FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Gross, ER AF Gross, ER TI 1998 changes to the ABIH Certification Maintenance Program SO AMERICAN INDUSTRIAL HYGIENE ASSOCIATION JOURNAL LA English DT Editorial Material RP Gross, ER (reprint author), DANA FARBER CANC INST,BOSTON,MA 02115, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER INDUSTRIAL HYGIENE ASSOC PI FAIRFAX PA 2700 PROSPERITY AVE #250, FAIRFAX, VA 22031-4307 SN 0002-8894 J9 AM IND HYG ASSOC J JI Am. Ind. Hyg. Assoc. J. PD AUG PY 1997 VL 58 IS 8 BP 560 EP 561 PG 2 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA XM636 UT WOS:A1997XM63600002 ER PT J AU Padial, LR Oliver, A Vivaldi, M Sagie, A Freitas, N Weyman, AE Levine, RA AF Padial, LR Oliver, A Vivaldi, M Sagie, A Freitas, N Weyman, AE Levine, RA TI Doppler echocardiographic assessment of progression of aortic regurgitation SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID LEFT-VENTRICULAR FUNCTION; ASYMPTOMATIC PATIENTS; VALVE-REPLACEMENT; OPERATIVE INTERVENTION; NATURAL-HISTORY; OPTIMUM TIME; INSUFFICIENCY; QUANTITATION; NIFEDIPINE AB The rate of progression of the degree of chronic aortic regurgitation (AR) is unknown. Furthermore, although left ventricular (LV) dilation has been studied in patients with severe AR, its rate and determining factors, and specifically, its relation to the degree of regurgitation remain to be established and have not previously been studied for mild and moderate AR. The purpose of this study was to explore the progression of chronic AR by 2-dimensional and Doppler echocardiography, and the relation of LV dilation to the fundamental regurgitant lesion and its progression in patients with a full spectrum of initial AR severity. We studied 127 patients with AR by 2-dimensional and Doppler echocardiography (69 men; 59 +/- 21 years; 67 with mild, 45 with moderate, 15 with severe AR). AR increased in 38 patients (30%) (25% of mild, 44% of moderate, and 50% of moderate to severe lesions; p <0.006). The ratio of proximal AR jet height to LV outflow tract height also increased (30.3 +/- 17.5% vs 35.2 +/- 19.7%; p <0.0001). Initial LV volumes and mass were larger in patients with more severe AR and increased significantly during follow-vp (138 +/- 53 to 164 +/- 70 ml; 59 +/- 32 to 71.7 +/- 42 ml; 203 +/- 89 to 241 +/- 114 g; p <0.0001). LV volumes and mass increased foster in patients with more severe AR, and in those in whom the degree of AR progressed more rapidly. Finally, patients with bicuspid aortic valve (n = 21) had a higher prevalence of severe AR than patients with tricuspid aortic valves (52% vs 4%; p <0.001). In conclusion, AR is a progressive disease not only in patients with severe AR but also in those with mild and moderate regurgitation. Patients with more severe AR have larger left ventricles that also dilate more rapidly. (C) 1997 by Excerpta Medica, Inc. C1 MASSACHUSETTS GEN HOSP,DEPT CARDIOL,BOSTON,MA 02114. NR 30 TC 18 Z9 20 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD AUG 1 PY 1997 VL 80 IS 3 BP 306 EP 314 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA XP486 UT WOS:A1997XP48600010 PM 9264424 ER PT J AU Raguso, CA Ajami, AM Gleason, R Young, VR AF Raguso, CA Ajami, AM Gleason, R Young, VR TI Effect of cystine intake on methionine kinetics and oxidation determined with oral tracers of methionine and cysteine in healthy adults SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE methionine balance; sulfur amino acid requirement; cysteine; cystine; carboxyl flux; methyl flux; humans ID AMINO-ACID REQUIREMENTS; RAT-LIVER; YOUNG MEN; LEUCINE; HUMANS; L-METHIONINE; GLUTATHIONE; METABOLISM; BALANCE; PROTEIN AB There is evidence based on nitrogen balance that dietary cystine spares, from similar to 16% to 89%, the total methionine requirement. In a previous study we did not detect, by tracer techniques, a sparing effect of cystine when the diet provided methionine at a limiting intake (requirement level: 13 mg.kg(-1).d(-1)). One reason could be that we used an intravenous infusion of the tracer, which may not, therefore, have labeled the carbon dioxide derived from the splanchnic oxidation of dietary methionine. The aim of this study was to compare methionine metabolism and oxidation in eight healthy adults given for 6 d each of three different diets: 13 mg (87.0 mu mol) methionine.kg(-1).d(-1) and no cystine (diet A); 5 mg (33.5 mu mol) methionine.kg(-1).d(-1) and no cystine (diet B); and 5 mg (33.5 mu mol) methionine.kg(-1).d(-1) and 6.5 mg (52.4 mu mol) cystine.kg(-1).d(-1) (diet C). On day 7, tracers ([1-C-13, methyl-H-2(3)]methionine and [H-2(2)]cysteine) were administered orally at 30-min intervals for 8 h. Blood and breath samples were obtained for analysis during 3-h fasting and consecutive 5-h feeding periods. During fasting, me thionine oxidation and methionine methyl (Q(m)) and carboxyl (Q(c)) fluxes and plasma concentrations were not affected by the amount of sulfur amino acids in the three diets. In the fed state methionine oxidation was significantly lower during diets B (3.0 +/- 0.5 mu mol.kg(-1).h(-1)) and C (2.8 +/- 0.6 mu mol.kg(-1).h(-1)) than during diet A (4.1 +/- 0.9 mu mol.kg(-1).h(-1)); there were no significant differences between diets B and C. Q(m) and Q(c) decreased with decreased methionine intake but no effect was observed by adding cystine. Cysteine flux (Q(cys)) was not affected by diet composition but it was lower during feeding than during fasting. In conclusion, replacing approximate to 60% of the total requirement for methionine with cystine over a short diet period did not result in a detectable sparing of methionine oxidation. C1 MASSACHUSETTS GEN HOSP,SHRINERS BURNS INST,BOSTON,MA 02114. RP Raguso, CA (reprint author), MIT,SCH SCI,HUMAN NUTR LAB,77 MASSACHUSETTS AVE,ROOM E17-434,CAMBRIDGE,MA 02139, USA. FU NCRR NIH HHS [RR88]; NIDDK NIH HHS [DK 15856]; NIGMS NIH HHS [GM 02700] NR 37 TC 41 Z9 42 U1 0 U2 1 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-2310, BETHESDA, MD 20814-3998 SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD AUG PY 1997 VL 66 IS 2 BP 283 EP 292 PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA XN547 UT WOS:A1997XN54700009 PM 9250106 ER PT J AU Lieberman, DA Oehlke, M Helfand, M AF Lieberman, DA Oehlke, M Helfand, M TI Risk factors for Barrett's esophagus in community-based practice SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID PREVALENCE AB Objectives: Endoscopy is often performed in patients with gastroesophageal reflux (GER) disease because of concern about the presence of Barrett's esophagus (BE). The purpose of this study was to determine,whether the duration of GER symptoms and/or a history of esophagitis was associated with an increased risk of BE. Methods: This was an observational, prospective, community-based study. Consecutive patients undergoing elective endoscopy because of GER symptoms were enrolled. Endoscopy reports and pathological findings were reviewed to classify patients as having no esophagitis, esophagitis, or probable BE. Correlations with duration of symptoms and a history of esophagitis were analyzed. Results: In all, 701 of 2641 patients (27%) undergoing elective endoscopy had GER symptoms, and 77 of these patients had probable BE. Compared with patients with GER symptoms for less than 1 yr, the odds ratio for BE in patients with GER symptoms for 1-5 years was 3.0 and increased to 6.4 in patients with symptoms for more than 10 yr (p < 0.001). A history of esophagitis was not an independent risk factor for BE (p = 0.17). Conclusions: Prevalence of BE is strongly associated with duration of GER symptoms. C1 OREGON HLTH SCI UNIV, DEPT MED, DIV GEN MED, PORTLAND, OR 97207 USA. PORTLAND VET AFFAIRS MED CTR, GASTROENTEROL SECT, PORTLAND, OR 97207 USA. RP OREGON HLTH SCI UNIV, DEPT MED, DIV GASTROENTEROL, 111-A, POB 1034, PORTLAND, OR 97207 USA. NR 12 TC 197 Z9 200 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD AUG PY 1997 VL 92 IS 8 BP 1293 EP 1297 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA XP756 UT WOS:A1997XP75600011 PM 9260792 ER PT J AU Strausbaugh, L AF Strausbaugh, L TI Antimicrobial resistance: Problems, laments, and hopes SO AMERICAN JOURNAL OF INFECTION CONTROL LA English DT Editorial Material ID STAPHYLOCOCCUS-AUREUS RP Strausbaugh, L (reprint author), PORTLAND VA MED CTR,648-111F,3710 SW VET HOSP RD,PORTLAND,OR 97207, USA. NR 15 TC 8 Z9 8 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0196-6553 J9 AM J INFECT CONTROL JI Am. J. Infect. Control PD AUG PY 1997 VL 25 IS 4 BP 294 EP 296 DI 10.1016/S0196-6553(97)90020-1 PG 3 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA XR045 UT WOS:A1997XR04500002 PM 9276540 ER PT J AU Hashimoto, H Bohmer, MJ Harrell, LC Palacios, IF AF Hashimoto, H Bohmer, MJ Harrell, LC Palacios, IF TI Continuous quality improvement decreases length of stay and adverse events: A case study in an interventional cardiology program SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID PERIPHERAL VASCULAR COMPLICATIONS; CORONARY ANGIOPLASTY; FOLLOW-UP; ATHERECTOMY; MULTICENTER; RESTENOSIS; MANAGEMENT; EXPERIENCE; LESION; CARE AB A study was performed to assess the effectiveness of continuous quality improvement in achieving a better quality of care for patients undergoing coronary interventions. Increasing utilization of new coronary interventional devices has incurred a higher incidence of complications, prolonged hospital stay, and related costs. Using a clinical information system, we adopted continuous quality improvement to control the incidence of complications and postprocedural length of stay. Multiple regression analysis and a matched case-control study were performed to detect complications related to postprocedural length of stay and their causes among 342 patients. The results led to the modification of the postprocedural heparin anticoagulation protocol, which was followed by the introduction of a ticlopidine-based poststent anticoagulation regimen. Two sequential groups of patients (n 261,n = 266) were selected to compare postprocedural length of stay and frequency of complications with those for the first group. Adjustments were made for patients and procedural characteristics through stratification and multiple regression methods. Blood transfusion was the most important predictor of prolonged hospital stay (partial R-2 = 0.26, P < 0.01). A high level of postprocedural anticoagulation and intracoronary stent use were significantly associated with blood transfusion (P 0.01, P 0.02, respectively). The comparison among the three groups showed that heparin protocol change reduced only postprocedural length of stay (P < 0.001) for patients without stents, whereas the stent change in anticoagulation protocol significantly reduced both transfusion and hospital stay for patients with stents (P < 0.001, P < 0.05, respectively). Continuous quality improvement based on clinical information is promising to control both complications and hospital costs. Physician involvement is necessary throughout the process. C1 MASSACHUSETTS GEN HOSP,CARDIAC UNIT,INTERVENT CARDIOL PROGRAM,BOSTON,MA 02114. HARVARD UNIV,SCH PUBL HLTH,TEIKYO HARVARD PROGRAM,CLIN PRACTICE EVALUAT & MANAGEMENT UNIT,BOSTON,MA 02115. NR 28 TC 12 Z9 12 U1 0 U2 2 PU AMER MED PUBLISHING, M W C COMPANY PI OLD BRIDGE PA 1816 ENGLISHTOWN RD, STE 101, OLD BRIDGE, NJ 08857 SN 1088-0224 J9 AM J MANAG C JI Am. J. Manag. Care PD AUG PY 1997 VL 3 IS 8 BP 1141 EP 1150 PG 10 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA YB754 UT WOS:A1997YB75400001 PM 10173131 ER PT J AU George, MJ Snydman, DR Werner, BG Griffith, J Falagas, ME Dougherty, NN Rubin, RH AF George, MJ Snydman, DR Werner, BG Griffith, J Falagas, ME Dougherty, NN Rubin, RH TI The independent role of cytomegalovirus as a risk factor for invasive fungal disease in orthotopic liver transplant recipients SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID VIRUS-INFECTION; OPPORTUNISTIC INFECTIONS; RENAL-TRANSPLANTATION; IMMUNE GLOBULIN; SUBSET AB PURPOSE: TO assess impact of cytomegalovirus (CMV) donor-recipient serostatus, infection, or disease on development of invasive fungal infection in orthotopic liver transplant recipients. PATIENTS AND METHODS: An analysis of prospectively collected data in 146 liver transplant recipients (intention to treat cohort) from 4 tertiary care, university-affiliated transplant centers in Boston (Boston Center for Liver Transplantation). Patients were observed for 1 year after transplantation for the development of CMV