attempted fiberoptic intubation. C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. NR 0 TC 2 Z9 2 U1 0 U2 1 PU BUTTERWORTH-HEINEMANN PI WOBURN PA 225 WILDWOOD AVE #UNITB PO BOX 4500, WOBURN, MA 01801-2084 SN 0952-8180 J9 J CLIN ANESTH JI J. Clin. Anesth. PD FEB PY 1995 VL 7 IS 1 BP 31 EP 34 DI 10.1016/0952-8180(94)00006-P PG 4 WC Anesthesiology SC Anesthesiology GA QQ246 UT WOS:A1995QQ24600007 PM 7772355 ER PT J AU ACQUADRO, MA NGHIEM, TX BEACH, TP DONLON, JV JOSEPH, MP AHERN, DK AF ACQUADRO, MA NGHIEM, TX BEACH, TP DONLON, JV JOSEPH, MP AHERN, DK TI ACQUIRED QT INTERVAL CHANGES AND NECK DISSECTIONS SO JOURNAL OF CLINICAL ANESTHESIA LA English DT Article DE ARRHYTHMIA, LONG QT SYNDROME, ACQUIRED; NECK, DISSECTION; TORSADE DE POINTES AB Study Objective: To determine if acquired long QT syndrome following right or left, radical or modified, neck dissections result in malignant an arrhythmias or deaths. Design: Prospective study. Setting: Inpatient head and neck service of the Massachusetts Eye and Ear Infirmary. Patients: 69 patients who underwent extensive neck surgery, without congenital long QT syndrome, medications Known to prolong the QT interval, preoperative ventricular arrhythmias, or electrolyte abnormalities. Interventions: None. Measurements and Main Results: Preoperative and postoperative electrolytes were evaluated. Preoperative and postoperative electrocardiograms and QT intervals were evaluated. Continuous intraoperative and 10- to 12-hour postoperative monitoring of lead II or V5 were evaluated. Twenty-six patients (Group 1) underwent either right radical neck dissection or modified right radical neck dissection, 25 patients (Group 2) underwent either left radical neck dissection or modified left neck dissection, and 18 patients (Group 3) underwent extensive neck surgery without radical or modified neck dissection. Postoperatively, 38 patients (19 Group 1, 11 Group 2, and 8 Group 3 patients) developed a QT interval corrected for heart rate (QTc) of greater than 440 milliseconds. Repeated measures analysis of variance, comparing preoperative and postoperative QTc showed a statistically significant preoperative to postoperative change, but no significant difference among the three groups. No malignant arrhythmias or deaths were recorded in any of the three groups. Conclusions: Acquired long QT syndrome following radical neck dissection, without congenital, metabolic, or pharmacologic disturbance, is unlikely to trigger malignant arrhythmias, as previously reported for right radical neck dissection. RP ACQUADRO, MA (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT ANESTHESIA,243 CHARLES ST,BOSTON,MA 02114, USA. NR 0 TC 6 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 FEB PY 1995 VL 7 IS 1 BP 54 EP 57 DI 10.1016/0952-8180(94)00015-V PG 4 WC Anesthesiology SC Anesthesiology GA QQ246 UT WOS:A1995QQ24600012 PM 7772360 ER PT J AU KHOURI, YF MCINTOSH, K CAVACINI, L POSNER, M PAGANO, M TUOMALA, R MARASCO, WA AF KHOURI, YF MCINTOSH, K CAVACINI, L POSNER, M PAGANO, M TUOMALA, R MARASCO, WA TI VERTICAL TRANSMISSION OF HIV-1 - CORRELATION WITH MATERNAL VIRAL LOAD AND PLASMA-LEVELS OF CD4 BINDING-SITE ANTI-GP120 ANTIBODIES SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE VERTICAL TRANSMISSION; AIDS; NEUTRALIZING ANTIBODIES; PASSIVE IMMUNOTHERAPY; HUMAN ANTI-GP 120 ANTIBODIES ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN MONOCLONAL-ANTIBODY; NEUTRALIZING ANTIBODIES; CONFORMATIONAL EPITOPE; PERINATAL TRANSMISSION; SEROPOSITIVE WOMEN; GP120; TYPE-1; INFECTION; PREVENTION AB Almost all childhood HIV-1 is now acquired through vertical transmission. Identifying factors that affect the rate of transmission may lead to the initiation of specific preventive strategies. In this study, antibody levels against different neutralizing epitopes on the envelope glycoprotein of HIV-1 (gp120) were measured in HIV-1-infected pregnant women that either transmitted HIV-1 to their infants (18 women) or did not (29 women). Differences in levels of antibodies directed against the monomeric gp120 molecule and against the V3 loop region of gp120 were not significantly different between the two groups studied. However, significant differences were observed in the levels of CD4 binding site antibodies, as determined by the ability of diluted maternal plasma to inhibit binding of the CD4 binding site monoclonal antibody F105 (mAb F105) to monomeric gp120. In addition, more nontransmitting mothers had low viral load as defined by having two or more negative HIV-1 viral cultures during pregnancy compared with transmitters. This pilot study suggests that in addition to higher viral load, low levels of CD4 binding site antibodies correlate with increased risk of HIV-1 vertical transmission. Passive immunotherapy with broadly neutralizing CD4 binding site antibodies should be considered as a strategy to reduce this risk. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HUMAN RETROVIROL,BOSTON,MA 02115. HARVARD UNIV,CHILDRENS HOSP,SCH MED,DIV INFECT DIS,BOSTON,MA 02115. HARVARD UNIV,NEW ENGLAND DEACONESS HOSP,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,DEPT OBSTET & GYNECOL,BOSTON,MA 02115. FU NIAID NIH HHS [AI31783, AI33802, AI26926] NR 42 TC 45 Z9 45 U1 0 U2 1 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 PY 1995 VL 95 IS 2 BP 732 EP 737 DI 10.1172/JCI117720 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA QG209 UT WOS:A1995QG20900040 PM 7860754 ER PT J AU FOX, JG YAN, LL DEWHIRST, FE PASTER, BJ SHAMES, B MURPHY, JC HAYWARD, A BELCHER, JC MENDES, EN AF FOX, JG YAN, LL DEWHIRST, FE PASTER, BJ SHAMES, B MURPHY, JC HAYWARD, A BELCHER, JC MENDES, EN TI HELICOBACTER BILIS SP-NOV, A NOVEL HELICOBACTER SPECIES ISOLATED FROM BILE, LIVERS, AND INTESTINES OF AGED, INBRED MICE SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID CAMPYLOBACTER-JEJUNI; SPIRAL BACTERIUM; GASTRIC-CARCINOMA; PYLORI INFECTION; HOMOSEXUAL MEN; MUCOSA; STOMACH; GASTROENTERITIS; PHYLOGENY; MUSTELAE AB A fusiform bacterium with 3 to 14 multiple bipolar sheathed flagella and periplasmic fibers wrapped around the cell was isolated from the liver, bile, and lower intestine of aged, inbred mice. The bacteria grew at 37 and 42 degrees C under microaerophilic conditions, rapidly hydrolyzed urea, were catalase and oxidase positive, reduced nitrate to nitrite, did not hydrolyze indoxyl acetate or hippurate, and were resistant to both cephalothin and nalidixic acid but sensitive to metronidazole. On the basis of 16S rRNA gene sequence analysis, the organism was classified as a novel helicobacter, Helicobacter bilis. This new helicobacter, like Helicobacter hepaticus, colonizes the bile, liver, and intestine of mice. Although the organism is associated with multifocal chronic hepatitis, further studies are required to ascertain whether H. bills is responsible for causing chronic hepatitis and/or hepatocellular tumors in mice. C1 FORSYTH DENT CTR,DEPT MOLEC GENET,BOSTON,MA 02115. UNIV FED MINAS GERAIS,FAC MED,BACTERIOL RES LAB,BR-31270 BELO HORIZONT,MG,BRAZIL. RP FOX, JG (reprint author), MIT,DIV COMPARAT MED,CAMBRIDGE,MA 02139, USA. FU NCRR NIH HHS [RR-01046, RR-07036]; OFP OPHS HHS [RFP594-69] NR 51 TC 313 Z9 320 U1 1 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 1995 VL 33 IS 2 BP 445 EP 454 PG 10 WC Microbiology SC Microbiology GA QC148 UT WOS:A1995QC14800036 PM 7536217 ER PT J AU LOEHRER, PJ JOHNSON, D ELSON, P EINHORN, LH TRUMP, D AF LOEHRER, PJ JOHNSON, D ELSON, P EINHORN, LH TRUMP, D TI IMPORTANCE OF BLEOMYCIN IN FAVORABLE-PROGNOSIS DISSEMINATED GERM-CELL TUMORS - AN EASTERN-COOPERATIVE-ONCOLOGY-GROUP TRIAL SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID DISSEMINATED TESTICULAR CANCER; COMBINATION CHEMOTHERAPY; CLINICAL-TRIALS; GROUP PROTOCOL; CISPLATIN; VINBLASTINE; ETOPOSIDE; THERAPY AB Purpose: This prospective, randomized trial was designed to determine if three cycles of cisplatin plus etoposide (PVP16) can produce therapeutic results comparable to three cycles of cisplatin, etoposide, and bleomycin (PVP16B) in patients with disseminated germ cell tumors. Patients and Methods: One hundred seventy-eight moderate-stage disease (Indiana staging system) were randomized to receive cisplatin (20 mg/m(2) on days 1 to 5) plus etoposide (100 mg/m(2) on days 1 to 5) with or without weekly bleomycin (30 IU/wk for 9 consecutive weeks). Following three cycles of chemotherapy over 9 weeks, patients with residual radiographic disease underwent surgical resection, If persistent carcinoma was noted, two additional 3-week courses of chemotherapy were administered. Results: One hundred seventy-one patients were fully assessable for response and survival. The two treatment groups were similar with respect to patient characteristics. The toxicities were comparable between the two arms. No clinically significant incidence of pulmonary toxicity occurred with PVP16B. Overall, 81 of 86 patients (94%) who received PVP16B and 75 of 85 patients (88%) who received PVP16 achieved a disease-free status with chemotherapy and/or surgery. However, greater numbers of treatment failures, including persistent carcinoma in postchemotherapy resected residual disease and relapses from complete remission, occurred on the arm without bleomycin (overall adverse outcome, P=.004). The failure-free (86% v 69%; P=.01) and overall survival (95% v 86%; P=.01) rates were inferior on the PVP16 arm. Conclusion: Bleomycin is an essential component of PVP16B therapy in patients who receive three cycles of treatment for minimal or moderate-stage disseminated germ cell tumors. C1 WALTHER CANC INST,INDIANAPOLIS,IN. VANDERBILT UNIV,NASHVILLE,TN. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. PITTSBURGH CANC INST,PITTSBURGH,PA 15213. RP LOEHRER, PJ (reprint author), INDIANA UNIV HOSP,MED CTR,DEPT MED,550 N UNIV BLVD,INDIANAPOLIS,IN 46202, USA. FU NCI NIH HHS [R10 CA 28171-04, 2 R 35 CA 39844-07]; NCRR NIH HHS [MO 1 RR 00 750-06] NR 26 TC 156 Z9 157 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB PY 1995 VL 13 IS 2 BP 470 EP 476 PG 7 WC Oncology SC Oncology GA QF298 UT WOS:A1995QF29800024 PM 7531223 ER PT J AU FAVA, M RAPPE, SM PAVA, JA NIERENBERG, AA ALPERT, JE ROSENBAUM, JF AF FAVA, M RAPPE, SM PAVA, JA NIERENBERG, AA ALPERT, JE ROSENBAUM, JF TI RELAPSE IN PATIENTS ON LONG-TERM FLUOXETINE TREATMENT - RESPONSE TO INCREASED FLUOXETINE DOSE SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 147th Annual Meeting of the American-Psychiatric-Association CY MAY 21-27, 1994 CL PHILADELPHIA, PA SP Amer Psychiat Assoc ID DRUG-THERAPY; DEPRESSION; TOLERANCE; CONTINUATION; PREVENTION; IMIPRAMINE; PHENELZINE; INHIBITORS; DISORDERS; UNIPOLAR AB Background: Although several studies have examined the long-term efficacy of antidepressants, relatively little attention has been paid to the management of relapses or recurrences during continued antidepressant treatment. This study examined whether depressed patients who had recovered and then relapsed on fluoxetine 20 mg/day would benefit from an increase in fluoxetine dose. Method: Eighteen patients who relapsed on fluoxetine 20 mg/day during long-term treatment with fluoxetine as part of a placebo-controlled study had their fluoxetine dose raised to 40 mg/day and were followed for at least 1 month (mean time = 4.7 months). Results: Twelve (67%) were full responders, 3 (17%) partial responders, and 3 (17%) dropped out because of side effects (e.g., insomnia and agitation). Of those patients who had either full or partial response (N = 15; 83%), 3 complete responders had a recurrence on 40 mg/day after a mean of 5.8 months and 1 partial responder had a recurrence 11 months later. Overall, 11 (61%) of 18 patients maintained their response during their follow-up while taking the higher dose of fluoxetine. Conclusion: An increase in dose of fluoxetine to 40 mg/day appears to be an effective strategy in the treatment of relapse among depressed patients who had initially responded to fluoxetine 20 mg/day. RP FAVA, M (reprint author), MASSACHUSETTS GEN HOSP,CLIN PSYCHOPHARMACOL UNIT,DEPRESS RES PROGRAM,ACC 815,BOSTON,MA 02114, USA. OI Alpert, Jonathan/0000-0002-4332-908X NR 24 TC 52 Z9 53 U1 0 U2 1 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD FEB PY 1995 VL 56 IS 2 BP 52 EP 55 PG 4 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA QG981 UT WOS:A1995QG98100001 PM 7852252 ER PT J AU REILLY, PM SEES, KL SHOPSHIRE, MS HALL, SM DELUCCHI, KL TUSEL, DJ BANYS, P CLARK, HW PIOTROWSKI, NA AF REILLY, PM SEES, KL SHOPSHIRE, MS HALL, SM DELUCCHI, KL TUSEL, DJ BANYS, P CLARK, HW PIOTROWSKI, NA TI SELF-EFFICACY AND ILLICIT OPIOID USE IN A 180-DAY METHADONE DETOXIFICATION TREATMENT SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article ID DRUG AB Self-efficacy ratings coincided with illicit opioid use across the 3 phases of a 180-day methadone detoxification treatment. Efficacy ratings increased after patients received their first dose of methadone, did not change while they were maintained on a stable dose of methadone, and declined during the taper as they attempted to face high-risk situations without the full benefit of methadone. Efficacy ratings measured at a point before a phase of treatment predicted illicit opioid use across that phase. For clarification of the relation between self-efficacy and illicit opioid use, 3 conceptual models proposed by J.S. Baer, C. S. Holt, and E. Lichtenstein (1986) were tested. Self-efficacy influenced subsequent drug use in parallel with previous behavior, but this influence was found only at the start of the stabilization phase and immediately before the start of the taper phase. These findings highlight the usefulness of the self-efficacy concept for the treatment of opioid addiction. C1 UNIV CALIF SAN FRANCISCO,DEPT PSYCHIAT,SAN FRANCISCO,CA 94143. RP REILLY, PM (reprint author), SAN FRANCISCO VET AFFAIRS MED CTR,SUBSTANCE ABUSE PROGRAMS,116-E,4150 CLEMENT ST,SAN FRANCISCO,CA 94121, USA. FU NIDA NIH HHS [1R18DA06097] NR 8 TC 33 Z9 33 U1 0 U2 1 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0022-006X J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD FEB PY 1995 VL 63 IS 1 BP 158 EP 162 PG 5 WC Psychology, Clinical SC Psychology GA QG936 UT WOS:A1995QG93600022 PM 7896984 ER PT J AU MANKIN, KP BISCHOFF, RJ GELBERMAN, RH ROSENBERG, AE AF MANKIN, KP BISCHOFF, RJ GELBERMAN, RH ROSENBERG, AE TI ANEURYSMAL BONE-CYST INVOLVING THE LUNATE SO JOURNAL OF HAND SURGERY-BRITISH AND EUROPEAN VOLUME LA English DT Article AB Aneurysmal bone cysts are rare lesions which even more rarely involve the bones of the hand, We report a case of a cyst involving the lunate which was initially mistaken for interosseous ganglion, Due to delay in diagnosis, marked destruction of the lunate occurred, necessitating excision and scapho-capitate arthrodesis. Although rare, aneurysmal bone cysts should be included in the differential diagnosis and ruled out prior to embarking on a course of treatment. RP MANKIN, KP (reprint author), MASSACHUSETTS GEN HOSP,DEPT ORTHOPAED SURG,15 PARKMAN ST WACC 507,BOSTON,MA 02114, USA. NR 0 TC 4 Z9 5 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 0266-7681 J9 J HAND SURG-BRIT EUR JI J. Hand Surg.-Br. Eur Vol. PD FEB PY 1995 VL 20B IS 1 BP 12 EP 15 DI 10.1016/S0266-7681(05)80006-3 PG 4 WC Orthopedics; Surgery SC Orthopedics; Surgery GA QK796 UT WOS:A1995QK79600004 PM 7759924 ER PT J AU DELAMONTE, SM QUERTERMOUS, T HONG, CC BLOCH, KD AF DELAMONTE, SM QUERTERMOUS, T HONG, CC BLOCH, KD TI REGIONAL AND MATURATION-ASSOCIATED EXPRESSION OF ENDOTHELIN-2 IN RAT GASTROINTESTINAL-TRACT SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE ENDOTHELIN 2; VASOACTIVE INTESTINAL CONTRACTOR PEPTIDE; GASTROINTESTINAL TRACT ID VASOACTIVE INTESTINAL CONTRACTOR; BETA-INTERFERON GENE; CHROMOSOMAL ASSIGNMENT; MOLECULAR-CLONING; MESSENGER-RNA; CDNA CLONING; SPINAL-CORD; PEPTIDE; CELLS; IMMUNOREACTIVITY AB Endothelin 2 (ET2), also referred to as vasoactive intestinal contractor peptide, is a member of a family of vasoactive peptides, ET2 is a potent constrictor of intestinal smooth muscle, and the mRNA that encodes it has been detected in murine intestinal extracts, To further investigate the potential physiological roles of ET2, we characterized the cellular distribution of ET2 gene expression in adult rat gastrointestinal tract, Using an RNAse protection assay, an overall proximal to distal gradient of increasing ET2 gene expression was observed from stomach to colon, In situ hybridization studies confirmed this finding and demonstrated ET2 mRNA localized in lamina propria stromal cells. Moreover, ET2 gene expression in stromal cells increased from crypt to villous tip. The results demonstrate that ET2 is produced by stromal cells in villi throughout the intestine, Increased ET2 gene expression at the villous tip is associated with more mature overlying epithelial cells, suggesting a possible role for this vasoactive peptide in intestinal epithelial differentiation or secretory activity, C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,CTR CANC,GEN MED SERV,CARDIAC UNIT,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,CTR CANC,GEN MED SERV,CARDIAC UNIT,BOSTON,MA. MASSACHUSETTS GEN HOSP,PATHOL LAB,BOSTON,MA. RI Hong, Charles/C-9989-2010 FU NHLBI NIH HHS [HL45895]; NIA NIH HHS [K11 AG-00425] NR 27 TC 29 Z9 29 U1 0 U2 0 PU HISTOCHEMICAL SOC INC PI NEW YORK PA MT SINAI MEDICAL CENTER 19 EAST 98TH ST SUTIE 9G, NEW YORK, NY 10029 SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD FEB PY 1995 VL 43 IS 2 BP 203 EP 209 PG 7 WC Cell Biology SC Cell Biology GA QC782 UT WOS:A1995QC78200009 PM 7822776 ER PT J AU WERSHIL, BK FURUTA, GT LAVIGNE, JA CHOUDHURY, AR WANG, ZS GALLI, SJ AF WERSHIL, BK FURUTA, GT LAVIGNE, JA CHOUDHURY, AR WANG, ZS GALLI, SJ TI DEXAMETHASONE OR CYCLOSPORINE-A SUPPRESS MAST CELL-LEUKOCYTE CYTOKINE CASCADES - MULTIPLE MECHANISMS OF INHIBITION OF IGE-DEPENDENT AND MAST-CELL-DEPENDENT CUTANEOUS INFLAMMATION IN THE MOUSE SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; LATE PHASE REACTIONS; FC-EPSILON-RI; MEDIATOR RELEASE; FACTOR-ALPHA; VASCULAR-PERMEABILITY; ADHESION MOLECULE-1; TNF-ALPHA; RECEPTOR; AUGMENTATION AB In allergic diseases, exposure of sensitized subjects to allergen induces the activation of tissue mast cells that results in an immediate-type hypersensitivity response and, in some individuals, a late phase response. We previously have reported that the neutrophil infiltration associated with IgE-dependent cutaneous inflammation in mice is mast cell-dependent and that TNF-alpha contributes significantly to this response. We report here that either dexamethasone or cyclosporin A can inhibit mouse mast cell TNF-alpha production in vitro, and that these agents also can significantly suppress the tissue swelling and leukocyte infiltration associated with two forms of TNF-alpha-associated inflammation in vivo: the entirely IgE- and mast cell-dependent inflammation at sites of passive cutaneous anaphylaxis reactions and the entirely TNF-alpha-dependent inflammation that is elicited by the direct intradermal injection of recombinant mouse TNF-alpha. Taken together, our in vitro and in vivo findings in mice indicate that dexamethasone or cyclosporin A can have at least three actions that interfere with the pathogenesis of IgE, mast cell-, and cytokine-dependent inflammatory reactions: suppression of the IgE-dependent increase in TNF-alpha mRNA by mast cells, inhibition of the IgE-dependent production of TNF-alpha protein by mast cells, and diminution of the responsiveness of target cells to TNF-alpha. Our findings in mice raise the possibility that similar actions of these agents in humans may account for some of the clinical efficacy of corticosteroids and cyclosporin A in allergic diseases. C1 CHILDRENS HOSP,COMBINED PROGRAM PEDIAT GASTROENTEROL,BOSTON,MA 02215. MASSACHUSETTS GEN HOSP,BOSTON,MA. HARVARD UNIV,SCH MED,BOSTON,MA 02215. RP WERSHIL, BK (reprint author), BETH ISRAEL HOSP,DIV EXPTL PATHOL-RES N,99 BROOKLINE AVE,BOSTON,MA 02215, USA. FU NIAID NIH HHS [AI 22674, AI 23990]; NIDDK NIH HHS [P01 DK 33506] NR 39 TC 87 Z9 87 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 1995 VL 154 IS 3 BP 1391 EP 1398 PG 8 WC Immunology SC Immunology GA QC546 UT WOS:A1995QC54600045 PM 7822805 ER PT J AU ROOK, AH KUBIN, M CASSIN, M VONDERHEID, EC VOWELS, BR WOLFE, JT WOLF, SF SINGH, A TRINCHIERI, G LESSIN, SR AF ROOK, AH KUBIN, M CASSIN, M VONDERHEID, EC VOWELS, BR WOLFE, JT WOLF, SF SINGH, A TRINCHIERI, G LESSIN, SR TI IL-12 REVERSES CYTOKINE AND IMMUNE ABNORMALITIES IN SEZARY-SYNDROME SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CELL STIMULATORY FACTOR; INTERFERON-GAMMA-PRODUCTION; MYCOSIS-FUNGOIDES; T-CELL; PERIPHERAL-BLOOD; INTERLEUKIN-12; SECRETION; LYMPHOMA; LYMPHOCYTES; PATTERN AB Cutaneous T cell lymphoma is a lymphoproliferative disorder typically characterized by skin invasion of clonally derived malignant CD4(+) lymphocytes that phenotypically resemble mature Th cells. Sezary syndrome (SzS) represents an advanced form of cutaneous T cell lymphoma associated with generalized erythroderma and involvement of the peripheral blood by the malignant cell population. We have previously demonstrated aberrant cytokine production by PBMC in SzS characterized by increased IL-4 and deficient IL-2 and IFN-gamma production, as well as increased expression of mRNA for IL-4 and IL-5 within active skin lesions, suggesting that the clonal T cell population is derived from the Th 2 subset of helper T lymphocytes. These findings have been associated with a constellation of immune abnormalities that have been attributed to the cytokine abnormalities. Because IL-12 is a potent inducer of IFN-gamma production, and causes the activation of cytotoxic lymphocytes, we examined the production of IL-12 by PBMC from SzS patients and whether IL-12 could alter the unfavorable cytokine balance typical of SzS and thus lead to correction of immune defects. Despite normal numbers of peripheral blood monocytes and normal TNF-alpha production, mean Staphyloccus aureus and LPS-induced IL-12 p40 and p70 production by SzS PBMC was significantly decreased compared with PBMC from normal controls. Mean IFN-gamma production by patient PBMC in response to PHA alone was depressed, but increased to levels comparable with normal after addition of 1 ng/ml IL-12. Pretreatment of PBMC for 24 h with IL-12, IFN-alpha, or both together resulted in a decrease in PHA-stimulated IL-4 production from a base line of 1818 pg/ml to 1520, 1350, and 1058 pg/ml, respectively. Lastly, culture of patient PBMC with IL-l 2 for 24 h also resulted in significant increases in NK activity against K562 cells. These results indicate that PBMC from patients with SzS manifest a defect in IL-12 production and that the cytokine abnormalities associated with SzS can be favorably altered by IL-12. C1 WISTAR INST ANAT & BIOL,PHILADELPHIA,PA 19104. HAHNEMANN UNIV,PHILADELPHIA,PA 19104. DEPT VET AFFAIRS MED CTR,PHILADELPHIA,PA 19104. GENET INST INC,CAMBRIDGE,MA 02140. RP ROOK, AH (reprint author), UNIV PENN,MED CTR,DEPT DERMATOL,3400 SPRUCE ST,PHILADELPHIA,PA 19104, USA. FU NCI NIH HHS [1RO1 CA58841, R29 CA55017] NR 26 TC 106 Z9 106 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 FEB 1 PY 1995 VL 154 IS 3 BP 1491 EP 1498 PG 8 WC Immunology SC Immunology GA QC546 UT WOS:A1995QC54600055 PM 7822812 ER PT J AU PETERSEN, MJ KAPLAN, J JORGENSEN, CM SCHMIDT, LA LI, LT MORGAN, JR KWAN, MK KRUEGER, GG AF PETERSEN, MJ KAPLAN, J JORGENSEN, CM SCHMIDT, LA LI, LT MORGAN, JR KWAN, MK KRUEGER, GG TI SUSTAINED PRODUCTION OF HUMAN TRANSFERRIN BY TRANSDUCED FIBROBLASTS IMPLANTED INTO ATHYMIC MICE - A MODEL FOR SOMATIC GENE-THERAPY SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE SKIN EQUIVALENTS; RETROVIRUS; VECTORS ID MODIFIED SKIN FIBROBLASTS; HUMAN ADENOSINE-DEAMINASE; GROWTH-HORMONE; EXPRESSION; TRANSPLANTATION; CELLS; MOUSE; LONG; DELIVERY; INVIVO AB Somatic gene therapy has been proposed as a means of treating inherited diseases involving defective or absent plasma proteins, viral diseases, and cancer, Introduction of the gene of interest into fibroblasts and implantation of these genetically modified fibroblasts using a skin equivalent system may be an attractive model for gene therapy because skin fibroblasts are easily obtained and propagated in culture, This study evaluated expression of the gene for human transferrin (hTf) by genetically modified fibroblasts in vitro and in vivo. NIH 3T3 fibroblasts, which form non-metastasizing tumors in athymic mice, mere transduced with a retroviral vector encoding hTf. The transduced cells were cloned by limiting dilution and hTf production by the cloned cells measured, Two clones of cells producing high levels of hTf were used to seed collagen-coated nylon matrices, which were maintained in culture for up to 53 d. The rate of synthesis of hTf by the seeded matrices was constant after 22 d in vitro. Matrices seeded with cloned, transduced cells were implanted subcutaneously into seven athymic mice, and plasma levels of hTf were assessed biweekly, In all animals, the plasma level of hTf was detectable at week 6 after implantation, Levels of hTf remained elevated in the animals until the implants were removed at week 12. At week 10, the level of hTf in the plasma correlated with tumor volume in tumors less than 2000 mm(3) in size, The half-life of hTf in the mice was 39.5 h. In this model, gene expression did not decline for the 12-week observation period. C1 UNIV UTAH,SCH MED,DEPT MED,DIV DERMATOL,SALT LAKE CITY,UT 84132. UNIV UTAH,SCH MED,DEPT PATHOL,SALT LAKE CITY,UT 84132. MASSACHUSETTS GEN HOSP,SURG SERV,BOSTON,MA 02114. SHRINERS BURN INST,BOSTON,MA 02114. ADV TISSUE SCI,LA JOLLA,CA. FU NIAMS NIH HHS [R29-AR41207]; NICHD NIH HHS [P01-HD28528]; NIDDK NIH HHS [R01-DK30534] NR 23 TC 20 Z9 20 U1 0 U2 5 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD FEB PY 1995 VL 104 IS 2 BP 171 EP 176 DI 10.1111/1523-1747.ep12612734 PG 6 WC Dermatology SC Dermatology GA QD424 UT WOS:A1995QD42400001 PM 7829871 ER PT J AU GRECO, MA LORAND, L LANE, WS BADEN, HP PARAMESWARAN, KNP KVEDAR, JC AF GRECO, MA LORAND, L LANE, WS BADEN, HP PARAMESWARAN, KNP KVEDAR, JC TI THE PANCORNULINS - A GROUP OF SMALL PROLINE RICH-RELATED CORNIFIED ENVELOPE PRECURSORS WITH BIFUNCTIONAL CAPABILITIES IN ISOPEPTIDE BOND FORMATION SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE EPIDERMIS; KERATINOCYTE; TRANSGLUTAMINASE ID CROSS-LINKED ENVELOPE; RESOLUTION 2-DIMENSIONAL ELECTROPHORESIS; ACCEPTOR DONOR RELATIONSHIPS; HUMAN EPIDERMAL-CELLS; AMINO-ACID-SEQUENCE; MAMMALIAN EPIDERMIS; HUMAN KERATINOCYTES; TRANSGLUTAMINASE; PROTEINS; LINKING AB In this report, the pancornulins are identified as members of the spr (small, proline-rich) multigene family by amino acid sequence and mass spectrometry analyses, One of the pancornulins (14.9 kDa) is identical to the protein predicted by spr-1 clone 128. The other pancornulins (16.9 kDa and 22 kDa) are novel members of the spr family, Immunoelectron microscopy of purified cornified envelopes with a pancornulin-specific antibody established these proteins more definitively as cornified envelope precursors, In addition, two-dimensional electrophoretic analyses of keratinocyte extracts labeled enzymatically with dansylcadaverine (to identify amine accepters) or dansylPGGQQIV (to identify amine donors) showed that both glutamine and lysine residues within the pancornulins participate in the isopeptide linkage characteristic of cornified envelope formation, These results contrasted with those obtained using involucrin, a prominent cornified envelope protein shown capable of acting only as an amine acceptor in this system, Novel partial cDNAs obtained after reverse transcription and polymerase chain reaction amplification of total messenger RNA with pancornulin-specific primers suggest that the spr multigene family may be even larger than previously described, The bifunctional reactivity of the pancornulins in cross-linking and the large number of family members identified to date suggest that the pancornulins and other spr-1-related proteins map be more important in cornified envelope formation than previously considered, perhaps functioning as ''bridge'' molecules during the early phases of cornified envelope assembly. C1 HARVARD UNIV, MASSACHUSETTS GEN HOSP,SCH MED,DEPT DERMATOL, CUTANEOUS BIOL RES CTR, BOSTON, MA 02129 USA. NORTHWESTERN UNIV, SCH MED, DEPT MOLEC & CELL BIOL, CHICAGO, IL USA. HARVARD UNIV, BIOL LABS, MICROCHEM FACIL, CAMBRIDGE, MA USA. FU NHLBI NIH HHS [HL-03512, HL-02212]; NIAMS NIH HHS [AR 0180402] NR 37 TC 41 Z9 44 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD FEB PY 1995 VL 104 IS 2 BP 204 EP 210 DI 10.1111/1523-1747.ep12612759 PG 7 WC Dermatology SC Dermatology GA QD424 UT WOS:A1995QD42400007 PM 7829876 ER PT J AU TERUYA, J CLUETTEBROWN, J SZCZEPIORKOWSKI, ZM LAPOSATA, M AF TERUYA, J CLUETTEBROWN, J SZCZEPIORKOWSKI, ZM LAPOSATA, M TI MODE OF TRANSPORT OF FATTY-ACID TO ENDOTHELIAL-CELLS INFLUENCES INTRACELLULAR FATTY-ACID METABOLISM SO JOURNAL OF LIPID RESEARCH LA English DT Article DE LDL; LIPOPROTEINS; OLEIC ACID; CHOLESTERYL ESTERS; TRIGLYCERIDES; PHOSPHOLIPIDS ID LOW-DENSITY LIPOPROTEIN; CHOLESTERYL ESTERS; SELECTIVE UPTAKE; ARACHIDONATE CONTENT; PLASMA-CHOLESTEROL; LDL RECEPTOR; DEFICIENCY; ENDOCYTOSIS; PROTEINS; EXPOSURE AB Fatty acids are transported to cells from a variety of different moieties in the plasma. In this study, using oleate and human umbilical vein endothelial cells, we asked whether the vehicle that delivers fatty acid to cells has an influence on its metabolism upon its incorporation into the cell. For oleate vehicles, we compared free oleate bound to albumin with oleate in low density lipoprotein (LDL) which was delipidated and reconstituted with either radiolabeled triolein or cholesteryl oleate. Using approximately physiologic concentrations of LDL and free oleate, we demonstrated by three lines of evidence unique patterns of cellular oleate metabolism for oleate delivered as triolein within LDL, for oleate delivered as cholesteryl oleate within LDL, and for oleate delivered as free oleate bound to albumin. In fact, the difference was most marked between cholesteryl oleate and triolein, even though the oleate in cholesteryl oleate and triolein was delivered in identically reconstituted LDL particles, which were presumably incorporated into the cells and degraded in lysosomes in a similar fashion. First, we demonstrated that oleate delivered as free oleate or as triolein in reconstituted LDL was desaturated and elongated to fatty acid metabolites, but cholesteryl oleate in reconstituted LDL was not similarly metabolized. The elongated and desaturated metabolites of oleate were preferentially esterified in cellular triglyceride when oleate was delivered as free oleate, but they were preferentially esterified in phospholipids when oleate was delivered as triolein in LDL. Second, we observed that there was a difference in the distribution of oleate among phospholipids when oleate was delivered as cholesteryl oleate in reconstituted LDL versus triolein in reconstituted LDL. When the oleate was delivered as triolein in reconstituted LDL, there was greater esterification in diacyl phosphatidylethanolamine, in phosphatidylserine, and in phosphalidylinositol. When oleate was delivered as cholesteryl oleate in reconstituted LDL, there was greater esterification in diacyl phosphatidylcholine. Third, there was a marked preference for oleate delivered from triolein in LDL over cholesteryl oleate in LDL for esterification into the sn-1 position of plasmalogens as a vinyl ether-linked fatty acid. These data indi cate that mode of transport of fatty acid to cells influences fatty acid metabolism upon its incorporation into the cell, even when the fatty acid is delivered from the core of the same lipoprotein. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. RI Szczepiorkowski, Zbigniew/A-1359-2007 OI Szczepiorkowski, Zbigniew/0000-0003-2357-9564 FU NIDDK NIH HHS [DK 37454, DK 43159] NR 31 TC 14 Z9 14 U1 0 U2 0 PU LIPID RESEARCH INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD FEB PY 1995 VL 36 IS 2 BP 266 EP 276 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QH014 UT WOS:A1995QH01400006 PM 7751814 ER PT J AU SABOLIC, I KATSURA, T VERBAVATZ, JM BROWN, D AF SABOLIC, I KATSURA, T VERBAVATZ, JM BROWN, D TI THE AQP2 WATER CHANNEL - EFFECT OF VASOPRESSIN TREATMENT, MICROTUBULE DISRUPTION, AND DISTRIBUTION IN NEONATAL RATS SO JOURNAL OF MEMBRANE BIOLOGY LA English DT Article; Proceedings Paper CT Membaires Symposium CY APR 06-09, 1994 CL BUENOS AIRES, ARGENTINA DE WATER CHANNELS; VASOPRESSIN; RAT KIDNEY; IMMUNOCYTOCHEMISTRY; MICROTUBULES; CELL POLARITY ID APICAL MEMBRANE GLYCOPROTEIN; TOAD URINARY-BLADDER; COLLECTING TUBULE; ADENYLATE-CYCLASE; EPITHELIAL-CELLS; MAMMALIAN KIDNEY; ABSORPTIVE CELLS; PRINCIPAL CELLS; AQUAPORIN CHIP; BRUSH-BORDER AB Aquaporin 2 is a collecting duct water channel that is located in apical vesicles and in the apical plasma membrane of collecting duct principal cells. It shares 42% identity with the proximal tubule/thin descending limb water channel, CHIP28. The present study was aimed at addressing three questions concerning the location and behavior of the AQP2 protein under different conditions. First, does the AQP2 channel relocate to the apical membrane after vasopressin treatment? Our results show that AQP2 is diffusely distributed in cytoplasmic vesicles in collecting duct principal cells of homozygous Brattleboro rats that lack vasopressin. In rats injected with exogenous vasopressin, however, AQP2 became concentrated in the apical plasma membrane of principal cells, as determined by immunofluorescence and immunogold electron microscopy. This behavior is consistent with the idea that AQP2 is the vasopressin-sensitive water channel. Second, is the cellular location of AQP2 modified by microtubule disruption? In normal rats, AQP2 has a mainly apical and subapical location in principal cells, but in colchicine-treated rats, it is distributed on vesicles that are scattered throughout the entire cytoplasm. This is consistent with the dependence on microtubules of apical protein targeting in many cell types, and explains the inhibitory effect of microtubule disruption on the hydroosmotic response to vasopressin in sensitive epithelia, including the collecting duct. Third, is AQP2 present in neonatal rat kidneys? We show that AQP2 is abundant in principal cells from neonatal rats at all days after birth. The detection of AQP2 in early neonatal kidneys indicates that a lack of this protein is not responsible for the relatively weak urinary concentrating response to vasopressin seen in neonatal rats. C1 MASSACHUSETTS GEN HOSP,RENAL UNIT,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02114. FU NIDDK NIH HHS [DK 42956, DK 38452] NR 49 TC 195 Z9 196 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0022-2631 J9 J MEMBRANE BIOL JI J. Membr. Biol. PD FEB PY 1995 VL 143 IS 3 BP 165 EP 175 DI 10.1007/BF00233445 PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Physiology GA QH880 UT WOS:A1995QH88000001 PM 7539496 ER PT J AU SCHULZ, JB MATTHEWS, RT MUQIT, MMK BROWNE, SE BEAL, MF AF SCHULZ, JB MATTHEWS, RT MUQIT, MMK BROWNE, SE BEAL, MF TI INHIBITION OF NEURONAL NITRIC-OXIDE SYNTHASE BY 7-NITROINDAZOLE PROTECTS AGAINST MPTP-INDUCED NEUROTOXICITY IN MICE SO JOURNAL OF NEUROCHEMISTRY LA English DT Note DE MPTP; EXCITOTOXICITY; PARKINSONS DISEASE; NITRIC OXIDE SYNTHASE; FREE RADICALS; ENERGY IMPAIRMENT; 7-NITROINDAZOLE ID GLUTAMATE-INDUCED NEUROTOXICITY; CORTICAL CELL-CULTURES; SUPEROXIDE-DISMUTASE; 7-NITRO INDAZOLE; PEROXYNITRITE; MECHANISMS; NITRATION; TOXICITY; PATHWAY; BRAIN AB Several studies suggest that nitric oxide (NO.) contributes to cell death following activation of NMDA receptors in cultured cortical, hippocampal, and striatal neurons. In the pres ent study we investigated whether 7-nitroindazole (7-NI), a specific neuronal nitric oxide synthase inhibitor, can block dopaminergic neurotoxicity seen in mice after systemic administration of MPTP. 7-NI dose-dependently protected against MPTP-induced dopamine depletions using two different dosing regimens of MPTP that produced varying degrees of dopamine depletion. At 50 mg/kg of 7-NI there was almost complete protection in both paradigms. Similar effects were seen with MPTP-induced depletions of both homovanillic acid and 3,4-dihydroxyphenylacetic acid. 7-NI had no significant effect on dopamine transport in vitro and on monoamine oxidase B activity both in vitro and in vivo. One mechanism by which NO. is thought to mediate its toxicity is by interacting with superoxide radical to form peroxynitrite (ONOO-), which then may nitrate tyrosine residues. Consistent with this hypothesis, MPTP neurotoxicity in mice resulted in a significant increase in the concentration of 3-nitrotyrosine, which was attenuated by treatment with 7-NI. Our results suggest that NO. plays a role in MPTP neurotoxicity, as well as novel therapeutic strategies for Parkinson's disease. C1 MASSACHUSETTS GEN HOSP,NEUROL SERV,NEUROCHEM LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RI Schulz, Jorg/D-9786-2012; OI Schulz, Jorg/0000-0002-8903-0593; Muqit, Miratul/0000-0001-9733-2404 FU NINDS NIH HHS [NS 31579, NS 10828]; PHS HHS [16367] NR 30 TC 354 Z9 356 U1 0 U2 4 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD FEB PY 1995 VL 64 IS 2 BP 936 EP 939 PG 4 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA QD027 UT WOS:A1995QD02700058 PM 7530297 ER PT J AU REITER, ER LIBERMAN, MC AF REITER, ER LIBERMAN, MC TI EFFERENT-MEDIATED PROTECTION FROM ACOUSTIC OVEREXPOSURE - RELATION TO SLOW EFFECTS OF OLIVOCOCHLEAR STIMULATION SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID TEMPORARY THRESHOLD SHIFTS; AUDITORY-NERVE FIBERS; ELECTRICAL-STIMULATION; BUNDLE; NEURONS; CAT; SENSITIVITY; DEPENDENCE; COCHLEA; SYSTEM AB 1. The present study attempts to resolve discrepancies in the reported role of olivocochlear (OC) efferent activation in protecting the inner ear from acoustic overstimulation: in previous studies, activating the OC system in guinea pigs reduced the threshold shift caused by 1 min monaural exposure to a 10-kHz tone: whereas unilateral OC activation in cats had no effect on threshold shifts following binaural exposure to a 10 min 6-kHz tone. 2. In this study, anesthetized and curarized guinea pigs were exposed either monaurally or binaurally to tones of different duration (1-5 min), frequency (6 to 10 kHz) and intensity (105-118 dB SPL). For each exposure condition, threshold shifts were compared among ears with different levers of OC activation: in some cases, the OC bundle (OCB) was electrically stimulated during (and/or before) the acoustic overexposure: in others, the OCB was cut before the exposure; in control cases. the OCB was neither cut nor electrically stimulated. 3. Electrical stimulation of the OCB delivered simultaneously with acoustic overstimulation produced significant reductions in threshold shift only for acoustic exposures at higher frequencies (8 and 10 kHz) and shorter durations( 1 and 2 min). The protective effects on 1-min exposures could be extinguished by prior stimulation of the OCB, i.e., if the OC stimulation was turned on 1 min before the acoustic overexposure. 4. These observations provide circumstantial evidence that protection is related to the newly discovered ''slow'' effects of OC activation rather than the classic ''fast'' effects because, in contrast to fast effects, slow effects 1) are maximal in frequency regions affected by 10-kHz exposures and are minimal in regions affected by 6-kHz exposures and 2) can only be maintained for 1-2 min in the face of continuous OC stimulation. C1 MASSACHUSETTS EYE & EAR INFIRM,EATON PEABODY LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02115. HARVARD MIT DIV HLTH SCI & TECHNOL,BOSTON,MA 02114. FU NIDCD NIH HHS [R01 DC-000188] NR 27 TC 109 Z9 111 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD FEB PY 1995 VL 73 IS 2 BP 506 EP 514 PG 9 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA QU215 UT WOS:A1995QU21500007 PM 7760114 ER PT J AU PAN, ZH BAHRING, R GRANTYN, R LIPTON, SA AF PAN, ZH BAHRING, R GRANTYN, R LIPTON, SA TI DIFFERENTIAL MODULATION BY SULFHYDRYL REDOX AGENTS AND GLUTATHIONE OF GABA-EVOKED AND GLYCINE-EVOKED CURRENTS IN RAT RETINAL GANGLION-CELLS SO JOURNAL OF NEUROSCIENCE LA English DT Article DE GABA(A) RECEPTOR; GLYCINE RECEPTOR; REDOX MODULATION; GLUTATHIONE; RETINAL GANGLION CELLS ID CALIFORNICA ACETYLCHOLINE-RECEPTOR; LIGAND-BINDING PROPERTIES; NMDA RECEPTOR; OXIDIZED GLUTATHIONE; CHANNEL COMPLEX; MOLECULAR-BIOLOGY; MEMBRANE PATCHES; NITRIC-OXIDE; THIOL-GROUP; TIME COURSE AB Some areas of the mammalian CNS, such as the retina, contain not one but two fast inhibitory neurotransmitter systems whose actions are mediated by GABA and glycine. Each inhibitory receptor system is encoded by a separate gene family and has a unique set of agonists and antagonists. Therefore, in rat retinal ganglion cells we were surprised to find that a single agent, extracellular glutathione, was capable of modulating currents activated by either GABA(A) or glycine receptor stimulation. Both oxidized and reduced glutathione influence inhibitory neurotransmission in a manner similar to that of the sulfhydryl redox agents dithiothreitol (DTT) and 5,5'-dithio-bis-(2-nitrobenzoic acid) (DTNB). Remarkably, the actions of glutathione are diametrically opposed on the GABA(A) and glycine systems. In whole-cell recordings of single retinal ganglion cells with patch pipettes, reduced glutathione enhances GABA-evoked currents but decreases glycine-evoked currents. These findings suggest that endogenous redox agents, such as glutathione, may constitute a novel modulatory system for the differential regulation of inhibitory neurotransmission in the mammalian retina. C1 CHILDRENS HOSP,MOLEC & CELLULAR NEUROSCI LAB,BOSTON,MA 02115. HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02115. MAX PLANCK INST PSYCHIAT,DEPT NEUROPHYSIOL,D-82152 MARTINSRIED,GERMANY. CHILDRENS HOSP,DEPT NEUROL,BOSTON,MA 02115. BETH ISRAEL HOSP,DEPT NEUROL,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT NEUROL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02115. RI Bahring, Robert/F-7146-2010 FU NEI NIH HHS [R01 EY05477] NR 71 TC 66 Z9 67 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD FEB PY 1995 VL 15 IS 2 BP 1384 EP 1391 PG 8 WC Neurosciences SC Neurosciences & Neurology GA QH371 UT WOS:A1995QH37100038 PM 7869105 ER PT J AU KAOUTZANIS, MC PETERSON, JW ANDERSON, RR MCAULIFFE, DJ SIBILIA, RF ZERVAS, NT AF KAOUTZANIS, MC PETERSON, JW ANDERSON, RR MCAULIFFE, DJ SIBILIA, RF ZERVAS, NT TI BASIC MECHANISM OF IN-VITRO PULSED-DYE LASER-INDUCED VASODILATION SO JOURNAL OF NEUROSURGERY LA English DT Article DE PULSED-DYE LASER; CAROTID ARTERY; VASODILATION; HEMOGLOBIN; EVANS BLUE DYE; RABBIT ID ENDOTHELIUM-DEPENDENT RELAXATIONS; CEREBRAL VASOSPASM; SUBARACHNOID HEMORRHAGE; SMOOTH-MUSCLE; ARTERY; HEMOGLOBIN; INHIBITION AB Vasodilation of rabbit carotid arteries induced by a pulsed-eye laser was studied in vitro to clarify the underlying mechanism. Artery segments were double cannulated in a pressure-perfusion apparatus which, under physiological conditions, allows for differential application of various solutions, pharmacological agents, and pulsed-dye laser light. Vasoconstriction was activated using both pharmacological and nonpharmacological agonists. Laser energy at a wavelength of either 480 or 575 nm was applied intraluminally in 1-mu sec pulses, which caused dilation of the arteries if hemoglobin was present in the lumen at sufficient concentration. Induced vasodilation did not specifically require the presence of hemoglobin; the same phenomenon could be repeated using an inert dye such as Evans blue as an optical absorber of laser energy. The optical density of the absorber, the number of applied laser pulses, and total amount of applied energy directly influenced the vasodilatory response. Laser-induced vasodilation was possible in both normal vessels and vessels denuded of endothelium. Pulsed-dye laser-induced vasodilation is therefore not a phenomenon mediated through chemical processes, but is rather a purely physical process initiated by the optical absorption of laser energy by the intraluminal medium, which probably induces cavitation bubble formation and collapse, resulting in the vasodilatory response of the vessel. C1 MASSACHUSETTS GEN HOSP,NEUROSURG SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,WELLMAN LABS PHOTOMED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. FU NHLBI NIH HHS [HL44554, HL22573] NR 25 TC 10 Z9 10 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 FEB PY 1995 VL 82 IS 2 BP 256 EP 261 DI 10.3171/jns.1995.82.2.0256 PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA QC296 UT WOS:A1995QC29600014 PM 7815154 ER PT J AU XIA, EN RAO, G VANREMMEN, H HEYDARI, AR RICHARDSON, A AF XIA, EN RAO, G VANREMMEN, H HEYDARI, AR RICHARDSON, A TI ACTIVITIES OF ANTIOXIDANT ENZYMES IN VARIOUS TISSUES OF MALE FISCHER-344 RATS ARE ALTERED BY FOOD RESTRICTIONS SO JOURNAL OF NUTRITION LA English DT Article DE GLUTATHIONE PEROXIDASE; FOOD RESTRICTION; SUPEROXIDE DISMUTASE; CATALASE; RATS ID DIETARY RESTRICTION; SUPEROXIDE-DISMUTASE; DROSOPHILA-MELANOGASTER; BIOCHEMICAL PARAMETERS; LIPID-PEROXIDATION; OXIDATIVE STRESS; WISTAR RATS; LIFE-SPAN; AGE; EXPRESSION AB The objective of this study was to determine how food restriction (40% restriction of food intake) altered the age-related changes in the activities of Cu,Zn superoxide dismutase, catalase and glutathione peroxidase in liver, brain cortex, heart, kidney and intestinal mucosa obtained from 6-, 16- and 26-mo-old male Fischer 344 rats. Food restriction increased the activity of one or more of the antioxidant enzymes in the liver, brain cortex, heart and kidney of the rats. However, the magnitude of the effect and the antioxidant enzyme(s) affected by food restriction varied from tissue to tissue, and food restriction had no significant effect on the activities of these enzymes in intestinal mucosa. Interestingly, the four tissues in which food restriction increased the activity of one or more of the antioxidant enzymes showed reduced lipid peroxidation as measured by thiobarbituric acid-reactive material. These data suggest that food restriction might enhance the survival of rodents by altering the levels of the antioxidant enzymes and hence reducing free radical damage. C1 AUDIE L MURPHY MEM VET ADM MED CTR,EDUC & CLIN CTR,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. FU NIA NIH HHS [AG01548] NR 41 TC 110 Z9 114 U1 2 U2 5 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 1995 VL 125 IS 2 BP 195 EP 201 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA QE851 UT WOS:A1995QE85100006 PM 7861246 ER PT J AU OGUCHI, S WALKER, WA SANDERSON, IR AF OGUCHI, S WALKER, WA SANDERSON, IR TI DIFFERENTIATION AND POLARITY ALTER THE BINDING OF IGF-I TO HUMAN INTESTINAL EPITHELIAL (CACO-2) CELLS SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Article DE TYPE 1 IGF RECEPTOR; INTESTINAL EPITHELIAL (CACO-2) CELLS; PROLIFERATION; POLARITY; DIFFERENTIATION ID GROWTH FACTOR-I; SUCRASE-ISOMALTASE EXPRESSION; HUMAN COLON CANCER; LINE CACO-2; GASTROINTESTINAL-TRACT; RECEPTOR EXPRESSION; HUMAN-MILK; PROLIFERATION; PROTEIN; CULTURE AB This study examined whether insulin-like growth factor-I (IGF-I) bound to specific functioning IGF receptors on the surface of Caco-2 cells and how this binding was affected by the differentiation and polarity of these cells. IGF-I, which increased cell proliferation in a dose-dependent manner, bound to a specific receptor on the surface of Caco-2 cells. Affinity cross-linking with labeled IGF-I followed by reducing sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE) showed M(r)s at 135,000, 270,000 and 355,000 bands, which was inhibited by unlabeled IGF-I. A Scatchard analysis of radioligand-receptor binding showed the presence of a single class of receptors with high affinity for IGF-I. This class of receptors was specific for IGF-I, the affinity of IGF-I to the receptor being four and 150 times greater than IGF-II and insulin, respectively. There was no difference in the affinity of IGF-I to type 1 IGF receptors between less-differentiated [dissociation constant (K-d) = 3.81 nM] and well-differentiated cells (K-d = 3.78 nM); however, well-differentiated cells showed a 2.4-fold higher maximum number of binding sites (B-max) than less-differentiated cells (3.45 vs. 1.44 X 10(4) sites/cell), indicating an increase in the density of IGF-I receptors with differentiation. Furthermore, the number of type 1 IGF receptors on the basolateral surface of well-differentiated cells was 2.4 times greater than that seen on the apical surface. In summary, IGF-I binds to a single class of specific Caco-2 cell-surface receptors, which increase in number with differentiation and are found on both aspects of the epithelium. C1 MASSACHUSETTS GEN HOSP,COMBINED PROGRAM PEDIAT GASTROENTEROL & NUTR,DEV GASTROENTEROL LAB,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA. FU NICHD NIH HHS [HD12437]; NIDDK NIH HHS [DK33506] NR 34 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0277-2116 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD FEB PY 1995 VL 20 IS 2 BP 148 EP 155 DI 10.1097/00005176-199502000-00003 PG 8 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA QD741 UT WOS:A1995QD74100003 PM 7714679 ER PT J AU REYNOLDS, EM RYAN, DP SHERIDAN, RL DOODY, DP AF REYNOLDS, EM RYAN, DP SHERIDAN, RL DOODY, DP TI LEFT-VENTRICULAR FAILURE COMPLICATING SEVERE PEDIATRIC BURN INJURIES SO JOURNAL OF PEDIATRIC SURGERY LA English DT Article; Proceedings Paper CT 25th Annual Meeting of the American-Pediatric-Surgical-Association CY MAY 14-17, 1994 CL TUCSON, AZ SP AMER PEDIAT SURG ASSOC DE BURNS; PEDIATRIC; SWAN-GANZ CATHETERIZATION; LEFT VENTRICULAR FAILURE ID ACUTE THERMAL-INJURY; PULMONARY-ARTERY CATHETERIZATION; MYOCARDIAL DEPRESSANT SUBSTANCE; RESPIRATORY-DISTRESS SYNDROME; ARTIFICIAL SKIN; SEPTIC SHOCK; MORTALITY; DYSFUNCTION; EXCISION; SURVIVAL AB Purpose: Despite improvements in the overall survival rates for critically burned children, failed resuscitation may account for 54% of deaths following burn injuries. Clinical and experimental studies have implicated failure of the right side of the heart in adults, biventricular failure in elderly patients, and inadequate resuscitation as causes of refractory burn shock, This retrospective study of resuscitation at a tertiary pediatric burn center showed that myocardial depression is a complicating factor in the treatment of the pediatric burn victim. Methods: From 1989 to 1992, 28 critically burned children (greater than or equal to 60% total burn surface area) were resuscitated primarily at our center (admission within 24 hours of injury). Twenty-seven children had central lines, nine of whom underwent pulmonary artery catheterization for intensive hemodynamic monitoring because standard resuscitative therapy had failed. The average amount of fluid received at 8 and 24 hours after injury was within 10% of the calculated volume based on the Parkland formula. Results: Indexes of a failing rescue attempt included respiratory distress (PaO2 FIO2 less than or equal to 200), central venous pressure of greater than 10 mm Hg, and urine output of less than 1 mL/kg/h. Filling pressures were found to be normal or elevated in all children, indicating adequate volume replacement. Evaluation of cardiac function was performed using a thermodilution technique and showed that 100% of the study group had depressed left ventricular function, with an average left ventricular stroke work index (LVSWI) of 19.9 g.m/m(2) (normal, 44 to 68 g.m/m(2)), whereas only 38% had concomitant right ventricular failure. This left-sided dysfunction persisted throughout the acute resuscitation period but was improved after appropriate modification of fluid resuscitation and initiation of vasopressors (average final LVSWI, 38.0 g.m/m(2)). There were no complications from placement of the Swan-Ganz catheters in this group. Conclusion: Cardiogenic failure is a major determinant of a failing pediatric burn resuscitation, and, contrary to the adult burn patient, the myocardial depression is predominantly left-sided. Information from pulmonary artery catheters can help direct therapy by providing indications for vasopressors and modifying fluid resuscitation. Copyright (C) 1995 by W.B. Saunders Company C1 MASSACHUSETTS GEN HOSP,SHRINERS BURNS INST,TRAUMA & BURN SERV,PEDIAT SURG SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 30 TC 39 Z9 40 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0022-3468 J9 J PEDIATR SURG JI J. Pediatr. Surg. PD FEB PY 1995 VL 30 IS 2 BP 264 EP 270 DI 10.1016/0022-3468(95)90572-3 PG 7 WC Pediatrics; Surgery SC Pediatrics; Surgery GA QG224 UT WOS:A1995QG22400020 PM 7738749 ER PT J AU ALLES, AJ LOSTY, PD DONAHOE, PK MANGANARO, TF SCHNITZER, JJ AF ALLES, AJ LOSTY, PD DONAHOE, PK MANGANARO, TF SCHNITZER, JJ TI EMBRYONIC-CELL DEATH PATTERNS ASSOCIATED WITH NITROFEN-INDUCED CONGENITAL DIAPHRAGMATIC-HERNIA SO JOURNAL OF PEDIATRIC SURGERY LA English DT Article; Proceedings Paper CT 25th Annual Meeting of the American-Pediatric-Surgical-Association CY MAY 14-17, 1994 CL TUCSON, AZ SP AMER PEDIAT SURG ASSOC DE CONGENITAL DIAPHRAGMATIC HERNIA; PULMONARY HYPOPLASIA; NITROFEN; CELL DEATH; SUPRAVITAL STAINING ID ETHER; DEFECTS; ORGANS; RATS AB The offspring of pregnant Sprague-Dawley rats exposed to nitrofen on gestational day 9.5 develop left-sided congenital diaphragmatic hernia (CDH). Twenty-four hours after treatment, on day 10.5, supravital staining with Nile blue sulfate and histological examination showed bilateral excessive cell death in cervical somites 2 through 4. After 48 hours, on day 11.5, cell death was absent in the cervical somites but was apparent in the mesoderm adjacent to the somites in the septum transversum and in the developing sympathetic ganglia adjacent to the dorsal aortae. Cell death was not apparent in the foregut or lung primordia on either day 10.5 or 11.5. The incidence of nitrofen-exposed embryos with such patterns of cell death closely paralleled that of left-sided CDH in similarly treated day 21.5 fetuses. Control animals treated with olive oil had normal programmed cell death patterns in the regions of interest and had no evidence of CDH on day 21.5. It is possible that these patterns of excessive cell death early in gestation may play a role in the genesis of diaphragmatic hernia. Mesoderm derived from cervical somites 3 through 5 contributes to the diaphragmatic anlage and forms the major portion of the muscle of the diaphragm. Because nitrofen damages mesodermal cell populations in cervical somites 2 through 4 and in the mesenchyme adjacent to the septum transversum 24 to 48 hours after administration, the authors propose that damage to these populations may reduce progenitor cells needed to populate the diaphragmatic anlage, thereby hindering pleuroperitoneal canal closure. Similar embryonic mesodermal perturbations caused by unknown genetic and/or environ mental phenomena may underlie the embryogenesis of human CDH. Copyright a 1995 by W.B. Saunders Company C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,PEDIAT SURG RES LABS,PEDIAT SURG SERV,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02114. NR 27 TC 28 Z9 28 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0022-3468 J9 J PEDIATR SURG JI J. Pediatr. Surg. PD FEB PY 1995 VL 30 IS 2 BP 353 EP 360 DI 10.1016/0022-3468(95)90589-8 PG 8 WC Pediatrics; Surgery SC Pediatrics; Surgery GA QG224 UT WOS:A1995QG22400037 PM 7537810 ER PT J AU BUCKNER, CK FISHLEDER, RI CONKLIN, R GRAZIANO, FM AF BUCKNER, CK FISHLEDER, RI CONKLIN, R GRAZIANO, FM TI A COMPARISON OF THE EFFECTS OF ISOPROTERENOL AND FORSKOLIN ON IMMUNOLOGICAL AND NONIMMUNOLOGICAL RELEASE OF HISTAMINE FROM GUINEA-PIG SUPERFUSED TRACHEA AND DISPERSED TRACHEAL CELLS SO JOURNAL OF PHARMACOLOGICAL AND TOXICOLOGICAL METHODS LA English DT Article DE GUINEA-PIG TRACHEA; HISTAMINE RELEASE; ISOPROTERENOL; FORSKOLIN; ANTIGEN; CURARE ID INDUCED CONTRACTION; EVOKE CONTRACTION; MEDIATOR RELEASE; LUNG; INHIBITION; OVALBUMIN; ABILITY; STRIPS AB This study has compared the abilities of isoproterenol and forskolin to inhibit immunologic- and nonimmunologic-induced histamine release from guinea-pig superfused trachea and enzymatically dispersed tracheal cells. Contraction was also measured in the former preparation. The potency of isoproterenol was similar for inhibition of all parameters associated with immunologic (ovalbumin) challenge in the two preparations. In contrast, forskolin appeared less potent in inhibiting ovalbumin-induced histamine release from dispersed tracheal cells. Histamine release by the nonimmunologic secretagogues d-tubocurarine and compound 48/80 was not altered by either substance. However, inhibition by isoproterenol and forskolin of tracheal contraction was evident when challenge was conducted with d-tubocurarine and compound 48/80. Inhibition of contraction appears to be a result of functional antagonism at the level of the smooth muscle. The superfused trachea is a useful preparation in which to explore the effects of substances that modulate mast cell mediator release. C1 SCH PHARM,MADISON,WI. DEPT ANESTHESIOL,MADISON,WI. DEPT MED,MADISON,WI. WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI. FU NHLBI NIH HHS [HL 28585] NR 14 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1056-8719 J9 J PHARMACOL TOXICOL JI J. Pharmacol. Toxicol. Methods PD FEB PY 1995 VL 33 IS 1 BP 47 EP 52 DI 10.1016/1056-8719(94)00056-A PG 6 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA QE859 UT WOS:A1995QE85900007 PM 7537127 ER PT J AU SCHUMACHER, HR AF SCHUMACHER, HR TI SYNOVIAL INFLAMMATION, CRYSTALS, AND OSTEOARTHRITIS SO JOURNAL OF RHEUMATOLOGY LA English DT Article; Proceedings Paper CT 3rd International Symposium on Osteoarthritis - Challenges for the 21st-Century CY OCT 04-07, 1994 CL VAL DAVID, CANADA DE OSTEOARTHRITIS; SYNOVIUM; SYNOVIAL FLUID; CPPD CRYSTALS; APATITE; INFLAMMATION ID CALCIUM PYROPHOSPHATE DIHYDRATE; ALIZARIN RED; OSTEO-ARTHRITIS; FLUID; KNEE; JOINT; HYDROXYAPATITE; DEPOSITION; MICROSCOPY; ACETAMINOPHEN AB Inflammation is now generally accepted as a component in the course of most patients with symptomatic osteoarthritis (OA), although the stage at which it occurs and how it affects the course has not been resolved. When joint effusions are present in OA they almost always contain more leukocytes than normal synovial fluid, although often still falling into what was considered a noninflammatory range. Multiple factors can contribute to this low grade inflammation, with crystals being only one of many such factors needing consideration. Crystals of calcium pyrophosphate dihydrate (CPPD) and apatite are more frequent in more severe radiographic OA, but whether these are a result, a contributing factor, or both is not known. Experimental studies and the few clinical observations do not show that either CPPD or apatite consistently cause either inflammation or more rapid destruction in OA. These attempts at correlations are plagued with technical questions about what crystal numbers may be meaningful, and about techniques for crystal identification. Continued efforts are indicated to identify a treatable component of OA. C1 UNIV PENN,SCH MED,DEPT MED,DIV RHEUMATOL,PHILADELPHIA,PA 19104. DEPT VET AFFAIRS MED CTR,CTR ARTHRITIS IMMUNOL,PHILADELPHIA,PA 19104. NR 33 TC 14 Z9 14 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 FEB PY 1995 VL 22 SU 43 BP 101 EP 103 PG 3 WC Rheumatology SC Rheumatology GA QH907 UT WOS:A1995QH90700032 ER PT J AU TRIPPEL, SB AF TRIPPEL, SB TI GROWTH-FACTOR ACTIONS ON ARTICULAR-CARTILAGE SO JOURNAL OF RHEUMATOLOGY LA English DT Article; Proceedings Paper CT 3rd International Symposium on Osteoarthritis - Challenges for the 21st-Century CY OCT 04-07, 1994 CL VAL DAVID, CANADA DE ARTICULAR CARTILAGE; GROWTH FACTORS; FIBROBLAST GROWTH FACTOR; INSULIN LIKE GROWTH FACTOR I; TRANSFORMING GROWTH FACTOR BETA ID SOMATOMEDIN-C RECEPTOR; FACTOR-I; FACTOR-BETA; PROTEOGLYCAN SYNTHESIS; MONOLAYER-CULTURE; ORGAN-CULTURES; CHONDROCYTES; INSULIN; HORMONE; OSTEOARTHRITIS AB Polypeptide growth factors play a major role in the regulation of cell behavior, including that of articular chondrocytes. Among the most influential of these factors identified for articular cartilage are insulin like growth factor I (ICE-I), basic fibroblast growth factor (bFGF), and transforming growth factor beta (TGF beta). IGF-I stimulates articular chondrocyte matrix synthetic and mitotic activity and inhibits chondrocyte mediated matrix catabolism. The role of bFGF as a potent mitogen for articular chondrocytes is well established. In contrast, this factor appears to play a complex role in matrix synthesis and degradation, promoting both anabolic and catabolic functions. Both IGF-I and bFGF have been shown to augment articular cartilage repair in vivo. TGF beta is particularly dependent upon the context in which it acts, eliciting seemingly opposite effects under different experimental conditions. These and other factors interact to modulate their respective actions, creating effector cascades and feedback loops of intercellular and intracellular events that control articular chondrocyte functions, Elucidation of the actions and interactions of these factors may be expected to clarify the etiopathogenesis of osteoarthritis and possibly offer novel methods for its treatment. C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP TRIPPEL, SB (reprint author), MASSACHUSETTS GEN HOSP,DEPT ORTHOPAED,ORTHOPAED RES LABS,JACKSON 11TH FLOOR,BOSTON,MA 02114, USA. NR 38 TC 38 Z9 40 U1 0 U2 1 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO ON M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD FEB PY 1995 VL 22 SU 43 BP 129 EP 132 PG 4 WC Rheumatology SC Rheumatology GA QH907 UT WOS:A1995QH90700038 ER PT J AU LEE, R NEYA, K SVIZZERO, TA KOSKI, G MITCHELL, JD VLAHAKES, GJ AF LEE, R NEYA, K SVIZZERO, TA KOSKI, G MITCHELL, JD VLAHAKES, GJ TI NOREPINEPHRINE INFUSION FOLLOWING CARDIOPULMONARY BYPASS - EFFECT OF INFUSION SITE SO JOURNAL OF SURGICAL RESEARCH LA English DT Article ID PULMONARY-HYPERTENSION; CIRCULATION; LUNGS; 5-HYDROXYTRYPTAMINE; EXTRACTION; REMOVAL; CATECHOLAMINES; NORADRENALINE; PLASMA AB The placement of left atrial catheters following cardiopulmonary bypass (CPB) allows accurate monitoring of left ventricular filling pressures, as well as access for the infusion of vasoactive drugs. While the left atrial administration of norepinephrine (NE) is thought to provide higher systemic arterial NE levels while minimizing any pulmonary vasoconstriction, no study critically compares central venous and left atrial NE infusion following cardiopulmonary bypass. A canine model was used to compare central venous and left atrial NE infusion at three dosages (0.2, 0.4, and 0.6 mu g/kg/min) both prior to CPB and following 2 hr of hypothermic CPB at 27 degrees C. Prior to CPB, there was no difference in the hemodynamic efficacy of central venous and left atrial NE infusion at any dosage. The pulmonary circulation metabolized 16-29% of circulating NE. Only at the 0.2 mu g/kg/min dose was there a difference in the arterial NE level between central venous (3474 +/- 486 pg/ml) and left atrial (5504 +/- 751 pg/ml, P = 0.019) NE administration. Above this dose, no difference in the arterial NE level was identified. Following 2 hr of CPB, the pulmonary endothelium metabolized a significantly higher percentage of circulating NE (35-42%). Despite this increased extent of pulmonary metabolism, there was no difference in the hemodynamic efficacy or the resulting arterial NE level of central venous and left atrial NE infusion at a given dose. In conclusion, the results demonstrate: (1) increased pulmonary NE uptake following CPB, and (2) no difference in hemodynamic efficacy between central venous and left atrial NE infusion over a wide range of three doses in a model with normal lungs. (C) 1995 Academic Press, Inc. C1 MASSACHUSETTS GEN HOSP,DEPT SURG,CARDIAC SURG UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,CARDIAC ANESTHESIA GRP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 17 TC 3 Z9 3 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD FEB PY 1995 VL 58 IS 2 BP 143 EP 148 DI 10.1006/jsre.1995.1023 PG 6 WC Surgery SC Surgery GA QH329 UT WOS:A1995QH32900005 PM 7861765 ER PT J AU WOZNIAK, J AF WOZNIAK, J TI DEVELOPING MINDS - CHALLENGE AND CONTINUITY ACROSS THE LIFE-SPAN - RUTTER,M, RUTTER,M SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Book Review C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP WOZNIAK, J (reprint author), HARVARD UNIV,SCH MED,BOSTON,MA 02115, 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 FEB PY 1995 VL 34 IS 2 BP 255 EP 256 DI 10.1097/00004583-199502000-00023 PG 2 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA QD091 UT WOS:A1995QD09100023 ER PT J AU ELEWSKI, B BERGSTRESSER, PR HANIFIN, J LESHER, J SAVIN, R SHUPACK, J STILLER, M TSCHEN, E ZAIAS, N BIRNBAUM, JE AF ELEWSKI, B BERGSTRESSER, PR HANIFIN, J LESHER, J SAVIN, R SHUPACK, J STILLER, M TSCHEN, E ZAIAS, N BIRNBAUM, JE TI LONG-TERM OUTCOME OF PATIENTS WITH INTERDIGITAL TINEA-PEDIS TREATED WITH TERBINAFINE OR CLOTRIMAZOLE SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Note C1 SANDOZ INC,E HANOVER,NJ 07936. CASE WESTERN RESERVE UNIV,CLEVELAND,OH. UNIV TEXAS,SW MED CTR,DALLAS,TX. OREGON HLTH SCI UNIV,PORTLAND,OR 97201. MED COLL GEORGIA,AUGUSTA,GA 30912. YALE UNIV,SCH MED,NEW HAVEN,CT. NYU,MED CTR,NEW YORK,NY. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. UNIV NEW MEXICO,SCH MED,ALBUQUERQUE,NM 87131. GREATER MIAMI SKIN & LASER CTR,MIAMI,FL. NR 1 TC 16 Z9 16 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD FEB PY 1995 VL 32 IS 2 BP 290 EP 292 DI 10.1016/0190-9622(95)90153-1 PN 1 PG 3 WC Dermatology SC Dermatology GA QE622 UT WOS:A1995QE62200026 PM 7829722 ER PT J AU LAUHON, CT SZOSTAK, JW AF LAUHON, CT SZOSTAK, JW TI RNA APTAMERS THAT BIND FLAVIN AND NICOTINAMIDE REDOX COFACTORS SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID DNA APTAMER; NUCLEOTIDES; SELECTION; THROMBIN; ASSOCIATION; COENZYMES; MOLECULES; SEQUENCE; ANALOGS; WORLD AB RNA molecules that specifically bind riboflavin (Rb) and beta-nicotinamide mononucleotide (NMN) have been isolated by in vitro selection, A simple structural motif containing intramolecular G-quartets was found to bind tightly to oxidized riboflavin (K-d = 1-5 mu M) DNA versions of the consensus sequence also bind, but with weaker affinity. DMS protection experiments show that the quartet structure of these aptamers is stabilized by interaction with the flavin. As a measure of their redox specificity, the aptamers do not show significant differential binding between oxidized and reduced forms of a 5-deazariboflavin derivative that is a close structural analog of riboflavin. In contrast to the lack of redox specificity of the riboflavin aptamers, RNAs selected for binding to the nicotinamide portion of NAD discriminate between NAD and NADH in solution by over an order of magnitude. A mutagenized pool based on one of the NMN aptamer sequences was used to reselect for NMN binding. Comparison of the reselected sequences led to the identification of the binding region of the aptamer. A complex secondary structure containing two interacting stem-loops is proposed for the minimal NMN-binding RNA. The same mutagenized pool was used to select for increased discrimination between NMN and NMNH. From these reselected sequences, a mutation within the binding region was identified that increases specificity for NMN. These experiments show that RNA can bind these cofactors with low micromolar affinity and, in the case of nicotinamide cofactors, can discriminate between the two redox states. These cofactor binding motifs may provide a framework for generating new ribozymes that catalyze redox reactions similar to those found in basic metabolic pathways. C1 MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. FU CSR NIH HHS [DRG-1157] NR 57 TC 157 Z9 161 U1 2 U2 38 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD FEB 1 PY 1995 VL 117 IS 4 BP 1246 EP 1257 DI 10.1021/ja00109a008 PG 12 WC Chemistry, Multidisciplinary SC Chemistry GA QE730 UT WOS:A1995QE73000008 PM 11539282 ER PT J AU RUFFIN, WK STACEYCLEAR, A YOUNGER, J HOOVER, HC AF RUFFIN, WK STACEYCLEAR, A YOUNGER, J HOOVER, HC TI RATIONALE FOR ROUTINE AXILLARY DISSECTION IN CARCINOMA OF THE BREAST SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Review ID I-II CARCINOMA; CLINICAL-TRIAL; RADICAL MASTECTOMY; ADJUVANT THERAPY; CANCER; RADIOTHERAPY; SURVIVAL; RISK; METASTASES; MANAGEMENT C1 MASSACHUSETTS GEN HOSP,DEPT SURG,DIV SURG ONCOL,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT SURG,CAMBRIDGE,MA. MASSACHUSETTS GEN HOSP,DEPT INTERNAL MED,DIV MED ONCOL,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT INTERNAL MED,CAMBRIDGE,MA. NR 36 TC 62 Z9 66 U1 0 U2 0 PU AMER COLL SURGEONS PI CHICAGO PA 54 EAST ERIE ST, CHICAGO, IL 60611 SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD FEB PY 1995 VL 180 IS 2 BP 245 EP 251 PG 7 WC Surgery SC Surgery GA QF440 UT WOS:A1995QF44000022 PM 7850065 ER PT J AU CRESS, ME SCHECHTMAN, KB MULROW, CD FIATARONE, MA GERETY, MB BUCHNER, DM AF CRESS, ME SCHECHTMAN, KB MULROW, CD FIATARONE, MA GERETY, MB BUCHNER, DM TI RELATIONSHIP BETWEEN PHYSICAL PERFORMANCE AND SELF-PERCEIVED PHYSICAL FUNCTION SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID HEALTH-STATUS; FICSIT TRIALS; VALIDITY; SCALES; AIMS AB OBJECTIVE: The objective of this study was to compare two methods of measuring physical function in subjects with a broad range of abilities and to evaluate the effects of cognitive, social, educational, and age factors on the relationship between the two methods. DESIGN: Multiple regression analysis was used to compare self-perceived (dependent variables) with performance measures (independent variables). Covariates included age, gender, Mini-Mental State Exam score, education, living status, and depression score. SETTING: Five community-dwelling and two nursing home sites. PARTICIPANTS: 417 community-dwelling subjects and 200 nursing home residents aged 62-98 years. MEASUREMENTS: Self-perceived physical function was assessed with the physical dimension summary score of the Sickness Impact Profile, which comprises three subscales: ambulation, mobility, and body care and movement. Physical performance was evaluated by self-selected gait speed, chair-stand time, maximal grip strength, and a balance score. RESULTS: Nursing home residents and community-dwellers were significantly different (P < .0001) in all variables except age and gender. Self-perceived and performance-based measures were moderately correlated, with a range from r = -.194 to r = -.625 (P < .05). Gait speed was the strongest independent predictor of self-perceived physical function in both groups. Symptoms of depression were also an independent predictor of self-perceived function in nursing home residents; subjects who had such symptoms report more self-perceived dysfunction than would be predicted based on performance tests. CONCLUSIONS: Self-selected gait speed is a global indicator of self-perceived physical function over a broad range of abilities. External determinants (depressive symptoms, cognitive function, marital status, etc.) affect self-perceived function in both groups, but gait speed is the greatest single predictor of self-perceived function. In nursing home residents depressive symptomatology is related to self-perceived C1 WASHINGTON UNIV,ST LOUIS,MO. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. HARVARD UNIV,SCH MED,BOSTON,MA. TUFTS UNIV,USDA,HUMAN NUTR RES CTR AGING,BOSTON,MA 02111. RP CRESS, ME (reprint author), UNIV WASHINGTON,HARBORVIEW MED CTR ZA87,325 9TH AVE,SEATTLE,WA 98104, USA. FU NIA NIH HHS [U-01AG09089] NR 27 TC 168 Z9 171 U1 4 U2 15 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD FEB PY 1995 VL 43 IS 2 BP 93 EP 101 PG 9 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA QF230 UT WOS:A1995QF23000001 PM 7836655 ER PT J AU WALD, TG MILLER, BA SHULT, P DRINKA, P LANGER, L GRAVENSTEIN, S AF WALD, TG MILLER, BA SHULT, P DRINKA, P LANGER, L GRAVENSTEIN, S TI CAN RESPIRATORY SYNCYTIAL VIRUS AND INFLUENZA-A BE DISTINGUISHED CLINICALLY IN INSTITUTIONALIZED OLDER PERSONS SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Note ID NURSING-HOME; INFECTION; OUTBREAK; PNEUMONIA; ILLNESS; TRANSMISSION; ADULTS C1 UNIV WISCONSIN,INST AGING,MADISON,WI 53706. UNIV WISCONSIN,DEPT MED,GERIATR & GERONTOL SECT,MADISON,WI. STATE LAB HYG,MADISON,WI. WILLIAM S MIDDLETON MEM VET ADM MED CTR,CTR GERIATR RES EDUC & CLIN,MADISON,WI 53705. WISCONSIN VET HOME,KING,WI 54946. RI Gravenstein, Stefan/G-1681-2011 FU NIA NIH HHS [AG09632, AG00548, 5AG00213] NR 33 TC 41 Z9 41 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 FEB PY 1995 VL 43 IS 2 BP 170 EP 174 PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA QF230 UT WOS:A1995QF23000013 PM 7836643 ER PT J AU JUNG, FF KENNEFICK, TM INGELFINGER, JR VORA, JP ANDERSON, S AF JUNG, FF KENNEFICK, TM INGELFINGER, JR VORA, JP ANDERSON, S TI DOWN-REGULATION OF THE INTRARENAL RENIN-ANGIOTENSIN SYSTEM IN THE AGING RAT SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article DE KIDNEY; ELDERLY; RENIN RELEASE; ANGIOTENSIN-CONVERTING ENZYME ID CONVERTING ENZYME; GLOMERULAR-FILTRATION; MOLECULAR-CLONING; SOLUTE EXCRETION; PLASMA-RENIN; INHIBITION; KIDNEY; AGE AB Progressive deterioration of renal function occurs during normal aging. Previous studies on the aging kidney have demonstrated glomerular hemodynamic changes, specifically, glomerular capillary hypertension, as maladaptations that lead to proteinuria and glomerular sclerosis over time. Aging rats treated with angiotensin-converting enzyme inhibition have relatively less proteinuria and sclerosis, suggesting that age-related changes in renal function may be associated with alterations in the intrarenal renin-angiotensin system, which thus may play a major role in the pathogenesis of these maladaptations. To investigate this possibility, renal and systemic renin-angiotensin systems were examined at an early phase of the aging process (3 months) and at a later phase (12 months) in male Sprague-Dawley rats. Although plasma renin and serum angiotensin-converting enzyme concentrations did not differ significantly, the intrarenal system showed down-regulation of renin mRNA and angiotensin-converting enzyme levels with aging, whereas angiotensinogen levels remained stable. The decrease in renin mRNA appeared to precede the fall in plasma renin concentration in the aging process. Additional studies in 15-month-old rats confirmed that, by this time, both basal and stimulated renal renin release rates were impaired in older rats. Thus, both decreased renin synthesis and impaired renin release underlie the fall in plasma renin with normal aging. This decrease may act to lower intrarenal baseline levels of angiotensin II, an adaptation of likely importance in the modulation of intrarenal vascular tone and tubular function in the aging kidney. C1 OREGON HLTH SCI UNIV,DIV NEPHROL & HYPERTENS,PORTLAND,OR 97201. VET ADM MED CTR,PORTLAND,OR. RP JUNG, FF (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,PEDIAT NEPHROL UNIT,PEDIAT NEPHROL LAB,BOSTON,MA 02114, USA. NR 35 TC 37 Z9 37 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 1995 VL 5 IS 8 BP 1573 EP 1580 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA QH761 UT WOS:A1995QH76100006 PM 7756590 ER PT J AU YANG, CW HATTORI, M VLASSARA, H HE, CJ CAROME, MA YAMATO, E ELLIOT, S STRIKER, GE STRIKER, LJ AF YANG, CW HATTORI, M VLASSARA, H HE, CJ CAROME, MA YAMATO, E ELLIOT, S STRIKER, GE STRIKER, LJ TI OVEREXPRESSION OF TRANSFORMING GROWTH-FACTOR-BETA-1 MESSENGER-RNA IS ASSOCIATED WITH UP-REGULATION OF GLOMERULAR TENASCIN AND LAMININ GENE-EXPRESSION IN NONOBESE DIABETIC MICE SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article DE GLOMERULOSCLEROSIS; COMPETITIVE POLYMERASE CHAIN REACTION; EXTRACELLULAR MATRIX; GROWTH FACTOR; ADVANCED GLYCOSYLATION ENDPRODUCTS ID EXTRACELLULAR-MATRIX PROTEIN; GLYCOSYLATION END-PRODUCTS; MESSENGER-RNA LEVELS; SMOOTH-MUSCLE CELLS; FACTOR-BETA; HUMAN GLOMERULOSCLEROSIS; ANGIOTENSIN-II; IV COLLAGEN; RATS; KIDNEY AB Nonobese diabetic (NOD) mice spontaneously develop immune-mediated insulin-dependent diabetes mellitus and nephropathy, providing an opportunity to study the early molecular events in a model of diabetic glomerulosclerosis. The expression of several genes coding for growth factors and extracellular matrix was examined in microdissected glomeruli, by the use of reverse transcription-competitive polymerase chain reaction, in diabetic NOD mice (mean duration of diabetes, 28.5 +/- 7 days) and age-matched nondiabetic NOD mice with normal glucose tolerance. The levels of mRNA coding for transforming growth factor-beta 1, tenascin, and laminin B1 increased 1.9-, 2.0-, and 1.7-fold, respectively, whereas platelet-derived growth factor (PDGF)-B, alpha 1(IV) collagen, 72-kd collagenase, alpha-smooth muscle actin, and beta-actin mRNA remained stable in the diabetic mice. The kidney advanced glycosylation endproducts levels increased 2.1-fold in the diabetic mice, and the diabetic glomeruli showed an accumulation of tenascin and laminin but not of type IV collagen by immunofluorescence microscopy. There was no increase in cell number per glomerulus after the onset of diabetes, a finding consistent with stable PDGF-B and alpha-smooth muscle actin mRNA levels. These findings provide evidence that increased glomerular transforming growth factor-beta 1, but not PDGF-B, mRNA is associated with the up-regulation of tenascin and laminin expression after advanced glycosylation endproduct accumulation, early after the onset of diabetes. C1 NIDDKD,METAB DIS BRANCH,RENAL CELL BIOL SECT,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,IMMUNOL & IMMUNOGENET SECT,BOSTON,MA 02115. PICOWER INST MED RES,MANHASSET,NY. WALTER REED ARMY MED CTR,DEPT MED,WASHINGTON,DC 20307. FU NIA NIH HHS [5 RO1 AGO4953-04]; NIDDK NIH HHS [R01DK43613, DK36836] NR 54 TC 86 Z9 87 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 1995 VL 5 IS 8 BP 1610 EP 1617 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA QH761 UT WOS:A1995QH76100011 PM 7538809 ER PT J AU AMOAHAPRAKU, B TANG, SS INGELFINGER, JR GUZMAN, NJ AF AMOAHAPRAKU, B TANG, SS INGELFINGER, JR GUZMAN, NJ TI GUANOSINE TRIPHOSPHATE CYCLOHYDROLASE-I REGULATES NITRIC-OXIDE SYNTHESIS IN RENAL PROXIMAL TUBULES SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Note DE TETRAHYDROBIOPTERIN; NITRIC OXIDE SYNTHASE; CYTOKINES; PTERIDINES; RENAL EPITHELIUM ID PHENYLALANINE-HYDROXYLASE; ENDOTHELIAL-CELLS; MESANGIAL CELLS; RAT-TISSUES; TETRAHYDROBIOPTERIN; MACROPHAGES; GENERATION; CYTOKINES; SYNTHASE AB The synthesis of nitric oxide by proximal tubule-inducible nitric oxide synthase requires tetrahydrobiopterin as a cofactor. To determine whether tetrahydrobiopterin synthesis is required for nitric oxide production, nitrite release by mouse proximal tubule cells treated with 2,4-diamino-6-hydroxypyrimidine, an inhibitor of the rate-limiting enzyme in the de nova synthesis of tetrahydrobiopterin from guanosine triphosphate, guanosine triphosphate cyclohydrolase I, was measured. Treatment with lipopolysaccharide (0.1 mu g/mL) and interferon-gamma (100 U/mL) for 12 h increased nitrite production from 2.7 +/- 0.2 to 25.4 +/- 1.3 nmol/mg of protein (P < 0.001; N = 9). 