infection, CMV disease, CMV pneumonia, as well as for the development of opportunistic fungal infections, graft survival, and mortality. Weekly cultures were taken of urine and throat and every other week of buffy coat for CMV for 2 months, then monthly for 6 months, at 1 year, and at the time of any clinical illness, Pre-and posttransplant variables including CMV-serostatus of donor and recipient, fungal isolation from sterile body sites, fungemia, bacteremia, antibiotic use, immunosuppression, treatment for rejection, and volumes of blood products were measured. RESULTS: Survival analysis demonstrated that 36% of patients with CMV disease developed invasive fungal disease within the first year post-transplant compared with 8% of those without CMV disease (P < 0.0001). One-year mortality in patients with invasive fungal disease was 15 of 22 (68%) compared with 23 of 124 (19%) in those without invasive fungal disease (P < 0.001). A multivariable, time-dependent analysis demonstrated that being a CMV-seronegative recipient of a CMV-seropositive donor organ (P < 0.001), having bacteremia (P = 0.001), UNOS (United Network for Organ Sharing) status 4 (need for life support measures) at transplant (P = 0.002), and volume of platelets (P = 0.002) were independently associated with invasive fungal disease. Restriction of cases of invasive fungal disease to those that occurred more than 2 weeks after transplant demonstrated an association with CMV disease (P = 0.003), bacteremia (P = 0.003), need for life support (P = 0.03), and volume of blood products transfused (P = 0.02). CONCLUSION: CMV disease or being a CMV-seronegative recipient of a CMV-seropositive donor organ is an important predictor for invasive fungal disease following orthotopic liver transplantation. (C) 1997 by Excerpta Medica, Inc. C1 TUFTS UNIV NEW ENGLAND MED CTR,DEPT MED,BOSTON,MA 02111. TUFTS UNIV NEW ENGLAND MED CTR,DEPT PATHOL,BOSTON,MA 02111. TUFTS UNIV NEW ENGLAND MED CTR,DEPT SURG,BOSTON,MA 02111. MASSACHUSETTS GEN HOSP,MED SERV TRANSPLANTAT UNIT,BOSTON,MA 02114. NEW ENGLAND DEACONESS HOSP,DEPT MED,BOSTON,MA 02215. NEW ENGLAND DEACONESS HOSP,DEPT SURG,BOSTON,MA 02215. CHILDRENS HOSP,DEPT PEDIAT,BOSTON,MA 02115. TUFTS UNIV,SCH MED,DEPT MED,MASSACHUSETTS STATE LAB INST,BOSTON,MA 02111. HARVARD UNIV,SCH MED,BOSTON,MA. RI Snydman, David/O-3889-2014 OI Snydman, David/0000-0003-0119-3978 FU NIDDK NIH HHS [R10 DK-31389] NR 29 TC 193 Z9 199 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9343 J9 AM J MED JI Am. J. Med. PD AUG PY 1997 VL 103 IS 2 BP 106 EP 113 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA XR346 UT WOS:A1997XR34600004 PM 9274893 ER PT J AU Stafford, RS Saglam, D Causino, N Blumenthal, D AF Stafford, RS Saglam, D Causino, N Blumenthal, D TI Low rates of hormone replacement in visits to United States primary care physicians SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 59th Annual Meeting of the South-Atlantic-Association-of-Obstetricians-and-Gynecologists CY JAN 25-28, 1997 CL HOT SPRINGS, VA SP S Atlantic Assoc Obstetricians & Gynecologists DE hormone replacement therapy; menopause; physician specialty; practice variations ID POSTMENOPAUSAL ESTROGEN; THERAPY; WOMEN; DISEASE; TRENDS AB Our objective was to determine national rates and predictors of hormone replacement therapy. We analyzed a nationally representative sample of 6341 office visits by women aged greater than or equal to 40 years to primary care physicians in the 1993 and 1994 National Ambulatory Medical Care Surveys. Independent predictors of estrogen use were determined by logistic regression. Time trends from 1989 through 1994 also were evaluated. Hormone replacement therapy was documented in 4.7% of visits in 1989 to 1990 and 8.0% in 1993 to 1994. In 1993 to 1994 women with menopausal symptoms were six times more likely to have hormone replacement reported. In the absence of symptoms, obstetrician-gynecologists were nearly four times as likely to report hormone replacement therapy. Age 50 to 59 years, white race, osteoporosis, hyperlipidemia, and residence in the West and in nonmetropolitan areas also independently predicted hormone replacement. Low rates of estrogen therapy by non-obstetrician-gynecologists and substantial practice variations suggest missed opportunities for hormone replacement therapy. C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP Stafford, RS (reprint author), MASSACHUSETTS GEN HOSP,GEN INTERNAL MED UNIT,HLTH POLICY RES & DEV UNIT,50 STANIFORD ST,BOSTON,MA 02114, USA. FU AHRQ HHS [R01HS07892-01A2] NR 24 TC 51 Z9 51 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD AUG PY 1997 VL 177 IS 2 BP 381 EP 387 DI 10.1016/S0002-9378(97)70202-3 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA XU865 UT WOS:A1997XU86500036 PM 9290455 ER PT J AU Zhu, JJ Leon, SP Folkerth, RD Guo, SZ Wu, JK Black, PM AF Zhu, JJ Leon, SP Folkerth, RD Guo, SZ Wu, JK Black, PM TI Evidence for clonal origin of neoplastic neuronal and glial cells in gangliogliomas SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID X-CHROMOSOME INACTIVATION; CENTRAL-NERVOUS-SYSTEM; TUMOR CLONALITY; DNA; METHYLATION; CHILDHOOD; M27-BETA; PATTERNS; TISSUE; PROBE AB Gangliogliomas are rare tumors of the central nervous system that account for approximately 1% of all brain tumors. Histologically, gangliogliomas are composed of intimately admired glial and neuronal components, the pathological origins of which remain to be characterized. Clonal analysis through examination of the pattern of the X chromosome inactivation allows one to distinguish monoclonal differentiation of a genetically abnormal progenitor cell from parallel, but independent, clonal expansion of two different cell types during tumorigenesis in biphasic neoplasms, such as gangliogliomas. In the present study, we investigated the clonality of eight gangliogliomas from female patients using both methylation- and transcription-based clonality assays at the androgen receptor locus (HUMARA) on the X chromosome. Among tumors from seven patients who were heterozygous at the HUMARA locus, five were identified as monoclonal with the methylation-based clonality assay, and the results were confirmed by the transcription-based method, whereas two were shown to be polyclonal by the methylation-based clonality assay but monoclonal by transcription-based clonality analysis. We conclude that the predominant cell types in most gangliogliomas are monoclonal in origin and derive from a common precursor cell that subsequently differentiates to form neoplastic glial and neuronal elements. C1 HARVARD UNIV,CHILDRENS HOSP,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,NEUROSURG LABS,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,BRAIN TUMOR CTR,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT PATHOL,DIV NEUROPATHOL,BOSTON,MA 02115. HARVARD UNIV,CHILDRENS HOSP,SCH MED,COMBINED TRAINING PROGRAMS NEUROPATHOL,BOSTON,MA 02115. TUFTS UNIV,NEW ENGLAND MED CTR,SCH MED,DEPT NEUROSURG,BOSTON,MA 02111. NR 40 TC 35 Z9 36 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 AUG PY 1997 VL 151 IS 2 BP 565 EP 571 PG 7 WC Pathology SC Pathology GA XP055 UT WOS:A1997XP05500027 PM 9250169 ER PT J AU Wewer, UM Thornell, LE Loechel, F Zhang, XM Durkin, ME Amano, S Burgeson, RE Engvall, E Albrechtsen, R Virtanen, I AF Wewer, UM Thornell, LE Loechel, F Zhang, XM Durkin, ME Amano, S Burgeson, RE Engvall, E Albrechtsen, R Virtanen, I TI Extrasynaptic localization of laminin beta 2 chain in developing and adult human skeletal muscle SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID CONGENITAL MUSCULAR-DYSTROPHY; S-LAMININ; NEUROMUSCULAR-JUNCTION; DIFFERENTIAL EXPRESSION; MONOCLONAL-ANTIBODIES; BASEMENT-MEMBRANES; SYNAPTIC CLEFT; SCHWANN-CELLS; BASAL LAMINAE; COLLAGEN-IV AB We have investigated the distribution of the laminin beta 2 chain (previously s-laminin) in human fetal and adult skeletal muscle and compared it to the distribution of laminin beta 1. Immunoblotting and transfection assays were used to characterize a panel of monoclonal and polyclonal antibodies to the laminin beta 2 chain. We found that laminin beta 1 chain was detected at all times during development from 10 weeks of gestation, Laminin beta 2 chain was first detected in 15 to 22-week-old fetal skeletal muscle as distinct focal immunoreactivity in the sarcolemmal basement membrane area of some myofibers. In the adult skeletal muscle, laminin beta 2 chain immunoreactivity was found along the entire perimeter of each of the individual myofibers in a large series of different muscles studied. Laminin beta 2 chain was similarly found in the skeletal muscle basement membranes in patients with Duchenne and Becker muscular dystrophy. Immunoaffinity chromatography of muscle extracts with a monoclonal antibody to the laminin alpha 2 chain followed by immunoblotting with various antibodies to the beta 2 chain demonstrated the presence of the laminin-4 (alpha 2-beta 2-gamma 1) isoform. Together the present results demonstrate a prominent extrasynaptic localization of laminin beta 2 in the human muscle, suggesting that it may have an important function in the sarcolemmal basement membrane. C1 UMEA UNIV, DEPT ANAT, S-90187 UMEA, SWEDEN. HARVARD UNIV, SCH MED, MASSACHUSETTS GEN HOSP, CUTANEOUS BIOL RES CTR, CHARLESTOWN, MA USA. BURNHAM INST, LA JOLLA, CA 92037 USA. UNIV HELSINKI, DEPT ANAT, INST BIOMED, HELSINKI, FINLAND. RP Wewer, UM (reprint author), UNIV COPENHAGEN, INST MOL PATHOL, FREDERIK V VEJ 11, DK-2100 COPENHAGEN, DENMARK. FU NIAMS NIH HHS [AR35689] NR 63 TC 34 Z9 35 U1 0 U2 2 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD AUG PY 1997 VL 151 IS 2 BP 621 EP 631 PG 11 WC Pathology SC Pathology GA XP055 UT WOS:A1997XP05500033 PM 9273822 ER PT J AU Arystarkhova, E Sweadner, KJ AF Arystarkhova, E Sweadner, KJ TI Hormonal and neurogenic control of Na-K-ATPase and myosin isoforms in neonatal rat cardiac myocytes SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE thyroid hormone; dexamethasone; sympathetic neurons; development ID THYROID-HORMONE; GENE-EXPRESSION; MESSENGER-RNA; HEAVY-CHAIN; SYMPATHETIC NEURONS; SKELETAL-MUSCLE; HEART-CELLS; NA,K-ATPASE; AFFINITY; DEXAMETHASONE AB In the rat heart there is a postnatal switch in the expression of isoforms of both Na-K-ATPase and myosin heavy chain (MHC). Here we investigated factors controlling isoform changes in cultures of neonatal cardiomyocytes. In serum-free medium, the compositions of either Na-E-ATPase or MHC isoforms resembled the neonatal phenotype. Thyroid hormone induced the MHC isoform switch but increased expression of all Na-K-ATPase isoforms to various extents. Dexamethasone failed to induce the MHC switch and inhibited Na-K-ATPase alpha(1) isoform expression without inducing the other isoforms. With both hormones, the adult phenotype for both MHC and Na-K-ATPase was seen but with low Na-K-ATPase alpha(2). The paucity of at protein was not predicted by studies of mRNA levels. In serum, there was a gradual decline of Na-K-ATPase alpha(3) and the appearance of alpha(2), but again at a relatively low level. Expression of Na-K-ATPase alpha(2) was significantly upregulated when cardiomyocytes were cocultured with sympathetic neurons from superior cervical ganglia, without changes in the MHC isoforms. Thus innervation is postulated to play a specific role in modulating Na-K-ATPase gene expression. C1 MASSACHUSETTS GEN HOSP, CTR NEUROSCI, LAB MEMBRANE BIOL, CHARLESTOWN, MA 02129 USA. FU NHLBI NIH HHS [HL-36271] NR 35 TC 11 Z9 11 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD AUG PY 1997 VL 273 IS 2 BP C489 EP C499 PG 11 WC Cell Biology; Physiology SC Cell Biology; Physiology GA XQ262 UT WOS:A1997XQ26200015 PM 9277346 ER PT J AU Guo, J Liu, BY Bringhurst, FR AF Guo, J Liu, BY Bringhurst, FR TI Mechanisms of homologous and heterologous desensitization of PTH/PTHrP receptor signaling in LLC-PK1 cells SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE receptor regulation; signal transduction; parathyroid hormone; calcitonin; parathyroid hormone-related protein ID PARATHYROID-HORMONE RECEPTORS; PROTEIN-KINASE-C; OSTEOBLASTIC OSTEOSARCOMA CELLS; MESSENGER-RIBONUCLEIC-ACID; OPOSSUM KIDNEY-CELLS; CULTURED BONE-CELLS; DOWN-REGULATION; ADENYLATE-CYCLASE; SAOS-2 CELLS; PEPTIDE RECEPTORS AB Parathyroid hormone (PTH) activates multiple intracellular effectors, including adenylyl cyclase (AC) and phospholipase C (PLC), via a single receptor [PTH/parathyroid hormone-related protein receptor (PTHR)] expressed in bone and kidney. Homologous desensitization of PTHR signaling occurs, but the relative importance of reduced receptor expression vs. impaired receptor-effector coupling in this process remains unclear. It also is not known ifAC and PLC responses to PTH are desensitized independently or interdependently. In LLC-PK1 cells that expressed transfected wild-type PTHRs, PTH caused dose- and time-dependent desensitization of both the AC and PLC responses to PTH without altering PTHR expression. Desensitization of AC was blocked in mutant cells resistant to adenosine 3',5'-cyclic monophosphate but not when cells expressed mutant PTHRs with defective PLC coupling. Desensitization of PLC was unaffected by PKA blockade, partially mimicked by phorbol ester, and not reproduced by agents that selectively activated AC. The finding that homologous PTHR desensitization in LLC-PK1 cells is signal specific suggests that prior exposure of other cells to PTH also may induce discordant regulation of subsequent PTHR signaling, altering the character as well as the intensity of the hormonal response. C1 HARVARD UNIV, SCH MED, BOSTON, MA 02114 USA. RP Guo, J (reprint author), MASSACHUSETTS GEN HOSP, ENDOCRINE UNIT, WELLMAN 5, BOSTON, MA 02114 USA. FU NIDDK NIH HHS [DK-11794] NR 30 TC 20 Z9 20 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD AUG PY 1997 VL 273 IS 2 BP E383 EP E393 PG 11 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA XQ274 UT WOS:A1997XQ27400021 PM 9277393 ER PT J AU Ogata, H Podolsky, DK AF Ogata, H Podolsky, DK TI Trefoil peptide expression and secretion is regulated by neuropeptides and acetylcholine SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE goblet cells; regulation; mucin ID PANCREATIC SPASMOLYTIC POLYPEPTIDE; INFLAMMATORY BOWEL-DISEASE; MESSENGER-RNA; CELL-LINE; MOLECULAR-CLONING; EPITHELIAL-CELLS; MUCIN; PROTEIN; GENE; IDENTIFICATION AB Trefoil peptides are a family of small proteins expressed by goblet cells that are secreted onto the apical gastrointestinal mucosal surface, where they are present in high concentrations. These peptides appear to both protect the epithelium and promote healing after injury. However, the factors regulating the expression and secretion of these proteins contributing to mucosal defense have not been characterized. To determine the mechanisms controlling production of trefoil peptides, the human colon cancer-derived model cell line HT-29 was exposed to a variety of potential secretagogues. Expression and secretion of human intestinal trefoil factor (hITF) as well as the intestinal apomucin MUC2 were assessed by Northern and Western blot analysis. Carbachol, an analog of acetylcholine, and the neuroendocrine peptides somatostatin and vasoactive intestinal polypeptide (VIP) stimulated increased expression of hITF mRNA within 5 min. These same factors stimulated parallel secretion of the hITF peptide, with maximal stimulation observed at concentrations ranging from 10(-6) M (carbachol and somatostatin) to 10(-7) M (VIP). Expression and secretion of hITF in response to carbachol, VIP, and somatostatin was independent of production of apomucin. hITF was not regulated by other neuroendocrine transmitters including histamine and substance P. Similarly, hITF expression and secretion was not modulated by peptide growth factors (epidermal growth factor, transforming growth factor-beta, and keratinocyte growth factor), cytokines [interleukin (IL)-1 beta, IL-2, IL-7, and IL-11], or arachidonic acid metabolites (prostaglandin E-1/E-2 and leukotriene B-4) In conclusion, trefoil peptides appear to be integrated into mechanisms of mucosal defense and repair through the enteric neuroendocrine system and independent of the classical mucosal immune cytokine network. C1 MASSACHUSETTS GEN HOSP, GASTROINTESTINAL UNIT, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, CTR STUDY INFLAMMATORY BOWEL DIS, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02114 USA. RI Ogata, Haruhiko/B-3964-2014 FU NIDDK NIH HHS [DK-43351, DK-46906] NR 32 TC 32 Z9 32 U1 0 U2 2 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 AUG PY 1997 VL 273 IS 2 BP G348 EP G354 PG 7 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA XQ263 UT WOS:A1997XQ26300013 PM 9277413 ER PT J AU Dell'Italia, LJ Balcells, E Meng, QC Su, XF Schultz, D Bishop, SP Machida, N Straeter-Knowlen, IM Hankes, GH Dillon, R Cartee, RE Oparil, S AF Dell'Italia, LJ Balcells, E Meng, QC Su, XF Schultz, D Bishop, SP Machida, N Straeter-Knowlen, IM Hankes, GH Dillon, R Cartee, RE Oparil, S TI Volume-overload cardiac hypertrophy is unaffected by ACE inhibitor treatment in dogs SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE angiotensin II; angiotensin-converting enzyme inhibitor; heart failure; congestive ID ANGIOTENSIN-CONVERTING ENZYME; MESSENGER-RNA; HEART-FAILURE; RECEPTOR SUBTYPE; FORMING PATHWAYS; II RECEPTOR; SYSTEM; RENIN; RATS; EXPRESSION AB We tested the hypothesis that angiotensin-converting enzyme (ACE) inhibitor therapy prevents volume-overload hypertrophy in dogs with chronic mitral regurgitation (MR). Seven adult mongrel dogs receiving ramipril (R; 10 mg orally, twice/day) for 4 mo were compared with 11 dogs receiving no R (N) for 4 mo after induction of MR. Cine-magnetic resonance imaging demonstrated that left ventricular (LV) mass increased in the R-MR dogs [80 +/- 4 (SE) to 108 +/- 7 g, P < 0.01] and in the N-MR dogs (92 +/- 7 to 112 +/- 8 g, P < 0.001). LV myocyte cell length was greater in the R-MR and N-MR dogs (203 +/- 6 and 177 +/- 10 mu m, respectively) than in normal (144 +/- 4 mu m, P < 0.05) dogs. There was significant loss of the collagen weave pattern by scanning electron microscopy in both R-MR and N-MR dogs. LV ACE and chymase activities were significantly elevated in R-MR and N-MR compared with normal dogs. LV angiotensin II (ANG II) levels in the R-MR dogs (28 +/- 12 pg/g) were reduced to levels seen in normal dogs (28 +/- 4 pg/g) compared with N-MR dogs (72 +/- 11 pg/g, P < 0.05). Steady-state AT(1)-receptor mRNA levels decreased 66% in N-MR compared with normal dogs (P < 0.001) and increased 1.5-fold in R-MR compared with normal dogs (P < 0.01). Thus upregulation of the AT(1) receptor in the R-MR hearts may provide a mechanism by which normal intracardiac ANG II levels could continue to mediate LV hypertrophy. However, the mechanism of dissolution collagen weave in both N-MR and R-MR hearts may be related to the stretch of volume overload. C1 Univ Alabama, Birmingham Vet Affairs Med Ctr, Div Cardiovasc Dis, Birmingham, AL 35294 USA. Auburn Univ, Coll Vet Med, Auburn, AL 36849 USA. RP Dell'Italia, LJ (reprint author), Univ Alabama, Dept Med, Div Cardiol, 310 Lyons Harrison Res Bldg,701 S 19th St, Birmingham, AL 35294 USA. RI Machida, Noboru/H-2729-2013 OI Machida, Noboru/0000-0003-2960-1523 FU NHLBI NIH HHS [2T32HL-07457-16A1, HL-17667, R01-HL-54816] NR 34 TC 80 Z9 82 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD AUG PY 1997 VL 273 IS 2 BP H961 EP H970 PG 10 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA XQ295 UT WOS:A1997XQ29500053 PM 9277516 ER PT J AU Carlat, DJ Camargo, CA Herzog, DB AF Carlat, DJ Camargo, CA Herzog, DB TI Eating disorders in males: A report on 135 patients SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 148th Annual Meeting of the American-Psychiatric-Association CY MAY 20-26, 1995 CL MIAMI BEACH, FL SP Amer Psychiat Assoc ID ANOREXIA-NERVOSA; BULIMIA-NERVOSA; CLINICAL-FEATURES; MEN; FEMALES; BEHAVIOR AB Objective: The goal of this study was to better understand the etiology, clinical characteristics, and prognosis of eating disorders in males. Method: All males with eating disorders who had been treated at Massachusetts General Hospital from Jan. 1, 1980, to Dec. 31, 1994, were identified. Hospital charts and psychiatric departmental records were reviewed to verify that the eating disorders met DSM-IV criteria and to abstract demographic and clinical data. Results: One hundred thirty-five males with eating disorders were identified, of whom 62 (46%) were bulimic, 30 (22%) were anorexic, and 43 (32%) met criteria for an eating disorder not otherwise specified. There were marked differences in sexual orientation by diagnostic group; 42% of the male bulimic patients were identified as either homosexual or bisexual, and 58% of the anorexic patients were identified as asexual. Comorbid psychiatric disorders were common, particularly major depressive disorder (54% of all patients), substance abuse (37%), and personality disorder (26%). Many patients had a family history of affective disorder (29%) or alcoholism (37%). Conclusions: While most characteristics of males and females with eating disorders are similar, homosexuality/bisexuality appears to be a specific risk factor for males, especially for those who develop bulimia nervosa. Future research on the link between sexual orientation and eating disorders would help guide prevention and treatment strategies. C1 MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT EMERGENCY MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,EATING DISORDERS UNIT,BOSTON,MA 02114. BRIGHAM & WOMENS HOSP,DEPT MED,CHANNING LAB,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. FU NHLBI NIH HHS [HL-03533] NR 35 TC 199 Z9 204 U1 3 U2 28 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD AUG PY 1997 VL 154 IS 8 BP 1127 EP 1132 PG 6 WC Psychiatry SC Psychiatry GA XN537 UT WOS:A1997XN53700016 PM 9247400 ER PT J AU Murakami, S Bacha, EA Mazmanian, GM Detruit, H Chapelier, A Dartevelle, P Herve, P AF Murakami, S Bacha, EA Mazmanian, GM Detruit, H Chapelier, A Dartevelle, P Herve, P TI Effects of various timings and concentrations of inhaled nitric oxide in lung ischemia-reperfusion SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID ISOLATED RAT LUNG; ENDOTHELIAL DYSFUNCTION; RABBIT LUNG; L-ARGININE; INJURY; PRESERVATION; PENTOXIFYLLINE; INHIBITION; PATHWAY AB Experimental studies reveal that inhaled nitric oxide (NO) can prevent, worsen, or have no effect on lung injury in the setting of ischemia-reperfusion (I-R). We tested the hypothesis that these disparate effects could be related to differences in the timing of administration and/or concentration of inhaled NO during I-R. Isolated rat lungs were subjected to 1-h periods of ischemia followed by 1-h periods of blood reperfusion. We investigated the effects of NO (30 ppm) given during ischemia, NO (30 or 80 ppm) begun immediately at reperfusion, or NO (30 ppm) given 15 min after the beginning of reperfusion, on total pulmonary vascular resistance (PVR), the coefficient of filtration (K-fc), the lung wet/dry weight ratio (W/D) of lung tissue, and lung myeloperoxidase activity (MPO). A control group did not receive NO. NO given during ischemia had no effect on K-fc or MPO, but decreased PVR. NO (30 ppm) during reperfusion (early or delayed) decreased PVR, W/D, K-fc and MPO. NO at 80 ppm decreased PVR and MPO but not W/D or K-fc. In conclusion, NO at 30 ppm, given immediately or in a delayed fashion during reperfusion, attenuates I-R-induced lung injury. NO at 30 ppm given during ischemia or at 80 ppm during reperfusion is not protective. C1 UNIV PARIS SUD,CHIRURG EXPT LAB,CTR CHIRURG MARIE LANNELONGUE,F-92350 LE PLESSIS ROBINS,FRANCE. UNIV PARIS SUD,DEPT THORAC & VASC SURG,CTR CHIRURG MARIE LANNELONGUE,F-92350 LE PLESSIS ROBINS,FRANCE. KANAZAWA UNIV,SCH MED,DEPT SURG,KANAZAWA,ISHIKAWA 920,JAPAN. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,GEN SURG SERV,BOSTON,MA. NR 33 TC 42 Z9 46 U1 0 U2 1 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD AUG PY 1997 VL 156 IS 2 BP 454 EP 458 PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA XR408 UT WOS:A1997XR40800015 PM 9279223 ER PT J AU Deneke, SM Harford, PH Lee, KY Deneke, CF Wright, SE Jenkinson, SG AF Deneke, SM Harford, PH Lee, KY Deneke, CF Wright, SE Jenkinson, SG TI Induction of cystine transport and other stress proteins by disulfiram: Effects on glutathione levels in cultured cells SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID ENDOTHELIAL-CELLS; SODIUM ARSENITE; DIETHYL MALEATE; SUPEROXIDE-DISMUTASE; LIPID-PEROXIDATION; HYPERBARIC-OXYGEN; PROTECTIVE AGENTS; MAMMALIAN-CELLS; ACID UPTAKE; RAT AB Disulfiram (Antabuse) (DSF) has been reported to protect rats and other animals from the effects of hyperbaric hyperoxia at 4 to 6 ATA (atmospheres). In contrast, DSF and diethyldithiocarbamate (DDC), its metabolite, accelerate the toxic effects in rats of 100% oxygen at 1 to 2 ATA. We have examined the effects of DSF and DDC on glutathione (GSH) levels in bovine pulmonary artery endothelial cells and Chinese hamster ovary cells. Increases in intracellular GSH occurred 8 to 24 h after addition of DSF to the culture media. These increases in intracellular GSH were associated with increases in the rate of uptake of cystine into the cells. DDC was a less effective inducer of cystine uptake and increased intracellular GSH levels than was DSF. At the concentrations used, neither DDC nor DSF caused significant decreases intracellular superoxide dismutase levels. Exogenous sulfhydryl compounds including GSH and cysteine partially blocked the induction of cystine transport by DSF or DDC, suggesting that the induction might be mediated through a sulfhydryl reaction between DSF and some cellular components. The increases in GSH in the cultured cells were not significant by 4 h of exposure, In contrast, other stress proteins including heme oxygenase are induced by 2 to 4 h after DSF addition, In previously reported in vitro studies, DSF treatment protected against hyperbaric oxygen damage after as little as 1 to 4 h pre-exposure. This suggests that effects of DSF exposure other than GSH augmentation may be responsible for the protective effects seen in vivo. C1 AUDIE L MURPHY MEM VET ADM MED CTR,S TEXAS VET HLTH CARE SYST,SAN ANTONIO,TX 78284. RP Deneke, SM (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV PULM DIS CRIT CARE MED,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. FU NHLBI NIH HHS [HL-32824] NR 47 TC 6 Z9 6 U1 1 U2 2 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD AUG PY 1997 VL 17 IS 2 BP 227 EP 234 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA XR280 UT WOS:A1997XR28000013 PM 9271311 ER PT J AU Ryan, JM Murphy, BL Lee, MJ Boland, GW Mueller, PR AF Ryan, JM Murphy, BL Lee, MJ Boland, GW Mueller, PR TI Percutaneous ultrasonic lithotripsy in a patient with horseshoe kidney SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID CALCULI; NEPHROLITHOTOMY; COMPLICATIONS; SURGERY C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,DIV ABDOMINAL IMAGING & INTERVENT RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. BEAUMONT HOSP,DEPT RADIOL,DUBLIN 7,IRELAND. 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 AUG PY 1997 VL 169 IS 2 BP 447 EP 451 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA XM758 UT WOS:A1997XM75800028 PM 9242752 ER PT J AU Kubaska, SM Chew, FS AF Kubaska, SM Chew, FS TI Biliary ascariasis SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 4 TC 14 Z9 14 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD AUG PY 1997 VL 169 IS 2 BP 492 EP 492 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA XM758 UT WOS:A1997XM75800036 PM 9242760 ER PT J AU Gilks, CB Young, RH Gersell, DJ Clement, PB AF Gilks, CB Young, RH Gersell, DJ Clement, PB TI Large cell carcinoma of the uterine cervix: A clinicopathologic study of 12 cases SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE cervix; neuroendocrine carcinoma; carcinoid; small cell carcinoma ID FEMALE GENITAL-TRACT; ENDOCRINE CARCINOMA; PEPTIDE-HORMONES; TUMOR; LIGHT; ADENOCARCINOMAS; DIFFERENTIATION AB Twelve cervical tumors showing morphologic evidence of neuroendocrine differentiation and lesional cells larger than those of typical small cell carcinoma are reported in women 21 to 62 (mean 34) years of age. The patients presented with an abnormal Papanicolaou smear or vaginal bleeding. Two tumors were stage Ia2, nine were stage Ib, and one was stage IIa. All patients were treated by radical hysterectomy, and most received adjuvant chemotherapy. Seven of 10 patients with >1 year of follow-up died of tumor 6 to 24 months after hysterectomy. The tumors had insular, trabecular, glandular, and solid growth patterns and contained medium to large cells with moderate to abundant cytoplasm; eosinophilic cytoplasmic granules were present in nine cases. The tumors were mitotically active, and necrosis was present in 10 of them. Nine of 10 tumors were argyrophilic, and all 12 were immunoreactive for chromogranin. Individual cells containing somatostatin, serotonin, or glucagon were identified in four of eight cases. Adenocarcinoma in situ was present adjacent to the tumor in eight cases; invasive adenocarcinoma of non-neuroendocrine type was present in three of these tumors, Using diagnostic criteria established for pulmonary neuroendocrine tumors, the 12 tumors were classified as large cell neuroendocrine carcinomas. Cervical large cell neuroendocrine carcinomas are distinctive cervical carcinomas that are frequently misdiagnosed and have an unfavorable outcome, similar to that of small cell carcinoma. C1 VANCOUVER HOSP & HLTH SCI CTR,DEPT PATHOL & LAB MED,VANCOUVER,BC V6T 2B5,CANADA. UNIV BRITISH COLUMBIA,VANCOUVER,BC V5Z 1M9,CANADA. MASSACHUSETTS GEN HOSP,JAMES HOMER WRIGHT PATHOL LABS,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. BARNES HOSP,DEPT PATHOL,ST LOUIS,MO 63110. WASHINGTON UNIV,ST LOUIS,MO. NR 35 TC 80 Z9 82 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD AUG PY 1997 VL 21 IS 8 BP 905 EP 914 DI 10.1097/00000478-199708000-00004 PG 10 WC Pathology; Surgery SC Pathology; Surgery GA XW924 UT WOS:A1997XW92400004 PM 9255253 ER PT J AU Manktelow, C Bigatello, LM Hess, D Hurford, WE AF Manktelow, C Bigatello, LM Hess, D Hurford, WE TI Physiologic determinants of the response to inhaled nitric oxide in patients with acute respiratory distress syndrome SO ANESTHESIOLOGY LA English DT Article; Proceedings Paper CT Annual International Conference of the American-Thoracic-Society CY MAY 11-22, 1996 CL NEW ORLEANS, LA SP Amer Thorac Soc DE gases, nitric oxide; lung, acute respiratory distress syndrome, pulmonary hypertension; ventilation, mechanical ID HYPOXIC PULMONARY VASOCONSTRICTION; NITROGEN-DIOXIDE; METHEMOGLOBIN PRODUCTION; MECHANICAL VENTILATION; GAS-EXCHANGE; FAILURE; HYPERTENSION; OXYGENATION; DISEASE; ADULTS AB Background: The response to inhaled nitric oxide (NO) in patients with acute respiratory distress syndrome (ARDS) varies. It is unclear which patients will respond favorably and whether the initial response persists over time. The authors defined a clinically useful response to inhaled NO as an increase of more than 20% of the ratio of the partial pressure of oxygen (Pa-O2) to the inspiratory fraction of oxygen (FiO(2)), a decrease of more than 20% of pulmonary vascular resistance, or both, The authors hypothesized that patients who initially respond favorably are likely to show persistent improvements of gas exchange and hemodynamics after 48 h of NO inhalation. Methods: The medical records and collected research data of 88 patients with ARDS who received 92 trials of NC, inhalation between March 1991 and February 1996 were reviewed. Results: Fifty-three of the 92 trials (58%) produced a clinically significant response to NO. In the responding patients who continued to receive NO therapy (n = 43), the Pa-O2/FiO(2) ratio remained higher (120 +/- 46 vs. 89 +/- 32 mmHg before NO; P < 0.01) and the mean pulmonary artery pressure remained lower (35 +/- 8 vs. 40 +/- 12 mmHg before NO; P < 0.01) at 48 h. Only 33% of the patients with septic shock responded to inhaled NO compared with 64% of those without septic shock (P < 0.02). Conclusions: Most patients with ARDS had clinically useful responses to NO inhalation. Patients with an initial favorable response maintained the improvement at 48 h, Patients with septic shock were less likely to respond favorably. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ANESTHESIA & CRIT CARE,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,RESP CARE SERV,BOSTON,MA 02114. RI Hurford, William/G-6386-2013 OI Hurford, William/0000-0003-1201-0313 NR 43 TC 63 Z9 63 U1 1 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD AUG PY 1997 VL 87 IS 2 BP 297 EP 307 DI 10.1097/00000542-199708000-00017 PG 11 WC Anesthesiology SC Anesthesiology GA XR406 UT WOS:A1997XR40600017 PM 9286894 ER PT J AU Green, DS Hayward, LJ George, AL Cannon, SC AF Green, DS Hayward, LJ George, AL Cannon, SC TI A proposed mutation, Val781Ile, associated with hyperkalemic periodic paralysis and cardiac dysrhythmia is a benign polymorphism SO ANNALS OF NEUROLOGY LA English DT Article ID SODIUM-CHANNEL MUTATIONS; EXPRESSION AB Twenty different point mutations have been identified in the gene coding for the alpha subunit of the adult skeletal muscle sodium channel in families with hyperkalemic periodic paralysis, paramyotonia congenita, and the potassium-aggravated myotonias. One novel mutation (Val781Ile) was reported in an adopted boy with potassium-sensitive weakness and cardiac dysrhythmia. The confidence in establishing this rare amino acid substitution as a causative mutation was limited by the absence of family members for segregation analysis. Functional expression studies herein show that Val781Ile is most likely a benign polymorphism and not a disease-associated mutation. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT NEUROBIOL,BOSTON,MA 02115. VANDERBILT UNIV,MED CTR,DEPT MED & PHARMACOL,NASHVILLE,TN. FU NIAMS NIH HHS [R01-AR42703]; NIGMS NIH HHS [GM15605]; NINDS NIH HHS [R01-NS32387] NR 14 TC 9 Z9 12 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD AUG PY 1997 VL 42 IS 2 BP 253 EP 256 DI 10.1002/ana.410420219 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA XQ524 UT WOS:A1997XQ52400018 PM 9266738 ER PT J AU Shults, CW Haas, RH Passov, D Beal, MF AF Shults, CW Haas, RH Passov, D Beal, MF TI Coenzyme Q(10) levels correlate with the activities of complexes I and II/III in mitochondria from parkinsonian and nonparkinsonian subjects SO ANNALS OF NEUROLOGY LA English DT Article ID DISEASE; PLATELETS; HUMANS AB The activities of complex I and complex II/III in platelet mitochondria are reduced in patients with early, untreated Parkinson's disease. Coenzyme a, is the electron acceptor far compiler I and complex II. We found that the level of coenzyme a, was significantly lower in mitochondria from parkinsonian patients than in mitochondria from age- and sex-matched control subjects and that the levels of coenzyme Q(10) and the activities of complex I and complex II/III were significantly correlated. C1 UNIV CALIF SAN DIEGO,DEPT NEUROSCI,LA JOLLA,CA 92093. MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114. RP Shults, CW (reprint author), VET AFFAIRS MED CTR,NEUROL SERV 127,3350 LA JOLLA VILLAGE DR,SAN DIEGO,CA 92161, USA. FU NINDS NIH HHS [R01 NS29504, R01 NS32365]; PHS HHS [P01 12992] NR 16 TC 164 Z9 170 U1 1 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD AUG PY 1997 VL 42 IS 2 BP 261 EP 264 DI 10.1002/ana.410420221 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA XQ524 UT WOS:A1997XQ52400020 PM 9266740 ER PT J AU Priller, J Scherzer, CR Faber, PW MacDonald, ME Young, AB AF Priller, J Scherzer, CR Faber, PW MacDonald, ME Young, AB TI Frataxin gene of Friedreich's ataxia is targeted to mitochondria SO ANNALS OF NEUROLOGY LA English DT Article ID GREEN FLUORESCENT PROTEIN; ALPHA-TOCOPHEROL; DISEASE; LOCALIZATION; EXPRESSION; HEART AB Friedreich's ataxia is caused by a triplet repeat expansion in intron 1, a noncoding region of the frataxin gene (X25). We have generated a chimeric gene composed of the frataxin gene fused with the green fluorescent protein (GFP) gene as a reporter. Transfection of the fusion construct into living COS cells revealed that the frataxin-GFP construct localizes to organelles that double-label with 8-(4'-chloromethyl) phenyl-2,3,5,6,11,12,14,15-octahydro-1H,4H,10H-13H-diquinolizino 8H-xanthylium chloride (CMXRos), a novel mitochondrial dye. Thus, frataxin appears to be a nuclear-encoded mitochondrial protein. C1 MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,MOL NEUROGENET UNIT,CHARLESTOWN,MA. FU NINDS NIH HHS [NS16367, NS32765] NR 27 TC 79 Z9 80 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD AUG PY 1997 VL 42 IS 2 BP 265 EP 269 DI 10.1002/ana.410420222 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA XQ524 UT WOS:A1997XQ52400021 PM 9266741 ER PT J AU Goldhirsch, A Gelber, RD Castiglione, M ONeill, A Thurlimann, B Rudenstam, CM Lindtner, J Collins, J Forbes, J Crivellari, D Coates, A Cavalli, F Simoncini, E Fey, MF Pagani, O Price, K Senn, HJ AF Goldhirsch, A Gelber, RD Castiglione, M ONeill, A Thurlimann, B Rudenstam, CM Lindtner, J Collins, J Forbes, J Crivellari, D Coates, A Cavalli, F Simoncini, E Fey, MF Pagani, O Price, K Senn, HJ TI Menstrual cycle and timing of breast surgery in premenopausal node-positive breast cancer: Results of the International Breast Cancer Study Group (IBCSG) Trial VI SO ANNALS OF ONCOLOGY LA English DT Article DE adjuvant chemotherapy; breast cancer; menstrual cycle; premenopausal; surgery ID SURGICAL-TREATMENT; ESTROGEN; EXPRESSION; SURVIVAL; GROWTH; PHASE; CURE AB Purpose: It has been postulated that breast cancer surgery performed during the follicular phase of the menstrual cycle is associated with poorer outcome. Patients and methods: We tested this hypothesis by evaluating disease-free survival (DFS) for 1033 premenopausal patients who received definitive surgery either during the follicular phase (n = 358) or the luteal phase (n = 675). All patients were enrolled in a randomized trial conducted between July 1986 and April 1993. All had node positive breast cancer and randomization was stratified by estrogen receptor (ER) status. All patients received at least three cycles of adjuvant cyclophosphamide, methotrexate, and 5-fluorouracil (CMF). The median follow-up was 60 months. Results. Patients who underwent definitive surgery for breast cancer in the follicular phase had a slightly worse disease-free survival than those operated on during the luteal phase (five-year DFS percentage: 53% versus 58%; hazard ratio, 1.13; 95% confidence interval (CI), 0.94-1.38; P = 0.20). The effect was significantly greater for the subpopulation of 300 patients with ER-negative primaries (P = 0.02 interaction effective-year DFS percentages 42% vs. 59%; hazard ratio 1.60; 95% CI, 1.12-2.25; P = 0.008). The effect of timing of surgery diminished for analyses based on lesser surgical procedures, e.g., excisional biopsies. In particular, no effect of timing was observed for fine needle aspiration procedures. Conclusions: Surgical procedures which are more extensive than a fine needle aspiration biopsy might be associated with worse prognosis if conducted during the follicular phase of the menstrual cycle. This phenomenon was seer, predominantly for high risk breast cancer with low levels or no estrogen receptors in the primary tumor. C1 DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. FRONTIER SCI & TECHNOL RES FDN INC,AMHERST,NY. AUCKLAND BREAST CANC STUDY GRP,AUCKLAND,NEW ZEALAND. CTR RIFERIMENTO ONCOL,I-33081 AVIANO,ITALY. SPEDALI CIVIL BRESCIA,I-25125 BRESCIA,ITALY. FDN BERETTA,BRESCIA,ITALY. GROOTE SCHUUR HOSP,ZA-7925 CAPE TOWN,SOUTH AFRICA. UNIV DUSSELDORF,D-4000 DUSSELDORF,GERMANY. PRESIDIO OSPED,GORIZIA,ITALY. W SWEDISH BREAST CANC STUDY GRP,GOTHENBURG,SWEDEN. INST ONCOL,LJUBLJANA,SLOVENIA. MADRID BREAST CANC GRP,MADRID,SPAIN. ANTICANC COUNSIL VICTORIA,MELBOURNE,VIC,AUSTRALIA. ROYAL ADELAIDE HOSP,ADELAIDE,SA 5000,AUSTRALIA. SIR CHARLES GAIRDNER HOSP,NEDLANDS,WA 6009,AUSTRALIA. UNIV NEWCASTLE,WARATAH,AUSTRALIA. UNIV SYDNEY,SYDNEY,NSW 2006,AUSTRALIA. ROYAL PRINCE ALFRED HOSP,SYDNEY,NSW,AUSTRALIA. UNIV BERN,INSELSPITAL,SAKK,CH-3010 BERN,SWITZERLAND. KANTONSSPITAL,ST GALLEN,SWITZERLAND. OSPED SAN GIOVANNI BELLINZONA,BELLINZONA,SWITZERLAND. KANTONSSPITAL,CH-4031 BASEL,SWITZERLAND. HOSP CADOLLES,NEUCHATEL,SWITZERLAND. KANTONSSPITAL,LUZERN,SWITZERLAND. KANTONSSPITAL,ZURICH,SWITZERLAND. CHU,LAUSANNE,SWITZERLAND. UNIV GENEVA,HOP CANTONAL,CH-1211 GENEVA,SWITZERLAND. SWISS CANC LEAGUE,BERN,SWITZERLAND. NR 25 TC 27 Z9 28 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD AUG PY 1997 VL 8 IS 8 BP 751 EP 756 DI 10.1023/A:1008220301866 PG 6 WC Oncology SC Oncology GA XX936 UT WOS:A1997XX93600011 PM 9332682 ER PT J AU Azar, T Berger, DL AF Azar, T Berger, DL TI Adult intussusception SO ANNALS OF SURGERY LA English DT Review ID COMPUTED-TOMOGRAPHY; MANAGEMENT; BOWEL AB Objective The objectives were to review adult intussusception, its diagnosis, and its treatment. Summary Background Data Adult intussusception represents 1% of all bowel obstructions, 5% of all intussusceptions, and 0.003%-0.02% of all hospital admissions. Intussusception is a different entity in adults than it is in chlidren. Methods The records of all patients 18 years and older with the postoperative diagnosis of intussusception at the Massachusetts General Hospital during the years 1964 through 1993 were reviewed retrospectively. The 58 patients were divided into those with benign enteric, malignant enteric, benign colonic, and malignant colonic lesions associated with their intussusception. The diagnosis and treatment of each were reviewed. Results In 30 years at the Massachusetts General Hospital, there are 58 cases of surgically proven adult intussusception. The patients' mean age was 54.4 years. Most patients presented with symptoms consistent with bowel obstruction. There were 44 enteric and 14 colonic intussusceptions. Ninety-three percent of the intussusceptions were associated with a pathologic lesion. Forty-eight percent of the enteric lesions were malignant and 52% were benign. Forty-three percent of the colonic lesions were malignant and 57% were benign. Conclusions Intussusception occurs rarely in adults. It presents with a variety of acute, intermittent, and chronic symptoms, thus making its preoperative diagnosis difficult. Computed tomography scanning proved to be the most useful diagnostic radiologic method. The diagnosis and treatment of adult intussusception are surgical. Surgical resection of the intussusception without reduction is the preferred treatment in adults, as almost half of both colonic and enteric intussusceptions are associated with malignancy. C1 MASSACHUSETTS GEN HOSP,DEPT GEN SURG,BOSTON,MA 02114. NR 20 TC 343 Z9 381 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD AUG PY 1997 VL 226 IS 2 BP 134 EP 138 DI 10.1097/00000658-199708000-00003 PG 5 WC Surgery SC Surgery GA XV482 UT WOS:A1997XV48200003 PM 9296505 ER PT J AU Wright, CD Wain, JC Grillo, HC Moncure, AC Macaluso, SM Mathisen, DJ AF Wright, CD Wain, JC Grillo, HC Moncure, AC Macaluso, SM Mathisen, DJ TI Pulmonary lobectomy patient care pathway: A model to control cost and maintain quality SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 33rd Annual Meeting of the Society-of-Thoracic-Surgeons CY FEB 03-05, 1997 CL SAN DIEGO, CA SP Soc Thorac Surgeons AB Background. Cost containment is a reality in thoracic surgery. Patient care pathways have proved effective in cardiac surgery to reduce length of stay and control costs. Methods. A multidisciplinary team formulated a pulmonary lobectomy patient care pathway to standardize care, reduce length of stay and costs, and maintain quality. Variance codes were developed to collect data prospectively on reasons for prolonged stay. A patient satisfaction survey was instituted to learn patients' responses to their hospitalization. Results. One hundred forty-seven patients underwent lobectomy in 1995 before institution of the pathway with a mean length of stay of 10.6 days and a mean cost of $16,063. The lobectomy pathway was instituted at the beginning of 1996. One hundred thirty patients underwent lobectomy in 1996 with a mean length of stay of 7.5 days (p = 0.03) and a mean cost of $14,792 (p = 0.47). Readmission and mortality rates were unchanged. Eighty-eight of 130 patients (68%) were able to be discharged by the target length of stay of 7 days in 1996 as opposed to 76 of 147 patients (52%) in 1995. The most common reason for delayed discharge was inadequate pain control. The majority of patients felt prepared for discharge by the seventh postoperative day (70 of 96 patients, 73%). Conclusions. The institution of a lobectomy patient care pathway appeared to reduce length of stay and costs. The pathway provided a framework to begin systematic quality control measures to enhance patient care. (C) 1997 by The Society of Thoracic Surgeons. C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP Wright, CD (reprint author), MASSACHUSETTS GEN HOSP,GEN THORAC SURG UNIT,BOSTON,MA 02114, USA. NR 4 TC 52 Z9 55 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD AUG PY 1997 VL 64 IS 2 BP 299 EP 302 DI 10.1016/S0003-4975(97)00548-1 PG 4 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA XR281 UT WOS:A1997XR28100001 PM 9262564 ER PT J AU Graybill, JR Najvar, LK Luther, MF Fothergill, AW AF Graybill, JR Najvar, LK Luther, MF Fothergill, AW TI Treatment of murine disseminated candidiasis with L-743,872 SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID IN-VIVO RESPONSE; AMPHOTERICIN-B; FLUCONAZOLE TREATMENT; CILOFUNGIN LY121019; ALBICANS INFECTION; RESISTANT CANDIDA; ANTIFUNGAL AGENT; CELL-WALL; SUSCEPTIBILITY; AIDS AB L-743,872 (M991), which is a pneumocandin derivative, was evaluated in a mouse model of disseminated candidiasis caused by a fluconazole-resistant isolate of Candida albicans, In immunocompetent mice M991 prolonged survival at doses as low as 0.0125 mg/kg of body weight per day. In neutropenic mice 0.05 mg/kg was the lowest effective dose. M991 is a very potent drug for treatment of disseminated candidiasis. C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX. RP Graybill, JR (reprint author), AUDIE L MURPHY MEM VET ADM MED CTR,INFECT DIS SECT 111F,7400 MERTON MINTER BLVD,SAN ANTONIO,TX 78284, USA. NR 21 TC 59 Z9 60 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD AUG PY 1997 VL 41 IS 8 BP 1775 EP 1777 PG 3 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA XP605 UT WOS:A1997XP60500028 PM 9257759 ER PT J AU McGinnis, MR Pasarell, L Sutton, DA Fothergill, AW Cooper, CR Rinaldi, MG AF McGinnis, MR Pasarell, L Sutton, DA Fothergill, AW Cooper, CR Rinaldi, MG TI In vitro evaluation of voriconazole against some clinically important fungi SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article AB Voriconazole was compared to amphotericin B. fluconazole, and itraconazole by using an in vitro macrobroth dilution test based upon current National Committee for clinical Laboratory Standards tentative standards against the dimorphic fungi and several opportunistic molds and yeasts, In all instances, the voriconazole MICs were lower than those of fluconazole. In most instances, tbe MICs were lower than the recorded MICs of amphotericin 15 and itraconazole. C1 UNIV TEXAS,MED BRANCH,WHO,COLLABORATING CTR TROP DIS,GALVESTON,TX 77555. UNIV TEXAS,HLTH SCI CTR,FUNGUS TESTING LAB,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,CLIN MICROBIOL LABS,SAN ANTONIO,TX 78284. RP McGinnis, MR (reprint author), UNIV TEXAS,MED BRANCH,DEPT PATHOL,301 UNIV BLVD,GALVESTON,TX 77555, USA. NR 21 TC 85 Z9 86 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD AUG PY 1997 VL 41 IS 8 BP 1832 EP 1834 PG 3 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA XP605 UT WOS:A1997XP60500042 PM 9257773 ER PT J AU CritsChristoph, P Siqueland, L Blaine, J Frank, A Luborsky, L Onken, LS Muenz, L Thase, ME Weiss, RD Gastfriend, DR Woody, G Barber, JP Butler, SF Daley, D Bishop, S Najavits, LM Lis, J Mercer, D Griffin, ML Moras, K Beck, AT AF CritsChristoph, P Siqueland, L Blaine, J Frank, A Luborsky, L Onken, LS Muenz, L Thase, ME Weiss, RD Gastfriend, DR Woody, G Barber, JP Butler, SF Daley, D Bishop, S Najavits, LM Lis, J Mercer, D Griffin, ML Moras, K Beck, AT TI The National Institute on Drug Abuse Collaborative Cocaine Treatment Study - Rationale and methods SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID ADDICTION SEVERITY INDEX; OPIATE ADDICTS; FOLLOW-UP; INTERPERSONAL PSYCHOTHERAPY; INTERACTIONAL THERAPIES; MATCHING ALCOHOLICS; CLINICAL-TRIALS; COPING SKILLS; PHARMACOTHERAPY; PREDICTOR AB The National Institute on Drug Abuse Collaborative Cocaine Treatment Study is a large, multisite psychotherapy clinical trial for outpatients who meet the DSM-IV criteria for cocaine dependence. For 480 randomized patients, the outcomes of 4 treatments are compared for an 18-month period. All treatments include group drug counseling. One treatment also adds cognitive therapy, one adds supportive-expressive psychodynamic therapy, and one adds individual drug counseling; one consists of group drug counseling alone. In addition, 2 specific interaction hypotheses, one involving psychiatric severity and the other involving degree of antisocial personality characteristics, are being tested. This article describes the main aims of the project, the background and rationale for the study design, the rationale for the choice of treatments and patient population, and a brief description of the research plan. C1 UNIV PENN,DEPT PSYCHIAT,PHILADELPHIA,PA 19104. PHILADELPHIA VET HOSP,PHILADELPHIA,PA. NIDA,ROCKVILLE,MD. BROOKSIDE HOSP,NASHUA,NH. UNIV PITTSBURGH,WESTERN PSYCHIAT INST & CLIN,PITTSBURGH,PA 15213. HARVARD UNIV,SCH MED,BOSTON,MA. MCLEAN