2,4-Diamino-6-hydroxypyrimidine (6 mM) reduced lipopolysaccharide/interferon-gamma-induced nitrite production by 53.1 +/- 3.4% Sepiapterin, a substrate for tetrahydrobiopterin synthesis via the dihydrofolate reductase-dependent pterin salvage pathway, prevented the inhibition by 2,4-diamino-6-hydroxypyrimidine, an effect that was blocked by methotrexate. In conclusion, guanosine triphosphate cyclohydrolase I activity is required for cytokine-induced nitric oxide production by proximal tubular epithelium. The inhibition of guanosine triphosphate cyclohydrolase I could prove useful in the treatment of nitric oxide-mediated renal disorders. C1 UNIV FLORIDA,COLL MED,DEPT PHARMACOL,GAINESVILLE,FL 32610. UNIV FLORIDA,COLL MED,DIV NEPHROL HYPERTENS & TRANSPLANTAT,GAINESVILLE,FL. HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,DIV PEDIAT NEPHROL,BOSTON,MA. FU NHLBI NIH HHS [HL43131, HL48455]; NIAAA NIH HHS [AA09888] NR 33 TC 7 Z9 7 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD FEB PY 1995 VL 5 IS 8 BP 1630 EP 1633 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA QH761 UT WOS:A1995QH76100014 PM 7756597 ER PT J AU ACKERMAN, RH AF ACKERMAN, RH TI NEUROIMAGING LOOKS TO THE FUTURE SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Editorial Material RP ACKERMAN, RH (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,NEUROMUSCULAR LAB,GRAY 2 GRB 285,BOX 9657,BOSTON,MA 02114, USA. NR 9 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD FEB PY 1995 VL 128 IS 2 BP 117 EP 121 DI 10.1016/0022-510X(94)00257-O PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA QD562 UT WOS:A1995QD56200001 PM 7738587 ER PT J AU DELAMONTE, SM BHAVANI, K XU, YY PUISIEUX, A WANDS, JR AF DELAMONTE, SM BHAVANI, K XU, YY PUISIEUX, A WANDS, JR TI MODULATION OF P36 GENE-EXPRESSION IN HUMAN NEURONAL CELLS SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article DE P36; ANNEXIN II; CENTRAL NERVOUS SYSTEM NEOPLASMS; PRIMITIVE NEUROECTODERMAL TUMORS; RETINOIC ACID; ETHANOL; INSULIN ID TYROSINE KINASE SUBSTRATE; ROUS-SARCOMA VIRUS; HEPATOCYTE DNA-SYNTHESIS; NON-ERYTHROID SPECTRIN; FACTOR RECEPTOR-KINASE; CALPACTIN-I; BINDING PROTEINS; HEAVY-CHAIN; PHOSPHOLIPID-BINDING; LIPOCORTIN-1 IMMUNOREACTIVITY AB p36 is a calcium/lipid-binding phosphoprotein that is expressed at high levels in proliferating and transformed cells, and at low levels in terminally differentiated cells, such as CNS neurons. The calcium-dependent binding to membrane phospholipids, and its capacity to interact with intermediate filament proteins suggest that p36 may be involved in the transduction of extracellular signals. The present work examines p36 gene expression in the mature CNS, primary primitive neuroectodermal tumors (PNETs), and transformed PNET cell lines. p36 immunoreactivity was not observed in normal adult human brain, but low levels of the protein were detected by Western blot analysis. Following acute anoxic cerebral injury, the mean levels of p36 protein were elevated two-fold, and injured neurons exhibited increased p36 immunoreactivity. This phenomenon was likely to have been mediated by post-transcriptional mechanisms since there was no corresponding change in the level p36 mRNA. p36 immunoreactivity was detected in 8 of 9 primary PNETs, and in 3 of 3 neurofilament-expressing PNET cell lines. The levels of p36 protein in PNET cell lines were 5-fold higher than in adult human brain tissue. Although p36 gene expression was generally high in proliferating PNET cells, the levels of p36 mRNA and protein were not strictly correlated with DNA synthesis. Instead, p36 gene expression was modulated in both proliferating and non-proliferating PNET cell cultures by treatment with 50 mIU/ml of insulin, 100 mM ethanol, or 5 mu M retinoic acid. The frequent discordances observed experimentally and in vivo between p36 mRNA and p36 protein expression suggest that the steady-state levels of p36 protein in neuronal cells may be regulated primarily by post-transcriptional mechanisms. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,MGH CANC CTR,BOSTON,MA 02129. RP DELAMONTE, SM (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,DIV NEUROPATHOL,ROOM 7308,MGH E,149 13TH ST,BOSTON,MA 02129, USA. FU NCI NIH HHS [CA-49832, CA-35711]; NINDS NIH HHS [NS-29793] NR 57 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD FEB PY 1995 VL 128 IS 2 BP 122 EP 133 DI 10.1016/0022-510X(94)00218-D PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA QD562 UT WOS:A1995QD56200002 PM 7738588 ER PT J AU FISCHMAN, AJ BABICH, JW BARROW, SA GRAHAM, W CARTER, E TOMPKINS, RG RUBIN, RH AF FISCHMAN, AJ BABICH, JW BARROW, SA GRAHAM, W CARTER, E TOMPKINS, RG RUBIN, RH TI DETECTION OF ACUTE BACTERIAL-INFECTION WITHIN SOFT-TISSUE INJURIES USING A TC-99M-LABELED CHEMOTACTIC PEPTIDE SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article DE CHEMOTACTIC PEPTIDE; TC-99M; RABBITS; GAMMA CAMERA IMAGING ID IMAGING FOCAL SITES; TC-99M-HMPAO LABELED LEUKOCYTES; POLYCLONAL IGG; IN-111; INFLAMMATION; ANALOGS; CELLS; RATS AB Objective: Infection imaging with a Tc-99m-labeled chemotactic peptide was evaluated in a rabbit model of Escherichia coli infections in burned tissue. Materials and Methods: The peptide was radiolabeled with Te-99m via the hydrazino nicotinamide derivative. Three groups of six animals were studied: (group A) unilateral infected burns; (group B) bilateral burns with unilateral infection; and (group C) uninfected burns. Twenty-four hours after injury, groups A and B were infected, and 8 hours later, all animals were injected with similar to 0.50 mCi of Tc-99m-peptide. Measurements and Main Results: In groups A and B, excellent images of the infections were obtained at 3 to 4 and 16 to 18 hours after injection of the peptide. At 3 to 4 hours after injection, the target-to-background ratios (T/B) were 3.12 +/- 0.28 for group A and 4.33 +/- 0.61 for group B (p = n.s.). At 16 to 18 hours; the T/B ratios increased significantly (p < 0.01): group A = 8.10 +/- 1.03 and B = 7.70 +/- 1.25. The T/B ratio for group C was only slightly greater than unity. Conclusions: These results indicate that Tc-99m-labeled chemotactic peptides are effective radiopharmaceuticals for the rapid detection of focal sites of infection within thermally injured tissues. C1 MASSACHUSETTS GEN HOSP,SHRINERS BURNS INST,MED SERV,CLIN INVEST PROGRAM,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,SHRINERS BURNS INST,TRAUMA SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT RADIOL,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA. RP FISCHMAN, AJ (reprint author), MASSACHUSETTS GEN HOSP,SHRINERS BURNS INST,DEPT RADIOL,DIV NUCL MED,32 FRUIT ST,BOSTON,MA 02114, USA. NR 29 TC 13 Z9 15 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1079-6061 J9 J TRAUMA JI J. Trauma-Injury Inf. Crit. Care PD FEB PY 1995 VL 38 IS 2 BP 223 EP 227 DI 10.1097/00005373-199502000-00013 PG 5 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA QK157 UT WOS:A1995QK15700013 PM 7869440 ER PT J AU SHERIDAN, RL RYAN, CM LEE, MJ MUELLER, PR TOMPKINS, RG AF SHERIDAN, RL RYAN, CM LEE, MJ MUELLER, PR TOMPKINS, RG TI PERCUTANEOUS CHOLECYSTOSTOMY IN THE CRITICALLY ILL BURN PATIENT SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article DE ACUTE CHOLECYSTITIS; MINIMALLY INVASIVE PROCEDURES; MULTIPLE ORGAN FAILURE; BURNS ID ACALCULOUS CHOLECYSTITIS; COMPLICATION; DIAGNOSIS AB Objective: We desired to demonstrate the utility of percutaneous cholecystostomy in the evaluation and management of critically ill burn patients with fever and rising cholestatic chemistries. Design: Retrospective review. Materials and Methods: Over a 2 1/2-year period there were 411 admissions to a regional adult burn unit of whom six patients (1.5%) were strongly suspected of having developed acute cholecystitis. Five were managed with percutaneous cholecystostomy. Measurements and Main Results: All patients had sonographic signs consistent with acute cholecystitis. One was managed with immediate laparotomy and the remaining five patients underwent ultrasound-guided percutaneous transhepatic cholecystostomy at the bedside (n = 4) or in the ultrasonography suite (n 1) without complication. One patient died of multiple organ failure 3 days after catheter placement despite good catheter position and function. Two of the surviving patients responded promptly to drainage of the gallbladder with resolution of fever and normalization of liver function tests. Two patients did not respond despite catheters that were properly placed and functioning, reliably eliminating the diagnosis of acute cholecystitis. One patient underwent interval cholecystectomy after wound closure and the remaining patients were discharged after catheters were removed. Conclusions: Bedside percutaneous cholecystostomy is a minimally invasive procedure that can facilitate the evaluation and management of the critically ill burn patient with fever and rising cholestatic chemistries in whom a diagnosis of acute cholecystitis is suspected. C1 MASSACHUSETTS GEN HOSP,SURG SERV,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA. MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA. RP SHERIDAN, RL (reprint author), SHRINERS BURN INST,51 BLOSSOM ST,BOSTON,MA 02114, USA. FU NIGMS NIH HHS [T32 GM07035, P50 GM21700] NR 18 TC 9 Z9 10 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1079-6061 J9 J TRAUMA JI J. Trauma-Injury Inf. Crit. Care PD FEB PY 1995 VL 38 IS 2 BP 248 EP 251 DI 10.1097/00005373-199502000-00019 PG 4 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA QK157 UT WOS:A1995QK15700019 PM 7869446 ER PT J AU CARR, MC BENACERRAF, BR ESTROFF, JA MANDELL, J AF CARR, MC BENACERRAF, BR ESTROFF, JA MANDELL, J TI PRENATALLY DIAGNOSED BILATERAL HYPERECHOIC KIDNEYS WITH NORMAL AMNIOTIC-FLUID - POSTNATAL OUTCOME SO JOURNAL OF UROLOGY LA English DT Article DE ULTRASONOGRAPHY, PRENATAL; KIDNEY; AMNIOTIC FLUID ID RENAL PARENCHYMAL ECHOGENICITY; DISEASE AB We evaluated a subset of infants with bilateral markedly hyperechoic ''bright'' kidneys noted prenatally in association with normal amniotic fluid volume during gestation. Prenatal ultrasound showed increased renal parenchymal echogenicity bilaterally with preservation of the medullary pyramid architecture. These children were followed for up to 3 years to determine potential changes in the sonographic appearance of the echogenic renal parenchyma and to assess renal function. In 3 years 8 cases of bilateral hyperechoic fetal kidneys were identified. During postnatal followup renal echogenicity resolved in 4 cases, diminished in 1 and remained the same in 3. The serum creatinine and electrolytes were normal in all cases followed for more than 3 months. Other renal findings included vesicoureteral reflux in 2 of 7 cases, mild pelvic ectasia in 1 and tiny medullary calcifications in 1. The specific etiology of increased echogenicity is unknown, although 1 infant appeared to have a form of autosomal recessive disease with liver hyperechogenicity as well. We conclude that fetuses with bilateral hyperechoic kidneys associated with normal amniotic fluid volume have a favorable outcome. Ultrasonographic finding of marked parenchymal hyperechogenicity appears to improve with time; in our experience renal function is normal and the infants thrive. Continued followup is necessary to determine the long-term natural history of this phenomenon, as is subsequent prenatal and postnatal evaluation of future siblings to assess genetic risk. C1 CHILDRENS HOSP,DEPT SURG,DIV UROL,BOSTON,MA 02115. CHILDRENS HOSP,DEPT RADIOL,DIV UROL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT OBSTET & GYNECOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 13 TC 19 Z9 19 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 FEB PY 1995 VL 153 IS 2 BP 442 EP 444 DI 10.1097/00005392-199502000-00051 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA QA146 UT WOS:A1995QA14600052 PM 7815614 ER PT J AU HAMDAN, AD AIELLO, LP QUIST, WC OZAKI, CK CONTRERAS, MA PHANEUF, MD RUIZ, C KING, GL LOGERFO, FW AF HAMDAN, AD AIELLO, LP QUIST, WC OZAKI, CK CONTRERAS, MA PHANEUF, MD RUIZ, C KING, GL LOGERFO, FW TI ISOLATION OF GENES DIFFERENTIALLY EXPRESSED AT THE DOWNSTREAM ANASTOMOSIS OF PROSTHETIC ARTERIAL GRAFTS WITH USE OF MESSENGER-RNA DIFFERENTIAL DISPLAY SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 42nd Scientific Meeting of the International-Society-for-Cardiovascular-Surgery, North-American-Chapter CY JUN 06, 1994 CL SEATTLE, WA SP INT SOC CARDIOVASC SURG, N AMER CHAPTER ID SMOOTH-MUSCLE CELL; HUMAN-BREAST-CANCER; MESSENGER-RNAS; PROLIFERATION; CLONING; EXTRACTION; INJURY; DNA AB Purpose: Downstream anastomotic intimal hyperplasia in prosthetic arterial grafts remains a major cause of delayed graft failure. The new method of messenger RNA (mRNA) differential display was used to screen numerous genes to gain insight into the molecular mechanisms of intimal hyperplasia. Methods: Fifty-centimeter-long 8 mm expanded polytetrafluoroethylene grafts were placed in four mongrel dogs from the carotid artery to the distal abdominal aorta. At 3 months the distal anastomoses and adjacent normal aortas were harvested; a portion was taken for histologic examination, and total RNA was isolated from the remainder. Differential mRNA display was used to identify candidate cDNA clones whose expression differed in anastomotic intimal hyperplasia as compared with adjacent unaffected aorta. The clones were sequenced, and national gene databases were searched. Northern blot analysis confirmed alteration of gene expression. Results: Approximately 5000 mRNA species mere screened, and 11 candidate clones were obtained. DNA sequence revealed homology of five clones to known gene sequences. Homologous genes included an interferon-gamma-induced human gene, (IGUP I-5111), alpha-1 protease inhibitor gene, human retinoblastoma susceptibility gene, and human creatine kinase gene (two clones). Northern blot analysis revealed altered gene expression in 4 of 11, nonregulation in 1 of 11, and undetectable signals in 6 of 11. Expression of the clone representing IGUP I-5111 in the segment of intimal hyperplasia was found to be decreased over threefold to only 31% +/- 16.4% SE of the level seen in normal aorta. Conclusions: The technique of mRNA differential display has identified differences in gene expression in an in vivo model of anastomotic intimal hyperplasia. Expression of RNA with homology to an interferon-gamma-induced human gene was consistently decreased within the hyperplastic region at the downstream polytetrafluoroethylene arterial anastomosis. C1 NEW ENGLAND DEACONESS HOSP, DEPT PATHOL, BOSTON, MA 02215 USA. HARVARD UNIV, NEW ENGLAND DEACONESS HOSP, SCH MED, BOSTON, MA 02215 USA. JOSLIN DIABET CTR, DIV RES, BOSTON, MA 02215 USA. JOSLIN DIABET CTR, BEETHAM EYE INST, BOSTON, MA 02215 USA. BRIGHAM & WOMENS HOSP, DEPT MED, BOSTON, MA 02115 USA. RP NEW ENGLAND DEACONESS HOSP, DIV VASC SURG, 110 FRANCIS ST, SUITE 5F, BOSTON, MA 02215 USA. RI Ozaki, C Keith/A-4937-2013 FU NEI NIH HHS [EY05110]; NHLBI NIH HHS [HL-217906-13, T32-HL07734-01A1] NR 29 TC 14 Z9 14 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD FEB PY 1995 VL 21 IS 2 BP 228 EP 234 DI 10.1016/S0741-5214(95)70264-4 PG 7 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA QH668 UT WOS:A1995QH66800006 PM 7853596 ER PT J AU PROVOOST, AP BROWN, DM DALY, MJ LANDER, ES JACOB, HJ AF PROVOOST, AP BROWN, DM DALY, MJ LANDER, ES JACOB, HJ TI IDENTIFICATION OF RF-1, A GENE RESPONSIBLE FOR RENAL-FAILURE IN THE FAWN-HOODED (FHH) RAT SO KIDNEY INTERNATIONAL LA English DT Meeting Abstract C1 ERASMUS UNIV ROTTERDAM,DEPT PEDIAT SURG,3000 DR ROTTERDAM,NETHERLANDS. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CARDIOVASC RES CTR,BOSTON,MA. MIT,CTR GENOME,WHITEHEAD INST BIOMED RES,CAMBRIDGE,MA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD FEB PY 1995 VL 47 IS 2 BP 702 EP 702 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA QD321 UT WOS:A1995QD32100249 ER PT J AU ODA, T TAMURA, S MATSUGUCHI, T GRIFFIN, JD DRUKER, BJ AF ODA, T TAMURA, S MATSUGUCHI, T GRIFFIN, JD DRUKER, BJ TI THE SH2 DOMAIN OF ABL IS NOT REQUIRED FOR FACTOR-INDEPENDENT GROWTH INDUCED BY BCR-ABL IN A MURINE MYELOID CELL-LINE SO LEUKEMIA LA English DT Article DE CML; BCR-ABL; PHILADELPHIA CHROMOSOME ID CHRONIC MYELOGENOUS LEUKEMIA; CHRONIC MYELOCYTIC-LEUKEMIA; MIDDLE-T-ANTIGEN; PHILADELPHIA-CHROMOSOME; C-SRC; TYROSINE PHOSPHORYLATION; POINT MUTATIONS; V-ABL; PROTEIN; TRANSFORMATION AB Chronic myelogenous leukemia (CML) is characterized by the presence of a specific chromosomal translocation between the long arms of chromosomes 9 and 22 that results in the fusion of BCR encoded sequences upstream of exon 2 of c-ABL. This fusion gene produces a 210-kDa chimeric BCR-ABL protein that has elevated tyrosine kinase activity. Several substrates of this activated tyrosine kinase have been reported. However, their necessity for the transforming functions of BCR-ABL has not been determined. A specific deletion of the SH2 domain of ABL was created to determine whether this mutation would after the ability of BCR-ABL to induce factor-independent growth of a murine myeloid cell line and to determine whether the SH2 domain mediates the interaction of BCR-ABL with any of its substates. Our results indicate that the SH2 domain of BCR-ABL is not required for the induction of growth factor independence and is not required for the association of BCR-ABL with rasGAP or SHC. However, myeloid cells expressing this mutant lack the tyrosine phosphorylation of a 62-kDa rasGAP associated protein. C1 OREGON HLTH SCI UNIV,DIV HEMATOL & MED ONCOL L586,PORTLAND,OR 97201. DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA. FU NCI NIH HHS [CA01422, CA36167] NR 41 TC 39 Z9 39 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS SN 0887-6924 J9 LEUKEMIA JI Leukemia PD FEB PY 1995 VL 9 IS 2 BP 295 EP 301 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA QP687 UT WOS:A1995QP68700013 PM 7869767 ER PT J AU HARRIS, MB CANTOR, AB GOORIN, AM SHOCHAT, SJ AYALA, AG FERGUSON, WS HOLBROOK, T LINK, MP AF HARRIS, MB CANTOR, AB GOORIN, AM SHOCHAT, SJ AYALA, AG FERGUSON, WS HOLBROOK, T LINK, MP TI TREATMENT OF OSTEOSARCOMA WITH IFOSFAMIDE - COMPARISON OF RESPONSE IN PEDIATRIC-PATIENTS WITH RECURRENT DISEASE VERSUS PATIENTS PREVIOUSLY UNTREATED - A PEDIATRIC-ONCOLOGY-GROUP STUDY SO MEDICAL AND PEDIATRIC ONCOLOGY LA English DT Article DE OSTEOSARCOMA; IFOSFAMIDE; PHASE II STUDY; METASTATIC OSTEOSARCOMA AT DIAGNOSIS ID HIGH-DOSE IFOSFAMIDE; OSTEO-SARCOMA; MESNA; CHEMOTHERAPY; TUMOR AB This study was designed to test if the activity of a phase II agent, ifosfamide, would have been underestimated if it was tested exclusively in a population of children and young adults with recurrent osteosarcoma. The response rate to ifosfamide was compared in patients younger than 30 years of age with previously untreated osteosarcoma with metastases at diagnosis and/or unresectable primary tumors (stratum 1) with that of patients with recurrent osteosarcoma following adjuvant chemotherapy who were not previously exposed to ifosfamide (stratum 2). Evaluation of response was conducted 3 weeks after two courses of ifosfamide (2400 mg/m(2) x 5 days) were administered 3 weeks apart. Nine of 33 (27%) evaluable patients in stratum 1 responded (1 complete and 8 partial responses) to ifosfamide. Among 30 evaluable patients in stratum 2, only 3 (10%) responded (1 complete and 2 partial responses; P=.04) Both groups of patients received equal doses of ifosfamide and experienced comparable toxicities. Results from this study suggest that the activity of new agents will be underestimated if tested in a population of heavily pretreated patients with recurrent disease. When possible, new chemotherapeutic agents should be tested in patients with a poor prognosis who have not been exposed to chemotherapy. (C) 1995 Wiley-Liss, Inc. C1 UNIV MED & DENT NEW JERSEY,HACKENSACK MED CTR,TOMORROWS CHILDRENS INST,HACKENSACK,NJ. POG,STAT OFF,GAINESVILLE,FL. CHILDRENS HOSP,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA. STANFORD UNIV,SCH MED,STANFORD,CA 94305. MD ANDERSON CANC CTR,HOUSTON,TX. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. E CAROLINA UNIV,SCH MED,GREENVILLE,NC. FU NCI NIH HHS [1U10 CA-35906, CA29139, CA30969] NR 15 TC 65 Z9 66 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0098-1532 J9 MED PEDIATR ONCOL JI Med. Pediatr. Oncol. PD FEB PY 1995 VL 24 IS 2 BP 87 EP 92 DI 10.1002/mpo.2950240205 PG 6 WC Oncology; Pediatrics SC Oncology; Pediatrics GA QH469 UT WOS:A1995QH46900004 PM 7990769 ER PT J AU STERLING, K BRENNER, MA AF STERLING, K BRENNER, MA TI THYROID-HORMONE ACTION - EFFECT OF TRIIODOTHYRONINE ON MITOCHONDRIAL ADENINE-NUCLEOTIDE TRANSLOCASE IN-VIVO AND IN-VITRO SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID RAT-LIVER MITOCHONDRIA; BINDING-SITES; GENE-EXPRESSION; RECEPTOR; LOCALIZATION; MEMBRANE; PATHWAY; STIMULATION; THYMOCYTES; KIDNEY AB Adenine nucleotide translocase (AdNT) levels were measured as the exchange of extramitochondrial against intramitochondrial adenosine diphosphate (ADP) in liver, spleen, and testes mitochondria isolated from normal and hypothyroid rats using the ''back-exchange'' and atractyloside-stop method of Pfaff and Klingenberg. The results provide confirmation of previous reports that mitochondria from hypothyroid rats show a markedly diminished AdNT activity, which is restored to normal levels within 72 hours by intraperitoneal injection of 10 to 20 mu g triiodothyronine (T-3)/100 g bodyweight. The latter dose was found in dose-response studies to result in maximal stimulation of AdNT in liver mitochondria. Qualitatively similar results on AdNT activity were obtained in liver mitochondria within 30 to 60 minutes following intravenous injection into hypothyroid rats of a more physiological dose of T-3 (40 ng/100 g body weight). AdNT in mitochondria isolated from spleen and testes (organs that do not exhibit a calorigenic response after administration of thyroid hormone to the whole animal) failed to respond to thyroidectomy and to administration of T-3. More recently, we have observed that in vitro replacement of T-3 also stimulates AdNT activity in hypothyroid liver mitochondria. The enzyme adenosine triphosphate (ATP) synthase was examined as another possible candidate for direct hormonal stimulation of mitochondria. Simultaneous determinations on the same rats after intraperitoneal injection of T-3 (20 mu g/100 g body weight) showed little or no effect on ATP synthase until after 37 to 85 hours, whereas enhanced activity of the translocator was regularly observed at 17 hours. These findings support the view that AdNT, which is considered to exert major control over the rate of oxidative phosphorylation, may be a direct target of Tg action on the mitochondria. Increased nuclear transcription may be regarded as a sustained delayed effect of T-3 administration, in contrast to the early effect an mitochondrial AdNT. A bolus intravenous injection of T-3 into the hypothyroid rat increases the activity of the mitochondrial carrier AdNT within a matter of minutes as an early direct effect, as also suggested by studies of addition of Tg in vitro to isolated rat liver mitochondria. In contrast, nuclear effects require 12 to 24 hours to show increased transcription, evidenced by increased specific mRNA directing the formation of more AdNT (Luciakova and Nelson). Copyright (C) 1995 by W.B. Saunders Company C1 BRONX VET ADM MED CTR,BRONX,NY. RP STERLING, K (reprint author), COLUMBIA UNIV,COLL PHYS & SURG,DEPT MED,630 W 168TH ST,NEW YORK,NY 10032, USA. FU NIDDK NIH HHS [DK 37870] NR 45 TC 29 Z9 30 U1 0 U2 1 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 1995 VL 44 IS 2 BP 193 EP 199 DI 10.1016/0026-0495(95)90264-3 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QJ039 UT WOS:A1995QJ03900011 PM 7869915 ER PT J AU RAVICHANDRAN, KS LORENZ, U SHOELSON, SE BURAKOFF, SJ AF RAVICHANDRAN, KS LORENZ, U SHOELSON, SE BURAKOFF, SJ TI INTERACTION OF SHC WITH GRB2 REGULATES ASSOCIATION OF GRB2 WITH MSOS SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID RECEPTOR TYROSINE KINASES; NUCLEOTIDE EXCHANGE; SIGNAL TRANSDUCTION; RAS; PROTEIN; ACTIVATION; DOMAIN; PHOSPHORYLATION; 3-KINASE; BINDING AB The adapter protein She has been implicated in Ras signaling via many receptors, including the T-cell antigen receptor (TCR), B-cell antigen receptor, interleukin-2 receptor, interleukin-3 receptor, erythropoietin receptor, and insulin receptor. Moreover, transformation via polyomavirus middle T antigen is dependent on its interaction with She and She tyrosine phosphorylation. One of the mechanisms of TCR-mediated, tyrosine kinase-dependent Ras activation involves the simultaneous interaction of phosphorylated She with the TCR zeta chain and with a second adapter protein, Grb2. Grb2, in turn, interacts with the Ras guanine nucleotide exchange factor mSOS, thereby leading to Ras activation. Although it has been reported that in fibroblasts Grb2 and mSOS constitutively associate with each other and that growth factor stimulation does not alter the levels of Grb2:mSOS association, we show here that TCR stimulation leads to a significant increase in the levels of Grb2 associated with mSOS. This enhanced Grb2:mSOS association, which occurs through an SH3-proline-rich sequence interaction, is regulated through the SH2 domain of Grb2. The following observations support a role for She in regulating the Grb2:mSOS association: (i) a phosphopeptide corresponding to the sequence surrounding Tyr-3l7 of She, which displaces She from Grb2, abolished the enhanced association between Grb2 and mSOS; and (ii) addition of phosphorylated She to unactivated T cell lysates was sufficient to enhance the interaction of Grb2 with mSOS. Furthermore, using fusion proteins encoding different domains of She, we show that the collagen homology domain of She (which includes the Tyr-317 site) can mediate this effect. Thus, the She-mediated regulation of Grb2:mSOS association may provide a means for controlling the extent of Ras activation following receptor stimulation. C1 HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,JOSLIN DIABET CTR,DEPT MED,BOSTON,MA 02115. BETH ISRAEL HOSP,MOLEC MED UNIT,BOSTON,MA 02215. RP RAVICHANDRAN, KS (reprint author), DANA FARBER CANC INST,DIV PEDIAT ONCOL,RM 1722,44 BINNEY ST,BOSTON,MA 02115, USA. NR 35 TC 159 Z9 159 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD FEB PY 1995 VL 15 IS 2 BP 593 EP 600 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QC385 UT WOS:A1995QC38500001 PM 7529871 ER PT J AU BLOBEL, GA SIMON, MC ORKIN, SH AF BLOBEL, GA SIMON, MC ORKIN, SH TI RESCUE OF GATA-1-DEFICIENT EMBRYONIC STEM-CELLS BY HETEROLOGOUS GATA-BINDING PROTEINS SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID GLOBIN GENE-EXPRESSION; ERYTHROID TRANSCRIPTION FACTOR; DNA-BINDING; ENDOTHELIAL-CELLS; HYPERSENSITIVE SITE; TRANSGENIC MICE; DIFFERENTIATION; FAMILY; FINGER; SPECIFICITY AB Totipotent murine embryonic stem (ES) cells can be differentiated in vitro to form embryoid bodies (EBs) containing hematopoietic cells of multiple lineages, including erythroid cells. In vitro erythroid development parallels that which is observed in vivo. ES cells in which the gene for the erythroid transcription factor GATA-1 has been disrupted fail to produce mature erythroid cells either in vivo or in vitro. With the EB in vitro differentiation assay, constructs expressing heterologous GATA-binding proteins were tested for their abilities to correct the developmental defect of GATA-1-deficient ES cells. The results presented here show that the highly divergent chicken GATA-1 can rescue GATA-1 deficiency to an extent similar to that of murine GATA-1 (mGATA-1), as determined by size and morphology of EBs, presence of red cells, and globin gene expression. Furthermore, GATA-3 and GATA-4, which are normally expressed in different tissues, and a protein consisting of the zinc fingers of GATA-1 fused to the herpes simplex virus VP16 transcription activation domain were able to compensate for the GATA-1 defect. Chimeric molecules in which both zinc fingers of mGATA-1 were replaced with the zinc fingers of human GATA-3 or with the single finger of the fungal GATA factor areA, as well as a construct bearing the zinc finger region alone, displayed rescue activity. These results suggest that neither the transcription activation domains of mGATA-1 nor its zinc fingers impart erythroid cell specificity for its action in vivo. Rather, it appears that specificity is mediated through the cis-acting control regions which determine spatial and temporal expression of the GATA-1 gene. Furthermore, our results demonstrate that the zinc finger region may have a biological function in addition to mediating DNA binding. C1 HARVARD UNIV,CHILDRENS HOSP,SCH MED,DANA FARBER CANC INST,DEPT PEDIAT,DIV HEMATOL ONCOL,BOSTON,MA 02115. HOWARD HUGHES MED INST,BOSTON,MA 02115. NR 44 TC 71 Z9 71 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD FEB PY 1995 VL 15 IS 2 BP 626 EP 633 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QC385 UT WOS:A1995QC38500004 PM 7823931 ER PT J AU QIN, XQ LIVINGSTON, DM EWEN, M SELLERS, WR ARANY, Z KAELIN, WG AF QIN, XQ LIVINGSTON, DM EWEN, M SELLERS, WR ARANY, Z KAELIN, WG TI THE TRANSCRIPTION FACTOR E2F-1 IS A DOWNSTREAM TARGET OF RE ACTION SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID RETINOBLASTOMA GENE-PRODUCT; LARGE T-ANTIGEN; CELL-CYCLE REGULATION; SV40 LARGE-T; SUSCEPTIBILITY GENE; C-MYC; BINDING PROTEIN; RB PROTEIN; GROWTH SUPPRESSION; COMPLEX-FORMATION AB Reintroduction of RE into SAOS2 (RB(-/-)) cells causes a G(1) arrest and characteristic cellular swelling. Coexpression of the cellular transcription factor E2F-1 could overcome these effects. The ability of E2F-1 to bind to RE was neither necessary nor sufficient for this effect, and S phase entry was not accompanied by RE hyperphosphorylation under these conditions. Furthermore, E2F-1 could overcome the actions of a nonphosphorylatable but otherwise intact RE mutant. These data, together with the fact that RE binds to E2F-1 in vivo, suggest that E2F-1 is a downstream target of RE action. Mutational analysis showed that the ability of E2F-1 to bind to DNA was necessary and sufficient to block the formation of large cells by RE, whereas the ability to induce S-phase entry required a functional transactivation domain as well. Thus, the induction of a G(1) arrest and the formation of large cells by RE in these cells can be genetically dissociated. Furthermore, the ability of the E2F-1 DNA-binding domain alone to block one manifestation of RE action is consistent with the notion that RB-E2F complexes actively repress transcription upon binding to certain E2F-responsive promoters. In keeping with this view, we shea here that coproduction of an E2F1 mutant capable of binding to DNA, yet unable to transactivate, is sufficient to block RB-mediated transcriptional repression. C1 DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 99 TC 162 Z9 163 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD FEB PY 1995 VL 15 IS 2 BP 742 EP 755 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QC385 UT WOS:A1995QC38500016 PM 7823942 ER PT J AU WEAVER, DR DEEDS, JD LEE, KC SEGRE, GV AF WEAVER, DR DEEDS, JD LEE, KC SEGRE, GV TI LOCALIZATION OF PARATHYROID HORMONE-RELATED PEPTIDE (PTHRP) AND PTH/PTHRP RECEPTOR MESSENGER-RNAS IN RAT-BRAIN SO MOLECULAR BRAIN RESEARCH LA English DT Article DE IN SITU HYBRIDIZATION; BRAIN MAPPING; NEUROPEPTIDE; GENE EXPRESSION ID MESSENGER RIBONUCLEIC-ACIDS; MEDIAL BASAL HYPOTHALAMUS; CENTRAL-NERVOUS-SYSTEM; CHRONIC-RENAL-FAILURE; MOLECULAR-CLONING; ADENOSINE-A2 RECEPTOR; HUMORAL HYPERCALCEMIA; EXPRESSION; CALCIUM; TISSUES AB Parathyroid hormone (PTH)-related peptide (PTHrP) has been identified in human tumors associated with the syndrome of humoral hypercalcemia of malignancy. PTHrP mRNA is also expressed in a variety of non-malignant tissues, suggesting that PTHrP is an endogenous peptide with as-yet unidentified autocrine or paracrine functions in normal tissues, including brain (Weir et al., Proc. Natl. Acad. Sci., 87 (1990) 108-112). In the present study, we used in situ hybridization to examine the expression of PTHrP and the common receptor for PTH and PTHrP in adult rat brain. Widespread yet anatomically discrete patterns of hybridization were observed using S-35-labeled antisense cRNA probes. PTHrP gene expression was highest in the supramamillary nucleus of the hypothalamus, medial superior olivary nucleus, and in subpopulations of cells in the neostriatum, hippocampus, and cerebral cortex. Other major sites of PTHrP gene expression included the amygdala, midline thalamic nuclei, pontine nuclei, choroid plexus, and the anterior pituitary gland. Highest levels of PTH/PTHrP receptor mRNA were in the mesencephalic portion of the trigeminal nucleus and the trigeminal ganglion, the lateral reticular, pontine and reticulotegmental nuclei, the hypoglossal nucleus and area postrema. Other major sites of PTH/PTHrP receptor expression included the anterodorsal nucleus of the thalamus, basolateral amygdala, entorhinal cortex, parasubiculum, cells in the Purkinje cell layer of the cerebellum, vestibular nuclei, ventral cochlear nucleus, the motor nucleus of the trigeminal, and the facial and external cuneate nuclei. The expression of genes encoding PTHrP and its receptor in discrete areas of the brain suggests that PTHrP may function as a neurotransmitter in the central nervous system. C1 HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA. MASSACHUSETTS GEN HOSP,DEPT MED,ENDOCRINE UNIT,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. RP WEAVER, DR (reprint author), MASSACHUSETTS GEN HOSP,DEV CHRONOBIOL LAB,CHILDRENS SERV,JACKSON BLDG,ROOM 1226,GRJ 1226,BOSTON,MA 02114, USA. NR 44 TC 61 Z9 61 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD FEB PY 1995 VL 28 IS 2 BP 296 EP 310 DI 10.1016/0169-328X(94)00222-Z PG 15 WC Neurosciences SC Neurosciences & Neurology GA QE617 UT WOS:A1995QE61700013 ER PT J AU LEE, JW CHOI, HS GYURIS, J BRENT, R MOORE, DD AF LEE, JW CHOI, HS GYURIS, J BRENT, R MOORE, DD TI 2 CLASSES OF PROTEINS DEPENDENT ON EITHER THE PRESENCE OR ABSENCE OF THYROID-HORMONE FOR INTERACTION WITH THE THYROID-HORMONE RECEPTOR SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID RETINOIC ACID RECEPTORS; DNA-BINDING; CONFORMATIONAL-CHANGES; TRANSCRIPTION FACTORS; AUXILIARY PROTEIN; RESPONSE ELEMENTS; ADP-RIBOSYLATION; NUCLEAR PROTEINS; X-RECEPTOR; ACTIVATION AB The thyroid hormone (T-3) receptors (TRs) are hormone-dependent transcription factors that regulate expression of a variety of specific target genes. To help elucidate the mechanisms that underlie this transcriptional regulation and other potential TR activities, we used the yeast interaction trap to isolate clones encoding proteins that specifically interact with the ligand binding domain of the rat TR beta. Several such proteins, called Trips (TR- interacting proteins), were isolated from independent selections carried out either in the presence or absence of T-3. Surprisingly, all of the Trips were dependent on hormone for interaction with the TR, with some interacting only when T-3 is present and others only when it is absent. Nearly all of the Trips also show similar ligand-dependent interaction with the retinoid X receptor (RXR), but none interact with the glucocorticoid receptor under any conditions. The sequences of three of the Trips predict specific functional roles: one is an apparent human homolog of a yeast transcriptional coactivator, one is a new member of a class of nonhistone chromosomal proteins, and one contains a conserved domain associated with ubiquitination of specific target proteins. Consistent with the pleiotropic effects of TR and RXR, several other Trips show significant amino acid sequence similarity with proteins involved in various regulatory pathways. The inherent transcriptional activity of the Trips was tested in yeast, and a chimeric protein consisting of a fusion of Trip4 to the bacterial LexA repressor protein is a relatively strong transcriptional activator. Similar LexA fusions to Trip9 and Trip10 had no transcriptional activity on their own but, when coexpressed with both TR and RXR, conferred T-3-dependent activation to a reporter gene controlled by LexA binding sites. We suggest that this indirect T-3 response provides a novel mechanism for hormonal activation of gene expression, and that studies of the Trips will provide important insights into the specific mechanisms of action of TRs and other receptors. C1 MASSACHUSETTS GEN HOSP, DEPT MOLEC BIOL, BOSTON, MA 02114 USA. RI Tang, Amy/L-3226-2016 OI Tang, Amy/0000-0002-5772-2878 FU NIDDK NIH HHS [R01 DK-43382] NR 70 TC 370 Z9 392 U1 0 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD FEB PY 1995 VL 9 IS 2 BP 243 EP 254 DI 10.1210/me.9.2.243 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QH152 UT WOS:A1995QH15200011 PM 7776974 ER PT J AU MASHAL, RD KOONTZ, J SKLAR, J AF MASHAL, RD KOONTZ, J SKLAR, J TI DETECTION OF MUTATIONS BY CLEAVAGE OF DNA HETERODUPLEXES WITH BACTERIOPHAGE RESOLVASES SO NATURE GENETICS LA English DT Article ID ENDONUCLEASE-VII; GEL-ELECTROPHORESIS; RAPID DETECTION; BASE MUTATIONS; PCR; PRODUCTS; DUPLEXES; GENE AB We have explored the application of the bacteriophage resolvases T4 endonuclease VII and T7 endonuclease I for detecting mutations in genomic DNA. Heteroduplex DNA fragments prepared by amplification from DNA containing known mutations were cleaved by one or both enzymes at nucleotide mismatches created by 3 of 3 short deletions and 13 of 14 point mutations in fragments as large as 940 basepairs. Heteroduplexes representing all four classes of possible single nucleotide mismatches were cleaved, and the sizes of the cleavage products generated correlated with the location of the mutation. We conclude that bacteriophage resolvases may be useful reagents for the rapid screening of DNA for mutations. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV MED ONCOL,BOSTON,MA 02115. RP MASHAL, RD (reprint author), HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT PATHOL,75 FRANCIS ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [K11 CA01556, P20 CA58203] NR 23 TC 102 Z9 110 U1 0 U2 9 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD FEB PY 1995 VL 9 IS 2 BP 177 EP 183 DI 10.1038/ng0295-177 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA QE672 UT WOS:A1995QE67200020 PM 7719346 ER PT J AU POLLOCK, JD WILLIAMS, DA GIFFORD, MAC LI, LL DU, XX FISHERMAN, J ORKIN, SH DOERSCHUK, CM DINAUER, MC AF POLLOCK, JD WILLIAMS, DA GIFFORD, MAC LI, LL DU, XX FISHERMAN, J ORKIN, SH DOERSCHUK, CM DINAUER, MC TI MOUSE MODEL OF X-LINKED CHRONIC GRANULOMATOUS-DISEASE, AN INHERITED DEFECT IN PHAGOCYTE SUPEROXIDE PRODUCTION SO NATURE GENETICS LA English DT Article ID NEUTROPHIL CYTOCHROME-B; NADPH OXIDASE; CHROMOSOMAL LOCATION; GENE; ASPERGILLOSIS; COMPONENT; ABSENCE; MICE; MACROPHAGES; DEFICIENCY AB Chronic granulomatous disease (CGD) is a recessive disorder characterized by a defective phagocyte respiratory burst oxidase, life-threatening pyogenic infections and inflammatory granulomas. Gene targeting was used to generate mice with a null allele of the gene involved in X-linked CGD, which encodes the 91 kD subunit of the oxidase cytochrome b. Affected hemizygous male mice lacked phagocyte superoxide production, manifested an increased susceptibility to infection with Staphylococcus aureus and Aspergillus fumigatus and had an altered inflammatory response in thioglycollate peritonitis. This animal model should aid in developing new treatments for CGD and in evaluating the role of phagocyte-derived oxidants in inflammation. C1 INDIANA UNIV,MED CTR,HERMAN B WELLS CTR PEDIAT RES,DEPT PEDIAT,INDIANAPOLIS,IN 46202. INDIANA UNIV,MED CTR,JAMES WHITCOMB RILEY HOSP CHILDREN,DEPT MED & MOLEC GENET,INDIANAPOLIS,IN 46202. INDIANA UNIV,SCH MED,HOWARD HUGHES MED INST,INDIANAPOLIS,IN 46202. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PEDIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CHILDRENS HOSP,DIV HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,HOWARD HUGHES MED INST,BOSTON,MA 02115. RI Pollock, Jonathan/B-1554-2009 NR 42 TC 597 Z9 603 U1 1 U2 8 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD FEB PY 1995 VL 9 IS 2 BP 202 EP 209 DI 10.1038/ng0295-202 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA QE672 UT WOS:A1995QE67200024 PM 7719350 ER PT J AU FINKEL, TH TUDORWILLIAMS, G BANDA, NK COTTON, MF CURIEL, T MONKS, C BABA, TW RUPRECHT, RM KUPFER, A AF FINKEL, TH TUDORWILLIAMS, G BANDA, NK COTTON, MF CURIEL, T MONKS, C BABA, TW RUPRECHT, RM KUPFER, A TI APOPTOSIS OCCURS PREDOMINANTLY IN BYSTANDER CELLS AND NOT IN PRODUCTIVELY INFECTED-CELLS OF HIV-INFECTED AND SIV-INFECTED LYMPH-NODES SO NATURE MEDICINE LA English DT Article ID CD4+ T-CELLS; ENVELOPE GLYCOPROTEIN; DEATH; AIDS; MECHANISM; DNA; LYMPHOCYTES; DEPLETION; RNA; PCR AB Although 13 years have passed since identification of human immunodeficiency virus-1 (HIV-1) as the cause of AIDS, we do not yet know how HIV kills its primary target, the T cell that carries the CD4 antigen. We and others have shown an increase in the percentage of apoptotic cells among circulating CD4(+) (and CD8(+)) T cells of HIV-seropositive individuals and an increase in frequency of apoptosis with disease progression. However, it is not known if this apoptosis occurs in infected or uninfected T cells. We show here, using in situ labelling of lymph nodes from HIV-infected children and SIV-infected macaques, that apoptosis occurs predominantly in bystander cells and not in the productively infected cells themselves. These data have implications for pathogenesis and therapy, namely, arguing that rational drug therapy may involve combination agents targeting viral replication in infected cells and apoptosis of uninfected cells. C1 UNIV COLORADO,HLTH SCI CTR,DEPT PEDIAT,DENVER,CO 80262. UNIV COLORADO,HLTH SCI CTR,DEPT IMMUNOL,DENVER,CO 80262. UNIV COLORADO,HLTH SCI CTR,DEPT BIOCHEM BIOPHYS & GENET,DENVER,CO 80262. UNIV COLORADO,HLTH SCI CTR,DEPT INFECT DIS,DENVER,CO 80262. UNIV COLORADO,HLTH SCI CTR,DEPT CELL & STRUCT BIOL,DENVER,CO 80262. NCI,PEDIAT BRANCH,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,VIRAL PATHOGENESIS LAB,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. TUFTS UNIV,SCH MED,DIV NEWBORN MED,DEPT PEDIAT,BOSTON,MA 02111. RP FINKEL, TH (reprint author), NATL JEWISH CTR IMMUNOL & RESP MED,DIV BASIC SCI,DEPT PEDIAT,1400 JACKSON ST,DENVER,CO 80206, USA. FU NIAID NIH HHS [P01-AI29903A, R01-AI35513]; PHS HHS [R01-A130575A] NR 34 TC 720 Z9 730 U1 0 U2 10 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 1995 VL 1 IS 2 BP 129 EP 134 DI 10.1038/nm0295-129 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA QX558 UT WOS:A1995QX55800022 PM 7585008 ER PT J AU CAPLAN, D GOW, D MAKRIS, N AF CAPLAN, D GOW, D MAKRIS, N TI ANALYSIS OF LESIONS BY MRI IN STROKE PATIENTS WITH ACOUSTIC-PHONETIC PROCESSING DEFICITS SO NEUROLOGY LA English DT Article ID PURE WORD DEAFNESS; SHORT-TERM-MEMORY; SELECTIVE IMPAIRMENT; CONDUCTION APHASIA; DISCRIMINATION; COMPREHENSION; PERCEPTION; LANGUAGE; SPEECH; VOICE AB We tested 10 aphasic stroke patients for the ability to discriminate and identify English phonemes. All patients underwent MRI and had their scans analyzed morphometrically. Patients with impairments in acoustic-phonetic processing tended to have lesions involving the left posterior supramarginal gyrus and the bordering parietal operculum, an observation further supported by regression and correlation analyses. These results are interpreted as evidence that the region including the left posterior supramarginal gyrus and parietal operculum plays a significant role in acoustic-phonetic processing. C1 MASSACHUSETTS GEN HOSP, NEUROPSYCHOL LAB, BOSTON, MA 02114 USA. FU NIDCD NIH HHS [DC00776] NR 33 TC 104 Z9 104 U1 0 U2 4 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD FEB PY 1995 VL 45 IS 2 BP 293 EP 298 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA QG533 UT WOS:A1995QG53300015 PM 7854528 ER PT J AU CUTRER, FM MOUSSAOUI, S GARRET, C MOSKOWITZ, MA AF CUTRER, FM MOUSSAOUI, S GARRET, C MOSKOWITZ, MA TI THE NONPEPTIDE NEUROKININ-1 ANTAGONIST, RPR-100893, DECREASES C-FOS EXPRESSION IN TRIGEMINAL NUCLEUS CAUDALIS FOLLOWING NOXIOUS CHEMICAL MENINGEAL STIMULATION SO NEUROSCIENCE LA English DT Article ID RAT SPINAL-CORD; GENE-RELATED PEPTIDE; NK1 RECEPTOR ANTAGONIST; SUBSTANCE-P; BINDING-SITES; NEUROGENIC INFLAMMATION; NONPEPTIDE ANTAGONIST; TACHYKININ RECEPTORS; NERVE-FIBERS; DURA-MATER AB The effect of RPR 100893, a selective and specific neurokinin-1 antagonist, or its enantiomer RPR 103253 was examined on c-fos antigen expression in brain stem and upper cervical cord 2 h after intracisternal capsaicin injection (30.5 mu g/ml) in pentobarbital-anesthetized Hartley guinea-pigs. Positive cells were counted at three levels corresponding to obex, -2.25 mm and -6.75 mm in 18 sections (50 mu m). Immunoreactivity was strongly expressed within laminae I and II0 of trigeminal nucleus caudalis, area postrema and the leptomeninges. Moderate labeling was present in the nucleus of the solitary tract and the medullary lateral reticular nucleus, whereas few positive cells were found in the ventral portion of the medullary reticular nucleus and Rexed laminae III-V and X. The distribution of labeled cells was consistent with previously reported results following subarachnoid placement of the noxious agents, blood or carrageenin. Pretreatment with RPR 100893 (1, 10 and 100 mu g/kg, i.v.) but not its enantiomer (100 mu g/kg, i.v.) 30 min prior to capsaicin injection significantly reduced the number of positive cells in the trigeminal nucleus caudalis (P < 0.01) in a dose-dependent manner, but not within area postrema or nucleus of the solitary tract. These results indicate that (i) the instillation of capsaicin into the subarachnoid space is an effective stimulus for the induction of c-fos antigen within trigeminal nucleus caudalis, presumably through activation of trigeminovascular afferents, and (ii) the neurokinin-1 antagonist RPR 100893 reduces the number of positive cells selectively within this nucleus. The findings are significant because drugs which alleviate Vascular headaches decrease the number of c-fos positive cells within trigeminal nucleus caudalis following noxious meningeal stimulation. Hence, strategies aimed at blocking the neurokinin-1 receptor may be useful for treating migraine and cluster headache. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,STROKE RES LAB,BOSTON,MA 02114. RHONE POULENC RORER SA,CTR RECH VITRY,VITRY,FRANCE. RI Moskowitz, Michael/D-9916-2011 FU NINDS NIH HHS [NS 21558] NR 54 TC 44 Z9 44 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD FEB PY 1995 VL 64 IS 3 BP 741 EP 750 DI 10.1016/0306-4522(94)00428-8 PG 10 WC Neurosciences SC Neurosciences & Neurology GA QD109 UT WOS:A1995QD10900014 PM 7536309 ER PT J AU BURNS, LH PAKZABAN, P DEACON, TW BROWNELL, AL TATTER, SB JENKINS, BG ISACSON, O AF BURNS, LH PAKZABAN, P DEACON, TW BROWNELL, AL TATTER, SB JENKINS, BG ISACSON, O TI SELECTIVE PUTAMINAL EXCITOTOXIC LESIONS IN NONHUMAN-PRIMATES MODEL THE MOVEMENT DISORDER OF HUNTINGTON DISEASE SO NEUROSCIENCE LA English DT Article ID BASAL GANGLIA; QUINOLINIC-ACID; CAUDATE-PUTAMEN; KAINIC ACID; CORTICOSTRIATAL PROJECTIONS; PARALLEL ORGANIZATION; PREFRONTAL CORTEX; EVOKED-POTENTIALS; RECEPTOR-BINDING; MACAQUE MONKEY AB While dyskinetic movements have been reported in primates with unilateral excitotoxic lesions following stimulation by dopaminergic agonists, the presence and intensity of the dyskinetic syndromes have Varied extensively with size and location of lesion. With the intent of producing a more reliable behavioral model of Huntington disease, anatomically-defined lesions of limited size were produced by magnetic resonance imaging-guided stereotaxic injection of quinolinic acid in specific regions within the caudate and putamen of rhesus monkeys. The location and extent of the lesions were verified by magnetic resonance imaging as well as quantitative positron emission tomography imaging with the dopamine D-1 specific receptor ligand SCH 39166 as a marker for striatal output neurons. The quality, frequency and duration of dyskinetic movements were assessed and quantified before and after administration of 0.5 mg/kg apomorphine in multiple test sessions over several months. Selective unilateral lesions in the posterior putamen, but not in the anterior putamen or the head of the caudate, produced marked dystonia and dyskinesia after apomorphine administration. While combined unilateral lesions of the caudate and posterior putamen produced dyskinesia similar to selective posterior putaminal lesions, combined unilateral lesions of the anterior and posterior putamen did not elicit dyskinesia. On the basis of these results, one monkey received a bilateral selective lesion in the posterior putamen. This animal remained healthy and exhibited marked spontaneous Huntington-like chorea spontaneously in the first 48 h after lesioning and persistent apomorphine-induced dyskinesia thereafter. We conclude that bilateral selective excitotoxic lesions of the posterior putamen provide an improved model of the movement disorder of Huntington disease. C1 MCLEAN HOSP,NEUROREGENERAT LAB,BELMONT,MA 02178. HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02115. HARVARD UNIV,NEW ENGLAND REG PRIMATE RES CTR,SCH MED,DIV BEHAV BIOL,SOUTHBOROUGH,MA 01772. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT NEUROSURG,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CTR NUCL MAGNET RESONANCE,BOSTON,MA 02129. FU NIMH NIH HHS [5T32 MH14275]; NINDS NIH HHS [NS30064, 5T32 NS07340] NR 44 TC 51 Z9 53 U1 0 U2 2 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 1995 VL 64 IS 4 BP 1007 EP 1017 DI 10.1016/0306-4522(94)00431-4 PG 11 WC Neurosciences SC Neurosciences & Neurology GA QH290 UT WOS:A1995QH29000013 PM 7753372 ER PT J AU SHRIEVE, DC ALEXANDER, E WEN, PY FINE, HA KOOY, HM BLACK, PML LOEFFLER, JS AF SHRIEVE, DC ALEXANDER, E WEN, PY FINE, HA KOOY, HM BLACK, PML LOEFFLER, JS TI COMPARISON OF STEREOTAXIC RADIOSURGERY AND BRACHYTHERAPY IN THE TREATMENT OF RECURRENT GLIOBLASTOMA-MULTIFORME SO NEUROSURGERY LA English DT Article DE BRACHYTHERAPY; RADIOSURGERY; RECURRENT GLIOMA ID ACTIVITY I-125 SOURCES; PRIMARY BRAIN-TUMORS; MALIGNANT GLIOMAS; INTERSTITIAL BRACHYTHERAPY; ANAPLASTIC ASTROCYTOMA; INITIAL MANAGEMENT; PATTERNS; CHEMOTHERAPY; REOPERATION; RADIOTHERAPY AB THE PURPOSE OF this study was to compare the efficacy of stereotactic radiosurgery (SRS) and brachytherapy in the treatment of recurrent glioblastoma multiforme (GBM). The patients had either progressive GBM or pathologically proven GBM at recurrence after previous treatment for a lower grade astrocytoma. Thirty-two patients were treated with interstitial brachytherapy, and 86 received treatment with stereotactic radiosurgery (SRS). The patient characteristics were similar in the two groups. Those patients treated with SRS had a median tumor volume of 10.1 cm(3) and received a median peripheral tumor dose of 13 Gy, Patients treated with brachytherapy had a median tumor volume of 29 cm(3). Median dose to the periphery of the tumor volume was 50 Gy delivered at a median dose rate of 43 cGy/hour. Twenty-one patients (24%) treated with SRS were alive, with a median follow-up of 17.5 months. Median actuarial survival, measured from the time of treatment for recurrence, for all patients treated with SRS was 10.2 months, with survivals of 12 and 24 months being 45 and 19%, respectively. A younger age and a smaller tumor volume were predictive of better outcome. The tumor dose, the interval from initial diagnosis, and the need for reoperation were not predictive of outcome after SRS. Five patients (16%) treated with brachytherapy were alive, with a median follow-up of 43.3 months. The median actuarial survival for all patients treated with brachytherapy was 11.5 months. Survivals of 12 and 24 months were 44 and 17%, respectively. The age of the patient (but not tumor volume, interval from initial diagnosis, or tumor dose) was predictive of outcome in these patients. A comparison of the results between patients treated with SRS and brachytherapy indicated a similar survival rate. Nineteen patients (22%) required reoperation after SRS, compared with 14 (44%) in the brachytherapy group. The actuarial risk for reoperation was 33% at 12 months and 48% at 24 months after SRS, compared with 54 and 65%, respectively, after brachytherapy (P = 0.195). Those patients undergoing reoperation after brachytherapy survived longer than similar patients not undergoing reoperation. The outcome after SRS was independent of a need for reoperation. The treatment of recurrent GBM with SRS resulted in a survival rate similar to that obtained with interstitial high-activity I-125 implantation. This outpatient procedure is currently the treatment of choice for recurrent GBM at our institution in patients whose disease is amenable to SRS. C1 HARVARD UNIV,SCH MED,DEPT RADIAT THERAPY,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT SURG NEUROSURG,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. RP SHRIEVE, DC (reprint author), BRIGHAM & WOMENS HOSP,CHILDRENS HOSP,JOINT CTR RADIAT THERAPY,DANA FARBER CANC INST,BOSTON,MA 02115, USA. FU NINDS NIH HHS [P20 NS31110] NR 30 TC 188 Z9 190 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 1995 VL 36 IS 2 BP 275 EP 282 PG 8 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA QE888 UT WOS:A1995QE88800018 PM 7731507 ER PT J AU HAFELI, UO SWEENEY, SM BERESFORD, BA HUMM, JL MACKLIS, RM AF HAFELI, UO SWEENEY, SM BERESFORD, BA HUMM, JL MACKLIS, RM TI EFFECTIVE TARGETING OF MAGNETIC RADIOACTIVE Y-90 MICROSPHERES TO TUMOR-CELLS BY AN EXTERNALLY APPLIED MAGNETIC-FIELD - PRELIMINARY IN-VITRO AND IN-VIVO RESULTS SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article ID MICROSPHERES; HYPERTHERMIA; Y-90 AB Magnetic biodegradable poly(lactic acid) microspheres that incorporate both magnetite and the beta-emitter Y-90 were prepared. By applying a directional external magnetic field gradient in excess of 0.02 Tesla/cm across a 96-well plate containing neuroblastoma cells incubated with the Y-90 magnetite loaded microspheres, the radiation dose to the cells could be enhanced or reduced relative to the dose from a uniform loading of the well with Y-90-DTPA. Using the MTT assay, cell survival was measured for the magnetic field directed from above (cell sparing) and from below (cell targeting) the well plate, resulting in 65 +/- 8% or 18 +/- 5% survival respectively. This method was then applied to an in vivo murine tumor model. The biodistribution of intraperitoneally injected magnetic radioactive microspheres, after 24 h in mice, showed that 73 +/- 32% of the radioactivity was found on the subcutaneous tumor that had a rare earth magnet fixed above it. In contrast, the tumor radioactivity with no attached magnet was 6 +/- 4%. Magnetically targeted radiopolymers such as Y-90-microspheres show great promise for regional or intracavitary radiotherapy. C1 HARVARD UNIV,SCH MED,JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT RADIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. MEM SLOAN KETTERING CANC CTR,DEPT MED PHYS,NEW YORK,NY 10021. RP HAFELI, UO (reprint author), CLEVELAND CLIN FDN,DEPT RADIAT ONCOL,DESK T-18,9500 EUCLID AVE,CLEVELAND,OH 44195, USA. RI Hafeli, Urs/B-4097-2012; OI Hafeli, Urs/0000-0003-0671-4509 NR 24 TC 81 Z9 85 U1 0 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0883-2897 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD FEB PY 1995 VL 22 IS 2 BP 147 EP 155 DI 10.1016/0969-8051(94)00124-3 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA QL604 UT WOS:A1995QL60400002 PM 7767307 ER PT J AU BRAZITIKOS, PD DAMICO, DJ BERNAL, MT WALSH, AW AF BRAZITIKOS, PD DAMICO, DJ BERNAL, MT WALSH, AW TI ERBIUM - YAG LASER-SURGERY OF THE VITREOUS AND RETINA SO OPHTHALMOLOGY LA English DT Article ID INTRAOCULAR ABLATIVE PHOTODECOMPOSITION; ER-YAG; EXCIMER LASER; MEMBRANES; RADIATION; NEODYMIUM; RABBITS; DAMAGE; 193-NM; CORNEA AB Purpose: These studies evaluated an erbium:YAG laser for transection of vitreous membranes, retinotomy, and incision and ablation of epiretinal membranes. Methods: Elevated vitreous membranes, detachments, and epiretinal membranes were induced in rabbit eyes. An erbium:YAG laser, emitting at a wavelength of 2.94 mu m and equipped with a flexible fiber and endoprobes with tips ranging from 75 to 375 mu m, was used to perform vitreous membrane transections, retinotomies, and epiretinal membrane incisions and ablations in nontransmitting aqueous media with the endoprobe in proximity to the tissue. Ablations of epiretinal membranes also were performed in transmitting media, including air and perfluoro-N-octane with the endoprobe elevated above the membrane. Results: Twenty-five vitreous membrane transections were made in 16 eyes at distances ranging from 0.5 to 4.5 mm from the retina with radiant exposures ranging from 2 to 50 J/cm(2) with nonhemorrhagic retinal damage in a single transection. Sharp, linear retinotomies were created successfully in five eyes. Epiretinal membrane ablations were performed with radiant exposures ranging from 1.8 to 22.6 J/cm(2). In aqueous media, results of microscopic examination showed partial- to full-thickness ablation with a maximum lateral thermal damage of 50 mu m. In air- and perfluoro-N-octane-filled eyes, there was increased lateral damage with desiccation of residual tissue. In 12 aqueous-filled eyes, 18 linear incisions were successfully performed, with retinal nonhemorrhagic damage in 2 eyes and hemorrhage in 5. Conclusion: The erbium:YAG laser may provide new approaches to maneuvers performed in vitreoretinal surgery. C1 MASSACHUSETTS EYE & EAR INFIRM,RETINA SERV,BOSTON,MA 02114. MASSACHUSETTS EYE & EAR INFIRM,LASER RES LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT OPHTHALMOL,BOSTON,MA. NR 25 TC 53 Z9 53 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD FEB PY 1995 VL 102 IS 2 BP 278 EP 290 PG 13 WC Ophthalmology SC Ophthalmology GA QG824 UT WOS:A1995QG82400024 PM 7862415 ER PT J AU BHATT, SM CABELLOS, C NADOL, JB HALPIN, C LAURETANO, A XU, WZ TUOMANEN, E AF BHATT, SM CABELLOS, C NADOL, JB HALPIN, C LAURETANO, A XU, WZ TUOMANEN, E TI THE IMPACT OF DEXAMETHASONE ON HEARING-LOSS IN EXPERIMENTAL PNEUMOCOCCAL MENINGITIS SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE MENINGITIS; HEARING LOSS; DEXAMETHASONE; STREPTOCOCCUS PNEUMONIAE ID CHILDHOOD BACTERIAL-MENINGITIS; B MENINGITIS; CHILDREN; THERAPY; INFLAMMATION; RESPONSES; SEQUELA; INFANTS AB Bacterial meningitis, particularly that resulting from Streptococcus pneumoniae, is a common cause of acquired profound sensorineural deafness in children. The pathogenesis of meningogenic hearing loss has been investigated in an experimental rabbit model. In this study significant deafness was documented within the first 15 hours of infection. Initiation of antibiotic therapy at this time diminished the severity of hearing loss in most animals. The addition of dexamethasone to antibiotic therapy prevented the development of profound deafness. These results suggest this model will be useful in developing antiinflammatory strategies to improve the outcome of bacterial meningitis. C1 ROCKEFELLER UNIV,MOLEC INFECT DIS LAB,NEW YORK,NY 10021. MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA. FU NIAID NIH HHS [AI-27938] NR 27 TC 33 Z9 33 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD FEB PY 1995 VL 14 IS 2 BP 93 EP 96 DI 10.1097/00006454-199502000-00002 PG 4 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA QG130 UT WOS:A1995QG13000002 PM 7746714 ER PT J AU LAVERDIERE, JT LAOR, T BENACERRAF, B AF LAVERDIERE, JT LAOR, T BENACERRAF, B TI CONGENITAL ABSENCE OF THE PORTAL-VEIN - CASE-REPORT AND MR DEMONSTRATION SO PEDIATRIC RADIOLOGY LA English DT Note AB Congenital absence of the portal vein (CAPV) is a rare anomaly that results from aberrant venous development in early embryonic life. The intestinal and splenic venous drainage bypasses the liver and drains directly into the inferior vena cava (IVC), the left renal vein, or the left hepatic vein. We describe a case where prenatal ultrasonography demonstrated an unusual C-shaped vessel between the umbilical vein and a dilated IVC, and failed to show a portal vein. Ultrasonography and magnetic resonance imaging and magnetic resonance angiography at 4 months of age again found no portal vein. The superior mesenteric vein drained into the left renal vein. C1 CHILDRENS HOSP,DEPT RADIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT OBSTET & GYNECOL,BOSTON,MA 02114. NR 9 TC 50 Z9 50 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0301-0449 J9 PEDIATR RADIOL JI Pediatr. Radiol. PD FEB PY 1995 VL 25 IS 1 BP 52 EP 53 DI 10.1007/BF02020848 PG 2 WC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging SC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging GA QN024 UT WOS:A1995QN02400019 PM 7761165 ER PT J AU CHIANG, HH HWANG, I GOODMAN, HM AF CHIANG, HH HWANG, I GOODMAN, HM TI ISOLATION OF THE ARABIDOPSIS GA4 LOCUS SO PLANT CELL LA English DT Article ID ZEA-MAYS-L; INTERNODE LENGTH; MUTANTS; DNA; THALIANA; PISUM; GIBBERELLIN-A20; TRANSFORMATION; EXPRESSION; DEFICIENT AB Progeny from a transgenic Arabidopsis plant generated by the Agrobacterium root transformation procedure were found to segregate for a gibberellin (GA)-responsive semidwarf phenotype. Complementation analysis with genetically characterized GA-responsive mutants revealed that the transgenic plant has an insertional mutation (ga4-2) that is an allele of the ga4 locus, The semidwarf phenotype of ga4-2 is inherited as a recessive mutation that cosegregates with both the T-DNA insert and the kanamycin resistance trait. DNA gel blot analysis indicated that the insertion site contains a complex T-DNA unit. A genomic library was constructed with DNA from the tagged ga4 mutant; a DNA clone was isolated from the library that flanks the T-DNA insert. The plant sequence isolated from this clone was used to isolate the corresponding full-length genomic and cDNA clones from wild-type libraries. DNA sequence comparison of the clones to the existing data bases suggests that they encode a hydroxylase. This conclusion is in agreement with a biochemical study that indicated that the ga4 mutant is deficient in 3 beta-hydroxylase in the GA biosynthetic pathway of Arabidopsis. RNA gel blot analysis showed that the message is ubiquitously expressed in different tissues of Arabidopsis but most abundantly in the silique. Unexpectedly, a higher level of transcription was detected in the ethyl methanesulfonate-induced ga4 mutant, and this overexpression was repressed by treatment with exogenous GA. C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. NR 26 TC 200 Z9 225 U1 1 U2 11 PU AMER SOC PLANT PHYSIOLOGISTS PI ROCKVILLE PA 15501 MONONA DRIVE, ROCKVILLE, MD 20855 SN 1040-4651 J9 PLANT CELL JI Plant Cell PD FEB PY 1995 VL 7 IS 2 BP 195 EP 201 DI 10.1105/tpc.7.2.195 PG 7 WC Biochemistry & Molecular Biology; Plant Sciences; Cell Biology SC Biochemistry & Molecular Biology; Plant Sciences; Cell Biology GA QJ993 UT WOS:A1995QJ99300007 PM 7756830 ER PT J AU LEE, WPA PAN, YC KESMARKY, S RANDOLPH, MA FIALA, TS AMARANTE, MTJ WEILAND, AJ YAREMCHUK, MJ AF LEE, WPA PAN, YC KESMARKY, S RANDOLPH, MA FIALA, TS AMARANTE, MTJ WEILAND, AJ YAREMCHUK, MJ TI EXPERIMENTAL ORTHOTOPIC TRANSPLANTATION OF VASCULARIZED SKELETAL ALLOGRAFTS - FUNCTIONAL ASSESSMENT AND LONG-TERM SURVIVAL SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID PERIPHERAL-NERVE ALLOGRAFT; EXPERIMENTAL SKIN ALLOGRAFTS; TISSUE LIMB ALLOGRAFTS; CYCLOSPORIN-A; BONE ALLOGRAFTS; INDEFINITE SURVIVAL; IMMUNOLOGICAL-UNRESPONSIVENESS; MUSCLE ALLOGRAFTS; HOST-DISEASE; RATS AB Vascularized skeletal tissue allografts would greatly expand the domain of reconstructive surgery. Few studies to date have examined the functional aspects of these allografts or their long-term fate. An orthotopic transplant model of rat distal femur and surrounding muscular cuff was developed to assess graft function in fracture healing and weight bearing. Isografts (RT1(l) to RT1(l), n = 40), weak-barrier allografts (RT1(l) to RT1(lv), n = 40), and strong-barrier allografts (RT1(l) to RT1(n), n = 40) were transplanted. As the histocompatibility barrier increased between the donor and recipient animals, the graft viability and performance deteriorated according to radiographic, histologic, and immunologic analyses. Administration of cyclosporine led to survival of strong-barrier allografts similar to that of isografts. A long-term study of these allografts (RT1(l) to RT1(n)) was then performed on various immunosuppressive regimens. After an initial 10-week course of cyclosporine to achieve bony union and remodeling, subsequent cessation (n = 20) or intermittent ''pulsing'' (n = 20) of the immunosuppressant was insufficient in maintaining graft survival. However, graft viability and function were preserved through 1 year on continuous daily cyclosporine (n = 32). There was no evidence of host renal or hepatic toxicity by serum chemistry or histologic sections. Thus long-term survival of functional skeletal allografts was achieved in this orthotopic model without significant host toxicity from immunosuppression. C1 MASSACHUSETTS GEN HOSP,DEPT SURG,DIV PLAST SURG,CTR AMBULATORY CARE 453,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. JOHNS HOPKINS UNIV,SCH MED,DEPT ORTHOPAED SURG,MICROSURG RES LAB,BALTIMORE,MD. FU NIADDK NIH HHS [R01 AM25791] NR 66 TC 45 Z9 52 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD FEB PY 1995 VL 95 IS 2 BP 336 EP 349 PG 14 WC Surgery SC Surgery GA QE564 UT WOS:A1995QE56400014 PM 7824614 ER PT J AU BASHOFF, EC BEASER, RS AF BASHOFF, EC BEASER, RS TI INSULIN THERAPY AND THE RELUCTANT PATIENT - OVERCOMING OBSTACLES TO SUCCESS SO POSTGRADUATE MEDICINE LA English DT Article ID DEPENDENT DIABETES-MELLITUS; GLYCEMIC CONTROL; SELF-CARE; IDDM AB Initiation of insulin therapy raises many patient concerns, hesitations, and fears that healthcare providers need to recognize and resolve when developing each patient's treatment program. The psychological aspects of insulin therapy are hard to characterize because of the great variation between patients. However, with the proper tools and resources, insulin regimens can be developed to accommodate individual differences in personality and lifestyle. C1 JOSLIN DIABET CTR, BOSTON, MA 02215 USA. NEW ENGLAND DEACONESS HOSP, BOSTON, MA USA. HARVARD UNIV, SCH MED, BOSTON, MA USA. NR 26 TC 22 Z9 23 U1 0 U2 2 PU JTE MULTIMEDIA PI BERWYN PA 1235 WESTLAKES DR, STE 220, BERWYN, PA 19312 USA SN 0032-5481 J9 POSTGRAD MED JI Postgrad. Med. PD FEB PY 1995 VL 97 IS 2 BP 86 EP + PG 0 WC Medicine, General & Internal SC General & Internal Medicine GA QF766 UT WOS:A1995QF76600007 PM 7855037 ER PT J AU GOODFRIEND, TL ELLIOTT, ME AF GOODFRIEND, TL ELLIOTT, ME TI FATTY-ACIDS IN CELL SIGNALING - PREFACE SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS LA English DT Editorial Material C1 UNIV WISCONSIN,SCH MED,DEPT PHARMACOL,MADISON,WI. WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI. RP GOODFRIEND, TL (reprint author), UNIV WISCONSIN,SCH MED,DEPT MED,MADISON,WI, USA. NR 0 TC 2 Z9 2 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 0952-3278 J9 PROSTAG LEUKOTR ESS JI Prostaglandins Leukot. Essent. Fatty Acids PD FEB-MAR PY 1995 VL 52 IS 2-3 BP 75 EP 75 DI 10.1016/0952-3278(95)90000-4 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism GA QJ382 UT WOS:A1995QJ38200001 ER PT J AU LAPOSATA, M SZCZEPIORKOWSKI, ZM BROWN, JE AF LAPOSATA, M SZCZEPIORKOWSKI, ZM BROWN, JE TI FATTY-ACID ETHYL-ESTERS - NONOXIDATIVE METABOLITES OF ETHANOL SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS LA English DT Article; Proceedings Paper CT 2nd International Round Table on Fatty Acids in Cell Signalling CY JUN 12-13, 1994 CL UNIV WISCONSIN MADISON, MADISON, WI HO UNIV WISCONSIN MADISON AB Fatty acid ethyl esters are esterification products of fatty acids and ethanol. These compounds have been detected in the serum and cells of individuals following ethanol ingestion. Fatty acid ethyl esters can be quantitated by gas chromatography-mass spectroscopy (CC-MS) in the serum following ethanol ingestion and have been found in concentrations up to 42 mu M. Fatty acid ethyl esters have also been isolated from adipose tissue of subjects ingesting fatty acid ethyl ester capsules as well as from subjects ingesting ethanol. HepG2 cells, a human hepatoblastoma cell line, have also been shown to generate fatty acid ethyl esters when incubated with 1.25 mu M fatty acid and 0.17 M ethanol. Fatty acid ethyl esters were found to be toxic to HepG2 cells when presented to the cells in the core of low density lipoprotein particles. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP LAPOSATA, M (reprint author), MASSACHUSETTS GEN HOSP,DEPT PATHOL,DIV CLIN LABS,ROOM 2325 GRAY BLDG,FRUIT ST,BOSTON,MA 02114, USA. RI Szczepiorkowski, Zbigniew/A-1359-2007 OI Szczepiorkowski, Zbigniew/0000-0003-2357-9564 FU NIDDK NIH HHS [DK43159, DK37454] NR 9 TC 32 Z9 34 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH, MIDLOTHIAN, SCOTLAND EH1 3AF SN 0952-3278 J9 PROSTAG LEUKOTR ESS JI Prostaglandins Leukot. Essent. Fatty Acids PD FEB-MAR PY 1995 VL 52 IS 2-3 BP 87 EP 91 DI 10.1016/0952-3278(95)90003-9 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism GA QJ382 UT WOS:A1995QJ38200004 PM 7784463 ER PT J AU GOODFRIEND, TL LEE, WMP BALL, DL ELLIOTT, ME AF GOODFRIEND, TL LEE, WMP BALL, DL ELLIOTT, ME TI SPECIFICITY AND MECHANISM OF FATTY-ACID INHIBITION OF ALDOSTERONE SECRETION SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS LA English DT Article; Proceedings Paper CT 2nd International Round Table on Fatty Acids in Cell Signalling CY JUN 12-13, 1994 CL UNIV WISCONSIN MADISON, MADISON, WI HO UNIV WISCONSIN MADISON ID ANGIOTENSIN-II; EICOSAPENTAENOIC ACID; BLOOD-PRESSURE; ADRENAL-CORTEX; RECEPTORS; IDENTIFICATION; EXPRESSION; CELLS AB We have shown that unesterified, unsaturated long-chain fatty acids inhibit angiotensin II (AII) binding to receptors in adrenal glomerulosa cells, In this report, we show that oleic and arachidonic acids are specific inhibitors of the AT(1) subtype of angiotensin receptor, and exert no effect on receptors of the AT(2) subtype. By contrast, decanoic acid is a weak inhibitor of the AT(2) subtype only, Our previous work on a post-receptor locus of inhibition by fatty acids of aldosterone biosynthesis showed that the 18-oxidase step is uniquely sensitive, In brief, the first and last steps involved in angiotensin-stimulated aldosterone secretion are particularly sensitive to inhibition by fatty acids. These results suggest a specific role for unesterified fatty acids in regulation of salt and water metabolism. C1 UNIV WISCONSIN,DEPT MED,MADISON,WI 53705. UNIV WISCONSIN,DEPT PHARMACOL,MADISON,WI 53705. RP GOODFRIEND, TL (reprint author), WILLIAM S MIDDLETON MEM VET ADM MED CTR,2500 OVERLOOK TERRACE,MADISON,WI 53705, USA. NR 20 TC 9 Z9 10 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH, MIDLOTHIAN, SCOTLAND EH1 3AF SN 0952-3278 J9 PROSTAG LEUKOTR ESS JI Prostaglandins Leukot. Essent. Fatty Acids PD FEB-MAR PY 1995 VL 52 IS 2-3 BP 145 EP 149 DI 10.1016/0952-3278(95)90013-6 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism GA QJ382 UT WOS:A1995QJ38200014 PM 7784450 ER PT J AU LEAF, A AF LEAF, A TI OMEGA-3-FATTY-ACIDS AND PREVENTION OF VENTRICULAR-FIBRILLATION SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS LA English DT Article; Proceedings Paper CT 2nd International Round Table on Fatty Acids in Cell Signalling CY JUN 12-13, 1994 CL UNIV WISCONSIN MADISON, MADISON, WI HO UNIV WISCONSIN MADISON AB Interest in the potential cardiovascular benefits of omega-3 long chain polyunsaturated fatty acids has been largely focused on possible antiatherothrombotic effects. In addition, however, definitive antiarrhythmic effects of these dietary omega-3 fatty acids have been reported by Charnock and McLennan, Our studies commenced with the observation that two of these fatty acids, eicosapentaenoic (C20:5n-3, EPA) and docosahexaenoic acid (C22:6n-3, DHA) prevented contracture and fibrillation of isolated neonatal cardiac myocytes when exposed to toxic levels of ouabain (0.1 mM). This protection was associated with prevention of excessively high intracellular calcium concentrations in the myocyte, Further, it was shown that these fatty acids modulate calcium currents through L-type calcium channels and that the effect occurs within a few minutes of adding EPA or DHA to the medium perfusing the cultured cardiac myocytes, Infusing an emulsion of the omega-3 fatty acids intravenously just prior to compression of a coronary artery in a conscious, prepared dog will prevent the expected subsequent ischemia-induced ventricular fibrillation, C1 HARVARD UNIV,SCH MED,BOSTON,MA. BROCKTON W ROXBURY VET AFFAIRS MED CTR,BOSTON,MA. RP LEAF, A (reprint author), MED SERV,MASSACHUSETTS GEN HOSP BLDG 149,13TH ST,BOSTON,MA 02129, USA. FU NIDDK NIH HHS [R01-DK38165] NR 9 TC 33 Z9 33 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 0952-3278 J9 PROSTAG LEUKOTR ESS JI Prostaglandins Leukot. Essent. Fatty Acids PD FEB-MAR PY 1995 VL 52 IS 2-3 BP 197 EP 198 DI 10.1016/0952-3278(95)90022-5 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism GA QJ382 UT WOS:A1995QJ38200023 PM 7784457 ER PT J AU SLATER, EJ GLAZER, W AF SLATER, EJ GLAZER, W TI USE OF OBRA-87 GUIDELINES FOR PRESCRIBING NEUROLEPTICS IN A VA NURSING-HOME SO PSYCHIATRIC SERVICES LA English DT Note ID FACILITIES; INDICATORS C1 YALE UNIV,SCH MED,NEW HAVEN,CT 06520. RP SLATER, EJ (reprint author), WILLIAM S MIDDLETON MEM VET ADM MED CTR,CTR GERIATR RES EDUC & CLIN,2500 OVERLOOK TERRACE,MADISON,WI 53705, USA. NR 17 TC 10 Z9 10 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 1075-2730 J9 PSYCHIATR SERV JI Psychiatr. Serv. PD FEB PY 1995 VL 46 IS 2 BP 119 EP 121 PG 3 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA QP099 UT WOS:A1995QP09900003 PM 7712245 ER PT J AU PONTIUS, AA AF PONTIUS, AA TI RETRODUCTIVE REASONING IN A PROPOSED SUBTYPE OF PARTIAL SEIZURES, EVOKED BY LIMBIC KINDLING SO PSYCHOLOGICAL REPORTS LA English DT Article ID PSYCHOTIC TRIGGER REACTION; FRONTAL-LOBE; QUESTIONABLE ASPECTS; SYSTEM; NARRATIVES; HOMICIDE; EPILEPSY AB This analysis provides a specific example of the generally applicable process of creative delineation of a novel pattern while searching for an explanatory hypothesis for puzzling observations. In so doing, the neglected retroductive form of inference or abduction was used. Central to such a process is the delineation of a specific ''generative mechanism'' capable of uniting and explaining heretofore unexplained phenomena. Herein the neurophysiologically known mechanism of limbic seizure ''kindling'' is offered as a unifying explanation for a dozen bizarre phenomena, proposed as a new subtype of partial seizures, ''Limbic Psychotic Trigger Reaction.'' This new syndrome has been proposed over 15 years in 17 male social loners. Upon encounter with an individualized stimulus, which revived in memory prior moderately hurtful experiences, these men suddenly committed motiveless, unplanned acts with flat affect, transient psychosis and autonomic arousal, showing no quantitative impairment of consciousness and so without memory loss for their perplexing homicidal acts (13 cases), firesetting (3 cases), or bank robbery (1 case). Events occurred in three phases reminiscent of seizures: (1) aura-like puzzlement, (2) transient ictus with a limbic release of predatory or defensive aggression (circa 20 min.), and (3) postictal inefficient actions, implicating a transient frontal lobe system dysfunction secondary to the limbic hyperactivation. The 17 men were of diverse backgrounds, but all without history of prior violence or severe emotional trauma. Seven of 17 had some abnormal brain tests at some time during their lives and eight known histories of typically overlooked closed-brain injury. Brain damage may facilitate seizure ''kindling'' but has been traditionally observed in mammals and in a few humans without such damage. RP PONTIUS, AA (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PSYCHIAT,FRUIT ST,BOSTON,MA 02114, USA. NR 34 TC 9 Z9 9 U1 0 U2 0 PU PSYCHOLOGICAL REPORTS PI MISSOULA PA P O BOX 9229, MISSOULA, MT 59807 SN 0033-2941 J9 PSYCHOL REP JI Psychol. Rep. PD FEB PY 1995 VL 76 IS 1 BP 55 EP 62 PG 8 WC Psychology, Multidisciplinary SC Psychology GA QV858 UT WOS:A1995QV85800012 PM 7770594 ER PT J AU GOFF, DC MIDHA, KK SARIDSEGAL, O HUBBARD, JW AMICO, E AF GOFF, DC MIDHA, KK SARIDSEGAL, O HUBBARD, JW AMICO, E TI A PLACEBO-CONTROLLED TRIAL OF FLUOXETINE ADDED TO NEUROLEPTIC IN PATIENTS WITH SCHIZOPHRENIA SO PSYCHOPHARMACOLOGY LA English DT Article DE FLUOXETINE; SCHIZOPHRENIA; NEUROLEPTICS ID PERFORMANCE LIQUID-CHROMATOGRAPHY; RAT-BRAIN; EXTRAPYRAMIDAL SYMPTOMS; NEGATIVE SYMPTOMS; DOUBLE-BLIND; PATHOLOGICAL JEALOUSY; PLASMA-CONCENTRATIONS; ULTRASENSITIVE METHOD; COULOMETRIC DETECTION; SECONDARY DEPRESSION AB Following a 2-week placebo lead-in, schizophrenic patients were randomly assigned to fluoxetine 20 mg/day or placebo added to depot neuroleptic for a 6-week, double blind trial. All patients had received a stable dose of depot neuroleptic for at least 6 months and did not meet criteria for depression, Serum samples were obtained at baseline and at weeks 4 and 6. Scores on the negative symptom subscale of the Brief Psychiatric Rating Scale (BPRS) were significantly lower at week 6, controlling for baseline scores, in patients receiving fluoxetine (n = 20) compared to patients receiving placebo (n = 21). Measures of psychosis, depression, global functioning and extrapyramidal symptoms (EPS) did not differ between groups at week 6. Fluoxetine administration was associated with a mean 65% increase in serum fluphenazine concentrations in 15 patients and a mean 20% increase in serum haloperidol concentrations in three patients. The change in negative symptoms at week 6 did not correlate with serum concentrations of fluoxetine or norfluoxetine, but did inversely correlate with S-norfluoxetine, an active stereoisomer of fluoxetine. For these chronically ill patients, fluoxetine significantly improved negative symptoms and did not worsen EPS, despite causing substantial elevation in serum concentrations of neuroleptics. C1 MASSACHUSETTS GEN HOSP,PSYCHIAT SERV,BOSTON,MA. VET AFFAIRS OUTPATIENT CLIN,BOSTON,MA. UNIV SASKATCHEWAN,COLL PHARM & MED,SASKATOON,SK,CANADA. RP GOFF, DC (reprint author), FREEDOM TRAIL CLIN,25 STANIFORD ST,BOSTON,MA 02114, USA. FU NIMH NIH HHS [MH-19052] NR 76 TC 108 Z9 116 U1 1 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD FEB PY 1995 VL 117 IS 4 BP 417 EP 423 DI 10.1007/BF02246213 PG 7 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA QK115 UT WOS:A1995QK11500005 PM 7604142 ER PT J AU GLIKLICH, RE HILINSKI, JM AF GLIKLICH, RE HILINSKI, JM TI LONGITUDINAL SENSITIVITY OF GENERIC AND SPECIFIC HEALTH MEASURES IN CHRONIC SINUSITIS SO QUALITY OF LIFE RESEARCH LA English DT Article DE QUALITY OF LIFE; QUESTIONNAIRES; SINUSITIS ID STATUS INSTRUMENTS; ETHMOIDECTOMY AB The utility of reliable health measures for longitudinal studies in chronic sinusitis depends on their ability to detect clinically relevant change. Sixty-three patients with chronic sinusitis were evaluated before and three months after ethmoid sinus surgery using the Chronic Sinusitis Survey (CSS) and the generic Short-Form 36-Item Health Survey (SF-36). Statistically significant improvement was found for several SF-36 subscales including physical functioning, role functioning-physical, bodily pain, vitality and all CSS subscales. However, the differences between the instruments in longitudinal sensitivity to change as measured by standardized response means (SRM) and effect sizes (ES) were large. For the SF-36, sensitivity to change ranged from minimal to small (SRM: 0.01-0.43; ES: 0.01-0.52) with bodily pain and role functioning-physical scores most sensitive. For the CSS, sensitivity to change ranged from moderate to large (SRM: 0.56-0.82; ES: 0.48-1.12) with symptom-based and total index scores most sensitive. Despite this, the SF-36 yielded useful information concerning the relative burden of chronic sinusitis and failure of these patients to achieve normal levels of general health 3 months after sinus surgery. We conclude that the disease-specific CSS was more sensitive to change than the SF-36 survey in patients following ethmoid sinus surgery. C1 HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02115. MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,CLIN OUTCOMES RES UNIT,BOSTON,MA 02114. NR 26 TC 84 Z9 88 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0962-9343 J9 QUAL LIFE RES JI Qual. Life Res. PD FEB PY 1995 VL 4 IS 1 BP 27 EP 32 DI 10.1007/BF00434380 PG 6 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA QM714 UT WOS:A1995QM71400004 PM 7711687 ER PT J AU SUIT, H AF SUIT, H TI TUMORS OF THE CONNECTIVE AND SUPPORTING TISSUES SO RADIOTHERAPY AND ONCOLOGY LA English DT Editorial Material DE SARCOMA; RADIATION; CHEMOTHERAPY; SURGERY ID GIANT-CELL TUMOR; SOFT-TISSUE; RADIATION-THERAPY; DESMOID TUMORS; LOCAL-CONTROL; RADIOBIOLOGICAL CHARACTERIZATION; POSTOPERATIVE RADIOTHERAPY; CONSERVATIVE SURGERY; SURGICAL MARGINS; EWINGS-SARCOMA AB There has been a continuous acceleration of medical/scientific inquiry and of actual improvements in management of patients with neoplasms of the mesenchymal tissues over the last four decades. The number of publications in this field has increased from 1140 in 1970 and then to 1700 in 1990, Important advances discussed over this period include: establishment of sarcoma teams in major oncology centers; staging systems for both soft tissue and osseous sarcomas; demonstration of genetic determinants in the development of, at least, some of the sarcomas; the revolutionary change in quality of diagnostic imaging by the introduction of CT and MRI; use of immunohistochemistry in diagnostic pathology; the drastic gains in survival of patients with osteogenic sarcoma, Ewing's sarcoma and rhabdomyosarcoma due to the efficacy of multi-drug and multi-cycle chemotherapy protocols; major advances in surgical techniques which have made limb salvage practical; cell lines derived from human sarcomas have been shown to have in vitro radiation sensitivity comparable to that of cell lines from epithelial tumors; the combination of conservative surgery and moderate doses of radiation yields local control and survival results equivalent to that of radical surgery with a much improved functional and cosmetic outcome; intra-operative electron beam radiation therapy improves the outcome of patients with retroperitoneal sarcomas when given after grossly complete resection combined with external beam radiation therapy (pre- or postoperatively); radiation is a highly effective alternative to extensive surgery for desmoid tumors; local control of giant cell tumors by modern radiation techniques is approximate to 80% and the incidence of radiation induced tumors at 10 years is approximate to 3%; to decrease the incidence of radiation induced sarcoma, resection has replaced radiation in the management of selected patients with primary Ewing's sarcoma when the response to chemotherapy has been excellent and the morbidity/functional decrement consequent upon the surgery judged reasonable; proton beam radiation therapy has been accepted as being superior to conventional external beam radiation therapy for chondrosarcoma and chordoma of the skull base; and attempts to utilize brachytherapy for sarcomas of the spine/sacrum appear to offer promise. Projected advances in the coming two decades include: designation of sarcoma type on genetic characterization; molecular genetics will provide prognostic information as to probability of distant metastasis, response to chemotherapeutic agents and radiation; important further reductions in the radiation treatment volume due to the many technical developments entering, or soon to enter, the clinic; non-invasive assessment of the response to chemotherapy; much increased appreciation of the late sequella of treatment, both radiation and chemotherapy. RP SUIT, H (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,BOSTON,MA 02114, USA. NR 76 TC 21 Z9 22 U1 0 U2 3 PU ELSEVIER SCI PUBL IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD FEB PY 1995 VL 34 IS 2 BP 93 EP 104 DI 10.1016/0167-8140(95)01512-F PG 12 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA QU921 UT WOS:A1995QU92100001 PM 7597217 ER PT J AU GUSELLA, JF MACDONALD, ME AF GUSELLA, JF MACDONALD, ME TI HUNTINGTONS-DISEASE SO SEMINARS IN CELL BIOLOGY LA English DT Review DE HUNTINGTONS DISEASE; NEURODEGENERATION; TRINUCLEOTIDE REPEAT; AGE AT ONSET; POLYGLUTAMINE ID AGE-OF-ONSET; CAG REPEAT NUMBER; TRINUCLEOTIDE REPEAT; MOLECULAR ANALYSIS; (CAG)(N) REPEAT; GENE; LENGTH; REGION; INSTABILITY; EXPANSION AB Early in 1993, an unstable, expanded trinucleotide repeat in a novel gene of unknown function was identified on HD chromosomes. This discovery unleased a flurry of experimentation that has established the expanded CAG repeat at the almost universal cause of the characteristic neurologic symptoms and pathology of this neurodegenerative disorder of midlife onset. The biochemical basis for the specific neuronal loss of HD remains uncertain, but the genetic lesion probably acts via its consequent polyglutamine segment in the protein product, huntingtin. This review will describe the basic parameters of the HD repeat's behavior and the Knowledge that has accumulated concerning its potential mechanisms of action. RP GUSELLA, JF (reprint author), MASSACHUSETTS GEN HOSP EAST,MOLEC NEUROGENET UNIT,BOSTON,MA 02129, USA. FU NINDS NIH HHS [NS32765, NS16367] NR 47 TC 60 Z9 62 U1 0 U2 9 PU ACADEMIC PRESS (LONDON) LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 1043-4682 J9 SEMIN CELL BIOL JI Semin. Cell Biol. PD FEB PY 1995 VL 6 IS 1 BP 21 EP 28 DI 10.1016/1043-4682(95)90011-X PG 8 WC Cell Biology SC Cell Biology GA RB603 UT WOS:A1995RB60300004 PM 7620118 ER PT J AU YOUNG, RH CLEMENT, PB AF YOUNG, RH CLEMENT, PB TI MALIGNANT LESIONS OF THE FEMALE GENITAL-TRACT AND PERITONEUM THAT MAY BE UNDERDIAGNOSED SO SEMINARS IN DIAGNOSTIC PATHOLOGY LA English DT Article AB Female genital tract neoplasms that may have a deceptively benign appearance and selected frankly malignant neoplasms that may be misinterepreted as less aggressive lesions are reviewed. In the uterine cervix, the two major neoplasms in this group are the minimal devition adenocarcinomas of mucinous and endometrioid types. The latter subtype has only recently been described. Endometrioid adenocarcinomas, usually of the uterine corpus, but occasionally of other sites, may have microglandular patterns that can lead to their misdiagnosis, sometimes as microglandular hyperplasia. Pure squamous cell carcinomas of the uterine corpus frequently are composed of very well differentiated epithelium, so that it is possible to misinterpret them as nonneoplastic, and a similar phenomenon may occur in association with the squamous element in some adenocarcinomas with squamous differentiation. Other uterine entities that may be underdiagnosed are malignant lymphoma of the cervix, placental site trophoblastic tumor, myxoid leiomyosarcoma, endometrial stromal sarcoma with glandular differentiation, and mullerian adenosarcoma. Consideration of a variety of architectural and cytological features should facilitate their interpretation. One recently described variant of adenocarcinoma of the fallopian tube that may be confused with the usually clinically benign female adnexal tumors of probable Wolffian origin is microfollicular endometrioid adenocarcinoma. Ovarian tumors subject to misinterpretation that are reviewed herein include metastatic tumors with deceptivity benign foci, endometrioid adenocarcinomas that may be misdiagnosed as sex cord tumors, and cystic granulosa cell tumors that may be misinterpreted as follicle cysts. Finally, rare variants of malignant mesothelioma that may be underdiagnosed are reviewed. Copyright (C) 1995 by W.B. Saunders Company RP YOUNG, RH (reprint author), MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114, USA. NR 0 TC 11 Z9 11 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0740-2570 J9 SEMIN DIAGN PATHOL JI Semin. Diagn. Pathol. PD FEB PY 1995 VL 12 IS 1 BP 14 EP 29 PG 16 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA QH460 UT WOS:A1995QH46000003 PM 7770671 ER PT J AU KOFF, RS DIENSTAG, JL AF KOFF, RS DIENSTAG, JL TI EXTRAHEPATIC MANIFESTATIONS OF HEPATITIS-C AND THE ASSOCIATION WITH ALCOHOLIC LIVER-DISEASE SO SEMINARS IN LIVER DISEASE LA English DT Review ID PORPHYRIA-CUTANEA-TARDA; ESSENTIAL MIXED CRYOGLOBULINEMIA; CHRONIC ACTIVE HEPATITIS; NON-B-HEPATITIS; CIRCULATING IMMUNE-COMPLEXES; VIRUS-INFECTION; APLASTIC-ANEMIA; NON-A; HEPATOCELLULAR-CARCINOMA; RHEUMATOID-ARTHRITIS C1 MASSACHUSETTS GEN HOSP,MED SERV,GASTROINTESTINAL UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CTR LIVER BILIARY PANCREAS,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. RP KOFF, RS (reprint author), METROWEST MED CTR,DEPT MED,FRAMINGHAM UNION CAMPUS,115 LINCOLN ST,FRAMINGHAM,MA 01701, USA. NR 79 TC 57 Z9 58 U1 1 U2 1 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 381 PARK AVE SOUTH, NEW YORK, NY 10016 SN 0272-8087 J9 SEMIN LIVER DIS JI Semin. Liver Dis. PD FEB PY 1995 VL 15 IS 1 BP 101 EP 109 DI 10.1055/s-2007-1007267 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QU745 UT WOS:A1995QU74500010 PM 7597440 ER PT J AU KANTOFF, PW AF KANTOFF, PW TI NEW AGENTS IN THE THERAPY OF HORMONE-REFRACTORY PATIENTS WITH PROSTATE-CANCER SO SEMINARS IN ONCOLOGY LA English DT Article; Proceedings Paper CT Symposium on Cancer and the Older Patient CY JUN 06, 1994 CL SEATTLE, WA ID TRIAL; SURAMIN; ANTIGEN RP KANTOFF, PW (reprint author), DANA FARBER CANC INST,DEPT GENITOURINARY ONCOL,44 BINNEY ST,ROOM 1846,BOSTON,MA 02115, USA. NR 11 TC 17 Z9 17 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD FEB PY 1995 VL 22 IS 1 SU 1 BP 32 EP 34 PG 3 WC Oncology SC Oncology GA QJ549 UT WOS:A1995QJ54900011 PM 7532323 ER PT J AU COLVETT, KT AF COLVETT, KT TI BILATERAL BREAST-CARCINOMA AFTER RADIATION-THERAPY FOR HODGKINS-DISEASE SO SOUTHERN MEDICAL JOURNAL LA English DT Note ID BOMB SURVIVORS; STAGE-IA; CANCER; IRRADIATION; EXPERIENCE; NEOPLASMS; RISK; MORTALITY; THYMUS AB The success of modern cancer therapy is resulting iq an increasing number of long-term cures. The price of success, however, is the incidence of treatment-related morbidity and mortality. The physician should be aware of the potential sequelae of cancer therapy. A case of bilateral breast cancer occurring 13 years after radiation therapy for Hodgkin's disease prompted me to examine the incidence of this problem and to make recommendations for surveillance of patients. RP COLVETT, KT (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,COX LL,BOSTON,MA 02114, USA. NR 31 TC 11 Z9 11 U1 0 U2 0 PU SOUTHERN MEDICAL ASSN PI BIRMINGHAM PA 35 LAKESHORE DR PO BOX 190088, BIRMINGHAM, AL 35219 SN 0038-4348 J9 SOUTHERN MED J JI South.Med.J. PD FEB PY 1995 VL 88 IS 2 BP 239 EP 242 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA QF505 UT WOS:A1995QF50500017 PM 7839173 ER PT J AU CATES, JA ABEDIN, MZ SAUNDERSKIRKWOOD, KD MOSER, AJ GIURGIU, DIN ROSLYN, JJ AF CATES, JA ABEDIN, MZ SAUNDERSKIRKWOOD, KD MOSER, AJ GIURGIU, DIN ROSLYN, JJ TI PROTEIN-KINASE-C REGULATES PRAIRIE DOG GALLBLADDER ION-TRANSPORT SO SURGERY LA English DT Article ID CHOLESTEROL GALLSTONE FORMATION; ELECTROLYTE TRANSPORT; PHOSPHATIDYLINOSITOL TURNOVER; CA-2+ CALMODULIN; NA+/H+ EXCHANGER; PHORBOL ESTERS; CALCIUM-ION; ABSORPTION; ACTIVATION; SECRETION AB Background. Gallstone formation is characterized by increased biliary calcium (Ca2+) level and altered gallbladder absorption. Recent studies suggest that luminal Ca2+ regulates gallbladder ion transport via intracellular calcium ([Ca2+](ic)). Ca2+-calmodulin and protein kinase C (PKC) are two major systems through which [Ca2+](ic) carries out second-messenger functions in many cell types. We have previously shown that Ca2+-calmodulin regulates basal gallbladder ion transport in prairie dog. The present study tests the hypothesis that PKC is also essential in regulation of gallbladder ion transport in this model. Methods. The role of PKC in regulation of gallbladder ion transport was determined by studying the effects of phorbol esters, synthetic analogues of diacylglycerol, which directly activates PKC. Gallbladders were mounted in Ussing chambers, and standard electrophysiologic parameters were recorded after exposing tissues to either 10(-5) mol/L of 4-alpha-phorbol 12, 13-didecanoate (PDD), 4-beta-phorbol 12-myristate 13-acetate, 4-beta-phorbol 12, 13-dibutyrate (PDB), or 10(-4) mol/L serotonin. Unidirectional Na+, Cl-, and H2O fluxes were measured before and after treatment with only inactive PDD and most active PDB. Results. Mucosal and serosal exposure of tissues to either 4-beta-phorbol 12-myristate 13-acetate or PDB resulted in a decrease in short-circuit current and transepithelial potential difference without any change in tissue resistance. Serotonin induced similar changes in gallbladder electrical properties. PDB caused an inhibition of mucosal to serosal fluxes of Na+, Cl-, and H2O, with a decrease in net Na+ absorption, an increase in net Cl- secretion, and a conversion of net H2O absorption to net H2O secretion. Serosal-to-mucosal fluxes of Na+, Cl-, and H2O did not change. Inactive PDD had no effect on either electrophysiologic parameters or ion and water fluxes. Pretreatment of tissues with PKC antagonist 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine blocked the phorbol ester-induced inhibition of ion transport. Conclusion. PKC regulates gallbladder ion transport in the prairie dog by inhibiting Na+ absorption and stimulating Cl- secretion. C1 MED COLL PENN,DEPT SURG,PHILADELPHIA,PA 19129. UNIV CALIF LOS ANGELES,SCH MED,DEPT SURG,LOS ANGELES,CA 90024. SEPULVEDA VET AFFAIRS MED CTR,DEPT SURG,RES SERV,SEPULVEDA,CA. PHILADELPHIA VET AFFAIRS MED CTR,DEPT SURG,PHILADELPHIA,PA. NR 42 TC 10 Z9 10 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0039-6060 J9 SURGERY JI Surgery PD FEB PY 1995 VL 117 IS 2 BP 206 EP 212 DI 10.1016/S0039-6060(05)80087-X PG 7 WC Surgery SC Surgery GA QF384 UT WOS:A1995QF38400013 PM 7846627 ER PT J AU CENDAN, JC SOUBA, WW COPELAND, EM LIND, DS AF CENDAN, JC SOUBA, WW COPELAND, EM LIND, DS TI CYTOKINES REGULATE ENDOTOXIN STIMULATION OF ENDOTHELIAL-CELL ARGININE TRANSPORT SO SURGERY LA English DT Article ID TUMOR-NECROSIS-FACTOR; SEPTIC SHOCK; NITRIC-OXIDE; INTERLEUKIN-1; RECEPTOR; OXYGEN AB Background. Endotoxin (lipopolysaccharide) stimulates transmembrane L-arginine transport In pulmonary artery endothelial cells (PAECs). The proinflammatory cytokines tumor necrosis factor (TNF) and interleukin-1 (IL-1) mediate many of the pathophysiologic effects of endotoxemia and sepsis. Endothelial cells secrete TNF and IL-1 in response to endotoxin. We hypothesize that lipopolysaccharide stimulation of plasma membrane L-arginine transport is mediated via an autocrine cytokine loop involving TNF and IL-1. Methods. Confluent porcine PAECs were incubated with various concentrations of lipopolysaccharide, TNF, or IL-1, and arginine uptake was determined by assaying the uptake of H-3-L-arginine in the presence or absence of Na+ at different time points. PAECs were then incubated with lipopolysaccharide or saline solution after pretreatment with either anti-TNF antibody or IL-1-receptor antagonist, and transport was measured 12 hours later. Results. Lipopolysaccharide, IL-1, and TNF all increased both Na+-dependent and Na+-independent carrier-mediated L-arginine transport in a fashion that was both time and dose dependent. Maximal increases in stimulated arginine uptake occurred 8 hours after exposure to the cytokines and 12 hours after exposure to lipopolysaccharide. Pretreatment of endothelial cells with anti-TNF antibody blocked lipopolysaccharide stimulation of both Na+-independent and Na+-dependent transport by 100% and 90%, respectively. In addition, IL-1-receptor antagonist inhibited lipopolysaccharide stimulation of both Na+-independent and Na+-dependent transport by 65% and 85%, respectively. Conclusions. The marked increase in carrier-mediated L-arginine transport activity produced by lipopolysaccharide, IL-1, and TNF may represent an adaptive response by the pulmonary endothelium to support arginine-dependent biosynthetic pathways during sepsis. Furthermore, lipopolysaccharide stimulation of arginine transport is mediated in part through an autocrine mechanism involving IL-1 and TNF. C1 UNIV FLORIDA,DEPT SURG,GAINESVILLE,FL 32610. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,DIV SURG ONCOL,BOSTON,MA. RI Cendan, Juan/F-2303-2011 OI Cendan, Juan/0000-0002-2744-4838 FU NCI NIH HHS [T32-CA09605-03] NR 23 TC 22 Z9 22 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0039-6060 J9 SURGERY JI Surgery PD FEB PY 1995 VL 117 IS 2 BP 213 EP 219 DI 10.1016/S0039-6060(05)80088-1 PG 7 WC Surgery SC Surgery GA QF384 UT WOS:A1995QF38400014 PM 7846628 ER PT J AU WALKER, RP LAWRENCE, AM PALOYAN, E AF WALKER, RP LAWRENCE, AM PALOYAN, E TI NODULAR DISEASE DURING PREGNANCY SO SURGICAL CLINICS OF NORTH AMERICA LA English DT Article AB Thyroid disease during pregnancy is a significant issue, especially because the incidence of autoimmune disease of the thyroid approaches 10% in women. Exposure to head and neck irradiation in childhood is one of the most significant factors in the development of thyroid neoplasia. However, genetic, environmental, and racial factors have prevailed throughout recorded history and will continue to prevail long after the radiation effect has waned. Well-differentiated thyroid carcinoma occurs predominantly in young women.(5) Pregnancy may be regarded as an enhancing factor in individuals genetically or environmentally predisposed to the development of thyroid neoplasia. The renal loss of iodine in certain developing countries and in mountainous areas of the world, due to the increase in the glomerular filtration rate that occurs in pregnancy, can lead to a relative iodine deficiency and the development of thyroid-stimulating hormone (TSH)induced goiters, especially if dietary supplements are not provided. Furthermore, elevated estrogen levels in pregnancy lead to the hyperproduction of thyroid-binding globulin by the liver, which results in a rise in the number of T-4 binding sites, which is responsible for a decrease in T-3 uptake and an elevated total serum T-4. However, free thyroid hormone levels (free T-3 or free T-4) corrected for the elevated thyroid-binding globulin are in the normal range in pregnancy. The role of TSH in the development of thyroid neoplasia in pregnancy is not well characterized. However, other stimulators of thyroid neoplasia occur in pregnancy in the form of chorionic TSH, and human chorionic gonadotropin (hCG) has a mild TSH effect. Other growth factors may also have a role in thyroid neoplasia, such as somatomedins, growth-stimulating immunoglobulins, placental lactogen, epidermal growth factor, and growth hormone itself. The survival of a placental allograft (the fetus) requires a state of altered immunologic tolerance that is regarded as a condition conducive to the growth of neoplasms and includes the presence of embryogenic antigens both in the placental allograft and in the neoplasms.(2) These immunologic changes which occur in pregnancy are reflected in a reduction in killer cells and helper T cells, the presence of serologic blocking factors, the presence of suppressor T cells and leukocyte migration and enhancement factors in amniotic fluid, alteration of surface antigenicity, and the natural immunosuppressive effect of estrogen, progesterone, and hCG.(1,2,6) C1 US DEPT VET AFFAIRS,VET AFFAIRS EDWARD HINES JR HOSP,RES SERV,HINES,IL 60141. LOYOLA UNIV,MED CTR,DEPT OTOLARYNGOL HEAD & NECK SURG,MAYWOOD,IL 60153. LOYOLA UNIV,MED CTR,DEPT MED,MAYWOOD,IL 60153. UNIV ILLINOIS,DEPT SURG,CHICAGO,IL 60680. NR 6 TC 2 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0039-6109 J9 SURG CLIN N AM JI Surg. Clin.-North Am. PD FEB PY 1995 VL 75 IS 1 BP 53 EP 58 PG 6 WC Surgery SC Surgery GA QG317 UT WOS:A1995QG31700006 PM 7855718 ER PT J AU PEARCE, LB BORODIC, GE JOHNSON, EA FIRST, ER MACCALLUM, R AF PEARCE, LB BORODIC, GE JOHNSON, EA FIRST, ER MACCALLUM, R TI THE MEDIAN PARALYSIS UNIT - A MORE PHARMACOLOGICALLY RELEVANT UNIT OF BIOLOGIC ACTIVITY FOR BOTULINUM TOXIN SO TOXICON LA English DT Article ID TORTICOLLIS; MUSCLE; NERVE AB Although the LD(50) has been used to quantify the biologically active toxin in clinical preparations of botulinum A toxin (Botox(R) and Dysport(R)), a discrepancy exists between the clinical potency of equivalent international units Of different formulations of botulinum A toxin for multiple clinical indications. Our laboratory previously reported that a regional chemodenervation assay in the mouse could be utilized to detect the difference in the potencies of the clinical preparations of toxin [Pearce et al. (1994) Toxic. appl. Pharmac. 128, 69-77]. The purpose of this study was to quantify the regional paralysis produced by botulinum toxin and define a new pharmacologic/biologic unit of activity that more accurately reflects the mechanism of action of botulinum toxin in the clinical setting. Quantal analysis of regional paralysis revealed that the ED(50), defined as the median paralysis unit (MPU) for Botox(R) and Dysport(R), was 0.41 +/- 0.01 and 1.00 +/- 0.02 LD(50) units, respectively. Differences in the potencies found in retrospective clinical studies comparing Botox(R) and Dysport(R) were accurately reflected, for the first time, by the dose of toxin expressed in terms of the MPU (median paralysis unit). The data suggested that the MPU may be a more appropriate measure of the biologic activity in therapeutic formulations of botulinum toxin. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,BOSTON,MA 02114. UNIV WISCONSIN,FOOD RES INST,DEPT MICROBIOL & TOXICOL,MADISON,WI 53706. RP PEARCE, LB (reprint author), BOSTON UNIV,SCH MED,DEPT PHARMACOL,80 E CONCORD ST,BOSTON,MA 02118, USA. NR 33 TC 43 Z9 44 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0041-0101 J9 TOXICON JI Toxicon PD FEB PY 1995 VL 33 IS 2 BP 217 EP 227 DI 10.1016/0041-0101(94)00137-W PG 11 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA QQ042 UT WOS:A1995QQ04200011 PM 7597725 ER PT J AU FERRARA, JLM AF FERRARA, JLM TI THE FEBRILE PLATELET TRANSFUSION REACTION - A CYTOKINE SHOWER SO TRANSFUSION LA English DT Editorial Material ID INTERLEUKIN-1; CONCENTRATE; STORAGE C1 CHILDRENS HOSP,BOSTON,MA 02115. RP FERRARA, JLM (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,44 BINNEY ST,BOSTON,MA 02115, USA. NR 14 TC 28 Z9 29 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD FEB PY 1995 VL 35 IS 2 BP 89 EP 90 DI 10.1046/j.1537-2995.1995.35295125744.x PG 2 WC Hematology SC Hematology GA QD664 UT WOS:A1995QD66400001 PM 7825217 ER PT J AU HAYASHI, H LEE, RS GERMANA, S FRASER, C SYKES, M SACHS, DH LEGUERN, C AF HAYASHI, H LEE, RS GERMANA, S FRASER, C SYKES, M SACHS, DH LEGUERN, C TI RETROVIRAL VECTORS FOR LONG-TERM EXPRESSION OF ALLOGENEIC MAJOR HISTOCOMPATIBILITY COMPLEX TRANSDUCED INTO SYNGENEIC BONE-MARROW CELLS SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT XVth World Congress of the Transplantation-Society CY AUG 28-SEP 02, 1994 CL KYOTO, JAPAN SP TRANSPLANTAT SOC, JAPAN SOC TRANSPLANTAT, JAPAN RES PROMOT SOC CARDIOVASC DIS C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP EAST,SCH MED,TRANSPLANTAT BIOL RES CTR,BOSTON,MA 02129. FU NHLBI NIH HHS [HL48049] NR 2 TC 6 Z9 6 U1 0 U2 0 PU APPLETON & LANGE PI E NORWALK PA 25 VAN ZANT ST, E NORWALK, CT 06855 SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD FEB PY 1995 VL 27 IS 1 BP 178 EP 179 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA QJ199 UT WOS:A1995QJ19900060 PM 7878962 ER PT J AU SHIMADA, H GERMANA, S BANERJEE, P HAYASHI, H SACHS, DH LEGUERN, C AF SHIMADA, H GERMANA, S BANERJEE, P HAYASHI, H SACHS, DH LEGUERN, C TI A SINGLE RETROVIRAL VECTOR FOR TRANSFER OF MULTIPLE MAJOR HISTOCOMPATIBILITY COMPLEX GENES - A GENETIC TOOL FOR TRANSPLANTATION TOLERANCE SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT XVth World Congress of the Transplantation-Society CY AUG 28-SEP 02, 1994 CL KYOTO, JAPAN SP TRANSPLANTAT SOC, JAPAN SOC TRANSPLANTAT, JAPAN RES PROMOT SOC CARDIOVASC DIS ID CLASS-II GENES; MINIATURE SWINE; EXPRESSION; CDNA C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP EAST,SCH MED,TRANSPLANTAT BIOL RES CTR,BOSTON,MA 02129. BIOTRANSPLANT INC,BOSTON,MA. FU PHS HHS [1RO1A133053] NR 8 TC 2 Z9 2 U1 0 U2 0 PU APPLETON & LANGE PI E NORWALK PA 25 VAN ZANT ST, E NORWALK, CT 06855 SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD FEB PY 1995 VL 27 IS 1 BP 180 EP 181 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA QJ199 UT WOS:A1995QJ19900061 PM 7878964 ER PT J AU YAMADA, K SACHS, DH DERSIMONIAN, H AF YAMADA, K SACHS, DH DERSIMONIAN, H TI DIRECT AND INDIRECT RECOGNITION OF PIG CLASS-II ANTIGENS BY HUMAN T-CELLS SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT XVth World Congress of the Transplantation-Society CY AUG 28-SEP 02, 1994 CL KYOTO, JAPAN SP TRANSPLANTAT SOC, JAPAN SOC TRANSPLANTAT, JAPAN RES PROMOT SOC CARDIOVASC DIS ID EPITOPES C1 MASSACHUSETTS GEN HOSP,TRANSPLANTAT BIOL RES CTR,BOSTON,MA 02129. NR 11 TC 19 Z9 20 U1 0 U2 0 PU APPLETON & LANGE PI E NORWALK PA 25 VAN ZANT ST, E NORWALK, CT 06855 SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD FEB PY 1995 VL 27 IS 1 BP 258 EP 259 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA QJ199 UT WOS:A1995QJ19900092 PM 7878993 ER PT J AU WEE, S BOSKOVIC, S EASON, JD WIDMER, MB COSIMI, AB AF WEE, S BOSKOVIC, S EASON, JD WIDMER, MB COSIMI, AB TI PRECLINICAL STUDY OF A RECOMBINANT SOLUBLE TUMOR-NECROSIS-FACTOR RECEPTOR - EFFECT ON IMMUNE-RESPONSE OF RENAL-ALLOGRAFT RECIPIENTS SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT XVth World Congress of the Transplantation-Society CY AUG 28-SEP 02, 1994 CL KYOTO, JAPAN SP TRANSPLANTAT SOC, JAPAN SOC TRANSPLANTAT, JAPAN RES PROMOT SOC CARDIOVASC DIS ID FACTOR-ALPHA; ENHANCEMENT C1 HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. IMMUNEX CORP,SEATTLE,WA. RP WEE, S (reprint author), MASSACHUSETTS GEN HOSP,DEPT SURG,TRANSPLANTAT UNIT,WHITE 546,BOSTON,MA 02114, USA. FU NHLBI NIH HHS [HL-18646] NR 13 TC 2 Z9 2 U1 0 U2 0 PU APPLETON & LANGE PI E NORWALK PA 25 VAN ZANT ST, E NORWALK, CT 06855 SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD FEB PY 1995 VL 27 IS 1 BP 411 EP 412 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA QJ199 UT WOS:A1995QJ19900162 PM 7879042 ER PT J AU EASON, JD WEE, SL KAWAI, T HONG, HZ POWELSON, J WIDMER, M COSIMI, AB AF EASON, JD WEE, SL KAWAI, T HONG, HZ POWELSON, J WIDMER, M COSIMI, AB TI RECOMBINANT HUMAN DIMERIC TUMOR-NECROSIS-FACTOR RECEPTOR (TNFR-FC) AS AN IMMUNOSUPPRESSIVE AGENT IN RENAL-ALLOGRAFT RECIPIENTS SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT XVth World Congress of the Transplantation-Society CY AUG 28-SEP 02, 1994 CL KYOTO, JAPAN SP TRANSPLANTAT SOC, JAPAN SOC TRANSPLANTAT, JAPAN RES PROMOT SOC CARDIOVASC DIS C1 IMMUNEX CORP,SEATTLE,WA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,TRANSPLANTAT UNIT,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA. FU NHLBI NIH HHS [HL-18646] NR 5 TC 2 Z9 2 U1 0 U2 0 PU APPLETON & LANGE PI E NORWALK PA 25 VAN ZANT ST, E NORWALK, CT 06855 SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD FEB PY 1995 VL 27 IS 1 BP 554 EP 554 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA QJ199 UT WOS:A1995QJ19900221 PM 7879095 ER PT J AU DELMONICO, FL COLVIN, R FARRELL, M THISTLETHWAITE, R SPARGO, B OLAUGHLIN, R MATAS, AJ BURKE, B MCHUGH, L LINDBLAD, AS STABLEIN, DM CARTERCAMPBELL, S SALOMON, D LAUBER, S HILLER, M RAYGOR, K HAVERTY, T KNOWLES, R KALE, R AF DELMONICO, FL COLVIN, R FARRELL, M THISTLETHWAITE, R SPARGO, B OLAUGHLIN, R MATAS, AJ BURKE, B MCHUGH, L LINDBLAD, AS STABLEIN, DM CARTERCAMPBELL, S SALOMON, D LAUBER, S HILLER, M RAYGOR, K HAVERTY, T KNOWLES, R KALE, R TI MURINE OKT4A IMMUNOSUPPRESSION IN CADAVER DONOR RENAL-ALLOGRAFT RECIPIENTS - A COOPERATIVE PILOT-STUDY (REPORT-1) SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT XVth World Congress of the Transplantation-Society CY AUG 28-SEP 02, 1994 CL KYOTO, JAPAN SP TRANSPLANTAT SOC, JAPAN SOC TRANSPLANTAT, JAPAN RES PROMOT SOC CARDIOVASC DIS C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. UNIV CHICAGO,MED CTR,CHICAGO,IL 60637. UNIV MINNESOTA,MINNEAPOLIS,MN 55455. RW JOHNSON PHARMACEUT RES INST,ORTHO,RARITAN,NJ. RI Salomon, Daniel/E-9380-2012 NR 0 TC 2 Z9 2 U1 0 U2 0 PU APPLETON & LANGE PI E NORWALK PA 25 VAN ZANT ST, E NORWALK, CT 06855 SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD FEB PY 1995 VL 27 IS 1 BP 863 EP 863 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA QJ199 UT WOS:A1995QJ19900340 ER PT J AU ALBIN, RL YOUNG, AB PENNEY, JB AF ALBIN, RL YOUNG, AB PENNEY, JB TI THE FUNCTIONAL-ANATOMY OF DISORDERS OF THE BASAL GANGLIA SO TRENDS IN NEUROSCIENCES LA English DT Article ID MOVEMENT-DISORDERS; PRIMATE MODELS; DISEASE; NEURONS C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. RP ALBIN, RL (reprint author), UNIV MICHIGAN,DEPT NEUROL,ANN ARBOR,MI 48109, USA. NR 11 TC 141 Z9 143 U1 3 U2 22 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD FEB PY 1995 VL 18 IS 2 BP 63 EP 64 PG 2 WC Neurosciences SC Neurosciences & Neurology GA QD402 UT WOS:A1995QD40200010 PM 7537410 ER PT J AU KATER, SB LIPTON, SA AF KATER, SB LIPTON, SA TI NEUROTRANSMITTER REGULATION OF NEURONAL OUTGROWTH, PLASTICITY AND SURVIVAL IN THE YEAR-2001 SO TRENDS IN NEUROSCIENCES LA English DT Article ID NEUROTOXICITY C1 HARVARD UNIV, SCH MED, PROGRAM NEUROSCI, BOSTON, MA 02115 USA. CHILDRENS HOSP, CELLULAR & MOLEC NEUROSCI LAB, BOSTON, MA 02115 USA. BETH ISRAEL HOSP, DEPT NEUROL, BOSTON, MA 02215 USA. BRIGHAM & WOMENS HOSP, DEPT NEUROL, BOSTON, MA 02115 USA. MASSACHUSETTS GEN HOSP, DEPT NEUROL, BOSTON, MA 02114 USA. CHILDRENS HOSP, DEPT NEUROL, BOSTON, MA 02115 USA. RP COLORADO STATE UNIV, DEPT ANAT & NEUROBIOL, PROGRAM NEURONAL GROWTH & DEV, FT COLLINS, CO 80523 USA. NR 7 TC 9 Z9 9 U1 2 U2 2 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD FEB PY 1995 VL 18 IS 2 BP 71 EP 72 DI 10.1016/0166-2236(95)93877-Z PG 2 WC Neurosciences SC Neurosciences & Neurology GA QD402 UT WOS:A1995QD40200015 ER PT J AU BERNSTEIN, PS CHOI, SY HO, YC RANDO, RR AF BERNSTEIN, PS CHOI, SY HO, YC RANDO, RR TI PHOTOAFFINITY-LABELING OF RETINOIC ACID-BINDING PROTEINS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PIGMENT-EPITHELIUM; BOVINE RHODOPSIN; RAT; DEHYDROGENASE; SKIN; BACTERIORHODOPSIN; IDENTIFICATION; PURIFICATION; EXPRESSION; METABOLISM AB Retinoid-binding proteins are essential mediators of vitamin A function in vertebrate organisms. They solubilize and stabilize retinoids, and they direct the intercellular and intracellular trafficking, transport, and metabolic function of vitamin A compounds in vision and in growth and development. Although many soluble retinoid-binding proteins and receptors have been purified and extensively characterized, relatively few membrane-associated enzymes and other proteins that interact with retinoids have been isolated and studied, due primarily to their inherent instabilities during purification. In an effort to identify and purify previously uncharacterized retinoid-binding proteins, it is shown that radioactively labeled all-trans-retinoic acid can be used as a photoaffinity labeling reagent to specifically tag two known retinoic acid-binding proteins, cellular retinoic acid-binding protein and albumin, in complex mixtures of cytosolic proteins. Additionally, a number of other soluble and membrane-associated proteins that bind all-trans-[11,12-H-3] retinoic acid with high specificity are labeled utilizing the same photoaffinity techniques. Most of these labeled proteins have molecular weights that do not correspond to any known retinoid-binding proteins. Thus, photoaffinity labeling with all-trans-retinoic acid and related photoactivatable retinoids is a method that should prove extremely useful in the identification and purification of novel soluble and membrane-associated retinoid-binding proteins from ocular and nonocular tissues. C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. MASSACHUSETTS EYE & EAR INFIRM,RETINA SERV,DEPT OPHTHALMOL,BOSTON,MA 02114. FU NEI NIH HHS [EY04096] NR 35 TC 28 Z9 28 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 31 PY 1995 VL 92 IS 3 BP 654 EP 658 DI 10.1073/pnas.92.3.654 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QF185 UT WOS:A1995QF18500003 PM 7846032 ER PT J AU GRIBBEN, JG FREEMAN, GJ BOUSSIOTIS, VA RENNERT, P JELLIS, CL GREENFIELD, E BARBER, M RESTIVO, VA KE, XY GRAY, GS NADLER, LM AF GRIBBEN, JG FREEMAN, GJ BOUSSIOTIS, VA RENNERT, P JELLIS, CL GREENFIELD, E BARBER, M RESTIVO, VA KE, XY GRAY, GS NADLER, LM TI CTLA4 MEDIATES ANTIGEN-SPECIFIC APOPTOSIS OF HUMAN T-CELLS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TUMOR-NECROSIS-FACTOR; MONOCLONAL-ANTIBODY; DNA FRAGMENTATION; RECEPTOR; CD28; LYMPHOCYTES; ACTIVATION; PROLIFERATION; INTERLEUKIN-2; FAS AB The regulation of T cell-mediated immune responses requires a balance between amplification and generation of effector function and subsequent selective termination by clonal deletion. Although apoptosis of previously activated T cells can be induced by signaling of the tumor necrosis factor receptor family, these molecules do not appear to regulate T-cell clonal deletion in an antigen-specific fashion. We demonstrate that cross-linking of the inducible T-cell surface molecule CTLA4 can mediate apoptosis of previously activated human T lymphocytes. This function appears to be antigen-restricted, since a concomitant signal T-cell receptor signal is required. Regulation of this pathway may provide a novel therapeutic strategy to delete antigen-specific activated T cells. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. REPLIGEN CORP,CAMBRIDGE,MA 02139. RP GRIBBEN, JG (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA 40416]; NIAID NIH HHS [AI 35225] NR 24 TC 319 Z9 323 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 31 PY 1995 VL 92 IS 3 BP 811 EP 815 DI 10.1073/pnas.92.3.811 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QF185 UT WOS:A1995QF18500035 PM 7846057 ER PT J AU WEISSMAN, D LI, YX ANANWORANICH, J ZHOU, LJ ADELSBERGER, J TEDDER, TF BASELER, M FAUCI, AS AF WEISSMAN, D LI, YX ANANWORANICH, J ZHOU, LJ ADELSBERGER, J TEDDER, TF BASELER, M FAUCI, AS TI 3 POPULATIONS OF CELLS WITH DENDRITIC MORPHOLOGY EXIST IN PERIPHERAL-BLOOD, ONLY ONE OF WHICH IS INFECTABLE WITH HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE INFECTION; DENDRITIC CELL; PRECURSOR ID CD4+ T-CELLS; GM-CSF; INFECTION; REPLICATION; MACROPHAGES; COMPETENT; TNF AB Conflicting data have been reported with regard to the infectability, dysfunction, and depletion of dendritic cells (DCs) in human immunodeficiency virus (HIV) disease. These discrepancies could potentially be explained by the existence of multiple subsets of cells with dendritic morphology in peripheral blood. The isolation of DCs in humans is accomplished through negative selection until a morphologically pure population is obtained. Recently, DC precursors purified from peripheral blood by negative selection have been observed to develop into functionally and morphologically mature DCs. In this report we identify three populations of cells in peripheral blood that have or can develop a dendritic morphology. The first population, when allowed to mature in culture, develops a dendritic morphology and gains the expression of HB15, a marker of DCs in blood, thymus, skin, and lymphoid organs. The second population expresses HB15 and has the phenotypic and morphologic characteristics of mature DCs. The third population is morphologically very similar to mature DCs but does not share the same T-cell-stimulatory activity and is the only population that is infectable with HIV. Understanding the heterogeneity of cells of dendritic lineage and/or morphology in the peripheral blood will aid in understanding their role as antigen-presenting cells in general and as potential participants in the immunopathogenesis of HIV disease. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,FREDERICK,MD 21702. RP WEISSMAN, D (reprint author), NIAID,IMMUNOREGULAT LAB,BLDG 10,ROOM 6A02,BETHESDA,MD 20892, USA. NR 19 TC 176 Z9 176 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 JAN 31 PY 1995 VL 92 IS 3 BP 826 EP 830 DI 10.1073/pnas.92.3.826 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QF185 UT WOS:A1995QF18500038 PM 7846060 ER PT J AU BOUBNOV, NV HALL, KT WILLS, Z LEE, SE HE, DM BENJAMIN, DM PULASKI, CR BAND, H REEVES, W HENDRICKSON, EA WEAVER, DT AF BOUBNOV, NV HALL, KT WILLS, Z LEE, SE HE, DM BENJAMIN, DM PULASKI, CR BAND, H REEVES, W HENDRICKSON, EA WEAVER, DT TI COMPLEMENTATION OF THE IONIZING-RADIATION SENSITIVITY, DNA END BINDING, AND V(D)J RECOMBINATION DEFECTS OF DOUBLE-STRAND BREAK REPAIR MUTANTS BY THE P86 KU AUTOANTIGEN SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID COMBINED IMMUNE-DEFICIENCY; HAMSTER OVARY CELL; SCID MUTATION; MOUSE THYMOCYTES; PROTEIN-KINASE; REARRANGEMENT; MECHANISM; ANTIGEN; MICE; MOLECULES AB Two ionizing radiation-sensitive (IR(s)) and DNA double-strand break (DSB) mutants, sxi-3 and sxi-2, were shown to be severely deficient in a DNA end binding activity, similar to a previously described activity of the Ku autoantigen, correlating with the xrs (XRCC5) mutations. Cell fusions with xrs-6, another IR(s), DSB repair-deficient cell line, defined these sri mutants in the XRCC5 group. sxi-3 cells have low expression levels of the p86Ku mRNA, Introduction of the Ku p86 gene, but not the p70 Ku gene, complemented the IR(s), DNA end binding, and variable(diversity)joining [V(D)J] recombination signal and coding junction deficiencies of sxi-3. Thus, the p86 Ku gene product is essential for DSB repair and V(D)J recombination. C1 CHILDRENS HOSP,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOLEC GENET,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT RHEUMATOL & IMMUNOL,LYMPHOCYTE BIOL SECT,BOSTON,MA 02115. UNIV N CAROLINA,THURSTON ARTHRITIS CTR,DIV RHEUMATOL & IMMUNOL,CHAPEL HILL,NC 27599. BROWN UNIV,DEPT MOLEC BIOL CELL BIOL & BIOCHEM,DIV BIOL & MED,PROVIDENCE,RI 02912. FU NCI NIH HHS [CA52694, CA13943]; NIAID NIH HHS [AI35763] NR 41 TC 138 Z9 138 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 JAN 31 PY 1995 VL 92 IS 3 BP 890 EP 894 DI 10.1073/pnas.92.3.890 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QF185 UT WOS:A1995QF18500051 PM 7846073 ER PT J AU PIERCE, EA AVERY, RL FOLEY, ED AIELLO, LP SMITH, LEH AF PIERCE, EA AVERY, RL FOLEY, ED AIELLO, LP SMITH, LEH TI VASCULAR ENDOTHELIAL GROWTH-FACTOR VASCULAR-PERMEABILITY FACTOR EXPRESSION IN A MOUSE MODEL OF RETINAL NEOVASCULARIZATION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ANGIOGENESIS; HYPOXIA; MULLER CELLS; RETINOPATHY OF PREMATURITY ID VASOPROLIFERATIVE MICROANGIOPATHY; CELL-DIFFERENTIATION; ANGIOGENESIS FACTOR; MINIATURE PIGS; TISSUE HYPOXIA; RNA; SECRETE; MITOGEN; INVIVO AB Neovascular diseases of the retina are a major cause of blindness worldwide. Hypoxia is thought to be a common precursor to neovascularization in many retinal diseases, but the factors involved in the hypoxic neovascular response have not been fully identified. To investigate the role of vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) in retinal neovascularization, the expression of VEGF/VPF mRNA and protein were studied in a mouse model of proliferative retinopathy. RNA (Northern) blot analysis revealed that retinal VEGF/VPF mRNA expression increased 3-fold between 6 and 12 hr of relative retinal hypoxia and remained elevated during the development of neovascularization. In situ hybridization localized VEGF/VPF mRNA to cells bodies in the inner nuclear layer of the retina. Immunohistochemical confocal microscopy demonstrated that VEGF/VPF protein levels increase with a time course similar to that of the mRNA. The cells in the inner nuclear layer of the retina that produce VEGF/VPF were identified morphologically as Muller cells. These data suggest that VEGF/WF expression in the retina plays a central role in the development of retinal ischemia-induced ocular neovascularization. C1 CHILDRENS HOSP,DEPT OPHTHALMOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. UNIV CALIF SANTA BARBARA,NEUROSCI RES INST,SANTA BARBARA,CA 93103. JOSLIN DIABET CTR,BEETHAM EYE INST,BOSTON,MA 02215. JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02215. FU NEI NIH HHS [EY08670, K11 EY00343] NR 38 TC 770 Z9 799 U1 1 U2 12 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 JAN 31 PY 1995 VL 92 IS 3 BP 905 EP 909 DI 10.1073/pnas.92.3.905 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QF185 UT WOS:A1995QF18500054 PM 7846076 ER PT J AU ODRISCOLL, GA ALPERT, NM MATTHYSSE, SW LEVY, DL RAUCH, SL HOLZMAN, PS AF ODRISCOLL, GA ALPERT, NM MATTHYSSE, SW LEVY, DL RAUCH, SL HOLZMAN, PS TI FUNCTIONAL NEUROANATOMY OF ANTISACCADE EYE-MOVEMENTS INVESTIGATED WITH POSITRON EMISSION TOMOGRAPHY SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CEREBRAL BLOOD-FLOW; SPATIAL-MOTOR PROCESSES; FRONTAL-LOBE LESIONS; BASAL GANGLIA; STIMULUS DIRECTION; PREFRONTAL CORTEX; SACCADES; PERFORMANCE; TASK; GOAL AB Increasing interest in the role of the frontal lobe in relation to psychiatric and neurologic disorders has popularized tests of frontal function. One of these is the antisaccade task, in which bath frontal lobe patients and schizophrenics are impaired despite normal performance on (pro)saccadic tasks. We used positron emission tomography to examine the cerebral blood flow changes associated with the performance of antisaccades in normal individuals. We found that the areas of the brain that were more active during antisaccades than saccades were highly consistent with the oculomotor circuit, including frontal eye fields (FEFs), supplementary motor area, thalamus, and putamen. Superior parietal lobe and primary visual cortex were also significantly more active. In contrast, prefrontal areas 46 and 9 were not more active during antisaccades than during saccades. Performance of some frontal patients on the antisaccade task has been likened to a bradykinesia, or the inability to initiate a willed movement. It is the necessity to will the movement and inhibit competing responses that intuitively linked this task to the dorsolateral prefrontal cortex in frontal patients. Our data suggest that it is the FEFs in prefrontal cortex that differentiate between conditions in which the required oculomotor response changes while the stimulus remains the same, rather than areas 46 and 9, which, in human studies, have been linked to the performance of complex cognitive tasks. Such a conclusion is consistent with single-unit studies of nonhuman primates that have found that the FEFs, the executive portion of the oculomotor circuit, can trigger, inhibit, and set the target of saccades. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT NUCL MED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BELMONT,MA 02178. MCLEAN HOSP,MAILMAN RES CTR,PSYCHOL LAB,BELMONT,MA 02178. RP ODRISCOLL, GA (reprint author), HARVARD UNIV,DEPT PSYCHOL,33 KIRKLAND ST,CAMBRIDGE,MA 02138, USA. FU NIMH NIH HHS [MH31154, MH31340, MH44860, R01 MH031340] NR 36 TC 223 Z9 226 U1 2 U2 4 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 JAN 31 PY 1995 VL 92 IS 3 BP 925 EP 929 DI 10.1073/pnas.92.3.925 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QF185 UT WOS:A1995QF18500058 PM 7846080 ER PT J AU STOLER, JM HERRIN, JT HOLMES, LB AF STOLER, JM HERRIN, JT HOLMES, LB TI GENITAL ABNORMALITIES IN FEMALES WITH BARDET-BIEDL SYNDROME SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE BARDET-BIEDL SYNDROME; VAGINAL ATRESIA; UROGENITAL SINUS; GENITAL ABNORMALITIES IN FEMALES ID MANIFESTATIONS AB The major manifestations of the Bardet-Biedl syndrome are digital anomalies, tapetoretinal degeneration, obesity, renal abnormalities, and hypogenitalism (described mainly in males). We report on 2 girls with Bardet-Biedl syndrome who also had vaginal atresia. A similar association in females with Bardet-Biedl syndrome was suggested in published reports of 11 affected individuals who had structural genital abnormalities, (some of which were missed in childhood), including persistent urogenital sinus, ectopic urethra, hypoplasia of the uterus, ovaries and fallopian tubes, uterus duplex, and septate vagina. The association of atresia of the vagina and other malformations of female genital structures in individuals with Bardet-Biedl syndrome has often been missed in childhood and should be looked for more systematically. (C) 1995 Wiley-Liss, Inc. C1 MASSACHUSETTS GEN HOSP,CHILDRENS SERV,BOSTON,MA 02114. RP STOLER, JM (reprint author), MASSACHUSETTS GEN HOSP,GENET & TERATOL UNIT,WARREN 801,32 FRUIT ST,BOSTON,MA 02114, USA. FU NIGMS NIH HHS [5T32GM07748-13] NR 13 TC 32 Z9 33 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 JAN 30 PY 1995 VL 55 IS 3 BP 276 EP 278 DI 10.1002/ajmg.1320550306 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA QH883 UT WOS:A1995QH88300005 PM 7726222 ER PT J AU BADIMON, L ROYO, T MARTINEZGONZALEZ, J BADIMON, JJ AF BADIMON, L ROYO, T MARTINEZGONZALEZ, J BADIMON, JJ TI DEVELOPMENT OF CORONARY ATHEROSCLEROSIS AND OF ITS CLINICAL COMPLICATIONS SO MEDICINA CLINICA LA Spanish DT Article ID ACUTE MYOCARDIAL-INFARCTION; SMOOTH-MUSCLE CELLS; ISCHEMIC-HEART-DISEASE; ARTERY DISEASE; GROWTH-FACTOR; UNSTABLE ANGINA; VESSEL WALL; VONWILLEBRANDS DISEASE; PLATELET DEPOSITION; ENDOTHELIAL-CELLS C1 HOSP SANTA CRUZ & SAN PABLO,CONSEJO SUPER INVEST CIENTIFICAS,UNIDAD & FDN INVEST CARDIOVASC,E-08025 BARCELONA,SPAIN. MASSACHUSETTS GEN HOSP,CARDIAC UNIT,BOSTON,MA 02114. RI BADIMON, LINA/O-4711-2014 OI BADIMON, LINA/0000-0002-9162-2459 FU NHLBI NIH HHS [HL-38943] NR 56 TC 2 Z9 2 U1 0 U2 0 PU EDICIONES DOYMA S/A PI BARCELONA PA TRAV DE GRACIA 17-21, 08021 BARCELONA, SPAIN SN 0025-7753 J9 MED CLIN-BARCELONA JI Med. Clin. PD JAN 28 PY 1995 VL 104 IS 3 BP 105 EP 114 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA QG913 UT WOS:A1995QG91300009 PM 7877359 ER PT J AU SPEELMAN, BA ALLEN, K GROUNDS, TL NEUTRA, MR KIRCHHAUSEN, T WILSON, JM AF SPEELMAN, BA ALLEN, K GROUNDS, TL NEUTRA, MR KIRCHHAUSEN, T WILSON, JM TI MOLECULAR CHARACTERIZATION OF AN APICAL EARLY ENDOSOMAL GLYCOPROTEIN FROM DEVELOPING RAT INTESTINAL EPITHELIAL-CELLS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DENSITY-LIPOPROTEIN RECEPTOR; FACTOR-II RECEPTOR; GROWTH-FACTOR; LDL-RECEPTOR; ALPHA-2-MACROGLOBULIN RECEPTOR; ABSORPTIVE CELLS; CYTOPLASMIC TAIL; PLASMA-MEMBRANE; BIOGENESIS; SEQUENCE AB The apical endosomal compartment is thought to be involved in the sorting and selective transport of receptors and ligands across polarized epithelia. To learn about the protein components of this compartment, we have isolated and sequenced a cDNA that encodes a glycoprotein that is located in the apical endosomal tubules of developing rat intestinal epithelial cells, The deduced amino acid sequence predicts a protein of 1216 amino acids with a molecular mass of 133,769 Da. The deduced amino acid sequence together with aminoterminal amino acid sequencing indicate that there is a cleaved 21-amino acid signal sequence at the NH2-terminal portion of the molecule, There is a single hydrophobic region near the carboxyl terminus that has the characteristics of a membrane-spanning domain and a 36-amino acid cytoplasmic tail, We have found that the major form of this protein in intestinal epithelial cells has a molecular mass of 55-60 kDa, which is significantly smaller than the size predicted from the cDNA sequence, suggesting that the protein is synthesized as a large precursor and processed to the smaller form, The smaller form remains associated with the membrane, however, possibly through noncovalent association with the transmembrane portion of the molecule or with another membrane protein, The extracytoplasmic do main is cysteine-rich, with three cysteine rich repeats that are similar to cysteine repeats present in several receptor proteins, However, there is no other significant similarity to other proteins in the GenBank. The cytoplasmic tail contains a possible internalization motif and several consensus motifs for serine/threonine kinases, Northern blot analysis suggests a single abundant message, and Southern blot analysis is consistent with a single gene and the absence of pseudogenes for this unique endosomal protein. C1 UNIV ARIZONA, STEELE MEM CHILDRENS RES CTR, DEPT CELL BIOL & ANAT, TUCSON, AZ 85724 USA. UNIV ARIZONA, STEELE MEM CHILDRENS RES CTR, DEPT PEDIAT, TUCSON, AZ 85724 USA. CHILDRENS HOSP, GASTROINTESTINAL CELL BIOL RES LAB, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DEPT CELL BIOL, BOSTON, MA 02135 USA. CTR BLOOD RES, BOSTON, MA 02135 USA. FU NIDDK NIH HHS [DK-43329] NR 39 TC 15 Z9 16 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 27 PY 1995 VL 270 IS 4 BP 1583 EP 1588 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QD204 UT WOS:A1995QD20400018 PM 7829488 ER PT J AU KARAPLIS, AC LIM, SK BABA, H ARNOLD, A KRONENBERG, HM AF KARAPLIS, AC LIM, SK BABA, H ARNOLD, A KRONENBERG, HM TI INEFFICIENT MEMBRANE TARGETING, TRANSLOCATION, AND PROTEOLYTIC PROCESSING BY SIGNAL PEPTIDASE OF A MUTANT PREPROPARATHYROID HORMONE PROTEIN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FAMILIAL ISOLATED HYPOPARATHYROIDISM; RECOGNITION PARTICLE RECEPTOR; POST-TRANSLATIONAL CLEAVAGE; MALTOSE-BINDING-PROTEIN; ENDOPLASMIC-RETICULUM; MICROSOMAL-MEMBRANES; ESCHERICHIA-COLI; GTP-BINDING; PARATHYROID-HORMONE; SECRETORY PROTEIN AB A preproparathyroid hormone allele from a patient with familial isolated hypoparathyroidism was shown to have a single point mutation in the hydrophobic core of the signal sequence, This mutation, changing a cysteine to an arginine codon at the -8 position of the signal peptide, was associated with deleterious effects on the processing of preproparathyroid hormone to proparathyroid hormone in vitro, To examine the biochemical consequence(s) of this mutation, proteins produced by cell-free translation of wild type and mutant cRNAs were used in assays that reconstitute the early steps of the secretory pathway, We find that the mutation impairs interaction of the nascent protein with signal recognition particle and the translocation machinery, Moreover, cleavage of the mutant signal sequence by solubilized signal peptidase is ineffective, The consequence of this mutation on processing and secretion of parathyroid hormone is confirmed in intact cells by pulse-chase experiments following transient expression of the mutant protein in COS-7 cells. The inability of the mutant signal sequence, however, to interfere with the targeting and processing of other secreted proteins does not support obstruction of the translocation apparatus as the mechanism underlying the dominant mode of inheritance of hypoparathyroidism in this family. C1 MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. FU NIDDK NIH HHS [DK11794] NR 29 TC 60 Z9 61 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 27 PY 1995 VL 270 IS 4 BP 1629 EP 1635 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QD204 UT WOS:A1995QD20400025 PM 7829495 ER PT J AU EASON, JD WEE, S KAWAI, T HONG, HZ POWELSON, JA WIDMER, MB COSIMI, AB AF EASON, JD WEE, S KAWAI, T HONG, HZ POWELSON, JA WIDMER, MB COSIMI, AB TI INHIBITION OF THE EFFECTS OF TNF IN RENAL-ALLOGRAFT RECIPIENTS USING RECOMBINANT HUMAN DIMERIC TUMOR-NECROSIS-FACTOR RECEPTORS SO TRANSPLANTATION LA English DT Article; Proceedings Paper CT 20th Annual Meeting of the American-Society-of-Transplant-Surgeons CY MAY 18-20, 1994 CL CHICAGO, IL SP AMER SOC TRANSPLANT SURGEONS ID FACTOR-ALPHA; MONOCLONAL-ANTIBODY; ACUTE REJECTION; FACTOR-BETA; T-CELLS; SURVIVAL; LYMPHOTOXIN; TRANSPLANTATION; INDUCTION; INVOLVEMENT AB Tumor necrosis factor alpha (TNFa) and lymphotoxin (LT) or TNF beta are closely linked cytokines produced by macrophages and activated T lymphocytes, which play important regulatory roles in the immune response to allografts. They have also been implicated as mediators of the adverse reactions observed during OKT3 therapy. Therefore, anti-TNF agents could be useful both for immunosuppression and for limiting the systemic response observed in patients receiving OKT3. Recombinant TNFR:Fc is a fusion protein that binds TNFa and LT, thereby neutralizing their effects in vitro. The present study investigates the potential clinical application of TNFR:Fc in a nonhuman primate renal allograft model. Cynomolgus renal allograft recipients were treated with TNFR:Fc induction therapy alone or in combination with subtherapeutic doses of cyclosporine. Control animals received no immunosuppression or subtherapeutic cyclosporine. TNFR:Fc, administered as the only immunosuppressive agent, successfully prolonged renal allograft survival in the majority of treated animals. The prolongation of allograft survival was even more impressive when TNFR:Fc was combined with subtherapeutic doses of cyclosporine. Onset of rejection was significantly delayed as well in the TNFR:Fc treated groups. No adverse side effects were observed in any of the TNFR:Fc treated animals. Precursor cytotoxic T cells were detected in peripheral blood samples of treated recipients but the level of effector CTLs in vivo was below the threshold of detection. These results demonstrate that TNFR:Fc can be safely administered and is effective in prolonging renal allograft survival and in delaying the onset of rejection when administered alone or in combination with cyclosporine. C1 MASSACHUSETTS GEN HOSP,GEN SURG SERV,TRANSPLANTAT UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02114. FU NHLBI NIH HHS [HL-18646] NR 35 TC 26 Z9 26 U1 1 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD JAN 27 PY 1995 VL 59 IS 2 BP 300 EP 305 DI 10.1097/00007890-199501270-00025 PG 6 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA QD469 UT WOS:A1995QD46900025 PM 7839455 ER PT J AU HOLLANDER, GA WANG, BP NICHOGIANNOPOULOU, A PLATENBURG, PP VANEWIJK, W BURAKOFF, SJ GUTIERREZRAMOS, JC TERHORST, C AF HOLLANDER, GA WANG, BP NICHOGIANNOPOULOU, A PLATENBURG, PP VANEWIJK, W BURAKOFF, SJ GUTIERREZRAMOS, JC TERHORST, C TI DEVELOPMENTAL CONTROL POINT IN INDUCTION OF THYMIC CORTEX REGULATED BY A SUBPOPULATION OF PROTHYMOCYTES SO NATURE LA English DT Article ID T-CELL DEVELOPMENT; LYMPHOCYTES-T; MICE; MICROENVIRONMENT; DIFFERENTIATION; RESTORATION; RECEPTOR AB T LYMPHOCYTES Of the alpha/beta T-cell receptor (TCR) lineage mature in the thymus, where they undergo a series of differentiation, expansion and selection events(1-7). For normal T-cell ontogeny to occur, thymocytes must interact physically with cortical and medullary thymic stroma cells(8-10). In parallel, interactions of the thymic stromal cells with TCR-positive thymocytes are necessary for the development of the thymic medulla(10-12). Comparable requirements for the differentiation of the cortex have not been defined, however. Here me analyse mutant mouse strains to assess the function of early prothymocytes in the induction of the thymic cortex. We find that animals with a developmental block at the earliest stage of T-lineage commitment lack a functional thymic cortex. This abnormality could be corrected in fetal but not adult animals by transplantation of either fetal or adult wild-type haematopoietic stem cells. Thus a developmentally restricted interaction of fetal stromal cells with early prothymocytes is required for the induction of a cortical microenvironment. In addition, a normal thymic architecture is necessary for sustained T-cell ontogeny. C1 BETH ISRAEL HOSP,DIV IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. ERASMUS UNIV ROTTERDAM,DEPT IMMUNOL,3000 DR ROTTERDAM,NETHERLANDS. RP HOLLANDER, GA (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115, USA. NR 27 TC 209 Z9 212 U1 0 U2 2 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD JAN 26 PY 1995 VL 373 IS 6512 BP 350 EP 353 DI 10.1038/373350a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QD404 UT WOS:A1995QD40400062 PM 7830770 ER PT J AU FISHMAN, JA MATTIA, AR LEE, MJ MARK, EJ DAVIS, BT AF FISHMAN, JA MATTIA, AR LEE, MJ MARK, EJ DAVIS, BT TI A 29-YEAR-OLD MAN WITH AIDS AND MULTIPLE SPLENIC ABSCESSES - DISSEMINATED PNEUMOCYSTIS-CARINII INFECTION AND MYCOBACTERIUM-AVIUM COMPLEX INFECTION INVOLVING THE SPLEEN AND LIVER SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Discussion ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; IMMUNE-DEFICIENCY-SYNDROME; VIRUS INFECTION; EXTRAPULMONARY PNEUMOCYSTOSIS; DISSEMINATED HISTOPLASMOSIS; CRYPTOCOCCUS-NEOFORMANS; SALMONELLA BACTEREMIA; FUNGAL-INFECTIONS; CANDIDA-ALBICANS; AMPHOTERICIN-B C1 MASSACHUSETTS GEN HOSP,TRANSPLANTAT UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RP FISHMAN, JA (reprint author), MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA 02114, USA. NR 50 TC 12 Z9 12 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 26 PY 1995 VL 332 IS 4 BP 249 EP 257 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA QC270 UT WOS:A1995QC27000009 ER PT J AU EMANUEL, EJ STEINER, D AF EMANUEL, EJ STEINER, D TI INSTITUTIONAL CONFLICT-OF-INTEREST SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID OF-INTEREST; CLINICAL-TRIAL; ISSUES C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. ROPES & GRAY,BOSTON,MA 02110. HARVARD UNIV,CAMBRIDGE,MA 02138. RP EMANUEL, EJ (reprint author), CHILDRENS HOSP,DANA FARBER CANC INST,BOSTON,MA 02115, USA. NR 36 TC 45 Z9 46 U1 0 U2 3 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 26 PY 1995 VL 332 IS 4 BP 262 EP 267 DI 10.1056/NEJM199501263320412 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA QC270 UT WOS:A1995QC27000012 PM 7808495 ER PT J AU EMANUEL, EJ DUBLER, NN AF EMANUEL, EJ DUBLER, NN TI PRESERVING THE PHYSICIAN-PATIENT RELATIONSHIP IN THE ERA OF MANAGED CARE SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID HEALTH-MAINTENANCE-ORGANIZATIONS; MEDICAL-CARE; MALPRACTICE CLAIMS; QUALITY; COSTS; COMMUNICATION; CERTIFICATION; DISENROLLMENT; SATISFACTION; DETERMINANTS AB Even without comprehensive health care reform legislation, the US health care system is undergoing significant changes. Probably the most important change is the expansion of managed care with significant price competition. One of the major concerns about this change is the effect of managed care on the physician-patient retationship. To provide a normative standard for evaluating the effect of changes, we need an ideal conception of the physician-patient relationship. This ideal can be summarized by six C's: choice, competence, communication, compassion, continuity, and (no) conflict of interest. For the 37 million uninsured Americans there is little chance of realizing the ideal physician-patient relationship, since they lack the choice of practice setting and physician, receive care in a rushed atmosphere that undermines communication and compassion, and have no continuity of care. While many insured Americans may believe they have an ideal physician-patient relationship, the relationship is threatened by lack of a regular assessment of competence, by financial incentives that undermine good communication, and by the persistence of conflict of interest. The shift to managed care may improve the choice of practice settings, especially in sections of the country that currently lack managed care; increase choice of preventive services; make quality assessments more routine; and improve communication by making greater use of primary care physicians and nonphysician providers. However, the expansion of managed care and the imposition of significant cost control have the potential to undermine all aspects of the ideal physician-patient relationship. Choice could be restricted by employers and by managed care selection of physicians; poor quality indicators could undermine assessments of competence; productivity requirements could eliminate time necessary for communication; changing from one to another managed care plan to secure the lowest costs could produce significant disruption in continuity of care; and use of salary schemes that reward physicians for not using medical services could increase conflict of interest. C1 HARVARD UNIV,SCH MED,DIV MED ETH,BOSTON,MA. MONTEFIORE MED CTR,ALBERT EINSTEIN COLL MED,DEPT EPIDEMIOL & SOCIAL MED,DIV BIOETH,BRONX,NY 10467. RP EMANUEL, EJ (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC EPIDEMIOL & CONTROL,44 BINNEY ST,BOSTON,MA 02115, USA. NR 91 TC 291 Z9 292 U1 0 U2 16 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 25 PY 1995 VL 273 IS 4 BP 323 EP 329 DI 10.1001/jama.273.4.323 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA QC057 UT WOS:A1995QC05700033 PM 7815662 ER PT J AU BUNKER, CA KINGSTON, RE AF BUNKER, CA KINGSTON, RE TI IDENTIFICATION OF A CDNA FOR SSRP1, AN HMG-BOX PROTEIN, BY INTERACTION WITH THE C-MYC ONCOPROTEIN IN A NOVEL BACTERIAL EXPRESSION SCREEN SO NUCLEIC ACIDS RESEARCH LA English DT Article ID DNA-BINDING; ESCHERICHIA-COLI; LAMBDA-REPRESSOR; TRANSCRIPTION; ENHANCER; DOMAIN; MAX; YEAST; PHOSPHATASE; RECOGNITION AB We describe a system for screening cDNA expression libraries in Escherichia coli based on protein-protein interactions. The system utilizes fusion proteins containing the DNA binding domain of the lambda phage cl repressor and a heterologous dimerization domain, which is the target of the screen. Such chimeric proteins were functional as transcriptional repressors in E.coli; function was dependent on the presence of the heterologous dimerization domain, and function of the chimeras was disrupted by expression of excess dimerization domain. A screen was designed to identify factors that could interact with the heterologous dimerization domain and thereby inactivate the chimeric repressor. We used this screen to identify factors that could interact with the basic helix-loop-helix/leucine zipper domains of c-Myc, and isolated the cDNA for a previously characterized HMG domain protein that interacts specifically with c-Myc in this system. This screening method could be used with proteins that have the ability to homo- or heterodimerize. C1 MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA. NR 44 TC 27 Z9 27 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 25 PY 1995 VL 23 IS 2 BP 269 EP 276 DI 10.1093/nar/23.2.269 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QJ418 UT WOS:A1995QJ41800012 PM 7862532 ER PT J AU YAMADA, K GONCALVES, E CARPENTIER, JL KAHN, CR SHOELSON, SE AF YAMADA, K GONCALVES, E CARPENTIER, JL KAHN, CR SHOELSON, SE TI TRANSMEMBRANE DOMAIN INVERSION BLOCKS ER RELEASE AND INSULIN-RECEPTOR SIGNALING SO BIOCHEMISTRY LA English DT Article ID TYROSINE KINASE-ACTIVITY; POINT MUTATION; ENDOPLASMIC-RETICULUM; MEMBRANE-PROTEINS; NEU ONCOGENE; BETA-SUBUNIT; ACTIVATION; DEGRADATION; SUBSTITUTION; RETENTION AB Activation of the insulin receptor, like other tyrosine kinase receptors, appears to require dimerization. We have shown previously that, even in the absence of insulin, full receptor activation can be induced by changes in the receptor transmembrane domain (TMD), suggesting that TMD dimerization is sufficient for receptor activation. To further understand the importance of the TMD in insulin receptor activation, we have inverted the entire TMD sequence including flanking basic amino acids, residue-for-residue. This mutation was predicted to alter the ability of a TMD alpha-helix to form homodimers and higher level aggregates. Despite apparently normal protein folding on either side of the membrane, this mutation caused ER retention and, for those receptors that reached the cell surface, blockade of insulin-stimulated kinase signal transmission. However, the signaling blockade could be overcome by proteolytic activation with trypsin. In contrast, shifting only the basic cytoplasmic residues to the opposite side of the TMD or mutation to neutral residues had no detectable effect on assembly, biosynthesis, topology, or signaling. These findings extend our previous observations to suggest that TMD interactions within the membrane are not only sufficient for receptor activation, but may be required. TMD interactions also appear to be necessary for oligomeric assembly and biosynthetic maturation of the insulin receptor. C1 JOSLIN DIABET CTR,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02215. UNIV GENEVA,DEPT MORPHOL,CH-1211 GENEVA 4,SWITZERLAND. FU NIDDK NIH HHS [DK 36836, DK 43123, DK 31026] NR 35 TC 10 Z9 10 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JAN 24 PY 1995 VL 34 IS 3 BP 946 EP 954 DI 10.1021/bi00003a029 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QD198 UT WOS:A1995QD19800029 PM 7827053 ER PT J AU YUAN, ZM KHARBANDA, S KUFE, D AF YUAN, ZM KHARBANDA, S KUFE, D TI 1-BETA-D-ARABINOFURANOSYLCYTOSINE ACTIVATES TYROSINE PHOSPHORYLATION OF P34(CDC2) ITS ASSOCIATION WITH THE SRC-LIKE P56/P53(LYN) KINASE IN HUMAN MYELOID-LEUKEMIA CELLS SO BIOCHEMISTRY LA English DT Article ID JUN GENE-EXPRESSION; PROTEIN-KINASE; PHOSPHATIDYLINOSITOL 3-KINASE; LYMPHOCYTES-B; DNA-SYNTHESIS; MEMBRANE IMMUNOGLOBULIN; CROSS-LINKING; DIFFERENTIATION; MECHANISM; ARABINOFURANOSYLCYTOSINE AB Recent studies have demonstrated that treatment of human myeloid leukemia cells with 1-beta-D-arabinofuranosylcytosine (ara-C) is associated with activation of serine/threonine protein kinases and early response gene expression. The present work has examined the involvement of protein tyrosine phosphorylation in ara-C induced responses of HL-60 myeloid leukemia cells. The results of immuno-precipitation studies demonstrate that HL-60 cells respond to ara-C with tyrosine phosphorylation of the cell cycle regulatory protein p34(cdc2) a decrease in the activity of this kinase. This effect was detectable at 15 min of ara-C exposure. Coimmunoprecipitations with anti-p34(cdc2) support binding of this protein to the Src-like p56/p53(lyn) tyrosine kinase in ara-C-treated, but not untreated, cells. The results further demonstrate that ara-C treatment is associated with a dose-dependent activation of p56/p53(lyn) and that ara-C-induced p56/p53(lyn) activity is blocked by the protein tyrosine inhibitors herbimycin A and genistein. Studies with a glutathione S-transferase-Lyn fusion protein confirm interaction of p34(cdc2) and p56/p53(lyn) in lysates of ara-C-treated cells. Moreover, we demonstrate that (1) p56/p53(lyn) phosphorylates Tyr-15 of p34(cdc2) in vitro and (2) phosphorylation of p34(cdc2) by p56/p53(lyn) inhibits p34(cdc2) activity. These findings indicate that the cellular response to ara-C includes activation of p56/p53(lyn) and that association of p56/p53(lyn) with p34(cdc2) may contribute to regulation of the cell cycle progression in ara-C-treated cells. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC PHARMACOL,BOSTON,MA 02115. FU NCI NIH HHS [CA29431] NR 45 TC 28 Z9 28 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JAN 24 PY 1995 VL 34 IS 3 BP 1058 EP 1063 DI 10.1021/bi00003a041 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QD198 UT WOS:A1995QD19800041 PM 7530044 ER PT J AU BURTON, MD NOURI, M KAZEMI, H AF BURTON, MD NOURI, M KAZEMI, H TI ACETYLCHOLINE AND CENTRAL RESPIRATORY CONTROL - PERTURBATIONS OF ACETYLCHOLINE SYNTHESIS IN THE ISOLATED BRAIN-STEM OF THE NEONATAL RAT SO BRAIN RESEARCH LA English DT Article DE CONTROL OF BREATHING; ACETYLCHOLINE; ISOLATED BRAIN-STEM; 3-BROMOPYRUVATE; HYDROXYCITRATE; CITRATE; TRIETHYLCHOLINE; ATROPINE ID STEM-SPINAL-CORD; ONDINES CURSE; VENTRAL MEDULLA; NEWBORN RAT; HIRSCHSPRUNGS-DISEASE; CONGENITAL FAILURE; RHYTHM GENERATION; AUTOMATIC-CONTROL; INVITRO; CHEMOSENSITIVITY AB The brainstem neurochemical processes which support spontaneous ventilation are not known. Cholinergic transmission may play an important role. If this is true, perturbations in acetylcholine (ACh) turnover should alter ventilatory output in a predictable manner. Using the isolated superfused brainstem-spinal axis from the neonatal rat, the effects of modifiers of ACh synthesis on spontaneous C-4 (phrenic) output were determined. S-Bromopyruvate and hydroxycitrate, inhibitors of acetyl-CoA (substrate for ACh synthesis) formation, caused depression of the C-4 output in a dose-dependent manner when added to the superfusate. Triethylcholine, a false-transmitter generating choline analog, caused a similar depression. Citrate, a cytosolic precursor to acetyl-CoA formation, caused stimulation of C-4 (phrenic) output. The stimulatory effects of citrate were blocked by the muscarinic cholinergic blocker, atropine. These findings are consistent with the view that the ACh synthetic pathway provides a continuous and important input to the normal brainstem elements that support ventilation. C1 HARVARD UNIV,SCH MED,PULM & CRIT CARE UNIT,BOSTON,MA 02114. RP BURTON, MD (reprint author), MASSACHUSETTS GEN HOSP,PULM & CRIT CARE UNIT,MED SERV,BOSTON,MA 02114, USA. NR 42 TC 36 Z9 37 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JAN 23 PY 1995 VL 670 IS 1 BP 39 EP 47 DI 10.1016/0006-8993(94)01249-H PG 9 WC Neurosciences SC Neurosciences & Neurology GA QD044 UT WOS:A1995QD04400004 PM 7719722 ER PT J AU SPECTOR, NL HARDY, L RYAN, C MILLER, WH HUMES, JL NADLER, LM LUEDKE, E AF SPECTOR, NL HARDY, L RYAN, C MILLER, WH HUMES, JL NADLER, LM LUEDKE, E TI 28-KDA MAMMALIAN HEAT-SHOCK PROTEIN, A NOVEL SUBSTRATE OF A GROWTH-REGULATORY PROTEASE INVOLVED IN DIFFERENTIATION OF HUMAN LEUKEMIA-CELLS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID ACUTE PROMYELOCYTIC LEUKEMIA; TRANS-RETINOIC ACID; COLONY-STIMULATING FACTOR; STRESS PROTEINS; TYROSINE PHOSPHORYLATION; T(15-17) TRANSLOCATION; ACTIN POLYMERIZATION; RAR-ALPHA; KINASE; ARREST AB Because of their differentiating effects in neoplastic cells in vitro, the use of retinoids in the treatment of various malignant and premalignant conditions is under investigation, To date, signal transduction pathways involved in retinoid-induced differentiation remain poorly understood. Differentiation of HL-60 cells by all trans-retinoic acid (tRA) is directly mediated by down-regulation of the serine protease myeloblastin (mbn). In this report, we investigate the possibility that the 28-kDa heat shock protein (hsp28), previously linked to differentiation of normal and neoplastic cells including HL-60, may be regulated by mbn, Using NB4 promyelocytic leukemic cells as a differentiative model, we show that tRA induces initial suppression and subsequent up regulation of hsp28 protein, mirroring tRA-induced changes in mbn protein. The progressive reduction in hsp28 mRNA levels in response to tRA suggests that changes in hsp28 protein levels might be posttranscriptionally mediated, raising the possibility that hsp28 may be targeted by mbn. To address this, we developed an assay using purified mbn and recombinant hsp28 and now show that hsp28 is hydrolyzed by mbn but not its homologue, human neutrophil elastase, Moreover, mbn does not indiscriminately hydrolyze other proteins, Identifying hsp28 as a substrate of mbn strongly suggests that hsp28 may be a key component of the tRA signaling pathway involved in regulating cell differentiation. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. JEWISH GEN HOSP,LADY DAVIS INST MED RES,MONTREAL,PQ 4365,CANADA. MERCK & CO INC,BIOCHEM & MOLEC PATHOL,RAHWAY,NJ 07065. AMGEN CORP,THOUSAND OAKS,CA 91320. RP SPECTOR, NL (reprint author), UNIV MIAMI,SCH MED,SYLVESTER COMPREHENS CANC CTR,DIV HEMATOL ONCOL,1475 NW 12TH AVE,D8-4,MIAMI,FL 33136, USA. FU NCI NIH HHS [CA-40216-06, IF32CA08954-01] NR 50 TC 47 Z9 47 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 20 PY 1995 VL 270 IS 3 BP 1003 EP 1006 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QB156 UT WOS:A1995QB15600005 PM 7836350 ER PT J AU MCDOUGAL, WS NICKELEIT, V PAPANICOLAOU, N SCULLY, RE ALTHAUSEN, AF AF MCDOUGAL, WS NICKELEIT, V PAPANICOLAOU, N SCULLY, RE ALTHAUSEN, AF TI A 71-YEAR OLD MAN WITH MASSES IN THE PANCREAS, PRESACRAL REGION, AND LEFT KIDNEY - ANATOMICAL DIAGNOSIS - XANTHOGRANULOMATOUS PYELONEPHRITIS, EXTENDING INTO PERIRENAL SOFT-TISSUE SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Discussion C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP MCDOUGAL, WS (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 11 TC 5 Z9 5 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 19 PY 1995 VL 332 IS 3 BP 174 EP 179 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA QB160 UT WOS:A1995QB16000008 ER PT J AU KOWLURU, A SEAVEY, SE RABAGLIA, ME METZ, SA AF KOWLURU, A SEAVEY, SE RABAGLIA, ME METZ, SA TI NONSPECIFIC STIMULATORY EFFECTS OF MASTOPARAN ON PANCREATIC-ISLET NUCLEOSIDE DIPHOSPHOKINASE ACTIVITY - DISSOCIATION FROM INSULIN-SECRETION SO BIOCHEMICAL PHARMACOLOGY LA English DT Note DE PANCREATIC BETA CELLS; INSULIN SECRETION; MASTOPARAN; NUCLEOSIDE DIPHOSPHOKINASE; GTP-BINDING PROTEINS; AMPHIPHILIC CATIONIC DRUGS ID DIPHOSPHATE KINASE; SUBSTANCE-P; WASP VENOM; CELLS; ACTIVATION; EXOCYTOSIS; PROTEINS AB We examined whether mastoparan (MAS)-induced insulin secretion might involve the activation of nucleoside diphosphokinase (NDP kinase), which catalyzes the conversion of GDP to GTP, a known permissive factor for insulin secretion. MAS and MAS 7 (which activate GTP-binding proteins), but not MAS 17 (an inactive analog), stimulated insulin secretion from normal rat islets. In contrast to their specific effects on insulin secretion, MAS, MAS 7 and MAS 17 each stimulated formation of the phosphoenzyme-intermediate of NDP kinase, as well as its catalytic activity. These effects were mimicked by several cationic drugs. Thus, caution is indicated in using MAS to study cellular regulation, since some of its effects appear to be non-specific, and may be due, in part, to its amphiphilic, cationic nature. C1 UNIV WISCONSIN,SCH MED,DEPT MED,MADISON,WI 53792. UNIV WISCONSIN,SCH MED,ENDOCRINOL SECT,MADISON,WI 53792. WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI 53705. FU NIDDK NIH HHS [DK37312] NR 16 TC 23 Z9 23 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD JAN 18 PY 1995 VL 49 IS 2 BP 263 EP 266 DI 10.1016/S0006-2952(94)00489-7 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QE673 UT WOS:A1995QE67300017 PM 7840804 ER PT J AU MILLER, VT LAROSA, J BARNABEI, V KESSLER, C LEVIN, G SMITHROTH, A GRIFFIN, M STOY, DB BUSH, T ZACUR, H FOSTER, D ANDERSON, J MCKENZIE, A MILLER, S WOOD, PD STEFANICK, ML MARCUS, R AKANA, A HEINRICHS, L KIRCHNER, C OHANLAN, K RUYLE, M SHEEHAN, M JUDD, HL GREENDALE, G BAYALOS, R LOZANO, K KAWAKAMI, K BARRETTCONNOR, E LANGER, R KRITZSILVERSTEIN, D CARRIONPETERSEN, ML CAVERO, C SCHROTT, HG JOHNSON, SR FEDDERSEN, DA KRUTZFELDT, DL BENDA, JA PAUERSTEIN, C TRABAL, J SCHENKEN, R STERN, MP RODRIGUEZSIFUENTES, M EASTON, C WELLS, HB ESPELAND, M HOWARD, G BYINGTON, R LEGAULT, C SHUMAKER, S HOGAN, P HIRE, D WASILAUSKAS, C JAMES, M LANE, K TERRELL, T REECE, S PIERCE, J SNOW, M ANTHONY, S MEBANESIMS, IL EINHORN, P HUNSBERGER, S WACLAWIW, M LIPPEL, K LUCAS, D VERTER, J JACKSON, S KELAGHAN, J PERLMAN, J WOLF, P MCGOWAN, J GORDON, S HEYSE, S FRADKIN, J SHERMAN, S PAGE, L SORENSON, A HULKA, B BRODY, B BURKMAN, R HEANEY, R KRAUSS, R ROBERTS, H WITTES, J RIGGS, L MOSS, R ALBERS, J MARCOVINA, S FINEBERG, SE TRACY, RP MERINO, M SCULLY, R LIVOLSI, V KESSLER, G AF MILLER, VT LAROSA, J BARNABEI, V KESSLER, C LEVIN, G SMITHROTH, A GRIFFIN, M STOY, DB BUSH, T ZACUR, H FOSTER, D ANDERSON, J MCKENZIE, A MILLER, S WOOD, PD STEFANICK, ML MARCUS, R AKANA, A HEINRICHS, L KIRCHNER, C OHANLAN, K RUYLE, M SHEEHAN, M JUDD, HL GREENDALE, G BAYALOS, R LOZANO, K KAWAKAMI, K BARRETTCONNOR, E LANGER, R KRITZSILVERSTEIN, D CARRIONPETERSEN, ML CAVERO, C SCHROTT, HG JOHNSON, SR FEDDERSEN, DA KRUTZFELDT, DL BENDA, JA PAUERSTEIN, C TRABAL, J SCHENKEN, R STERN, MP RODRIGUEZSIFUENTES, M EASTON, C WELLS, HB ESPELAND, M HOWARD, G BYINGTON, R LEGAULT, C SHUMAKER, S HOGAN, P HIRE, D WASILAUSKAS, C JAMES, M LANE, K TERRELL, T REECE, S PIERCE, J SNOW, M ANTHONY, S MEBANESIMS, IL EINHORN, P HUNSBERGER, S WACLAWIW, M LIPPEL, K LUCAS, D VERTER, J JACKSON, S KELAGHAN, J PERLMAN, J WOLF, P MCGOWAN, J GORDON, S HEYSE, S FRADKIN, J SHERMAN, S PAGE, L SORENSON, A HULKA, B BRODY, B BURKMAN, R HEANEY, R KRAUSS, R ROBERTS, H WITTES, J RIGGS, L MOSS, R ALBERS, J MARCOVINA, S FINEBERG, SE TRACY, RP MERINO, M SCULLY, R LIVOLSI, V KESSLER, G TI EFFECTS OF ESTROGEN OR ESTROGEN/PROGESTIN REGIMENS ON HEART-DISEASE RISK-FACTORS IN POSTMENOPAUSAL WOMEN - THE POSTMENOPAUSAL ESTROGEN/PROGESTIN INTERVENTIONS (PEPI) TRIAL SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID HORMONE-REPLACEMENT THERAPY; DENSITY LIPOPROTEIN CHOLESTEROL; ATHEROSCLEROTIC VASCULAR-DISEASE; ACUTE MYOCARDIAL-INFARCTION; CARDIOVASCULAR-DISEASE; PROGESTOGEN REPLACEMENT; CARBOHYDRATE-METABOLISM; PLASMA-LIPOPROTEIN; INSULIN-RESISTANCE; SERUM-LIPIDS AB Objective.-To assess pairwise differences between placebo, unopposed estrogen, and each of three estrogen/progestin regimens on selected heart disease risk factors in healthy postmenopausal women. Design.-A 3-year, multicenter, randomized, double-blind, placebo-controlled trial. Participants.-A total of 875 healthy postmenopausal women aged 45 to 64 years who had no known contraindication to hormone therapy. Intervention.-Participants were randomly assigned in equal numbers to the following groups: (1) placebo; (2) conjugated equine estrogen (CEE), 0.625 mg/d; (3) CEE, 0.625 mg/d plus cyclic medroxyprogesterone acetate (MPA), 10 mg/d for 12 d/mo; (4) CEE, 0.625 mg/d plus consecutive MPA, 2.5 mg/d; or (5) CEE, 0.625 mg/d plus cyclic micronized progesterone (MP), 200 mg/d for 12 d/mo. Primary Endpoints.-Four endpoints were chosen to represent four biological systems related to the risk of cardiovascular disease: (1) high-density lipoprotein cholesterol (HDL-C), (2) systolic blood pressure, (3) serum insulin, and (4) fibrinogen. Analysis.-Analyses presented are by intention to treat. P values for primary endpoints are adjusted for multiple comparisons; 95% confidence intervals around estimated effects were calculated without this adjustment. Results.-Mean changes in HDL-C segregated treatment regimens into three statistically distinct groups: (1) placebo (decrease of 0.03 mmol/L [1.2 mg/dL]); (2) MPA regimens (increases of 0.03 to 0.04 mmol/L [1.2 to 1.6 mg/dl]); and (3) CEE with cyclic MP (increase of 0.11 mmol/L [4.1 mg/dL]) and CEE alone (increase of 0.14 mmol/L [5.6 mg/dL]). Active treatments decreased mean low-density lipoprotein cholesterol (0.37 to 0.46 mmol/L [14.5 to 17.7 mg/dL]) and increased mean triglyceride (0.13 to 0.15 mmol/L [11.4 to 13.7 mg/dL]) compared with placebo. Placebo was associated with a significantly greater increase in mean fibrinogen than any active treatment (0.10 g/L compared with -0.02 to 0.06 g/L); differences among active treatments were not significant. Systolic blood pressure increased and postchallenge insulin levels decreased during the trial, but neither varied significantly by treatment assignment. Compared with other active treatments, unopposed estrogen was associated with a significantly increased risk of adenomatous or atypical hyperplasia (34% vs 1%) and of hysterectomy (6% vs 1%). No other adverse effect differed by treatment assignment or hysterectomy status. Conclusions.-Estrogen alone or in combination with a progestin improves lipoproteins and lowers fibrinogen levels without detectable effects on postchallenge insulin or blood pressure. Unopposed estrogen is the optimal regimen for elevation of HDL-C, but the high rate of endometrial hyperplasia restricts use to women without a uterus. In women with a uterus, CEE with cyclic MP has the most favorable effect on HDL-C and no excess risk of endometrial hyperplasia. C1 JOHNS HOPKINS UNIV,BALTIMORE,MD. STANFORD UNIV,STANFORD,CA. UNIV CALIF LOS ANGELES,LOS ANGELES,CA. UNIV CALIF SAN DIEGO,SAN DIEGO,CA. IOWA STATE UNIV SCI & TECHNOL,AMES,IA. UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX. BOWMAN GRAY SCH MED,WINSTON SALEM,NC. NICHHD,BETHESDA,MD. NIAMSD,BETHESDA,MD. NIDDKD,BETHESDA,MD. NIA,BETHESDA,MD. US PHS,CTR SUPPLY SERV,CTR DRUG DISTRIBUT,PERRY POINT,MD. NW LIPID RES CTR,LIPID LAB,SEATTLE,WA. WISHARD MEM HOSP,GLUCOSE INSULIN LAB,INDIANAPOLIS,IN. UNIV VERMONT,HEMOSTASIS LAB,BURLINGTON,VT. NCI,PATHOL LAB,BETHESDA,MD. MASSACHUSETTS GEN HOSP,BOSTON,MA. JEWISH HOSP ST LOUIS,ST LOUIS,MO. GEORGE WASHINGTON UNIV,WASHINGTON,DC. NHLBI,BETHESDA,MD 20892. NR 58 TC 1670 Z9 1690 U1 4 U2 35 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 18 PY 1995 VL 273 IS 3 BP 199 EP 208 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA QB234 UT WOS:A1995QB23400023 ER PT J AU RAHMAN, MU HUDSON, AP AF RAHMAN, MU HUDSON, AP TI NATURE AND TRANSCRIPTIONAL ROLE OF CATALYTIC SUBUNITS OF YEAST MITOCHONDRIAL CAMP-DEPENDENT PROTEIN-KINASE SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID SACCHAROMYCES-CEREVISIAE; CYCLIC-AMP; STRINGENT RESPONSE; CATABOLITE REPRESSION; REGULATORY SUBUNIT; GLUCOSE REPRESSION; STRAINS; BINDING; GENES; RNA AB We have shown that mitochondrial (mt) transcription in yeast (S. cerevisiae) is governed in part by cAMP via a mt cAMP-dependent protein kinase (cAPK), and that the BCY1 gene product acts as regulatory subunit for that organellar enzyme, as it does for cytoplasmic cAPK. Here we assess mt cAPK activity and mt transcription in mutants for the TPK1, TPK2, and TPK3 genes, which encode catalytic subunits of cytoplasmic cAPK. Protein extracts from purified mitochondria from each of the three possible double TPK mutants show mt cAMP-dependent protein phosphorylation. Relative mt transcript levels in these mutants, however, suggest that TPK2 functions less well than does TPK1 or TPK3 in organellar transcriptional control. Thus, both mt and cytoplasmic cAPKs employ the same species of regulatory and catalytic proteins, and versions of the enzyme having various combinations of catalytic species function differentially in cAMP-dependent mt transcriptional control. (C) 1995 Academic Press, Inc. C1 DEPT VET AFFAIRS MED CTR,MED RES SERV,PHILADELPHIA,PA 19104. MED COLL PENN,DEPT MICROBIOL & IMMUNOL,PHILADELPHIA,PA 19129. NR 22 TC 11 Z9 11 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JAN 17 PY 1995 VL 206 IS 2 BP 756 EP 763 DI 10.1006/bbrc.1995.1107 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA QC115 UT WOS:A1995QC11500046 PM 7826397 ER PT J AU HUIZENGA, DE SZOSTAK, JW AF HUIZENGA, DE SZOSTAK, JW TI A DNA APTAMER THAT BINDS ADENOSINE AND ATP SO BIOCHEMISTRY LA English DT Article ID OXYTRICHA TELOMERIC DNA; QUADRUPLEX STRUCTURE; HUMAN THROMBIN; RNA; INVITRO; OLIGONUCLEOTIDE; SELECTION; MOLECULES; NMR; LIGANDS AB We have used in vitro selection to isolate adenosine/ATP-binding DNA sequences from a pool of approximate to 2 x 10(14) different random-sequence single-stranded DNA molecules. One of these aptamers has been characterized and binds adenosine in solution with a dissociation constant of 6 +/- 3 mu M. Experiments with ATP analogs indicate that functional groups on both the base and the sugar of ATP are involved in the ligand/aptamer interaction. The binding domain of this aptamer was localized to a 42 base sequence by deletion analysis. A pool of mutagenized versions of this sequence was then synthesized and screened for functional adenosine binding sequences; comparison of the selected variants revealed two highly conserved guanosine-rich regions, two invariant adenosine residues, and two regions of predominantly Watson-Crick covariation. This data led us to propose a model of the ATP-binding DNA structure which is based on a stable framework composed of two stacked G-quartets. The two highly conserved adenosine residues may stack between the top G-quartet and the two short stems, forming a pocket in which the adenosine or ATP ligand binds. Site-directed mutagenesis, base analog substitution studies, and the design of highly divergent but functional sequences provide support for this model. C1 MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,PROGRAM BIOL & BIOMED SCI,BOSTON,MA. NR 40 TC 632 Z9 640 U1 31 U2 292 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JAN 17 PY 1995 VL 34 IS 2 BP 656 EP 665 DI 10.1021/bi00002a033 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QB821 UT WOS:A1995QB82100033 PM 7819261 ER PT J AU GUHA, A DASHNER, K BLACK, PM WAGNER, JA STILES, CD AF GUHA, A DASHNER, K BLACK, PM WAGNER, JA STILES, CD TI EXPRESSION OF PDGF AND PDGF RECEPTORS IN HUMAN ASTROCYTOMA OPERATION SPECIMENS SUPPORTS THE EXISTENCE OF AN AUTOCRINE LOOP SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID GROWTH-FACTOR RECEPTORS; MESSENGER-RNA; GLIAL ORIGIN; BRAIN-TUMOR; AMPLIFICATION; TISSUE; CELLS; COEXPRESSION; SUGGESTS; CHAIN AB Established cell lines derived from human malignant astrocytomas typically express a combination of platelet-derived growth factor (PDGF) and PDGF receptor which could form an autocrine loop. In this study, we screened for the essential components of a PDGF autocrine loop in fresh surgical isolates of human astrocytomas, using in situ hybridization and immunohistochemical techniques. Eight malignant astrocytomas (6 glioblastomas and 2 anaplastic astrocytomas), 5 low-grade astrocytomas and 4 non-neoplastic glial specimens (mesial temporal sclerosis) were evaluated. Malignant astrocytomas, and to a lesser extent low-grade astrocytomas, expressed more PDGF-A and PDGF-B than non-neoplastic glia. PDGF-a-receptor expression was elevated both in malignant and in low-grade astrocytomas. These data support the argument that PDGF autocrine loops contribute to the unregulated growth of human astrocytomas. Expression of PDGF and PDGF receptor in low-grade astrocytomas suggests that activation of PDGF autocrine loops may be an early event in the pathogenesis of malignant astrocytomas. (C) 1995 Wiley-Liss, Inc. C1 HARVARD UNIV,SCH MED,BOSTON,MA. HARVARD UNIV,DANA FARBER CANC INST,BOSTON,MA. UNIV TORONTO,DIV NEUROSURG & SURG ONCOL,TORONTO,ON,CANADA. BRIGHAM & WOMENS HOSP,DIV NEUROSURG,BOSTON,MA 02115. CORNELL UNIV,SCH MED,DEPT NEUROL & NEUROSCI,NEW YORK,NY 10021. CORNELL UNIV,SCH MED,DEPT CELL BIOL & ANAT,NEW YORK,NY 10021. FU NCI NIH HHS [CA22042]; NEI NIH HHS [EY06454]; NIGMS NIH HHS [GM31489] NR 18 TC 205 Z9 210 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 JAN 17 PY 1995 VL 60 IS 2 BP 168 EP 173 DI 10.1002/ijc.2910600206 PG 6 WC Oncology SC Oncology GA QH518 UT WOS:A1995QH51800005 PM 7829210 ER PT J AU MATSUGUCHI, T INHORN, RC CARLESSO, N XU, G DRUKER, B GRIFFIN, JD AF MATSUGUCHI, T INHORN, RC CARLESSO, N XU, G DRUKER, B GRIFFIN, JD TI TYROSINE PHOSPHORYLATION OF P95(VAV) IN MYELOID CELLS IS REGULATED BY GM-CSF, IL-3 AND STEEL FACTOR AND IS CONSTITUTIVELY INCREASED BY P210(BCR/ABL) SO EMBO JOURNAL LA English DT Article DE BCR; ABL; GM-CSF; IL-3; VAV ID CHRONIC MYELOGENOUS LEUKEMIA; VAV PROTOONCOGENE PRODUCT; HEMATOPOIETIC-CELLS; SH2 DOMAIN; PROTEIN; KINASE; BCR; GENE; ACTIVATION; IDENTIFICATION AB Vav is a recently described proto-oncogene expressed only in hematopoietic cells which contains an SH2 and two SH3 domains and shares homology with the Dbl GDP-GTP exchange factor and BCR. p95(Vav) is phosphorylated on tyrosine residues in response to stimulation of the T cell antigen receptor, cross-linking of IgE or IgM receptors and stimulation of immature hematopoietic cells by Steel factor. Monoclonal antibodies to human Vav were generated and used to examine the events which regulate tyrosine phosphorylation of p95(Vav) in myeloid cells. In the factor-dependent MO7e cell line, p95(Vav) was rapidly phosphorylated on tyrosine residues in a dose- and time-dependent manner by GM-CSF, IL-3 and Steel factor. Introduction of the BCR/ABL oncogene into this cell line resulted in factor-independent proliferation and constitutive phosphorylation of p95(Vav) Tyrosine phosphorylation of p95(Vav) was also substantially increased by treatment of cytokine-deprived cells with the tyrosine phosphatase inhibitor sodium vanadate, Since many of the cytokines known to induce tyrosine phosphorylation of p95(Vav) are also known to activate JAK family tyrosine kinases, we looked for an interaction of p95(Vav) with JAK kinases, p95(Vav) coprecipitated with JAK2 in MO7e cells stimulated with GM-CSF, but not in unstimulated cells. Also, JAK2 was found to be constitutively associated with p95(Vav) in vivo when expressed at high levels in insect cells using baculovirus vectors. A fusion protein consisting of glutathione-S-transferase and the SH2 domain of p95(Vav) (GST-Vav-SH2) precipitated JAK2, suggesting that this interaction is mediated by the SH2 domain of p95(Vav). GST-Vav-SH2, but not GST, also precipitated JAK1, JAK3 and Tyk2, suggesting that other JAK family kinases might interact with p95(Vav). These results suggest that tyrosine phosphorylation of p95(Vav) is potentially directly regulated by JAK kinases, and further suggest that Vav is broadly involved in signal transduction in myeloid cells initiated by many cytokines and the oncogene BCR/ABL. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. OREGON HLTH SCI UNIV,DIV HEMATOL & ONCOL,PORTLAND,OR 97261. FU NCI NIH HHS [CA36167] NR 40 TC 147 Z9 148 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD JAN 16 PY 1995 VL 14 IS 2 BP 257 EP 265 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QD399 UT WOS:A1995QD39900007 PM 7530656 ER PT J AU HARIHARAN, IK HU, KQ ASHA, H QUINTANILLA, A EZZELL, RM SETTLEMAN, J AF HARIHARAN, IK HU, KQ ASHA, H QUINTANILLA, A EZZELL, RM SETTLEMAN, J TI CHARACTERIZATION OF RHO GTPASE FAMILY HOMOLOGS IN DROSOPHILA-MELANOGASTER - OVEREXPRESSING RHO1 IN RETINAL CELLS CAUSES A LATE DEVELOPMENTAL DEFECT SO EMBO JOURNAL LA English DT Article DE DROSOPHILA; EYE; GTPASE; RAC; RHO ID GUANINE-NUCLEOTIDE EXCHANGE; PROTEIN TYROSINE KINASE; BINDING PROTEIN; FINGER PROTEIN; DOMAIN PROTEIN; GENE-PRODUCT; SEVENLESS; RAS; EXPRESSION; ENCODES AB The rho family of GTPases has been implicated in regulating changes in cell morphology in response to extracellular signals. We have cloned three widely expressed members of this family from Drosophila melanogaster; a rho homologue (Rho1) and two rac homologues (Rad and Rac2). Flies harbouring a Rho1 transgene that is specifically expressed in the eye exhibit a dramatic dose dependent disruption of normal eye development. Flies bearing at least two copies of the transgene display a severe rough eye phenotype characterized by missing secondary and tertiary pigment cells, a substantial reduction in the number of photoreceptor cells and a grossly abnormal morphology of the rhabdomeres. Cell fate determination in the imaginal disc occurs normally and abnormalities become manifest late in pupariation, coincident with the phase when the cells undergo major morphological changes. This phenotype is modified by mutations at several other loci that have been implicated in signal transduction, but not by mutations in ras pathway components. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02129. FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98109. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,SURG RES LAB,BOSTON,MA 02129. RP HARIHARAN, IK (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CTR CANC,BLDG 149,13TH ST,BOSTON,MA 02129, USA. NR 60 TC 88 Z9 93 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD JAN 16 PY 1995 VL 14 IS 2 BP 292 EP 302 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QD399 UT WOS:A1995QD39900011 PM 7835340 ER PT J AU KLEYMAN, TR ROBERTS, C LING, BN AF KLEYMAN, TR ROBERTS, C LING, BN TI A MECHANISM FOR PENTAMIDINE-INDUCED HYPERKALEMIA - INHIBITION OF DISTAL NEPHRON SODIUM-TRANSPORT SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE HYPERKALEMIA; PENTAMIDINE; ACQUIRED IMMUNODEFICIENCY SYNDROME; ION TRANSPORT; POTASSIUM ID PNEUMOCYSTIS-CARINII PNEUMONIA; CORTICAL COLLECTING TUBULE; POTASSIUM CHANNELS; PRIMARY CULTURES; THERAPY; AIDS AB Objectives: To determine whether pentamidine directly affects the transport of renal ions and thus provides a mechanism for hyperkalemia, which develops in as many as 100% of patients with the acquired immunodeficiency syndrome (AIDS) who receive pentamidine for more than 6 days. Design: Transepithelial and single-channel electrical measurements were made on two models of distal-nephron ion transport: an amphibian distal-nephron cell line (A6) and primary cultures of rabbit cortical collecting tubules. Results: Luminal bath application of pentamidine to A6 monolayers inhibited the amiloride-sensitive, short-circuit current with a 50% inhibitory concentration of 700 mu M (five experiments). In the principal cell apical membranes of cortical collecting tubule primary cultures, amiloride-sensitive, 4-picosiemen Na+ channels in cell-attached patches were also identified. When the luminal membrane was directly exposed to 1.0 mu M of pentamidine in the patch pipette solution, channel activity decreased by 40% (11 experiments). Channel inhibition rapidly reversed with washout of intrapipette pentamidine (four experiments). In contrast, replacement of either the luminal bath outside the patch pipette (four experiments) or the serosal bath (five experiments) with pentamidine did not significantly affect Na+ channel activity in the patches. Conclusions: Luminal or ''urinary'' pentamidine inhibits distal nephron reabsorption of Na+ by blocking apical Na+ channels in a manner similar to ''potassium-sparing'' diuretics (for example, amiloride and triamterene). This results in a decrease in the electrochemical gradients that drive secretion of distal nephron K+. Because pentamidine is eliminated through urinary excretion, this renal tubular effect provides a mechanism for pentamidine-induced hyperkalemia. C1 EMORY UNIV,SCH MED,DIV RENAL,ATLANTA,GA 30322. UNIV PENN,SCH MED,PHILADELPHIA,PA 19104. DEPT VET AFFAIRS MED CTR,PHILADELPHIA,PA 19104. VET AFFAIRS MED CTR,ATLANTA,GA 30033. FU NIDDK NIH HHS [K08-DK02111] NR 22 TC 46 Z9 47 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JAN 15 PY 1995 VL 122 IS 2 BP 103 EP 106 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA QC059 UT WOS:A1995QC05900004 PM 7992983 ER PT J AU DZIENNIS, S VANETTEN, RA PAHL, HL MORRIS, DL ROTHSTEIN, TL BLOSCH, CM PERLMUTTER, RM TENEN, DG AF DZIENNIS, S VANETTEN, RA PAHL, HL MORRIS, DL ROTHSTEIN, TL BLOSCH, CM PERLMUTTER, RM TENEN, DG TI THE CD11B PROMOTER DIRECTS HIGH-LEVEL EXPRESSION OF REPORTER GENES IN MACROPHAGES IN TRANSGENIC MICE SO BLOOD LA English DT Note ID MYELOID DIFFERENTIATION; BONE-MARROW; CELLS; MOUSE; IMMUNOGLOBULIN; SEQUENCE; FAMILY; IDENTIFICATION; PROTOONCOGENE; GLYCOPROTEIN AB CD11b is the alpha chain of the Mac-1 integrin and is preferentially expressed in myeloid cells (neutrophils, monocytes, and macrophages). We have previously shown that the CD11b promoter directs cell-type-specific expression in myeloid lines using transient transfection assays. To confirm that these promoter sequences contain the proper regulatory elements for correct myeloid expression of CD11b in vivo, we have used the -1.7-kb human CD11b promoter to direct reporter gene expression in transgenic mice, Stable founder lines were generated with two different reporter genes, a Thy 1.1 surface marker and the Escherichia coli lacZ (beta-galaclosidase) gene, Analysis of founders generated with each reporter demonstrated that the CD11b promoter was capable of driving high levels of transgene expression in murine macrophages for the lifetime of the animals, Similar to the endogenous gene, transgene expression was preferentially found in mature monocytes, macrophages, and neutrophils and not in myeloid precursors. These experiments indicate that the -1.7 CD11b promoter contains the regulatory elements sufficient for high-level macrophage expression. This promoter should be useful for targeting heterologous gene expression to mature myeloid cells. (C) 1995 by The American Society of Hematology, C1 BETH ISRAEL HOSP,DEPT MED,DIV HEMATOL ONCOL,BOSTON,MA 02215. HARVARD UNIV,CTR BLOOD RES,SCH MED,BOSTON,MA. BOSTON UNIV,MED CTR,DEPT MED,BOSTON,MA. BOSTON UNIV,MED CTR,DEPT MICROBIOL,BOSTON,MA. UNIV WASHINGTON,HOWARD HUGHES MED INST,SEATTLE,WA. UNIV WASHINGTON,DEPT IMMUNOL,SEATTLE,WA. UNIV WASHINGTON,DEPT MED,SEATTLE,WA. UNIV WASHINGTON,DEPT BIOCHEM,SEATTLE,WA. FU NCI NIH HHS [CA41456]; NHLBI NIH HHS [T32-HL-07501]; NIAID NIH HHS [AI29690] NR 44 TC 66 Z9 67 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 JAN 15 PY 1995 VL 85 IS 2 BP 319 EP 329 PG 11 WC Hematology SC Hematology GA QB546 UT WOS:A1995QB54600003 PM 7811988 ER PT J AU REMOLDODONNELL, E PARENT, D AF REMOLDODONNELL, E PARENT, D TI DOWN-REGULATION OF NEUTROPHIL CD43 BY OPSONIZED ZYMOSAN SO BLOOD LA English DT Note ID SERINE PROTEASE INHIBITOR; WISKOTT-ALDRICH SYNDROME; CELL-SURFACE EXPRESSION; NADPH OXIDASE; SIALOPHORIN CD43; MAJOR SIALOGLYCOPROTEIN; HUMAN-LEUKOCYTES; ACTIVATION; LEUKOSIALIN; ADHESION AB CD43, a prevalent white blood cell molecule distinguished by its mucin-like surface region, has been proposed as a ''functional barrier'' that prevents or negatively regulates a variety of cell surface interactions. Implicit in this hypothesis is the expectation that CD43 will be altered or removed when white blood cells are activated. To investigate alterations of CD43 in a dramatic example of functional cell activation, suspension neutrophils were challenged with opsonized zymosan, a characterized stimulator of phagocytosis and respiratory burst oxidase. Flow cytometry showed decreased surface density of CD43 in opsonized zymosan-treated neutrophils, and immune precipitation showed decreased cellular CD43 content, indicating that opsonized zymosan downregulates CD43 by a proteolytic mechanism. Based on densitometry of immune precipitates, CD43 levels were decreased 42% +/- 6% in neutrophils treated for 10 minutes with opsonized zymosan and decreased 70% +/- 3% in neutrophils treated with phorbol 12-myristate 13-acetate (PMA). CD43 downregulation in response to opsonized zymosan, like PMA-induced CD43 downregulation, was insensitive to the serine protease inhibitor diisopropylfluorophosphate (DFP). In contrast, CD43 downregulation in response to opsonized zymosan or PMA was prevented by 4-(2-aminoethyl)-benzenesulfonylfluoride (AEBSF) and 3'4'dichloroisocoumarin (3,4-DCI), both of which are characterized serine protease inhibitors. Activation of the neutrophil respiratory burst oxidase by opsonized zymosan or PMA was also insensitive to DFP and prevented by AEBSF and 3,4-DCI. These findings indicate a requirement for a proteolytic step in activation of the respiratory burst of intact suspension neutrophils by opsonized zymosan and PMA and suggest that CD43 cleavage may be a required proteolytic event. (C) 1995 by The American Society of Hematology. C1 HARVARD UNIV, SCH MED, DEPT PEDIAT, BOSTON, MA USA. RP REMOLDODONNELL, E (reprint author), HARVARD UNIV, CTR BLOOD RES, SCH MED, 800 HUNTINGTON AVE, BOSTON, MA 02115 USA. FU NIAID NIH HHS [AI29880] NR 38 TC 25 Z9 25 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD JAN 15 PY 1995 VL 85 IS 2 BP 337 EP 342 PG 6 WC Hematology SC Hematology GA QB546 UT WOS:A1995QB54600005 PM 7811990 ER PT J AU MATHERLY, LH TAUB, JW RAVINDRANATH, Y PROEFKE, SA WONG, SC GIMOTTY, P BUCK, S WRIGHT, JE ROSOWSKY, A AF MATHERLY, LH TAUB, JW RAVINDRANATH, Y PROEFKE, SA WONG, SC GIMOTTY, P BUCK, S WRIGHT, JE ROSOWSKY, A TI ELEVATED DIHYDROFOLATE-REDUCTASE AND IMPAIRED METHOTREXATE TRANSPORT AS ELEMENTS IN METHOTREXATE RESISTANCE IN CHILDHOOD ACUTE LYMPHOBLASTIC-LEUKEMIA SO BLOOD LA English DT Article ID HUMAN-TUMOR-CELLS; GENE AMPLIFICATION; DECREASED POLYGLUTAMYLATION; MEMBRANE CARRIER; P-GLYCOPROTEIN; FLOW-CYTOMETRY; CARCINOMA; POLYGLUTAMATES; ANTIBODIES; PATIENT AB A retrospective study of clinical resistance to methotrexate (MTX) was performed on 29 archival specimens of frozen lymphoblasts obtained from children with acute lymphoblastic leukemia (ALL), including 19 at initial presentation and 10 at first relapse. Blasts were assayed for dihydrofolate reductase and MTX transport by flow cytometry using the fluorescent methotrexate analog, PT430 (Rosowsky et al, J Biol Chem 257:14162, 1982). In contrast to tissue culture cells, patient blasts were often heterogeneous for dihydrofolate reductase content. Of the 19 specimens at initial diagnosis, 7 exhibited dual blast populations, characterized by threefold to 10-fold differences in relative dihydrofolate reductase; the dihydrofolate reductase-overproducing populations comprised 12% to 68% of the total blasts for these specimens. Remission duration intervals for patients exhibiting dual blast populations were notably shorter than for patients expressing a single blast population with lower dihydrofolate reductase (less than or equal to 9 months v greater than or equal to 15 months, respectively), a difference that was statistically significant (P = .045). There was no apparent correlation between expression of increased dihydrofolate reductase at diagnosis and known patient and disease prognostic features (immuno-phenotype, age, sex, and white blood count). For the relapsed patients, 4 of 10 exhibited dual lymphoblast populations with elevated dihydrofolate reductase. The majority of the patient lymphoblast specimens were entirely competent for MTX transport and, likewise, expressed immunoreactive reduced folate carriers by indirect immunofluorescence staining with specific antiserum to the transporter. Three patients (2 at relapse and 1 at diagnosis) exhibited heterogeneous expression of impaired MTX transport (14% to 73% of blasts). In only 1 of these patients did the majority of the lymphoblasts (73%) show impaired MTX transport and for this specimen, immunoreactive carrier proteins were virtually undetectable. These results suggest that heterogeneous expression of elevated dihydrofolate reductase and impaired MTX transport are important modes of resistance in childhood ALL patients undergoing chemotherapy with MTX and that these parameters may serve as predictive indices of clinical response to MTX. (C) 1995 by The American Society of Hematology. C1 MICHIGAN CANC FDN,BIOSTAT UNIT,DETROIT,MI 48201. CHILDRENS HOSP MICHIGAN,DIV HEMATOL ONCOL,DETROIT,MI 48201. WAYNE STATE UNIV,SCH MED,DEPT PEDIAT,DETROIT,MI 48201. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM,BOSTON,MA 02115. RP MATHERLY, LH (reprint author), MICHIGAN CANC FDN,DEV THERAPEUT PROGRAM,110 E WARREN AVE,DETROIT,MI 48201, USA. FU NCI NIH HHS [R01-CA53535, P01-CA19589, R01 CA076641, R01-CA25394] NR 42 TC 69 Z9 70 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JAN 15 PY 1995 VL 85 IS 2 BP 500 EP 509 PG 10 WC Hematology SC Hematology GA QB546 UT WOS:A1995QB54600025 PM 7812005 ER PT J AU CARLSON, JA DICKERSIN, GR SOBER, AJ BARNHILL, RL AF CARLSON, JA DICKERSIN, GR SOBER, AJ BARNHILL, RL TI DESMOPLASTIC NEUROTROPIC MELANOMA - A CLINICOPATHOLOGICAL ANALYSIS OF 28 CASES SO CANCER LA English DT Article DE DESMOPLASTIC NEUROTROPIC MELANOMA; REVIEW; S100; HMB-45; FXIIIA; EPITHELIAL MEMBRANE ANTIGEN; PERINEURIUM; AND SCHWANN CELLS ID MALIGNANT EPITHELIOID SCHWANNOMA; ELECTRON-MICROSCOPY; FACTOR-XIIIA; TUMORS; CELL; VARIANT; METASTASIS; EXPRESSION; SURGERY; FACE AB Background. Desmoplastic neurotropic melanoma (DNM) is a rare variant of malignant melanoma, the natural history and histogenesis of which still are being defined. Methods. The clinical and histologic features of 28 cases of DNM were studied. All published cases of DNM to date were reviewed. Paraffin sections from 26 cases were investigated with a panel of 10 tissue markers. The ultrastructural features of seven cases were evaluated. Results. A comparison of this study's findings with that of other published cases revealed many similarities regarding clinical and pathologic findings and outcome. The patients were white (15 men:13 women; mean and median age, 59 years; range, 22-83 years). Most tumors were located on the head and neck (75%) and were nonpigmented (57%). An associated intraepidermal melanocytic proliferation was identified in 85% of the patients (lentigo maligna in 56%). Histologically, the dermal tumors were composed of tapered, nonpigmented spindle cells in peripheral nerve sheath patterns resembling neuromas, schwannomas, neurofibromas, and perineurial proliferations accompanied by variable neurotropism and desmoplasia; desmoplasia was the most notable feature in most tumors. The mean depth of tumor invasion was 4.1 mm (range, 0.32-9.0 mm). Tumors with continuity between the epidermal and dermal components had a significantly thinner depth of invasion and a more extensive intraepidermal melanocytic proliferation than those tumors with a grenz zone between the two components (2.3 mm vs. 4.6 mm, P = 0.015). Mitotic activity ranged from O/HPF in 10 cases, 1-6/high power field (HPF) in 12 cases, and to greater than 6/HPF in 4 cases. An ulcer was present in 5/27 tumors, regression in 4/27, a microsatellite in 1, and brisk and had nonbrisk tumor infiltrating lymphocytic responses in 2 and 14, respectively. Vimentin was uniformly positive and keratins AE1.3 and Cam 5.2 and Leu-7 were uniformly negative. S100 protein, also uniformly positive, had patchy reactivity in most tumors that expressed EMA (43%). Smooth muscle actin (52%), neuron-specific enolase (42%), and FXIIIa (30%) had patchy positivity. HMB-45 was reactive only in the epidermal and superficial papillary dermal component in 21% of cases. Ultrastructurally, the common features were long, often intertwining cellular processes, intercellular junctions, and discontinuous basal lamina. Melanosomes were not identified. Follow-up data available on 26/28 patients (mean, 36 months; median, 24 months; range, 5-132 months) showed 20 (70%) alive without disease, 2 alive with disease and 3 dead from disease. Seven patients had recurrent local tumor (multiple in four); four had lymph node metastases, and three had visceral metastases. Patients with recurrent disease of any type had significantly thicker tumors (5.4 mm vs. 3.4 mm, P = 0.046) and were more likely to have an ulcerated tumor (P = 0.03). Actuarial 5-year survival for tumors with greater than a 4-mm thickness was 72%, which was greater than that for other types of melanoma with greater than a 4-mm thickness. Conclusions. Desmoplastic neurotropic melanomas are neuroectodermal tumors that usually arise from an intraepidermal melanocytic proliferation but rarely develop de novo in the dermis. Schwannian and perineurial differentiation may account for the desmoplasia and neurotropism encountered in,these neoplasms. Desmoplastic neurotropic melanomas present at a more advanced stage locally and may be associated with a better survival than associated with conventional melanomas of similar depth of invasion. C1 BRIGHAM & WOMENS HOSP,DEPT PATHOL,DIV DERMATOPATHOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT DERMATOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. OI Carlson, John Andrew/0000-0002-6866-6314 NR 80 TC 188 Z9 189 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 JAN 15 PY 1995 VL 75 IS 2 BP 478 EP 494 DI 10.1002/1097-0142(19950115)75:2<478::AID-CNCR2820750211>3.0.CO;2-O PG 17 WC Oncology SC Oncology GA QA968 UT WOS:A1995QA96800010 PM 7812919 ER PT J AU SOBER, AJ BURSTEIN, JM AF SOBER, AJ BURSTEIN, JM TI PRECURSORS TO SKIN-CANCER SO CANCER LA English DT Article; Proceedings Paper CT American-Cancer-Society National Conference on Skin Cancers CY APR 14-16, 1994 CL PHOENIX, AZ SP AMER CANC SOC DE ACTINIC KERATOSIS; BOWENS DISEASE; BASAL CELL CARCINOMA; SQUAMOUS CELL CARCINOMA; DYSPLASTIC NEVUS; CLINICALLY ATYPICAL MOLE; CONGENITAL NEVUS; MELANOMA ID CONGENITAL NEVOCELLULAR NEVI; RENAL-ALLOGRAFT RECIPIENTS; BUSCHKE-LOEWENSTEIN TUMOR; LENTIGO MALIGNA MELANOMA; SOLAR KERATOSES; CUTANEOUS MELANOMA; DYSPLASTIC NEVUS; FAMILIAL MELANOMA; PRONE FAMILIES; RISK AB Certain cutaneous lesions serve as both precursors of skin cancer and markers for increased risk. The solar or actinic keratosis serves such a role for the nonmelanoma (NMSC) forms of skin cancer (basal cell carcinoma and squamous cell carcinoma). Clinically, these keratoses manifest as rough, scaly, erythematous patches on chronically sun-exposed surfaces, Conversion to squamous cell carcinoma in an individual lesion is uncommon and has been estimated at 1 per 1000 per year, Individuals with actinic keratoses have had sufficient chronic photodamage to produce skin cancer, and regular surveillance is recommended. The second precursor for invasive NMSC is Bowen's disease (squamous cell carcinoma in situ). Invasion of the dermis results in frank squamous cell carcinoma. Some types of viral warts may develop into squamous cell carcinoma. The most important precursor/marker for melanoma is the clinically atypical mole (CAM) or dysplastic nevus. CAMs occur in 5-10% of the U.S. population, CAMs, under photographic follow-up, have been observed to evolve into cutaneous melanoma, The frequency of conversion to melanoma of any single CAM is quite low; however, in melanoma-prone families, prospectively diagnosed melanomas arise in association with a histopathologically observed dysplastic nevus in more than 80% of the cases. Giant congenital melanocytic nevi have an approximately 6% lifetime risk of melanoma development. The risk associated with small congenital nevi is uncertain. Lentigo maligna develop into invasive melanoma with a frequency reported in the literature ranging from 5-50%. RP SOBER, AJ (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT DERMATOL,BARTLETT 410,BOSTON,MA 02114, USA. NR 40 TC 93 Z9 95 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 JAN 15 PY 1995 VL 75 IS 2 SU S BP 645 EP 650 DI 10.1002/1097-0142(19950115)75:2+<645::AID-CNCR2820751405>3.0.CO;2-1 PG 6 WC Oncology SC Oncology GA QB793 UT WOS:A1995QB79300004 PM 7804989 ER PT J AU KOLODNER, RD HALL, NR LIPFORD, J KANE, MF MORRISON, PT FINAN, PJ BURN, J CHAPMAN, P EARABINO, C MERCHANT, E BISHOP, DT AF KOLODNER, RD HALL, NR LIPFORD, J KANE, MF MORRISON, PT FINAN, PJ BURN, J CHAPMAN, P EARABINO, C MERCHANT, E BISHOP, DT TI STRUCTURE OF THE HUMAN MLH1 LOCUS AND ANALYSIS OF A LARGE HEREDITARY NONPOLYPOSIS COLORECTAL-CARCINOMA KINDRED FOR MLH1 MUTATIONS SO CANCER RESEARCH LA English DT Note ID MICROSATELLITE INSTABILITY; COLON-CANCER; TUMOR SPECTRUM; HOMOLOG; DNA AB Hereditary nonpolyposis colorectal carcinoma is a major cancer susceptibility syndrome known to be caused by inheritance of mutations in at least four genes such as hMSH2, hMLH1, hPMS1, and hPMS2 which encode components of a DNA mismatch repair system. The hMLH1 genomic locus on chromosome 3p has been cloned and shown to cover similar to 58 kilobases of genomic DNA and contain 19 exons. The sequence of all of the intron-exon junctions has been determined and used to develop methods for analyzing each hMLH1 exon for mutations. Using these methods to analyze a 3p-linked hereditary nonpolyposis colorectal carcinoma kindred, we have demonstrated that cancer susceptibility in this family is due to the inheritance of a frame shift mutation in the hMLH1 gene. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,MOLEC BIOL CARE FACIL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. ST JAMES UNIV HOSP,IMPERIAL CANC RES FUND,GENET EPIDEMIOL LAB,LEEDS LS9 7TF,W YORKSHIRE,ENGLAND. GEN INFIRM,DEPT SURG,LEEDS LS1 3EX,W YORKSHIRE,ENGLAND. GEN INFIRM,CTR DIGEST DIS,LEEDS LS1 3EX,W YORKSHIRE,ENGLAND. UNIV NEWCASTLE UPON TYNE,DEPT HUMAN GENET,NEWCASTLE TYNE NE2 4AA,TYNE & WEAR,ENGLAND. RP KOLODNER, RD (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELL & MOLEC BIOL,44 BINNEY ST,BOSTON,MA 02115, USA. OI Bishop, Tim/0000-0002-8752-8785 FU NCI NIH HHS [CA06516]; NHGRI NIH HHS [HG00305]; NIGMS NIH HHS [GM50006] NR 41 TC 221 Z9 224 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 1995 VL 55 IS 2 BP 242 EP 248 PG 7 WC Oncology SC Oncology GA QB808 UT WOS:A1995QB80800008 PM 7812952 ER PT J AU PEREZ, LA DOMBKOWSKI, D EFIRD, J PREFFER, F SUIT, HD AF PEREZ, LA DOMBKOWSKI, D EFIRD, J PREFFER, F SUIT, HD TI CELL-PROLIFERATION KINETICS IN HUMAN TUMOR XENOGRAFTS MEASURED WITH IODODEOXYURIDINE LABELING AND FLOW-CYTOMETRY - A STUDY OF HETEROGENEITY AND A COMPARISON BETWEEN DIFFERENT METHODS OF CALCULATION AND OTHER PROLIFERATION MEASUREMENTS SO CANCER RESEARCH LA English DT Article ID POTENTIAL DOUBLING TIME; MONOCLONAL-ANTIBODIES; SINGLE SAMPLE; DNA-SYNTHESIS; BROMODEOXYURIDINE; RADIOTHERAPY; HEAD; NECK; RADIATION; CANCER AB The influence of overall treatment time in the results of fractionated radiation treatment was initially established in experimental tumors and, subsequently, in the clinic The availability of techniques (antibodies against halogenated thymidine analogues and flow cytometry) which permit determinations of the duration of the synthesis phase, the labeling index, and the tumor potential doubling time (T-pot) in a short period of time and requiring only a small biopsy of tumor tissue, has expanded interest in the relationship between tumor cell proliferation and response to irradiation. A valuable tool in the study of this relationship are human tumor xenografts. Previous studies have shown a substantial intratumoral heterogeneity in the determinations of T-pot. Different methods of calculation of the kinetic parameters have been published. We have conducted a heterogeneity analysis and an evaluation of the different calculation methods in order to define the validity of T-pot as a proliferation rate measurement in human tumor xenografts. Results show the intertumoral variability in T-pot [between different types of human tumor xenografts systems (coefficient of variation = 88.2%)] to be greater than mean intratumoral variation (coefficient of variation = 30.8%); this suggests that this variation is potentially adequate to serve as a predictor of response. The diverse calculation methods provided significantly different absolute values but not different tumor ranking, probably because the time interval between labeling and sampling was maintained, for all the samples, between 6 and 8 h. Our study has found significant differences between the labeling index and the S-phase fraction determined with the DNA profile in 9 out of 10 tumor types. No correlation was found between the DNA index of the tumors in this series and their proliferation rate. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BIOSTAT UNIT,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,DEPT PATHOL,BOSTON,MA 02114. RP PEREZ, LA (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,EDWIN L STEELE LAB RADIAT BIOL,BOSTON,MA 02114, USA. RI Perez-Romasanta, Luis/B-7771-2016 OI Perez-Romasanta, Luis/0000-0001-8117-5459 FU NCI NIH HHS [CA13311] NR 41 TC 20 Z9 20 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 JAN 15 PY 1995 VL 55 IS 2 BP 392 EP 398 PG 7 WC Oncology SC Oncology GA QB808 UT WOS:A1995QB80800032 PM 7812972 ER PT J AU EWEN, ME OLIVER, CJ SLUSS, HK MILLER, SJ PEEPER, DS AF EWEN, ME OLIVER, CJ SLUSS, HK MILLER, SJ PEEPER, DS TI P53-DEPENDENT REPRESSION OF CDK4 TRANSLATION IN TGF-BETA-INDUCED G(1) CELL-CYCLE ARREST SO GENES & DEVELOPMENT LA English DT Article DE P53; CDK4; TGF-BETA; TRANSLATION; CELL CYCLE CONTROL ID GROWTH-FACTOR-BETA; WILD-TYPE P53; RETINOBLASTOMA GENE-PRODUCT; DEPENDENT KINASES; MAMMALIAN-CELLS; PROTEIN-KINASE; CANCER-CELLS; EXPRESSION; INHIBITION; SUPPRESSION AB Transforming growth factor beta 1 (TGF-beta 1) can cause a cell-cycle arrest in G(1). Inhibition of cyclin-dependent kinase 4 (cdk4) synthesis plays a significant role in the mechanism by which this cytokine causes G(1) growth arrest. Deregulated expression of cdk4 confers resistance to TGF-beta 1. Here, we show that TGF-beta 1 down regulates cdk4 expression by inhibiting its translation. Moreover, mutant p53 confers resistance to TGF-beta 1 by interfering with the down-regulation of cdk4 in response to the cytokine. In contrast, we demonstrate that wild-type p53 represses the translation of CDK4. Regulation of cdk4 synthesis by both p53 and TGF-beta 1 is mediated by the 5'-untranslated region of the CDK4 message. Thus, regulation of CDK4 translation may be involved in control of G(1) progression by p53. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP EWEN, ME (reprint author), CHILDRENS HOSP,DANA FARBER CANC INST,BOSTON,MA 02115, USA. NR 99 TC 153 Z9 154 U1 0 U2 2 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0890-9369 J9 GENE DEV JI Genes Dev. PD JAN 15 PY 1995 VL 9 IS 2 BP 204 EP 217 DI 10.1101/gad.9.2.204 PG 14 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA QF719 UT WOS:A1995QF71900006 PM 7851794 ER PT J AU ALANI, E CHI, NW KOLODNER, R AF ALANI, E CHI, NW KOLODNER, R TI THE SACCHAROMYCES-CEREVISIAE MSH2 PROTEIN SPECIFICALLY BINDS TO DUPLEX OLIGONUCLEOTIDES CONTAINING MISMATCHED DNA-BASE PAIRS AND INSERTIONS SO GENES & DEVELOPMENT LA English DT Article DE MSH2; MISMATCH BINDING; MISMATCH REPAIR; SACCHAROMYCES CEREVISIAE ID HETERODUPLEX PLASMID DNA; MUTS-ENCODED PROTEIN; ESCHERICHIA-COLI; NUCLEOTIDE-SEQUENCE; REPAIR; EXTRACTS; YEAST; MUTATIONS; GENES; TRANSFORMATION AB The yeast Saccharomyces cerevisiae encodes four proteins, Msh1, Msh2, Msh3, Msh4, that show strong amino acid sequence similarity to MutS, a central component of the bacterial mutHLS mismatch repair system. MutS has been shown to recognize base pair mismatches in DNA in vitro. Previous studies have suggested that Msh2 is the major mismatch recognition protein in yeast. In this study, the 109-kD Msh2 polypeptide was overexpressed and purified to analyze its DNA-binding properties. This analysis demonstrated that Msh2 can bind selectively to duplex oligonucleotide substrates containing a G/T mismatch, 1- to 14-nucleotide insertion mismatches, and palindromic (12- to 14-nucleotide) insertion mismatches. A general trend was that the affinity of Msh2 for substrate was proportional to the size of the insertion mispair present (+14 PAL, +12 PAL>+14>+8>GT, +6, +4, +2, +1). Kinetic studies indicated that the specificity of Msh2 to mismatch substrates was a function of its ability to form stable complexes with mispair-containing duplex DNAs. These complexes decayed more slowly than Msh2 complexes formed with homoduplex DNA. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELLULAR & MOLEC BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. FU NCI NIH HHS [CA06516]; NHGRI NIH HHS [HG00305]; NIGMS NIH HHS [GM50006] NR 56 TC 103 Z9 103 U1 0 U2 3 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0890-9369 J9 GENE DEV JI Genes Dev. PD JAN 15 PY 1995 VL 9 IS 2 BP 234 EP 247 DI 10.1101/gad.9.2.234 PG 14 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA QF719 UT WOS:A1995QF71900008 PM 7851796 ER PT J AU DITZEL, HJ BINLEY, JM MOORE, JP SODROSKI, J SULLIVAN, N SAWYER, LSW HENDRY, RM YANG, WP BARBAS, CF BURTON, DR AF DITZEL, HJ BINLEY, JM MOORE, JP SODROSKI, J SULLIVAN, N SAWYER, LSW HENDRY, RM YANG, WP BARBAS, CF BURTON, DR TI NEUTRALIZING RECOMBINANT HUMAN-ANTIBODIES TO A CONFORMATIONAL V2-BINDING AND CD4-BINDING SITE-SENSITIVE EPITOPE OF HIV-1 GP120 ISOLATED BY USING AN EPITOPE-MASKING PROCEDURE SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN MONOCLONAL-ANTIBODIES; ENVELOPE GLYCOPROTEIN GP120; AMINO-ACID CHANGES; TYPE-1 GP120; COMBINATORIAL LIBRARIES; SURFACE GLYCOPROTEIN; SYNCYTIUM FORMATION; VARIABLE REGIONS; RECEPTOR-BINDING AB As part of the goal of assembling a mixture of neutralizing human mAbs for possible prophylaxis and therapy of HIV-1 disease, we describe a strategy by which neutralizing human Abs to a weakly immunogenic epitope can be accessed. From a phage display library derived from an asymptomatic HIV-1 seropositive donor, a panel of recombinant Fabs against the CD4 binding site (CD4bs) of gp120 was retrieved by affinity selection using recombinant gp120 (strain LAI). Two Fabs corresponding to the dominant clones were used to mask the CD4bs epitope(s) before repeating the selection procedure. Four Fabs were then retrieved that had novel heavy chain sequences. Three recognized a novel epitope distinct from that recognized by conventional CD4bs Abs and were defined by the following criteria: 1) second V region (V2 region) dependence indicated by sensitivity to amino acid changes in the V2 loop and by competition with murine anti-V2 mAbs; 2) CD4bs dependence indicated by sensitivity to amino acid changes usually associated with CD4 binding and by inhibition of Fab binding to gp120 by soluble CD4; this dependence seemed to arise via conformational changes rather than by direct binding, as CD4bs Abs enhanced binding of two of the novel Fabs and, in a reversal of the competition format, the novel Fabs did not inhibit soluble CD4 binding to gp120; and 3) equivalent binding to glycosylated and deglycosylated gp120 and significant, although much reduced, binding to denatured gp120 in contrast with CD4bs Abs, which do not bind to deglycosylated or denatured gp120. One of the novel Fabs efficiently neutralized the MN and LAI strains of HIV-1. These results indicate the presence of a novel neutralizing conformational epitope on gp120 sensitive to the V2 loop and the CD4bs and further highlight the conformational flexibility of gp120. The strategy of masking highly immunogenic epitopes with Abs to rescue a broader range of specific Abs from combinatorial libraries should be widely applicable. C1 SCRIPPS RES INST, DEPT MOLEC BIOL, LA JOLLA, CA 92037 USA. ODENSE UNIV, SCH MED, DEPT MED MICROBIOL, ODENSE, DENMARK. NYU, SCH MED, AARON DIAMOND AIDS RES CTR, NEW YORK, NY 10016 USA. HARVARD UNIV, SCH MED, DANA FARBER CANC INST, DIV HUMAN RETROVIROL, BOSTON, MA 02115 USA. CALIF DEPT HLTH SERV, VIRAL & RICKETTSIAL DIS LAB, BERKELEY, CA 94704 USA. RP DITZEL, HJ (reprint author), SCRIPPS RES INST, DEPT IMMUNOL, 10666 N TORREY PINES RD, LA JOLLA, CA 92037 USA. OI Ditzel, Henrik J./0000-0003-3927-5135 FU NIAID NIH HHS [AI24755, AI31783, AI33292-02] NR 70 TC 82 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 JAN 15 PY 1995 VL 154 IS 2 BP 893 EP 906 PG 14 WC Immunology SC Immunology GA QA636 UT WOS:A1995QA63600044 PM 7529290 ER PT J AU SHEKELLE, PG MARKOVICH, M LOUIE, R AF SHEKELLE, PG MARKOVICH, M LOUIE, R TI COMPARING THE COSTS BETWEEN PROVIDER TYPES OF EPISODES OF BACK PAIN CARE SO SPINE LA English DT Article AB Study Design. This study was a prospective, community-based, observational design. Objectives. The authors compared the costs of episodes of back pain care between different provider types in a population representative of the U.S. Summary of Background Data. Previous comparisons between provider types of the costs for back pain care have been restricted to the worker's compensation population or have used something other than the episode as the unit of analysis. Methods. Data from the RAND Health Insurance Experiment (HIE) were analyzed. Insurance claims forms were examined for all visits specified by the patient as occurring for back pain. Visits were grouped into episodes using decision rules and clinical judgement. The primary provider was defined as the provider who delivered most of the care. Comparisons of costs between provider types were made. Results. There were 1020 episodes of back pain care made by 686 different persons and encompassing 8825 visits. Chiropractors and general practitioners were the primary providers for 40% and 26% of episodes, respectively. Chiropractors had a significantly greater mean number of visits per episode (10.4) than did other practitioners. Orthopedic physicians and ''other'' basis. Orthopedists had the highest mean total cost per episode, and general practitioners the lowest. Chiropractors had the highest, and general practitioners the lowest mean outpatient cost per episode. Conclusions. These are economically significant differences in the costs of back pain care of persons seeing chiropractors, general practitioners, internists, and orthopedists. C1 W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA. FU AHRQ HHS [1RO3HS06920-01] NR 0 TC 70 Z9 71 U1 2 U2 4 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0362-2436 J9 SPINE JI SPINE PD JAN 15 PY 1995 VL 20 IS 2 BP 221 EP 226 DI 10.1097/00007632-199501150-00018 PG 6 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA QD345 UT WOS:A1995QD34500018 PM 7716629 ER PT J AU SORKIN, A MCKINSEY, T SHIH, W KIRCHHAUSEN, T CARPENTER, G AF SORKIN, A MCKINSEY, T SHIH, W KIRCHHAUSEN, T CARPENTER, G TI STOICHIOMETRIC INTERACTION OF THE EPIDERMAL GROWTH-FACTOR RECEPTOR WITH THE CLATHRIN-ASSOCIATED PROTEIN COMPLEX AP-2 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LIGAND-INDUCED INTERNALIZATION; COATED VESICLE PROTEINS; AMINO-ACID SEQUENCE; PLASMA-MEMBRANE; MEDIATED ENDOCYTOSIS; ADAPTER PROTEIN; INVITRO BINDING; KINASE-ACTIVITY; PITS; CLONING AB Plasma membrane clathrin-associated protein complexes (AP-2) have been shown to co-immunoprecipitate with the epidermal growth factor (EGF) receptor (Sorkin A., and Carpenter, G. (1993) Science 261, 612-615). Hence, we analyzed the stoichiometry of the EGF receptor interaction with AP-2 using a new antibody that efficiently immunoprecipitates native AP-2. EGF receptor AP-2 complexes were isolated from S-35-labeled cells treated with EGF by EGF receptor affinity chroma tography followed by precipitation with the antibody to AP-2. Quantitation of the relative molar concentrations of the proteins found in the complex revealed that 1 mol of AP-2 was associated with approximately 1.1 mol of EGF receptor. No other proteins were present in significant molar concentrations relative to AP-2. indicating that other proteins are not stoichiometrically involved in the interaction of EGF receptors and AP-2 in vitro. Co-immunoprecipitation experiments in cells expressing a mutant EGF receptor demonstrated that the cyto plasmic carboxyl-terminal 214 residues of the EGF receptor are essential for interaction with AP-2. C1 VANDERBILT UNIV,SCH MED,DEPT BIOCHEM,NASHVILLE,TN 37232. HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. CTR BLOOD RES,BOSTON,MA 02115. FU NCI NIH HHS [CA24071]; NIDDK NIH HHS [DK46817]; NIGMS NIH HHS [GM36548] NR 50 TC 99 Z9 100 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 13 PY 1995 VL 270 IS 2 BP 619 EP 625 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QB816 UT WOS:A1995QB81600020 PM 7822287 ER PT J AU KOVACSOVICSBANKOWSKI, M ROCK, KL AF KOVACSOVICSBANKOWSKI, M ROCK, KL TI A PHAGOSOME-TO-CYTOSOL PATHWAY FOR EXOGENOUS ANTIGENS PRESENTED ON MHC CLASS-I MOLECULES SO SCIENCE LA English DT Article ID TOXIC LYMPHOCYTES-T; CELLS; PROTEIN; EXPRESSION; GELONIN AB Peptides from endogenous proteins are presented by major histocompatibility complex class I molecules, but antigens (Ags) in the extracellular fluids are generally not. However, pathogens or particulate Ags that are internalized into phagosomes of macrophages (MOs) stimulate CD8 T cells. The presentation of these Ags is resistant to chloroquine but is blocked by inhibitors of the proteasome, a mutation in the TAP1-TAP2 transporter, and brefeldin A. Moreover, phagocytosis of a ribosomal-inactivating protein inhibited MM protein synthesis. These results demonstrate that MOs transfer Ags from phagosomes into the cytosol and that endogenous and exogenous Ags use a final common pathway for class I presentation. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV LYMPHOCYTE BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. FU NIAID NIH HHS [AI20248, AI31337] NR 27 TC 624 Z9 628 U1 1 U2 17 PU AMER ASSOC ADVAN SCIENCE PI WASHINGTON PA 1333 H ST NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JAN 13 PY 1995 VL 267 IS 5195 BP 243 EP 246 DI 10.1126/science.7809629 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QB153 UT WOS:A1995QB15300037 PM 7809629 ER PT J AU JO, SA ZHU, XJ MARCHIONNI, MA BURDEN, SJ AF JO, SA ZHU, XJ MARCHIONNI, MA BURDEN, SJ TI NEUREGULINS ARE CONCENTRATED AT NERVE-MUSCLE SYNAPSES AND ACTIVATE ACH-RECEPTOR GENE-EXPRESSION SO NATURE LA English DT Article ID ACETYLCHOLINE-RECEPTOR; SUBUNIT GENE; TRANSGENIC MICE; EPSILON-SUBUNIT; BASAL LAMINA; FAMILY; PROTEIN; MEMBER; NEU; HER4/P180(ERBB4) AB Two different signalling pathways mediate the localization of acetylcholine receptors (AChRs) to synaptic sites in skeletal muscle. The signal for one pathway is agrin, a protein that triggers a redistribution of previously unlocalized cell surface AChRs to synaptic sites(1). The signal for the other pathway is not known, but this signal stimulates transcription of AChR genes in myofibre nuclei near the synaptic site(2). Neuregulins, identified originally as a potential ligand for erbB2 (Neu differentiation factor, NDF)(3), stimulate proliferation of Schwann cells (glial growth factor, GGF)(4), increase the rate of AChR synthesis in cultured muscle cells (AChR-inducing activity)(5) and are expressed in motor neurons(4,5). These results raise the possibility that neuregulin is the signal that activates AChR genes in synaptic nuclei. Here we show that neuregulin activates AChR gene expression in C2 muscle cells and that the neuregulin response element in the AChR delta-subunit gene is contained in the same 181 base pairs that confer synapse-specific expression in transgenic mice. We use antibodies to show that neuregulins are concentrated at synaptic sites and that, like the extracellular signal that stimulates synapse-specific expression, neuregulins remain at synaptic sites in the absence of nerve and muscle. We show that C2 muscle cells contain erbB2 and erbB3 messenger RNA but little or no erbB4 mRNA, and that neuregulin stimulates tyrosine phosphorylation of erbB2 and erbB3, indicating that neuregulin signalling in skeletal muscle may be mediated by a complex of erbB2 and erbB3. C1 MIT,DEPT BIOL,CAMBRIDGE,MA 02139. CAMBRIDGE NEUROSCI INC,CAMBRIDGE,MA 02139. RP JO, SA (reprint author), HARVARD UNIV,SCH MED,CTR BLOOD RES,200 LONGWOOD AVE,BOSTON,MA 02115, USA. NR 28 TC 228 Z9 230 U1 0 U2 0 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD JAN 12 PY 1995 VL 373 IS 6510 BP 158 EP 161 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QB063 UT WOS:A1995QB06300061 PM 7816098 ER PT J AU KANOFSKY, JR SIMA, PD AF KANOFSKY, JR SIMA, PD TI REACTIVE ABSORPTION OF OZONE BY AQUEOUS BIOMOLECULE SOLUTIONS - IMPLICATIONS FOR THE ROLE OF SULFHYDRYL COMPOUNDS AS TARGETS FOR OZONE SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE ASCORBIC ACID; CYSTEINE; GLUTATHIONE; METHIONINE; OZONE; REACTIVE ABSORPTION; THIOSULFATE ID REVERSE MICELLES; WATER; OZONATION; LYSOZYME; OLEATE; MODEL; RATES; ACID AB The rates of reactive absorption of ozone by various biomolecule solutions were measured. At pH 7, the ability of various biomolecules to reactively absorb ozone was in the following sequence: thiosulfate > ascorbate > cysteine approximate to methionine > glutathione. The rates of reactive absorption under a variety of conditions were then analyzed using a mathematical model in order to estimate the reaction rate constants for the various ozone-biomolecule reactions. Compared to the ozone-methionine rate constant, the relative rate constants for thiosulfate, ascorbate, cysteine, and glutathione reactions were 18 +/- 2, 12 +/- 1, 1.1 +/- 0.1, and 0.62 +/- 0.03, respectively. Using an ozone-methionine reaction rate constant of 4 x 10(6) M(-1) s(-1), the rate constants for thiosulfate, ascorbate, cysteine, and glutathione were 7:2 X 10(7), 4.8 X 10(7), 4.4 X 10(6), and 2.5 X 10(6) M(-1) s(-1), respectively. Competitive studies using tryptophan as a standard ozone target were consistent with these rate constants. Compared to tryptophan, the relative ozone reaction rate constants for methionine, cysteine, and glutathione were 0.77 +/- 0.08, 0.88 +/- 0.19, and 0.42 +/- 0.01, respectively. These relative rate constants refer to ozone consumption rather than biomolecule consumption, so they may be compared with the relative rate constants obtained from reactive absorption. In addition, various inconsistencies in the literature regarding the rates of the ozone-cysteine and the ozone-glutathione reactions were reviewed. (C) 1995 Academic Press, Inc. C1 US DEPT VET AFFAIRS,VET AFFAIRS EDWARD HINES JR HOSP,RES SERV,HINES,IL 60141. LOYOLA UNIV,STRITCH SCH MED,DEPT MED,MAYWOOD,IL 60153. LOYOLA UNIV,STRITCH SCH MED,DEPT MOLEC & CELLULAR BIOCHEM,MAYWOOD,IL 60153. RP KANOFSKY, JR (reprint author), US DEPT VET AFFAIRS,VET AFFAIRS EDWARD HINES JR HOSP,MED SERV,POB 278,HINES,IL 60141, USA. NR 26 TC 50 Z9 52 U1 0 U2 4 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD JAN 10 PY 1995 VL 316 IS 1 BP 52 EP 62 DI 10.1006/abbi.1995.1009 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA QJ933 UT WOS:A1995QJ93300009 PM 7840660 ER PT J AU BERARDI, AC WANG, AL LEVINE, JD LOPEZ, P SCADDEN, DT AF BERARDI, AC WANG, AL LEVINE, JD LOPEZ, P SCADDEN, DT TI FUNCTIONAL ISOLATION AND CHARACTERIZATION OF HUMAN HEMATOPOIETIC STEM-CELLS SO SCIENCE LA English DT Article ID ERYTHROPOIETIN RECEPTOR GENE; IL-6 SIGNAL TRANSDUCER; COLONY-FORMING CELLS; MURINE BONE-MARROW; LONG-TERM CULTURE; PROGENITOR CELLS; LIMITING-DILUTION; C-KIT; MONOCLONAL-ANTIBODY; SOYBEAN AGGLUTININ AB Hematopoietic cells differentiate in steps marked by the acquisition or loss of specific phenotypic characteristics. Human bone marrow cells that were responsive to the early-acting cytokines Kit ligand and interleukin-3 were forced to a metabolic death. The subfraction remaining represented 1 in 10(5) bone marrow mononuclear cells, was determined to be quiescent by cell cycle analysis, and had a stem cell immunophenotype, The cells were highly enriched for long-term culture-initiating cells, were capable of secondary colony formation, and produced both myeloid and lymphoid progeny. Thus, this technically simple strategy led to the efficient purification of cells with characteristics of hematopoietic stem cells. C1 HARVARD UNIV,DEACONESS HOSP,SCH MED,DIV HEMATOL ONCOL,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,CELL SORTING FACIL,BOSTON,MA 02115. OI Berardi, Anna C./0000-0002-5078-6158 FU NHLBI NIH HHS [R01-HL44851] NR 55 TC 348 Z9 359 U1 0 U2 9 PU AMER ASSOC ADVAN SCIENCE PI WASHINGTON PA 1333 H ST NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JAN 6 PY 1995 VL 267 IS 5194 BP 104 EP 108 DI 10.1126/science.7528940 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QA235 UT WOS:A1995QA23500040 PM 7528940 ER PT J AU CLAFFEY, KP SENGER, DR SPIEGELMAN, BM AF CLAFFEY, KP SENGER, DR SPIEGELMAN, BM TI STRUCTURAL REQUIREMENTS FOR DIMERIZATION, GLYCOSYLATION, SECRETION, AND BIOLOGICAL FUNCTION OF VPF/VEGF SO BIOCHIMICA ET BIOPHYSICA ACTA-PROTEIN STRUCTURE AND MOLECULAR ENZYMOLOGY LA English DT Article DE ANGIOGENESIS; CYTOKINE; GROWTH FACTOR; MUTANT; VASCULAR PERMEABILITY FACTOR; (ENDOTHELIUM) ID ENDOTHELIAL GROWTH-FACTOR; VASCULAR-PERMEABILITY FACTOR; TYROSINE KINASE; CELL MITOGEN; FACTOR GENE; CDNA SEQUENCES; AMINO-ACID; IDENTIFICATION; ANGIOGENESIS; EXPRESSION AB Vascular permeability factor (VPF) also known as vascular endothelial growth factor (VEGF), is a dimeric protein that affects endothelial cell (EC) and vascular functions including enhancement of microvascular permeability and stimulation of EC growth. To investigate the structural features of VPF/VEGF necessary for efficient dimerization, secretion, and biological activities, we employed site-directed mutagenesis with a Cos-1 cell expression system. Several cysteine residues essential for VPF dimerization were identified by mutation analysis of the Cys-25, Cys-56, and Cys-67 residues. Mutant VPF isoforms lacking either of these cysteines were secreted as monomers and were completely inactive in both vascular permeability and endothelial cell mitotic assays. VPF Cys-145 mutant protein was efficiently secreted as a glycosylated, dimeric polypeptide, but had a reduction in biological activities. The site of N-linked glycosylation was directly identified as Asn-74, which, when mutated produced an inefficiently secreted dimeric protein without post-translational glycosylation, yet maintained full vascular permeability activity. Finally, we found that one VPF mutant isoform Cys-101 was not secreted and this mutant functioned as a dominant-negative suppressor of wild-type VPF secretion as demonstrated by co-expression assays in Cos-1 cells. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02215. HARVARD UNIV,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. RP CLAFFEY, KP (reprint author), BETH ISRAEL HOSP,DEPT PATHOL,330 BROOKLINE AVE,BOSTON,MA 02215, USA. FU NCI NIH HHS [CA 43967]; NIDDK NIH HHS [DK 08278, DK 42420] NR 43 TC 62 Z9 65 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4838 J9 BBA-PROTEIN STRUCT M JI Biochim. Biophys. Acta-Protein Struct. Molec. Enzym. PD JAN 5 PY 1995 VL 1246 IS 1 BP 1 EP 9 DI 10.1016/0167-4838(94)00144-6 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA QA913 UT WOS:A1995QA91300001 PM 7811723 ER PT J AU ROBERTS, TM CAMPBELL, K WEN, S KAI, X AUGER, K JING, W AGARWAL, S JUN, T NARSIMHAN, R HASER, W KING, F WEI, L YAMAKAWA, A FU, H COLLIER, J OGRIS, E PALLAS, D SCHAFFHAUSEN, B AF ROBERTS, TM CAMPBELL, K WEN, S KAI, X AUGER, K JING, W AGARWAL, S JUN, T NARSIMHAN, R HASER, W KING, F WEI, L YAMAKAWA, A FU, H COLLIER, J OGRIS, E PALLAS, D SCHAFFHAUSEN, B TI POLYOMA T ANTIGENS - OLD ONCOGENES - NEW TRICKS SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. TUFTS UNIV,SCH MED,BOSTON,MA 02111. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 5 PY 1995 SU 19A BP 3 EP 3 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QQ997 UT WOS:A1995QQ99700005 ER PT J AU LORENZ, U RAVICHANDRAN, KS BURAKOFF, SJ KINGMULLER, U LODISH, H NEEL, BG AF LORENZ, U RAVICHANDRAN, KS BURAKOFF, SJ KINGMULLER, U LODISH, H NEEL, BG TI MULTIPLE HEMATOPOEITIC SIGNAL-TRANSDUCTION PATHWAYS ARE NEGATIVELY REGULATED BY THE SH2-CONTAINING TYROSINE PHOSPHATASE SH-PTP1 SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 BETH ISRAEL HOSP,MOLEC MED UNIT,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. WHITEHEAD INST,CAMBRIDGE,MA 02138. NR 0 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 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 5 PY 1995 SU 19A BP 21 EP 21 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QQ997 UT WOS:A1995QQ99700070 ER PT J AU LOW, KG COMB, MJ AF LOW, KG COMB, MJ TI SYNERGISTIC INTERACTIONS BETWEEN HTLV-1 TAX AND ONCOGENIC RAS ON PROENKEPHALIN GENE-TRANSCRIPTION SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,MOLEC NEUROBIOL LAB,BOSTON,MA 02129. NR 0 TC 0 Z9 0 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 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 5 PY 1995 SU 19A BP 21 EP 21 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QQ997 UT WOS:A1995QQ99700069 ER PT J AU RAVICHANDRAN, KS LORENZ, U SHOELSON, SE BURAKOFF, SJ AF RAVICHANDRAN, KS LORENZ, U SHOELSON, SE BURAKOFF, SJ TI INTERACTION OF SHC WITH GRB2 REGULATES THE GRB2 ASSOCIATION WITH MSOS SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,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 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 5 PY 1995 SU 19A BP 26 EP 26 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QQ997 UT WOS:A1995QQ99700091 ER PT J AU BAO, JX ZERVOS, AS AF BAO, JX ZERVOS, AS TI ISOLATION AND CHARACTERIZATION OF PROTEINS THAT INTERACT WITH THE HUMAN N-MYC PROTOONCOGENE SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,CBRC,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 5 PY 1995 SU 19A BP 28 EP 28 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QQ997 UT WOS:A1995QQ99700098 ER PT J AU BODOR, J HABENER, JF AF BODOR, J HABENER, JF TI MODULATION OF HTLV-I LTR PROMOTER EXPRESSION BY TAX AND PKA VIA CAMP RESPONSE ELEMENT-BINDING PROTEIN CREB AND CRE MODULATOR PROTEIN CREM SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,HOWARD HUGHES MED INST,MOLEC ENDOCRINOL LAB,BOSTON,MA 02114. NR 0 TC 0 Z9 0 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 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 5 PY 1995 SU 19A BP 30 EP 30 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QQ997 UT WOS:A1995QQ99700105 ER PT J AU LO, SH WONG, WK LIU, Y BOUTON, AH PARSONS, JT CHEN, LB AF LO, SH WONG, WK LIU, Y BOUTON, AH PARSONS, JT CHEN, LB TI ASSOCIATION OF TENSIN WITH TYROSINE-PHOSPHORYLATED P130 - A POTENTIAL ROLE IN NUCLEUS-FOCAL CONTACTS COMMUNICATIONS SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. UNIV VIRGINIA,HLTH SCI CTR,CHARLOTTESVILLE,VA 22908. UNIV CHICAGO,HOWARD HUGHES MED INST,CHICAGO,IL 60637. NR 0 TC 0 Z9 0 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 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 5 PY 1995 SU 19A BP 40 EP 40 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QQ997 UT WOS:A1995QQ99700144 ER PT J AU VANETTEN, RA DEBNATH, J ZHOU, H CASASNOVAS, JM AF VANETTEN, RA DEBNATH, J ZHOU, H CASASNOVAS, JM TI INTRODUCTION OF A LOSS-OF-FUNCTION POINT MUTATION FROM THE SH3 REGION OF THE CAENORHABDITIS-ELEGANS SEM-5 GENE ACTIVATES THE TRANSFORMING ABILITY OF C-ABL IN-VIVO AND ABOLISHES BINDING OF PROLINE-RICH LIGANDS IN-VITRO SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,DEPT GENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. NR 0 TC 0 Z9 0 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 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 5 PY 1995 SU 19A BP 45 EP 45 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QQ997 UT WOS:A1995QQ99700163 ER PT J AU PESTELL, RG EKLUND, N JOHNSON, J VU, D ARNOLD, A ALBANESE, C AF PESTELL, RG EKLUND, N JOHNSON, J VU, D ARNOLD, A ALBANESE, C TI DISTINGUISHABLE PROLIFERATIVE PATHWAYS ACTIVATE TRANSCRIPTION OF HUMAN CYCLIN D1 THROUGH DISTINCT PROMOTER REGIONS SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,ENDOCRINE ONCOL UNIT,BOSTON,MA 02114. NORTHWESTERN UNIV,SCH MED,DIV ENDOCRINOL METAB & MOLEC MED,CHICAGO,IL 60611. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 5 PY 1995 SU 19A BP 57 EP 57 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QQ997 UT WOS:A1995QQ99700211 ER PT J AU TAGUE, BW GOODMAN, HM AF TAGUE, BW GOODMAN, HM TI A ROLE FOR C2H2 ZINC-FINGER PROTEIN GENES IN ARABIDOPSIS SHOOT DEVELOPMENT SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. NR 0 TC 0 Z9 0 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 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 5 PY 1995 SU 19A BP 159 EP 159 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QQ997 UT WOS:A1995QQ99700579 ER PT J AU JAIN, RK AF JAIN, RK TI PHYSIOLOGICAL BARRIERS TO TRANSPORT IN TISSUES SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 4 TC 0 Z9 0 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 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 5 PY 1995 SU 19A BP 164 EP 164 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QQ997 UT WOS:A1995QQ99700588 ER PT J AU YUAN, F AF YUAN, F TI TRANSVASCULAR TRANSPORT IN NORMAL AND TUMOR-TISSUE SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract ID MICROVASCULAR PERMEABILITY C1 MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 4 TC 0 Z9 0 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 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 5 PY 1995 SU 19A BP 164 EP 164 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QQ997 UT WOS:A1995QQ99700590 ER PT J AU BERK, DA AF BERK, DA TI LYMPHATIC TRANSPORT OF MACROMOLECULES SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT NEUROPHARMACOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 2 TC 0 Z9 0 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 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 5 PY 1995 SU 19A BP 165 EP 165 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QQ997 UT WOS:A1995QQ99700591 ER PT J AU BOUCHER, Y AF BOUCHER, Y TI INTERSTITIAL HYPERTENSION IN TUMORS AND ITS ROLE IN ANTIBODY DELIVERY SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT RADIAT ONCOL,BOSTON,MA 02115. NR 4 TC 0 Z9 0 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 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 5 PY 1995 SU 19A BP 165 EP 165 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QQ997 UT WOS:A1995QQ99700592 ER PT J AU MERISKOLIVERSIDGE, E SHAW, MJ MCINTIRE, G SARPOTDAR, P COOPER, E WOLF, G CORBETT, T LIVERSIDGE, GG AF MERISKOLIVERSIDGE, E SHAW, MJ MCINTIRE, G SARPOTDAR, P COOPER, E WOLF, G CORBETT, T LIVERSIDGE, GG TI NANOPARTICLES IN DRUG-DELIVERY SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 STERLING WINTHROP,MALVERN,PA. MASSACHUSETTS GEN HOSP,CIPR,BOSTON,MA. WAYNE STATE UNIV,DETROIT,MI 48202. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 5 PY 1995 SU 19A BP 168 EP 168 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QQ997 UT WOS:A1995QQ99700602 ER PT J AU MELDER, RJ AF MELDER, RJ TI DELIVERY OF EFFECTOR-CELLS TO NORMAL AND TUMOR-TISSUES SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT RADIAT ONCOL,BOSTON,MA 02115. NR 5 TC 0 Z9 0 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 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 5 PY 1995 SU 19A BP 169 EP 169 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QQ997 UT WOS:A1995QQ99700603 ER PT J AU BORRIELLO, F TIVOL, EA FREEMAN, GJ MATLOUBIAN, M AHMED, R SHARPE, AH AF BORRIELLO, F TIVOL, EA FREEMAN, GJ MATLOUBIAN, M AHMED, R SHARPE, AH TI COSTIMULATORY SIGNALS AND VIRAL IMMUNITY SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA 90024. NR 0 TC 0 Z9 0 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 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 5 PY 1995 SU 19A BP 271 EP 271 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QQ997 UT WOS:A1995QQ99700936 ER PT J AU JOHNSON, RP WILSON, C MANSON, K WYAND, M WALKER, B DESROSIERS, RC AF JOHNSON, RP WILSON, C MANSON, K WYAND, M WALKER, B DESROSIERS, RC TI IMMUNE-RESPONSES TO LIVE ATTENUATED RETROVIRAL VACCINES SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NEW ENGLAND REG PRIMATE RES CTR,SOUTHBOROUGH,MA 01772. MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA 02114. TSI MASON,WORCESTER,MA. NR 0 TC 0 Z9 0 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 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 5 PY 1995 SU 19A BP 281 EP 281 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QQ997 UT WOS:A1995QQ99700967 ER PT J AU KALAMS, SA HARRER, T HARRER, E JOHNSON, RP BARBOSA, P FEINBERG, M BUCHBINDER, S WALKER, BD AF KALAMS, SA HARRER, T HARRER, E JOHNSON, RP BARBOSA, P FEINBERG, M BUCHBINDER, S WALKER, BD TI HIV-1-SPECIFIC CTL RESPONSE AND TCR USAGE IN HIV-1 INFECTION SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 0 TC 0 Z9 0 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 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 5 PY 1995 SU 19A BP 282 EP 282 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QQ997 UT WOS:A1995QQ99700968 ER PT J AU CZEISLER, CA SHANAHAN, TL KLERMAN, EB MARTENS, H BROTMAN, DJ EMENS, JS KLEIN, T RIZZO, JF AF CZEISLER, CA SHANAHAN, TL KLERMAN, EB MARTENS, H BROTMAN, DJ EMENS, JS KLEIN, T RIZZO, JF TI SUPPRESSION OF MELATONIN SECRETION IN SOME BLIND PATIENTS BY EXPOSURE TO BRIGHT LIGHT SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID MAMMALIAN CIRCADIAN-RHYTHMS; ENTRAINMENT; TEMPERATURE; SYSTEM; SHIFTS; PHASE AB Background. Complete blindness generally results in the loss of synchronization of circadian rhythms to the 24-hour day and in recurrent insomnia. However, some blind patients maintain circadian entrainment. We undertook this study to determine whether some blind patients' eyes convey sufficient photic information to entrain the hypothalamic circadian pacemaker acid suppress melatonin secretion, despite an apparently complete loss of visual function. Methods. We evaluated the input of light to the circadian pacemaker by testing the ability of bright light to decrease plasma melatonin concentrations in 11 blind patients with no conscious perception of light and in 6 normal subjects. We also evaluated circadian entrainment over time in the blind patients. Results. Plasma melatonin concentrations decreased during exposure to bright light in three sightless patients by an average (+/-SD) of 69+/-21 percent and in the normal subjects by an average of 66+/-15 percent. When two of these blind patients were tested with their eyes covered during exposure to light, plasma melatonin did not decrease. The three blind patients reported no difficulty sleeping and maintained apparent circadian entrainment to the 24-hour day. Plasma melatonin concentrations did not decrease during exposure to bright light in seven of the remaining blind patients; in the eighth, plasma melatonin was undetectable. These eight patients reported a history of insomnia, and in four the circadian temperature rhythm was not entrained to the 24-hour day. Conclusions. The visual subsystem that mediates the light-induced suppression of melatonin secretion remains functionally intact in some sightless patients. The absence of photic input to the circadian system thus constitutes a distinct form of blindness, associated with periodic insomnia, that afflicts most but not ail patients with no conscious perception of light. C1 BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT OPHTHALMOL,BOSTON,MA. MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. RP CZEISLER, CA (reprint author), HARVARD UNIV,SCH MED,DEPT MED,DIV ENDOCRINOL,SLEEP DISORDERS & CIRCADIAN MED SECT,BOSTON,MA 02115, USA. FU NIA NIH HHS [1-P01-AG09975, 1-R01-AG06072]; NIMH NIH HHS [1-R01-MH451] NR 33 TC 355 Z9 367 U1 0 U2 21 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 5 PY 1995 VL 332 IS 1 BP 6 EP 11 DI 10.1056/NEJM199501053320102 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA PZ497 UT WOS:A1995PZ49700002 PM 7990870 ER PT J AU ALEXANDER, E MORIARTY, TM DAVIS, RB WEN, PY FINE, HA BLACK, PM KOOY, HM LOEFFLER, JS AF ALEXANDER, E MORIARTY, TM DAVIS, RB WEN, PY FINE, HA BLACK, PM KOOY, HM LOEFFLER, JS TI STEREOTAXIC RADIOSURGERY FOR THE DEFINITIVE, NONINVASIVE TREATMENT OF BRAIN METASTASES SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID CEREBRAL ARTERIOVENOUS-MALFORMATIONS; LINEAR-ACCELERATOR RADIOSURGERY; RADIATION-THERAPY; MALIGNANT-MELANOMA; IRRADIATION; SURGERY; MANAGEMENT; RESECTION; CARCINOMA; SYSTEM AB Background: The spread of systemic cancer to the brain is a common complication for cancer patients. Conventional radiotherapy offers modest palliation, and surgery is helpful only for the patient with a single metastasis in an accessible location. Stereotactic radiosurgery, a technique that permits the precise delivery of a high dose of radiation to a small intracranial target while sparing the surrounding normal brain, has been used as an alternative treatment for brain metastases. Purpose: Our medical center's 7-year experience with radiosurgery for metastases was reviewed to establish the effectiveness of the treatment and to understand the prognoses in patients so treated. Methods: Retrospective analysis of hospital records, from 248 consecutive patients (421 lesions) that were treated with radiosurgery between May 1986 and May 1993, was performed. Patients were only excluded for a Karnofsky performance score of less than 70, evidence of acute neurologic deterioration, or tumor diameter more than 4 cm. Median follow-up was 26.2 months, Seventy-six percent of patients had recurrent disease, 69% had evidence of systemic disease, 69% had a single metastasis, Treatment was performed using a 6-MeV linear accelerator. The median tumor volume was 3 cm(3) The median treatment dose was 1500 cGy, Whole brain radiotherapy was given to all newly diagnosed patients, Patients were followed by neurological examination and neuroimaging at regular intervals. Local control of disease was defined as a lack of progression of solid-contrast enhancement on computed tomography scan or magnetic resonance imaging. Results: Median overall survival from radiosurgery was 9.4 months. The absence of active systemic disease, younger than 60 years of age, two or fewer lesions, and female sex were significantly associated with increased survival (two-sided P<.05). Actuarial local control rates were approximately 85% at 1 year and 65% at 2 years. Factors associated with a significantly decreased local control rate were location below the tentorium, recurrent tumor, and larger tumor volume (two-sided P<.05). Radioresponsive and radioresistant tumor types had similar control rates, The median drop in Karnofsky performance score at 1 year was 10%. Conclusions: The results of this retrospective analysis show that radiosurgery is an effective, minimally invasive outpatient treatment option for small intracranial metastases. Results of this study also indicate that radiosurgery not only provides local control rates equivalent to those from surgical series but is also effective in treating patients with surgically inaccessible lesions, with multiple lesions, or with tumor types conventional treatment. C1 BRIGHAM & WOMENS HOSP,CHILDRENS HOSP,CTR BRAIN TUMOR,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT SURG NEUROSURG,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT RADIAT ONCOL,BOSTON,MA 02115. BETH ISRAEL HOSP,DIV GEN MED,BOSTON,MA 02215. HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. RP ALEXANDER, E (reprint author), BRIGHAM & WOMENS HOSP,DEPT NEUROSURG,75 FRANCIS ST,BOSTON,MA 02115, USA. FU NINDS NIH HHS [1P20NS3110-01] NR 54 TC 402 Z9 409 U1 1 U2 7 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JAN 4 PY 1995 VL 87 IS 1 BP 34 EP 40 DI 10.1093/jnci/87.1.34 PG 7 WC Oncology SC Oncology GA PZ215 UT WOS:A1995PZ21500009 PM 7666461 ER PT J AU SCHLENSTEDT, G SAAVEDRA, C LOEB, JDJ COLE, CN SILVER, PA AF SCHLENSTEDT, G SAAVEDRA, C LOEB, JDJ COLE, CN SILVER, PA TI THE GTP-BOUND FORM OF THE YEAST RAN/TC4 HOMOLOG BLOCKS NUCLEAR-PROTEIN IMPORT AND APPEARANCE OF POLY(A)(+) RNA IN THE CYTOPLASM SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SACCHAROMYCES-CEREVISIAE; MESSENGER-RNA; CHROMOSOME CONDENSATION; BINDING PROTEIN; RCC1 PROTEIN; 2 STEPS; PORE; TRANSLOCATION; TRANSPORT; REGULATOR AB Ran/TC4, a Ras-like GTP-binding protein, and its nucleotide exchanger, RCC1, have been implicated in control of protein movement into the nucleus and cytoplasmic accumulation of mRNA. Saccharomyces cerevisiae contains two homologues of the mammalian Ran/TC4, encoded by the GSP1 and GSP2 genes. We have constructed yeast strains that overproduce either wild-type Gsp1 or a form of Gsp1 with glycine-21 converted to valine (Gsp1-G21V), which we show stabilizes the GTP-bound form. Cells producing Gsp1-G21V have defects in localization of nuclear proteins; nuclear proteins accumulate in the cytoplasm following galactose induction of Gsp1-G21V. Similarly, cells Producing Gsp1-G21V retain poly(A)(+) RNA in their nuclei. These findings suggest that hydrolysis of GTP by Ran/TC4 is necessary for proper import of proteins into the nucleus and appearance of poly(A)(+) RNA in the cytoplasm. C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. DARTMOUTH COLL,SCH MED,DEPT BIOCHEM,HANOVER,NH 03755. MIT,WHITEHEAD INST BIOMED RES,CAMBRIDGE,MA 02142. MIT,DEPT BIOL,CAMBRIDGE,MA 02142. FU NIGMS NIH HHS [R01 GM033998] NR 42 TC 179 Z9 179 U1 1 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 3 PY 1995 VL 92 IS 1 BP 225 EP 229 DI 10.1073/pnas.92.1.225 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QB238 UT WOS:A1995QB23800046 PM 7816822 ER PT J AU KOSOFSKY, BE GENOVA, LM HYMAN, SE AF KOSOFSKY, BE GENOVA, LM HYMAN, SE TI POSTNATAL AGE DEFINES SPECIFICITY OF IMMEDIATE-EARLY GENE INDUCTION BY COCAINE IN DEVELOPING RAT-BRAIN SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE STRIATUM; GENE EXPRESSION; DRUGS OF ABUSE; BRAIN DEVELOPMENT; ONTOGENY OF SIGNAL TRANSDUCTION ID C-FOS GENE; NERVOUS-SYSTEM; VISUAL-CORTEX; EXPRESSION; STRIATUM; ZIF268; ACTIVATION; MOUSE; JUN; PROTEIN AB Clinical and animal data suggest that exposure of developing brain to cocaine has adverse consequences. One candidate mechanism for such effects is drug regulation of gene expression. In adult rats, cocaine induces expression of nuclear immediate early genes with specific spatial and temporal patterns. The products of such genes (e.g., c-Fos, c-Jun, and Zif/268) subserve the coupling of cell surface receptor stimulation to transcriptional regulation. Thus, activation of immediate early gene expression in developing brain by cocaine could alter programs of neural gene expression and, thereby, neuronal phenotype and function. We report that, during rat brain development, cocaine produced brain region-specific and developmental age-specific induction of c-fos, c-jun, and zif/268 mRNAs. At each age studied (P8, P15, P28, and adults), we found that acute cocaine administration resulted in a unique cell-specific pattern of c-fos mRNA induction and c-Fos protein expression in striatum. We also observed cocaine-induced activation of AP-1 DNA binding activity in striatal extracts prepared at these different ages, suggesting that the observed induction of c-fos and c-jun may have biological consequences for the developing brain. These findings suggest a mechanism by which cocaine could alter patterns of gene expression during critical developmental periods with differential regional, temporal, and cellular vulnerabilities and, therefore, consequences for developing brain. (C) 1995 Wiley-Liss, Inc C1 MASSACHUSETTS GEN HOSP,MOLEC & DEV NEUROSCI LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02115. FU NIDA NIH HHS [DA07134, DA00175]; NIMH NIH HHS [MH00892] NR 48 TC 42 Z9 43 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD JAN 2 PY 1995 VL 351 IS 1 BP 27 EP 40 DI 10.1002/cne.903510104 PG 14 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA QF850 UT WOS:A1995QF85000002 PM 7896938 ER PT J AU KOSOFSKY, BE GENOVA, LM HYMAN, SE AF KOSOFSKY, BE GENOVA, LM HYMAN, SE TI SUBSTANCE-P PHENOTYPE DEFINES SPECIFICITY OF C-FOS INDUCTION BY COCAINE IN DEVELOPING RAT STRIATUM SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE ENKEPHALIN; D1 RECEPTOR; D2 RECEPTOR; NONRADIOACTIVE IN SITU HYBRIDIZATION; DRUGS OF ABUSE ID RECEPTOR MESSENGER-RNA; INSITU HYBRIDIZATION HISTOCHEMISTRY; CENTRAL NERVOUS-SYSTEM; OPIATE RECEPTORS; DOPAMINERGIC INNERVATION; ONTOGENIC EXPRESSION; TYROSINE-HYDROXYLASE; MATRIX COMPARTMENTS; CAUDATE-PUTAMEN; GENE-EXPRESSION AB Activation of c-fos, a member of the class of immediate early genes that act as transcription factors, may be one of the initial molecular mechanisms underlying plastic changes in gene expression in response to drugs of abuse. By combining c-fos (radioactive) in situ hybridization histochemistry with nonradioactive in situ hybridization histochemistry for mRNAs encoding other striatal markers [preprotachykinin (substance P), proenkephalin, and D1 and D2 receptors], we have identified the cellular phenotype of striatal neurons activated by acute administration of cocaine to P8, P15, P28, and adult rats. At each age examined, substance P+, enkephalin(-) striatal neurons were the predominant class of cells in which cocaine induced c-fos gene expression. In addition, the topography of cellular activation at each age examined was distinct and reflected the topography of distribution of cells expressing high levels of substance P mRNA. We conclude that there is a marked specificity of cellular activation in striatum following acute cocaine administration restricted predominantly to subsets of substance P-expressing cells, with age-specific patterns in their topographic distribution. (C) 1995 Wiley-Liss, Inc. C1 MASSACHUSETTS GEN HOSP,MOLEC & DEV NEUROSCI LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02115. FU NIDA NIH HHS [DA00175, DA07134]; NIMH NIH HHS [MH00892] NR 45 TC 45 Z9 46 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD JAN 2 PY 1995 VL 351 IS 1 BP 41 EP 50 DI 10.1002/cne.903510105 PG 10 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA QF850 UT WOS:A1995QF85000003 PM 7534774 ER PT B AU Niemieriko, A AF Niemieriko, A BE Purdy, JA Emami, B TI Treatment plan optimization SO 3-D RADIATION TREATMENT PLANNING AND CONFORMAL THERAPY LA English DT Proceedings Paper CT International Conference on 3-D Radiation Treatment Planning and Conformal Therapy CY APR 21-23, 1993 CL ST LOUIS, MO SP Radiat Oncol Ctr, Mallinckrodt Inst Radiol, Washington Univ Sch Med St Louis C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RAD ONCOL,BOSTON,MA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU MEDICAL PHYSICS PUBLISHING PI MADISON PA 4513 VERNON BLVD, MADISON, WI 53705 BN 0-944838-51-0 PY 1995 BP 49 EP 55 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA BF57B UT WOS:A1995BF57B00006 ER PT J AU GERVAIS, DA BAGLEY, L CONNOLLY, S AF GERVAIS, DA BAGLEY, L CONNOLLY, S TI NEONATE WITH RESPIRATORY-DISTRESS AND DIFFUSE SKELETAL ABNORMALITIES SO ACADEMIC RADIOLOGY LA English DT Note ID HYPOPHOSPHATASIA C1 HOSP UNIV PENN,DEPT RADIOL,PHILADELPHIA,PA 19104. RP GERVAIS, DA (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,14 FRUIT ST,BOSTON,MA 02114, USA. NR 5 TC 0 Z9 0 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 JAN PY 1995 VL 2 IS 1 BP 83 EP 85 DI 10.1016/S1076-6332(05)80254-5 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA QM166 UT WOS:A1995QM16600015 PM 9419531 ER PT J AU Cigarroa, JE Midha, S Jang, IK AF Cigarroa, JE Midha, S Jang, IK TI Directional atherectomy, rotational atherectomy and coronary stent, followed by coronary bypass operation in a patient with the aggressive restenotic process SO ACTA CARDIOLOGICA LA English DT Article DE coronary angioplasty; new coronary devices; restenosis AB In the era of multiple coronary interventional devices, most lesions can now be treated by a percutaneous technique. Because of these powerful tools, it has become more difficult for the cardiologist to choose between percutaneous revascularization and coronary artery bypass surgery. Recent randomized studies of coronary angioplasty versus bypass surgery have provided insights into the selection of balloon angioplasty versus bypass surgery but did not consider the use of advanced interventional devices such as directional atherectomy, rotational atherectomy or coronary stents (King et al., 1994; Hamm et al., 1994; Hillis et al., 1994). C1 MASSACHUSETTS GEN HOSP,CARDIAC UNIT,BOSTON,MA 02114. NR 6 TC 0 Z9 0 U1 0 U2 0 PU ACTA CARDIOLOGICA PI BRUSSELS PA AVENUE CIRCULAIRE 138A, 1180 BRUSSELS, BELGIUM SN 0001-5385 J9 ACTA CARDIOL JI Acta Cardiol. PY 1995 VL 50 IS 6 BP 469 EP 475 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA TU970 UT WOS:A1995TU97000006 PM 8932567 ER PT J AU TATTER, SB EDGAR, MA KLIBANSKI, A SWEARINGEN, B AF TATTER, SB EDGAR, MA KLIBANSKI, A SWEARINGEN, B TI SYMPTOMATIC SALIVARY-REST CYST OF THE SELLA TURCICA SO ACTA NEUROCHIRURGICA LA English DT Article DE ECTOPIC SALIVARY GLAND; PITUITARY GLAND; SELLA TURCICA; MAGNETIC RESONANCE IMAGING ID CLEFT CYSTS; FEATURES AB Although ectopic salivary tissue in the posterior pituitary is frequently observed in microscopic examination at autopsy, this tissue is considered clinically insignificant. The authors report a case of sella turcica mass causing progressive menstrual irregularities and mild hyperprolactinemia in a 22-year-old woman. Magnetic resonance imaging revealed a 1.2 X 0.9 cm non-enhancing mass of the postero-inferior sella turcica. The lesion was isointense to brain on T1-weighted images and hypo- to iso-intense on T2-weighted images. Transsphenoidal exploration revealed that the cyst wall consisted entirely of normal appearing salivary gland. The clinical, radiographic, and pathologic features of this unique entity are discussed. C1 MASSACHUSETTS GEN HOSP,NEUROSURG SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,NEUROENDOCRINE UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 21 TC 12 Z9 12 U1 0 U2 0 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 VIENNA, AUSTRIA SN 0001-6268 J9 ACTA NEUROCHIR JI Acta Neurochir. PY 1995 VL 135 IS 3-4 BP 150 EP 153 DI 10.1007/BF02187760 PG 4 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA RN606 UT WOS:A1995RN60600008 PM 8748806 ER PT J AU GERWECK, LE KOUTCHER, J ZAIDI, ST AF GERWECK, LE KOUTCHER, J ZAIDI, ST TI ENERGY STATUS PARAMETERS, HYPOXIA FRACTION AND RADIOCURABILITY ACROSS TUMOR TYPES SO ACTA ONCOLOGICA LA English DT Article; Proceedings Paper CT International Workshop on the Tumour Microenvironment - Its Characterization, Modification and Clinical Implications CY SEP 23-25, 1994 CL UNIV GRANADA, FAC MED, GRANADA, SPAIN HO UNIV GRANADA, FAC MED ID MAGNETIC-RESONANCE SPECTROSCOPY; MURINE TUMORS; METABOLISM; INVIVO; OXYGEN AB Under full nutrient in vitro conditions, the cellular adenylate energy charge of six different rodent and human tumor cell types was identical, i.e., 0.94 +/- 0.01, suggesting the potential utility of this parameter as a cell (and tissue) independent marker of nutrient deprivation and hypoxia, across tumor types. The adenylate energy charge values of tumors, arising from these cells, was reduced and variable ranging from 0.72 to 0.91 for the various tumor types. However, neither the tumor adenylate energy charge, NTP/Pi, nor PCr/Pi ratios correlated with the radiobiologic hypoxic cell fractions across tumor types. The reduced adenylate energy charge in vivo suggests varying degrees of nutrient deprivation in the different tumor types, however, factors other than or in addition to hypoxia likely contribute to tumor energy status. C1 MEM SLOAN KETTERING CANC CTR,DEPT MED PHYS,NEW YORK,NY. RP GERWECK, LE (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,BOSTON,MA 02114, USA. FU NCI NIH HHS [CA-22860] NR 11 TC 8 Z9 8 U1 0 U2 0 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0284-186X J9 ACTA ONCOL JI Acta Oncol. PY 1995 VL 34 IS 3 BP 335 EP 338 PG 4 WC Oncology SC Oncology GA RB020 UT WOS:A1995RB02000010 PM 7779419 ER PT J AU ASHBERNAL, R WALL, C KOMAROFF, AL BELL, D OAS, JG PAYMAN, RN FAGIOLI, LR AF ASHBERNAL, R WALL, C KOMAROFF, AL BELL, D OAS, JG PAYMAN, RN FAGIOLI, LR TI VESTIBULAR FUNCTION-TEST ANOMALIES IN PATIENTS WITH CHRONIC FATIGUE SYNDROME SO ACTA OTO-LARYNGOLOGICA LA English DT Article DE VESTIBULOOCULAR REFLEX; VESTIBULOSPINAL REFLEX; OTOLITH ORGANS; OPTOKINETIC NYSTAGMUS ID OCULAR MOTOR DEFICITS; PARKINSONS-DISEASE; AXIS ROTATION; DEFINITION; REFLEX AB Chronic fatigue syndrome (CFS) is distinguished by the new onset of debilitating fatigue that lasts at least 6 months, concomitant with other symptoms to be described later. Many CFS patients complain of disequilibrium, yet the exact type of the balance dysfunction and its function and its location (peripheral vs. central) have not been described. Herein we report results of vestibular function testing performed on 11 CFS patients. These results revealed no predominant pattern of abnormalities. Patients typically performed below average in dynamic posturography testing, with a significant number of falls in the tests requiring subjects to depend heavily on the vestibular system. One patient had abnormal caloric testing, while 3 had abnormally low earth vertical axis relation (EVA) gains at the higher frequencies tested. As a group, the average gain of EVA was significantly lower than normals in the 0.1-1.0 Hz range (p < 0.05). In earth horizontal axis rotation, the CFS group had a higher than normal bias value for the optokinetic (OKN) and eyes open in the dark conditions (p < 0.05), but had normal scores during visual vestibular reflex testing. Five of the 11 subjects had an abnormal OKN bias build up over the course of the run, equal to or actually exceeding the 60 degrees/s target velocity by as much as 14 degrees/s. Altogether, these results are more suggestive of central nervous system deficits than of peripheral vestibular disfunction. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02114. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DIV GEN MED & PRIMARY CARE,BOSTON,MA 02115. CAMBRIDGE HOSP,DEPT PEDIAT,CAMBRIDGE,MA 02139. RI Oas, John/E-3772-2011 FU NIAID NIH HHS [U01 AI32246]; NIDCD NIH HHS [DC00290] NR 20 TC 13 Z9 13 U1 0 U2 1 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0001-6489 J9 ACTA OTO-LARYNGOL JI Acta Oto-Laryngol. PD JAN PY 1995 VL 115 IS 1 BP 9 EP 17 DI 10.3109/00016489509133339 PG 9 WC Otorhinolaryngology SC Otorhinolaryngology GA QH471 UT WOS:A1995QH47100003 PM 7762393 ER PT J AU NADOL, JB ADAMS, JC KIM, JR AF NADOL, JB ADAMS, JC KIM, JR TI DEGENERATIVE CHANGES IN THE ORGAN OF CORTI AND LATERAL COCHLEAR WALL IN EXPERIMENTAL ENDOLYMPHATIC HYDROPS AND HUMAN MENIERES-DISEASE SO ACTA OTO-LARYNGOLOGICA LA English DT Article; Proceedings Paper CT International Symposium on Vestibular Disorders CY JAN 21-22, 1994 CL HIROSHIMA, JAPAN DE IMMUNOHISTOCHEMISTRY; HISTOPATHOLOGY; SENSORINEURAL HEARING LOSS; IONIC HOMEOSTASIS ID OUTER HAIR-CELLS; INNER-EAR; ION-TRANSPORT; STEREOCILIA; FIBROCYTES AB The pathogenesis of sensorineural hearing loss in Meniere's disease and experimental endolymphatic hydrops is not fully understood. At the light microscopic level, there is poor correlation between the histopathology and loss of sensitivity and speech discrimination. The results of electron microscopic investigation of histopathology and alterations in immunoreactivity in the organ of Corti and lateral cochlear wall in the hydropic guinea pig are presented. Loss of outer and inner hair cells and spiral ganglion cells, particularly in the apical turn was evident by light microscopy. By electron microscopy, further evidence of degeneration was detected in the cuticular plate of outer hair cells, neural endings of both inner and outer hair cells, myelinated dendritic fibers, spiral ganglion cells, and types I and II fibrocytes of the lateral cochlear wall. There was a marked decrease in immunoreactivity for a variety of enzymes, calcium binding proteins, structural proteins, and integral membrane proteins of gap junctions, particularly among type I and type II fibrocytes of the lateral cochlear wall. The evidence suggests that dysfunction and degeneration of hair cells, afferent neurons and fibrocytes of the lateral cochlear wall are involved in the pathogenesis of hearing loss in endolymphatic hydrops. C1 HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA. KEIMYUNG UNIV,SCH MED,DEPT OTOLARYNGOL,SEOUL,SOUTH KOREA. RP NADOL, JB (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,243 CHARLES ST,BOSTON,MA 02114, USA. NR 29 TC 14 Z9 14 U1 0 U2 0 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0001-6489 J9 ACTA OTO-LARYNGOL JI Acta Oto-Laryngol. PY 1995 SU 519 BP 47 EP 59 PG 13 WC Otorhinolaryngology SC Otorhinolaryngology GA QT876 UT WOS:A1995QT87600010 ER PT J AU Grabowski, EF Jang, IK Gold, H Palacios, IF Boor, SE Rodino, LJ Michelson, AD AF Grabowski, EF Jang, IK Gold, H Palacios, IF Boor, SE Rodino, LJ Michelson, AD TI Platelet degranulation induced by some contrast media is independent of their nonionic vs ionic nature SO ACTA RADIOLOGICA LA English DT Article DE contrast media, flow cytometry; platelet aggregation ID FIBRINOLYSIS; COAGULATION; AGGREGATION; INVITRO; INVIVO; BLOOD AB We confirm that the phenomenon of platelet degranulation exists for both iohexol and diatrizoate, as reported earlier. In contrast to previous conclusions, however, we have determined that the degranulation is independent of the nonionic vs. ionic nature of the media per se, since degranulation was neither seen with nonionic iodixanol nor ionic ioxaglate. The degranulation, further, does not significantly augment platelet function, as measured by flowing whole blood platelet aggregometry. C1 UNIV MASSACHUSETTS,MED CTR,WORCESTER,MA. RP Grabowski, EF (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CARDIOVASC THROMBOSIS LAB,JACKSON 1306,BOSTON,MA 02114, USA. NR 12 TC 7 Z9 8 U1 1 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0284-1851 J9 ACTA RADIOL JI Acta Radiol. PY 1995 VL 36 SU 399 BP 182 EP 184 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA TY021 UT WOS:A1995TY02100021 ER PT J AU WEAVER, DT AF WEAVER, DT TI V(D)J RECOMBINATION AND DOUBLE-STRAND BREAK REPAIR SO ADVANCES IN IMMUNOLOGY, VOL 58 SE ADVANCES IN IMMUNOLOGY LA English DT Review ID COMBINED IMMUNE-DEFICIENCY; ACTIVATED PROTEIN-KINASE; RAY-SENSITIVE MUTANTS; CELL RECEPTOR-GAMMA; SEVERE COMBINED IMMUNODEFICIENCY; WILD-TYPE P53; PRE-B-CELLS; GENE JUNCTIONAL SEQUENCES; CODING JOINT FORMATION; CHINESE-HAMSTER CELLS C1 HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOLEC GENET,BOSTON,MA 02115. RP WEAVER, DT (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,44 BINNEY ST,BOSTON,MA 02115, USA. NR 215 TC 55 Z9 55 U1 1 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0065-2776 J9 ADV IMMUNOL JI Adv.Immunol. PY 1995 VL 58 BP 29 EP 85 DI 10.1016/S0065-2776(08)60619-7 PG 57 WC Immunology SC Immunology GA BD02M UT WOS:A1995BD02M00002 PM 7741029 ER PT J AU DRANOFF, G MULLIGAN, RC AF DRANOFF, G MULLIGAN, RC TI GENE-TRANSFER AS CANCER-THERAPY SO ADVANCES IN IMMUNOLOGY, VOL 58 SE ADVANCES IN IMMUNOLOGY LA English DT Review ID COLONY-STIMULATING FACTOR; MAJOR HISTOCOMPATIBILITY COMPLEX; TUMOR-INFILTRATING LYMPHOCYTES; NECROSIS-FACTOR-ALPHA; CYTOTOXIC T-CELLS; ESTABLISHED PULMONARY METASTASES; IMMUNODEFICIENCY-VIRUS TYPE-1; LASTING ANTITUMOR IMMUNITY; ANTIGEN-PRESENTING CELLS; POLYLYSINE DNA COMPLEXES C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. WHITEHEAD INST BIOMED RES,CAMBRIDGE,MA 02142. MIT,DEPT BIOL,CAMBRIDGE,MA 02142. RP DRANOFF, G (reprint author), DANA FARBER CANC INST,BOSTON,MA 02115, USA. NR 241 TC 139 Z9 141 U1 2 U2 4 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0065-2776 J9 ADV IMMUNOL JI Adv.Immunol. PY 1995 VL 58 BP 417 EP 454 DI 10.1016/S0065-2776(08)60624-0 PG 38 WC Immunology SC Immunology GA BD02M UT WOS:A1995BD02M00007 PM 7741031 ER PT S AU SMITH, DJ TAUBMAN, MA AF SMITH, DJ TAUBMAN, MA BE Mestecky, J Russell, MW Jackson, S Michalek, SM TlaskalovaHogenova, H Sterzl, J TI Development of salivary IgA antibody to oral streptococcal antigens associated with virulence SO ADVANCES IN MUCOSAL IMMUNOLOGY, PTS A AND B SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Proceedings Paper CT 7th International Congress of Mucosal Immunology CY AUG 16-20, 1992 CL PRAGUE, CZECH REPUBLIC SP Soc Mucosal Immunol RP FORSYTH DENT CTR,DEPT IMMUNOL,BOSTON,MA 02115, USA. FU NIDCR NIH HHS [DE-06153] NR 0 TC 4 Z9 4 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0065-2598 BN 0-306-45012-7 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1995 VL 371 BP 1141 EP 1143 PN A-B PG 3 WC Cell Biology; Immunology SC Cell Biology; Immunology GA BD67X UT WOS:A1995BD67X00248 PM 7502771 ER PT S AU SMITH, DJ TAUBMAN, MA AF SMITH, DJ TAUBMAN, MA BE Mestecky, J Russell, MW Jackson, S Michalek, SM TlaskalovaHogenova, H Sterzl, J TI Potential for glucosyltransferase-based peptides in a dental caries vaccine synthetic SO ADVANCES IN MUCOSAL IMMUNOLOGY, PTS A AND B SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Proceedings Paper CT 7th International Congress of Mucosal Immunology CY AUG 16-20, 1992 CL PRAGUE, CZECH REPUBLIC SP Soc Mucosal Immunol RP FORSYTH DENT CTR,DEPT IMMUNOL,BOSTON,MA 02115, USA. FU NIDCR NIH HHS [DE-04733, DE-06153] NR 0 TC 4 Z9 4 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0065-2598 BN 0-306-45012-7 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1995 VL 371 BP 1157 EP 1159 PN A-B PG 3 WC Cell Biology; Immunology SC Cell Biology; Immunology GA BD67X UT WOS:A1995BD67X00252 PM 7502775 ER PT S AU Sweet, WH AF Sweet, WH BE Meyerson, BA Ostertag, C TI Pain - Old and new methods of study and treatment SO ADVANCES IN STEREOTACTIC AND FUNCTIONAL NEUROSURGERY 11 SE ADVANCES IN STEREOTACTIC AND FUNCTIONAL NEUROSURGERY LA English DT Proceedings Paper CT 11th Meeting of the European-Society-for-Stereotactic-and-Functional-Neurosurgery CY SEP, 1994 CL ANTALYA, TURKEY SP European Soc Stereotact & Funct Neurosurg DE pain; psychosurgery; functional MR imaging; cognitive process C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER-VERLAG PI VIENNA PA MOLKERBASTEI 5, POSTFACH 367, A-1011 VIENNA, AUSTRIA SN 0720-7972 BN 3-211-82720-X J9 ADV STER F PY 1995 VL 11 BP 83 EP 87 PG 5 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA BE83D UT WOS:A1995BE83D00018 PM 8748590 ER PT B AU OZELIUS, LJ BRESSMAN, SB KRAMER, PL RISCH, N DELEON, D FAHN, S BREAKEFIELD, XO AF OZELIUS, LJ BRESSMAN, SB KRAMER, PL RISCH, N DELEON, D FAHN, S BREAKEFIELD, XO BE Segawa, M Nomura, Y TI Early-onset, generalized dystonia caused by DYT1 gene on chromosome 9q34 SO AGE-RELATED DOPAMINE-DEPENDENT DISORDERS SE MONOGRAPHS IN NEURAL SCIENCES LA English DT Proceedings Paper CT International Symposium on Age-Related Monoamine-Dependent Disorders and Their Modulation by Gene and Gender/20 Anniversary Symposium of the Segawa-Neurological-Clinic-for-Children CY NOV 12-13, 1993 CL TOKYO, JAPAN SP SEGAWA NEUROL CLIN CHILDREN, FDN ADV INT SCI C1 MASSACHUSETTS GEN HOSP,NEUROL SERV,MOLEC NEUROGENET UNIT,BOSTON,MA 02114. RP MASSACHUSETTS GEN HOSP E,CTR NEUROSCI,BLDG 149,13TH ST,BOSTON,MA 02129, USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND BN 3-8055-5960-7 J9 MG NEUR SCI PY 1995 VL 14 BP 126 EP 132 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BC71E UT WOS:A1995BC71E00015 ER PT J AU DAVIS, RF METZGER, DS MEYERS, K MCLELLAN, AT MULVANEY, FD NAVALINE, HA WOODY, GE AF DAVIS, RF METZGER, DS MEYERS, K MCLELLAN, AT MULVANEY, FD NAVALINE, HA WOODY, GE TI LONG-TERM CHANGES IN PSYCHOLOGICAL SYMPTOMATOLOGY ASSOCIATED WITH HIV SEROSTATUS AMONG MALE INJECTING DRUG-USERS SO AIDS LA English DT Article DE INJECTING DRUG USERS; METHADONE; PSYCHOLOGICAL SYMPTOMATOLOGY; HIV; AIDS ID DEPENDENCE TREATMENT PROGRAMS; HUMAN-IMMUNODEFICIENCY-VIRUS; METHADONE-MAINTENANCE; ABUSE PATIENTS; RISK; SEVERITY; AIDS AB Objective: To examine long-term changes in psychological symptomatology from 6 to 24 months after notification of HIV serostatus among male injecting drug users (IDU). Design: Self-report and interview data were collected at 6-month intervals as part of a longitudinal study monitoring HIV infection and risk-associated behaviors among IDU. Setting: A community-based methadone-maintenance clinic. Participants: Ninety-seven male IDU (81 HIV-seronegative, 16 HIV-seropositive), including both methadone-maintained and out-of-treatment IDU. Main outcome measures: Analyses of long-term changes in psychological symptomatology associated with HIV serostatus among male IDU. Results: Analyses of long-term changes in psychological symptomatology between groups revealed no significantly greater levels of overall psychological distress or significant elevations on subscales of the Symptom Checklist-90 for HIV-seropositive compared with HIV-seronegative male IDU. Also, no significantly higher scores on the Beck Depression Inventory or the psychiatric composite score of the Addiction Severity Index were observed between groups. Conclusions: Our results suggest that HIV-seropositive male IDU do not express greater levels of psychological symptomatology from 6 to 24 months following notification of seropositivity compared with HIV-seronegative male IDU. Several explanations for these findings are considered. Future work should examine why male IDU do not report significant and long-term elevations in symptoms post-notification of HIV seropositivity. Also, studies of changes in psychological symptomatology as a function of HIV serostatus among female IDU need to be conducted to assess implications for treatment interventions among this underserved population. C1 UNIV PENN,CTR STUDIES ADDICT,PHILADELPHIA,PA 19104. DEPT VET AFFAIRS MED CTR,PHILADELPHIA,PA 19104. RI Metzger, David/D-9499-2012 FU NIAID NIH HHS [Y01-AI-20025-01]; NIDA NIH HHS [R01-DA05593] NR 23 TC 19 Z9 19 U1 1 U2 2 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0269-9370 J9 AIDS JI Aids PD JAN PY 1995 VL 9 IS 1 BP 73 EP 79 DI 10.1097/00002030-199501000-00010 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA QB059 UT WOS:A1995QB05900010 PM 7893444 ER PT J AU AGAPITE, J GRETHER, M LAMBLIN, AF WHITE, K STELLER, H AF AGAPITE, J GRETHER, M LAMBLIN, AF WHITE, K STELLER, H TI PROGRAMMED CELL-DEATH IN DROSOPHILA SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 MIT,HOWARD HUGHES MED INST,DEPT BRAIN & COGNIT SCI,CAMBRIDGE,MA 02139. MIT,HOWARD HUGHES MED INST,DEPT BIOL,CAMBRIDGE,MA 02139. MASSACHUSETTS GEN HOSP,BOSTON,MA 02129. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PY 1995 VL 11 SU 1 BP S78 EP S78 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA RQ689 UT WOS:A1995RQ68900059 ER PT J AU HOGLUND, S GONCALVES, J OHAGEN, A GABUZDA, D AF HOGLUND, S GONCALVES, J OHAGEN, A GABUZDA, D TI ULTRASTRUCTURE OF HIV-1 GENOMIC RNA SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 BIOMED CTR,UPPSALA,SWEDEN. DANA FARBER CANC INST,BOSTON,MA 02115. RI iMed.ULisboa, iMed.ULisboa/C-6292-2014; Goncalves, Joao/B-2013-2008; iMed.ULisboa, M2B /B-5277-2014 OI Goncalves, Joao/0000-0002-1245-3715; NR 0 TC 0 Z9 0 U1 0 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PY 1995 VL 11 SU 1 BP S105 EP S105 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA RQ689 UT WOS:A1995RQ68900162 ER PT J AU JIMOH, AG WISE, DL BARTELS, CJ YANG, JC TRANTOLO, DJ GUPTA, R FRIDEN, PM RASMUSSEN, RA RUPRECHT, RM AF JIMOH, AG WISE, DL BARTELS, CJ YANG, JC TRANTOLO, DJ GUPTA, R FRIDEN, PM RASMUSSEN, RA RUPRECHT, RM TI RELEASE OF ANTIGENS FROM BIODEGRADABLE MICROPARTICLES SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NORTHEASTERN UNIV,CTR BIOTECHNOL,DEPT CHEM ENGN,BOSTON,MA 02115. NCI,BETHESDA,MD 20892. CAMBRIDGE SCI INC,BELMONT,MA 02178. MASSACHUSETTS DEPT PUBL HLTH,BOSTON,MA 02130. PERIODONTIX INC,WATERTOWN,MA 02172. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PY 1995 VL 11 SU 1 BP S147 EP S147 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA RQ689 UT WOS:A1995RQ68900330 ER PT J AU KALAMS, SA JOHNSON, RP DYNAN, MD HARTMAN, KE TROCHA, AK WALKER, BD AF KALAMS, SA JOHNSON, RP DYNAN, MD HARTMAN, KE TROCHA, AK WALKER, BD TI THE IDENTIFICATION OF UNIQUE T-CELL RECEPTOR SEQUENCES OF HIV-SPECIFIC CYTOTOXIC T-LYMPHOCYTES ALLOWS ASSESSMENT OF CTL PERSISTENCE IN PBMC OF INFECTED SUBJECTS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,CTR AIDS RES,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PY 1995 VL 11 SU 1 BP S132 EP S132 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA RQ689 UT WOS:A1995RQ68900272 ER PT J AU LIEBERMAN, J SKOLNIK, PR PARKERSON, GR FABRY, JA FONG, DM BEYER, D WANG, A LANDRY, B AF LIEBERMAN, J SKOLNIK, PR PARKERSON, GR FABRY, JA FONG, DM BEYER, D WANG, A LANDRY, B TI IMMUNOTHERAPY WITH EX VIVO-EXPANDED HIV-SPECIFIC CYTOTOXIC T-LYMPHOCYTES IN SUBJECTS WITH CD4 COUNTS OF 100-400/MM(3) SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. TUFTS UNIV NEW ENGLAND MED CTR,DEPT MED,BOSTON,MA 02111. NIH,DIV AIDS,BETHESDA,MD. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PY 1995 VL 11 SU 1 BP S132 EP S132 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA RQ689 UT WOS:A1995RQ68900271 ER PT J AU PARDEE, AB LI, CJ BISWAS, DK AF PARDEE, AB LI, CJ BISWAS, DK TI ROLES OF TAT IN HIV-INFECTION SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. NR 3 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PY 1995 VL 11 SU 1 BP S87 EP S87 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA RQ689 UT WOS:A1995RQ68900094 ER PT J AU PROFY, AT PALLAI, PV NEIDHARDT, EA SINGH, SK VANSCHRAVENDIJK, MR WU, J WILLIS, KJ GORDON, K SAMPO, TM OSBURNE, MS RUSCONI, S MERRIL, D MOONIS, M HIRSCH, MS BUCKHEIT, RW WORTEL, CH JENSON, JC AF PROFY, AT PALLAI, PV NEIDHARDT, EA SINGH, SK VANSCHRAVENDIJK, MR WU, J WILLIS, KJ GORDON, K SAMPO, TM OSBURNE, MS RUSCONI, S MERRIL, D MOONIS, M HIRSCH, MS BUCKHEIT, RW WORTEL, CH JENSON, JC TI IDENTIFICATION OF A CLASS OF COMPOUNDS THAT BLOCK GP120 BINDING TO CD4 AND SUPPRESS HIV-1 INFECTION IN-VITRO SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 PROCEPT INC,CAMBRIDGE,ENGLAND. FREDERICK RES CTR,SO RES INST,FREDERICK,MD. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PY 1995 VL 11 SU 1 BP S169 EP S169 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA RQ689 UT WOS:A1995RQ68900417 ER PT J AU RUPRECHT, RM AYEHUNIE, S BABA, TW AN, L LISKA, V PENNINCK, D GREENE, M MONTEFIORI, DC AF RUPRECHT, RM AYEHUNIE, S BABA, TW AN, L LISKA, V PENNINCK, D GREENE, M MONTEFIORI, DC TI SIV PATHOGENESIS DURING ONTOGENY - THE VIRUS THRESHOLD HYPOTHESIS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA. TUFTS UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. DUKE UNIV,DURHAM,NC 27706. NR 0 TC 2 Z9 2 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PY 1995 VL 11 SU 1 BP S129 EP S129 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA RQ689 UT WOS:A1995RQ68900261 ER PT J AU SCADDEN, DT FREEDMAN, AF ZHOU, H CHENG, T KALLEMS, S BERARDI, A AF SCADDEN, DT FREEDMAN, AF ZHOU, H CHENG, T KALLEMS, S BERARDI, A TI IN-VITRO MODELS OF GENE-THERAPY SO AIDS RESEARCH AND HUMAN RETROVIRUSES 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 MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PY 1995 VL 11 SU 1 BP S166 EP S166 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA RQ689 UT WOS:A1995RQ68900406 ER PT J AU WEBER, GF ASHKAR, S GLIMCHER, M CANTOR, H AF WEBER, GF ASHKAR, S GLIMCHER, M CANTOR, H TI INTERACTION BETWEEN CD44 AND ETA-1/OSTEOPONTIN AND LYMPHOCYTE RECIRCULATION IN HIV-INFECTION SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 DANA FARBER CANC INST,IMMUNOPATHOL LAB,BOSTON,MA. CHILDRENS HOSP,ORTHOPED RES & SKELETAL DISORDERS & REHABIL LAB,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT ORTHOPED SURG,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PY 1995 VL 11 SU 1 BP S79 EP S79 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA RQ689 UT WOS:A1995RQ68900060 ER PT J AU YANG, OO KALAMS, SK JOHNSON, RP WALKER, BD AF YANG, OO KALAMS, SK JOHNSON, RP WALKER, BD TI INHIBITION OF HIV-1 REPLICATIONS BY HIV-1-SPECIFIC CTL CLONES SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PY 1995 VL 11 SU 1 BP S132 EP S132 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA RQ689 UT WOS:A1995RQ68900270 ER PT J AU FOSTER, CS AF FOSTER, CS TI THE PATHOPHYSIOLOGY OF OCULAR ALLERGY - CURRENT THINKING SO ALLERGY LA English DT Article ID NEDOCROMIL SODIUM; CONJUNCTIVITIS AB Seasonal allergic conjunctivitis is the only ocular disease to involve solely Type-1 hypersensitivity, the other main forms of ocular allergy - perennial allergic conjunctivitis, vernal and atopic keratoconjunctivitis and giant papillary conjunctivitis - each having a more complex immunological basis and a chronic inflammatory component. Involvement of secondary inflammatory cells, particularly eosinophils, in addition to the mast cells resident in the conjunctival substantia propria, can lead to more serious corneal damage with vision-threatening potential. Thoughtful management of allergic conjunctivitis is needed in order to control the ocular inflammation without incurring steroid-induced side-effects, and patient education is also an important factor in maintaining optimal allergen avoidance, especially in the more severe and chronic cases. Laboratory models can be helpful in assessing the potential of new drugs, and SWR mice (topically sensitised and challenged with short ragweed) show clinical signs of allergic conjunctivitis, together with mast cell and eosinophil involvement, remarkably similar to the human pathophysiology. The antiinflammatory activity of both steroids and nedocromil sodium observed in this animal model supports therapeutic evidence of the usefulness of second-generation mast cell stabilising drugs in the treatment of ocular allergy. RP FOSTER, CS (reprint author), HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BOSTON,MA, USA. NR 5 TC 27 Z9 31 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-4538 J9 ALLERGY JI Allergy PY 1995 VL 50 IS 21 SU S BP 6 EP 9 DI 10.1111/j.1398-9995.1995.tb04250.x PG 4 WC Allergy; Immunology SC Allergy; Immunology GA QN118 UT WOS:A1995QN11800002 PM 7785749 ER PT J AU BENEZRA, D ALEXANDER, M KJELLMAN, NIM PELIKAN, Z FOSTER, CS LIGHTMAN, S BONINI, S KNOTTNERUS, I COLLUM, L AF BENEZRA, D ALEXANDER, M KJELLMAN, NIM PELIKAN, Z FOSTER, CS LIGHTMAN, S BONINI, S KNOTTNERUS, I COLLUM, L TI UNTITLED - DISCUSSION SO ALLERGY LA English DT Discussion C1 LINKOPING UNIV HOSP,S-58185 LINKOPING,SWEDEN. GREATER NIAGARA GEN HOSP,NIAGARA FALLS,ON,CANADA. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BOSTON,MA. MOORFIELDS EYE HOSP,LONDON,ENGLAND. RP BENEZRA, D (reprint author), HADASSAH UNIV HOSP,IL-91120 JERUSALEM,ISRAEL. RI Bonini, Stefano/A-2250-2012 OI Bonini, Stefano/0000-0002-7787-2144 NR 0 TC 1 Z9 1 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-4538 J9 ALLERGY JI Allergy PY 1995 VL 50 IS 21 SU S BP 34 EP 38 PG 5 WC Allergy; Immunology SC Allergy; Immunology GA QN118 UT WOS:A1995QN11800007 ER PT J AU CUMMINGS, JL ROSS, W ABSHER, J GORNBEIN, J HADJIAGHAI, L AF CUMMINGS, JL ROSS, W ABSHER, J GORNBEIN, J HADJIAGHAI, L TI DEPRESSIVE SYMPTOMS IN ALZHEIMER-DISEASE - ASSESSMENT AND DETERMINANTS SO ALZHEIMER DISEASE & ASSOCIATED DISORDERS LA English DT Article DE DEPRESSION; DELUSIONS; ACETYLCHOLINE ID COGNITIVE STATUS EXAMINATION; MINI-MENTAL STATE; RATING-SCALE; BIOCHEMICAL MANIFESTATIONS; PSYCHIATRIC-SYMPTOMS; PARKINSONS-DISEASE; DEMENTIA; MOOD; NEUROBIOLOGY; INDUCTION AB Depression is difficult to assess in Alzheimer disease (AD) and controversy surrounds the prevalence, etiology, and characteristics of mood alterations in patients with this disorder. We used a variety of standardized instruments to assess mood changes in 33 patients with AD. The frequency of depression ranged from 6 to 30%, depending on the diagnostic criteria employed. No relationship was found between patient depression and dementia severity, self-awareness of cognitive deficits (as measured by a memory self-rating scale), or mood of the caregiver. Delusional patients had higher scores on mood rating scales than nondelusional patients. The results suggest that depression in AD is not severe and is unrelated to patient self-awareness of illness. We hypothesize that the cholinergic deficit of AD may ameliorate depressive symptoms. C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT PSYCHIAT,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT BIOMATH,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,PSYCHIAT SERV,BEHAV NEUROSCI SECT,LOS ANGELES,CA 90073. RP CUMMINGS, JL (reprint author), UNIV CALIF LOS ANGELES,SCH MED,REED NEUROL RES CTR,DEPT NEUROL,710 WESTWOOD PLAZA,LOS ANGELES,CA 90024, USA. FU NIA NIH HHS [AG 10123] NR 57 TC 82 Z9 84 U1 1 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0893-0341 J9 ALZ DIS ASSOC DIS JI Alzheimer Dis. Assoc. Dis. PY 1995 VL 9 IS 2 BP 87 EP 93 DI 10.1097/00002093-199509020-00005 PG 7 WC Clinical Neurology; Pathology SC Neurosciences & Neurology; Pathology GA RB473 UT WOS:A1995RB47300005 PM 7662328 ER PT J AU BROOKS, R GARAN, H MCGOVERN, BA RUSKIN, JN AF BROOKS, R GARAN, H MCGOVERN, BA RUSKIN, JN TI IMPLANTATION OF TRANSVENOUS NONTHORACOTOMY CARDIOVERTER-DEFIBRILLATOR SYSTEMS IN PATIENTS WITH PERMANENT ENDOCARDIAL PACEMAKERS SO AMERICAN HEART JOURNAL LA English DT Article AB Among 177 patients in whom a nonthoracotomy approach was initially used to implant a cardioverter-defibrillator system, 11 (6%) patients also received a separately implanted permanent pacemaker. The main problem encountered in these patients were previously implanted unipolar pacemakers (n = 3) and ventricular pacing leads positioned at the right ventricular apex, the latter interfering with optimal placement of the tripolar implantable cardioverter-defibrillator (ICD) lead (n = 9). The approaches used to solve these problems were individualized and included placemen of the ICD sensing lead at the right ventricular outflow tract (n = 3), initial placement (n = 1) or subsequent repositioning (n = 2) of the right ventricular pacing lead at the outflow tract, upgrade from unipolar to bipolar systems (n = 2), reprogramming from the DDD to AAI mode (n = 2), inactivation of the pacemaker (n = 1), and simultaneous placement of a single-chamber atrial pacemaker with the ICD lead (n = 2). These revisions fulfilled the pacing needs in each patient and prevented unfavorable sensing interaction between the two systems. C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP BROOKS, R (reprint author), MASSACHUSETTS GEN HOSP,CARDIAC UNIT,CARDIAC ARRHYTHMIA SERV,BOSTON,MA 02114, USA. NR 9 TC 23 Z9 23 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 JAN PY 1995 VL 129 IS 1 BP 45 EP 53 DI 10.1016/0002-8703(95)90041-1 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA QB188 UT WOS:A1995QB18800008 PM 7817923 ER PT J AU SINGH, BN KEHOE, R WOOSLEY, RL SCHEINMAN, M QUART, B BAUERNFEIND, R GREENSPON, A HEGER, JJ ZIPES, DP KERIN, NZ KEHOE, RF MARTINS, JB PETER, T RUFFY, R RUSKIN, JN SCHEINMAN, MM NADEMANEE, K ECHT, D AF SINGH, BN KEHOE, R WOOSLEY, RL SCHEINMAN, M QUART, B BAUERNFEIND, R GREENSPON, A HEGER, JJ ZIPES, DP KERIN, NZ KEHOE, RF MARTINS, JB PETER, T RUFFY, R RUSKIN, JN SCHEINMAN, MM NADEMANEE, K ECHT, D TI MULTICENTER TRIAL OF SOTALOL COMPARED WITH PROCAINAMIDE IN THE SUPPRESSION OF INDUCIBLE VENTRICULAR-TACHYCARDIA - A DOUBLE-BLIND, RANDOMIZED PARALLEL EVALUATION SO AMERICAN HEART JOURNAL LA English DT Article ID CORONARY-ARTERY DISEASE; ISOLATED CARDIAC-MUSCLE; ANTI-ARRHYTHMIC ACTION; ANTIARRHYTHMIC DRUGS; ANTIFIBRILLATORY ACTIONS; DEXTROROTATORY ISOMERS; ORAL SOTALOL; EFFICACY; TACHYARRHYTHMIAS; PROLONGATION AB Sotalol is the prototype class III agent that combines beta-blocking properties with the propensity to prolong the effective refractory period by lengthening the action potential duration. Its precise effect on the prevention of ventricular tachycardia-ventricular fibrillation (VTVF) compared to class I agents has not been evaluated in a blinded study. In a double-blind parallel-design multicenter study, the electrophysiologic and antiarrhythmic effects of intravenous and oral sotalol (n = 55) and procainamide (n = 55) were therefore compared in patients with VTVF inducible by programmed electric stimulation. Sotalol produced a greater effect on lengthening the ventricular effective refractory period (VERP), It prevented the inducibility of VTVF in 30% versus 20% for procainamide, but this was not significantly different. In an alternate therapy group (n = 41) of similar patients previously refractory to or intolerant of procainamide, intravenous sotalol prevented inducibility in 32%. The pooled overall sotalol efficacy rate was 31%. There was a significant relation between the increase in the VERP and the prevention of inducibility of VTVF (n = 56; p < 0.02). VERP of greater than or equal to 300 msec was critical for the prevention of VTVF inducibility. Thirteen sotalol and 6 procainamide responders from the randomized group and 30 from the nonrandomized groups completed 1 year of oral sotalol therapy follow-up. Life-table analysis of these patient in each group showed a trend in favor of sotalol; however, statistical analysis was not possible because of the small numbers of patients. Both sotalol and procainamide were well tolerated. In the randomized group there was one case of sudden death during treatment with sotalol and two cases of nonfatal torsades de pointes in the procainamide group and two in the sotalol group; in the nonrandomized alternate therapy group, there were 6 cases of nonfatal torsades de pointes. The data support the emerging role of sotalol in the control of symptomatic ventricular tachycardia and fibrillation. C1 UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA. NORTHWESTERN UNIV,SCH MED,CHICAGO,IL. GEORGETOWN UNIV,SCH MED,WASHINGTON,DC. UNIV CALIF SAN FRANCISCO,SCH MED,SAN FRANCISCO,CA. BRISTOL MYERS SQUIBB CO,PRINCETON,NJ. RP SINGH, BN (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,DEPT CARDIOL,CARDIOL SECT,691-W111E,WILSHIRE SAWTELLE BLVDS,LOS ANGELES,CA 90073, USA. NR 49 TC 36 Z9 37 U1 0 U2 3 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 JAN PY 1995 VL 129 IS 1 BP 87 EP 97 DI 10.1016/0002-8703(95)90048-9 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA QB188 UT WOS:A1995QB18800015 PM 7817931 ER PT J AU BROOKS, R JACKSON, G MCGOVERN, BA RUSKIN, JN AF BROOKS, R JACKSON, G MCGOVERN, BA RUSKIN, JN TI TRANSVENOUS CARDIOVERTER-DEFIBRILLATOR IMPLANTATION VIA PERSISTENT LEFT SUPERIOR VENA-CAVA SO AMERICAN HEART JOURNAL LA English DT Note RP BROOKS, R (reprint author), MASSACHUSETTS GEN HOSP,CARDIAC ARRHYTHMIA SERV,CARDIAC UNIT,BOSTON,MA 02114, USA. NR 6 TC 9 Z9 9 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD JAN PY 1995 VL 129 IS 1 BP 195 EP 197 DI 10.1016/0002-8703(95)90060-8 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA QB188 UT WOS:A1995QB18800028 PM 7817915 ER PT J AU Scurfield, RM AF Scurfield, RM TI Healing the warrior: Admission of two American Indian war-veteran cohort groups to a specialized inpatient PTSD unit SO AMERICAN INDIAN AND ALASKA NATIVE MENTAL HEALTH RESEARCH LA English DT Article ID THERAPY AB The American Lake VA Post-Traumatic Stress Disorder (PTSD) Treatment Program provides intensive inpatient treatment for war-related PTSD and associated conditions. As part of a substantial outreach effort to American Indians (Al) in the Northwest U.S., the program significantly modified its admission criteria and treatment to be more clinically and culturally relevant. An all-Al cohort, and then a group that was 50% Al, were admitted. Highlighted are lessons learned regarding: treating ''traditional'' versus more ''assimilated'' Al veterans; culture-specific additions of building and utilizing a sweatlodge on the hospital grounds, hiring an Al spiritual leader as a clinical advisor, and promoting attendance at weekend Pow-Wows; the relevance of the ''regular'' treatment components; and the need for regular debriefings about counter-transference dynamics among staff. RP Scurfield, RM (reprint author), US DEPT VET AFFAIRS,PTSD,CTR PACIFIC,1132 BISHOP ST,SUITE 307,HONOLULU,HI 96813, USA. NR 17 TC 4 Z9 4 U1 0 U2 2 PU UNIVERSITY PRESS COLORADO PI NIWOT PA PO BOX 849, NIWOT, CO 80544 SN 0893-5394 J9 AM INDIAN ALASKA NAT JI Am. Indian Alsk. Nativ. Ment. Health Res. PY 1995 VL 6 IS 3 BP 1 EP 22 PG 22 WC Psychology, Clinical SC Psychology GA TL534 UT WOS:A1995TL53400001 PM 8555350 ER PT J AU SINGARAM, C TORBEY, CF JACOBY, RF AF SINGARAM, C TORBEY, CF JACOBY, RF TI DELAYED POSTPOLYPECTOMY BLEEDING SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Note ID COMPLICATIONS; POLYPECTOMY; COLONOSCOPY; HEMORRHAGE AB Complications of colonoscopic polypectomy include perforation, infection, and bleeding. The incidence of bleeding after polypectomy is reported to range from one to seven per 1000 polypectomies. This complication usually occurs within a few days after the standard procedure using bipolar electrocautery. The longest time interval between polypectomy and significant bleeding thus far reported is 14 days. Most cases of postpolypectomy bleeding are easily recognizable and can be effectively treated by colonoscopic electrocauterization. We report here a patient who underwent colonoscopic removal of a flat adenomatous polyp at the cecum and presented 29 days postprocedure with acute onset of severe bleeding from the polypectomy site. A repeat colonoscopy identified this lesion, and cauterization successfully stopped this bleeding. C1 WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI. RP SINGARAM, C (reprint author), UNIV WISCONSIN HOSP & CLIN,CTR CLIN SCI,DEPT MED,DIV GASTROENTEROL,H6-510,MADISON,WI 53792, USA. FU NCI NIH HHS [1U01-CA 59352] NR 8 TC 31 Z9 32 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 JAN PY 1995 VL 90 IS 1 BP 146 EP 147 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QA696 UT WOS:A1995QA69600034 PM 7801918 ER PT J AU NAROD, SA FORD, D DEVILEE, P BARKARDOTTIR, RB LYNCH, HT SMITH, SA PONDER, BAJ WEBER, BL GARBER, JE BIRCH, JM CORNELIS, RS KELSELL, DP SPURR, NK SMYTH, E HAITES, N SOBOL, H BIGNON, YJ CHANGCLAUDE, J HAMANN, U LINDBLOM, A BORG, A PIVER, MS GALLION, HH STRUEWING, JP WHITTEMORE, A TONIN, P GOLDGAR, DE EASTON, DF MILNER, B ALLAN, L SIMARD, J ROMMENS, J MCGILLIVRAY, B GREEN, R IVES, E BOYD, N ROSEN, B COLE, D MORGAN, K MOSLEHI, R PONDER, B PETO, J SMITH, S STRATTON, M DICIOCCIO, RA GALLION, H SANTIBANEZKOREF, MS TEARE, MD EVANS, DG STOPPALYONNET, D LALLE, P BONAITI, C ESSIOUX, L GIRODET, C MAUGARDLOUBOUTIN, C NICOLLEAU, G LONGY, M TOULOUSE, C HORSTEIN, I BIRNBAUM, D EISINGER, F KARENGUEVEN, F NOGUCHI, T HARDOUIN, A RIO, P MACHELARDROUMAGNAC, M NOGUES, C COHENHAGUENAUER, O LORTHOLARY, A BAY, JO ARASON, A BARKDARDOTTIR, RB EGILSSON, V BISHOP, DT KELSELL, D MURDAY, VA SOLOMON, E SPURR, N TURNER, G LENOIR, G FEUNTEUN, J LYNCH, H LYNCH, J WATSON, P CONWAY, T BONNARDEL, C SEROVA, O TORCHARD, D LARSSON, C VASEN, H VANLEEUWEN, I CORNELISSE, CJ STEEL, M PORTER, D COHEN, BB CAROTHERS, A CANNONALBRIGHT, LA GOLDGAR, D SKOLNICK, M BECHER, H JOHANNSSON, O WEBER, B COLLINS, F BOEHNKE, M GARBER, J LI, F AF NAROD, SA FORD, D DEVILEE, P BARKARDOTTIR, RB LYNCH, HT SMITH, SA PONDER, BAJ WEBER, BL GARBER, JE BIRCH, JM CORNELIS, RS KELSELL, DP SPURR, NK SMYTH, E HAITES, N SOBOL, H BIGNON, YJ CHANGCLAUDE, J HAMANN, U LINDBLOM, A BORG, A PIVER, MS GALLION, HH STRUEWING, JP WHITTEMORE, A TONIN, P GOLDGAR, DE EASTON, DF MILNER, B ALLAN, L SIMARD, J ROMMENS, J MCGILLIVRAY, B GREEN, R IVES, E BOYD, N ROSEN, B COLE, D MORGAN, K MOSLEHI, R PONDER, B PETO, J SMITH, S STRATTON, M DICIOCCIO, RA GALLION, H SANTIBANEZKOREF, MS TEARE, MD EVANS, DG STOPPALYONNET, D LALLE, P BONAITI, C ESSIOUX, L GIRODET, C MAUGARDLOUBOUTIN, C NICOLLEAU, G LONGY, M TOULOUSE, C HORSTEIN, I BIRNBAUM, D EISINGER, F KARENGUEVEN, F NOGUCHI, T HARDOUIN, A RIO, P MACHELARDROUMAGNAC, M NOGUES, C COHENHAGUENAUER, O LORTHOLARY, A BAY, JO ARASON, A BARKDARDOTTIR, RB EGILSSON, V BISHOP, DT KELSELL, D MURDAY, VA SOLOMON, E SPURR, N TURNER, G LENOIR, G FEUNTEUN, J LYNCH, H LYNCH, J WATSON, P CONWAY, T BONNARDEL, C SEROVA, O TORCHARD, D LARSSON, C VASEN, H VANLEEUWEN, I CORNELISSE, CJ STEEL, M PORTER, D COHEN, BB CAROTHERS, A CANNONALBRIGHT, LA GOLDGAR, D SKOLNICK, M BECHER, H JOHANNSSON, O WEBER, B COLLINS, F BOEHNKE, M GARBER, J LI, F TI AN EVALUATION OF GENETIC-HETEROGENEITY IN 145 BREAST-CANCER OVARIAN-CANCER FAMILIES SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID BRCA1 REGION; ALLELE LOSS; CHROMOSOME-17Q21; SUSCEPTIBILITY; LINKAGE; ONSET; MAPS; INTERVAL; MARKERS; RISKS AB The breast-ovary cancer-family syndrome is a dominant predisposition to cancer of the breast and ovaries which has been mapped to chromosome region 17q12-q21. The majority, but not all, of breast-ovary cancer families show linkage to this susceptibility locus, designated BRCA1. We report here the results of a linkage analysis of 145 families with both breast and ovarian cancer. These families contain either a total of three or more cases of early-onset (before age 60 years) breast cancer or ovarian cancer. All families contained at least one case of ovarian cancer, Overall, an estimated 76% of the 145 families are linked to the BRCA1 locus. None of 13 families with cases of male breast cancer appear to be linked, but it is estimated that 92% (95% confidence interval 76%-100%) of families with no male breast cancer and with two or more ovarian cancers are linked to BRCA1. These data suggest that the breast-ovarian cancer-family syndrome is genetically heterogeneous. However, the large majority of families with early-onset breast cancer and with two or more cases of ovarian cancer are likely to be due to BRCA1 mutations. C1 MCGILL UNIV,DEPT MED,DIV MED GENET,MONTREAL,PQ,CANADA. MCGILL UNIV,DEPT HUMAN GENET,MONTREAL,PQ,CANADA. INST CANC RES,EPIDEMIOL SECT,SUTTON,SURREY,ENGLAND. LEIDEN UNIV,DEPT PATHOL,LEIDEN,NETHERLANDS. LEIDEN UNIV,DEPT HUMAN GENET,LEIDEN,NETHERLANDS. UNIV HOSP ICELAND,DEPT PATHOL,REYKJAVIK,ICELAND. CREIGHTON UNIV,SCH MED,DEPT PREVENT MED & PUBL HLTH,OMAHA,NE 68178. UNIV CAMBRIDGE,DEPT PATHOL,HUMAN CANC GENET RES GRP,CANC RES CAMPAIGN,CAMBRIDGE,ENGLAND. UNIV MICHIGAN,SCH MED,DEPT INTERNAL MED,ANN ARBOR,MI. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. UNIV MANCHESTER,PEDIAT & FAMILIAL CANC RES GRP,CANC RES CAMPAIGN,MANCHESTER,LANCS,ENGLAND. IMPERIAL CANC RES FUND,HUMAN GENET RESOURCES LAB,POTTERS BAR,HERTS,ENGLAND. WESTERN GEN HOSP,HUMAN GENET UNIT,MRC,EDINBURGH,MIDLOTHIAN,SCOTLAND. UNIV ABERDEEN,DEPT MOLEC & CELL BIOL,ABERDEEN,SCOTLAND. INST J PAOLI I CALMETTES,DEPT ONCOL GENET,MARSEILLE,FRANCE. CTR JEAN PERRIN,MOLEC ONCOL LAB,CLERMONT FERRAND,FRANCE. GERMAN CANC RES CTR,DIV EPIDEMIOL,HEIDELBERG,GERMANY. KAROLINSKA HOSP,DEPT CLIN GENET,S-10401 STOCKHOLM,SWEDEN. UNIV LUND HOSP,LUND,SWEDEN. ROSWELL PK CANC INST,BUFFALO,NY. NIH,GENET EPIDEMIOL BRANCH,BETHESDA,MD. STANFORD UNIV,SCH MED,DIV EPIDEMIOL,STANFORD,CA. UNIV UTAH,GENET EPIDEMIOL GRP,SALT LAKE CITY,UT. RI Struewing, Jeffery/C-3221-2008; Struewing, Jeffery/I-7502-2013 OI Struewing, Jeffery/0000-0002-4848-3334 NR 39 TC 242 Z9 243 U1 1 U2 6 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 JAN PY 1995 VL 56 IS 1 BP 254 EP 264 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA QC101 UT WOS:A1995QC10100033 PM 7825586 ER PT J AU GARCIACLOSAS, M CHRISTIANI, DC AF GARCIACLOSAS, M CHRISTIANI, DC TI ASBESTOS-RELATED DISEASES IN CONSTRUCTION CARPENTERS SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE CHEST X-RAY ABNORMALITIES; ASBESTOS; PLEURAL ABNORMALITIES; INTERSTITIAL PULMONARY FIBROSIS; CARPENTERS ID SHEET-METAL WORKERS; LUNG-FUNCTION; PLEURAL PLAQUES; PULMONARY-FUNCTION; ABNORMALITIES; EXPOSURE AB To assess the association of minimal parenchymal fibrosis and pleural plaques with respiratory functional impairment, we conducted a survey of 631 asbestos-exposed construction carpenters. This population had a relatively low prevalence of radiographic abnormalities and lung function impairment. Pleural plaques was the asbestos-related disease most prevalent, followed by interstitial fibrosis with predominantly low profusion scores. The most frequent functional impairment was the obstructive pattern, followed by restrictive and mixed patterns. After adjusting for potential confounders, the presence of pleural plaques was significantly associated with a mixed respiratory pattern of impairment (OR = 3.7, 95% CI 1.3-12.3). Furthermore, our data were consistent with a weak association between pleural plaques and a predominately restrictive defect (OR-1.3, 95% CI 0.4-3.9). This study also suggested an association between minimally detectable profusions and both obstructive (OR = 1.9, 95% CI 0.6-6.3) and mixed (OR = 1.6, 95% CI 0.3-7.1) defects. Although only 631 of a potential 7,649 active and retired union members participated in this first-time survey and were relatively young, these findings add new evidence to the functional importance of pleural fibrosis and minimal parenchymal fibrosis. (C) 1995 Wiley-Liss, Inc. C1 HARVARD UNIV,SCH PUBL HLTH,DEPT ENVIRONM HLTH,OCCUPAT HLTH PROGRAM,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT MED,PULM & CRIT CARE UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS RESP HOSP,BRAINTREE,MA. RI Garcia-Closas, Montserrat /F-3871-2015 OI Garcia-Closas, Montserrat /0000-0003-1033-2650 FU NIEHS NIH HHS [P30 ES00002]; PHS HHS [P0106409] NR 26 TC 21 Z9 21 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 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD JAN PY 1995 VL 27 IS 1 BP 115 EP 125 DI 10.1002/ajim.4700270111 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA QF923 UT WOS:A1995QF92300010 PM 7900729 ER PT J AU WEINGER, K JACOBSON, AM DRAELOS, MT FINKELSTEIN, DM SIMONSON, DC AF WEINGER, K JACOBSON, AM DRAELOS, MT FINKELSTEIN, DM SIMONSON, DC TI BLOOD-GLUCOSE ESTIMATION AND SYMPTOMS DURING HYPERGLYCEMIA AND HYPOGLYCEMIA IN PATIENTS WITH INSULIN-DEPENDENT DIABETES-MELLITUS SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID GLYCEMIC CONTROL; IDDM; COUNTERREGULATION; RADIOIMMUNOASSAY; UNAWARENESS; SECRETION; RESPONSES; ADULTS; HUMANS; PLASMA AB PURPOSE: To investigate hypoglycemic and hyperglycemic symptoms, accuracy of estimating blood glucose, and their relation to glycemic control and counterregulatory hormone levels in insulin-dependent diabetes mellitus. PATIENTS AND METHODS: During randomly ordered stepped hypoglycemic and hyperglycemic insulin clamps on two separate days, 42 patients with insulin-dependent diabetes mellitus rated the intensity of 40 moods and symptoms when glucose was 8.9, 5.6 and 2.2 mmol/L, and 8.9, 14.4 and 21.1 mmol/l. The subjects were blinded to their actual glucose levels and asked to estimate them at each step. Epinephrine, norepinephrine, cortisol, growth hormone, and glucagon were measured at each glucose plateau. RESULTS: Cluster analysis yielded five symptom groups during hypoglycemia: autonomic symptoms, negative moods, positive moods, feeling weak/dizzy, and feeling relaxed. At 2.2 mmol/L, mean scores for all five symptom groups and 11 of 17 unclustered symptoms differed from those reported at the baseline glucose of 8.9 mmol/L (P <0.05), but 34% of patients reported no awareness of autonomic symptoms. The intensity of autonomic symptoms correlated positively with HbA(1) (r =.43, P <0.01), epinephrine (r = .59, P <0.001), norepinephrine (r =.45, P <0.01) and cortisol (r =.62, P < 0.001), and negatively with glucose estimation error (r = -.45, P = 0.01). Six patients (15%) were unaware of both autonomic and neuroglycopenic symptoms during hypoglycemia. At 21.1 mmol/L, only 5 of 40 symptoms differed (P <0.05) from baseline. Seventeen percent of subjects made potentially serious errors when estimating glucose at 2.2 mmol/L, and 66% at 21.1 mmol/L. Many patients experienced symptoms different from those they reported as their usual manifestations of changing glucose levels. CONCLUSIONS: Since the majority of patients made clinically serious errors in glucose estimation, and many used symptoms that did not discriminate hyperglycemia and hypoglycemia, individualized training to increase awareness of glucose-related symptoms and glucose levels may help patients reduce the frequency or severity of hyperglycemic and hypoglycemic events. C1 JOSLIN DIABET CTR,PSYCHOSOCIAL UNIT,BOSTON,MA 02215. BRIGHAM & WOMENS HOSP,NEW ENGLAND DEACONESS HOSP,BOSTON,MA. HARVARD UNIV,SCH MED,BOSTON,MA. HARVARD UNIV,GRAD SCH EDUC,CAMBRIDGE,MA. HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. FU NIDDK NIH HHS [DK36836, DK42315] NR 41 TC 33 Z9 34 U1 1 U2 5 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0002-9343 J9 AM J MED JI Am. J. Med. PD JAN PY 1995 VL 98 IS 1 BP 22 EP 31 DI 10.1016/S0002-9343(99)80077-1 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA QB680 UT WOS:A1995QB68000005 PM 7825615 ER PT J AU PROVENZALE, JM WEBER, AL KLINTWORTH, GK MCLENDON, RE AF PROVENZALE, JM WEBER, AL KLINTWORTH, GK MCLENDON, RE TI RADIOLOGIC-PATHOLOGICAL CORRELATION - BILATERAL RETINOBLASTOMA WITH COEXISTENT PINEALOBLASTOMA (TRILATERAL RETINOBLASTOMA) SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article DE RETINA, NEOPLASMS; PINEAL GLAND, NEOPLASMS; CHILDREN, NEOPLASMS; RADIOLOGIC-PATHOLOGICAL CORRELATIONS ID COMPUTED-TOMOGRAPHY; MAGNETIC-RESONANCE; CT; DIAGNOSIS; MANAGEMENT; MUTATION; RETINOMA; LESIONS; TUMORS C1 DUKE UNIV,MED CTR,DEPT PATHOL,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT OPHTHALMOL,DURHAM,NC 27710. MASSACHUSETTS EYE & EAR INFIRM,DEPT RADIOL,BOSTON,MA 02114. RP PROVENZALE, JM (reprint author), DUKE UNIV,MED CTR,DEPT RADIOL,BOX 3808,DURHAM,NC 27710, USA. NR 55 TC 19 Z9 21 U1 0 U2 0 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD JAN PY 1995 VL 16 IS 1 BP 157 EP 165 PG 9 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA QB206 UT WOS:A1995QB20600025 PM 7900586 ER PT J AU ZEITELS, SM DAVIS, RK AF ZEITELS, SM DAVIS, RK TI ENDOSCOPIC LASER MANAGEMENT OF SUPRAGLOTTIC CANCER SO AMERICAN JOURNAL OF OTOLARYNGOLOGY LA English DT Review RP ZEITELS, SM (reprint author), HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,VET AFFAIRS MED CTR,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02130, USA. NR 0 TC 14 Z9 14 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0196-0709 J9 AM J OTOLARYNG JI Am. J. Otolaryngol. PD JAN-FEB PY 1995 VL 16 IS 1 BP 2 EP 11 DI 10.1016/0196-0709(95)90002-0 PG 10 WC Otorhinolaryngology SC Otorhinolaryngology GA QD548 UT WOS:A1995QD54800001 PM 7717468 ER PT J AU MEGERIAN, CA MCKENNA, MJ NADOL, JB AF MEGERIAN, CA MCKENNA, MJ NADOL, JB TI NON-PARAGANGLIOMA JUGULAR FORAMEN LESIONS MASQUERADING AS GLOMUS-JUGULARE TUMORS SO AMERICAN JOURNAL OF OTOLOGY LA English DT Article ID SKULL BASE; EXTRAMEDULLARY PLASMACYTOMA; INFRATEMPORAL APPROACH; SURGICAL-MANAGEMENT; TEMPORAL BONE; HEMANGIOPERICYTOMA; DIAGNOSIS; NECK; PRESERVATION; MENINGIOMAS AB Pulsatile tinnitus, hearing loss, lower cranial nerve deficits, and radiographic evidence of a vascular lesion of the jugular foramen have been considered diagnostic of a glomus jugulare tumor. Angiographic evidence of a blood supply from the external carotid artery system, including the ascending pharyngeal artery, further substantiates this diagnosis. This diagnostic algorithm for tumors of the jugular fossa is usually followed by either a surgical exenteration of a presumed glomus jugulare tumor via an infratemporal fossa approach or radiation therapy in selected patients. Pre-treatment biopsy of such lesions is typically not done, nor is it recommended widely in the literature. As demonstrated in this report, a number of lesions, including hemangiopericytoma and extramedullary plasmacytoma presenting in the jugular foramen can mimic glomus jugulare tumors in all aspects of their clinical and radiographic presentation. Omission of a pre-treatment biopsy can lead to a treatment plan appropriate for glomus tumors but suboptimal for these rare pathologic entities. A pre-treatment biopsy of lesions of the jugular foramen by exploratory tympanotomy or postauricular mastoidotomy provides a pathologic diagnosis on which to base treatment of lesions of the jugular foramen, without adding substantial morbidity or decreasing the chances of cure. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OTOLARYNGOL,DEPT OTOL & LARYNGOL,BOSTON,MA 02114. NR 39 TC 27 Z9 27 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0192-9763 J9 AM J OTOL JI Am. J. Otol. PD JAN PY 1995 VL 16 IS 1 BP 94 EP 98 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA QA480 UT WOS:A1995QA48000016 PM 8579185 ER PT J AU INSOFT, RM SOLA, A AF INSOFT, RM SOLA, A TI PERINATALLY ACQUIRED PSEUDOMONAS INFECTION - A NEWLY RECOGNIZED MATERNAL RISK FACTOR SO AMERICAN JOURNAL OF PERINATOLOGY LA English DT Article DE PSEUDOMONAS; NEWBORN; PERINATAL INFECTION AB Pseudomonas aeruginosa is a less common but, nonetheless, serious bacterial pathogen implicated in early-onset neonatal sepsis. This report demonstrates perinatal transmission from a mother with a long smoking history who had an oral abscess surgically drained prior to delivery and never received antibiotic therapy. This case emphasizes the need to consider prophylactic antibiotic coverage in similiar patients to prevent the morbidity and mortality associated with this type of perinatally acquired infection. RP INSOFT, RM (reprint author), MASSACHUSETTS GEN HOSP,ELLISON 317,BOSTON,MA 02114, USA. NR 0 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 0735-1631 J9 AM J PERINAT JI Am. J. Perinatol. PD JAN PY 1995 VL 12 IS 1 BP 25 EP 26 DI 10.1055/s-2007-994393 PG 2 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA QF098 UT WOS:A1995QF09800007 PM 7710571 ER PT J AU KOVACS, TOG LLOYD, KCK WONG, H WALSH, JH AF KOVACS, TOG LLOYD, KCK WONG, H WALSH, JH TI INHIBITION OF BOMBESIN-STIMULATED ACID-SECRETION BY IMMUNONEUTRALIZATION OF GASTRIN IN DOGS SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE GASTRIN-RELEASING PEPTIDE; MONOCLONAL ANTIBODY; NEURAL REGULATION ID SOMATOSTATIN SECRETION; PEPTIDES; RAT; CHOLECYSTOKININ; RELEASE; REGULATORS; STOMACH; POTENCY AB Bombesin-like peptides stimulate gastrin release and gastric acid secretion. The increase in gastric acid output is thought to be secondary to gastrin release. A monoclonal antibody (MAb) directed specifically to gastrin (MAb 28.2) was used to study the role of circulating gastrin in the regulation of bombesin-stimulated acid secretion in dogs. Seven conscious, fasted dogs with gastric fistulas received intravenous bombesin infusions in fourfold increasing doses from 200 to 3,200 pmol.kg(-1).h(-1). Each dose was given for 45 min. On separate days, dogs were pretreated with an intravenous infusion of 7 mg of MAb 28.2 or vehicle (0.1% canine serum albumin). Samples of gastric effluent were collected by gravity drainage through the gastric fistula, and acid output was measured by titration of gastric effluent to pH 7.0, using 0.2 N NaOH. Plasma gastrin concentrations were determined by radioimmunoassay. Bombesin infusion produced dose-dependent increases in plasma gastrin concentrations and gastric acid output. Administration of gastrin MAb 28.2 abolished bombesin-stimulated gastric acid output. Immunoneutralization of circulating gastrin in vivo using a gastrin monoclonal antibody in dogs indicates that the acid stimulatory response to bombesin is mediated by gastrin. C1 W LOS ANGELES VET AFFAIRS MED CTR, RES SERV, LOS ANGELES, CA 90073 USA. W LOS ANGELES VET AFFAIRS MED CTR, MED SERV, LOS ANGELES, CA 90073 USA. UNIV CALIF LOS ANGELES, SCH MED, DEPT PHYSIOL, LOS ANGELES, CA 90073 USA. UNIV CALIF LOS ANGELES, SCH MED, DEPT MED, LOS ANGELES, CA 90073 USA. UNIV CALIF LOS ANGELES, GASTROENTER BIOL CTR, CTR ULCER RES & EDUC, LOS ANGELES, CA 90073 USA. FU NIDDK NIH HHS [DK-41301] NR 34 TC 6 Z9 6 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD JAN PY 1995 VL 268 IS 1 BP G54 EP G58 PG 5 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA QB678 UT WOS:A1995QB67800008 PM 7840208 ER PT J AU LLOYD, KCK WANG, J AURANG, K GRONHED, P COY, DH WALSH, JH AF LLOYD, KCK WANG, J AURANG, K GRONHED, P COY, DH WALSH, JH TI ACTIVATION OF SOMATOSTATIN RECEPTOR SUBTYPE-2 INHIBITS ACID-SECRETION IN RATS SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE STOMACH; RECEPTOR AGONIST; ACID INHIBITION ID ENTEROCHROMAFFIN-LIKE CELLS; HISTAMINE-RELEASE; GASTRIN RECEPTORS; PARIETAL-CELLS; CLONING; IMMUNOREACTIVITY; IDENTIFICATION; EXPRESSION; ATROPINE; STOMACH AB Somatostatin is a potent inhibitor of gastric acid secretion. Recently, at least five distinct somatostatin receptor subtypes (SSTR) have been characterized and evaluated using relatively selective peptide analogues of somatostatin. We sought to determine which somatostatin receptor subtypes are involved in peripheral regulation of gastric acid secretion. Fasted, male Sprague-Dawley rats were anesthetized and were implanted with a double-lumen cannula in the stomach. Acid secretion was measured in gastric samples collected every 10 min by backtitration to pH 7. After a 30-min basal period, a 2-h intravenous infusion of pentagastrin (24 mu g.kg(-1).h(-1) iv) was started. During the second pentagastrin hour, a l-h intravenous infusion of either vehicle (0.1% canine serum albumin in 0.9% saline) or somatostatin receptor agonists was begun. The somatostatin receptor agonists included peptides with relative specificity for SSTR(1-5) (somatostatin-14; 10 nmol.kg(-1).h(-1)); SSTR(2), SSTR(3), and SSTR(5) [SMS-(201--995); 10 nmol kg(-1).h(-1)]; SSTR(2) (1-1,000 nmol kg(-1).h(-1)); SSTR(3) (10-1,000 nmol.kg(-1).h(-1)); and SSTR(5) (10-1,000 nmol.kg(-1).h(-1)). The SSTR(2) agonist decreased pentagastrin-stimulated acid secretion dose dependently, from 82 +/- 7% of maximum acid output at 1 nmol.kg(-1).h(-1) to 4 +/- 7% of maximum at 100 nmol.kg(-1).h(-1). At 10 nmol.kg(-1).h(-1), the SSTR(2) agonist inhibited acid secretion (40 +/- 7% of maximum) similarly to somatostatin (37 +/- 4% of maximum) and SMS-(201--995) (31 +/- 4% of maximum). The SSTR(2) agonist inhibited acid secretion approximately 10- to 100-fold more potently than either the SSTR(3) or the SSTR(5) agonist. These results indicate that somatostatin regulates gastric acid secretion by activation of SSTR(2) receptors. C1 W LOS ANGELES VET AFFAIRS MED CTR, RES SERV, LOS ANGELES, CA 90073 USA. W LOS ANGELES VET AFFAIRS MED CTR, MED SERV, LOS ANGELES, CA 90073 USA. UNIV CALIF LOS ANGELES, CTR GASTROENTER BIOL, CTR ULCER RES & EDUC, LOS ANGELES, CA 90073 USA. UNIV CALIF LOS ANGELES, SCH MED, DEPT MED, LOS ANGELES, CA 90073 USA. UNIV CALIF LOS ANGELES, SCH MED, DEPT PHYSIOL, LOS ANGELES, CA 90073 USA. TULANE UNIV, MED CTR, SCH MED, DEPT MED, NEW ORLEANS, LA 70112 USA. FU NIDDK NIH HHS [DK-41301, DK-45752] NR 34 TC 41 Z9 42 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD JAN PY 1995 VL 268 IS 1 BP G102 EP G106 PG 5 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA QB678 UT WOS:A1995QB67800014 PM 7840190 ER PT J AU BUKOWSKI, DM DENEKE, SM LAWRENCE, RA JENKINSON, SG AF BUKOWSKI, DM DENEKE, SM LAWRENCE, RA JENKINSON, SG TI A NONINDUCIBLE CYSTINE TRANSPORT-SYSTEM IN RAT ALVEOLAR TYPE-II CELLS SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE GLUTATHIONE; EPITHELIAL CELLS; CYSTEINE; ENDOTHELIAL CELLS ID MOUSE PERITONEAL-MACROPHAGES; HUMAN-DIPLOID FIBROBLASTS; ENDOTHELIAL-CELLS; MEMBRANE-TRANSPORT; GLUTATHIONE LEVELS; SODIUM ARSENITE; DIETHYL MALEATE; ACID UPTAKE; HYPEROXIA; INDUCTION AB Type II lung epithelial cells are different from other lung cell types in their means of processing and regulating intracellular glutathione (GSH) levels. In lung cell types, including endothelial cells, fibroblasts, smooth muscle cells, and macrophages, oxidants, sulfhydryl reagents, and electrophilic agents have been shown to induce cystine uptake and concomitantly increase GSH levels, suggesting that cysteine, formed by intracellular reduction of cystine, is a rate-limiting substrate for GSH synthesis. The cystine transport increase was reportedly due to increase in activity of a sodium-independent transport system designated x(c)(-). We have now examined cultures of rat lung type II cells exposed to diethylmaleic acid and arsenite. Although a rise in cellular GSH occurred, cystine transport was not induced. Cystine transport in type II cells was found to differ from the x(c)(-) system previously described. Type II cell cystine transport is primarily sodium dependent and is inhibitable by aspartate as well as glutamate and homocysteate. We conclude that the type II cell. differs from other lung cell types in both its cystine transport mechanism and method of GSH regulation. C1 AUDIE L MURPHY MEM VET ADM MED CTR, PULM DIS SECT 111E, SAN ANTONIO, TX 78284 USA. UNIV TEXAS, HLTH SCI CTR, DEPT MED, DIV PULM DIS CRIT CARE MED, SAN ANTONIO, TX 78284 USA. FU NHLBI NIH HHS [HL-32824] NR 36 TC 31 Z9 31 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD JAN PY 1995 VL 268 IS 1 BP L21 EP L26 PG 6 WC Physiology; Respiratory System SC Physiology; Respiratory System GA QB292 UT WOS:A1995QB29200005 PM 7840224 ER PT J AU WEINDRUCH, R MARRIOTT, BM CONWAY, J KNAPKA, JJ LANE, MA CUTLER, RG ROTH, GS INGRAM, DK AF WEINDRUCH, R MARRIOTT, BM CONWAY, J KNAPKA, JJ LANE, MA CUTLER, RG ROTH, GS INGRAM, DK TI MEASURES OF BODY-SIZE AND GROWTH IN RHESUS AND SQUIRREL-MONKEYS SUBJECTED TO LONG-TERM DIETARY RESTRICTION SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Article DE NUTRITION; OBESITY; ADIPOSITY; DEVELOPMENT; AGING; MORPHOMETRY; SKIN-FOLD THICKNESS; MACACA MULATTA; SAIMIRI SP ID FOOD RESTRICTION; PHYSICAL GROWTH; ENERGY-INTAKE; BABOONS; MALNUTRITION; WEIGHT; MICE; NUTRITION; PRIMATES; BIRTH AB Although many studies have reported the robust effects of dietary restriction (DR) in retarding numerous aging processes in rodents, little is known about the outcomes of reducing caloric intake of a nutritious diet on aging in primates. Most primate studies have concerned the effects of malnutrition. We hypothesized that DR influences aging processes in primate species as it does in rodents. In the present study, 24 male rhesus (Macaca mulatta) monkeys (ages 0.6-5 years) and 25 male squirrel (Saimiri sp.) monkeys (ages 0.3-10 years) were provided diets formulated differently for each species but both fortified with vitamins and minerals (40% above recommended levels) as controls (approximating ad libitum levels) or experimentals (about 30% below the level of diet provided controls of comparable age and body weight). The results reported here concern the hypothesis that DR imposed during various developmental stages in these two primate species would affect morphometric parameters obtained at different occasions during the first 5 years of the study. Groups of older monkeys (rhesus: 18-25 years, n = 3; squirrel: 10-15 years, n = 4) were also included as controls for comparative purposes. Among groups of rhesus monkeys begun on DR prior to 6 years of age, growth in body weight and crown-rump length was reduced about 10-20% beginning after 1 year on the diet, with estimated food intake being reduced about 30-35% over this period. Measures of skin-fold thickness and various body circumference measures were also reduced in experimental groups of rhesus monkeys. In contrast, the DR regimen involving a different diet produced little impact on comparable measures in squirrel monkeys, with the estimated food intake being reduced only about 20-25% over this period. However, evidence of divergence in some morphometric parameters in squirrel monkeys was beginning to emerge in young groups (<5 years) after 3 years on the diet. (C) 1995 Wiley-Liss, Inc.* C1 UNIV WISCONSIN,SCH MED,DEPT MED,MADISON,WI. WILLIAM S MIDDLETON MEM VET ADM MED CTR,CTR GERIATR RES EDUC & CLIN,MADISON,WI. NATL ACAD SCI,FOOD & NUTR BOARD,WASHINGTON,DC 20418. USDA,BELTSVILLE HUMAN NUTR RES CTR,ENERGY & PROT NUTR LAB,BELTSVILLE,MD 20705. NIH,NATL CTR RES RESOURCES,BETHESDA,MD 20892. NIA,HOPKINS BAYVIEW MED CTR,CTR GERONTOL RES,MOLEC PHYSIOL & GENET SECT,BALTIMORE,MD 21224. NR 47 TC 25 Z9 25 U1 0 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PY 1995 VL 35 IS 3 BP 207 EP 228 DI 10.1002/ajp.1350350304 PG 22 WC Zoology SC Zoology GA QJ092 UT WOS:A1995QJ09200003 ER PT J AU WHALEN, C HORSBURGH, CR HOM, D LAHART, C SIMBERKOFF, M ELLNER, J AF WHALEN, C HORSBURGH, CR HOM, D LAHART, C SIMBERKOFF, M ELLNER, J TI ACCELERATED COURSE OF HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION AFTER TUBERCULOSIS SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID TUMOR-NECROSIS-FACTOR; NEW-YORK-CITY; HIV-INFECTION; COHORT; RISK; AIDS; PROGRESSION; EXPRESSION; SURVIVAL; CELLS AB To determine the effect of active tuberculosis on survival and the incidence of opportunistic infections in HIV-infected patients, we performed a retrospective cohort study at four U.S. medical centers to compare the survival and incidence rate of opportunistic infections in 106 HIV-infected patients with active tuberculosis (cases) with that of 106 HIV-infected patients without tuberculosis (control subjects) but with a similar level of immunosuppression (measured by the absolute CD4+ lymphocyte count) as the cases. Cases and control subjects were similar with regard to age, sex, race, previous opportunistic infection, and use of antiretroviral therapy, but they were more likely than control subjects to have a history of intravenous drug use (49 versus 19%). The mean CD4+ counts were similar for cases and control subjects (154 versus 153 cells/mu l, respectively). The incidence rate of new AIDS-defining opportunistic infections in cases was 4.0 infections per 100 person-months compared with 2.8 infections per 100 person-months in control subjects for an incidence rate ratio (RR) of 1.42 (95% confidence interval: 0.94-2.11). Cases also had a shorter overall survival than did controls subjects (p = 0.001). Active tuberculosis was associated with an increased risk for death (odds ratio = 2.17), even when controlling for age, intravenous drug use, previous opportunistic infection, baseline CD4+ count, and antiretroviral therapy. Although active tuberculosis may be an independent marker of advanced immunosuppression in HIV-infected patients, it may also act as a cofactor to accelerate the clinical course of HIV infection. C1 CLEVELAND VET AFFAIRS MED CTR,DEPT MED,DIV GEN INTERNAL MED & INFECT DIS,CLEVELAND,OH. UNIV CLEVELAND HOSP,DEPT MED,CLEVELAND,OH 44106. NYU,MANHATTAN VET AFFAIRS MED CTR,SCH MED,DEPT MED,DIV INFECT DIS,NEW YORK,NY. BAYLOR COLL MED,HOUSTON VET AFFAIRS MED CTR,DEPT MED,MED SERV,AIDS UNIT,HOUSTON,TX 77030. CTR DIS CONTROL,NATL CTR INFECT DIS,DIV HIV AIDS,ATLANTA,GA 30333. EMORY UNIV,DEPT MED,ATLANTA,GA 30322. GRADY MEM HOSP,ATLANTA,GA. RP WHALEN, C (reprint author), CASE WESTERN RESERVE UNIV,SCH MED,DEPT EPIDEMIOL & BIOSTAT,WG-49,2109 ADELBERT RD,CLEVELAND,OH 44106, USA. NR 35 TC 385 Z9 393 U1 0 U2 4 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 JAN PY 1995 VL 151 IS 1 BP 129 EP 135 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA QA903 UT WOS:A1995QA90300021 PM 7812542 ER PT J AU PALMER, WE CASLOWITZ, PL CHEW, FS AF PALMER, WE CASLOWITZ, PL CHEW, FS TI MR ARTHROGRAPHY OF THE SHOULDER - NORMAL INTRAARTICULAR STRUCTURES AND COMMON ABNORMALITIES SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID ROTATOR CUFF AB MR imaging with gadopentetate dimeglumine (MR arthrography) is a new technique for evaluating the shoulder. Early clinical experience indicates that MR arthrography improves the visualization of intraarticular structures [1-3]. On T1-weighted images, high-signal contrast solution outlines the low-signal surface of the cuff tendons, the contour of the glenoid labrum, and the course of the glenohumeral ligaments. This essay illustrates the anatomic features of normal glenohumeral structures seen on MR arthrography and common pathologic disorders of the labral-ligamentous complex and rotator cuff. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP PALMER, WE (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,WACC SUITE 515,15 PARKMAN ST,BOSTON,MA 02114, USA. OI Chew, Felix/0000-0003-2711-2013 NR 6 TC 76 Z9 80 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JAN PY 1995 VL 164 IS 1 BP 141 EP 146 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PY679 UT WOS:A1995PY67900026 PM 7998527 ER PT J AU MCFARLAND, EG LEE, MJ BOLAND, GW MUELLER, PR AF MCFARLAND, EG LEE, MJ BOLAND, GW MUELLER, PR TI GASTROPEXY BREAKDOWN AND PERITONITIS AFTER PERCUTANEOUS GASTROJEJUNOSTOMY IN A PATIENT WITH ASCITES SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Discussion ID TRANSGASTRIC JEJUNOSTOMY; ENDOSCOPIC GASTROSTOMY; GASTROENTEROSTOMY; COMPLICATIONS; EXPERIENCE; FIXATION C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 19 TC 10 Z9 10 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JAN PY 1995 VL 164 IS 1 BP 189 EP 193 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PY679 UT WOS:A1995PY67900036 PM 7998537 ER PT J AU LEE, MJ MUELLER, PR DAWSON, SL GAZELLE, SG HAHN, PF GOLDBERG, MA BOLAND, GW AF LEE, MJ MUELLER, PR DAWSON, SL GAZELLE, SG HAHN, PF GOLDBERG, MA BOLAND, GW TI PERCUTANEOUS ETHANOL INJECTION FOR THE TREATMENT OF HEPATIC-TUMORS - INDICATIONS, MECHANISM OF ACTION, TECHNIQUE, AND EFFICACY SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article; Proceedings Paper CT 94th Annual Meeting of the American-Roentgen-Ray-Society CY APR, 1994 CL NEW ORLEANS, LA SP AMER ROENTGEN RAY SOC ID SMALL HEPATOCELLULAR-CARCINOMA; ALCOHOL INJECTION; ABLATION THERAPY; LIVER NEOPLASMS; FOLLOW-UP; GUIDANCE AB Percutaneous injection of ethanol far treatment of hepatic tumors was first described by Sugiura et al. [1] in 1983. To date, reported experience with the procedure has focused mainly on therapy of hepatocellular carcinoma (HCC) [2-15], with little information available regarding its use in treating metastatic liver lesions [16]. Interest in this technique has grown recently as a possible means of treating patients with metastatic liver disease. The purpose of this perspective is to review the indications, mechanism of action, technique, complications, and efficacy of percutaneous ethanol injection for liver tumor treatment. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP LEE, MJ (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,FRUIT ST,BOSTON,MA 02114, USA. NR 29 TC 60 Z9 67 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JAN PY 1995 VL 164 IS 1 BP 215 EP 220 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PY679 UT WOS:A1995PY67900040 PM 7998542 ER PT J AU HOTZ, HG SCHMIDT, J RYSCHICH, EW FOITZIK, T BUHR, HJ WARSHAW, AL HERFARTH, C KLAR, E AF HOTZ, HG SCHMIDT, J RYSCHICH, EW FOITZIK, T BUHR, HJ WARSHAW, AL HERFARTH, C KLAR, E TI ISOVOLEMIC HEMODILUTION WITH DEXTRAN PREVENTS CONTRAST-MEDIUM INDUCED IMPAIRMENT OF PANCREATIC MICROCIRCULATION IN NECROTIZING PANCREATITIS OF THE RAT SO AMERICAN JOURNAL OF SURGERY LA English DT Article; Proceedings Paper CT 35th Annual Meeting of the Society-for-Surgery-of-the-Alimentary-Tract CY MAY 16-18, 1994 CL NEW ORLEANS, LA SP SOC SURG ALIMENTARY TRACT ID TRYPSINOGEN-ACTIVATION PEPTIDES; ACUTE BILIARY PANCREATITIS; COMPUTED-TOMOGRAPHY; HEMORRHAGIC-PANCREATITIS; EARLY DIAGNOSIS; NECROSIS; ISCHEMIA; THERAPY; MODEL AB BACKGROUND: Previous studies demonstrated that intravenous contrast medium (CM), as used in contrast enhanced computed tomography, aggravates the impairment of pancreatic microcirculation (PM) characteristic of severe pancreatitis slid increases necrosis and mortality in necrotizing pancreatitis (NP) in rats. This study evaluates the us of isovolemic hemodilution, which call enhance the microcirculation in sever pancreatitis, for preventing CM-induced injury. METHODS: NP was induced in 30 dextran-tolerant Wister rats by intraductal glycodeoxycholic acid and intravenous cerulein for 6 hours. PM was quantified by intravital microscopy using fluorescein isothiocyanate labeled erythrocytes. Based On previous results, areas with low blood flow (<1.6 nL/min/cap) were identified and baseline recordings of capillary blood flow taken, A reduction of hematocrit to 75% of baseline was achieved by replacement of 5 mL/kg of blood with 25 mL/kg Ringer's lactate (RL) or by exchange of 8 mL/kg of blood for the same amount of dextran 70 6%. Thereafter, the nonionic CM iopamidol (Solutrast, Byk Gulden, Konstanz, Germany) was injected during 1 minute and PM measurements repeated after 30 and 60 minutes. RESULTS: Despite hemodilution with RL, pancreatic capillary perfusion was significantly decreased to 87% of baseline (0.83 +/- 0.04 nL/min/cap; n = 216) 60 minutes after CM infusion (P <0.05). In contrast, capillary blood flow was significantly increased to 161% (1.56 +/- 0.05 nL/min/cap; n = 278) in the group, treated with dextran. Moreover, the percentage of capillaries developing complete stasis was significantly lower in the dextran group (2.3 +/- 1.2%) compared to animals diluted with RL (22.3 +/- 4.8%) (p <0.002). CONCLUSIONS: Isovolemic hemodilution with dextran prevents the additional impairment of pancreatic microcirculation induced by CM in NP. C1 MASSACHUSETTS GEN HOSP, BOSTON, MA 02114 USA. RP HOTZ, HG (reprint author), UNIV HEIDELBERG, DEPT SURG, NEUENHEIMER FELD 110, D-69120 HEIDELBERG, GERMANY. NR 41 TC 29 Z9 30 U1 0 U2 0 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD JAN PY 1995 VL 169 IS 1 BP 161 EP 166 DI 10.1016/S0002-9610(99)80126-3 PG 6 WC Surgery SC Surgery GA QA176 UT WOS:A1995QA17600024 PM 7529462 ER PT J AU FRICK, TW MITHOFER, K CASTILLO, CF RATTNER, DW WARSHAW, AL AF FRICK, TW MITHOFER, K CASTILLO, CF RATTNER, DW WARSHAW, AL TI HYPERCALCEMIA CAUSES ACUTE-PANCREATITIS BY PANCREATIC SECRETORY BLOCK, INTRACELLULAR ZYMOGEN ACCUMULATION, AND ACINAR CELL INJURY SO AMERICAN JOURNAL OF SURGERY LA English DT Article; Proceedings Paper CT 35th Annual Meeting of the Society-for-Surgery-of-the-Alimentary-Tract CY MAY 16-18, 1994 CL NEW ORLEANS, LA SP SOC SURG ALIMENTARY TRACT ID CALCIUM; ULTRASTRUCTURE; ACTIVATION; CATS AB BACKGROUND: Because hypercalcemia is a known etiologic factor for human acute pancreatitis, studies of the pancreatic pathophysiology and pathomorphology of experimental hypercalcemia have potential clinical significance. MATERIALS AND METHODS: Rats received central venous infusion of either 0.6 mmol/kg per hour CaCl2 or 0.9% NaCl infusion for 12 hours, Pancreatic tissue samples were obtained and prepared for electron microscopy. Tissue homogenates were examined for DNA, lactate dehydrogenase (LDH), protein, amylase, and calcium contents, Basal or stimulated (cerulein 0.25 mu L/kg per hour) pancreatic secretions were analyzed for volume, protein, and amylase output, as well as protein composition on sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). RESULTS: The tissue calcium content and the ratio of LDI-I to DNA was unchanged after calcium infusion, but the ratios of total protein to DNA and of amylase to DNA were significantly larger. Basal output of pancreatic juice vola volume, protein, and amylase were significantly lower. SDS-PAGE of pancreatic juice revealed weakening of a 70,000-d band and appearance of lower molecular weight bands in two samples. Ultrastructural examination demonstrated accumulation of zymogen granules in the acinar cell, large autophagic vacuoles containing remnants of condensing vacuoles. CONCLUSIONS: These findings suggest that hypercalcemia induces pancreatic injury via a secretory block, accumulation of secretory proteins, and possibly activation of proteases. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP FRICK, TW (reprint author), UNIV ZURICH HOSP,DEPT CHIRURG,CH-8091 ZURICH,SWITZERLAND. NR 24 TC 25 Z9 25 U1 0 U2 0 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD JAN PY 1995 VL 169 IS 1 BP 167 EP 172 DI 10.1016/S0002-9610(99)80127-5 PG 6 WC Surgery SC Surgery GA QA176 UT WOS:A1995QA17600025 PM 7817987 ER PT J AU INOUE, Y BODE, BP SOUBA, WW AF INOUE, Y BODE, BP SOUBA, WW TI DIETARY-REGULATION OF THE HEPATIC SYSTEM-N GLUTAMINE TRANSPORTER IN TUMOR-BEARING RATS SO AMERICAN JOURNAL OF SURGERY LA English DT Article; Proceedings Paper CT 35th Annual Meeting of the Society-for-Surgery-of-the-Alimentary-Tract CY MAY 16-18, 1994 CL NEW ORLEANS, LA SP SOC SURG ALIMENTARY TRACT ID PLASMA-MEMBRANE VESICLES; AMINO-ACID-TRANSPORT; LIVER; METABOLISM; GROWTH AB BACKGROUND: Hepatocytes possess a novel, plasma-membrane, sodium ion (Na+)-independent, glutamine transporter (system n), which functions to transport glutamine out of the cell into the blood, In the tumor-bearing rat, the activity of system n increases but its regulation is unknown. We hypothesized that the increase in system a that occurs in rats with cancer was related to a fall in the circulating glutamine concentration. METHODS: Tell male rats underwent flank implantation with a cube of methylchoanthrene-induced fibrosarcoma cells and 10 rats underwent a sh,un operation. After 9 days of standard diet, all rats were randomized to receive either a glutamine-enriched oral diet or an isonitrogenous diet without supplemental glutamine, for 1 week. Tumors and livers were harvested 16 days postimplantation. Arterial blood samples were obtained from all animals. Hepatic plasma membrane vesicles were prepared and the carrier-mediated, Na+-independent transport of glutamine was assayed. RESULTS: When compared to nontumor-bearing animals, tumor-hearing rats that were fed a control diet exhibited hypoglutaminemia and a 2.3-fold increase in the activity of system n. Glutamine dietary supplementation produced blood glutamine levels that were similar in both tumor-bearing and nontumor-hearing rats, apparently abrogating the increase in system n activity that was observed in tumor-bearing rats that were not fed supplemental glutamine, Tumor-bearing animals receiving supplemental glutamine had a decreased number of system n carriers (V-max) in the hepatic plasma membrane compared to that of tumor-bearing animals receiving a control diet; this apparently abrogated the glutamine efflux rate. Glutamine feeding did not alter system n activity in nontumor-bearing controls. CONCLUSIONS: In the tumor-bearing animal model, system n is modulated by the circulating glutamine concentration. This is the first study that demonstrates the ability of specialized nutrition to ''downregulat'' transport activity in vivo. C1 MASSACHUSETTS GEN HOSP,DEPT SURG,DIV SURG ONCOL,BOSTON,MA 02114. UNIV FLORIDA,COLL MED,DEPT SURG,GAINESVILLE,FL. HARVARD UNIV,SCH MED,BOSTON,MA. FU NCI NIH HHS [R01CA57690] NR 19 TC 8 Z9 9 U1 0 U2 0 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD JAN PY 1995 VL 169 IS 1 BP 173 EP 178 DI 10.1016/S0002-9610(99)80128-7 PG 6 WC Surgery SC Surgery GA QA176 UT WOS:A1995QA17600026 PM 7817988 ER PT J AU SZYFELBEIN, WM YOUNG, RH SCULLY, RE AF SZYFELBEIN, WM YOUNG, RH SCULLY, RE TI STRUMA OVARII SIMULATING OVARIAN-TUMORS OF OTHER TYPES - A REPORT OF 30 CASES SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE OVARY; STRUMA; OXYPHIL CELLS; CLEAR CELLS ID CLINICOPATHOLOGICAL ANALYSIS; CELL TUMORS; CARCINOMA AB Thirty cases of struma ovarii with unusual microscopic features are described. They occurred in women 23 to 71 (average 49) years of age. Most of the patients had the usual symptoms and signs of an adnexal mass. Three patients had ascites and two had Meigs' syndrome. The tumors, all unilateral and confined to the ovary, ranged from 4 to 25 (average 12) cm in greatest dimension. They were typically predominantly solid and red-brown but cysts were present within foci of struma in several cases; an associated dermoid cyst was noted grossly in nine cases. Microscopic examination showed a prominent diffuse pattern in 21 cases, prominent microfollicles imparting in many cases a pseudotubular appearance in 20 cases, abundant eosinophilic cytoplasm in nine cases, and abundant clear cytoplasm in four cases. A contiguous dermoid cyst which had not been recognized on gross examination was documented in five cases. The typical paucity of thyroid follicles in cellular areas of these tumors often caused either a failure to consider a diagnosis of struma ovarii or led to serious consideration of other diagnoses. Clues to the correct diagnosis were the presence of rare typical thyroid follicles in foci that were pre dominantly diffuse or pseudotubular, the presence of larger areas of typical struma in 22 cases, and the association with a dermoid cyst in 14 cases. Immunohistochemical staining for thyroglobulin confirmed the nature of the tumor in all five cases in which it was performed. The diagnosis of struma should be entertained when one is examining an ovarian neoplasm with solid or pseudotubular patterns or a content of oxyphilic or clear cells. A careful search for thyroid follicles should be undertaken to establish the diagnosis and immunohistochemical staining for thyroglobulin performed to confirm it in problematic cases. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RP SZYFELBEIN, WM (reprint author), MASSACHUSETTS GEN HOSP,DEPT PATHOL,JAMES HOMER WRIGHT PATHOL LABS,BOSTON,MA 02114, USA. NR 33 TC 52 Z9 54 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD JAN PY 1995 VL 19 IS 1 BP 21 EP 29 DI 10.1097/00000478-199501000-00003 PG 9 WC Pathology; Surgery SC Pathology; Surgery GA PX943 UT WOS:A1995PX94300003 PM 7802134 ER PT J AU FERGUSON, CM RATTNER, DW AF FERGUSON, CM RATTNER, DW TI INITIAL EXPERIENCE WITH LAPAROSCOPIC NISSEN FUNDOPLICATION SO AMERICAN SURGEON LA English DT Article; Proceedings Paper CT 62nd Annual Scientific Meeting of the Southeastern Surgical Conference CY FEB 06-10, 1994 CL LAKE BUENA VISTA, FL ID GASTROESOPHAGEAL REFLUX DISEASE; REPAIR AB In an effort to explore the utility of classic Nissen fundoplication performed laparoscopically, 16 adult patients with well documented gastroesophageal reflux underwent laparoscopic Nissen fundoplication. A full gastric fundal dissection was performed, with division of at least 2 short gastric vessels. The crura were approximated with 1-3 sutures, and a loose fundoplication was performed over an esophageal dilator (minimum 46 F) with three stitches, encompassing the esophageal wall (2.5 em in length). All patients had symptoms of reflux refractory to medical therapy, and four had an esophageal stricture requiring preoperative dilatation. Fifteen of 16 procedures were completed laparoscopically; one patient required conversion to an open procedure to control bleeding from a posterior gastric vein, There were no other operative complications. The average operative time was 180 minutes (range 120-285). Clear liquids were begun at the passage of flatus (average 2.7 days postop), and patients were discharged an average of 4.1 days postoperatively. Postoperative complications included ileus (1 patient for 6 days), severe subcutaneous emphysema (1 patient), and dysphagia requiring dilatation (5 patients). In short follow-up (mean 4.43 mo., range 1-12 mo.) 14 of 15 patients had complete abolition of reflux symptoms, but one patient with persistent heartburn had reflux demonstrated on a postoperative upper GI series. Thirteen of 16 patients returned to full function within 14 days of surgery. We conclude that standard Nissen fundoplication is possible laparoscopically, and allows a rapid recovery from surgery, However, it is difficult, time consuming, and associated with a significant rate of recurrence in the short term (6%). C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,BOSTON,MA 02114. NR 12 TC 9 Z9 9 U1 0 U2 0 PU SOUTHEASTERN SURGICAL CONGRESS PI ATLANTA PA 1776 PEACHTREE RD, NW., SUITE 410N, ATLANTA, GA 30309-2352 SN 0003-1348 J9 AM SURGEON JI Am. Surg. PD JAN PY 1995 VL 61 IS 1 BP 21 EP 23 PG 3 WC Surgery SC Surgery GA QC078 UT WOS:A1995QC07800005 PM 7832376 ER PT J AU BROTHERS, TE ELLIOTT, BM ROBISON, JG RAJAGOPALAN, PR AF BROTHERS, TE ELLIOTT, BM ROBISON, JG RAJAGOPALAN, PR TI STRATIFICATION OF MORTALITY RISK FOR RENAL-ARTERY SURGERY SO AMERICAN SURGEON LA English DT Article; Proceedings Paper CT 62nd Annual Scientific Meeting of the Southeastern Surgical Conference CY FEB 06-10, 1994 CL LAKE BUENA VISTA, FL ID ABDOMINAL AORTIC-ANEURYSM; RENOVASCULAR HYPERTENSION; INTESTINAL ISCHEMIA; SURGICAL-TREATMENT; NATURAL-HISTORY; LUNG INJURY; DISEASE; RECONSTRUCTION; REVASCULARIZATION; RADICALS AB Seventy consecutive operations involving the renal arteries were reviewed to identify factors linked to perioperative mortality. Aortorenal bypass (n=29), endarterectomy (n=12), extraanatomic bypass (n=12), thrombectomy (n=4), and reimplantation (n=13) were associated with a 16% perioperative mortality that was often secondary to multisystem organ failure. Patients who died exhibited a higher serum creatinine (3.4 vs 2.1 mg/dL; P<0.05). Stratification of patients by risk revealed higher American Society of Anesthesiologists (ASA) (P<0.005) and modified Acute Physiology Score, and Chronic Health Evaluation (APACHE II) (P<0.02) score among patients who died. Higher mortality was also observed after bilateral renal artery operations (31% vs 5%; P<0.005) or concomitant mesenteric revascularization (37% vs 12%; P<0.05), but not simultaneous aortic procedures (18% vs 11%; P=NS). Bilateral operation (P<0.0001), age (P<0.001), and ASA class (P<0.01) were independent predictors of mortality according to multivariate analysis. Because of higher mortality in these specific situations, modification or limitation of operative scope may be appropriate. C1 MED UNIV S CAROLINA,CHARLESTON,SC. RALPH HENRY JOHNSON DEPT VET AFFAIRS MED CTR,CHARLESTON,SC. NR 41 TC 6 Z9 7 U1 0 U2 0 PU SOUTHEASTERN SURGICAL CONGRESS PI ATLANTA PA 1776 PEACHTREE RD, NW., SUITE 410N, ATLANTA, GA 30309-2352 SN 0003-1348 J9 AM SURGEON JI Am. Surg. PD JAN PY 1995 VL 61 IS 1 BP 45 EP 51 PG 7 WC Surgery SC Surgery GA QC078 UT WOS:A1995QC07800010 PM 7832381 ER PT J AU WRIGHT, JE TRETYAKOV, O AYASH, LJ ELIAS, A ROSOWSKY, A FREI, E AF WRIGHT, JE TRETYAKOV, O AYASH, LJ ELIAS, A ROSOWSKY, A FREI, E TI ANALYSIS OF 4-HYDROXYCYCLOPHOSPHAMIDE IN HUMAN BLOOD SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID CYCLOPHOSPHAMIDE; PHARMACOKINETICS; IDENTIFICATION; METABOLITES; TOXICITY; ACTIVATION; INVIVO AB Cyclophosphamide is a prodrug activated by cytochrome P450 isozymes in the liver. The product of hepatic activation of cyclophosphamide is 4-hydroxycyclophosphamide. Previously reported methods for determining 4-hydroxycyclophosphamide were either impractical or unreliable for monitoring infusion pharmacokinetics in conjunction with clinical trials. One procedure in which a fluorescent hydroxyquinoline derivative was prepared from 4-hydroxycyclophosphamide and analyzed by HPLC appeared to work at first, but gradually lost its selectivity due to degradation of the column by the strongly acidic mobile phase. An alternative procedure was developed using a weakly acidic eluent and postcolumn treatment with trifluoroacetic acid. This provided for protonation of the hydroxyquinoline, required for sensitive fluorescence detection, but spared the column. The resulting assay was sensitive, selective, reproducible, and accurate. The method was used to monitor 4-hydroxycyclophosphamide pharmacokinetics during and after 4 day infusions of 1.5 g/m(2)-day of cyclophosphamide given to three patients. It was also used to measure the time-dependent disappearance of acrolein and 4-hydroxycyclophosphamide added to human blood from healthy donors and that of metabolically derived Li-hydroxycyclophosphamide in the blood of a patient treated with cyclophosphamide. Slower decomposition was observed in the latter two cases than in the blood spiked with acrolein. Reliable data were obtained from >1000 determinations using the same column without significant degradation of its stationary phase. (C) 1995 Academic Press, Inc. C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. RP WRIGHT, JE (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. NR 23 TC 20 Z9 20 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD JAN 1 PY 1995 VL 224 IS 1 BP 154 EP 158 DI 10.1006/abio.1995.1021 PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA QB306 UT WOS:A1995QB30600021 PM 7710063 ER PT J AU SHAPIRO, F CAHILL, C MALATANTIS, G NAYAK, RC AF SHAPIRO, F CAHILL, C MALATANTIS, G NAYAK, RC TI TRANSMISSION ELECTRON-MICROSCOPIC DEMONSTRATION OF VIMENTIN IN RAT OSTEOBLAST AND OSTEOCYTE CELL-BODIES AND PROCESSES USING THE IMMUNOGOLD TECHNIQUE SO ANATOMICAL RECORD LA English DT Article DE RAT; BONE; OSTEOBLAST; OSTEOCYTE; GAP JUNCTIONS; VIMENTIN; IMMUNOLOCALIZATION; ULTRASTRUCTURE ID MAJOR 66-KDA PHOSPHOPROTEIN; INTERMEDIATE FILAMENTS; ULTRASTRUCTURAL IMMUNOLOCALIZATION; BONE-CELLS; CHICKEN; IMMUNOCYTOCHEMISTRY; JUNCTIONS; BIOLOGY AB Background: The immunogold labeling technique and transmission electron microscopy were used to demonstrate the expression and position of the intermediate filament vimentin in rat osteoblast and osteocyte cell bodies and cell processes. Conventional light and transmission electron microscopic studies of bone cells demonstrated adjacent cell linkage to be mediated by osteoblast and osteocyte processes present within the canalicular system traversing the bone matrix. The cell processes were filled with densely packed filaments, many of which have been shown previously to be actin microfilaments. The appearance, however, of 10 nn diameter filaments in some cell processes and the fact that the intermediate filament vimentin has been defined in many cells of mesenchymal origin raised the possibility that some of these filaments might be vimentin. The ultrastructural colloidal gold immunochemical technique allowed for demonstration in situ of the expression of vimentin filaments plus accurate definition of their position. Methods: The studies were performed in newborn rat femoral and tibial diaphyseal cortical bone and in 1-week-old repair bone from 2.4 mm diameter defects made through the lateral cortex in 6-week-old rat femurs and tibias. The bone tissues for the immunochemical study were fixed in 1% glutaraldehyde, 4% paraformaldehyde, and 0.1 M phosphate buffer (pH 7.4) for 2 days. Decalcification was performed in 6% EDTA for 2-3 days. Infiltration involved use of Lowicryl resin K4M, and the embedding and curing processes were performed in a cryostat with temperatures -30 degrees C. An antivimentin monoclonal antibody was used for labeling using the postembedding technique. Effective antibody dilutions ranged from 1:10 to 1:200, with the dilutions of 1:25 and 1:100 showing the best combination of filament labeling with the least matrix background. The grids were exposed to 10 nanometer gold colloid conjugated goat anti-mouse IgM for demonstration of binding. Results: Vimentin immunolabeling was defined clearly in relation to filaments within the osteoblast and osteocyte cell body cytoplasm, throughout the entire length of the osteoblast and osteocyte cell processes, and in close relationship to the intercellular gap junctions which were present within the cell processes both close to the cell bodies and within the canaliculi well away from them. Conclusions: Immunogold labeling demonstrates the presence of the intermediate filament vimentin in osteoblast and osteocyte cell bodies and processes of rat bone. Vimentin distribution is not concentrated to specific areas, is present throughout the extent of the bodies and processes, and is seen immediately adjacent to gap junctions. (C) 1995 Wiley-Liss, Inc. C1 JOSLIN DIABET CTR,BOSTON,MA 02215. TUFTS UNIV NEW ENGLAND MED CTR,BOSTON,MA 02111. RP SHAPIRO, F (reprint author), HARVARD UNIV,CHILDRENS HOSP,SCH MED,DEPT ORTHOPAED SURG,STUDY SKELETAL DISORDERS LAB,ENDERS 11,BOSTON,MA 02115, USA. FU NIAMS NIH HHS [AR39965] NR 24 TC 32 Z9 32 U1 1 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0003-276X J9 ANAT REC JI Anat. Rec. PD JAN PY 1995 VL 241 IS 1 BP 39 EP 48 DI 10.1002/ar.1092410107 PG 10 WC Anatomy & Morphology SC Anatomy & Morphology GA QF983 UT WOS:A1995QF98300006 PM 7879923 ER PT J AU KURREK, MM WINKLER, M ROBINSON, DR ZAPOL, WM AF KURREK, MM WINKLER, M ROBINSON, DR ZAPOL, WM TI PLATELET FACTOR-4 INJECTION PRODUCES ACUTE PULMONARY-HYPERTENSION IN THE AWAKE LAMB SO ANESTHESIOLOGY LA English DT Article DE HEPARIN; PF4; PULMONARY HYPERTENSION; THROMBOXANE ID HEPARIN-PROTAMINE REACTIONS; FACTOR-IV; INTRAVASCULAR MACROPHAGES; VASOCONSTRICTION; SHEEP; ANTICOAGULATION; REVERSAL AB Background: Reversal of heparin anticoagulation by intravenous protamine sulfate consistently produces acute pulmonary vasoconstriction mediated by the release of thromboxane in the awake lamb. Recently, recombinant platelet factor 4 (rPF4) has been cloned, expressed in Escherichia coli, and infused to reverse heparin anticoagulation in the rat, without producing adverse hemodynamic or pulmonary morpholopic effects. The authors sought to learn whether intravenous administration of PF4 is devoid of side effects in the pulmonary circulation of lambs. Methods: The authors evaluated the hemodynamic response and plasma release rates of thromboxane during intravenous challenges with heparin-rPF4 (n = 2), rPF-free carrier (n = 5), rPF4 (n = 5), rPF4 after indomethacin (n = 5), protamine (n = 5) and heparin-protamine (n = 5) in 17 awake, hemodynamically monitored lambs. Each lamb underwent up to three random challenges with a 2-h recovery period between each challenge. Results: In two lambs, systemic anticoagulation with heparin followed by reversal of anticoagulation with an intravenous bolus of rPE4 (4 mg/kg) led to acute pulmonary vasoconstriction and hypertension with the release of thromboxane (peak pulmonary artery pressure [Ppa] 40 and 33 mmHg and peak plasma thromboxane B-2 50 and 30 ng/ml, respectively). Intravenous administration of rPF4 (1.5 mg/kg) alone increased the Ppa from 17.2 +/- 0.7 mmHg (mean +/- SEM) at baseline to 31.2 +/- 2 mmHg at 1 min (n = 5, P < 0.05). This was associated with an increase of plasma thromboxane B-2 from 0.06 +/- 0.02 to 3.96 +/- 1.21 ng/ml. Acute pulmonary vasoconstriction lasted approximately 5 min and was completely prevented by pretreatment with oral indomethacin (10 mg/kg). Intravenous bolus administration of rPF4 carrier (n = 5) or protamine (2 mg/kg) alone (n = 5) did not induce pulmonary hypertension or the release of thromboxane. In five lambs, intravenous heparin (200 U/kg) followed by protamine (2 mg/kg) consistently produced acute pulmonary vasoconstriction and hypertension. Conclusions: Intravenous injection of human rPE4 into the awake lamb produces acute pulmonary vasoconstriction and hypertension associated with thromboxane release into circulating blood. The effects of rPF4 on the pulmonary vasculature should be evaluated in primates before rPF4 is substituted for protamine in reversing heparin anticoagulation in humans. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ANESTHESIA,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,BOSTON,MA 02114. HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DEPT ANESTHESIA,BOSTON,MA. FU NHLBI NIH HHS [HL42397] NR 20 TC 9 Z9 9 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD JAN PY 1995 VL 82 IS 1 BP 183 EP 187 DI 10.1097/00000542-199501000-00023 PG 5 WC Anesthesiology SC Anesthesiology GA QC460 UT WOS:A1995QC46000024 PM 7832299 ER PT J AU RAINES, DE RANKIN, SE MILLER, KW AF RAINES, DE RANKIN, SE MILLER, KW TI GENERAL-ANESTHETICS MODIFY THE KINETICS OF NICOTINIC ACETYLCHOLINE-RECEPTOR DESENSITIZATION AT CLINICALLY RELEVANT CONCENTRATIONS SO ANESTHESIOLOGY LA English DT Article DE ALCOHOLS; ANESTHETICS, VOLATILE; DESENSITIZATION; NEUROMUSCULAR JUNCTION; NICOTINIC ACETYLCHOLINE RECEPTOR; THEORIES OF ANESTHETIC ACTION ID TORPEDO POSTSYNAPTIC MEMBRANES; VOLATILE ANESTHETICS; FLUORESCENT AGONIST; ACTIVATED CHANNELS; BINDING; ISOFLURANE; MARMORATA; CURRENTS; PROTEIN; 60 years it has been possible to separate BCG strains (defined here as a BCG vaccine maintained in a particular laboratory and used in a particular trial or set of trials) on the basis of in vitro and in vivo tests. Investigators have concluded that differences in the BCG strains used in efficacy trials on humans may be responsible for the wide range in levels of protection from tuberculosis reported in those trials, We review the development of the separate strains used in the trials included in a recent meta-analysis and examine data for and against the protective efficacy of different BCG strains, The difficulties in correlating results of in vitro and in vivo tests with protective efficacy in humans are discussed, The limited data available from human studies suggest that the BCG strain used for vaccination is not a significant determinant of the overall efficacy in the prevention of tuberculosis. C1 MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA 02114. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH PUBL HLTH,CHANNING LAB,TECHNOL ASSESSMENT GRP,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA. RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 NR 83 TC 65 Z9 70 U1 2 U2 5 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 JAN PY 1995 VL 20 IS 1 BP 126 EP 135 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA QC639 UT WOS:A1995QC63900021 PM 7727638 ER PT J AU BREWER, TF COLDITZ, GA AF BREWER, TF COLDITZ, GA TI BACILLE CALMETTE-GUERIN VACCINATION FOR THE PREVENTION OF TUBERCULOSIS IN HEALTH-CARE WORKERS SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; NEW-YORK-CITY; MYCOBACTERIUM-TUBERCULOSIS; RESISTANT TUBERCULOSIS; TUBERCLE-BACILLI; CONTROL PROGRAMS; INFECTION; PHYSICIANS; RISK; EPIDEMIOLOGY AB For 60 years vaccination with bacille Calmette-Guerin (BCG) has been used for the prevention of tuberculosis in health care workers. In 1988 the U.S. Advisory Committee on Immunization Practices removed the category of health care worker from the list of persons for whom vaccination with BCG should be considered. Nosocomial epidemics of tuberculosis, especially those caused by multidrug-resistant strains, have led to the reconsideration of vaccination with BCG for this population. We review the available studies of the efficacy of BCG vaccine in health care workers. Although the studies had too many methodological flaws to be combined in a quantitative meta-analysis, they suggest that vaccination with BCG is effective in reducing the incidence of tuberculosis among health care workers. C1 MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA 02114. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH PUBL HLTH,CHANNING LAB,TECHNOL ASSESSMENT GRP,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA. RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 NR 38 TC 37 Z9 39 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 JAN PY 1995 VL 20 IS 1 BP 136 EP 142 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA QC639 UT WOS:A1995QC63900022 PM 7727639 ER PT J AU Minassian, BA Sainz, J DelgadoEscueta, AV AF Minassian, BA Sainz, J DelgadoEscueta, AV TI Genetics of myoclonic and myoclonus epilepsies SO CLINICAL NEUROSCIENCE LA English DT Article DE myoclonic and myoclonus epilepsies; chromosomal locus; genetic linkage mapping ID DENTATORUBRAL-PALLIDOLUYSIAN ATROPHY; RAGGED-RED FIBERS; IDIOPATHIC GENERALIZED EPILEPSY; BATTEN-DISEASE; UNVERRICHT-LUNDBORG; LINKAGE ANALYSIS; CHROMOSOME 6P; LOCUS; LOCALIZATION; REGION AB Mendelian forms of benign myoclonic epilepsies where a chromosomal locus has been defined include (1) the autosomal dominant (AD) juvenile myoclonic epilepsy (JME) in chr. 6p11, (2) the autosomal dominant childhood absence epilepsy which evolves to JME in chr. 1p, (3) familial adult myoclonic epilepsy of Yasuda and Inazuki, and (4) possibly JME within the idiopathic generalized epilepsy susceptibility gene in chr. 8 reported by Zara et al (1995). Other myoclonic epilepsy syndromes with onset in the first year of life (Aicardi's Neonatal (Early) Myoclonic Encephalopathy, West's Syndrome, Dravet's Severe Myoclonic Epilepsy, and Dravet's Benign Myoclonic Epilepsy of Infancy), in early childhood (Lennox-Gastaut-Dravet Syndrome, Myoclonic Variant of Lennox Gastaut Dravet Syndrome, Myoclonic-Astatic Epilepsy of Doose, Benign Myoclonic Epilepsies (BME), or even in late childhood (Childhood Absence Epilepsy with myoclonias, vs. Myoclonic Absence Epilepsy) are probably genetically complex diseases. Amongst the progressive myoclonus epilepsy syndromes, specific mutations have already been defined in Unverricht Lundborg disease, ceroid lipofuscinoses 3 or Spielmayer Voight syndrome within Battens disease, sialidosis, dentadorubropallidoluysian atrophy and the mitochondrial syndrome MERRF. Most recently our laboratories established the locus for Lafora's disease in chr. 6q and results are speadily moving towards the definition of its mutation. (C) 1996 Wiley-Liss, Inc. C1 W LOS ANGELES VET AFFAIRS MED CTR,CTR EPILEPSY,LOS ANGELES,CA 90073. UNIV TORONTO,HOSP SICK CHILDREN,DEPT NEUROL,TORONTO,ON M5G 1X8,CANADA. CALIF COMPREHENS EPILEPSY PROGRAM,LOS ANGELES,CA. UNIV CALIF LOS ANGELES,DEPT NEUROL,LOS ANGELES,CA 90024. NR 87 TC 13 Z9 14 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 1065-6766 J9 CLIN NEUROSCI JI Clin. Neurosci. PY 1995 VL 3 IS 4 BP 223 EP 235 PG 13 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA VK158 UT WOS:A1995VK15800008 PM 8891396 ER PT J AU TRAUNER, KB NISHIOKA, NS FLOTTE, T PATEL, D AF TRAUNER, KB NISHIOKA, NS FLOTTE, T PATEL, D TI ACUTE AND CHRONIC RESPONSE OF ARTICULAR-CARTILAGE TO HOLMIUM-YAG LASER IRRADIATION SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID PULSED HOLMIUM; ABLATION; FIBROCARTILAGE; RABBIT; ENERGY AB A Ho:YAG (holmium-yttrium-aluminum-garnet) laser system operating at a wavelength of 2.1 microns has been introduced recently for use in arthroscopic surgery. The acceptability of this new tool will be determined not only by its ability to resect tissue, but also by its long-term effects on articular surfaces. Two studies were performed to evaluate the acute and chronic effects of the laser on cartilaginous tissue. The acute in vitro effects of 2.1-micron laser irradiation were evaluated, including measurement of ablation efficiency, ablation threshold, and thermal damage in meniscal and articular cartilage. To document the chronic effects on articular cartilage in vivo, a 10-week healing study was performed. Eight sheep weighing 30 to 30 kg underwent bilateral arthrotomy procedures. Multiple full-thickness and partial-thickness defects were created. Animals were euthanized at 0, 2, 4, and 10 weeks. The results of the healing study showed (1) no healing of full- or partial-thickness defects in hyaline cartilage at 10 weeks; (2) fibrocartilaginous granulation tissue filling full-thickness defects at 2 and 4 weeks that was no longer evident at 10 weeks; (3) chondrocyte necrosis extending to >900 microns distal to ablation craters at 4 weeks, with no evidence of repair at later dates; (4) chondrocyte hyperplasia at the borders of the damage zone at 2 weeks but not at euthanization occurring at later periods. C1 MASSACHUSETTS GEN HOSP,WELLMAN LABS PHOTOMED,BOSTON,MA. MASSACHUSETTS GEN HOSP,ARTHROSCOP SURG UNIT,BOSTON,MA. RP TRAUNER, KB (reprint author), UNIV CALIF DAVIS,DEPT ORTHOPAED SURG,2230 STOCKTON BLVD,SACRAMENTO,CA 95817, USA. NR 19 TC 39 Z9 39 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD JAN PY 1995 IS 310 BP 52 EP 57 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA QB447 UT WOS:A1995QB44700011 PM 7641459 ER PT J AU LLOYD, J JELLINEK, MS LITTLE, M MURPHY, JM PAGANO, M AF LLOYD, J JELLINEK, MS LITTLE, M MURPHY, JM PAGANO, M TI SCREENING FOR PSYCHOSOCIAL DYSFUNCTION IN PEDIATRIC INPATIENTS SO CLINICAL PEDIATRICS LA English DT Article ID SYMPTOM CHECKLIST; PRIMARY CARE; CHILDREN; PSYCHOPATHOLOGY; SCHOOL; HEALTH AB Screening pediatric inpatients for psychosocial dysfunction offers physicians an opportunity to identify emotional and behavioral problems that might otherwise go unrecognized. In this study, the Pediatric Symptom Checklist (PSC), a brief, parent-completed questionnaire, which has been validated in a variety of outpatient settings, was used to screen 98 pediatric inpatients. Results indicated that the PSC can be easily administered in a busy inpatient setting and is well-tolerated by both house staff and patients' parents as a routine part of the admissions process. The percentage of children who screened positive with the PSC in this inpatient setting was similar to the percentages generated by using the PSC in outpatient settings. Routine use of the PSC in inpatient settings serves to heighten house staff awareness of psychosocial concerns and facilitate parent-physician discussion of pediatric mental health issues. C1 MASSACHUSETTS GEN HOSP,CHILD PSYCHIAT SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CHILDRENS SERV,BOSTON,MA 02114. NR 25 TC 15 Z9 15 U1 0 U2 0 PU WESTMINSTER PUBL INC PI GLEN HEAD PA 708 GLEN COVE AVE, GLEN HEAD, NY 11545 SN 0009-9228 J9 CLIN PEDIATR JI Clin. Pediatr. PD JAN PY 1995 VL 34 IS 1 BP 18 EP 24 DI 10.1177/000992289503400104 PG 7 WC Pediatrics SC Pediatrics GA QB638 UT WOS:A1995QB63800004 PM 7720323 ER PT J AU Frueh, BC Turner, SM Beidel, DC AF Frueh, BC Turner, SM Beidel, DC TI Exposure therapy for combat-related PTSD: A critical review SO CLINICAL PSYCHOLOGY REVIEW LA English DT Review ID POSTTRAUMATIC-STRESS-DISORDER; OBSESSIVE-COMPULSIVE DISORDER; VIETNAM VETERANS; PSYCHOPHYSIOLOGICAL ASSESSMENT; PERSONALITY-DISORDERS; EMOTIONAL IMAGERY; CARDIAC RESPONSE; RELEVANT STIMULI; FLOODING THERAPY; ANXIETY AB This review critically examines the treatment outcome literature using exposure treatment for combat-related Posttraumatic Stress Disorder (PTSD). Although the current literature is quite underdeveloped, available data suggest that exposure is superior to wait-list controls and ''standard treatment.'' In particular; exposure treatment results in decreased symptoms of intrusive images, cognitions, and physiological arousal. Treatment gains are maintained for as long as 6 months. Limitations of current studies, important procedural variables, patient characteristics, and issues of measurement are highlighted. Finally, efficacy of exposure alone as a treatment for PTSD and the need for addition of other behavioral treatment strategies to exposure is discussed. C1 MED UNIV S CAROLINA, DEPT PSYCHIAT & BEHAV SCI, ANXIETY PREVENT & TREATMENT RES CTR, CHARLESTON, SC USA. MED UNIV S CAROLINA, DEPT PSYCHIAT & BEHAV SCI, RALPH H JOHNSON VET AFFAIRS MED CTR, CHARLESTON, SC USA. NR 115 TC 41 Z9 41 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0272-7358 J9 CLIN PSYCHOL REV JI Clin. Psychol. Rev. PY 1995 VL 15 IS 8 BP 799 EP 817 DI 10.1016/0272-7358(95)00049-6 PG 19 WC Psychology, Clinical SC Psychology GA TK788 UT WOS:A1995TK78800005 ER PT J AU Gould, RA Otto, MW Pollack, MH AF Gould, RA Otto, MW Pollack, MH TI A meta-analysis of treatment outcome for panic disorder SO CLINICAL PSYCHOLOGY REVIEW LA English DT Article ID COGNITIVE-BEHAVIORAL TREATMENT; DOUBLE-BLIND; SHORT-TERM; MULTICENTER TRIAL; ANXIETY DISORDERS; EXPOSURE INVIVO; DRUG-TREATMENT; FOLLOW-UP; AGORAPHOBIA; ALPRAZOLAM AB We compared the effectiveness of pharmacological, cognitive-behavioral and combined pharmacological and cognitive-behavioral treatments in a meta-analysis of 43 controlled studies that included 76 treatment interventions. Cognitive-behavioral treatments yielded the highest mean effect sizes (ES = 0.68) relative to pharmacological (ES = 0.47) and combination treatments (ES = 0.56). In addition, the proportion of subjects who dropped out of cognitive-behavioral treatments was 5.6% relative to 19.8% in pharmacological treatments and 22.0% in combined treatments. Among cognitive-behavioral treatments, those studies that combined cognitive restructuring with interoceptive exposure yielded the strongest effect sires (ES = 0.88). With regard to pharmacological treatments, there was no significant difference between antidepressants (ES = 0.55) and benzodiazepines (ES = 0.40). Long-term outcome analyses suggested that cognitive-behavioral interventions were the most successful at maintaining treatment gains. Cost analyses indicated that the lowest cost interventions were imipramine treatment and group cognitive-behavioral therapy. In general, cognitive-behavioral treatments yielded the largest effects sires and the smallest attrition rates relative to pharmacotherapy and combined treatments, and are cost-effective. C1 HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138. RP Gould, RA (reprint author), MASSACHUSETTS GEN HOSP,WACC 815,BEHAV THERAPY UNIT,15 PARKMAN ST,BOSTON,MA 02114, USA. NR 71 TC 280 Z9 283 U1 4 U2 47 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0272-7358 J9 CLIN PSYCHOL REV JI Clin. Psychol. Rev. PY 1995 VL 15 IS 8 BP 819 EP 844 DI 10.1016/0272-7358(95)00048-8 PG 26 WC Psychology, Clinical SC Psychology GA TK788 UT WOS:A1995TK78800006 ER PT J AU WATERS, GS CAPLAN, D ROCHON, E AF WATERS, GS CAPLAN, D ROCHON, E TI PROCESSING CAPACITY AND SENTENCE COMPREHENSION IN PATIENTS WITH ALZHEIMERS-DISEASE SO COGNITIVE NEUROPSYCHOLOGY LA English DT Article ID MINI-MENTAL STATE; SHORT-TERM-MEMORY; WORKING MEMORY; INDIVIDUAL-DIFFERENCES; SENILE DEMENTIA; SYNTACTIC COMPREHENSION; SEMANTIC MEMORY; IMPAIRMENT; APHASIA; SPAN AB A sentence-picture matching task was used to test the ability of patients with dementia of the Alzheimer's type (DAT) and age- and education-matched control subjects to interpret nine different sentences. These sentences differed on two dimensions-syntactic complexity and number of propositions. Subjects were tested on this task with no concurrent task (alone) and while concurrently remembering a digit load that was on less than their span or equivalent to their span. Neither group of subjects showed an effect of syntactic complexity, but DAT patients did show an effect of the number of propositions in a sentence. For all subjects, comprehension of sentences with more propositions was more greatly affected by larger digit loads, but comprehension of more complex syntactic structures was not. The performance of DAT patients was more affected than that of the control subjects on the digit task, but they were not disproportionately impaired on the sentence types which were more complex or had more propositions compared to normals. The results are discussed in relationship to the hypothesis that there is a sentence comprehension impairment in DAT that is related, to the processing resource requirements of different aspects of the sentence comprehension process. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP WATERS, GS (reprint author), MCGILL UNIV,SCH COMMUN SCI & DISORDERS,1266 PINE AVE W,MONTREAL,PQ H3G 1A8,CANADA. OI Rochon, Elizabeth/0000-0001-5521-0513 NR 66 TC 75 Z9 75 U1 1 U2 4 PU LAWRENCE ERLBAUM ASSOC LTD PI HOVE PA 27 PALMEIRA MANSIONS CHURCH RD, HOVE, E SUSSEX, ENGLAND BN3 2FA SN 0264-3294 J9 COGNITIVE NEUROPSYCH JI Cogn. Neuropsychol. PY 1995 VL 12 IS 1 BP 1 EP 30 DI 10.1080/02643299508251990 PG 30 WC Psychology; Psychology, Experimental SC Psychology GA QE193 UT WOS:A1995QE19300001 ER PT J AU CAPLAN, D WATERS, GS AF CAPLAN, D WATERS, GS TI APHASIC DISORDERS OF SYNTACTIC COMPREHENSION AND WORKING-MEMORY CAPACITY SO COGNITIVE NEUROPSYCHOLOGY LA English DT Article ID ALZHEIMER-TYPE DEMENTIA; SENTENCE COMPREHENSION; INDIVIDUAL-DIFFERENCES AB Miyake, Carpenter, and Just (1994) present results of two sentence comprehension experiments using RSVP in normal subjects, which they say simulate important features of aphasic patients' comprehension of syntactic structures. On this basis, they claim that normal and aphasic subjects' performance represents a continuum of limitations in working memory capacity. In this paper, we argue that the Miyake et al. data do not resemble the performance of aphasic patients in crucial respects, and that their results provide evidence for the opposite conclusion-namely, that the processing resource system that underlies syntactic processing and that is affected in aphasia is substantially separate from the one used for other verbal tasks, such as reasoning and problem solving, which is tested in tasks such as the Daneman and Carpenter (1980) reading span task. C1 MCGILL UNIV,MONTREAL,PQ,CANADA. RP CAPLAN, D (reprint author), MASSACHUSETTS GEN HOSP,NEUROPSYCHOL LAB,VINCENT BURNHAM 827,FRUIT ST,BOSTON,MA 02114, USA. NR 25 TC 67 Z9 68 U1 1 U2 2 PU LAWRENCE ERLBAUM ASSOC LTD PI HOVE PA 27 PALMEIRA MANSIONS CHURCH RD, HOVE, E SUSSEX, ENGLAND BN3 2FA SN 0264-3294 J9 COGNITIVE NEUROPSYCH JI Cogn. Neuropsychol. PY 1995 VL 12 IS 6 BP 637 EP 649 DI 10.1080/02643299508252011 PG 13 WC Psychology; Psychology, Experimental SC Psychology GA RX451 UT WOS:A1995RX45100004 ER PT J AU Sadasivan, BK Cariappa, A Waneck, GL Cresswell, P AF Sadasivan, BK Cariappa, A Waneck, GL Cresswell, P TI Assembly, peptide loading, and transport of MHC class I molecules in a calnexin-negative cell line SO COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY LA English DT Article; Proceedings Paper CT Cold Spring Harbor Symposia on Quantitative Biology - Protein Kinesis: The Dynamics of Protein Trafficking and Stability CY 1995 CL COLD SPRING HARBOR, NY ID LONG TERMINAL REPEAT; ENDOPLASMIC-RETICULUM; T-CELL; ANTIGEN PRESENTATION; MONOCLONAL-ANTIBODY; SIGNAL SEQUENCE; CHAPERONE; BINDING; PROTEIN; BETA-2-MICROGLOBULIN C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,CHARLESTOWN,MA 02129. RP Sadasivan, BK (reprint author), YALE UNIV,SCH MED,HOWARD HUGHES MED INST,IMMUNOBIOL SECT,NEW HAVEN,CT 06510, USA. FU NIAID NIH HHS [AI-23081]; NIDDK NIH HHS [DK-38452]; NIGMS NIH HHS [GM-4546] NR 35 TC 66 Z9 66 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0091-7451 J9 COLD SPRING HARB SYM JI Cold Spring Harbor Symp. Quant. Biol. PY 1995 VL 60 BP 267 EP 275 PG 9 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA VA125 UT WOS:A1995VA12500030 PM 8824400 ER PT J AU Goldberg, AL Gaczynska, M Grant, E Michalek, M Rock, KL AF Goldberg, AL Gaczynska, M Grant, E Michalek, M Rock, KL TI Functions of the proteasome in antigen presentation SO COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY LA English DT Article; Proceedings Paper CT Cold Spring Harbor Symposia on Quantitative Biology - Protein Kinesis: The Dynamics of Protein Trafficking and Stability CY 1995 CL COLD SPRING HARBOR, NY ID MAJOR HISTOCOMPATIBILITY COMPLEX; MULTICATALYTIC PROTEINASE COMPLEX; CLASS-II REGION; UBIQUITIN-ACTIVATING ENZYME; RESTRICTED LYMPHOCYTES-T; MHC-LINKED LMP; INTERFERON-GAMMA; PEPTIDASE ACTIVITIES; PROTEOLYTIC PATHWAY; YEAST PROTEASOME C1 DANA FARBER CANC INST,DIV LYMPHOCYTE BIOL,BOSTON,MA 02115. RP Goldberg, AL (reprint author), HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115, USA. FU NIAID NIH HHS [AI-20248]; NIGMS NIH HHS [GM-46147] NR 73 TC 41 Z9 41 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0091-7451 J9 COLD SPRING HARB SYM JI Cold Spring Harbor Symp. Quant. Biol. PY 1995 VL 60 BP 479 EP 490 PG 12 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA VA125 UT WOS:A1995VA12500051 PM 8824421 ER PT B AU BAUMAN, RA AF BAUMAN, RA BE Lemke, HU Inamura, K Jaffe, CC Vannier, MW TI Large Picture Archiving and Communication Systems (PACS) SO COMPUTER ASSISTED RADIOLOGY LA English DT Proceedings Paper CT International Symposium on Computer and Communication Systems for Image Guided Diagnosis and Therapy (CAR 95) CY JUN 21-24, 1995 CL BERLIN, GERMANY SP European Soc PACS, Int Symp Planning Radiol Dept, Int Soc Comp Aided Surg C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN 33 PA HEIDELBERGER PLATZ 3, W-1000 BERLIN 33, GERMANY BN 3-540-59177-X PY 1995 BP 537 EP 541 PG 5 WC Computer Science, Interdisciplinary Applications; Medical Laboratory Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Medical Laboratory Technology; Radiology, Nuclear Medicine & Medical Imaging GA BE22E UT WOS:A1995BE22E00086 ER PT J AU Aoba, T Taya, Y Sato, A Shimada, T MuraGalelli, MJ AF Aoba, T Taya, Y Sato, A Shimada, T MuraGalelli, MJ TI Mechanistic understanding of enamel mineralization under fluoride regime SO CONNECTIVE TISSUE RESEARCH LA English DT Article; Proceedings Paper CT 5th International Conference on Tooth Morphogenesis and Differentiation CY MAY 04-08, 1994 CL KERKRADE, NETHERLANDS SP Acad Centrum Tandheelkunde Amsterdam, BSN Grp, CABA Int Ltd, Henkel KGaA, Netherlands Inst Dental Sci, Royal Netherlands Acad Arts & Sci, Suiker Stichting Nederland DE biomineralization; amelogenesis; fluoride; matrix proteins; amelogenin degradation ID SECRETORY ENAMEL; CALCIUM APATITES; RAT; HYDROXYAPATITE; AMELOGENESIS; ADSORPTION; PHOSPHATE; PROTEINS AB In order to learn more about how the microenvironment for enamel mineralization is modified by fluoride at low concentrations (0 through 1 ppm) and how excess fluoride retards the degradation and removal of amelogenins, we studied precipitation reactions in an in vitro model utilizing a dialysis chamber. The results showed that, with the limited supply of Ca ions through the ultrafiltration membrane, the solution composition surrounding the seed crystals showed a proximity to the steady-state condition after 12-24 h equilibration. Major findings were that (a) fluoride overcame partially the inhibition of precipitation and growth reactions by enamel proteins and (b), with this accelerating effect of fluoride, the steady-state Ca concentrations in the media surrounding the seed crystals decreased substantially as a function of fluoride concentration. The overall results support the concept that the presence of fluoride in the mineralizing milieu can modify markedly the steady-state concentrations of mineral lattice ions, particularly decreasing free Ca2+ concentrations, which in turn may modulate protease activities in situ. C1 NIPPON DENT UNIV TOKYO,DEPT PATHOL,TOKYO,JAPAN. FORSYTH DENT CTR,BOSTON,MA 02115. NR 20 TC 0 Z9 0 U1 0 U2 1 PU GORDON BREACH SCI PUBL LTD PI READING PA C/O STBS LTD PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 0300-8207 J9 CONNECT TISSUE RES JI Connect. Tissue Res. PY 1995 VL 32 IS 1-4 BP 467 EP 471 PG 5 WC Cell Biology; Orthopedics SC Cell Biology; Orthopedics GA VT030 UT WOS:A1995VT03000062 ER PT B AU GAA, JC SAINI, S AF GAA, JC SAINI, S BE Balzer, T Hamm, B Niendorf, HP TI Future techniques in MR imaging of the liver: Echo planar imaging SO CONTRAST AGENTS IN LIVER IMAGING SE SERIES IN RADIOLOGY LA English DT Proceedings Paper CT Workshop on Contrast Agents in Liver Imaging CY APR 17, 1993 CL BERLIN, GERMANY C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIOL,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 2 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 0-7923-3130-3 J9 SER RADIOL PY 1995 VL 25 BP 91 EP 96 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA BD74M UT WOS:A1995BD74M00010 ER PT J AU WALLER, SG STEINERT, RF WAGONER, MD AF WALLER, SG STEINERT, RF WAGONER, MD TI LONG-TERM RESULTS OF EPIKERATOPLASTY FOR KERATOCONUS SO CORNEA LA English DT Article DE EPIKERATOPLASTY; KERATOCONUS AB By analysis of outpatient records at the Massachusetts Eye and Ear Infirmary, the clinical course of 10 consecutive patients who underwent epikeratoplasty for keratoconus was reviewed to determine their clinical and functional status 5 years after surgery. Eight of 10 patients (80%) had clear, intact lenticules at 12 months. During a mean follow-up of 67 months (range = 35-101 months), each maintained long-term stability of best corrected vision, refractive astigmatism, and keratometric astigmatism. The mean uncorrected visual acuity improved from 20/660 to 20/134, whereas the mean spectacle corrected acuity improved from 20/260 to 20/30. All but one patient had a spectacle acuity equal to hard contact lens acuity. However, no patients were corrected to 20/20 at the end of the follow-up period. Refractive and keratometric astigmatism stabilized by 12 months (mean = 3.62 and 3.05 D, respectively), and decreased slightly during the longer period of follow-up (mean = 2.94 and 2.17 D, respectively). Epikeratoplasty is a useful method of visual rehabilitation in highly selected cases of keratoconus in which there is no central opacity, preoperative hard contact lens acuity is worse than 20/40, the average keratometry is <60 D, contact lens intolerance is present, and in which the patient will tolerate some degree of reduced contrast sensitivity and <20/20 high contrast acuity. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,CORNEA SERV,BOSTON,MA. NR 0 TC 16 Z9 19 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0277-3740 J9 CORNEA JI Cornea PD JAN PY 1995 VL 14 IS 1 BP 84 EP 88 PG 5 WC Ophthalmology SC Ophthalmology GA PZ188 UT WOS:A1995PZ18800014 PM 7712742 ER PT B AU Yaremchuck, M Sims, D Casanova, R Amarante, M AF Yaremchuck, M Sims, D Casanova, R Amarante, M BE Marchac, D TI Long-term follow-up of expanded polyethylene implants for aesthetic and reconstructive facial skeletal surgery SO CRANIOFACIAL SURGERY 6 LA English DT Proceedings Paper CT 6th International Congress of the International-Society-of-Cranio-Facial-Surgery CY OCT 21-24, 1995 CL ST TROPEZ, FRANCE SP Int Soc Craniofacial Surg RP Yaremchuck, M (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DIV PLAST SURG,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MONDUZZI EDITORE PI 40128 BOLOGNA PA VIA FERRARESE 119/2, 40128 BOLOGNA, ITALY PY 1995 BP 329 EP 329 PG 1 WC Surgery SC Surgery GA BH77C UT WOS:A1995BH77C00092 ER PT J AU NELSON, D KUPPERMANN, N FLEISHER, GR HAMMER, BK THOMPSON, CM GARCIA, CT NOVITSKY, TJ PARSONNET, J ONDERDONK, A SIBER, GR SALADINO, RA AF NELSON, D KUPPERMANN, N FLEISHER, GR HAMMER, BK THOMPSON, CM GARCIA, CT NOVITSKY, TJ PARSONNET, J ONDERDONK, A SIBER, GR SALADINO, RA TI RECOMBINANT ENDOTOXIN NEUTRALIZING PROTEIN IMPROVES SURVIVAL FROM ESCHERICHIA-COLI SEPSIS IN RATS SO CRITICAL CARE MEDICINE LA English DT Article DE ENDOTOXIN; SHOCK; SEPSIS; TUMOR NECROSIS FACTOR; GRAM-NEGATIVE BACTERIA; ESCHERICHIA COLI; BACTERIAL INFECTION; ANIMAL MODEL; CRITICAL ILLNESS ID SEPTIC SHOCK; CHILDREN; ANTIBODY; MURINE; TRIAL AB Objective: A recombinant endotoxin neutralizing protein was evaluated for its ability to ameliorate the effects of Escherichia coli sepsis in rats. Design: Prospective, controlled animal trial. Setting: Hospital animal research laboratory. Subjects: Wistar rats, treated with gentamicin 1 hr after challenge with intraperitoneal E. coli O18ac. Interventions: The animals received a recombinant endotoxin neutralizing protein, in doses of 5, 25, or 50 mg/kg, either 30 or 60 mins after challenge; controls received saline. Measurements and Main Results: Geometric mean serum endotoxin concentrations in endotoxin neutralizing protein-treated animals did not differ from control animals. Tumor necrosis factor concentrations in animals treated with endotoxin neutralizing protein 30 mins after challenge were significantly lower than controls. Animals treated with 25 or 50 mg/kg of endotoxin neutralizing protein 30 mins after E. cell challenge had significant improvements in survival compared with controls. Animals treated with 50 mg/kg of endotoxin neutralizing protein 60 mins after E. coli challenge had significant improvements in survival compared with controls. Conclusion: Endotoxin neutralizing protein significantly reduces mortality from Gramnegative sepsis in an antibiotic-treatment model of E. coli peritonitis and bacteremia in rats, mediated by a neutralization of the biological effects of endotoxin. C1 CHILDRENS HOSP,DEPT MED,DIV EMERGENCY MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,INFECT DIS LAB,BOSTON,MA 02115. CAPE COD INC,WOODS HOLE,MA. DARTMOUTH COLL,HITCHCOCK MED CTR,DEPT MED,DIV INFECT DIS,HANOVER,NH 03756. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RI Hammer, Brian/I-7282-2013 FU NIAID NIH HHS [AI18125] NR 24 TC 20 Z9 22 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JAN PY 1995 VL 23 IS 1 BP 92 EP 98 DI 10.1097/00003246-199501000-00017 PG 7 WC Critical Care Medicine SC General & Internal Medicine GA QA059 UT WOS:A1995QA05900017 PM 8001394 ER PT J AU SALEM, M KASINSKI, N MUNOZ, R CHERNOW, B AF SALEM, M KASINSKI, N MUNOZ, R CHERNOW, B TI PROGRESSIVE MAGNESIUM, DEFICIENCY INCREASES MORTALITY FROM ENDOTOXIN CHALLENGE - PROTECTIVE EFFECTS OF ACUTE MAGNESIUM REPLACEMENT THERAPY SO CRITICAL CARE MEDICINE LA English DT Article DE MAGNESIUM; MAGNESIUM DEFICIENCY; SEPSIS; ENDOTOXIN; SHOCK; LIPOPOLYSACCHARIDE; INFECTION; POTASSIUM; HYPOKALEMIA; ION CHANNELS ID ISCHEMIC-INJURY; SEPTIC SHOCK; VITAMIN-E; CALCIUM; HYPOMAGNESEMIA; RATS; SEPSIS; PATHOGENESIS; POPULATION; CYTOKINES AB Objectives: To study the effects of endotoxin on magnesium homeostasis; to determine if progressive magnesium deficiency alters outcome from endotoxin challenge; and to evaluate the efficacy of magnesium therapy in reducing endotoxin-induced mortality. Design: Prospective, placebo-controlled, randomized, multiexperiment studies. Setting: Research laboratory of a university hospital. Subjects: Male Sprague Dawley rats (n = 299). Interventions: Experiment 1 was designed to test if endotoxin alters magnesium homeostasis. Circulating total and ionized magnesium (estimated by ultrafilterable values) concentrations were determined in blood samples collected from animals after the randomized administration of placebo or 0.3, 3.0, or 30 mg/kg of endotoxin. A baseline blood sample was collected and then a second blood sample was obtained at 5, 15, 30, 60, 120, or 180 mins after endotoxin or placebo administration. In experiment 2, animals were randomized to receive magnesium-sufficient diets or magnesium-deficient diets for 6 wks. After 6 wks, the effects of the randomized administration of 3.0 mg/kg endotoxin or placebo were evaluated on mortality and analyte values (pH and blood gases, sodium, potassium, chloride, glucose, ionized calcium, hematocrit, total and ultrafilterable magnesium concentrations) in the three study groups (magnesium-sufficient, 3-wk magnesium-deficient, or 6-wk magnesium-deficient). In experiment 3, magnesium-deficient animals mere randomized to receive 50 mmol/kg magnesium chloride or placebo, before or after the administration of 3.0 mg/kg of endotoxin. Baseline and 24-hr analyte determinations were performed and outcome was analyzed. Measurements and Main Results: Experiment 1: Significant increases (p < .05) in circulating total magnesium concentrations were found in animals that received 30 mg/kg of endotoxin, at 120 mins (0.79 +/- 0.10 vs. 0.60 +/- 0.05 mmol/L), and 180 mins (0.74 +/- 0.01 vs. 0.56 +/- 0.04 mmol/L) compared with baseline values. Similarly, significant increases (p < .05) in ionized magnesium concentrations were observed 120 and 180 mins after 3.0 and 30 mg/kg of endotoxin compared with baseline values. Experiment 2: Magnesium deficiency was strongly (p < .02) associated with increased mortality from endotoxin challenge. Endotoxin administration (3.0 mg/ kg) was lethal in 10 (43%) of 23 magnesium-sufficient animals, 15 (65%) of 23 3-wk magnesium-deficient animals, and 20 (83%) of 24 6-wk magnesium-deficient animals. Experiment 3: In magnesium-deficient animals, rats treated with magnesium replacement therapy had significantly increased survival from endotoxin administration (15 [52%] of 29 vs. five [17%] of 29, p < .01) compared with placebo-treated animals. Conclusions: a) Endotoxin challenge causes significant increases in circulating total and ionized magnesium concentrations. b) Progressive magnesium deficiency is strongly associated with increased lethality, and magnesium replacement therapy provides significant protection from endotoxin challenge. c) These experimental results support the concept that cellular injury is probably associated with increases in circulating magnesium concentrations. Furthermore, these experimental findings suggest that magnesium deficiency predisposes to worse outcome from endotoxin challenge, and that replacement therapy in the setting of magnesium deficiency may be warranted, especially in critically ill subjects. C1 SINAI HOSP,DEPT MED,BALTIMORE,MD 21215. GEORGE WASHINGTON UNIV,SCH MED & HLTH SCI,DEPT SURG,WASHINGTON,DC 20052. GEORGE WASHINGTON UNIV,SCH MED & HLTH SCI,DEPT ANESTHESIA & CRIT CARE,WASHINGTON,DC 20052. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ANESTHESIA & CRIT CARE,BOSTON,MA. HARVARD UNIV,CHILDRENS HOSP,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. SINAI HOSP,DEPT MED,BALTIMORE,MD 21215. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT ANESTHESIOL & CRIT CARE MED,BALTIMORE,MD 21205. NR 49 TC 44 Z9 46 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JAN PY 1995 VL 23 IS 1 BP 108 EP 118 DI 10.1097/00003246-199501000-00019 PG 11 WC Critical Care Medicine SC General & Internal Medicine GA QA059 UT WOS:A1995QA05900019 PM 8001362 ER PT J AU BOLLAND, GW LEE, MJ AF BOLLAND, GW LEE, MJ TI MAGNETIC-RESONANCE-IMAGING OF THE ADRENAL-GLAND SO CRITICAL REVIEWS IN DIAGNOSTIC IMAGING LA English DT Review DE ADRENAL; MAGNETIC RESONANCE IMAGING ID FINE-NEEDLE ASPIRATION; CELL LUNG-CARCINOMA; COMPUTED-TOMOGRAPHY; ONCOLOGIC PATIENTS; CORTICAL LESIONS; CHEMICAL-SHIFT; MR; MASSES; CT; BIOPSY AB The authors review their experience with magnetic resonance imaging (MRI) of the adrenal gland and discuss the appearances of adrenal diseases where MRI is clinically useful. A basic description of some of the newer pulse sequences is provided. Fat-suppressed MRI is advantageous because of reduction of cardiac and respiratory motion induced artifacts, accentuation of small differences in tissue contrast, and elimination of chemical shift artifacts. These advantages far outweigh the disadvantages of inhomogeneity of fat suppression and the fewer slices obtained per acquisition. Chemical shift imaging is used to differentiate benign from malignant adrenal diseases based on a gradient echo phase cycling technique. Detailed descriptions of MRI findings in adrenal pheochromocytomas, hemorrhage, cysts, adenomas, myelolipomas, and metastases are provided. Most pheochromocytomas appear markedly hyperintense to the liver on T2-weighted images. However, this appearance is not specific as adrenal metastases and adrenal adenomas may occasionally produce a similar appearance. In addition, pheochromocytomas may occasionally be isointense or hypointense to the liver on T2-weighted images, Differentiation of adrenal metastases from adrenal adenomas with MRI is problematic using signal intensity ratios (33% overlap) or T2 calculations. The future of discriminating between adrenal metastases and adenomas may rest with chemical shift MRI, which uses in- and out-of-phase gradient echo pulse sequences for differentiation. This approach relies on the fact that adrenal adenomas contain fat, while adrenal metastases do not. The reported accuracy of chemical shift imaging in differentiating between adrenal adenomas and adrenal metastases ranges from 96 to 100%. An algorithmic approach to differentiating benign from malignant adrenal diseases is presented that relies on an initial noncontrast CT with CT attenuation values obtained from the adrenal mass. If CT attenuation values are less than zero, the mass is characterized as benign. If the mass remains indeterminate after CT, chemical shift MR is performed. If the mass remains indeterminate after MR, biopsy is required. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. NR 71 TC 0 Z9 0 U1 0 U2 0 PU CRC PRESS INC PI BOCA RATON PA 2000 CORPORATE BLVD NW, BOCA RATON, FL 33431 SN 1040-8371 J9 CRIT REV DIAGN IMAG JI Crit. Rev. Diagn. Imaging PY 1995 VL 36 IS 2 BP 115 EP 174 PG 60 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA QX937 UT WOS:A1995QX93700002 ER PT S AU Hsu, YPP Schuback, DE Tivol, EA Shalish, C Murphy, DL Breakefield, XO AF Hsu, YPP Schuback, DE Tivol, EA Shalish, C Murphy, DL Breakefield, XO BE Yu, PM Tipton, KF Boulton, AA TI Analysis of MAOA mutations in humans SO CURRENT NEUROCHEMICAL AND PHARMACOLOGICAL ASPECTS OF BIOGENIC AMINES SE PROGRESS IN BRAIN RESEARCH LA English DT Article; Proceedings Paper CT International Joint Meeting of the 6th Amine Oxidase Workshop/5th Trace Amine Conference CY AUG, 1994 CL SASKATOON, CANADA SP Int Soc Neurochem, Burroughs Wellcome, Canada, Ciba Geigy Canada, Ciba Geigy Ltd, Basel, Chiesi Pharm, Italy, Eli Lilly Canada, Nordic Merrell Dow, Canada, Orion Corp, Finland, Rhone Poulenc Pharma, Canada, Synthelabo Res, France, Upjohn Canada ID MONOAMINE OXIDASE-A; NORRIE DISEASE; PARKINSONS-DISEASE; X-CHROMOSOME; PRENATAL-DIAGNOSIS; PEPTIDE SEQUENCES; MOLECULAR-BASIS; ENZYME-ACTIVITY; CANDIDATE GENE; HUMAN-LIVER C1 VET ADM MED CTR,W ROXBURY,MA 02132. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. NIMH,CLIN SCI LAB,BETHESDA,MD 20892. NR 59 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL B V PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 BN 0-444-81938-X J9 PROG BRAIN RES PY 1995 VL 106 BP 67 EP 75 PG 9 WC Biochemistry & Molecular Biology; Neurosciences; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Pharmacology & Pharmacy GA BF87C UT WOS:A1995BF87C00007 PM 8584675 ER PT J AU PODOLSKY, DK AF PODOLSKY, DK TI INFLAMMATORY BOWEL-DISEASE - OVERVIEW SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Editorial Material RP PODOLSKY, DK (reprint author), MASSACHUSETTS GEN HOSP,32 FRUIT ST,GRJ719,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0267-1379 J9 CURR OPIN GASTROEN JI Curr. Opin. Gastroenterol. PY 1995 VL 11 IS 4 BP 289 EP 291 DI 10.1097/00001574-199507000-00001 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RJ229 UT WOS:A1995RJ22900001 ER PT B AU LOCKE, JL AF LOCKE, JL BE Zimmermann, E Newman, JD Jurgens, U TI Linguistic capacity: An ontogenetic theory with evolutionary implications SO CURRENT TOPICS IN PRIMATE VOCAL COMMUNICATION LA English DT Proceedings Paper CT XIV Congress of the International-Primatological-Society CY AUG 16-21, 1992 CL STRASBOURG, FRANCE SP Int Primatol Soc C1 MASSACHUSETTS GEN HOSP,NEUROLINGUIST LAB,BOSTON,MA 02114. NR 0 TC 2 Z9 2 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 BN 0-306-45064-X PY 1995 BP 253 EP 272 PG 20 WC Behavioral Sciences; Zoology SC Behavioral Sciences; Zoology GA BD38P UT WOS:A1995BD38P00014 ER PT J AU ROSEN, DR TROFATTER, JA BROWN, RH AF ROSEN, DR TROFATTER, JA BROWN, RH TI MAPPING OF THE HUMAN TATA-BINDING PROTEIN GENE (TBP) TO CHROMOSOME 6QTER SO CYTOGENETICS AND CELL GENETICS LA English DT Article ID REPEAT AB TATA-binding protein (TBP) is a general transcription factor involved in transcriptional initiation. We have used oligonucleotide primers flanking a polymorphic stretch of 38 glutamine codons in the 5' coding region of the TBP gene to genetically map this gene. We report the location of the human TBP gene to be at 6qter. C1 MASSACHUSETTS GEN HOSP,DAY NEUROMUSCULAR LAB,BOSTON,MA. MASSACHUSETTS GEN HOSP,NEUROGENET LAB,BOSTON,MA. FU NHGRI NIH HHS [HG0001-6]; NINDS NIH HHS [1-F32-NS0926-01A1, 1-P01-NS31248-01] NR 15 TC 2 Z9 2 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 1995 VL 69 IS 3-4 BP 279 EP 280 DI 10.1159/000133979 PG 2 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA QT857 UT WOS:A1995QT85700027 PM 7698028 ER PT J AU TASCHNER, PEM DEVOS, N BARIH, PG BREUNING, MH GARDINER, RM CALLEN, DF DOGGETT, NA LERNER, TJ DOOLEY, T AF TASCHNER, PEM DEVOS, N BARIH, PG BREUNING, MH GARDINER, RM CALLEN, DF DOGGETT, NA LERNER, TJ DOOLEY, T TI D16S298 NULL ALLELE MAY BE ASSOCIATED WITH A DELETION OF (PART OF) THE CLN3 GENE INVOLVED IN JUVENILE NEURONAL CEROID-LIPOFUSCINOSIS (BATTEN-DISEASE IN A MOROCCAN PATIENT) SO CYTOGENETICS AND CELL GENETICS LA English DT Meeting Abstract C1 LEIDEN UNIV, DEPT HUMAN GENET, 2300 RA LEIDEN, NETHERLANDS. AMSTERDAM MED CTR, DEPT PAEDIAT, AMSTERDAM, NETHERLANDS. UCL, SCH MED, LONDON W1N 8AA, ENGLAND. ADELAIDE CHILDRENS HOSP INC, ADELAIDE, SA 5006, AUSTRALIA. LOS ALAMOS NATL LAB, LOS ALAMOS, NM USA. MASSACHUSETTS GEN HOSP, BOSTON, MA 02114 USA. SW FDN BIOMED RES, SAN ANTONIO, TX 78284 USA. RI Mole, Sara/C-2024-2008; Callen, David/G-1975-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 1995 VL 68 IS 3-4 BP 179 EP 179 PG 1 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA PX890 UT WOS:A1995PX89000055 ER PT J AU KOZMAN, HM KEITH, TP GERKEN, S DONISKELLER, H WHITE, RL WEISSENBACH, J AKSENTIJEVICH, I KASTNER, DL VERGNAUD, G KIDD, K GUSELLA, J JEFFREYS, A SUTHERLAND, GR MULLEY, JC AF KOZMAN, HM KEITH, TP GERKEN, S DONISKELLER, H WHITE, RL WEISSENBACH, J AKSENTIJEVICH, I KASTNER, DL VERGNAUD, G KIDD, K GUSELLA, J JEFFREYS, A SUTHERLAND, GR MULLEY, JC TI THE CEPH CONSORTIUM LINKAGE MAP OF HUMAN-CHROMOSOME-16 SO CYTOGENETICS AND CELL GENETICS LA English DT Meeting Abstract C1 WOMENS & CHILDRENS HOSP,DEPT CYTOGENET & MOLEC GENET,ADELAIDE,SA,AUSTRALIA. WASHINGTON UNIV,SCH MED,DEPT GENET,ST LOUIS,MO 63110. UNIV UTAH,HOWARD HUGHES MED INST,SALT LAKE CITY,UT. INST PASTEUR,PARIS,FRANCE. NIAMSD,ARTHRIT & RHEUMATISM BRANCH,BETHESDA,MD 20892. CTR ETUD BOUCHET,F-91710 VERT LE PETIT,FRANCE. YALE UNIV,SCH MED,DEPT HUMAN GENET,NEW HAVEN,CT 06510. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. UNIV LEICESTER,DEPT GENET,LEICESTER LE1 7RH,LEICS,ENGLAND. RI Sutherland, Grant/D-2606-2012; Vergnaud, Gilles/P-1304-2015 OI Vergnaud, Gilles/0000-0003-0913-194X NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 1995 VL 68 IS 3-4 BP 182 EP 182 PG 1 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA PX890 UT WOS:A1995PX89000066 ER PT J AU JARVELA, IE MITCHISON, HM GARDINER, RM CALLEN, DF BREUNING, MH LEMER, TJ MOLE, SE DOGGETT, NA DOOLEY, TP AF JARVELA, IE MITCHISON, HM GARDINER, RM CALLEN, DF BREUNING, MH LEMER, TJ MOLE, SE DOGGETT, NA DOOLEY, TP TI LONG-RANGE RESTRICTION MAP OF A YAC CONTIG IN THE BATTEN-DISEASE REGION OF CHROMOSOME-16 AND EXCLUSION OF POTENTIAL CANDIDATE GENES FROM THIS REGION SO CYTOGENETICS AND CELL GENETICS LA English DT Meeting Abstract C1 UCL, RAYNE INST, DEPT PAEDIAT, LONDON, ENGLAND. WOMENS & CHILDRENS HOSP, DEPT CYTOGENET & MOLEC GENET, ADELAIDE, SA, AUSTRALIA. LEIDEN UNIV, DEPT HUMAN GENET, SYLVIUS LABS, 2300 RA LEIDEN, NETHERLANDS. MASSACHUSETTS GEN HOSP, MOLEC NEUROGENET UNIT, BOSTON, MA USA. LOS ALAMOS NATL LAB, DIV LIFE SCI, LOS ALAMOS, NM USA. LOS ALAMOS NATL LAB, CTR HUMAN GENOME STUDIES, LOS ALAMOS, NM 87545 USA. SW FDN BIOMED RES, DEPT GENET, SAN ANTONIO, TX USA. RI Callen, David/G-1975-2012 NR 6 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 1995 VL 68 IS 3-4 BP 183 EP 184 PG 2 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA PX890 UT WOS:A1995PX89000069 ER PT J AU LEMER, TJ DARIGO, KL HAINES, JL DOGGETT, NA BUCKLER, A AF LEMER, TJ DARIGO, KL HAINES, JL DOGGETT, NA BUCKLER, A TI ISOLATION OF TRANSCRIBED SEQUENCES FROM THE BATTEN CANDIDATE REGION USING EXON AMPLIFICATION SO CYTOGENETICS AND CELL GENETICS LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP, MOLEC NEUROGENET UNIT, BOSTON, MA USA. HARVARD UNIV, SCH MED, DEPT NEUROL, BOSTON, MA 02115 USA. LOS ALAMOS NATL LAB, DIV LIFE SCI, LOS ALAMOS, NM USA. LOS ALAMOS NATL LAB, CTR HUMAN GENOME STUDIES, LOS ALAMOS, NM 87545 USA. UCL, SCH MED, DEPT PAEDIAT, LONDON W1N 8AA, ENGLAND. ADELAIDE CHILDRENS HOSP INC, DEPT CYTOGENET & MOLEC GENET, ADELAIDE, SA 5006, AUSTRALIA. LEIDEN UNIV, DEPT HUMAN GENET, 2300 RA LEIDEN, NETHERLANDS. SW INSR BIOMED RES, DEPT GENET, SAN ANTONIO, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 1995 VL 68 IS 3-4 BP 183 EP 183 PG 1 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA PX890 UT WOS:A1995PX89000068 ER PT B AU Podolsky, DK AF Podolsky, DK BE Keusch, GT Kawakami, M TI Regulatory peptides and integration of the intestinal epithelium in mucosal responses - Regulatory peptides modulate epithelial proliferation and function SO CYTOKINES, CHOLERA, AND THE GUT LA English DT Proceedings Paper CT 1995 Joint Meeting of the United-States/Japan Cooperative Medical Sciences Program Panels on Malnutrition and Cholera CY NOV 30-DEC 03, 1995 CL KIAWAH ISLAND, SC RP Podolsky, DK (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,GASTROINTESTINAL UNIT,32 FRUIT ST,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU I O S PRESS PI AMSTERDAM PA VAN DIEMENSTRAAT 94, 1013 CN AMSTERDAM, NETHERLANDS BN 90-5199-298-X PY 1995 BP 3 EP 10 PG 8 WC Gastroenterology & Hepatology; Immunology; Infectious Diseases; Microbiology SC Gastroenterology & Hepatology; Immunology; Infectious Diseases; Microbiology GA BJ63E UT WOS:A1995BJ63E00001 ER PT B AU Ouellette, AJ AF Ouellette, AJ BE Keusch, GT Kawakami, M TI Paneth cell defensins: Peptide mediators of enteric host defense SO CYTOKINES, CHOLERA, AND THE GUT LA English DT Proceedings Paper CT 1995 Joint Meeting of the United-States/Japan Cooperative Medical Sciences Program Panels on Malnutrition and Cholera CY NOV 30-DEC 03, 1995 CL KIAWAH ISLAND, SC AB Cryptdins are microbicidal peptides of the defensin family that are released by Paneth cells into the lumen of the small intestine. The six known mouse cryptdin peptides have diverse primary structures and 14 additional isoforms of cryptdins 1-3 and 6 are predicted on the basis of cDNA cloning results. In situ hybridization and immunolocalization experiments show that cryptdin expression is specific to Paneth cells in the small intestine, and the peptides have been detected in saline rinses of adult mouse small intestine. Cryptdins 1-6 are coded by separate genes, and certain mouse defensin genes are differentially expressed during development and also along the longitudinal intestinal axis in adults. The mouse cryptdin gene family includes transcription units that utilize the conserved first exons of the defensins but have highly divergent second exons that code for novel cysteine-rich peptides. Cryptdins are potent antimicrobial agents, and they exhibit selective activities against particular target microorganisms. Thus, mouse cryptdins constitute a diverse population of antimicrobial peptides, evidence that Paneth cell secretions contribute to mucosal immunity in the small bowel. RP Ouellette, AJ (reprint author), MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,50 BLOSSOM ST,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU I O S PRESS PI AMSTERDAM PA VAN DIEMENSTRAAT 94, 1013 CN AMSTERDAM, NETHERLANDS BN 90-5199-298-X PY 1995 BP 11 EP 19 PG 9 WC Gastroenterology & Hepatology; Immunology; Infectious Diseases; Microbiology SC Gastroenterology & Hepatology; Immunology; Infectious Diseases; Microbiology GA BJ63E UT WOS:A1995BJ63E00002 ER PT J AU ALTSTIEL, LD LAWLOR, B MOHS, R SCHMEIDLER, J DALTON, A MEHTA, P DAVIS, K AF ALTSTIEL, LD LAWLOR, B MOHS, R SCHMEIDLER, J DALTON, A MEHTA, P DAVIS, K TI ELEVATED ALPHA(1)-ANTICHYMOTRYPSIN SERUM LEVELS IN A SUBSET OF NONDEMENTED FIRST-DEGREE RELATIVES OF ALZHEIMERS-DISEASE PATIENTS SO DEMENTIA LA English DT Article DE ALZHEIMERS-DISEASE; FIRST-DEGREE RELATIVE; ACUTE PHASE REACTANT; ALPHA(1)-ANTICHYMOTRYPSIN ID DOWNS-SYNDROME; ALPHA-1-ANTICHYMOTRYPSIN; PLAQUES; STATE AB A portion of Alzheimer's disease (AD) patients have elevated serum levels of the acute phase reactant a(1)-antichymotrypsin (A1ACT) compared to age-matched controls. We measured serum levels of A1ACT in AD patients, age-matched controls, Down's syndrome patients, and nondemented first-degree relatives of AD patients. Significantly elevated levels of A1ACT were found in both AD patients and first-degree-relatives. In AD patients, serum A1ACT concentrations decreased with increasing severity of cognitive impairment. These results may suggest that inflammatory phenomena may be an early component of AD pathophysiology. C1 BRONX VET ADM MED CTR,PSYCHIAT SERV,NEW YORK,NY. ST JAMES HOSP,DEPT PSYCHIAT TCD,DUBLIN 8,IRELAND. NEW YORK STATE INST BASIC RES DEV DISABIL,STATEN ISL,NY 10314. RP ALTSTIEL, LD (reprint author), CUNY MT SINAI SCH MED,DEPT PSYCHIAT,1 GUSTAVE LEVY PL,NEW YORK,NY 10029, USA. FU NIA NIH HHS [AG-02219, AG-05138]; NIDDK NIH HHS [DK-31775] NR 23 TC 28 Z9 28 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1013-7424 J9 DEMENTIA JI Dementia PD JAN-FEB PY 1995 VL 6 IS 1 BP 17 EP 20 DI 10.1159/000106917 PG 4 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA QF036 UT WOS:A1995QF03600003 PM 7728215 ER PT J AU SHARP, R BABYATSKY, MW TAKAGI, H TAGERUD, S WANG, TC BOCKMAN, DE BRAND, SJ MERLINO, G AF SHARP, R BABYATSKY, MW TAKAGI, H TAGERUD, S WANG, TC BOCKMAN, DE BRAND, SJ MERLINO, G TI TRANSFORMING GROWTH-FACTOR-ALPHA DISRUPTS THE NORMAL PROGRAM OF CELLULAR-DIFFERENTIATION IN THE GASTRIC-MUCOSA OF TRANSGENIC MICE SO DEVELOPMENT LA English DT Article DE TGF-ALPHA; STOMACH; PARIETAL CELL; CHIEF CELL; APOPTOSIS; MENETRIERS DISEASE; ACHLORHYDRIA; IN SITU HYBRIDIZATION; MOUSE ID ACID-SECRETION; MOUSE STOMACH; DEVELOPMENTAL EXPRESSION; MENETRIERS DISEASE; EPITHELIAL-CELLS; PRECURSOR CELLS; FUNDIC MUCOSA; TGF-ALPHA; RAT; PANCREAS AB Transforming growth factor alpha (TGF alpha) evokes diverse responses in transgenic mouse tissues in which it is overexpressed, including the gastric mucosa, which experiences aberrant growth and a coincident repression of hydrochloric acid production. Here we show that ectopically expressed TGF alpha induces an age-dependent cellular reorganization of the transgenic stomach, in which the surface mucous cell population in the gastric pit is greatly expanded at the expense of cells in the glandular base. Immunohistochemical analysis of BrdU incorporation into DNA demonstrated that although mature surface mucous cells were not proliferating, DNA synthesis was enhanced by approximately 67% in the glandular base and isthmus, where progenitor cells reside. RNA blot and in situ hybridization were employed to determine temporal and spatial expression patterns of specific markers representing a variety of exocrine and endocrine gastric cell types. Mature parietal and chief cells mere specifically depleted from the glandular mucosa, as judged by a 6- to 7-fold decrease in the expression of genes encoding H+,K+-ATPase, which is required for acid secretion, and pepsinogen C, respectively. The reduction of these markers coincided in time with the activation of TGF alpha transgene expression in the neonatal stomach. The rate of cell death in the glandular region was not overtly different. Significantly, the loss of parietal and chief cells occurred without a concomitant loss of their respective cellular precursors. In contrast to exocrine cells, D and G endocrine cells were much less severely affected, based on analysis of somatostatin and gastrin expression. Analysis of these dynamic changes indicates that TGF alpha can induce selective alterations in terminal differentiation and proliferation in the gastric mucosa, and suggests that TGF alpha plays an important physiological role in the normal regulation of epithelial cell renewal. C1 NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. MASSACHUSETTS GEN HOSP,DEPT MED,GASTROINTESTINAL UNIT,BOSTON,MA 02114. MED COLL GEORGIA,DEPT CELLULAR BIOL & ANAT,AUGUSTA,GA 30912. NR 49 TC 81 Z9 85 U1 0 U2 0 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 JAN PY 1995 VL 121 IS 1 BP 149 EP 161 PG 13 WC Developmental Biology SC Developmental Biology GA QD185 UT WOS:A1995QD18500014 PM 7867496 ER PT J AU Gerwin, N Jia, GQ Kulbacki, R GutierrezRamos, JC AF Gerwin, N Jia, GQ Kulbacki, R GutierrezRamos, JC TI Interleukin gene expression in mouse preimplantation development SO DEVELOPMENTAL IMMUNOLOGY LA English DT Article DE interleukins; cytokines; preimplantation development ID TRANSFORMING GROWTH-FACTOR; LEUKEMIA INHIBITORY FACTOR; TUMOR-NECROSIS-FACTOR; MATERNAL MESSENGER-RNA; STIMULATORY FACTOR-I; CDNA CLONE; TGF-BETA; CELL DIFFERENTIATION; MONKEY CELLS; EMBRYO AB Control of growth and differentiation during mammalian embryogenesis is regulated by growth factors from embryonic and/or maternal sources. Cytokines are polypeptide growth factors that are released by a variety of activated immune and nonimmune cells. To identify novel members of the cytokine family that could be involved in the growth and differentiation of the preimplantation embryo, we studied the expression pattern of several genes encoding cytokines and their receptors during mouse preimplantation development in vitro. We found that poly(A)(+) mRNAs for IL-1, IL-3, IL-6, IL-7, and TNF alpha are differentially expressed at several stages of mouse preimplantation development, including unfertilized oocytes. Immunostaining of preimplantation embryos using monoclonal antibodies specific for several cytokines and their receptors revealed that at least some of these mRNAs are translated into mature proteins during preimplantation development (IL-1, IL-6, and TNF alpha). Positive staining for IL-1 and IL-6 receptors was also detected at these stages of development. The controlled expression of these ''inflammatory-type'' cytokines and their receptors suggests a role for these growth factors during the early phases of mouse ontogeny. C1 CTR BLOOD RES INC, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DEPT GENET, BOSTON, MA 02115 USA. FU NHLBI NIH HHS [1P01HL 148675-02] NR 64 TC 12 Z9 12 U1 0 U2 0 PU HARWOOD ACAD PUBL GMBH, TAYLOR & FRANCIS GROUP PI PHILADELPHIA PA 325 CHESTNUT ST, 8TH FL, PHILADELPHIA, PA 19106 USA SN 1044-6672 J9 DEV IMMUNOL JI Dev. Immunol. PY 1995 VL 4 IS 3 BP 169 EP + DI 10.1155/1995/26830 PG 0 WC Immunology SC Immunology GA TM195 UT WOS:A1995TM19500002 PM 8770556 ER PT J AU DYER, CA PHILIBOTTE, TM BILLINGSGAGLIARDI, S WOLF, MK AF DYER, CA PHILIBOTTE, TM BILLINGSGAGLIARDI, S WOLF, MK TI CYTOSKELETON IN MYELIN-BASIC-PROTEIN-DEFICIENT SHIVERER OLIGODENDROCYTES SO DEVELOPMENTAL NEUROSCIENCE LA English DT Article DE 2',3'-CYCLIC NUCLEOTIDE 3'-PHOSPHOHYDROLASE; MICROFILAMENTS; MICROTUBULES; MYELIN BASIC PROTEIN; OLIGODENDROCYTE; SHIVERER ID MICROTUBULE STABILITY; REGULATED EFFECTORS; MEMBRANE SHEETS; MOUSE MYELIN; MUTANT MICE; RAT-BRAIN; EXPRESSION; GENE; IDENTIFICATION; CULTURES AB Production of CNS myelin by oligodendrocytes requires the regulated synthesis and assembly of cytoskeletal components. However, the molecular signals that mediate this process are not known. Here we use the shiverer mutant mouse, which is missing a large segment of the myelin basic protein (MBP) gene, to investigate the possible role in cytoskeletal assembly of an MBP gene product or of other myelin components whose expression may be linked to that of MBP. In axon-free cultures, we find that approximately half of shiverer oligodendrocytes have enlarged cell bodies, abnormal processes and fail to elaborate extensive membrane sheets. In those membrane sheets that are elaborated by shiverer oligodendrocytes, microtubular structures are abnormal in size and distribution. Additionally, 2',3'-cyclic nucleotide 3'-phosphohydrolase and microfilaments are not colocalized with microtubular structures as they would be in mature wild-type membrane sheets. These observations suggest that an MBP gene product has a direct or indirect role in regulating various aspects of cytoskeleton assembly in wild-type oligodendrocytes. In the absence of this signal, oligodendrocytes apparently do not normally assemble cytoskeleton; this may be one important basis for the abnormal morphology of intact shiverer CNS. C1 MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. UNIV MASSACHUSETTS,SCH MED,DEPT CELL BIOL,WORCESTER,MA 01655. RP DYER, CA (reprint author), EUNICE KENNEDY SHRIVER CTR MENTAL RETARDAT INC,DEPT BIOMED SCI,200 TRAPELO RD,WALTHAM,MA 02254, USA. FU NINDS NIH HHS [NS-11425] NR 34 TC 41 Z9 42 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-5866 J9 DEV NEUROSCI-BASEL JI Dev. Neurosci. PD JAN-FEB PY 1995 VL 17 IS 1 BP 53 EP 62 DI 10.1159/000111273 PG 10 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA QW336 UT WOS:A1995QW33600006 PM 7542583 ER PT J AU OGAWA, Y NOMA, Y DAVALLI, AM WU, YJ THORENS, B BONNERWEIR, S WEIR, GC AF OGAWA, Y NOMA, Y DAVALLI, AM WU, YJ THORENS, B BONNERWEIR, S WEIR, GC TI LOSS OF GLUCOSE-INDUCED INSULIN-SECRETION AND GLUT2 EXPRESSION IN TRANSPLANTED BETA-CELLS SO DIABETES LA English DT Article ID MOUSE PANCREATIC-ISLETS; DIABETES-MELLITUS; KIDNEY CAPSULE; HYPERGLYCEMIA; DYSFUNCTION; RATS; HUMANS AB Either 200 or 400 syngeneic islets were transplanted under the kidney capsule of normal or streptozocin-induced diabetic B6/AF1 mice, The diabetic mice with 400 islets became normoglycemic, but those with 200 islets, an insufficient number, were still diabetic after the transplantation (Tx), Two weeks after Tx, GLUT2 expression in the islet grafts was evaluated by immunofluorescence and Western blots, and graft function was examined by perfusion of the graft-bearing kidney. Immunofluorescence for GLUT2 was dramatically reduced in the beta-cells of grafts with 200 islets exposed to hyperglycemia. However, it was plentiful in grafts with 400 islets in a normoglycemic environment, Densitometric analysis of Western blots on graft homogenates demonstrated that GLUT2 protein levels in the islets, when exposed to chronic hyperglycemia for 2 weeks, were decreased to 16% of those of normal recipients, Moreover, these grafts had defective glucose-induced insulin secretion, while the effects of arginine were preserved, We conclude that GLUT2 expression in normal beta-cells is promptly downregulated during exposure to hyperglycemia and may contribute to the loss of glucose-induced insulin secretion of diabetes. C1 JOSLIN DIABET CTR,EP JOSLIN LABS,BOSTON,MA 02215. NEW ENGLAND DEACONESS HOSP,DEPT MED,BOSTON,MA. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,BOSTON,MA 02115. SCI INST SAN RAFFAELE,MILAN,ITALY. UNIV LAUSANNE,INST PHARMACOL & TOXICOL,GENEVA,SWITZERLAND. FU NIDDK NIH HHS [DK-35449, DK-36846] NR 23 TC 31 Z9 33 U1 1 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD JAN PY 1995 VL 44 IS 1 BP 75 EP 79 DI 10.2337/diabetes.44.1.75 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PZ998 UT WOS:A1995PZ99800012 PM 7813817 ER PT J AU THIEME, H AIELLO, LP TAKAGI, H FERRARA, N KING, GL AF THIEME, H AIELLO, LP TAKAGI, H FERRARA, N KING, GL TI COMPARATIVE-ANALYSIS OF VASCULAR ENDOTHELIAL GROWTH-FACTOR RECEPTORS ON RETINAL AND AORTIC VASCULAR ENDOTHELIAL-CELLS SO DIABETES LA English DT Article ID PERMEABILITY FACTOR; TYROSINE KINASE; BINDING-SITES; ANGIOGENESIS; IDENTIFICATION; EXPRESSION; PROTEINS; INVIVO AB Ischemic eye disease often results in ocular neovascularization, presumably due to the elaboration of growth factors. Diabetic retinopathy is a classic example in which dramatic retinal neovascularization arises after ischemic retinal damage. The characterization of vascular endothelial growth factor (VEGF) as an angiogenic molecule whose expression is markedly induced by hypoxia makes it a promising candidate for mediating ischemic retinal neovascularization. Thus, we have characterized the structure, binding, and regulation of VEGF receptors in bovine retinal (BREC) and aortic endothelial cells (BAEC). VEGF stimulated a 2.1-fold increase in BREC number and DNA content at 0.6 nmol/l VEGF (P < 1 x 10(-7)). Scatchard binding analysis demonstrated specific high-affinity VEGF receptors on BREC with a K-d of 4.9 +/- 0.6 x 10(-11) mmol/l, similar to that observed for BAEC at 5.1 +/- 0.4 x 10(-11) mmol/l. BREC, however, possess 1.5 x 10(5) high-affinity receptors/cell, threefold more than BAEC (P < 0.003) and more than any cell type reported previously. I-125-VEGF affinity cross-linking revealed complexes at 220 and 170 kDa in BREC, but only a 220-kDa band of lesser intensity in BAEC. Cross-linking was displaceable in a dose-dependent manner by VEGF (P < 0.01) but not by other hormones. Hypoxia increased VEGF receptor number 50% in BREC without altering affinity. Antiphosphotyrosine immunoblotting showed VEGF-stimulated tyrosine autophosphorylation of VEGF receptor bands at 225 and 220 kDa and another band at 80 kDa within 1 min. These findings suggest that VEGF may mediate retinal vascular proliferation through large numbers of high-affinity receptors on retinal vascular endothelial cells and suggest that VEGF may be an important mediator of neovascularization induced by ischemic retinopathies such as diabetes. C1 JOSLIN DIABET CTR,BEETHAM EYE INST,DIV RES,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA. BRIGHAM & WOMENS HOSP,DEPT MED,BOSTON,MA 02115. GENENTECH INC,SAN FRANCISCO,CA 94080. FU NEI NIH HHS [EY-05110]; PHS HHS [36836] NR 29 TC 153 Z9 162 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD JAN PY 1995 VL 44 IS 1 BP 98 EP 103 DI 10.2337/diabetes.44.1.98 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PZ998 UT WOS:A1995PZ99800016 PM 7529203 ER PT J AU DAVALLI, AM OGAWA, Y SCAGLIA, L WU, YJ HOLLISTER, J BONNERWEIR, S WEIR, GC AF DAVALLI, AM OGAWA, Y SCAGLIA, L WU, YJ HOLLISTER, J BONNERWEIR, S WEIR, GC TI FUNCTION, MASS, AND REPLICATION OF PORCINE AND RAT ISLETS TRANSPLANTED INTO DIABETIC NUDE-MICE SO DIABETES LA English DT Article ID INSULIN INDEPENDENCE; PANCREATIC-ISLETS; PURIFIED ISLETS; CELL; IMPLANTATION; LANGERHANS; PIG; NORMOGLYCEMIA; SECRETION; CANINE AB Well-characterized aliquots of adult porcine and rat islets of comparable beta-cell mass were transplanted under the kidney capsule of streptozotocin-induced diabetic nude mice. In both porcine and rat islet grafts, beta-cell mass decreased significantly in the first 2 months and stabilized thereafter. As with beta-cell mass, insulin content decreased significantly in the first 2 months to almost 40% of that originally implanted. In porcine grafts, however, insulin content at 4 months was significantly higher than at 2 months. The endocrine non-beta-cell mass of grafts also decreased significantly after transplantation: in porcine grafts, the decrease was less than in rat and was limited to the first 2 months. beta-cell replication of engrafted islets was significantly lower in porcine than in rat grafts. Although beta-cell mass of porcine and rat grafts was similar at all time periods, recipients of porcine islets required a significantly longer time to reach normal glucose levels; nonetheless, their blood glucose levels continued to decrease and stabilized at levels significantly lower than those of normal mice. During oral and intraperitoneal glucose tolerance tests, blood glucose increased only slightly in both the recipients of porcine and rat grafts. When graft-bearing kidneys were perfused in situ, porcine islet grafts showed a 20-fold increase in insulin release in response to both glucose and arginine. In conclusion, this evidence that adult porcine islet grafts can bring glucose levels to those that are normal for humans provides further support of their potential for human islet replacement therapy. C1 HARVARD UNIV,NEW ENGLAND DEACONESS HOSP,SCH MED,DEPT MED,BOSTON,MA 02215. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT MED,BOSTON,MA 02115. SCI INST SAN RAFFAELE,MILAN,ITALY. RP DAVALLI, AM (reprint author), JOSLIN DIABET CTR,EP JOSLIN LABS,BOSTON,MA 02215, USA. FU NIDDK NIH HHS [DK-35449, DK-36836] NR 39 TC 105 Z9 107 U1 1 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD JAN PY 1995 VL 44 IS 1 BP 104 EP 111 DI 10.2337/diabetes.44.1.104 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PZ998 UT WOS:A1995PZ99800017 PM 7813803 ER PT S AU Tan, KN Akhtar, I AF Tan, KN Akhtar, I BE Baba, S Kaneko, T TI CD4(+) T cell clones that suppress autoimmune diabetes in nonobese diabetic (NOD) mice SO DIABETES 1994 SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT 15th International-Diabetes-Federation Congress CY NOV 06-11, 1994 CL KOBE, JAPAN SP Int Diabet Federat DE autologous mixed lymphocyte reaction; autoreactive T cells; insulin-dependent diabetes mellitus; suppressor factor; T cell receptor; type I diabetes C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL B V PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-81725-5 J9 INT CONGR SER PY 1995 VL 1100 BP 126 EP 132 PG 7 WC Endocrinology & Metabolism; Medicine, General & Internal SC Endocrinology & Metabolism; General & Internal Medicine GA BE46T UT WOS:A1995BE46T00017 ER PT S AU Li, FQ Guo, J Fu, YE Yan, G Faustman, D AF Li, FQ Guo, J Fu, YE Yan, G Faustman, D BE Baba, S Kaneko, T TI MHC class I assembly and peptide presentation defects in the diabetic NOD mouse SO DIABETES 1994 SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT 15th International-Diabetes-Federation Congress CY NOV 06-11, 1994 CL KOBE, JAPAN SP Int Diabet Federat DE cytotoxic T lymphocytes; diabetes-prone mice; Tap-1; Tap-2 C1 MASSACHUSETTS GEN HOSP EAST,IMMUNOBIOL LABS,DIABET UNIT,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL B V PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-81725-5 J9 INT CONGR SER PY 1995 VL 1100 BP 133 EP 141 PG 9 WC Endocrinology & Metabolism; Medicine, General & Internal SC Endocrinology & Metabolism; General & Internal Medicine GA BE46T UT WOS:A1995BE46T00018 ER PT S AU BonnerWeir, S Scaglia, L Montana, E Juang, JH Weir, GC AF BonnerWeir, S Scaglia, L Montana, E Juang, JH Weir, GC BE Baba, S Kaneko, T TI Beta-Cell reserve: Compensatory mechanisms of the beta-cell SO DIABETES 1994 SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT 15th International-Diabetes-Federation Congress CY NOV 06-11, 1994 CL KOBE, JAPAN SP Int Diabet Federat DE beta-cell mass; beta-cell replication; islets of Langerhans C1 BRIGHAM & WOMENS HOSP,JOSLIN DIABET CTR,BOSTON,MA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL B V PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-81725-5 J9 INT CONGR SER PY 1995 VL 1100 BP 179 EP 183 PG 3 WC Endocrinology & Metabolism; Medicine, General & Internal SC Endocrinology & Metabolism; General & Internal Medicine GA BE46T UT WOS:A1995BE46T00027 ER PT S AU LopesVirella, MF Virella, G AF LopesVirella, MF Virella, G BE Baba, S Kaneko, T TI Immune-mediated mechanisms of atherogenesis in diabetes SO DIABETES 1994 SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT 15th International-Diabetes-Federation Congress CY NOV 06-11, 1994 CL KOBE, JAPAN SP Int Diabet Federat DE adhesion molecules; cytokines; endothelial damage; foam cells; glycation; LDL-immune complexes; macrophages; modified lipoproteins; oxidation C1 RALPH H JOHNSON DEPT VET AFFAIRS MED CTR,DIV METAB ENDOCRINOL & NUTR,DEPT MED,CHARLESTON,SC 29403. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL B V PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-81725-5 J9 INT CONGR SER PY 1995 VL 1100 BP 399 EP 405 PG 3 WC Endocrinology & Metabolism; Medicine, General & Internal SC Endocrinology & Metabolism; General & Internal Medicine GA BE46T UT WOS:A1995BE46T00069 ER PT S AU Bursell, SE Eppstein, JA Harrell, JT Krantz, BS Samuels, MA AF Bursell, SE Eppstein, JA Harrell, JT Krantz, BS Samuels, MA BE Baba, S Kaneko, T TI Noninvasive detection of type II diabetes using normalized lens fluorescence measurements SO DIABETES 1994 SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT 15th International-Diabetes-Federation Congress CY NOV 06-11, 1994 CL KOBE, JAPAN SP Int Diabet Federat DE fasting plasma glucose; screening; sensitivity; specificity C1 BEETHAM EYE INST,JOSLIN DIABET CTR,BOSTON,MA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE PUBL B V PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-81725-5 J9 INT CONGR SER PY 1995 VL 1100 BP 603 EP 608 PG 4 WC Endocrinology & Metabolism; Medicine, General & Internal SC Endocrinology & Metabolism; General & Internal Medicine GA BE46T UT WOS:A1995BE46T00107 ER PT S AU Horton, ES AF Horton, ES BE Baba, S Kaneko, T TI The role of physical activity in preventing NIDDM SO DIABETES 1994 SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT 15th International-Diabetes-Federation Congress CY NOV 06-11, 1994 CL KOBE, JAPAN SP Int Diabet Federat C1 HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL B V PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-81725-5 J9 INT CONGR SER PY 1995 VL 1100 BP 770 EP 773 PG 2 WC Endocrinology & Metabolism; Medicine, General & Internal SC Endocrinology & Metabolism; General & Internal Medicine GA BE46T UT WOS:A1995BE46T00138 ER PT J AU KINSLEY, BT WIDOM, B SIMONSON, DC AF KINSLEY, BT WIDOM, B SIMONSON, DC TI DIFFERENTIAL REGULATION OF COUNTERREGULATORY HORMONE-SECRETION AND SYMPTOMS DURING HYPOGLYCEMIA IN IDDM - EFFECT OF GLYCEMIC CONTROL SO DIABETES CARE LA English DT Article ID INSULIN-INDUCED HYPOGLYCEMIA; DEPENDENT DIABETES-MELLITUS; DEFECTIVE GLUCOSE COUNTERREGULATION; GROWTH-HORMONE; PLASMA ADRENOCORTICOTROPIN; SUBSEQUENT HYPOGLYCEMIA; RECURRENT HYPOGLYCEMIA; AUTONOMIC FAILURE; NERVOUS-SYSTEM; GH RESPONSES AB OBJECTIVE - To determine 1) if there was a differential effect of glycemic control on individual counterregulatory hormone responses to hypoglycemia in patients with insulin-dependent diabetes mellitus (IDDM), 2) whether these modifications affect hypoglycemic symptom perception, and 3) if there was a level of glycemic control below which counterregulatory and symptomatic responses to hypoglycemia become consistently altered. RESEARCH DESIGN AND METHODS - We performed hypoglycemic clamp studies on 38 patients with IDDM and 38 healthy control subjects. Glucose was lowered from 5.0 to 2.2 mmol/l over 3 h in decrements of 0.6 mmol/l each 30 min. Epinephrine, cortisol, growth hormone (GH), glucagon, and symptom score were measured at each glucose plateau. RESULTS - In IDDM patients, HbA(1) levels were positively correlated with incremental epinephrine (r = 0.58, P < 0.001) and cortisol (r = 0.52, P < 0.01)responses, but inversely correlated with GH responses (r = -0.31, P < 0.05). The increase in symptom score correlated with the epinephrine response in the IDDM patients (r = 0.57, P < 0.001), but not in the healthy control subjects (r = -0.02, NS). In IDDM patients with HbA(1) less than or equal to 7.8% (n = 7), the epinephrine, cortisol, and symptomatic responses to hypoglycemia were blunted, but GH secretion was preserved. CONCLUSIONS - These data suggest that 1) there is differential regulation of counterregulatory hormone secretion that is dependent on the level of glycemic control, 2) epinephrine is an important determinant of symptom perception in IDDM patients, but not in healthy control subjects, and 3) multiple defects in counterregulatory hormone secretion and symptom perception are consistently observed in patients with HbA, levels less than or equal to 7.8%. C1 JOSLIN DIABET CTR, DEPT MED, BOSTON, MA 02215 USA. NEW ENGLAND DEACONESS HOSP, DEPT MED, BOSTON, MA 02215 USA. BRIGHAM & WOMENS HOSP, DEPT MED, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DEPT MED, BOSTON, MA USA. FU NIDDK NIH HHS [DK-36836] NR 51 TC 19 Z9 19 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD JAN PY 1995 VL 18 IS 1 BP 17 EP 26 DI 10.2337/diacare.18.1.17 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QG882 UT WOS:A1995QG88200003 PM 7698043 ER PT J AU COSIMI, AB AF COSIMI, AB TI FUTURE OF MONOCLONAL-ANTIBODIES IN SOLID-ORGAN TRANSPLANTATION SO DIGESTIVE DISEASES AND SCIENCES LA English DT Review DE MONOCLONAL ANTIBODIES; IMMUNOSUPPRESSION; TOLERANCE; TRANSPLANTATION; RECOMBINANT DNA ID RENAL-ALLOGRAFT RECIPIENTS; CARDIAC ALLOGRAFT; SURVIVAL; THERAPY; REJECTION; TRIAL; INDUCTION; MURINE; ICAM-1; OKT4A AB The ultimate objective of immunosuppressive therapy is to block transplant recipient reactivity to allograft incompatibilities while sparing other responses. Increased clarification of rejection mechanisms has made possible the precise suppression of specific elements of the immune response using murine anti-human monoclonal antibodies. In addition, recombinant DNA technology has made available novel agents including ''humanized,'' bispecific, or toxin-conjugated molecules, which avoid some of the limitations of murine reagents. Using such agents, donor-specific tolerance has been induced in experimental models after a limited course of therapy directed against selected effector cell surface-associated molecules such as CD4, CD25, and CD54. It remains to be determined how such observations can be successfully transferred to the human situation. It seems likely, however, that as new molecular agents are developed, increasingly effective suppression of specific cellular targets will become an essential element of clinical protocols. Such agents may provide long-term immunosuppression with limited periods of immunosuppressive agent administration. C1 HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02114. RP COSIMI, AB (reprint author), MASSACHUSETTS GEN HOSP,DEPT SURG,TRANSPLANTAT UNIT,BOSTON,MA 02114, USA. FU NHLBI NIH HHS [HL-18646] NR 25 TC 4 Z9 6 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD JAN PY 1995 VL 40 IS 1 BP 65 EP 72 DI 10.1007/BF02063943 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QC388 UT WOS:A1995QC38800011 PM 7821121 ER PT B AU TEMIN, HM RUBIN, H AF TEMIN, HM RUBIN, H BE Cooper, GM Temin, RG Sugden, B TI Characteristics of an assay for Rous sarcoma virus and Revs sarcoma cells in tissue culture (Reprinted from Virology, vol 6, pg 669-688, 1958) SO DNA PROVIRUS: HOWARD TEMIN'S SCIENTIFIC LEGACY LA English DT Proceedings Paper CT Howard Temin Commemorative Symposium - DNA Provirus CY OCT 13-15, 1994 CL MADISON, WI C1 HARVARD UNIV,DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVE NW, WASHINGTON, DC 20005-4171 BN 1-55581-098-5 PY 1995 BP 3 EP 24 PG 22 WC Oncology; Genetics & Heredity; Microbiology; Virology SC Oncology; Genetics & Heredity; Microbiology; Virology GA BE26J UT WOS:A1995BE26J00001 ER PT B AU TEMIN, HM AF TEMIN, HM BE Cooper, GM Temin, RG Sugden, B TI Nature of the provirus of Rous sarcoma (Reprinted, 1964) SO DNA PROVIRUS: HOWARD TEMIN'S SCIENTIFIC LEGACY LA English DT Proceedings Paper CT Howard Temin Commemorative Symposium - DNA Provirus CY OCT 13-15, 1994 CL MADISON, WI C1 DANA FARBER CANC INST,DIV MOLEC GENET,BOSTON,MA 02115. NR 0 TC 1 Z9 1 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVE NW, WASHINGTON, DC 20005-4171 BN 1-55581-098-5 PY 1995 BP 25 EP 26 PG 2 WC Oncology; Genetics & Heredity; Microbiology; Virology SC Oncology; Genetics & Heredity; Microbiology; Virology GA BE26J UT WOS:A1995BE26J00002 ER PT B AU COOPER, GM AF COOPER, GM BE Cooper, GM Temin, RG Sugden, B TI On the origin of oncogenes SO DNA PROVIRUS: HOWARD TEMIN'S SCIENTIFIC LEGACY LA English DT Proceedings Paper CT Howard Temin Commemorative Symposium - DNA Provirus CY OCT 13-15, 1994 CL MADISON, WI C1 CHILDRENS HOSP,DANA FARBER CANC INST,DIV MOLEC GENET,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVE NW, WASHINGTON, DC 20005-4171 BN 1-55581-098-5 PY 1995 BP 63 EP 80 PG 18 WC Oncology; Genetics & Heredity; Microbiology; Virology SC Oncology; Genetics & Heredity; Microbiology; Virology GA BE26J UT WOS:A1995BE26J00006 ER PT S AU ROSS, SR GRAVES, RA CHOY, L SOLEVEVA, V SPIEGELMAN, BM AF ROSS, SR GRAVES, RA CHOY, L SOLEVEVA, V SPIEGELMAN, BM BE Chambers, DA TI TRANSGENIC MOUSE MODELS OF DISEASE - ALTERING ADIPOSE-TISSUE FUNCTION IN-VIVO SO DNA: THE DOUBLE HELIX: PERSPECTIVE AND PROSPECTIVE AT FORTY YEARS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on DNA: The Double Helix - Forty Years, Perspective and Prospective CY OCT 13-16, 1993 CL CHICAGO, IL SP New York Acad Sci, Univ Illinois Chicago, Green Coll, Univ Oxford ID BETA-GLOBIN GENE; BINDING-PROTEIN; REGIONAL DIFFERENCES; THYMIDINE KINASE; MICRO-INJECTION; FUSION GENE; GERM-LINE; FAT-CELLS; EXPRESSION; OBESITY C1 UNIV ILLINOIS,SCH MED,DEPT BIOCHEM MC536,CHICAGO,IL 60612. UNIV CHICAGO,DEPT MED,GASTROENTEROL SECT,CHICAGO,IL 60637. HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 01225. DANA FARBER CANC INST,BOSTON,MA 01225. NR 55 TC 0 Z9 0 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 SN 0077-8923 BN 0-89766-906-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1995 VL 758 BP 297 EP 313 DI 10.1111/j.1749-6632.1995.tb24835.x PG 17 WC Biochemistry & Molecular Biology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Science & Technology - Other Topics GA BD16X UT WOS:A1995BD16X00029 PM 7625699 ER PT J AU RODRIGUEZ, A POWER, WJ NEVES, RA FOSTER, CS AF RODRIGUEZ, A POWER, WJ NEVES, RA FOSTER, CS TI RECURRENCE RATE OF HERPETIC UVEITIS IN PATIENTS ON LONG-TERM ORAL ACYCLOVIR SO DOCUMENTA OPHTHALMOLOGICA LA English DT Article DE ACYCLOVIR; HERPETIC UVEITIS; HERPES SIMPLEX VIRUS ID KERATOUVEITIS; KERATITIS AB We examined the recurrence rate of herpetic uveitis (HU) in 13 patients (group A) treated prophylactically with long-term systemic acyclovir (600-800 mg/day) and compared it with that of 7 patients with no prophylactic therapy (group B). HU was diagnosed on the basis of a history of dendritic or disciform keratitis accompanied by iridocyclitis and iris atrophy. The study population consisted of 12 men and 8 women with a mean age at onset of uveitis of 52.9 years (range 19-78 years). All patients were followed for at least 8 months. The mean follow-up time of patients on long-term oral acyclovir was 26.0 months. In this group, only one patient experienced a single recurrent episode of uveitis while on 600-800 mg/day of acyclovir therapy; two additional patients had recurrence of HU within 16.2 months after the acyclovir dose was tapered below 600 mg/day. In striking contrast, 16 recurrences occurred in the 7 patients of group B (p < 0.05). Of these, the initial recurrence occurred within an average of 4.3 months following cessation of therapy. There was a significant difference (p < 0.05) in the mean recurrence-free interval between patients in group A (24.6 months) and those in group B (3.4 months). Herpetic uveitis is a serious ocular disease in which recurrence of inflammation results in severe ocular complications. The long-term use of oral acyclovir may be of benefit in the prevention of recurrences, and hence may reduce the blinding complications of this disease. Efforts at completing a randomized, placebo-controlled trial on this matter by the Herpes Epithelial Disease Study Group were unsuccessful due to insufficient patient recruitment. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,IMMUNOL & UVEITIS SERV,BOSTON,MA 02114. NR 23 TC 14 Z9 14 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0012-4486 J9 DOC OPHTHALMOL JI Doc. Ophthalmol. PY 1995 VL 90 IS 4 BP 331 EP 340 DI 10.1007/BF01268121 PG 10 WC Ophthalmology SC Ophthalmology GA TG630 UT WOS:A1995TG63000002 PM 8620818 ER PT J AU DAVIS, KL YANG, RK DAVIDSON, M MOHS, RC RYAN, TM SCHMEIDLER, J KNOTT, PJ THAL, LJ GAMZU, ER AF DAVIS, KL YANG, RK DAVIDSON, M MOHS, RC RYAN, TM SCHMEIDLER, J KNOTT, PJ THAL, LJ GAMZU, ER TI ALZHEIMERS-DISEASE - TACRINE AND TACRINE METABOLITE CONCENTRATIONS IN PLASMA AND COGNITIVE CHANGE SO DRUG DEVELOPMENT RESEARCH LA English DT Article DE ALZHEIMERS DISEASE; TACRINE; TACRINE METABOLITES; COGNITIVE IMPROVEMENT ID PERFORMANCE LIQUID-CHROMATOGRAPHY; DOUBLE-BLIND; HUMAN-SERUM; PHARMACOKINETICS; HYDROCHLORIDE; MEMORY; TETRAHYDROAMINOACRIDINE; LECITHIN; DEMENTIA; 9-AMINO-1,2,3,4-TETRAHYDROACRIDINE AB In a clinical trial of tacrine in patients with Alzheimer's disease, improvement, measured by changes on both total (ADAST) and the cognitive sub-component (ADASC) of the Alzheimer's Disease Assessment Scale (ADAS) over a 6-week period, correlated significantly with plasma levels of tacrine. Change on the ADAS (both total and the cognitive subcomponent) also correlated significantly with three monohydroxylated metabolites of tacrine 1,hydroxy-tacrine (1-OH-THA), 2,hydroxy-tacrine (2-OH-THA), and 4,hydroxy-tacrine (4-OH-THA). However, changes of the relatively small non-cognitive component of the ADAS were not significantly correlated with plasma levels of tacrine. Multiple correlational analysis revealed that the combined influences of these metabolites were no greater than the effects of tacrine alone in ameliorating the symptoms of Alzheimer's disease. An alternative measure of cognitive performance, the Mini Mental State Exam (MMSE) did not correlate significantly with plasma concentrations of tacrine or its metabolites. Tacrine and these metabolites are bound to plasma proteins. In 10 patients with Alzheimer's disease receiving tacrine, the percentage of tacrine, 1-OH-THA, 2-OH-THA, and 4-OH-THA, that was free in plasma was found to be 19.7 +/- 3.3, 51.3 +/- 7.7, 40.7 +/- 6.9, and 42.4 +/- 6.3 (mean +/- SD), respectively. (C) 1995 Wiley-Liss, Inc. C1 CUNY MT SINAI SCH MED,DEPT PSYCHIAT,NEW YORK,NY 10029. CUNY MT SINAI SCH MED,DEPT PHARMACOL,NEW YORK,NY 10029. CUNY MT SINAI SCH MED,DEPT NEUROBIOL,NEW YORK,NY 10029. BRONX VET ADM MED CTR,DIV PSYCHIAT,BRONX,NY. UNIV CALIF SAN DIEGO,DEPT NEUROSCI,SAN DIEGO,CA 92103. CAMBRIDGE NEUROSCI INC,CAMBRIDGE,MA. NR 35 TC 3 Z9 3 U1 1 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0272-4391 J9 DRUG DEVELOP RES JI Drug Dev. Res. PD JAN PY 1995 VL 34 IS 1 BP 55 EP 65 DI 10.1002/ddr.430340109 PG 11 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QH392 UT WOS:A1995QH39200008 ER PT B AU FREEDMAN, R LEONARD, S ADLER, L BICKFORD, P BYERLEY, W COON, H MILLER, C LUNTZLEYBMAN, V MYLESWORSLEY, M NAGAMOTO, H ROSE, G STEVENS, K WALDO, M AF FREEDMAN, R LEONARD, S ADLER, L BICKFORD, P BYERLEY, W COON, H MILLER, C LUNTZLEYBMAN, V MYLESWORSLEY, M NAGAMOTO, H ROSE, G STEVENS, K WALDO, M BE Clarke, PBS Quik, M Adlkofer, F Thurau, K TI Nicotinic receptors and the pathophysiology of schizophrenia SO EFFECTS OF NICOTINE ON BIOLOGICAL SYSTEMS II SE ADVANCES IN PHARMACOLOGICAL SCIENCES LA English DT Proceedings Paper CT Satellite Symposium on The Effects of Nicotine on Biological Systems II, at the Congress of the International-Union-of-Pharmacology CY JUL 21-24, 1994 CL SAINTE ADELE, CANADA SP INT UNION PHARM, VERUM FDN RP DENVER VAMC,DEPT PSYCHIAT,DENVER,CO 80262, USA. RI Bickford, Paula/J-5970-2012 OI Bickford, Paula/0000-0001-9657-7725 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIRKHAUSER VERLAG PI BASEL PA PO BOX 133, CH-4010 BASEL, SWITZERLAND BN 3-7643-5083-0 J9 ADV PHAR SC PY 1995 BP 307 EP 312 PG 6 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA BC71W UT WOS:A1995BC71W00040 ER PT J AU GWOSDOW, AR AF GWOSDOW, AR TI MECHANISMS OF INTERLEUKIN-1-INDUCED HORMONE-SECRETION FROM THE RAT ADRENAL-GLAND SO ENDOCRINE RESEARCH LA English DT Article; Proceedings Paper CT 6th Conference on the Adrenal Cortex CY JUN 21-24, 1994 CL ARDMORE, OK ID CORTICOTROPIN-RELEASING FACTOR; CHROMAFFIN CELLS; STIMULATION; CORTEX AB The aim of these studies was to determine the intraadrenal mechanism of interleukin-1 (IL-1)-induced corticosterone release from the rat adrenal gland. To accomplish this, the role of catecholamines and eicosanoids on IL-1-induced corticosterone release was determined. Experiments were conducted on primary cultures of dispersed rat adrenal cells. Dose-dependent increases (P<0.05) in corticosterone concentration were observed when primary adrenal cells were incubated with different doses (10(-10) to 10(-8) M) of IL-1 alpha. IL-1 alpha and IL-1 beta elevated corticosterone release after a 24 hr incubation period. ACTH elevated corticosterone levels at 4 and 24 hr. The stimulatory effect of IL-1 on corticosterone release was mimicked by epinephrine (1 mu M), and was selectively blocked by the alpha-adrenergic antagonist, phentolamine (10 mu M). The beta-adrenergic antagonist, propranolol (10 mu M), did not change IL-1 induced corticosterone release. Neither phentolamine nor propranolol had an effect on ACTH stimulated corticosterone release. Both IL-1 alpha and IL-1 beta significantly elevated (P<0.05) epinephrine levels after a 24 hr incubation period compared to media-treated controls. Untreated adrenal cells fixed for immunohistochemical staining with a specific anti-rat tyrosine hydroxylase antibody indicate that the primary adrenal cell preparation contained 3.1 +/- 0.45% tyrosine hydroxylase positive cells. On the ultrastructural level, the chromaffin cells were found to be in direct cellular contact with cortical cells. Although IL-1 alpha significantly increased (P<0.05) prostaglandin E(2) (PGE(2)) levels from primary adrenal cells, the presence of the cyclooxygenase inhibitor, indomethacin (10 mu M) significantly inhibited IL-1 alpha-induced PGE(2) secretion without altering the effect of IL-1 alpha on corticosterone release. Inhibitors of the lipoxygenase system (5-lipoxygenase, 10 mu M) and the lipoxygenase and cytochrome P450 monooxygenase systems (nordihydroguaiaretic acid, 10 mu M) did not effect IL-1 alpha-induced corticosterone or PGE(2) release. These observations indicate that IL-1 stimulates the local release of catecholamines, which, in turn, stimulates corticosterone release through an alpha-adrenergic receptor; this mechanism is independent of PGE(2). RP GWOSDOW, AR (reprint author), MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BULFINCH 3,FRUIT ST,BOSTON,MA 02114, USA. FU NIDDK NIH HHS [DK41419] NR 13 TC 13 Z9 13 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 0743-5800 J9 ENDOCR RES JI Endocr. Res. PY 1995 VL 21 IS 1-2 BP 25 EP 37 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QZ872 UT WOS:A1995QZ87200005 PM 7588387 ER PT J AU UDDIN, S KIRSTEINS, L LAPAGLIA, N EMANUELE, NV LAWRENCE, AM KELLEY, MR EMANUELE, MA AF UDDIN, S KIRSTEINS, L LAPAGLIA, N EMANUELE, NV LAWRENCE, AM KELLEY, MR EMANUELE, MA TI FAILURE OF ETHANOL METABOLITES TO ALTER GONADOTROPIN-SECRETION OR LUTEINIZING-HORMONE SYNTHESIS IN-VITRO SO ENDOCRINE RESEARCH LA English DT Article ID PITUITARY-GONADAL AXIS; TESTOSTERONE SYNTHESIS; FEMALE RATS; CELLS; RELEASE; TRANSCRIPTION; ACETALDEHYDE; INHIBITION; ALCOHOL; LEVEL AB The impact of ethanol on the male reproductive axis are multiple and varied, with both gonadal and control hypothalamic-pituitary pertubations being reported. There appears to be a discrepancy, however, between the in vivo and in vitro effects of ethanol on hypothalamic luteinizing hormones releasing hormone (LHRH) and the pituitary gonadotropins luteinizing hormone (LH) and follicle stimulating hormone(FSH). While in vivo data suggests a decrease in LHRH release after EtOH, in vitro studies find no effect on secretion. Similarity, in vivo acute EtOH profoundly diminishes LH synthesis and secretion, while in vitro impaired release with no alteration in the transcription of beta LH has been found. A potential exploration for these discrept results could be the in vivo metabolism of EtOH into acetaldehyde and acetate, or the subsequent formation of salsolinol, a product of acetate combining with dopamine. To test this possibility, a series of in vitro experiments were conducted exposing dispensed anterior pituitary cells from male rats to different doses of acetaldehyde, acetate or salsolinol for varying amounts of time for which gonadotropin secretion and beta LH mRNA levels were assessed. The results demonstrated no effect of either acetaldehyde or acetate on basal or LHRH stimulated LH release, FSH release or steady-state beta LH mRNA levels. These data suggest that the metabolites of EtOH, which occur in vivo but not in vitro, are not responsible for the discrepant gonadotropin changes reported between the in vivo and in vitro setting. Other potential mechanisms to explain this phenomenon include differences in the molarity of EtOH, hyperprolactinemia and suprapituitary influences including hypothalamic LHRH, catecholamines, excitatory amino acids, substance P and beta endorphin. C1 LOYOLA UNIV,STRITCH SCH MED,PROGRAM MOLEC BIOL,MAYWOOD,IL 60153. US DEPT VET AFFAIRS,VET AFFAIRS EDWARD HINES JR HOSP,RES SERV,HINES,IL 60141. US DEPT VET AFFAIRS,VET AFFAIRS EDWARD HINES JR HOSP,MED SERV,HINES,IL 60141. INDIANA UNIV,SCH MED,DEPT PEDIAT,PEDIAT ENDOCRINOL SECT,INDIANAPOLIS,IN 46202. INDIANA UNIV,SCH MED,DEPT BIOCHEM & MOLEC BIOL,INDIANAPOLIS,IN 46202. RP UDDIN, S (reprint author), LOYOLA UNIV,STRITCH SCH MED,DEPT MED,MAYWOOD,IL 60153, USA. FU NIAAA NIH HHS [5 R01 AA08661-05]; PHS HHS [2 R01 A067555-08] NR 36 TC 2 Z9 2 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 0743-5800 J9 ENDOCR RES JI Endocr. Res. PY 1995 VL 21 IS 3 BP 653 EP 670 PG 18 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RT309 UT WOS:A1995RT30900012 PM 7588434 ER PT J AU WEISS, J COTE, CR JAMESON, JL CROWLEY, WF AF WEISS, J COTE, CR JAMESON, JL CROWLEY, WF TI HOMOLOGOUS DESENSITIZATION OF GONADOTROPIN-RELEASING-HORMONE (GNRH)-STIMULATED LUTEINIZING-HORMONE SECRETION IN-VITRO OCCURS WITHIN THE DURATION OF AN ENDOGENOUS GNRH PULSE SO ENDOCRINOLOGY LA English DT Article ID FOLLICLE-STIMULATING-HORMONE; PITUITARY-CELLS; RAT PITUITARY; RESPONSES; INTACT; LH AB A pulsatile GnRH signal is required for the maintenance of LH and FSH secretion. Studies in animals and in perifused pituitary cells have shown that continuous exposure to GnRH leads to decreased gonadotropin secretion and a blunted secretory response to subsequent pulses of GnRH, a process referred to as homologous desensitization. In the current study, we demonstrate that the duration of continuous GnRH exposure required to desensitize the gonadotrope in vitro is less than the durations of most in. vivo GnRH pulses. Perifused male rat pituitary cells were tested with 20-sec pulses of 100 nM GnRH at 5-min intervals before, immediately upon termination of, and after GnRH infusions of varying concentration and duration. Desensitization in response to a GnRH infusion was calculated as the decrease in the LH response to the pulse of GnRH immediately after the infusion (Dsn pulse) compared to the mean LH response to GnRH pulses before and after the infusion. Gonadotropes were completely desensitized after a 2-min infusion of 10 rud GnRH (P < 0.05), the shortest duration tested. Endogenous GnRH pulses, by contrast, average more than 5 min in length. When the duration of GnRH infusion was held constant at 4 min, a concentration response for GnRH-induced desensitization was observed. Gonadotropes were desensitized by GnRH concentrations as low as 1 nM (P < 0.05), and maximal desensitization was observed with 5 nM GnRH. To determine the recovery period for GnRH-induced desensitization, a second series of experiments was performed. Experiments were conducted as described above, except the cells were perifused with medium that did not contain GnRH (recovery) for varying periods between the GnRH infusion and the Dsn pulse. A small response (16% of control) to the Dsn pulse of GnRH was observed after 1 min of recovery, and the response was not different from the control value (P > 0.05) after a S-min recovery period. This recovery period is consistent with the ability to respond to endogenous GnRH pulses, which rarely exceed two per h. We conclude that GnRH-induced secretory desensitization and recovery occur within endogenous GnRH pulse durations and interpulse intervals, respectively. These data raise the possibility that homologous desensitization occurs under some in vivo conditions, providing an unexpected mechanism for physiological regulation of gonadotropin secretion. C1 MASSACHUSETTS GEN HOSP, REPROD ENDOCRINE UNIT, BOSTON, MA 02114 USA. RP WEISS, J (reprint author), NORTHWESTERN UNIV, CTR ENDOCRINOL METAB & MOLEC MED, S217, 303 E CHICAGO AVE, CHICAGO, IL 60611 USA. OI Jameson, James/0000-0001-9538-4059 FU NICHD NIH HHS [R01 HD015788, T32 HD007396, U54-HD-29164, P30-HD-28138] NR 19 TC 37 Z9 37 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD JAN PY 1995 VL 136 IS 1 BP 138 EP 143 DI 10.1210/en.136.1.138 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QD584 UT WOS:A1995QD58400019 PM 7828524 ER PT J AU Klitzman, D Almenoff, PL Cardozo, C Lesser, M AF Klitzman, D Almenoff, PL Cardozo, C Lesser, M TI Bradykinin-induced airway microvascular leakage is potentiated by enalaprilat but not by phosphoramidon SO ENZYME & PROTEIN LA English DT Article DE endopeptidase 24.11; neutral endopeptidase; angiotensin-converting enzyme; bradykinin; phosphoramidon; enalaprilat; microvascular permeability ID PLATELET-ACTIVATING-FACTOR; GUINEA-PIG AIRWAYS; PLASMA EXUDATION; INDUCED BRONCHOCONSTRICTION; NEUTRAL ENDOPEPTIDASE; PULMONARY CIRCULATION; SUBSTANCE-P; HUMAN-LUNG; HISTAMINE; ASTHMA AB The objective of the study was to determine if bradykinin-induced airway microvascular leakage in rats was altered by pretreatment of animals with enalaprilat, an inhibitor of angiotensin-converting enzyme (ACE), or phosphoramidon, an inhibitor of endopeptidase 24.11 (EP 24.11). We found that the intravascular infusion of bradykinin induced microvascular leakage of Evans blue dye in tracheal tissue (0.088+/-0.035 mu g/mg tissue) that was significantly amplified by pretreatment with 3.27 mM enalaprilat (0.458+/-0.226 mu g/mg tissue), but not by pretreatment with 10 mM phosphoramidon (0.082+/-0.0453 mu g/mg tissue). Leakage in carinal tissue was also amplified by pretreatment with 3.27 mM enalaprilat (0.205+/-0.050 vs. 0.036+/-0.006 mu g/mg tissue for bradykinin alone), whereas no amplification was observed in parenchymal tissue by pretreatment with either inhibitor. These findings indicate that in the rat, ACE, but not EP 24.11, modulates bradykinin-induced airway microvascular leakage following intravascular infusion of these agents. C1 BRONX VET AFFAIRS MED CTR,PULM SECT,BRONX,NY 10468. MT SINAI SCH MED,DEPT MED,NEW YORK,NY. MT SINAI SCH MED,DEPT PHARMACOL,NEW YORK,NY. NR 37 TC 2 Z9 2 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1019-6773 J9 ENZYME PROTEIN JI Enzyme Protein PY 1995 VL 48 IS 4 BP 191 EP 196 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TU473 UT WOS:A1995TU47300001 ER PT J AU SWARTZ, BE HALGREN, E KRISTAKUMDORN, T DAIMES, R AF SWARTZ, BE HALGREN, E KRISTAKUMDORN, T DAIMES, R TI LATERALIZATION OF FUNCTION DURING THE INTRACAROTID AMYTAL TEST (IAP) - TEMPORAL-LOBE EPILEPSY (TLE) SO EPILEPSIA LA English DT Meeting Abstract C1 UNIV CALIF LOS ANGELES,W LOS ANGELES VET ADM MED CTR,LOS ANGELES,CA 90024. SANTA MONICA HOSP MED CTR,CAL CEP & NEUROEPILEPSY PROGRAM,SANTA MONICA,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 0013-9580 J9 EPILEPSIA JI Epilepsia PY 1995 VL 36 SU 4 BP 127 EP 127 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA TD347 UT WOS:A1995TD34700038 ER PT J AU OAS, KH AF OAS, KH TI PRESURGICAL VOCATIONAL STATUS AS AN INDICATOR OF POSTSURGICAL VOCATIONAL OUTCOME SO EPILEPSIA LA English DT Meeting Abstract C1 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 0013-9580 J9 EPILEPSIA JI Epilepsia PY 1995 VL 36 SU 4 BP 415 EP 415 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA TD347 UT WOS:A1995TD34700388 ER PT J AU LICHT, EA SANKAR, R GEE, M MASON, BA AF LICHT, EA SANKAR, R GEE, M MASON, BA TI PREGNANCIES OF WOMEN WITH EPILEPSY - A SURVEY OF PHYSICIAN PRACTICE PATTERNS SO EPILEPSIA LA English DT Meeting Abstract C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT PEDIAT,DIV PEDIAT NEUROL,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,DEPT NEUROL,EPILEPSY UNIT,LOS ANGELES,CA 90073. WAYNE STATE UNIV,DEPT OBSTET & GYNECOL,DETROIT,MI. 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 0013-9580 J9 EPILEPSIA JI Epilepsia PY 1995 VL 36 SU 4 BP 616 EP 616 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA TD347 UT WOS:A1995TD34700611 ER PT J AU COLE, AJ JIANG, H BUCHBINDER, BR COSGROVE, GR AF COLE, AJ JIANG, H BUCHBINDER, BR COSGROVE, GR TI 3-D VOLUMETRIC MR-IMAGING OF DEVELOPMENTAL MIGRATIONAL ABNORMALITIES - ROLE IN PREMORBID PATHOLOGICAL DIAGNOSIS AND CLASSIFICATION SO EPILEPSIA LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,CTR EPILEPSY,NEUROL SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CTR EPILEPSY,NEUROSURG SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CTR EPILEPSY,SERV NEURORADIOL,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 0013-9580 J9 EPILEPSIA JI Epilepsia PY 1995 VL 36 SU 4 BP 679 EP 679 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA TD347 UT WOS:A1995TD34700674 ER PT J AU COSGROVE, GR BUCHBINDER, BR JIANG, H COLE, A ROSEN, BR AF COSGROVE, GR BUCHBINDER, BR JIANG, H COLE, A ROSEN, BR TI MAPPING HUMAN SENSORIMOTOR CORTEX WITH FUNCTIONAL MRI SO EPILEPSIA LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,MGH,CTR EPILEPSY,DEPT NEUROL,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROSURG,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIOL,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 0013-9580 J9 EPILEPSIA JI Epilepsia PY 1995 VL 36 SU 4 BP A3 EP A3 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA TD347 UT WOS:A1995TD34700088 ER PT J AU OHARA, K CHIN, M COOKE, C HYNEMAN, A AF OHARA, K CHIN, M COOKE, C HYNEMAN, A TI SEIZURE PRECAUTIONS - A NEW LOOK SO EPILEPSIA LA English DT Meeting Abstract C1 VET AFFAIRS MED CTR,PHILADELPHIA,PA. COLL PHARM & SCI,PHILADELPHIA,PA. 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 0013-9580 J9 EPILEPSIA JI Epilepsia PY 1995 VL 36 SU 4 BP H6 EP H6 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA TD347 UT WOS:A1995TD34700367 ER PT J AU HILL, RA CHIAPPA, KH JENKINS, BG HUANGHELLINGER, F AF HILL, RA CHIAPPA, KH JENKINS, BG HUANGHELLINGER, F TI FUNCTIONAL MAGNETIC-RESONANCE-IMAGING AND SPECTROSCOPY IN PRIMARY GENERALIZED EPILEPSY WITH AND WITHOUT PHOTOSENSITIVITY SO EPILEPSIA LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. 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 0013-9580 J9 EPILEPSIA JI Epilepsia PY 1995 VL 36 SU 3 BP S212 EP S212 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA RQ685 UT WOS:A1995RQ68501032 ER PT J AU POHLMANNEDEN, B HOCH, D COCHIUS, J CHIAPPA, K AF POHLMANNEDEN, B HOCH, D COCHIUS, J CHIAPPA, K TI SIGNIFICANCE OF SUBCLINICAL EPILEPTIFORM PROCESSES AFTER STROKE - RESULTS OF A PRELIMINARY PROSPECTIVE-STUDY SO EPILEPSIA LA English DT Meeting Abstract C1 UNIV HEIDELBERG,MANNHEIM HOSP,DEPT NEUROL,W-6800 MANNHEIM,GERMANY. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROL,BOSTON,MA 02114. NR 0 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 1995 VL 36 SU 3 BP S88 EP S88 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA RQ685 UT WOS:A1995RQ68500421 ER PT J AU Compton, CC Press, W Gill, JM Bantick, G Nadire, KB Warland, G Fallon, JT Vamvakas, EC AF Compton, CC Press, W Gill, JM Bantick, G Nadire, KB Warland, G Fallon, JT Vamvakas, EC TI The generation of anchoring fibrils by epidermal keratinocytes: A quantitative long-term study SO EPITHELIAL CELL BIOLOGY LA English DT Article DE anchoring fibrils; basement membrane zone; morphometry; type VII collagen; wound healing ID DYSTROPHIC EPIDERMOLYSIS BULLOSA; CULTURED EPITHELIAL AUTOGRAFTS; VII COLLAGEN; BASEMENT-MEMBRANE; BURN WOUNDS; COMPONENTS; JUNCTION; SKIN; ONTOGENY; GROWTH AB Anchoring fibrils (AFs) are derived from basal keratinocytes, but the kinetics of their formation is unknown, In this study, de novo generation of AFs by cultured human keratinocyte autografts was assessed from 1 week to 6 years postgrafting. Within 2 weeks, AF population densities were equal to those of normal controls and remained normal thereafter. However, AF diameters were narrow compared to controls (P < 0.05) until 3 years postgrafting. The depth of extension of AF-anchoring plaque lattices into the subjacent stroma was normal by 3 weeks but, after 1 month, was typically 1.5- to 2-fold greater than normal. The findings indicate that: (1) basal keratinocytes immediately re-establish a full complement of AFs; (2) once reformed, AF populations remain normal in density over time; (3) nascent AFs are thin and require several years to reach full maturity; and (4) abnormally thick AF lattices may form over time in healed wounds. C1 SHRINERS HOSP CRIPPLED CHILDREN,DEPT PATHOL,BURNS INST,BOSTON UNIT,BOSTON,MA. RP Compton, CC (reprint author), MASSACHUSETTS GEN HOSP,DEPT PATHOL,15 FRUIT ST,BOSTON,MA 02114, USA. FU NIGMS NIH HHS [R01-GM35242] NR 35 TC 1 Z9 2 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0940-9912 J9 EPITHELIAL CELL BIOL JI Epithelial Cell Biol. PY 1995 VL 4 IS 3 BP 93 EP 103 PG 11 WC Cell Biology SC Cell Biology GA VW705 UT WOS:A1995VW70500001 PM 8971484 ER PT J AU CASTRESANA, JS RUBIO, MP GOMEZ, L KREICBERGS, A ZETTERBERG, A BARRIOS, C AF CASTRESANA, JS RUBIO, MP GOMEZ, L KREICBERGS, A ZETTERBERG, A BARRIOS, C TI DETECTION OF TP53 GENE-MUTATIONS IN HUMAN SARCOMAS SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE TUMOR SUPPRESSOR GENE; TP53; POINT MUTATION; SARCOMAS; PCR-SSCP; DIRECT SEQUENCING ID SOFT-TISSUE SARCOMAS; P53 GENE; BREAST-CANCER; ABNORMALITIES; MECHANISMS; DNA; POLYMORPHISMS; CARCINOMAS; SPECTRUM; LINE AB To determine the frequency and type of TP53 mutations in human sarcomas, we examined exons 5-8 of the TP53 gene in 48 sarcomas using single-strand conformation polymorphism (SSCP) analysis and direct sequencing. Nine tumours had mobility-shifts on SSCP analysis, and sequencing of six of these tumours revealed 10 mutations: one insertion, two deletions and seven point mutations (four transitions and three transversions). Four of these mutations resulted in frame-shifts, one in a truncated protein, four cases in mono-allelic point mutations and one case in an altered splice site. These data show that approximately 20% of sarcomas harbour TP53 gene alterations and illustrate a variety of TP53 gene mutation types. C1 MASSACHUSETTS GEN HOSP,MOLEC NEUROONCOL LAB,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,NEUROSURG SERV,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02129. KAROLINSKA HOSP,DEPT TUMOUR PATHOL,S-10401 STOCKHOLM,SWEDEN. KAROLINSKA INST,DEPT TUMOUR PATHOL,S-10401 STOCKHOLM,SWEDEN. KAROLINSKA INST,DEPT ORTHOPAED,S-10401 STOCKHOLM,SWEDEN. KAROLINSKA HOSP,DEPT ORTHOPAED,S-10401 STOCKHOLM,SWEDEN. UNIV VALENCIA,SCH MED,DEPT SURG,INST ORTHOPAED & TRAUMA,E-46010 VALENCIA,SPAIN. RP CASTRESANA, JS (reprint author), CSIC,INST INVEST BIOMED,ARTURO DUPERIER 4,E-28029 MADRID,SPAIN. RI Rubio, Mari-Paz/K-4364-2014; OI Rubio, Mari-Paz/0000-0003-3963-5903; Castresana, Javier S./0000-0002-2373-482X NR 29 TC 27 Z9 30 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PY 1995 VL 31A IS 5 BP 735 EP 738 DI 10.1016/0959-8049(95)00121-X PG 4 WC Oncology SC Oncology GA RF159 UT WOS:A1995RF15900019 PM 7640047 ER PT J AU MARSCHANG, P SODROSKI, J WURZNER, R DIERICH, MP AF MARSCHANG, P SODROSKI, J WURZNER, R DIERICH, MP TI DECAY-ACCELERATING FACTOR (CD55) PROTECTS HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 FROM INACTIVATION BY HUMAN-COMPLEMENT SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE HUMAN IMMUNODEFICIENCY VIRUS TYPE 1; DECAY-ACCELERATING FACTOR; COMPLEMENT; HOST CELL PROTEINS ID PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA; MEMBRANE-ATTACK-COMPLEX; RNA TUMOR-VIRUSES; HUMAN-SERUM; INFECTED-CELLS; TRANSMEMBRANE CHANNELS; HOMOLOGOUS COMPLEMENT; HUMAN-ERYTHROCYTES; HTLV-III; SYSTEM AB HIV-1, in contrast to animal retroviruses; is not lysed by human complement, but is readily inactivated by the sera from different animal species. To identify a possible species-specific protection mechanism, HIV-1 was expressed in cells of non-human origin. Recombinant HIV-1 virions that could encode the chloramphenicol acetyltransferase (CAT) protein were produced in African green monkey COS-1 cells, mink cells and, as a control, in human HEp-2 cells and were then used to infect CD4-positive target cells. Analysis of the CAT activity of the target cells revealed that fresh HIV-l-negative human serum reduced the infectivity of HIV-1 derived from monkey and mink cells five- to tenfold, but had no effect on HIV-1 produced in human cells. In addition, human serum efficiently lysed HIV-1 produced in non-human cells in contrast to HIV-1 originating from human cells, suggesting lysis as an important mechanism of virus inactivation. Mammalian cells are protected against lysis by homologous complement by membrane-bound regulatory molecules. Two of these complement inhibitors, namely decay-accelerating factor (DAF) and, to a lesser extent, CD59 were found on the surface of HIV-1 virions by means of a virus capture assay. Antibodies against DAF, but not against other host cell molecules found on the viral surface, efficiently blocked the resistance of HIV-1 produced in human cells to human complement. These results suggest that the acquisition of DAF during the budding process from human cells protects HIV-1 in a species-specific way against the attack of human complement. C1 UNIV INNSBRUCK, INST HYG, A-6020 INNSBRUCK, AUSTRIA. HARVARD UNIV, SCH MED, DANA FARBER CANC INST, DIV HUMAN RETROVIROL, BOSTON, MA USA. FU NIAID NIH HHS [AI 28691] NR 60 TC 85 Z9 88 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD JAN PY 1995 VL 25 IS 1 BP 285 EP 290 DI 10.1002/eji.1830250147 PG 6 WC Immunology SC Immunology GA QQ478 UT WOS:A1995QQ47800046 PM 7531147 ER PT J AU MARDER MELTZER AF MARDER MELTZER TI INTOLERANCE TO NEUROLEPTIC DRUGS - THE ART OF AVOIDING EXTRAPYRAMIDAL SYNDROMES - DISCUSSION SO EUROPEAN PSYCHIATRY LA English DT Article RP MARDER (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,PSYCHIAT SERV,11301 WILSHIRE BLVD,LOS ANGELES,CA 90073, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES ELSEVIER PI PARIS CEDEX 15 PA 141 RUE JAVEL, 75747 PARIS CEDEX 15, FRANCE SN 0767-399X J9 EUR PSYCHIAT JI Eur. Psychiat. PY 1995 VL 10 SU 1 BP S32 EP S32 PG 1 WC Psychiatry SC Psychiatry GA QW115 UT WOS:A1995QW11500008 ER PT J AU MARDER, S AF MARDER, S TI DEFINING AND CHARACTERIZING TREATMENT-RESISTANT SCHIZOPHRENIA SO EUROPEAN PSYCHIATRY LA English DT Article DE SCHIZOPHRENIA; TREATMENT; CLOZAPINE AB This paper argues for a brooder definition of treatment refractoriness that would include patients with partial drug responses, a relatively recent onset, less dramatic symptoms and intolerance to conventional drugs. The drug trials that define their responsiveness should be carefully conducted over a prolonged period of time, but need not include high doses or supplemental medications. If the consensus conference can agree on a definition of responsiveness, it will provide important guidance to clinicians as well as researchers. RP MARDER, S (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,PSYCHIAT SERV,11301 WILSHIRE BLVD,LOS ANGELES,CA 90073, USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES ELSEVIER PI PARIS CEDEX 15 PA 141 RUE JAVEL, 75747 PARIS CEDEX 15, FRANCE SN 0767-399X J9 EUR PSYCHIAT JI Eur. Psychiat. PY 1995 VL 10 SU 1 BP S7 EP S10 DI 10.1016/0767-399X(96)80078-2 PG 4 WC Psychiatry SC Psychiatry GA QW115 UT WOS:A1995QW11500002 PM 19698382 ER PT J AU CORZO, D SALAZAR, M GRANJA, CB YUNIS, EJ AF CORZO, D SALAZAR, M GRANJA, CB YUNIS, EJ TI ADVANCES IN HLA GENETICS SO EXPERIMENTAL AND CLINICAL IMMUNOGENETICS LA English DT Article; Proceedings Paper CT International Conference on Immunogenetic Risk Assessment in Human Disease CY MAR 06-08, 1994 CL CHARLESTON, SC SP Med Univ South Carolina, Environm Hazards Assessment Program DE MAJOR HISTOCOMPATIBILITY COMPLEX; HLA; IMMUNE RESPONSE ID MAJOR-HISTOCOMPATIBILITY-COMPLEX; HEPATITIS-B VACCINE; T-CELL RECOGNITION; CLASS-II REGION; GLUTEN-SENSITIVE ENTEROPATHY; BONE MARROW ALLOGRAFTS; SURFACE-ANTIGEN HBSAG; IMMUNE-RESPONSE; IGA DEFICIENCY; DERMATITIS-HERPETIFORMIS AB The major histocompatibility complex (MHC) is a genetic system of over 70 known genes that occupies the midportion of the short arm of the sixth chromosome (C6p) and spans about 4 million base pairs of DNA. The high-resolution typing of class I and class II MHC genes and the identification of genes between and near them has increased the definition of the genetic basis of immune responses and diseases of unknown etiology such as autoimmune diseases in man. Although there are many more genetic systems that participate in the rejection of tissues and in the immune response, the MHC plays a central role in tissue compatibility and immune response against cancer and infectious diseases. In this paper, the authors review evidence about the role of HLA polymorphism in the pathogenesis and development of cancer, infectious diseases, autoimmune diseases and transplantation. RP CORZO, D (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PATHOL,DIV IMMUNOGENET,44 BINNEY ST,BOSTON,MA 02115, USA. NR 89 TC 12 Z9 14 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0254-9670 J9 EXP CLIN IMMUNOGENET JI Exp. Clin. Immunogenet. PY 1995 VL 12 IS 3 BP 156 EP 170 PG 15 WC Biochemistry & Molecular Biology; Genetics & Heredity; Immunology SC Biochemistry & Molecular Biology; Genetics & Heredity; Immunology GA RT568 UT WOS:A1995RT56800005 PM 8534502 ER PT J AU ALPER, CA AF ALPER, CA TI THE HUMAN IMMUNE-RESPONSE TO HEPATITIS-B SURFACE-ANTIGEN SO EXPERIMENTAL AND CLINICAL IMMUNOGENETICS LA English DT Article; Proceedings Paper CT International Conference on Immunogenetic Risk Assessment in Human Disease CY MAR 06-08, 1994 CL CHARLESTON, SC SP Med Univ South Carolina, Environm Hazards Assessment Program DE HEPATITIS B VACCINE; HUMAN IMMUNE RESPONSE; HUMAN MAJOR HISTOCOMPATIBILITY COMPLEX; EXTENDED HAPLOTYPES ID MAJOR-HISTOCOMPATIBILITY-COMPLEX; HAPLOTYPE CONTROLS NONRESPONSIVENESS; EXTENDED MHC HAPLOTYPES; SUPPRESSOR T-CELLS; GENETIC-REGULATION; NONSELF DISCRIMINATION; IMMUNOGENIC PEPTIDES; PEMPHIGUS-VULGARIS; NON-RESPONSIVENESS; PRESENTING CELLS AB The anti-HBs response is bimodal with 4.2% of healthy persons producing no antibody and an additional 10% being hyporesponders. In the study of nonresponders, 2 extended haplotypes, [HLA-B8, SC01, DR3] and [HLA-B44, FC31, DR7], were found to be enriched in a pattern suggesting recessive inheritance. In the prospective immunization of homozygotes and heterozygotes for [HLA-B8, SC01, DR3], the homozygotes had less antibody than the heterozygotes. Family studies confirmed that the anti-HBs response was dominant and MHC linked, whereas nonresponse was recessive. In studies in vitro, it was shown that nonresponders failed to show lymphoproliferation in response to hepatitis B surface antigen (HBsAg) or an immunodominant nonapeptide. The lymphoproliferative response of responders to these stimuli was comparable and inhibited by anti-DR but not antibody to DQ or DP. The removal of CD8(+) T cells did not produce lymphoproliferation to HBsAg in nonresponders. From mixtures of antigen-presenting cells and T cells from MHC-identical response discordant pairs, it was shown that the defect in the nonresponders was in their T cells and not their antigen-presenting cells, ruling out defective MHC binding or antigen processing as the basis of nonresponse. C1 HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. RP ALPER, CA (reprint author), HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115, USA. FU NHLBI NIH HHS [HL-29583] NR 83 TC 41 Z9 47 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0254-9670 J9 EXP CLIN IMMUNOGENET JI Exp. Clin. Immunogenet. PY 1995 VL 12 IS 3 BP 171 EP 181 PG 11 WC Biochemistry & Molecular Biology; Genetics & Heredity; Immunology SC Biochemistry & Molecular Biology; Genetics & Heredity; Immunology GA RT568 UT WOS:A1995RT56800006 PM 8534503 ER PT B AU MOSKOWITZ, MA CUTRER, FM LEE, WS WAEBER, C LIMMROTH, V YU, XJ AF MOSKOWITZ, MA CUTRER, FM LEE, WS WAEBER, C LIMMROTH, V YU, XJ BE Olesen, J Moskowitz, MA TI Drug discovery in migraine circa 1995 SO EXPERIMENTAL HEADACHE MODELS SE FRONTIERS IN HEADACHE RESEARCH LA English DT Proceedings Paper CT 5th International Headache Research Seminar CY NOV 18-20, 1994 CL COPENHAGEN, DENMARK C1 MASSACHUSETTS GEN HOSP,STROKE & NEUROVASC REGULAT LAB,BOSTON,MA 02114. NR 0 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA E WASHINGTON SQ, PHILADELPHIA, PA 19105 BN 0-7817-0330-1 J9 FR HEAD RES PY 1995 VL 5 BP 63 EP 73 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BE25B UT WOS:A1995BE25B00008 ER PT J AU NEY, PA FARINA, SF BODINE, DM ANDREWS, NC ORKIN, SH NIENHUIS, AW AF NEY, PA FARINA, SF BODINE, DM ANDREWS, NC ORKIN, SH NIENHUIS, AW TI MICROCYTIC ANEMIA IN MK/MK MICE IS NOT CORRECTED BY RETROVIRAL-MEDIATED GENE-TRANSFER OF WILD-TYPE P45 NF-E2 SO EXPERIMENTAL HEMATOLOGY LA English DT Note DE NF-E2; RETROVIRUS; ANEMIA; MK MUTATION ID PORPHOBILINOGEN DEAMINASE GENE; TRANSCRIPTION FACTOR NF-E2; DOMINANT CONTROL REGION; LEUCINE ZIPPER PROTEIN; LOCUS-CONTROL REGION; ERYTHROID PROMOTER; GLOBIN GENE; ENHANCER; ORGANIZATION; BINDING AB Mice homozygous for the mk mutation have a severe hypochromic, microcytic anemia that is characterized by a decreased mean-corpuscular hemoglobin concentration and balanced alpha- and beta-globin-chain synthesis. Transplantation studies have shown that the defect in homozygous mk/mk mice is intrinsic to both the hematopoietic system and the gut. The gene for the hematopoietic-specific transcription factor, p45 NF-E2, has been found to cosegregate with the mk phenotype and contain a point mutation in mk/mk mice that results in an amino acid substitution (V-173-->A). In order to test the hypothesis that this amino acid substitution is responsible for the mk phenotype, we have used recombinant retroviruses to introduce wild-type p45 NF-E2 into the bone marrow of mk/mk mice. Despite gene transfer and expression of p45 NF-E2 in erythroid cells, we found no evidence for correction of the phenotype in mk/mk mice. These results indicate that the ink mutation cannot be corrected by enforced expression of wild-type p45 NF-E2 and suggest that the V-173-->A mutation of the p45 NF-E2 gene is not the cause of anemia in mk/mk mice. C1 ST JUDE CHILDRENS RES HOSP, DEPT EXPTL HEMATOL, MEMPHIS, TN 38101 USA. NIH, NATL CTR HUMAN GENOME RES, GENE TRANSFER LAB, HEMATOPOIESIS SECT, BETHESDA, MD 20892 USA. CHILDRENS HOSP, DEPT PEDIAT, DIV HEMATOL ONCOL, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DANA FARBER CANC INST, BOSTON, MA 02115 USA. HOWARD HUGHES MED INST, BOSTON, MA 02115 USA. RP NEY, PA (reprint author), ST JUDE CHILDRENS RES HOSP, DEPT BIOCHEM, 332 N LAUDERDALE ST, MEMPHIS, TN 38101 USA. OI Andrews, Nancy/0000-0003-0243-4462 FU NCI NIH HHS [P30 CA21765] NR 38 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JAN PY 1995 VL 23 IS 1 BP 74 EP 80 PG 7 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA PY648 UT WOS:A1995PY64800013 PM 7995373 ER PT J AU HEILIGENHAUS, A WELLS, PA FOSTER, CS AF HEILIGENHAUS, A WELLS, PA FOSTER, CS TI IMMUNIZATION AGAINST HSV-1 KERATITIS WITH A SYNTHETIC GD PEPTIDE SO EYE LA English DT Article ID HERPES-SIMPLEX VIRUS; MONOCLONAL-ANTIBODIES; GLYCOPROTEIN-D; PROTECTIVE IMMUNITY; TYPE-1; MICE; INFECTION; IMMUNIZATION; LOCALIZATION; CHALLENGE AB The authors tested the protective efficacy of, and the immune response to, immunisation with a synthetic peptide of glycoprotein D (gD) of HSV-1 in a murine model of herpes stromal keratitis (HSK), HSV-1 susceptible A/J mice were immunised subcutaneously ,vith a peptide corresponding to the N-terminal epitope gD(5-23) prior to corneal HSV-1 challenge. Divergent immunisation protocols were compared for their protective potency, their ability to prevent the establishment of latency in the trigeminal ganglion, and their effect on the immune system, Low dosages (31 mu g) of gD(5-23) protected against encephalitis and HSK, Protective efficacy was higher when gD(5-23) was coupled to the carrier protein keyhole limpet haemocyanin (KLH) and was emulsified with adjuvant, Latent infection was found in all control mice but in only 50-75% of immunised mice, The most potent protection was correlated with anti-HSV-l neutralising antibodies of IgG(1) and IgG(2), isotypes, but free gD(5-23) protected in the absence of anti-HSV-l antibodies, Our results suggest that immunisation with gD(5-23) stimulates both humoral and cellular immune mechanisms which protect against HSV-1 keratitis. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,BOSTON,MA 02114. UNIV ESSEN GESAMTHSCH,DEPT OPHTHALMOL,ESSEN,GERMANY. UPJOHN CO,KALAMAZOO,MI 49001. HARVARD UNIV,SCH MED,DEPT OPHTHALMOL,IMMUNOL LAB,BOSTON,MA. FU NEI NIH HHS [EY06008, EY05813] NR 41 TC 12 Z9 12 U1 0 U2 0 PU ROYAL COLL OPHTHALMOLOGISTS PI LONDON PA 17 CORNWALL TERRACE, LONDON, ENGLAND NW1 4QW SN 0950-222X J9 EYE JI Eye PY 1995 VL 9 BP 89 EP 95 PN 1 PG 7 WC Ophthalmology SC Ophthalmology GA QK628 UT WOS:A1995QK62800014 PM 7713256 ER PT J AU PEDROZASERES, M GOEI, S MERAYOLLOVES, J DUTT, JE LEE, SJ ARRUNATEGUICORREA, V FOSTER, CS AF PEDROZASERES, M GOEI, S MERAYOLLOVES, J DUTT, JE LEE, SJ ARRUNATEGUICORREA, V FOSTER, CS TI T-CELL RECEPTOR V-BETA GENE-EXPRESSION IN EXPERIMENTAL HERPES STROMAL KERATITIS SO EYE LA English DT Article DE HERPES SIMPLEX KERATITIS; POLYMERASE CHAIN REACTION; T CELL RECEPTOR ID LYMPHOCYTIC CHORIOMENINGITIS VIRUS; MULTIPLE-SCLEROSIS; PREFERENTIAL USAGE; MICE; SUSCEPTIBILITY; INFECTION; DISEASE; CHAIN AB Our study examined T cell receptor (TCR) V beta mRNA expression in a murine model of experimental herpes simplex keratitis (HSK). We employed a polymerase chain reaction (PCR) technique to detect TCR V beta mRNA expression in the inoculated eyes of both HSK-susceptible and HSK-resistant mice at different time points after corneal inoculation with herpes simplex virus type 1 (HSV-1), followed by Southern blotting and densitometry analysis. In eyes from HSK-susceptible C.AL-20 mice, a more diverse TCR V beta transcript usage pattern was detected as compared with that seen in HSK-resistant C.B-17 mice. V beta 8 family members were expressed in both strains of mice at days 11, 14 and 21 post-inoculation. By densitometry, at day 11, the intensity of expression of V beta 8.2 and V beta 8.3 message was significantly greater in the eyes of C.AL-20 mice; V beta 8.1 was expressed only in C.B-17 mice. There were obvious differences in the TCR V beta expression between HSK-susceptible and HSK-resistant mice. The differences in the intensity of the message expressed by V beta 8 family members between the two strains could be correlated to previous experiments that showed V beta 8.1,2+ T cells as the main infiltrating cells in the corneas of HSK-susceptible mice by day 11 and 14 after challenge with HSV-1. C1 HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,HILLES IMMUNOL LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,RHOADS MOLEC IMMUNOL LAB,BOSTON,MA 02114. UNIV NACL AUTONOMA MEXICO,FAC MED,MEXICO CITY,DF,MEXICO. FU NEI NIH HHS [EY06008] NR 26 TC 2 Z9 2 U1 0 U2 0 PU ROYAL COLL OPHTHALMOLOGISTS PI LONDON PA 17 CORNWALL TERRACE, LONDON, ENGLAND NW1 4QW SN 0950-222X J9 EYE JI Eye PY 1995 VL 9 BP 599 EP 604 PN 5 PG 6 WC Ophthalmology SC Ophthalmology GA TE338 UT WOS:A1995TE33800012 PM 8543080 ER PT J AU HALL, M ELDRIDGE, DB SAUNDERS, RD FAIRCLOUGH, DL BATEMAN, RC AF HALL, M ELDRIDGE, DB SAUNDERS, RD FAIRCLOUGH, DL BATEMAN, RC TI A RAPID DIPSTICK TEST FOR HISTAMINE IN TUNA SO FOOD BIOTECHNOLOGY LA English DT Article ID DIAMINE OXIDASE; LIQUID-CHROMATOGRAPHY; FISH; SCOMBROTOXICOSIS; ETIOLOGY; ASSAY AB This study describes the production of a solid phase assay (dipstick test) for histamine in tuna based on the coupling of diamine oxidase to a peroxidase/dye system. The optimized dipstick preparation consisted of a diamine oxidase/peroxidase/Stabilcoat mixture layered onto a tetramethylbenzidine color strip. The assay was linear to 1.0 mM histamine (RSQ=0.994) and the minimum detectable concentration was 0.07 mM corresponding to 2.3 mg% in tuna extracts. Quality control samples gave intra and interassay precisions of 9.14-9.84 %CV and 7.08-13.86 %CV respectively. Similarly, the assay was accurate (p > 0.05) for both low and high controls. Histidine and cadaverine did not interfere with the assay whereas putrescine reacted slightly with the dipstick. Histamine determinations of fresh and spoiled tuna gave good agreement between the dipstick method and both the official reference and modified AOAC flurometric methods. C1 UNIV SO MISSISSIPPI,DEPT CHEM & BIOCHEM,HATTIESBURG,MS 39406. DANA FARBER CANC INST,DEPT BIOSTAT,BOSTON,MA 02115. RP HALL, M (reprint author), UNIV SO MISSISSIPPI,DEPT MED TECHNOL,HATTIESBURG,MS 39406, USA. NR 31 TC 15 Z9 15 U1 0 U2 2 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 0890-5436 J9 FOOD BIOTECHNOL JI Food Biotechnol. PY 1995 VL 9 IS 1-2 BP 39 EP 57 PG 19 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA RD055 UT WOS:A1995RD05500004 ER PT J AU POU, S DAVIS, PL WOLF, GL ROSEN, GM AF POU, S DAVIS, PL WOLF, GL ROSEN, GM TI USE OF NITROXIDES AS NMR CONTRAST ENHANCING AGENTS FOR JOINTS SO FREE RADICAL RESEARCH LA English DT Article DE NITROXIDES; NMR; NMR CONTRAST ENHANCING AGENTS; SPIN LABELS ID REDUCTION; RADICALS AB NMR imaging is a well-established technology for obtaining cross-sectional anatomic pictures of organs and tissues. In addition, NMR can provide valuable information about the physiologic state of organs and tissues, especially, as a consequence of cellular injury. With this in mind, NMR in combination with gadolinium-based contrast enhancing agents has been used to assist in the detection of abnormalities to joints as well as to evaluate the status of damage resulting from an injury to this site. We describe the synthesis of a new nitroxide, which is bioresistant to the one-electron reduction mediated by superoxide in the presence of cysteine. This model mimics the reduction of nitroxides by extracellular secretion of superoxide by PMA-stimulated neutrophils. With this nitroxide, we found, in the range from 15 to 17.5 mu moles, enhancement of an NMR image in the knee joint of rabbits. Of interest is the finding that the contrast image remained for at least 90 minutes. These results demonstrate the utility of nitroxides as contrast enhancing agents for NMR imaging of joints. C1 UNIV MARYLAND,SCH PHARM,DEPT PHARMACEUT SCI,PROGRAM PHARMACOL & TOXICOL,BALTIMORE,MD 21201. UNIV PITTSBURGH,DEPT RADIOL,PITTSBURGH,PA 15213. MASSACHUSETTS GEN HOSP,CTR IMAGING & PHARMACEUT RES,BOSTON,MA 02129. NR 28 TC 12 Z9 13 U1 0 U2 1 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 1071-5762 J9 FREE RADICAL RES JI Free Radic. Res. PY 1995 VL 23 IS 4 BP 353 EP 364 DI 10.3109/10715769509065256 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RN642 UT WOS:A1995RN64200005 PM 7493041 ER PT J AU REINECKER, HC LOH, EY RINGLER, DJ MEHTA, A ROMBEAU, JL MACDERMOTT, RP AF REINECKER, HC LOH, EY RINGLER, DJ MEHTA, A ROMBEAU, JL MACDERMOTT, RP TI MONOCYTE-CHEMOATTRACTANT PROTEIN-1 GENE-EXPRESSION IN INTESTINAL EPITHELIAL-CELLS AND INFLAMMATORY BOWEL-DISEASE MUCOSA SO GASTROENTEROLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; ACTIVATING FACTOR MCAF; CROHNS-DISEASE; MONONUCLEAR-CELLS; ALVEOLAR MACROPHAGES; ENHANCED PRODUCTION; ULCERATIVE-COLITIS; ENDOTHELIAL-CELLS; MCP-1 EXPRESSION; BLOOD MONOCYTES AB Background: Monocyte-chemoattractant protein 1 (MCP-1) activates macrophages and increases the migration of monocytes into tissue during inflammation. It was hypothesized that MCP-1 expression is involved in intestinal inflammation. Methods: MCP-1 protein was detected by immunohistochemistry and immunoprecipitation. Biological activity of MCP-1 was assessed using a chemotactic assay. MCP-1 messenger RNA (mRNA) levels were measured by quantitative reverse-transcription polymerase chain reaction. Results: In normal mucosa, MCP-1 was predominantly present in surface epithelium. In contrast, inflamed mucosa from patients with ulcerative colitis or Crohn's disease contained multiple cells immunoreactive for MCP-1, including spindle cells, mononuclear cells, and endothelial cells. Furthermore, MCP-1 mRNA expression was markedly increased in inflamed intestinal biopsy specimens from patients with inflammatory bowel disease. MCP-1 was detected in isolated intestinal epithelial cells and in conditioned media from Caco-2 cells. Caco-2 cell-conditioned media stimulated monocyte chemotaxis activity that was inhibited by anti-MCP-1 antibodies. Constituitive MCP-1 mRNA levels in Caco-2 cells were up-regulated by interleukin 1 beta and down-regulated by dexamethasone. Conclusions In addition to lamina propria macrophages, endothelial cells, and spindle cells, intestinal epithelial cells are able to produce MCP-1. MCP-1 is expressed constitutively in the intestinal colonic mucosa and is up-regulated during inflammation. C1 LAHEY CLIN MED CTR,GASTROINTESTINAL SECT,BURLINGTON,MA 01805. UNIV PENN,MED CTR,DIV GASTROENTEROL,PHILADELPHIA,PA. UNIV PENN,MED CTR,DIV ONCOL,PHILADELPHIA,PA. UNIV PENN,MED CTR,DEPT SURG,PHILADELPHIA,PA. LEUKOSITE INC,BOSTON,MA. MASSACHUSETTS GEN HOSP,CTR STUDY INFLAMMATORY BOWEL DIS,BOSTON,MA. FU NIDDK NIH HHS [DK-21474, DK-43351] NR 53 TC 210 Z9 213 U1 0 U2 4 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 JAN PY 1995 VL 108 IS 1 BP 40 EP 50 DI 10.1016/0016-5085(95)90006-3 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PZ135 UT WOS:A1995PZ13500005 PM 7806062 ER PT J AU TAKAHASHI, H NAKADA, T NAKAKI, M WANDS, JR AF TAKAHASHI, H NAKADA, T NAKAKI, M WANDS, JR TI INHIBITION OF HEPATIC METASTASES OF HUMAN COLON-CANCER IN NUDE-MICE BY A CHIMERIC SF-25 MONOCLONAL-ANTIBODY SO GASTROENTEROLOGY LA English DT Article ID BIOLOGICAL RESPONSE MODIFIERS; TUMOR CELL-LINES; ADJUVANT THERAPY; COLORECTAL-CANCER; ATHYMIC NUDE; MOUSE; GROWTH; LIVER; CARCINOMA; RECEPTOR AB Background/Aims: Hepatic metastasis is one of the most serious complications of human colon cancer. A murine-human chimeric SF-25 monoclonal antibody was prepared, and this construct recognizes a cell surface antigen highly present in human colon adenocarcinoma. Methods: This study determined if the chimeric SF-25 monoclonal antibody inhibits the outgrowth of hepatic metastases of human colon adenocarcinoma using an athymic nude mouse model. Results: A single intravenous injection of chimeric SF-25 monoclonal antibody significantly inhibited the outgrowth of 5 and 7-day hepatic micrometastases (P = 0.0001 and 0.004, respectively, vs. untreated) and improved the survival of the animals. No detectable tumor was found in the liver when mice were treated by multiple injections of the antibody immediately after tumor cell grafting into the portal vein. In contrast, F(ab')(2) fragments did not show antitumor effects, and the administration of natural killer cell or macrophage depleting agents (anti-asialo GM1 antibody and carrageenan, respectively) substantially inhibited the antitumor effects of chimeric SF-25 monoclonal antibody in vivo. Conclusions: Chimeric SF-25 monoclonal antibody inhibits growth of hepatic metastasis of human colon cancer, and cell-mediated host immune mechanisms seem to be important for its in vivo antitumor activity. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,CTR CANC,MOLEC HEPATOL LAB,BOSTON,MA. RP TAKAHASHI, H (reprint author), MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,JACKSON 7,FRUIT ST,BOSTON,MA 02114, USA. FU NCI NIH HHS [CA 57584, CA 35711]; NIDDK NIH HHS [DK 43351] NR 45 TC 14 Z9 14 U1 1 U2 1 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 JAN PY 1995 VL 108 IS 1 BP 172 EP 182 DI 10.1016/0016-5085(95)90022-5 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PZ135 UT WOS:A1995PZ13500021 PM 7806039 ER PT J AU TAKEMOTO, C FISHER, DE AF TAKEMOTO, C FISHER, DE TI STRUCTURAL CONSTRAINTS FOR DNA RECOGNITION BY MYC AND OTHER B-HLH-ZIP PROTEINS - DESIGN OF ONCOPROTEIN ANALOGS SO GENE EXPRESSION LA English DT Article DE TRANSCRIPTION; DNA BINDING; B-HLH-ZIP; MYC; ONCOPROTEIN ID LOOP-HELIX PEPTIDES; HUMAN C-MYC; LEUCINE-ZIPPER; BINDING PROTEINS; MAX; FAMILY; OLIGOMERIZATION; SPECIFICITY; TRANSITION; DOMAIN AB DNA recognition is a critical property of many transcription factors, some of which play important roles in human disease. Disruption of this recognition may profoundly influence the biology of these factors. One such factor, the Myc oncoprotein, utilizes a basic/helix-loop-helix/leucine zipper motif to recognize the DNA target CACGTG. As discussed here, this recognition appears to occur through recognition by one face of a basic region alpha helix utilizing amino acid side chains highly conserved among CACGTG binding proteins. This basic domain alpha helix, however, requires DNA binding for stabilization. To circumvent this energetic requirement, analogues were produced that introduce multiple alanines, displaying substantially increased spontaneous alpha helicity and significantly enhanced DNA affinity. These studies simplify our understanding of the structural constraints for DNA recognition by this family and may serve as a template for the design of small molecule transcription-targeted therapeutics. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. NR 26 TC 6 Z9 6 U1 0 U2 1 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 SN 1052-2166 J9 GENE EXPRESSION JI Gene Expr. PY 1995 VL 4 IS 6 BP 311 EP 317 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA RC415 UT WOS:A1995RC41500003 PM 7549463 ER PT S AU Lees, MB Smith, FI Dyer, CA Greer, JM Pakaski, M AF Lees, MB Smith, FI Dyer, CA Greer, JM Pakaski, M BE Yu, ACH Eng, LF McMahan, UJ Schulman, H Shooter, EM Stadlin, A TI Expression of myelin proteolipid protein in oligodendrocytes and transfected cells SO GENE EXPRESSION IN THE CENTRAL NERVOUS SYSTEM SE PROGRESS IN BRAIN RESEARCH LA English DT Article; Proceedings Paper CT 2nd Stanford International Neuroscience Symposium CY OCT 19-22, 1993 CL BEIJING, PEOPLES R CHINA SP Stanford Univ, Sch Med, Beijing Med Univ, Chinese Univ Hong Kong, Fac Med, N Amer Med Assoc Fdn, Hong Kong ID BOVINE BRAIN MYELIN; GENE FAMILY; IDENTIFICATION C1 HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114. RP Lees, MB (reprint author), EUNICE KENNEDY SHRIVER CTR MENTAL RETARDAT INC,DEPT BIOMED SCI,200 TRAPELO RD,WALTHAM,MA 02254, USA. RI Greer, Judith/C-4945-2009 OI Greer, Judith/0000-0003-4440-4309 FU NIDDK NIH HHS [DK38381]; NINDS NIH HHS [NS16945]; PHS HHS [04147] NR 21 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL B V PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 BN 0-444-81852-9 J9 PROG BRAIN RES PY 1995 VL 105 BP 295 EP 303 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Neurosciences; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Cell Biology; Neurosciences & Neurology; Pharmacology & Pharmacy GA BE39G UT WOS:A1995BE39G00029 PM 7568890 ER PT J AU RAFTERY, LA TWOMBLY, V WHARTON, K GELBART, WM AF RAFTERY, LA TWOMBLY, V WHARTON, K GELBART, WM TI GENETIC SCREENS TO IDENTIFY ELEMENTS OF THE DECAPENTAPLEGIC SIGNALING PATHWAY IN DROSOPHILA SO GENETICS LA English DT Article ID SERINE THREONINE KINASE; DORSAL-VENTRAL PATTERN; II RECEPTOR; BINDING-PROTEIN; BONE-FORMATION; BETA FAMILY; GERM LAYERS; EMBRYO; COMPLEX; EXPRESSION AB Pathways for regulation of signaling by transforming growth factor-beta family members are poorly understood at present. The best genetically characterized member of this family is encoded by the Drosophila gene decapentaplegic (dpp), which is required for multiple events during fly development. We describe here the results of screens for genes required to maximize dpp signaling during embryonic dorsal-ventral patterning. Screens for genetic interactions in the zygote have identified an allele of tolloid, as well as two novel alleles of screw a gene recently shown to encode another bone morphogenetic protein-like polypeptide. Both genes are required for patterning the dorsalmost tissues of the embryo. Screens for dpp interactions with maternally expressed genes have identified loss of function mutations in Mothers against dpp and Medea. These mutations are homozygous pupal lethal, engendering gut defects and severely reduced imaginal disks, reminiscent of dpp mutant phenotypes arising during other dpp dependent developmental events. Genetic interaction phenotypes are consistent with reduction of dpp activity in the early embryo and in the imaginal disks. We propose that the novel screw mutations identified here titrate out some component(s) of the dpp signaling pathway. We propose that Mad and Medea encode rate-limiting components integral to dpp pathways throughout development. C1 MASSACHUSETTS GEN HOSP,CUTANEOUS BIOL RES CTR,CHARLOTTETOWN,MA. HARVARD UNIV,SCH MED,BOSTON,MA. HARVARD UNIV,DEPT DEV & CELL BIOL,CAMBRIDGE,MA 02138. RI Raftery, Laurel/H-1406-2012 OI Raftery, Laurel/0000-0003-4797-4163 NR 55 TC 214 Z9 229 U1 1 U2 3 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 SN 0016-6731 J9 GENETICS JI Genetics PD JAN PY 1995 VL 139 IS 1 BP 241 EP 254 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA PZ248 UT WOS:A1995PZ24800020 PM 7705627 ER PT J AU KOZMAN, HM KEITH, TP DONISKELLER, H WHITE, RL WEISSENBACH, J DEAN, M VERGNAUD, G KIDD, K GUSELLA, J ROYLE, NJ SUTHERLAND, GR MULLEY, JC AF KOZMAN, HM KEITH, TP DONISKELLER, H WHITE, RL WEISSENBACH, J DEAN, M VERGNAUD, G KIDD, K GUSELLA, J ROYLE, NJ SUTHERLAND, GR MULLEY, JC TI THE CEPH CONSORTIUM LINKAGE MAP OF HUMAN-CHROMOSOME-16 SO GENOMICS LA English DT Article ID HUMAN GENOME; LENGTH POLYMORPHISM; DISEASE LOCUS; MARKERS; CLN3 AB A Centre d'Etude du Polymorphisme Humain (CEPH) consortium map of human chromosome 16 has been constructed. The map contains 158 loci defined by 191 different probe/restriction enzyme combinations or primer pairs. The marker genotypes, contributed by 9 collaborating laboratories, originated from the CEPH families DNA. A total of 60 loci, with an average heterozygosity of 68%, have been placed on the framework genetic map. The genetic map contains 7 genes. The length of the sex-averaged map is 165 cM, with a mean genetic distance between loci of 2.8 cM; the median distance between markers is 2.0 cM. The male map length is 136 cM, and the female map length is 197 cM. The map covers virtually the entire chromosome, from D16S85, within 170 to 430 kb of the 16p telomere, to D16S303 at 16qter. The markers included in the linkage map have been physically mapped on a partial human chromosome 16 somatic cell hybrid panel, thus anchoring the genetic map to the cytogenetic-based physical map. (C) 1995 Academic Press, Inc. C1 WOMENS & CHILDRENS HOSP,CTR MED GENET,DEPT CYTOGENET & MOLEC GENET,ADELAIDE,SA 5006,AUSTRALIA. UNIV ADELAIDE,DEPT PAEDIAT,ADELAIDE,SA,AUSTRALIA. COLLABORAT RES INC,DEPT HUMAN & MOLEC GENET,WALTHAM,MA. WASHINGTON UNIV,SCH MED,DEPT SURG,ST LOUIS,MO 63110. UNIV UTAH,HOWARD HUGHES MED INST,SALT LAKE CITY,UT. INST PASTEUR,PARIS,FRANCE. NCI,FREDERICK CANC RES FACIL,FREDERICK,MD. CTR ETUD BOUCHET,NANTES,FRANCE. INST BIOL,NANTES,FRANCE. YALE UNIV,SCH MED,DEPT HUMAN GENET,NEW HAVEN,CT 06510. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. UNIV LEICESTER,DEPT GENET,LEICESTER LE1 7RH,LEICS,ENGLAND. RI Sutherland, Grant/D-2606-2012; Vergnaud, Gilles/P-1304-2015; OI Vergnaud, Gilles/0000-0003-0913-194X; Dean, Michael/0000-0003-2234-0631 NR 38 TC 21 Z9 21 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD JAN 1 PY 1995 VL 25 IS 1 BP 44 EP 58 DI 10.1016/0888-7543(95)80108-X PG 15 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA QE734 UT WOS:A1995QE73400006 PM 7774955 ER PT J AU MURRELL, J TROFATTER, J RUTTER, M CUTONE, S STOTLER, C RUTTER, J LONG, K TURNER, A DEAVEN, L BUCKLER, A MCCORMICK, MK AF MURRELL, J TROFATTER, J RUTTER, M CUTONE, S STOTLER, C RUTTER, J LONG, K TURNER, A DEAVEN, L BUCKLER, A MCCORMICK, MK TI A 500-KILOBASE REGION CONTAINING THE TUBEROUS SCLEROSIS LOCUS (TSC1) IN A 1.7-MEGABASE YAC AND COSMID CONTIG SO GENOMICS LA English DT Article ID HUMAN GENOME AB A complete overlapping clone map of a 1.7-Mb region from DBH to D9S67 that includes the TSC1 candidate region has been constructed. The map includes YAC and cosmid clones, contains STS approximately every 50 kb on average, and establishes the order of five previously unordered loci, The overall physical length of this segment of chromosome 9q34 (1.7 Mb) is significantly less than expected compared to its estimated genetic length (similar to 10 cM). Consequently, the physical length of the TSC1 candidate region is substantially less than predicted by a genetic distance of similar to 2 cM. (C) 1995 Academic Press, Inc. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,MOLEC NEUROGENET UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02114. LOS ALAMOS NATL LAB,CTR HUMAN GENOME STUDIES,LOS ALAMOS,NM 87545. LOS ALAMOS NATL LAB,DIV LIFE SCI,LOS ALAMOS,NM 87545. OI Rutter, Joni/0000-0002-6502-2361 NR 14 TC 14 Z9 14 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD JAN 1 PY 1995 VL 25 IS 1 BP 59 EP 65 DI 10.1016/0888-7543(95)80109-Y PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA QE734 UT WOS:A1995QE73400007 PM 7774956 ER PT J AU PULKKINEN, L GERECKE, DR CHRISTIANO, AM WAGMAN, DW BURGESON, RE UITTO, J AF PULKKINEN, L GERECKE, DR CHRISTIANO, AM WAGMAN, DW BURGESON, RE UITTO, J TI CLONING OF THE BETA-3 CHAIN GENE (LAMB3) OF HUMAN LAMININ-5, A CANDIDATE GENE IN JUNCTIONAL EPIDERMOLYSIS-BULLOSA SO GENOMICS LA English DT Article ID A-CHAIN; ADHESION MOLECULE; B2 CHAIN; EXPRESSION; ACID; SEQUENCE; PROTEIN; KALININ; ASSIGNMENT; HOMOLOGY AB Laminin 5 consists of three polypeptides, alpha 3, beta 3, and gamma 2, encoded by the genes LAMA3, LAMB3, and LAMC2, respectively. In this study, we have elucidated the exon-intron organization of the human LAMBS gene. Characterization of five overlapping lambda phage DNA clones revealed that the gene was approximately 29 kb in size. Subsequent sequence data revealed that the gene consisted of 23 exons that varied from 64 to 379 bp in size, accounting for the full-length cDNA with an open reading frame of 3516 bp encoding 1172 amino acids. Comparison of the LAMBS gene structure with the previously characterized LAMB1 gene revealed that LAMB3 was considerably more compact. Knowledge of the exon-intron organization of the LAMB3 gene will facilitate elucidation of mutations in patients with the junctional forms of epidermolysis bullosa, some of which have been associated with mutations in the laminin 5 genes. (C) 1995 Academic Press, Inc. C1 THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,JEFFERSON INST MOLEC MED,DEPT DERMATOL,PHILADELPHIA,PA 19107. THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,JEFFERSON INST MOLEC MED,DEPT BIOCHEM & MOLEC BIOL,PHILADELPHIA,PA 19107. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CUTANEOUS BIOL RES CTR,BOSTON,MA 02129. FU NIAMS NIH HHS [P01-AR38923]; PHS HHS [T32-07561] NR 33 TC 49 Z9 51 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD JAN 1 PY 1995 VL 25 IS 1 BP 192 EP 198 DI 10.1016/0888-7543(95)80125-6 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA QE734 UT WOS:A1995QE73400023 PM 7774918 ER PT J AU MAGOVCEVIC, I WEREMOWICZ, S MORTON, CC FONG, SL BERSON, EL DRYJA, TP AF MAGOVCEVIC, I WEREMOWICZ, S MORTON, CC FONG, SL BERSON, EL DRYJA, TP TI MAPPING OF THE HUMAN CONE TRANSDUCIN ALPHA-SUBUNIT (GNAT2) GENE TO 1P13 AND NEGATIVE MUTATION ANALYSIS IN PATIENTS WITH STARGARDT DISEASE SO GENOMICS LA English DT Note ID DOMINANT RETINITIS-PIGMENTOSA; JUVENILE MACULAR DEGENERATION; POINT MUTATIONS; BETA-SUBUNIT; MOUSE; ELECTRORETINOGRAMS; PHOSPHODIESTERASE; RHODOPSIN; FOVEAL AB We report localization of the human cone transducin (GNATS) gene using fluorescence in situ hybridization on chromosome 1 in band p13. The recent assignment of a gene for Stargardt disease to the same chromosomal region by linkage analysis prompted us to investigate the possible role of GNATS in the pathogenesis of this disease. We investigated 66 unrelated patients for mutations in the coding region of the GNATS gene using polymerase chain reaction-single strand conformation polymorphism analysis (SSCP) and direct sequencing. No disease-specific mutations were found, indicating that GNATS is probably not involved in the pathogenesis of most cases of Stargardt disease. (C) 1995 Academic Press, Inc. C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,HOWE LAB OPHTHALMOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BERMAN GUND LAB,BOSTON,MA 02115. INDIANA UNIV,SCH MED,DEPT OPHTHALMOL,INDIANAPOLIS,IN 46202. FU NEI NIH HHS [EY08663, EY00169]; NIDCD NIH HHS [DC00871] NR 19 TC 8 Z9 8 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD JAN 1 PY 1995 VL 25 IS 1 BP 288 EP 290 DI 10.1016/0888-7543(95)80139-D PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA QE734 UT WOS:A1995QE73400037 PM 7774932 ER PT J AU AIELLO, LP ARRIGG, PG AIELLO, LM AF AIELLO, LP ARRIGG, PG AIELLO, LM TI REVERSIBLE LEUKOCORIA ASSOCIATED WITH CLINICALLY SIGNIFICANT DIABETIC MACULAR EDEMA SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY LA English DT Note RP AIELLO, LP (reprint author), JOSLIN DIABET CTR,BEETHAM EYE INST,1 JOSLIN PL,BOSTON,MA 02215, USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0721-832X J9 GRAEF ARCH CLIN EXP JI Graefes Arch. Clin. Exp. Ophthalmol. PD JAN PY 1995 VL 233 IS 1 BP 54 EP 55 DI 10.1007/BF00177788 PG 2 WC Ophthalmology SC Ophthalmology GA PZ711 UT WOS:A1995PZ71100011 PM 7721125 ER PT J AU FRISCH, RE SNOW, RC JOHNSON, LA MCFARLAND, EG ROSEN, B ERAT, K BARBIERI, R AF FRISCH, RE SNOW, RC JOHNSON, LA MCFARLAND, EG ROSEN, B ERAT, K BARBIERI, R TI INSULIN-RESPONSE OF WOMEN ATHLETES IN RELATION TO BODY-FAT QUANTIFIED BY MAGNETIC-RESONANCE-IMAGING SO GYNECOLOGIC AND OBSTETRIC INVESTIGATION LA English DT Article DE BODY FAT; GLUCOSE; INSULIN, WOMEN ATHLETES; MAGNETIC RESONANCE IMAGING, INSULIN RESPONSE; WOMEN ATHLETES ID METABOLISM; SENSITIVITY AB We report the glucose and insulin response to a 300-min glucose tolerance test among 17 women athletes as compared with 11 normal, nonatheletic controls. Also reported is the relationship of the insulin area under the curve as a function of percentages of total fat (TF), subcutaneous fat, and internal fat of total volume (TV) quantified by magnetic resonance imaging overall and at six regional sites. Athletes had a more sensitive insulin response to the glucose tolerance test as compared with controls. The insulin area under the curve of athletes and controls was significantly (p = 0.05) related to their overall TF/TV%; athletes had significantly less TF/TV% as compared with the controls. C1 HARVARD UNIV,SCH PUBL HLTH,DEPT POPULAT SCI & INT HLTH,BOSTON,MA 02115. UNIV CALIF SAN DIEGO,MED CTR,DEPT RADIOL,SAN DIEGO,CA 92103. MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP EAST,NMR IMAGING CTR,BOSTON,MA. BRIGHAM & WOMENS HOSP,DEPT OBSTET & GYNECOL,BOSTON,MA 02115. RP FRISCH, RE (reprint author), HARVARD UNIV,SCH PUBL HLTH,CTR POPULAT & DEV STUDIES,9 BOW ST,CAMBRIDGE,MA 02138, USA. FU NICHD NIH HHS [HD23536] NR 17 TC 1 Z9 1 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-7346 J9 GYNECOL OBSTET INVES JI Gynecol.Obstet.Invest. PY 1995 VL 40 IS 3 BP 195 EP 199 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA TA980 UT WOS:A1995TA98000010 PM 8529954 ER PT J AU HERMAN, JB AF HERMAN, JB TI MANAGED CARE AND RESIDENCY TRAINING IN PSYCHIATRY SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article RP HERMAN, JB (reprint author), MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BULFINCH 3,32 FRUIT ST,BOSTON,MA 02114, USA. NR 4 TC 6 Z9 6 U1 1 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD JAN-FEB PY 1995 VL 2 IS 5 BP 290 EP 292 DI 10.3109/10673229509017149 PG 3 WC Psychiatry SC Psychiatry GA QF068 UT WOS:A1995QF06800007 PM 9384914 ER PT J AU FURST, M LEVINE, RA KORCZYN, AD FULLERTON, BC TADMOR, R ALGOM, D AF FURST, M LEVINE, RA KORCZYN, AD FULLERTON, BC TADMOR, R ALGOM, D TI BRAIN-STEM LESIONS AND CLICK LATERALIZATION IN PATIENTS WITH MULTIPLE-SCLEROSIS SO HEARING RESEARCH LA English DT Article DE CLICK LATERALIZATION; MULTIPLE SCLEROSIS; MAGNETIC RESONANCE IMAGING; AUDITORY PATHWAY ID AUDITORY-EVOKED-POTENTIALS; CAT AB The ability to lateralize dichotic clicks with either interaural time delays (ITD) or interaural level differences (ILD) was tested in seven multiple sclerosis (MS) subjects who had normal audiograms. Along with the psychoacoustical tests, magnetic resonance images (MRI) of the subjects' brainstem were obtained. After matching each MRI section with the corresponding section of a computerized atlas of the brainstem, the parts of the auditory pathway affected by each MS lesion were determined. Of the seven subjects two performed normally with both types of interaural asymmetry and had no brainstem lesions involving the auditory pathway. Two subjects performed normally only with level differences, but perceived all the dichotic clicks with different ITDs in the center of the head; both had lesions involving the trapezoid body. Three subjects could not perform normally with either task, perceiving the clicks to the sides and never in the center for both ITDs and ILDs; all three had unilateral lesions of the lateral lemniscus. A multi-level decision making model is proposed to account for these results. C1 MASSACHUSETTS EYE & EAR INFIRM,EATON PEABODY LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. TEL AVIV UNIV,SACKLER FAC MED,DEPT NEUROL,IL-69978 TEL AVIV,ISRAEL. TEL AVIV UNIV,SACKLER FAC MED,DEPT PHYSIOL & PHARMACOL,IL-69978 TEL AVIV,ISRAEL. TEL AVIV UNIV,SACKLER FAC MED,DEPT RADIOL,IL-69978 TEL AVIV,ISRAEL. BAR ILAN UNIV,DEPT PSYCHOL,IL-52900 RAMAT GAN,ISRAEL. RP FURST, M (reprint author), TEL AVIV UNIV,FAC ENGN,DEPT ELECT ENGN SYST,IL-69978 TEL AVIV,ISRAEL. RI Korczyn, Amos/C-3461-2017 OI Korczyn, Amos/0000-0003-0125-2579 FU NIDCD NIH HHS [P01 DC00119] NR 26 TC 23 Z9 23 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD JAN PY 1995 VL 82 IS 1 BP 109 EP 124 PG 16 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA QH195 UT WOS:A1995QH19500012 PM 7744707 ER PT J AU CARROLL, DL AF CARROLL, DL TI THE IMPORTANCE OF SELF-EFFICACY EXPECTATIONS IN ELDERLY PATIENTS RECOVERING FROM CORONARY-ARTERY BYPASS-SURGERY SO HEART & LUNG LA English DT Article AB Objective: To describe and test a model of recovery in the elderly after coronary artery bypass surgery derived from Self-Care and Self-Efficacy Theory. Design: Prospective, longitudinal, repeated measures. Setting: Two large urban teaching hospitals on the East Coast. Patients: One hundred thirty-three adults over the age of 65 years who had coronary artery bypass surgery on hospital admission. There were 32 women and 101 men with an age range of 65 to 87 years (M = 71.8 years +/- 4.8 years) in whom 77.5% were in a New York Heart Association class of 3 or 4, indicating significant functional limitations. Outcome measures: Self-care agency, self-efficacy expectations, and the performance of self-care/recovery behaviors at discharge, 6, and 12 weeks after coronary artery bypass surgery. Instruments: The exercise of self-care agency was measured with the Exercise of Self-Care Agency Scale, self-efficacy expectation, and the performance of self-care/recovery behavior by the Jenkins Self-Efficacy Expectation Scales and Activity Checklists. Data were collected at discharge, 6 weeks, and 12 weeks after surgery for the specific behaviors of walking, climbing stairs, resuming general activities, and the performance of roles. Results: Repeated measures analysis of variance revealed significant changes in self-care agency, the self-efficacy expectations for all behaviors, and the performance of the behaviors for walking, resuming general activities, and performance of roles over the recovery period (p < 0.01). Conclusions: In support of the model, self-efficacy expectations mediated between self-care agency and all self-care/recovery behaviors at selected times. Comparison of the performance of self-care/recovery behaviors with other samples from the literature found recovery in the elderly to be protracted. Nurses can be pivotal in providing the elderly with accurate projections of recovery and an environment to support the initial mastery of self-care/recovery behaviors to promote optimal health in this vulnerable population. C1 MASSACHUSETTS GEN HOSP,DEPT NURSING,BOSTON,MA 02114. FU NINR NIH HHS [F31 NR06739-02] NR 0 TC 54 Z9 54 U1 0 U2 3 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0147-9563 J9 HEART LUNG JI Heart Lung PD JAN-FEB PY 1995 VL 24 IS 1 BP 50 EP 59 DI 10.1016/S0147-9563(05)80095-0 PG 10 WC Cardiac & Cardiovascular Systems; Nursing; Respiratory System SC Cardiovascular System & Cardiology; Nursing; Respiratory System GA QC922 UT WOS:A1995QC92200007 PM 7706100 ER PT S AU Kalams, SA Walker, BD AF Kalams, SA Walker, BD BE Oldstone, MB Vitkovic, L TI Cytotoxic T lymphocytes and HIV-1-related neurologic disorders SO HIV AND DEMENTIA SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Article; Proceedings Paper CT Conference on Pathogenesis of HIV Infection of the Brain - Impact on Function and Behavior CY APR 04-07, 1994 CL CHANTILLY, VA SP NIMH ID HUMAN-IMMUNODEFICIENCY-VIRUS; AIDS DEMENTIA COMPLEX; MAJOR HISTOCOMPATIBILITY COMPLEX; TUMOR-NECROSIS-FACTOR; LIMITING DILUTION ANALYSIS; INFECTED RHESUS-MONKEYS; CEREBROSPINAL-FLUID; HIV-1 INFECTION; INTERFERON-GAMMA; FINE SPECIFICITY C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP Kalams, SA (reprint author), HARVARD UNIV,SCH MED,INFECT DIS UNIT,55 FRUIT ST,BOSTON,MA 02114, USA. NR 52 TC 18 Z9 19 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN 33 PA HEIDELBERGER PLATZ 3, W-1000 BERLIN 33, GERMANY SN 0070-217X BN 3-540-59117-6 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 1995 VL 202 BP 79 EP 88 PG 10 WC Infectious Diseases; Clinical Neurology; Neurosciences SC Infectious Diseases; Neurosciences & Neurology GA BE60P UT WOS:A1995BE60P00006 PM 7587372 ER PT J AU WERSHIL, BK AF WERSHIL, BK TI ROLE OF MAST-CELLS AND BASOPHILS IN GASTROINTESTINAL INFLAMMATION SO HUMAN BASOPHILS AND MAST CELLS: CLINICAL ASPECTS SE CHEMICAL IMMUNOLOGY LA English DT Review ID C-KIT LIGAND; LEUKOCYTE ADHESION MOLECULE-1; EPIDERMAL LANGERHANS CELLS; ACTIVE ULCERATIVE-COLITIS; TUMOR-NECROSIS-FACTOR; FC-EPSILON-RI; CROHNS-DISEASE; IMMUNOGLOBULIN-E; SUBSTANCE-P; HELICOBACTER-PYLORI C1 CHILDRENS HOSP,MASSACHUSETTS GEN HOSP,COMBINED PROGRAM PEDIAT GASTROENTEROL & NUTR,BOSTON,MA. BETH ISRAEL HOSP,DEPT PATHOL,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA. FU NIDDK NIH HHS [P01 DK-33506] NR 83 TC 13 Z9 13 U1 1 U2 1 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 1015-0145 J9 CHEM IMMUNOL JI Chem.Immunol. PY 1995 VL 62 BP 187 EP 203 PG 17 WC Allergy; Immunology SC Allergy; Immunology GA BD73L UT WOS:A1995BD73L00008 PM 7546281 ER PT J AU HuangHellinger, FR Breiter, HC McCormack, G Cohen, MS Kwong, KK Sutton, JP Savoy, RL Weisskoff, RM Davis, TL Baker, JR Belliveau, JW Rosen, BR AF HuangHellinger, FR Breiter, HC McCormack, G Cohen, MS Kwong, KK Sutton, JP Savoy, RL Weisskoff, RM Davis, TL Baker, JR Belliveau, JW Rosen, BR TI Simultaneous functional magnetic resonance imaging and electrophysiological recording SO HUMAN BRAIN MAPPING LA English DT Article DE echo planar MRI; brain; function ID CEREBRAL BLOOD-FLOW; HUMAN VISUAL-CORTEX; HUMAN-BRAIN; SENSORY STIMULATION; NEURONAL-ACTIVITY; POWER DEPOSITION; MRI; NMR; CONTRAST; SUSCEPTIBILITY AB The purpose of this study was to develop a method for obtaining simultaneous electrophysiological and functional magnetic resonance imaging data. Using phantom experiments and tests on several of the investigators, a method for obtaining simultaneous electrophysiological and fMRI data was developed and then tested in three volunteers including two task activation experiments. It was then applied in a sleep experiment (n = 12). Current limiting resistance and low-pass filtering were added to the electrophysiological circuit. Potential high frequency current loops were avoided in the electrical layout near the subject. MRI was performed at 1.5 T using conventional and echo planar imaging sequences. There was no evidence of subject injury. Expected correlations were observed between the electrophysiological and fMRI data in the task activation experiments. The fMRI data were not significantly degraded by the electrophysiological apparatus. Alpha waves were detected from within the magnet in seven of the 15 experimental sessions. There was degradation of the electrophysiological data due to ballistocardiographic artifacts (pulsatile whole body motion time-locked to cardiac activity) which varied between subjects from being minimal to becoming large enough to make detection of alpha waves difficult. We concluded that simultaneous fMRI and electrophysiological recording is possible with minor modifications of standard electrophysiological equipment. Our initial results suggest this can be done safely and without compromise of the fMRI data. The usefulness of this technique for studies of such things as sleep and epilepsy is promising. Applications requiring higher precision electrophysiological data, such as evoked response measurements, may require modifications based on ballistocardiographic effects. (C) 1995 Wiley-Liss, Inc. C1 MASSACHUSETTS GEN HOSP, NMR CTR, DEPT RADIOL, BOSTON, MA 02129 USA. MASSACHUSETTS GEN HOSP, DEPT PSYCHIAT, BOSTON, MA 02129 USA. MASSACHUSETTS GEN HOSP, BOSTON, MA 02114 USA. NEW ENGLAND COLL OPTOMETRY, BOSTON, MA USA. UNIV CALIF LOS ANGELES, SCH MED, REED NEUROL RES CTR, DEPT NEUROL, LOS ANGELES, CA 90024 USA. UNIV CALIF LOS ANGELES, SCH MED, REED NEUROL RES CTR, DEPT RADIOL SCI, LOS ANGELES, CA 90024 USA. ROWLAND INST SCI INC, CAMBRIDGE, MA 02142 USA. RI Cohen, Mark/C-6610-2011 OI Cohen, Mark/0000-0001-6731-4053 NR 57 TC 92 Z9 92 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PY 1995 VL 3 IS 1 BP 13 EP 23 DI 10.1002/hbm.460030103 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA TU287 UT WOS:A1995TU28700002 ER PT J AU Fisher, RE Morris, ED Alpert, NM Fischman, AJ AF Fisher, RE Morris, ED Alpert, NM Fischman, AJ TI In vivo imaging of neuromodulatory synaptic transmission using PET: A review of relevant neurophysiology SO HUMAN BRAIN MAPPING LA English DT Article DE receptor; positron emission tomography; dopamine; endogenous; brain; activation ID POSITRON EMISSION TOMOGRAPHY; D2-DOPAMINE RECEPTOR OCCUPANCY; SUBSTANTIA NIGRA; ENDOGENOUS DOPAMINE; C-11 RACLOPRIDE; RESERPINE TREATMENT; INVIVO VOLTAMMETRY; H-3 RACLOPRIDE; PARS COMPACTA; IMPULSE FLOW AB Recent data from positron emission tomography (PET) imaging studies suggest the possibility of studying synaptic transmission in vivo in humans. The approach will require a synthesis of two established techniques: brain activation studies (conventionally performed by measuring regional cerebral blood flow or metabolism) and neurotransmitter receptor imaging (using radiolabelled ligands that bind to specific neuroreceptors). By comparing neuroreceptor binding in subjects at rest and while performing an activation task, it may be possible to determine whether a particular neurotransmitter is involved in performance of the task. The underlying principle is that endogenous neurotransmitter competes with the injected radioligand for the same receptors, thereby inhibiting ligand binding. This effect will be even more pronounced during activation, as the synaptic concentration of transmitter rises. Thus, activation of a specific neurotransmitter will be detected as a decrease in specific binding of the radioligand. In this paper we review neurophysiological and biochemical literature to estimate the endogenous neurotransmitter concentration changes that will be expected to occur during an activation task, using the dopamine system as an example. We calculate that the average synaptic dopamine concentration is approximate to 100 nM and that it approximately doubles during activation. This, along with consideration of the concentration of radioligand and affinities of the ligand and dopamine for dopamine receptors, suggests that physiological activation of a specific neurotransmitter system is likely to be detectable with PET. (C) 1995 Wiley-Liss, Inc. C1 MASSACHUSETTS GEN HOSP,DIV NUCL MED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 51 TC 40 Z9 40 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PY 1995 VL 3 IS 1 BP 24 EP 34 DI 10.1002/hbm.460030104 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA TU287 UT WOS:A1995TU28700003 ER PT J AU Morris, ED Fisher, RE Alpert, NM Rauch, SL Fischman, AJ AF Morris, ED Fisher, RE Alpert, NM Rauch, SL Fischman, AJ TI In vivo imaging of neuromodulation using positron emission tomography: Optimal ligand characteristics and task length for detection of activation SO HUMAN BRAIN MAPPING LA English DT Article DE endogenous; dopamine; receptor; activation; mathematical model; optimization ID ENDOGENOUS DOPAMINE; COCAINE RECEPTORS; C-11 RACLOPRIDE; BINDING; INVIVO; PET; 3-(2'-FLUOROETHYL)SPIPERONE; INVITRO; CELLS; MODEL AB Considerable evidence suggests that cognitive state affects local levels of neurotransmitter in the brain. We introduce a compartment model of neuroreceptor ligand kinetics to describe the effect of change in cognitive state on positron emission tomography (PET) signal dynamics. The model is used to establish optimal experimental conditions, timing of activation, and ligand characteristics, for detecting cognitive activation. The model, which follows free and bound endogenous neurotransmitter, describes the PET curve predicted for a single injection of radioligand in the presence or absence of activation. Activation was conceptualized as the performance of a task that raises the level of neurotransmitter that competes for receptor sites with the radioligand. Simulating the dopamine system, for example, required making assumptions regarding the kinetic rate constants for binding/dissociation of endogenous dopamine to/from the receptor and dopamine concentrations in the synapse. Simulations suggest that activation of dopamine should be detectable with PET and the D2 receptor ligand [C-11]raclopride, although this ligand might not be optimal. Aspects of experimental design can be modified to optimize the likelihood of detecting neurotransmitter changes. The ideal radioligand for these studies should bind irreversibly to its receptor. Furthermore, the task should commence at injection time and last for at least 7 minutes. Optimal task duration depends on the dynamics of free radioligand in the tissue and can be determined via model simulations for any well-characterized receptor ligand. Flow effects were shown to be distinguishable from those of neurotransmitter activation. General principles regarding desirable ligand characteristics and activation timing held for both the D2 receptor and the dopamine transporter site. (C) 1995 Wiley-Liss, Inc. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 24 TC 44 Z9 44 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PY 1995 VL 3 IS 1 BP 35 EP 55 DI 10.1002/hbm.460030105 PG 23 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA TU287 UT WOS:A1995TU28700004 ER PT J AU Kosslyn, SM Alpert, NM Thompson, WL AF Kosslyn, SM Alpert, NM Thompson, WL TI Identifying objects at different levels of hierarchy: A positron emission tomography study SO HUMAN BRAIN MAPPING LA English DT Article DE PET; object identification; object naming; hierarchical categorization; vision; visual cognition,; cognitive neuroscience ID EXTRASTRIATE CORTEX; VISUAL-CORTEX; ATTENTION; PET; SYSTEM AB Subjects decided whether names were appropriate for accompanying pictures while their local cerebral blood flow was monitored using positron emission tomography (PET); in one condition, the names were at the ''entry'' level (i.e., the level spontaneously named, as in ''bird'' for a robin), in another condition they were at a superordinate level (e.g., ''animal''), and in another they were at a subordinate level (e.g., ''robin''). The results indicated that different processes are used to evaluate terms at the different levels of analysis. Specifically, there was evidence that memory search is used to evaluate superordinates, but one must collect additional perceptual information to evaluate subordinates. In addition, in another condition the subjects saw written words that named the entry-level term and decided whether the object could be named by superordinate terms. Similar, but not identical, activation was observed as was found when subjects evaluated superordinate terms for pictures. (C) 1995 Wiley-Liss, Inc. C1 HARVARD UNIV,DEPT PSYCHOL,CAMBRIDGE,MA 02138. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. NR 23 TC 56 Z9 57 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 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PY 1995 VL 3 IS 2 BP 107 EP 132 DI 10.1002/hbm.460030207 PG 26 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA TU288 UT WOS:A1995TU28800005 ER PT J AU Jiang, AP Kennedy, DN Baker, JR Weisskoff, RM Tootell, RBH Woods, RP Benson, RR Kwong, KK Brady, TJ Rosen, BR Belliveau, JW AF Jiang, AP Kennedy, DN Baker, JR Weisskoff, RM Tootell, RBH Woods, RP Benson, RR Kwong, KK Brady, TJ Rosen, BR Belliveau, JW TI Motion detection and correction in functional MR imaging SO HUMAN BRAIN MAPPING LA English DT Article DE motion detection; motion correction; functional magnetic resonance imaging; functional neuroimaging ID SENSORY STIMULATION; AUTOMATED ALGORITHM; BRAIN AB Subject motion present during the time course of functional activation studies is a pervasive problem in mapping the spatial and temporal characteristics of brain activity. In functional MRI (fMRI) studies, the observed signal changes are small. Therefore, it is crucial to reduce the effect of subject motion during the acquisition of image data in order to differentiate true brain activation from artifactual signal changes due to subject motion. We have adapted a technique for automatic motion detection and correction which is based on the ratio-variance minimization algorithm to the fMRI subject motion problem. This method was used for retrospective correction of subject motion in the acquired data and resulted in improved functional maps. In this paper we have designed and applied a series of tests to evaluate the performance of this technique which span the classes of image characteristics common to fMRI. These areas include tests of the accuracy and range of motion as well as measurement of the effect of image signal to noise ratio, focal activation, image resolution, and image coverage on the motion detection system. Also, rye have evaluated the amount of residual motion remaining after motion correction, and the ability of this technique to reduce the motion-induced artifacts and restore regions of activation lost due to subject motion. In summary, this method performed well in the range of image characteristics common for fMRI experiments, reducing residual motion to under 0.5 mm, and removed significant motion-induced artifacts while restoring true regions of activation. Motion correction is expected to become a routine requirement in the analysis of fMRI experiments. (C) 1996 Wiley-Liss, Inc. C1 MASSACHUSETTS GEN HOSP EAST,NMR CTR,DEPT RADIOL,BOSTON,MA 02129. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,CTR MORPHOMETR ANAL,DEPT NEUROL,BOSTON,MA. UNIV CALIF LOS ANGELES,SCH MED,DEPT NEUROL,LOS ANGELES,CA 90024. RI Kennedy, David/H-3627-2012 NR 14 TC 124 Z9 124 U1 0 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PY 1995 VL 3 IS 3 BP 224 EP 235 DI 10.1002/hbm.460030306 PG 12 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA TY222 UT WOS:A1995TY22200005 ER PT J AU Loftus, WC Tramo, MJ Gazzaniga, MS AF Loftus, WC Tramo, MJ Gazzaniga, MS TI Cortical surface modeling reveals gross morphometric correlates of individual differences SO HUMAN BRAIN MAPPING LA English DT Article DE cerebral cortex; cerebral hemispheres; telencephalon; magnetic resonance imaging; quantitative neuroanatomy; monozygotic twins; sex differences; dyslexia ID PLANUM TEMPORALE ASYMMETRY; DEVELOPMENTAL DYSLEXIA; CEREBRAL ASYMMETRY; MONOZYGOTIC TWINS; SCHIZOPHRENIA; BRAIN; RECONSTRUCTION; ABNORMALITIES; LOCALIZATION; HANDEDNESS AB Advances in human neurobiology are now made possible through methods which combine structural magnetic resonance imaging (MRI), three-dimensional reconstruction, and statistical analysis. MRI-based reconstruction enables the in vivo quantification of regional cortical surface area (rCSA) while inter-group comparisons uncover relationships of cortical morphometry with genotype, sex, and developmental abnormalities. In studies on normals we have found strong associations between the rCSA of monozygotic twins as compared to unrelated pairings. Further analysis of this data uncovered significant differences between the male and female twins in left hemisphere rCSA. When these methods were applied to brains of dyslexic subjects and controls, we identified a pattern of differences involving all major subdivisions of both hemispheres. Taken together, these techniques can illuminate structure-function issues in both normal and diseased brains. (C) 1996 Wiley-Liss, Inc. C1 HARVARD UNIV,SCH MED,DEPT NEUROBIOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02115. RP Loftus, WC (reprint author), UNIV CALIF DAVIS,CTR NEUROSCI,DAVIS,CA 95616, USA. NR 78 TC 11 Z9 11 U1 1 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PY 1995 VL 3 IS 4 BP 257 EP 270 DI 10.1002/hbm.460030402 PG 14 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA UE953 UT WOS:A1995UE95300001 ER PT J AU Rauch, SL Savage, CR Brown, HD Curran, T Alpert, NM Kendrick, A Fischman, AJ Kosslyn, SM AF Rauch, SL Savage, CR Brown, HD Curran, T Alpert, NM Kendrick, A Fischman, AJ Kosslyn, SM TI A PET investigation of implicit and explicit sequence learning SO HUMAN BRAIN MAPPING LA English DT Article DE memory; striatum; premotor cortex ID MULTIPLE MEMORY-SYSTEMS; HUNTINGTONS-DISEASE; PARKINSONS-DISEASE; FUNCTIONAL-ANATOMY; WORKING-MEMORY; MOTOR; PERFORMANCE; KNOWLEDGE; DEMENTIA; AMNESIA AB The purpose of this study was to determine the mediating neuroanatomy of implicit and explicit sequence learning using a modified version of the serial reaction time (SRT) paradigm. Subjects were seven healthy, right-handed adults (three male, four female, mean age 26.7, range 18-43 yr). PET data were acquired via the oxygen-15-labeled-carbon dioxide inhalation method while subjects performed the SRT. Subjects were scanned during two blocks each of 1) no sequence (Random), 2) single-blind, 12-item sequence (Implicit), and 3) unblinded, same sequence (Explicit). Whole-brain-normalized images reflecting relative regional cerebral blood flow (rCBF) were transformed to Talairach space, and statistical parametric maps (SPMs) of z-scores were generated for comparisons of interest. The threshold for significant activation was defined as z-score greater than or equal to 3.00. Behavioral data demonstrated significant learning (P <.05) for Implicit and Explicit conditions. Tests of explicit knowledge reflected non-significant explicit contamination during the Implicit condition. Foci of significant activation in the Implicit condition were found in right ventral premotor cortex, right ventral caudate/nucleus accumbens, right thalamus, and bilateral area 19; activation in the Explicit condition included primary visual cortex, peri-sylvian cortex, and cerebellar vermis. Activations in visual and language areas during the Explicit condition may reflect conscious learning strategies including covert verbal rehearsal and visual imagery. Right-sided premotor, striatal, and thalamic activations support the notion that implicit sequence learning is mediated by cortico-striatal pathways, preferentially within the right hemisphere. (C) 1996 Wiley-Liss, Inc. C1 MASSACHUSETTS GEN HOSP, DEPT PSYCHIAT, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, DEPT RADIOL, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, DEPT NEUROL, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, DEPT PSYCHIAT, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DEPT PSYCHOL, BOSTON, MA 02115 USA. NR 69 TC 183 Z9 184 U1 3 U2 13 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PY 1995 VL 3 IS 4 BP 271 EP 286 DI 10.1002/hbm.460030403 PG 16 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA UE953 UT WOS:A1995UE95300002 ER PT J AU CHEN, ZY DENNEY, RM BREAKEFIELD, XO AF CHEN, ZY DENNEY, RM BREAKEFIELD, XO TI NORRIE DISEASE AND MAO GENES - NEAREST NEIGHBORS SO HUMAN MOLECULAR GENETICS LA English DT Review ID MONOAMINE OXIDASE-A; FAMILIAL EXUDATIVE VITREORETINOPATHY; HUMAN-SKIN FIBROBLASTS; CLONED DNA-SEQUENCE; X-CHROMOSOME; B GENES; PRENATAL-DIAGNOSIS; DELETION; LOCUS; MUTATION AB The Norrie disease and MAO genes are tandemly arranged in the p11.4-p11.3 region of the human X chromosome in the order tel-MAOA-MAOB-NDP-cent. This relationship is conserved in the mouse in the order tel-MAOB-MAOA-NDP-cent. The MAO genes appear to have arisen by tandem duplication of an ancestral MAO gene, but their positional relationship to NDP appears to be random. Distinctive X-linked syndromes have been described for mutations in the MAOA and NDP genes, and in addition, individuals have been identified with contiguous gene syndromes due to chromosomal deletions which encompass two or three of these genes. Loss of function of the NDP gene causes a syndrome of congenital blindness and progressive hearing loss, sometimes accompanied by signs of CNS dysfunction, including variable mental retardation and psychiatric symptoms. Other mutations in the NDP gene have been found to underlie another X-linked eye disease, exudative vitreo-retinopathy. An MAOA deficiency state has been described in one family to date, with features of altered amine and amine metabolite levels, low normal intelligence, apparent difficulty in impulse control and cardiovascular difficulty in affected males. A contiguous gene syndrome in which all three genes are lacking, as well as other as yet unidentified flanking genes, results in severe mental retardation, small stature, seizures and congenital blindness, as well as altered amine and amine metabolites. Issues that remain to be resolved are the function of the NDP gene product, the frequency and phenotype of the MAOA deficiency state, and the possible occurrence and phenotype of an MAOB deficiency state. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. UNIV TEXAS,MED BRANCH,DEPT HUMAN BIOL CHEM & GENET,GALVESTON,TX 77550. RP CHEN, ZY (reprint author), MASSACHUSETTS GEN HOSP,DEPT NEUROL,MOLEC NEUROGENET UNIT,BOSTON,MA 02114, USA. NR 101 TC 21 Z9 25 U1 1 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PY 1995 VL 4 SI SI BP 1729 EP 1737 PG 9 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA TC033 UT WOS:A1995TC03300006 PM 8541872 ER PT J AU DRYJA, TP LI, T AF DRYJA, TP LI, T TI MOLECULAR-GENETICS OF RETINITIS-PIGMENTOSA SO HUMAN MOLECULAR GENETICS LA English DT Review ID DEGENERATION SLOW RDS; SYNDROME TYPE-I; PHOTORECEPTOR CGMP PHOSPHODIESTERASE; RETINAL DEGENERATION; BETA-SUBUNIT; FUNCTIONAL EXPRESSION; RHODOPSIN MUTATIONS; MEMBRANE-PROTEIN; POINT MUTATION; NULL MUTATION AB Hereditary degenerations and dysfunctions of the retina are an extremely heterogeneous group of diseases. This summary deals with recent advances in the molecular genetics of a subset of those disorders, namely, those encompassed under the diagnosis 'retinitis pigmentosa'. Over 20 loci where mutations cause retinitis pigmentosa have been mapped; the review focuses on the seven retinitis pigmentosa loci that have been identified. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BERMAN GUND LAB STUDY RETINAL DEGENERAT,BOSTON,MA 02114. RP DRYJA, TP (reprint author), HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,OCULAR MOLEC GENET LAB,BOSTON,MA 02114, USA. NR 85 TC 219 Z9 230 U1 1 U2 9 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PY 1995 VL 4 SI SI BP 1739 EP 1743 PG 5 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA TC033 UT WOS:A1995TC03300007 PM 8541873 ER PT J AU SCHUBACK, DE CHEN, ZY CRAIG, IW BREAKEFIELD, XO SIMS, KB AF SCHUBACK, DE CHEN, ZY CRAIG, IW BREAKEFIELD, XO SIMS, KB TI MUTATIONS IN THE NORRIE DISEASE GENE SO HUMAN MUTATION LA English DT Article DE RETINA; HEARING; MUTATION; NORRIE DISEASE; MENTAL RETARDATION ID X-CHROMOSOME; CANDIDATE GENE; DELETION; DNA; MICRODELETION; SEQUENCE; LOCUS AB We report our experience to date in mutation identification in the Norrie disease (ND) gene. We carried out mutational analysis in 26 kindreds in an attempt to identify regions presumed critical to protein function and potentially correlated with generation of the disease phenotype. All coding exons, as well as noncoding regions of exons 1 and 2, 636 nucleotides in the noncoding region of exon 3, and 197 nucleotides of 5' flanking sequence, were analyzed for single-strand conformation polymorphisms (SSCP) by polymerase chain reaction (PCR) amplification of genomic DNA. DNA fragments that showed altered SSCP band mobilities were sequenced to locate the specific mutations. In addition to three previously described submicroscopic deletions encompassing the entire ND gene, we have now identified 6 intragenic deletions, 8 missense (seven point mutations, one 9-bp deletion), 6 nonsense (three point mutations, three single bp deletions/frameshift) and one 10-bp insertion, creating an expanded repeat in the 5' noncoding region of exon 1. Thus, mutations have been identified in a total of 24 of 26 (92%) of the kindreds we have studied to date. With the exception of two different mutations, each found in two apparently unrelated kindreds, these mutations are unique and expand the genotype database. Localization of the majority of point mutations at or near cysteine residues, potentially critical in protein tertiary structure, supports a previous protein model for norrin as member of a cystine knot growth factor family (Meitinger et al., 1993). Genotype-phenotype correlations were not evident with the limited clinical data available, except in the cases of larger submicroscopic deletions associated with a more severe neurologic syndrome. This lack of correlation suggests that complex epigenetic factors may play a significant role in the physiological and neurodevelopmental expression of the disease phenotype. Given the remarkable intra- and interfamilial variability in hearing and brain dysfunction in this disease, it may be expected that other phenotypic expressions of the disease gene, which do not match the ''classical'' Norrie phenotype, may be identified in the future. (C) 1995 Wiley-Liss, Inc. C1 MASSACHUSETTS GEN HOSP EAST,NEUROL SERV,MOLEC NEUROGENET UNIT,BOSTON,MA 02129. HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02115. UNIV OXFORD,DEPT BIOCHEM,GENET LAB,OXFORD OX1 3QU,ENGLAND. FU NINDS NIH HHS [NS21921] NR 36 TC 51 Z9 52 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PY 1995 VL 5 IS 4 BP 285 EP 292 DI 10.1002/humu.1380050403 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA QZ864 UT WOS:A1995QZ86400002 PM 7627181 ER PT J AU MARK, EJ MULLER, KM MCCHESNEY, T DONGHWAN, S HONIG, C MARK, MA AF MARK, EJ MULLER, KM MCCHESNEY, T DONGHWAN, S HONIG, C MARK, MA TI PLACENTOID BULLOUS LESION OF THE LUNG SO HUMAN PATHOLOGY LA English DT Article DE PLACENTOID; EMPHYSEMA; BULLA; VILLI ID CYSTIC ADENOMATOID MALFORMATION AB Four adult patients presented with unilateral multicystic lung disease. The cysts had been detected years previously on chest radiographs in three patients. Two patients had histories of repeated childhood pneumonias. Preoperative diagnosis of bullous emphysema with rupture was made in three patients who presented with pneumothorax. Lobectomy was done in two patients and pneumonectomy in two patients.,Macroscopically, each lung was spongy with cysts that contained gelatinous vesicular or grape-like structures resembling normal or molar placental tissue. Bullous emphysema was evident in one lung and marked panacinar emphysema in another. In one patient who had a lobectomy, the ipsilateral lobe of compressed lung reexpanded after surgery and proved to be cystic as well on subsequent radiographs. The vesicular and grape-like structures histopathologically are papillary structures with central edematous cores and a covering of cuboidal epithelial cells. Degenerate villi became either hydatidiform, fibrotic, or calcified. At low magnification the histology was similar to that of placenta with hydatidiform change. Emphysematous lung in which villiform structures appeared at the edges of bullae was found histologically in two patients. Lymphangiectasia was present in all patients. The placentoid bullous lesion has distinct macroscopic and microscopic features and is clinically unusual in that the cysts are unilateral and appear in otherwise healthy young adults. We do not know whether the lesion is a malformation or a peculiar devolution of localized bullous emphysema. We favor the latter interpretation. Torsion of lung may cause the lymphangiectasia and contribute to the unusual histology. Excision is curative. HUM PATHOL 26:74-79. Copyright (C) 1995 by W.B. Saunders Company C1 HARVARD UNIV,SCH MED,BOSTON,MA. BAPTIST MEM HOSP,MEMPHIS,TN 38146. UNIV KLIN BOCHUM,BOCHUM,GERMANY. YONSEI UNIV HOSP,SEOUL,SOUTH KOREA. WHITE PLAINS HOSP,MED CTR,WHITE PLAINS,NY. RP MARK, EJ (reprint author), MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114, USA. NR 24 TC 15 Z9 16 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD JAN PY 1995 VL 26 IS 1 BP 74 EP 79 DI 10.1016/0046-8177(95)90117-5 PG 6 WC Pathology SC Pathology GA QB220 UT WOS:A1995QB22000011 PM 7821919 ER PT J AU GOODFRIEND, TL EGAN, B STEPNIAKOWSKI, K BALL, DL AF GOODFRIEND, TL EGAN, B STEPNIAKOWSKI, K BALL, DL TI RELATIONSHIPS AMONG PLASMA-ALDOSTERONE, HIGH-DENSITY-LIPOPROTEIN CHOLESTEROL, AND INSULIN IN HUMANS SO HYPERTENSION LA English DT Article DE INSULIN RESISTANCE; ADRENAL GLOMERULOSA; HYPERTENSION, CORONARY DISEASE RISK ID ZONA GLOMERULOSA CELLS; BLOOD-PRESSURE; ESSENTIAL-HYPERTENSION; WEIGHT-REDUCTION; OBESE PATIENTS; FATTY-ACIDS; GLUCOSE; RENIN; SECRETION; MEN AB To investigate the pathogenesis of hypertension in patients with obesity and insulin resistance and to explore the role of plasma lipids, we studied 30 subjects at the end of 7 days of low (20 mEq/d) then high (200 mEq/d) sodium diets. Glucose and insulin tolerance tests were performed at the end of each week and blood and urine collected for measurements of plasma aldosterone, renin activity, electrolytes, insulin, and lipoproteins. There was a strong negative correlation between plasma aldosterone and high-density lipoprotein cholesterol during both diets. There were weaker positive correlations between plasma aldosterone and insulin or triglycerides. When the aldosterone-renin ratio was the dependent variable and the correlation controlled for serum potassium, the inverse relationship with high-density lipoprotein cholesterol and the positive correlation with insulin remained, but only during the high salt diet. Subjects were divided into three groups based on high-density lipoprotein cholesterol. Subjects with the lowest high-density lipoprotein cholesterol levels showed the highest aldosterone, plasma triglycerides, body mass index, and waist-to-hip ratio. Those subjects also demonstrated the greatest resistance to insulin action on glucose and plasma unesterified fatty acids. There was a weak direct correlation between plasma aldosterone and systolic blood pressure during the high salt diet. These data suggest that high aldosterone levels may be a link between dyslipidemia, insulin resistance, and hypertension, a relationship made more evident by high salt intake. C1 UNIV WISCONSIN,DEPT MED,MADISON,WI. UNIV WISCONSIN,DEPT PHARMACOL,MADISON,WI 53706. MED UNIV S CAROLINA,DEPT PHARMACOL,DIV CLIN PHARMACOL,CHARLESTON,SC 29425. MED UNIV S CAROLINA,DEPT MED,CHARLESTON,SC 29425. RP GOODFRIEND, TL (reprint author), WILLIAM S MIDDLETON MEM VET ADM MED CTR,2500 OVERLOOK TERRACE,MADISON,WI 53705, USA. FU NCRR NIH HHS [M01-RR00058, M01-RR01070]; PHS HHS [R01-43164] NR 26 TC 53 Z9 56 U1 0 U2 3 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0194-911X J9 HYPERTENSION JI Hypertension PD JAN PY 1995 VL 25 IS 1 BP 30 EP 36 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA QA740 UT WOS:A1995QA74000004 PM 7843750 ER PT J AU GIRARD, JP SPRINGER, TA AF GIRARD, JP SPRINGER, TA TI CLONING FROM PURIFIED HIGH ENDOTHELIAL VENULE CELLS OF HEVIN, A CLOSE RELATIVE OF THE ANTIADHESIVE EXTRACELLULAR-MATRIX PROTEIN SPARC SO IMMUNITY LA English DT Article ID NODE VASCULAR ADDRESSIN; LYMPH-NODE; L-SELECTIN; RECIRCULATING LYMPHOCYTES; BINDING; EXPRESSION; MIGRATION; SEQUENCE; TISSUES; MACROPHAGES AB High endothelial venules (HEV) in lymphoid tissues support high levels of lymphocyte extravasion from the blood. We purified high endothelial cells from human tonsils by immunomagnetic selection with MECA-79 MAb to construct an HEV cDNA library. Differential screening of this library using cDNA probes from HEV (plus) or flat-walled vessel (minus) endothelial cells allowed us to characterize a novel human cDNA expressed to high levels in HEV. The cDNA encodes a secreted acidic calcium-binding glycoprotein of 664 aa residues, designated hevin, exhibiting 62% identify with the antiadhesive extracellular matrix protein SPARC, over a region of 232 aa spanning more than four fifths of the SPARC coding sequence. The primary structure and sequence of hevin are similar to SPARC-like proteins from rat and quail, called SC1 or QR1. Hevin could contribute to the induction or maintenance of features of the HEV endothelium that facilitate lymphocyte migration. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RP GIRARD, JP (reprint author), HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115, USA. RI GIRARD, Jean-Philippe/F-5229-2010 FU NCI NIH HHS [CA-31788] NR 51 TC 118 Z9 119 U1 1 U2 4 PU CELL PRESS PI CAMBRIDGE PA 50 CHURCH ST CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 1074-7613 J9 IMMUNITY JI Immunity PD JAN PY 1995 VL 2 IS 1 BP 113 EP 123 DI 10.1016/1074-7613(95)90083-7 PG 11 WC Immunology SC Immunology GA QC593 UT WOS:A1995QC59300010 PM 7600298 ER PT S AU Khan, WN Sideras, P Rosen, FS Alt, FW AF Khan, WN Sideras, P Rosen, FS Alt, FW BE Casali, P Silberstein, LE TI The role of Bruton's tyrosine kinase in B-cell development and function in mice and man SO IMMUNOGLOBULIN GENE EXPRESSION IN DEVELOPMENT AND DISEASE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Immunoglobulin Gene Expression in Development and Disease CY JUL 13-17, 1994 CL MONTREAL, CANADA SP New York Acad Sci ID X-LINKED AGAMMAGLOBULINEMIA; CBA-N MICE; BONE-MARROW; SIGNALING PROTEINS; PH DOMAIN; XID MICE; RESPONSIVENESS; DEFICIENCY; GENES; NUDE C1 CTR BLOOD RES,BOSTON,MA 02115. UMEA UNIV,APPL CELL & MOLEC BIOL UNIT,S-90187 UMEA,SWEDEN. RP Khan, WN (reprint author), CHILDRENS HOSP,HOWARD HUGHES MED INST,300 LONGWOOD AVE,BOSTON,MA 02115, USA. FU NIAID NIH HHS [P01AI35714, AI20047] NR 36 TC 21 Z9 21 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 SN 0077-8923 BN 0-89766-933-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1995 VL 764 BP 27 EP 38 PG 12 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology; Immunology GA BE39E UT WOS:A1995BE39E00005 PM 7486535 ER PT S AU Weaver, D Boubnov, N Wills, Z Hall, K Staunton, J AF Weaver, D Boubnov, N Wills, Z Hall, K Staunton, J BE Casali, P Silberstein, LE TI V(D)J recombination: Double-strand break repair gene products used in the joining mechanism SO IMMUNOGLOBULIN GENE EXPRESSION IN DEVELOPMENT AND DISEASE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Immunoglobulin Gene Expression in Development and Disease CY JUL 13-17, 1994 CL MONTREAL, CANADA SP New York Acad Sci ID ACTIVATED PROTEIN-KINASE; BROKEN DNA-MOLECULES; HAMSTER OVARY CELL; SCID MUTATION; KU-PROTEIN; N-REGIONS; MICE; MUTANTS; PHOSPHORYLATION; LYMPHOCYTES C1 HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOLEC GENET,BOSTON,MA 02115. RP Weaver, D (reprint author), DANA FARBER CANC INST,DIV TUMOR IMMUNOL,44 BINNEY ST,BOSTON,MA 02115, USA. NR 48 TC 8 Z9 8 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 SN 0077-8923 BN 0-89766-933-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1995 VL 764 BP 99 EP 111 PG 13 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology; Immunology GA BE39E UT WOS:A1995BE39E00014 PM 7486596 ER PT S AU Kunkel, LA Vescio, R Cao, J Hong, CH Kim, A Schiller, GJ Lichtenstein, AK Berenson, JR AF Kunkel, LA Vescio, R Cao, J Hong, CH Kim, A Schiller, GJ Lichtenstein, AK Berenson, JR BE Casali, P Silberstein, LE TI Analysis of multiple myeloma third complementarity-determining regions reveals characteristics of prenatal B cells SO IMMUNOGLOBULIN GENE EXPRESSION IN DEVELOPMENT AND DISEASE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Immunoglobulin Gene Expression in Development and Disease CY JUL 13-17, 1994 CL MONTREAL, CANADA SP New York Acad Sci ID DIVERSITY C1 W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90024. RP Kunkel, LA (reprint author), UNIV CALIF LOS ANGELES,SCH MED,DIV HEMATOL ONCOL,LOS ANGELES,CA 90024, USA. NR 3 TC 0 Z9 0 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 SN 0077-8923 BN 0-89766-933-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1995 VL 764 BP 519 EP 522 PG 4 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology; Immunology GA BE39E UT WOS:A1995BE39E00079 PM 7486579 ER PT J AU CHIAPPELLI, F KUNG, MA VILLANUEVA, P LEE, P FROST, P PRIETO, N AF CHIAPPELLI, F KUNG, MA VILLANUEVA, P LEE, P FROST, P PRIETO, N TI IMMUNOTOXICITY OF COCAETHYLENE SO IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY LA English DT Article ID COCAINE; ETHANOL; ALCOHOL; METABOLITE; CONCURRENT AB This report describes the response of normal human T cells to stimulation in vitro in the presence of nano-micromolar concentrations of cocaethylene. Thymidine incorporation by concanavalin A-stimulated peripheral blood mononuclear cells was generally blunted by cocaethylene, albeit to different degrees depending upon the donor tested. The formation of concanavalin A-induced blast cells was decreased by increasing concentrations of cocaethylene. The production of interleukin-2 was also blunted in a dose-dependent fashion by cocaethylene, and this outcome was more consistently observed in stimulated peripheral blood mononuclear cells, compared to unseparated whole blood preparations. An inverse dose dependence was obtained in relation to the response of blast cells to recombinant human interleukin-2 in the presence of cocaethylene. These lines of evidence, taken together with our preliminary studies aimed at testing the effect of cocaethylene on the expression of certain membrane markers of activation (i.e., interleukin-2 receptor, transferrin receptor, serine aminopeptidase IV) and the expression of the proliferating cell nuclear antigen (cyclin PCNA), suggest that cocaethylene modulates relatively early events following T cell stimulation probably related to the interleukin-2 system. C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT NEUROBIOL,LOS ANGELES,CA 90073. W LOS ANGELES VET AFFAIRS MED CTR,HUMAN IMMUNOL & PSYCHONEUROIMMUNOL LAB,LOS ANGELES,CA 90073. RP CHIAPPELLI, F (reprint author), UNIV CALIF LOS ANGELES,SCH DENT,DIV DIAGNOST SCI,HUMAN ORAL & MOLEC IMMUNOL LAB,LOS ANGELES,CA 90024, USA. OI Frost, Patrick/0000-0003-3348-5983 FU NIDA NIH HHS [DA07683] NR 31 TC 4 Z9 4 U1 0 U2 1 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 0892-3973 J9 IMMUNOPHARM IMMUNOT JI Immunopharmacol. Immunotoxicol. PY 1995 VL 17 IS 2 BP 399 EP 417 DI 10.3109/08923979509019759 PG 19 WC Immunology; Pharmacology & Pharmacy; Toxicology SC Immunology; Pharmacology & Pharmacy; Toxicology GA RB111 UT WOS:A1995RB11100012 PM 7650298 ER PT B AU RACHMILEWITZ, D STAMLER, JS KARMELI, F LOSCALZO, J XAVIER, RJ PODOLSKY, DK AF RACHMILEWITZ, D STAMLER, JS KARMELI, F LOSCALZO, J XAVIER, RJ PODOLSKY, DK BE Monteiro, E Veloso, FT TI Role of nitric oxide in the pathogenesis of IBD SO INFLAMMATORY BOWEL DISEASES: NEW INSIGHTS INTO MECHANISMS OF INFLAMMATION AND CHALLENGES IN DIAGNOSIS AND TREATMENT SE FALK SYMPOSIUM LA English DT Proceedings Paper CT 76th Falk Symposium on Inflammatory Bowel Diseases - New Insights into Mechanisms of Inflammation and Challenges in Diagnosis and Treatment CY MAY 05-07, 1994 CL ESTORIL, PORTUGAL C1 MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,BOSTON,MA 02114. NR 0 TC 5 Z9 5 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 0-7923-8884-4 J9 FALK SYMP PY 1995 VL 76 BP 53 EP 60 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA BE21K UT WOS:A1995BE21K00008 ER PT B AU PODOLSKY, DK AF PODOLSKY, DK BE Monteiro, E Veloso, FT TI Advances in the understanding of the pathophysiology of IBD: Clinical implications SO INFLAMMATORY BOWEL DISEASES: NEW INSIGHTS INTO MECHANISMS OF INFLAMMATION AND CHALLENGES IN DIAGNOSIS AND TREATMENT SE FALK SYMPOSIUM LA English DT Proceedings Paper CT 76th Falk Symposium on Inflammatory Bowel Diseases - New Insights into Mechanisms of Inflammation and Challenges in Diagnosis and Treatment CY MAY 05-07, 1994 CL ESTORIL, PORTUGAL C1 MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 0-7923-8884-4 J9 FALK SYMP PY 1995 VL 76 BP 91 EP 99 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA BE21K UT WOS:A1995BE21K00012 ER PT B AU Zielstorff, RD AF Zielstorff, RD BE Henry, SB Holzemer, WL Tallberg, M Grobe, SJ TI Capturing and using clinical outcome data: Implications for information systems design SO INFORMATICS: INFRASTRUCTURE FOR QUALITY ASSESSMENT & IMPROVEMENT IN NURSING LA English DT Proceedings Paper CT Working Conference on Informatics: The Infrastructure for Quality Assessment and Improvement in Nursing CY JUN 22-25, 1994 CL AUSTIN, TX SP WHO, IMIA ID HEALTH-CARE; INDICATORS; PATIENT AB There is an urgent need to capture and record data related to clinical outcomes, but there are many barriers. The range of problems includes lack of agreement on conceptualization of the term "outcome," inadequate measures of outcomes, and inadequate information systems to capture and manipulate data that would reflect outcomes. This paper focuses on information system requirements to capture, store and utilize clinical outcome data. For greatest accuracy, outcome data should be captured as close to the source as possible, including direct data capture from patients themselves, and from their families. To make maximum use of outcome data, systems must be designed to 1) store data in multipurpose databases; 2) share data across different platforms; 3) link outcome data to other data that might influence or explain outcomes; 4) allow querying of the data by authorized personnel; and 5) protect patient confidentiality. C1 Massachusetts Gen Hosp, Dept Nursing, Boston, MA 02114 USA. NR 35 TC 0 Z9 0 U1 0 U2 0 PU UNIV CALIF SAN FRANCISCO SCHOOL OF NURSING PI SAN FRANCISCO PA 3RD & PARNASSUS AVE, SAN FRANCISCO, CA 94143 USA BN 0-943671-11-6 PY 1995 BP 87 EP 91 PG 5 WC Nursing SC Nursing GA BR89B UT WOS:000167919600014 ER PT J AU GRAFF, S JUPITER, J AF GRAFF, S JUPITER, J TI FRACTURE OF THE DISTAL RADIUS - CLASSIFICATION OF TREATMENT AND INDICATIONS FOR EXTERNAL FIXATION SO INJURY-INTERNATIONAL JOURNAL OF THE CARE OF THE INJURED LA English DT Article DE DISTAL RADIAL FRACTURE; FRACTURE CLASSIFICATION; EXTERNAL FIXATION AB A number of classifications have been created for fractures of the distal radius. We describe those of Older et al., Frykman, Thomas, Melone, McMurtry, Fernandez, the Mayo and the AO/ASIF. These classifications help to identify unstable fractures and offer insight into the indications for external skeletal fixation. C1 MASSACHUSETTS GEN HOSP,DEPT ORTHOPAED,15 PARKMAN ST,BOSTON,MA 02114. NR 0 TC 1 Z9 1 U1 0 U2 1 PU BUTTERWORTH-HEINEMANN LTD PI OXFORD PA LINACRE HOUSE JORDAN HILL, OXFORD, OXON, ENGLAND OX2 8DP SN 0020-1383 J9 INJURY JI Inj.-Int. J. Care Inj. PY 1995 VL 25 SU 4 BP SD14 EP SD25 DI 10.1016/0020-1383(95)90533-4 PG 12 WC Critical Care Medicine; Emergency Medicine; Orthopedics; Surgery SC General & Internal Medicine; Emergency Medicine; Orthopedics; Surgery GA QA458 UT WOS:A1995QA45800003 ER PT B AU Mankin, HJ AF Mankin, HJ BE Jackson, DW TI Metabolic bone disease SO INSTRUCTIONAL COURSE LECTURES, VOL 44, 1995 SE AMERICAN ACADEMY OF ORTHOPAEDIC SURGEONS INSTRUCTIONAL COURSE LECTURES LA English DT Proceedings Paper CT 1994 Instructional Course Lectures, at the 61st Annual Meeting of the American-Academy-of-Orthopaedic-Surgeons CY 1994 CL NEW ORLEANS, LA SP Amer Acad Orthopaed Surgeons RP Mankin, HJ (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU AMER ACAD ORTHOPAEDIC SURGEONS PI ROSEMONT PA 6300 NORTH RIVER RD, ROSEMONT, IL 60018 BN 0-89203-115-8 J9 AAOS INSTR COURS LEC PY 1995 VL 44 BP 3 EP 29 PG 27 WC Orthopedics SC Orthopedics GA BH44U UT WOS:A1995BH44U00001 ER PT B AU Jupiter, JB AF Jupiter, JB BE Jackson, DW TI Complex fractures of the distal part of the humerus and associated complications SO INSTRUCTIONAL COURSE LECTURES, VOL 44, 1995 SE AMERICAN ACADEMY OF ORTHOPAEDIC SURGEONS INSTRUCTIONAL COURSE LECTURES LA English DT Proceedings Paper CT 1994 Instructional Course Lectures, at the 61st Annual Meeting of the American-Academy-of-Orthopaedic-Surgeons CY 1994 CL NEW ORLEANS, LA SP Amer Acad Orthopaed Surgeons RP Jupiter, JB (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 0 TC 9 Z9 9 U1 0 U2 0 PU AMER ACAD ORTHOPAEDIC SURGEONS PI ROSEMONT PA 6300 NORTH RIVER RD, ROSEMONT, IL 60018 BN 0-89203-115-8 J9 AAOS INSTR COURS LEC PY 1995 VL 44 BP 187 EP 198 PG 12 WC Orthopedics SC Orthopedics GA BH44U UT WOS:A1995BH44U00017 ER PT S AU Kopf, M Ramsay, A Brombacher, F Baumann, H Freer, G Galanos, C Gutierrez-Ramos, JC Kohler, G AF Kopf, M Ramsay, A Brombacher, F Baumann, H Freer, G Galanos, C Gutierrez-Ramos, JC Kohler, G BE Mackiewicz, A Koj, A Sehgal, PB TI Pleiotropic defects of IL-6-deficient mice including early hematopoiesis, T and B cell function, and acute phase responses SO INTERLEUKIN-6 TYPE CYTOKINES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Interleukin-6-Type Cytokines CY JUN 19-22, 1994 CL POZNAN, POLAND SP New York Acad Sci, State Comm Sci Res, Warsaw, Poland, Acad Med, Poznan, Ares Serono, Switzerland, Maria Skoldowska Curie II Fund, Syntex Pharm AG, Poland, Abbott Labs, Alab, AVL Diagnost, Biomedica, Bristol Myers, Cheminst, Cormay, Genzyme Corp Arcid, Poland, Glaxo, Immunex Res & Dev Corp, Jenoptic Merazet Polska, Kebo Lab, Miles Inc, Pfizer Cent Res, Polish Soc Immunol, Prospecta, R W Johnson Pharm Res Inst, Stefan Batory Fdn, Sy Lab ID TUMOR-NECROSIS-FACTOR; LEUKEMIA INHIBITORY FACTOR; STEM-CELLS; ENDOTOXIC-SHOCK; DEFICIENT MICE; PROTECTS MICE; GROWTH-FACTOR; IN-VIVO; INTERLEUKIN-6; RECEPTOR C1 John Curtin Sch Med Res, Canberra, ACT 2601, Australia. New York State Dept Hlth, Roswell Pk Mem Inst, Dept Mol & Cellular Biol, Buffalo, NY 14263 USA. Univ Zurich, CH-8006 Zurich, Switzerland. Ctr Blood Res, Boston, MA 02115 USA. RP Kopf, M (reprint author), Max Planck Inst Immunbiol, Postbach 1169, D-79111 Freiburg, Germany. RI freer, giulia/H-4609-2012 NR 43 TC 66 Z9 66 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 0-89766-931-2 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1995 VL 762 BP 308 EP 318 PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Immunology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Cell Biology; Immunology; Science & Technology - Other Topics GA BK04C UT WOS:000070968500027 PM 7545368 ER PT J AU DENCKER, SJ GOLDBERG, D LADER, M LIBERMAN, RP AF DENCKER, SJ GOLDBERG, D LADER, M LIBERMAN, RP TI IMPROVEMENT OF THE QUALITY-OF-LIFE IN SCHIZOPHRENIA - IMPROVEMENT OF COMPLIANCE - QUALITY ASSURANCE - INCREASED QUALITY-OF-LIFE IN COMMUNITY CARE OF SCHIZOPHRENIA - PAPERS PRESENTED DURING THE XIITH AEP CONGRESS, COPENHAGEN, SEPTEMBER 1994 SO INTERNATIONAL CLINICAL PSYCHOPHARMACOLOGY LA English DT Editorial Material C1 GOTHENBURG UNIV,DEPT CLIN NEUROSCI,GOTHENBURG,SWEDEN. INST PSYCHIAT,LONDON SE5 8AF,ENGLAND. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,DEPT PSYCHIAT & BIOBEHAV SCI,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,CAMARILLO STATE HOSP,CAMARILLO RES CTR,LOS ANGELES,CA. RP DENCKER, SJ (reprint author), SAHLGRENS UNIV HOSP,PSYCHIAT SECT,S-41345 GOTHENBURG,SWEDEN. NR 0 TC 0 Z9 0 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0268-1315 J9 INT CLIN PSYCHOPHARM JI Int. Clin. Psychopharmacol. PD JAN PY 1995 VL 9 SU 5 BP 3 EP 3 PG 1 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA QT372 UT WOS:A1995QT37200001 ER PT J AU LIBERMAN, RP KOPELOWICZ, A AF LIBERMAN, RP KOPELOWICZ, A TI BASIC ELEMENTS IN BIOBEHAVIORAL TREATMENT AND REHABILITATION OF SCHIZOPHRENIA SO INTERNATIONAL CLINICAL PSYCHOPHARMACOLOGY LA English DT Article; Proceedings Paper CT XIIth AEP (Average Evoked Potential) Congress CY SEP, 1994 CL COPENHAGEN, DENMARK DE SCHIZOPHRENIA; BIOBEHAVIORAL THERAPY ID SOCIAL SKILLS; EXPRESSED EMOTION; CONTROLLED TRIAL; MENTALLY-ILL; MANAGEMENT; INTERVENTION; HALOPERIDOL; FAMILIES; RELAPSE AB The psychopathology and associated disabilities experienced by persons with schizophrenia have only partially responded to conventional pharmacological and psychosocial treatment approaches. Biobehavioral therapy employs behavioral and symptomatic assessment, social learning principles, and skills training, to amplify the effects of pharmacotherapy. Comprehensive, continuous, and integrated biobehavioral therapy-aiming at early detection and treatment of schizophrenic symptoms, family and social skills training, and teaching coping and illness self-management skills-has been documented to improve the course and outcome of schizophrenia as measured by symptom recurrence, social functioning, and quality of life, Biobehavioral therapies must be delivered in the context of a collaborative relationship among patients, families and clinicians that together can optimize outcomes. Services need to be provided by assertive, outreach, community-based teams that tailor the type, frequency and scope of services to the phase of the individual's illness. C1 UNIV CALIF LOS ANGELES,DEPT PSYCHIAT & BIOBEHAV SCI,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,CAMARILLO STATE HOSP,CAMARILLO RES CTR,LOS ANGELES,CA. LOS ANGELES CTY DEPT MENTAL HLTH,SAN FERNANDO MENTAL HLTH CLIN,LOS ANGELES,CA. RP LIBERMAN, RP (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,11301 WILSHIRE BLVD,LOS ANGELES,CA 90073, USA. OI kopelowicz, alex/0000-0002-1728-4105 NR 52 TC 17 Z9 17 U1 2 U2 2 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0268-1315 J9 INT CLIN PSYCHOPHARM JI Int. Clin. Psychopharmacol. PD JAN PY 1995 VL 9 SU 5 BP 51 EP 58 DI 10.1097/00004850-199501005-00009 PG 8 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA QT372 UT WOS:A1995QT37200009 PM 7622835 ER PT J AU DENCKER, SJ LIBERMAN, RP AF DENCKER, SJ LIBERMAN, RP TI FROM COMPLIANCE TO COLLABORATION IN THE TREATMENT OF SCHIZOPHRENIA SO INTERNATIONAL CLINICAL PSYCHOPHARMACOLOGY LA English DT Article; Proceedings Paper CT XIIth AEP (Average Evoked Potential) Congress CY SEP, 1994 CL COPENHAGEN, DENMARK ID MANAGEMENT C1 GOTHENBURG UNIV,DEPT CLIN NEUROSCI,GOTHENBURG,SWEDEN. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,DEPT PSYCHIAT & BIOBEHAV SCI,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,CAMARILLO STATE HOSP,CAMARILLO RES CTR,LOS ANGELES,CA. RP DENCKER, SJ (reprint author), SAHLGRENS UNIV HOSP,PSYCHIAT SECT,S-41345 GOTHENBURG,SWEDEN. NR 12 TC 16 Z9 17 U1 2 U2 2 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0268-1315 J9 INT CLIN PSYCHOPHARM JI Int. Clin. Psychopharmacol. PD JAN PY 1995 VL 9 SU 5 BP 75 EP 78 DI 10.1097/00004850-199501005-00012 PG 4 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA QT372 UT WOS:A1995QT37200012 PM 7622838 ER PT J AU CRAIG, WA AF CRAIG, WA TI KINETICS OF ANTIBIOTICS IN RELATION TO EFFECTIVE AND CONVENIENT OUTPATIENT PARENTERAL THERAPY SO INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS LA English DT Article DE OUTPATIENT PARENTERAL ANTIBIOTIC THERAPY (OPAT); KINETICS OF DRUGS ID PENICILLIN-G; PHARMACOKINETICS; SUSCEPTIBILITY; EFFICACY; INVITRO AB An important goal of outpatient parenteral antibiotic therapy (OPAT) is to provide a drug and dosing regimen that allows for convenient administration of the antibiotic in the outpatient setting. While once-daily administration or handling of the drug would be ideal, dosing frequencies up to three times a day for intravenous administration and twice daily for intramuscular injection can be tolerated by most patients. The frequency and method of antimicrobial administration is dependent not only on the kinetics of drug concentrations in serum and tissues (i.e pharmacokinetics), but also on the kinetics or time course of the drug's antimicrobial activity (i.e. pharmacodynamics). This short review will focus on the interaction between pharmacokinetics and pharmacodynamics for the major classes of antibacterial agents used for outpatient parenteral therapy. C1 UNIV WISCONSIN,DEPT MED,MADISON,WI 53705. RP CRAIG, WA (reprint author), WILLIAM S MIDDLETON MEM VET ADM MED CTR,DEPT MED,2500 OVERLOOK TERRACE,MADISON,WI 53705, USA. NR 19 TC 9 Z9 9 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-8579 J9 INT J ANTIMICROB AG JI Int. J. Antimicrob. Agents PD JAN PY 1995 VL 5 IS 1 BP 19 EP 22 DI 10.1016/0924-8579(94)00048-Y PG 4 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA QE147 UT WOS:A1995QE14700005 PM 18611640 ER PT J AU GUINAN, EC GILLIO, AP AF GUINAN, EC GILLIO, AP TI THERAPEUTIC USE OF CYTOKINES IN CHILDREN SO INTERNATIONAL JOURNAL OF PEDIATRIC HEMATOLOGY/ONCOLOGY LA English DT Editorial Material C1 MEM SLOAN KETTERING CANC CTR,DEPT PEDIAT,NEW YORK,NY 10021. CHILDRENS HOSP,DEPT MED,BOSTON,MA. RP GUINAN, EC (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT HEMATOL ONCOL,44 BINNEY ST,BOSTON,MA 02115, USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 1070-2903 J9 INT J PEDIAT HEM ONC JI Int. J. Pediatr. Hematol-Oncol. PY 1995 VL 2 IS 2 BP 85 EP 85 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA RJ129 UT WOS:A1995RJ12900001 ER PT J AU GILLIO, AP GUINAN, EC AF GILLIO, AP GUINAN, EC TI CYTOKINE TREATMENT OF INHERITED BONE-MARROW FAILURE SYNDROMES SO INTERNATIONAL JOURNAL OF PEDIATRIC HEMATOLOGY/ONCOLOGY LA English DT Article ID DIAMOND-BLACKFAN ANEMIA; COLONY-STIMULATING FACTOR; RECOMBINANT HUMAN INTERLEUKIN-3; CONGENITAL HYPOPLASTIC-ANEMIA; FORMING UNIT-MEGAKARYOCYTE; ACUTE MYELOCYTIC-LEUKEMIA; FANCONIS ANEMIA; APLASTIC-ANEMIA; PROGENITOR CELLS; FACTOR RECEPTORS AB The inherited bone marrow failure states are rare hematologic disorders which result in peripheral blood cytopenias. To date, various treatment modalities have resulted in partial and usually short-lived responses. The recent large scale production of recombinant human hematopoietic stimulating factors (cytokines) has offered a new possible treatment modality. Recent phase I-II studies indicate a significant but unpredictable proportion of these patients will respond to cytokines with an improvement in blood counts. Multilineage responses in pancytopenic patients are rare. Duration of response, effect on natural history and potential adverse effects of long-term treatment have yet to be determined. C1 CHILDRENS HOSP,DEPT MED,BOSTON,MA. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT HEMATOL ONCOL,BOSTON,MA 02115. RP GILLIO, AP (reprint author), MEM SLOAN KETTERING CANC CTR,DEPT PEDIAT,1275 YORK AVE,NEW YORK,NY 10021, USA. NR 58 TC 1 Z9 1 U1 0 U2 0 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 1070-2903 J9 INT J PEDIAT HEM ONC JI Int. J. Pediatr. Hematol-Oncol. PY 1995 VL 2 IS 2 BP 125 EP 133 PG 9 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA RJ129 UT WOS:A1995RJ12900006 ER PT J AU MENDEZ, MF AF MENDEZ, MF TI THE NEUROPSYCHIATRY OF MULTIPLE-SCLEROSIS SO INTERNATIONAL JOURNAL OF PSYCHIATRY IN MEDICINE LA English DT Article DE MULTIPLE SCLEROSIS; DEMENTIA; DEPRESSION; APRAXIA; CORPUS CALLOSUM; DISCONNECTION; DEMYELINATION ID COGNITIVE FUNCTION; CORPUS-CALLOSUM; DEMENTIA; IMPAIRMENT; DISORDER; DISEASE; ANTEROGRADE; DISABILITY; DEPRESSION; ATROPHY AB Objective: This article examines the cognitive and psychiatric features of multiple sclerosis. MS can manifest as a neuropsychiatric disturbance even in the absence of physical disabilities. Method: Two MS patients with predominant behavioral symptoms are described, and the literature is reviewed. Results: The first patient had an interhemispheric disconnection syndrome, and the second patient had cognitive fatigue and depression. Other patients have slowed information processing speed, memory retrieval difficulty, frontal-executive dysfunction, and visuospatial difficulty. Conclusions: MS results in specific cognitive deficits and mood disorders. These two patients had organic mental disorders from cerebral demyelination particularly affecting the corpus callosum. Other patients have neuropsychiatric symptoms from extensive demyelination of prefrontal-subcortical circuits. Evaluation and management strategies are discussed. C1 UNIV CALIF LOS ANGELES,LOS ANGELES,CA. RP MENDEZ, MF (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,NEUROBEHAV UNIT,WILSHIRE & SAWTELLE BLVD,LOS ANGELES,CA 90073, USA. NR 53 TC 12 Z9 13 U1 2 U2 4 PU BAYWOOD PUBL CO INC PI AMITYVILLE PA 26 AUSTIN AVE, AMITYVILLE, NY 11701 SN 0091-2174 J9 INT J PSYCHIAT MED JI Int. J. Psychiatr. Med. PY 1995 VL 25 IS 2 BP 123 EP 135 DI 10.2190/NK8F-MTUW-QHH1-0531 PG 13 WC Psychiatry SC Psychiatry GA RN036 UT WOS:A1995RN03600001 PM 7591490 ER EF