HOSP,BOSTON,MA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. OI Butler, Stephen/0000-0002-6132-5883 FU NIDA NIH HHS [U18-DA07663, U18-DA07673, U18-DA07090, U18 DA007090] NR 42 TC 75 Z9 76 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD AUG PY 1997 VL 54 IS 8 BP 721 EP 726 PG 6 WC Psychiatry SC Psychiatry GA XQ037 UT WOS:A1997XQ03700006 PM 9283507 ER PT J AU Volpicelli, JR Rhines, KC Rhines, JS Volpicelli, LA Alterman, AI OBrien, CP AF Volpicelli, JR Rhines, KC Rhines, JS Volpicelli, LA Alterman, AI OBrien, CP TI Naltrexone and alcohol dependence - Role of subject compliance SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID ETHANOL-CONSUMPTION; STRATEGIES AB Background: Two previous double-blind, placebo-controlled studies demonstrated that naltrexone (50 mg/d) reduces alcohol drinking in alcohol-dependent subjects. In both studies, treatment compliance was excellent. However, a robust treatment effect size for naltrexone relative to placebo has been shown for compliant subjects but not for subjects who missed research visits. The goal of this study was to determine the effectiveness of naltrexone in subjects who received psychosocial treatment in a more naturalistic setting with respect to the role of treatment attendance and medication compliance. Methods: Ninety-seven alcohol-dependent subjects were randomly assigned to receive either naltrexone (n=48) or matching placebo (n=49) for 12 weeks. All subjects received individual counseling (twice per week for the first month followed by once per week). Results: Overall, naltrexone showed only modest effects in reducing alcohol drinking for the 12 weeks of treatment. However, naltrexone treatment efficacy improved across a variety of outcome measures for subjects who completed treatment and were highly compliant with taking medication. Conclusions: Naltrexone is clinically effective relative to placebo in individuals who comply with the treatment protocol and take medication. The modest treatment effects in the entire sample suggest that the clinical efficacy of naltrexone could be improved by enhancing treatment compliance. C1 UNIV PENN, DEPT PSYCHIAT, PHILADELPHIA, PA 19104 USA. VET AFFAIRS MED CTR, PHILADELPHIA, PA USA. RUTGERS STATE UNIV, DEPT PSYCHOL, PISCATAWAY, NJ USA. FU NIAAA NIH HHS [AA-07517]; NIDA NIH HHS [DA-06107] NR 26 TC 297 Z9 310 U1 1 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-990X EI 1538-3636 J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD AUG PY 1997 VL 54 IS 8 BP 737 EP 742 PG 6 WC Psychiatry SC Psychiatry GA XQ037 UT WOS:A1997XQ03700008 PM 9283509 ER PT J AU Litvan, I Goetz, CG Jankovic, J Wenning, GK Booth, V Bartko, JJ McKee, A Jellinger, K Lai, EC Brandel, JP Verny, M Chaudhuri, KR Pearce, RKB Agid, Y AF Litvan, I Goetz, CG Jankovic, J Wenning, GK Booth, V Bartko, JJ McKee, A Jellinger, K Lai, EC Brandel, JP Verny, M Chaudhuri, KR Pearce, RKB Agid, Y TI What is the accuracy of the clinical diagnosis of multiple system atrophy? A clinicopathologic study SO ARCHIVES OF NEUROLOGY LA English DT Article; Proceedings Paper CT 4th Annual Meeting of the Movement-Disorder-Society CY JUN 16-20, 1996 CL VIENNA, AUSTRIA SP Movement Disorder Soc ID PROGRESSIVE SUPRANUCLEAR PALSY; IDIOPATHIC PARKINSONS-DISEASE; GLIAL CYTOPLASMIC INCLUSIONS; STRIATONIGRAL DEGENERATION; OLIVOPONTOCEREBELLAR ATROPHY; DIFFERENTIAL-DIAGNOSIS; GLUCOSE-METABOLISM; NATURAL-HISTORY; LEWY BODIES; FEATURES AB Background: The presentation of symptoms for multiple system atrophy (MSA) varies. Because there are no specific markers for its clinical diagnosis, the diagnosis rests on the results of the neuropathologic examination. Despite several clinicopathologic studies, the diagnostic accuracy for MSA is unknown. Objectives: To determine the accuracy for the clinical diagnosis of MSA and to identify, as early as possible, those features that would best predict MSA. Design: One hundred five autopsy-confirmed cases of MSA and related disorders (MSA [n = 16], non-MSA [n = 89]) were presented as clinical vignettes to 6 neurologists (raters) who were unaware of the study design. Raters identified the main clinical features and provided a diagnosis based on descriptions of the patients' first and last clinic visits. Methods: Interrater reliability was evaluated with the use of kappa statistics. Raters' diagnoses and those of the primary neurologists (who followed up the patients) were compared with the autopsy-confirmed diagnoses to estimate the sensitivity and positive predictive values at the patients' first and last visits. Logistic regression analysis was used to determine the best predictors to diagnose MSA. Results: For the first visit (median, 42 months after the onset of symptoms), the raters' sensitivity (median, 56%; range, 50%-69%) and positive predictive values (median, 76%; range, 61%-91%) for the clinical diagnosis of MSA were not optimal. For the last visit (74 months after the onset of symptoms), the raters' sensitivity (median, 69%; range, 56%-94%) and positive predictive values (median, 80%; range, 77%-92%) improved. Primary neurologists correctly identified 25% and 50% of the patients with MSA at the first and last visits, respectively. False-negative and -positive misdiagnoses frequently occurred in patients with Parkinson disease and progressive supranuclear palsy. Early severe autonomic;failure, absence of cognitive impairment, early cerebellar symptoms, and early gait disturbances were identified as the best predictive features to diagnose MSA. Conclusions: The low sensitivity for the clinical diagnosis of MSA, particularly among neurologists who followed up these patients in the tertiary centers, suggests that this disorder is underdiagnosed. The misdiagnosis of MSA is usually due to its confusion with Parkinson disease or progressive supranuclear palsy, thus compromising the research on all 3 disorders. C1 NIMH,DEPT EPIDEMIOL & RES STUDIES,NIH,BETHESDA,MD 20892. RUSH MED COLL,DEPT NEUROL,CHICAGO,IL 60612. BAYLOR COLL MED,DEPT NEUROL,HOUSTON,TX 77030. INST PSYCHIAT,NEUROL INST,LONDON,ENGLAND. INST PSYCHIAT,DEPT NEUROL,LONDON SE5 8AF,ENGLAND. PARKINSONS DIS SOC BRAIN TISSUE BANK,LONDON,ENGLAND. MASSACHUSETTS GEN HOSP,DEPT NEUROPATHOL,BOSTON,MA 02114. LAINZ HOSP,LUDWIG BOLTZMANN INST CLIN NEUROBIOL,A-1130 VIENNA,AUSTRIA. HOP LA PITIE SALPETRIERE,RAYMOND ESCOUROLLE NEUROPATHOL LAB,INSERM,U360,PARIS,FRANCE. HOP LA PITIE SALPETRIERE,FEDERAT NEUROL,PARIS,FRANCE. HOP LA PITIE SALPETRIERE,INSERM,U289,PARIS,FRANCE. RP Litvan, I (reprint author), NINCDS,NIH,NEUROEPIDEMIOL BRANCH,FED BLDG,ROOM 714,BETHESDA,MD 20814, USA. OI Litvan, Irene/0000-0002-3485-3445; Ray Chaudhuri, K/0000-0003-2815-0505 NR 55 TC 135 Z9 139 U1 0 U2 2 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 AUG PY 1997 VL 54 IS 8 BP 937 EP 944 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA XQ778 UT WOS:A1997XQ77800003 PM 9267967 ER PT J AU Sanders, VJ Felisan, SL Waddell, AE Conrad, AJ Schmid, P Kaufman, M Walsh, GO DeSalles, AAF Tourtellotte, WW AF Sanders, VJ Felisan, SL Waddell, AE Conrad, AJ Schmid, P Kaufman, M Walsh, GO DeSalles, AAF Tourtellotte, WW TI Presence of herpes simplex DNA in surgical tissue from human epileptic seizure foci detected by polymerase chain reaction - Preliminary study SO ARCHIVES OF NEUROLOGY LA English DT Article ID TEMPORAL-LOBE EPILEPSY; VIRUS; BRAIN; ENCEPHALITIS; PATHOLOGY; TYPE-1 AB Objectives: To determine whether herpes simplex virus causes monofocal epilepsy and to assess the presence of herpes simplex virus 1 (HSV-1) and HSV-2 in surgical specimens from patients with epilepsy by using polymerase chain reaction and Southern blot analysis. Background: Herpes simplex virus is a common neurotropic virus capable of latency within the central nervous system; it has a predilection for the temporal lobe. Central nervous system infection with HSV has been associated with seizure activity. Design and Methods: Surgical specimens were removed from 50 patients as part of a treatment protocol for monofocal epilepsy. Neuropathological classification was done, and adjacent sections were screened for HSV by using polymerase chain reaction. Tissues obtained post mortem from the temporal lobe cortex of persons with Alzheimer disease (n = 17), Parkinson disease (n = 14), or nonneurological disease (n = 17) served as controls. Results: Twenty (40%) of the 50 epilepsy cases and 2 (4%) of the 48 control cases had at least one sample that tested positive for HSV (P < .001). Sixty-seven percent (8/12) of the epilepsy cases with heterotopia were positive for HSV. Conclusions: There was a statistically significant difference in the frequency of HSV-positive surgical specimens from monofocal seizure epicenters compared with nonepilepsy control specimens. These data suggest an association of the virus with seizure activity. All specimens positive for HSV (surgical specimens and control specimens) should be examined to determine the activity or latency state of the virus and cellular localization. C1 W LOS ANGELES VET AFFAIRS MED CTR,NEUROL SERV 127A,LOS ANGELES,CA 90073. W LOS ANGELES VET AFFAIRS MED CTR,RES SERV,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,SCH MED,DEPT NEUROL,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT SURG,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,INST BRAIN RES,LOS ANGELES,CA 90024. CALIF COMPREHENS EPILEPSY PROGRAM,LOS ANGELES,CA. FU NINDS NIH HHS [NS21908B] NR 21 TC 24 Z9 25 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 AUG PY 1997 VL 54 IS 8 BP 954 EP 960 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA XQ778 UT WOS:A1997XQ77800005 PM 9267969 ER PT J AU Chen, MY Metson, R AF Chen, MY Metson, R TI Effects of sinus surgery on speech SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article; Proceedings Paper CT 129th Meeting of the Acoustical-Society-of-America CY MAY 30-JUN 03, 1995 CL WASHINGTON, DC SP Acoust Soc Amer AB Objective: To determine the effects of sinus surgery on the production and perception of speech. Design: Vocal recordings were performed before, 1 week after, and at least 1 month after sinus surgery. Acoustic spectra were analyzed for nasal consonants /m/ and /n/, nasalized vowels, and nonnasalized vowels. Results for nasal consonants were compared with similar recordings obtained from a group of normal subjects with no history of sinus disease. Perceptual analysis of nasalized vowels was conducted by trained phoneticians. Setting: Private practice at an academic medical center. Subjects: Five patients who underwent endoscopic sinus surgery and 3 normal subjects. Main Ou)come Measures: The spectral characteristics and perceptual attributes of nasal sounds. Results: Significant differences in spectral properties were observed for the consonants and nasalized vowels recorded before and after surgery (P<.001). Perceptual experiments for nasalized vowels demonstrated a postoperative decrease in nasality for the high vowel /i/, as in ''beep,'' and an increase in nasality for the non-high vowel /ae/, as in ''bad.'' These perceived changes correlated well with acoustic measures of nasal peak amplitudes and the lowest resonance peak amplitude of the vocal tract. Conclusions: Sinus surgery results in measurable effects on the produced acoustic signal and the perceived nasality of a patient's speech. The identified acoustic correlates may be useful for preoperative counseling of patients concerning expected changes in speech quality following surgery. C1 HARVARD UNIV,DIV HLTH SCI & TECHNOL,CAMBRIDGE,MA 02138. MIT,ELECT RES LAB,CAMBRIDGE,MA 02139. HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOL & LARYNGOL,BOSTON,MA 02115. FU NIDCD NIH HHS [DC 00075] NR 8 TC 24 Z9 24 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD AUG PY 1997 VL 123 IS 8 BP 845 EP 852 PG 8 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA XQ525 UT WOS:A1997XQ52500010 PM 9260551 ER PT J AU Bailet, JW Lichtenstein, A Chen, G Mickel, RA AF Bailet, JW Lichtenstein, A Chen, G Mickel, RA TI Inhibition of lymphocyte function by head and neck carcinoma cell line soluble factors SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article; Proceedings Paper CT 35th Annual Meeting of the American-Society-for-Head-and-Neck-Surgery CY APR 21-22, 1993 CL LOS ANGELES, CA SP Amer Soc Head & Neck Surg ID ACTIVATED KILLER-CELLS; CANCER-PATIENTS; RECOMBINANT INTERLEUKIN-2; ADOPTIVE IMMUNOTHERAPY; CYTO-TOXICITY; LAK CELLS; SUPPRESSION; NODES; LYSIS; METASTASES AB Background: Immunosuppression in patients with head and neck cancer is well recognized. Previous investigations have demonstrated graded immunosuppression that becomes more pronounced as lymphocyte activity is measured closer to the primary neoplasm. In fresh tumors, a soluble factor has been identified that may partly account for the observed graded immunosuppression. Objective: To examine the effect of soluble factors produced by head and neck sqamous cell carcinoma cell lines on the generation of lymphokine activated killer cell cytotoxicity and peripheral blood lymphocyte proliferation induced by interleukin 2, concanavalin A, and phytohemagglutinin. Design: Conditioned supernatant fluids were generated in a 4-day incubation period, using 5 head and neck squamous cell carcinoma cell lines, and were assayed for the ability to inhibit the generation of lymphokine activated killer cell cytotoxicity and naive peripheral blood lymphocyte proliferation induced by interleukin 2, concanavalin A, and phytohemagglutinin. Results: All conditioned supernatant fluids significantly inhibited the generation of lymphokine activated killer cell cytotoxicity relative to controls, and this inhibition was dose dependent. In contrast, supernatant fluids from a myelogenous leukemic tumor cell line, K562, and an ovarian epithelial cell line, SKOV-3, failed to inhibit cytotoxicity. Supernatant fluids conditioned with head and neck squamous cell carcinoma cell lines also profoundly inhibited the naive peripheral blood lymphocyte proliferation induced by interleukin 2, concanavalin A, and phytohemagglutinin. Conclusions: These studies demonstrate that the cell lines of head and neck squamous cell carcinoma produce soluble factors that inhibit lymphocyte function. Furthermore, these experiments suggest that the inhibition previously observed with enzymatically disaggregated fresh tumors is due to factors produced by the tumor cells rather than by other cells within the tumor matrix. C1 UNIV CALIF LOS ANGELES,W LOS ANGELES VET AFFAIRS MED CTR,DEPT MED,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,W LOS ANGELES VET AFFAIRS MED CTR,DIV HEAD & NECK SURG,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA 90024. JONSSON COMPREHENS CANC CTR,LOS ANGELES,CA 90034. W LOS ANGELES VET AFFAIRS MED CTR,CTR CANC,LOS ANGELES,CA 90073. NR 31 TC 4 Z9 4 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD AUG PY 1997 VL 123 IS 8 BP 855 EP 862 PG 8 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA XQ525 UT WOS:A1997XQ52500011 PM 9260552 ER PT J AU Loeser, RF Varnum, BC Carlson, CS Goldring, MB Liu, ET Sadiev, S Kute, TE Wallin, R AF Loeser, RF Varnum, BC Carlson, CS Goldring, MB Liu, ET Sadiev, S Kute, TE Wallin, R TI Human chondrocyte expression of growth-arrest-specific gene 6 and the tyrosine kinase receptor AXL - Potential role in autocrine signaling in cartilage SO ARTHRITIS AND RHEUMATISM LA English DT Article; Proceedings Paper CT 60th National Scientific Meeting of the American-College-of-Rheumatology CY OCT, 1996 CL ORLANDO, FL SP Amer Coll Rheumatol ID ARTICULAR CHONDROCYTES; EXTRACELLULAR-MATRIX; CULTURE; CELLS; PROTEINS AB Objective. To determine if human articular chondrocytes express the axl tyrosine kinase receptor and its ligand Gas-6, a protein product of growth-arrest-specific gene 6, and to determine if Gas-6 and axl function in the regulation of chondrocyte growth. and survival. Methods. The presence of Gas-6 and axl was examined in situ in human articular cartilage by immunohistochemistry and in vitro in cell culture studies using primary human chondrocytes and immortalized human chondrocytes. The ability of recombinant Gas-6 to mediate adhesion of chondrocytes and to stimulate chondrocyte axl phosphorylation was determined. Studies of the role of Gas-6 and axl in cell proliferation and survival were also performed. Results. Both Gas-6 and axl were detected in cartilage by immunohistochemical staining. Gas-6 and axl messenger RNA (mRNA) and protein were also detected in cultures of primary and immortalized human chondrocytes. Compared with cells cultured in medium containing 10% serum, Gas-6 mRNA levels were increased in immortalized chondrocytes cultured in serum-free medium, while axl expression decreased. Chondrocytes attached to Gas-6-coated plastic, and the attachment was blocked by a soluble Ig fusion protein containing the axl extracellular domain. Recombinant human Gas-6 and serum-free conditioned medium from primary and immortalized human chondrocyte cultures stimulated chondrocyte axl tyrosine phosphorylation. A mitogenic effect was noted both when immortalized chondrocytes were stimulated with recombinant Gas-6 or when they were made to overexpress axl by transfection, Addition of recombinant Gas-6 to serum-free medium resulted in increased survival of primary chondrocytes cultured at low density in agarose. Conclusion. These findings present evidence for an autocrine signaling pathway in cartilage involving Gas-6 and the axl tyrosine kinase adhesion receptor, Stimulation of axl by Gas-6 may play an important role in the control of chondrocyte growth and survival. C1 AMGEN CORP,THOUSAND OAKS,CA 91320. MASSACHUSETTS GEN HOSP,CHARLESTOWN,MA. HARVARD UNIV,SCH MED,CHARLESTOWN,MA. NCI,BETHESDA,MD 20892. RP Loeser, RF (reprint author), WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT INTERNAL MED,MED CTR BLVD,WINSTON SALEM,NC 27157, USA. RI Liu, Edison/C-4141-2008 FU NCRR NIH HHS [NCRR-08562]; NIAMS NIH HHS [AR-41656] NR 22 TC 51 Z9 51 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD AUG PY 1997 VL 40 IS 8 BP 1455 EP 1465 DI 10.1002/art.1780400814 PG 11 WC Rheumatology SC Rheumatology GA XP456 UT WOS:A1997XP45600013 PM 9259426 ER PT J AU Rollins, BJ AF Rollins, BJ TI Chemokines SO BLOOD LA English DT Review ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; MACROPHAGE INFLAMMATORY PROTEIN-1-ALPHA; GROWTH-STIMULATORY ACTIVITY; PLATELET FACTOR-IV; NEUTROPHIL-ACTIVATING PEPTIDE; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; INTERFERON-INDUCIBLE PROTEIN-10; ENDOTHELIAL-CELL PROLIFERATION; HUMAN INTERLEUKIN-8 RECEPTOR; HISTAMINE-RELEASING FACTOR C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP Rollins, BJ (reprint author), DANA FARBER CANC INST,DEPT ADULT ONCOL,44 BINNEY ST,BOSTON,MA 02115, USA. RI Yang, Chen/G-1379-2010 NR 272 TC 2079 Z9 2126 U1 5 U2 49 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD AUG 1 PY 1997 VL 90 IS 3 BP 909 EP 928 PG 20 WC Hematology SC Hematology GA XN126 UT WOS:A1997XN12600002 PM 9242519 ER PT J AU Kupfer, GM Yamashita, T Naf, D Suliman, A Asano, S DAndrea, AD AF Kupfer, GM Yamashita, T Naf, D Suliman, A Asano, S DAndrea, AD TI The Fanconi anemia polypeptide, FAC, binds to the cyclin-dependent kinase, cdc2 SO BLOOD LA English DT Article ID 2 COMPLEMENTATION GROUPS; HAMSTER OVARY CELLS; PROTEIN-KINASE; NITROGEN-MUSTARD; P34CDC2 KINASE; DNA-SYNTHESIS; G2 ARREST; S-PHASE; PHOSPHORYLATION; IRRADIATION AB Fanconi anemia (FA) is an autosomal recessive disorder characterized by developmental defects, bone marrow failure, and cancer susceptibility. Cells derived from FA patients are sensitive to crosslinking agents and have a prolonged G(2) phase, suggesting a cell cycle abnormality, Although transfection of type-C FA cells with the FAC cDNA corrects these cellular abnormalities, the molecular function of the FAC polypeptide remains unknown, In the current study we show that expression of the FAC polypeptide is regulated during cell cycle progression, In synchronized HeLa cells, FAC protein expression increased during S phase, was maximal at the G(2)/M transition, and declined during M phase. In addition, the FAC protein coimmunoprecipitated with the cyclin-dependent kinase, cdc2. We next tested various mutant forms of the FAC polypeptide for binding to cdc2. A patient-derived mutant FAC polypeptide, containing a point mutation at L554P, failed to bind to cdc2, The FAC/cdc2 binding interaction therefore correlated with the functional activity of the FAC protein. Moreover, binding of FAC to cdc2 was mediated by the carboxyl-terminal 50 amino acids of FAC in a region of the protein required for FAC function. Taken together, our results suggest that the binding of FAC and cdc2 is required for normal G(2)/M progression in mammalian cells. Absence of a functional interaction between FAC and cdc2 in FA cells may underlie the cell cycle abnormality and clinical abnormalities of FA. (C) 1997 by The American Society of Hematology. C1 HARVARD UNIV, SCH MED, CHILDRENS HOSP, DEPT HEMATOL, BOSTON, MA USA. UNIV TOKYO, INST MED SCI, TOKYO, JAPAN. RP Kupfer, GM (reprint author), DANA FARBER CANC INST, DIV PEDIAT ONCOL, 44 BINNEY ST, BOSTON, MA 02115 USA. FU NHLBI NIH HHS [R01-HL5725]; PHS HHS [K08-H103420] NR 61 TC 77 Z9 80 U1 1 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD AUG 1 PY 1997 VL 90 IS 3 BP 1047 EP 1054 PG 8 WC Hematology SC Hematology GA XN126 UT WOS:A1997XN12600018 PM 9242535 ER PT J AU Trede, NS Warwick, AB Rosoff, PM Rohrer, R Bierer, BE Guinan, E AF Trede, NS Warwick, AB Rosoff, PM Rohrer, R Bierer, BE Guinan, E TI Tacrolimus (FK506) in allogeneic bone marrow transplantation for severe aplastic anemia following orthotopic liver transplantation SO BONE MARROW TRANSPLANTATION LA English DT Article DE FK506; liver transplantation; severe aplastic anemia; bone marrow transplantation ID VERSUS-HOST-DISEASE; NON-B-HEPATITIS; NON-A; FK-506; CYCLOSPORINE; METHOTREXATE; PREVENTION; CHILDREN; INVITRO; GRAFTS AB Severe aplastic anemia (SAA) is a frequent complication of orthotopic liver transplantation for non-typeable viral hepatitis, Allogeneic bone marrow transplantation (BMT) may successfully reconstitute hematopoiesis but the optimal conditioning regimen and graft-versus-host disease (GVHD) prophylaxis in such patients are unknown, Allogeneic BMT was undertaken in an 8-year-old male patient who developed SAA 6 weeks after cadaveric orthotopic liver transplantation for fulminant hepatic failure secondary to presumed non-typeable viral hepatitis, The preparative regimen for his HLA genotypically identical sibling BMT consisted of cytoxan and anti-thymocyte globulin, Tacrolimus (FK506) and prednisone, used to prevent liver graft rejection, were supplemented with methotrexate on post-BMT days, 1, 3, 6 and 11 for GVHD prophylaxis, Engraftment proceeded promptly and without complications, Transfusion dependence resolved 6 weeks after BMT. The patient is alive and well 1 year after his BMT on FK506 and prednisone without any signs of GVHD or liver allograft rejection, This case is the first demonstration of the feasibility of continuing FK506 used for prevention of liver graft rejection as GVHD prophylaxis for allogeneic BMT. C1 CHILDRENS HOSP,DIV HEMATOL ONCOL,BOSTON,MA 02115. MIDWEST CHILDRENS CANC CTR,DEPT PEDIAT ONCOL,MILWAUKEE,WI. DUKE UNIV,MED CTR,DEPT PEDIAT,DIV PEDIAT HEMATOL ONCOL,DURHAM,NC 27710. TUFTS UNIV NEW ENGLAND MED CTR,DEPT SURG,BOSTON,MA 02111. RP Trede, NS (reprint author), DANA FARBER CANC INST,DEPT PEDIAT ONCOL,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [P01 CA39542]; NHLBI NIH HHS [5T32HL07574-15] NR 22 TC 18 Z9 18 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD AUG PY 1997 VL 20 IS 3 BP 257 EP 260 DI 10.1038/sj.bmt.1700872 PG 4 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA XN345 UT WOS:A1997XN34500013 PM 9257897 ER PT J AU Garber, JE Offit, K Olopade, OI Fink, D Barbasch, A Barr, P Gleeson, RK LeStage, B AF Garber, JE Offit, K Olopade, OI Fink, D Barbasch, A Barr, P Gleeson, RK LeStage, B TI The American Society of Clinical Oncology Position on Genetic Testing - Implications for health care providers - Workshop no. 4 SO CANCER LA English DT Article RP Garber, JE (reprint author), DANA FARBER CANC INST,DIV CANC EPIDEMIOL & CONTROL,BOSTON,MA 02115, USA. NR 1 TC 7 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 0008-543X J9 CANCER JI Cancer PD AUG 1 PY 1997 VL 80 IS 3 SU S BP 632 EP 634 DI 10.1002/(SICI)1097-0142(19970801)80:3+<632::AID-CNCR16>3.0.CO;2-F PG 3 WC Oncology SC Oncology GA XW281 UT WOS:A1997XW28100016 PM 11657063 ER PT J AU Hardman, WE Cameron, IL Beer, WH Speeg, KV Kadakia, SC Lang, KA AF Hardman, WE Cameron, IL Beer, WH Speeg, KV Kadakia, SC Lang, KA TI Transforming growth factor alpha distribution in rectal crypts as a biomarker of decreased colon cancer risk in patients consuming cellulose SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID LOSE PROLIFERATIVE RESPONSE; CELL-PROLIFERATION; DIETARY CELLULOSE; TGF-ALPHA; CARCINOGENESIS; RATS; DIFFERENTIATE; NEOPLASIA; RECEPTOR; CALCIUM AB Data from rat experimental carcinogenesis studies indicate that supplemental dietary cellulose reduces the incidence of colon cancer. Epidemiology studies also indicate that high dietary fiber reduces the risk of colorectal cancer in humans. Patients diagnosed with sporadic adenomas were entered into a randomized clinical trial to determine if supplemental dietary cellulose would reduce the patients' risk for colon cancer. Immunohistochemical staining for transforming growth factor alpha (TGF-alpha) was done on biopsies of rectal mucosa taken from patients at the time of initial polypectomy and 1 year later. Results were evaluated for utility as a surrogate end point biomarker for reduction in colon cancer risk. There was a significant decrease in the fraction of the rectal crypt cells that stained for TGF-alpha in six of seven of the patients given the cellulose supplements but in only one of six of the patients not given cellulose. Thus, whether evaluated as a group or in individual patients, there was a significant decrease in TGF-alpha in rectal crypts due to cellulose intervention, which correlated with the expected ability of supplemental dietary cellulose to decrease the risk for colon cancer. Long-term testing of the ability of dietary cellulose to reduce adenoma recurrence is under way to validate the use of TGF-alpha as a surrogate end point biomarker. C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. AUDIE MURPHY DIV,S TEXAS VET HLTH CARE SYST,SAN ANTONIO,TX 78284. BROOKE ARMY MED CTR,SAN ANTONIO,TX 78234. WILFORD HALL USAF MED CTR,SAN ANTONIO,TX 78236. RP Hardman, WE (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT CELLULAR & STRUCT BIOL,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. NR 38 TC 10 Z9 10 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD AUG PY 1997 VL 6 IS 8 BP 633 EP 637 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA XR010 UT WOS:A1997XR01000012 PM 9264277 ER PT J AU Uy, HL Mundy, GR Boyce, BF Story, BM Dunstan, CR Yin, JJ Roodman, GD Guise, TA AF Uy, HL Mundy, GR Boyce, BF Story, BM Dunstan, CR Yin, JJ Roodman, GD Guise, TA TI Tumor necrosis factor enhances parathyroid hormone-related protein-induced hypercalcemia and bone resorption without inhibiting bone formation in vivo SO CANCER RESEARCH LA English DT Article ID COLONY-STIMULATING FACTOR; SQUAMOUS-CELL CARCINOMA; HUMORAL HYPERCALCEMIA; IN-VIVO; NUDE-MICE; FORMATION INVITRO; TNF-ALPHA; MALIGNANCY; INTERLEUKIN-1-ALPHA; SERUM AB Humoral hypercalcemia of malignancy results from the effects of tumor-produced factors on bone, kidney, and intestine that disrupt normal calcium homeostasis, Although parathyroid hormone-related protein (PTHrP) is a major mediator of the syndrome, tumors also produce other hypercalcemic factors, such as tumor necrosis factor (TNF), which may modulate the effects of PTHrP, It has been postulated that TNF may counteract the stimulatory effects of PTHrP on bone formation, To examine the effects of TNF on PTHrP-induced changes in calcium and bone metabolism a murine tumor model of hypercalcemia was used. Nude mice were inoculated with Chinese hamster ovarian (CHO) cells expressing human TNF (CHO/TNF) or nontransfected CHO cells (CHO/-) and further treated with injections of human PTHrP(1-34) or vehicle, The effects of TNF, PTHrP, and the combination of the two factors on blood ionized calcium, osteoclast recruitment, and bone histomorphometry were evaluated. Mice bearing CHO/TNF tumors that were injected with PTHrP had significantly higher calcium concentrations, increased committed osteoclast progenitors, and mature osteoclasts as well as enhanced bone resorption compared with mice bearing CHO/TNF tumors injected with vehicle or those bearing CHO/- tumors injected with PTHrP or vehicle, A 2-fold increase in new woven bone formed in the calvaria at sites of previous bone resorption was observed in CHO/TNF mice treated with PTHrP, Bone formation rates in the vertebrae were similar in both CHO/- and CHO/TNF mice treated with PTHrP, These data demonstrate that the hypercalcemic effects of PTHrP are enhanced by TNF and that this effect is due to the increased production of committed osteoclast precursors with a subsequent increase in osteoclastic bone resorption, Furthermore, PTHrP caused a coupled increase in osteoclastic bone resorption and new bone formation that was not inhibited by TNF, These findings highlight the complex interactions that may occur between tumor-produced factors on bone that result in malignancy-associated hypercalcemia and suggest that TNF may not be responsible for the decreased bone formation seen in some patients with this condition. C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV ENDOCRINOL,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT PATHOL,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. AMGEN INC,THOUSAND OAKS,CA 91320. RI Dunstan, Colin/G-6214-2013 OI Dunstan, Colin/0000-0001-7586-4071 FU NCI NIH HHS [CA 40035]; NIAMS NIH HHS [AR 01899] NR 36 TC 44 Z9 45 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 1997 VL 57 IS 15 BP 3194 EP 3199 PG 6 WC Oncology SC Oncology GA XM812 UT WOS:A1997XM81200024 PM 9242449 ER PT J AU vanEps, RGS Adili, F LaMuraglia, GM AF vanEps, RGS Adili, F LaMuraglia, GM TI Photodynamic therapy inactivates cell-associated basic fibroblast growth factor: a silent way of vascular smooth muscle cell eradication SO CARDIOVASCULAR RESEARCH LA English DT Article DE photodynamic therapy; bovine, smooth muscle cell; bFGF; free radicals; smooth muscle cell proliferative ID EXPERIMENTAL INTIMAL HYPERPLASIA; HUMAN-ENDOTHELIAL-CELLS; RAT CAROTID ARTERIES; LESION FORMATION; DNA-SYNTHESIS; INJURY; PROLIFERATION; RELEASE; PREVENTION; INHIBITION AB Objective: Procedurally related vascular injury results in a smooth muscle cell (SMC) proliferative response which is in part initiated by SMC release of mitogens, including basic fibroblast growth factor (bFGF). This injury-induced proliferative response is believed to be a key event in intimal hyperplasia development. Photodynamic therapy (PDT), a novel approach found to be effective in inhibiting experimental intimal hyperplasia, produces cytotoxic free radicals resulting in localized SMC eradication. However, this form of SMC injury does not induce an inflammatory or proliferative response in the vessel wall. This study investigated whether PDT-generated free radicals could inactivate cell-associated bFGF normally released with cell injury. Methods: PDT of bovine SMC was performed in vitro with the photosensitizer CASPc (5 mu g/ml) and 675 nm laser light using three different fluences: 10, 50, and 100 J/cm(2). After PDT, SMC viability was determined with the tetrazolium salt (MTT) assay and cell-associated bFGF was quantitated by ELISA. A SMC mitogenesis assay was utilized to detect cell-associated bFGF activity released with SMC injury. Results: In a dose-dependent manner, PDT-generated free radicals reduced cell-associated bFGF levels. After PDT with 100 J/cm(2), cell-associated bFGF content was reduced by 88% (P < 0.0002). Of special interest was the finding that PDT with 10 J/cm(2) significantly (P < 0.0002) reduced cell viability to around 50%, without affecting cellular bFGF levels. Consequently, a higher PDT dose (100 J/cm(2)) was needed to significantly (P < 0.001) inhibit the SMC mitogenic response associated with SMC injury. Conclusion: These results provide a mechanism to explain how, unlike mechanical or other forms of SMC injury, optimal doses of PDT can locally eradicate medial vascular SMC without resulting in a bFGF-induced initiation of cell proliferation. (C) 1997 Elsevier Science B.V. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DIV VASC SURG,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,WELLMAN LABS PHOTOMED,BOSTON,MA 02114. NR 32 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD AUG PY 1997 VL 35 IS 2 BP 334 EP 340 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA XU015 UT WOS:A1997XU01500018 ER PT J AU Levine, G Khan, MM Kleiman, NS Raizner, AE Jeroudi, MO Mickelson, J Ali, MN AF Levine, G Khan, MM Kleiman, NS Raizner, AE Jeroudi, MO Mickelson, J Ali, MN TI Use of bare-mounted Palmaz-Schatz stents employing the stent saddle technique on the delivery balloon: A single center experience SO CATHETERIZATION AND CARDIOVASCULAR DIAGNOSIS LA English DT Article DE Palmaz-Schatz stent; coronary angioplasty; abrupt vessel closure AB The major limitations of the Palmaz-Schatz stent stem from the design of its stent delivery system (SDS). The SDS is bulky and has poor trackability in lesions with proximal tortuosity and/or vessel calcification. The use of bare-mounted Palmaz-Schatz stents on low profile balloons represents an alternate approach for lesions that are not accessible for stenting with the SDS, Thus we evaluated the indications, procedural success rate, and in-hospital complications of patients undergoing bare stenting at a single center between 1 October 1995 through 30 September 1996. A total of 363 coronary interventions were performed during this period, including coronary stenting in 194 vessels. In 18 of these 194 vessels, bare-mounted Palmaz-Schatz stents were used. The indications for bare stenting were: inability to deliver the Palmaz-Schatz stent on SDS for suboptimal angioplasty results or acute/threatened abrupt closure; use of half stents; stenting in vessels < 3.0 mm; intermediate disease in the proximal segment that would have precluded optimal visualization of stent placement; and use of guides 7 French or smaller. Bare stenting was successful in 15 of the 18 patients (vessels) in whom it was attempted, There were no deaths, myocardial infarctions, stent thrombosis, repeat interventions, or significant bleeding in patients with successful bare stent delivery, The stents were successfully retrieved in the three patients in whom the stent could not be advanced into the target coronary segment, One of these patients had a propagated spiral dissection prior to attempts at bare stenting and required emergent bypass surgery. The remaining two patients with failed deployment had suboptimal angioplasty results but had an uncomplicated hospital course, Thus bare stenting represents an alternate percutaneous approach to tackle suboptimal procedural results and/or complications in patients who have failed stent deployment with the standard sheathed stent delivery system currently available in the United States. (C) 1997 Wiley-Liss, Inc. C1 BAYLOR COLL MED,VA MED CTR,CARDIOL SECT,DEPT MED,HOUSTON,TX 77030. METHODIST HOSP,HOUSTON,TX 77030. NR 12 TC 7 Z9 7 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0098-6569 J9 CATHETER CARDIO DIAG JI Catheter. Cardiovasc. Diagn. PD AUG PY 1997 VL 41 IS 4 BP 361 EP 368 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA XN788 UT WOS:A1997XN78800001 PM 9258473 ER PT J AU Raptis, L Brownell, HL Corbley, MJ Wood, KW Wang, D Haliotis, T AF Raptis, L Brownell, HL Corbley, MJ Wood, KW Wang, D Haliotis, T TI Cellular ras gene activity is required for full neoplastic transformation by the large tumor antigen of SV40 SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID LARGE-T-ANTIGEN; RETROVIRUS SHUTTLE VECTOR; MOUSE NIH-3T3 CELLS; PROTEIN-KINASE-C; SIMIAN VIRUS-40; SIGNAL-TRANSDUCTION; 10T1/2 FIBROBLASTS; EXPRESSION; GROWTH; POLYOMAVIRUS AB To investigate the role of the cellular ras gene product in neoplastic transformation by the SV40 large tumor antigen (SVLT), murine C3H10T1/2 cells were rendered deficient in Ras activity by transfection with inducible or constitutive antisense ras gene constructs or through the introduction of the dominant-negative mutant, ras(asn17). Consistent with previous results, SVLT-induced morphological transformation was unaffected by the down-regulation of c-ras gene product activity, On the other hand, colony formation in soft agar and tumorigenicity in nude mice were drastically reduced in c-Ras-deficient cells. In addition, SVLT expression in C3H10T1/2 cells led to increased c-Ras activity, as determined by an increase in the Ras-bound GTP/GTP + GDP ratio, These results suggest that c-Ras is required for full neoplastic transformation by SVLT. C1 QUEENS UNIV,DEPT PATHOL,KINGSTON,ON K7L 3N6,CANADA. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. RP Raptis, L (reprint author), QUEENS UNIV,DEPT MICROBIOL & IMMUNOL,BOTTERELL HALL,ROOM 715,KINGSTON,ON K7L 3N6,CANADA. NR 62 TC 28 Z9 28 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD AUG PY 1997 VL 8 IS 8 BP 891 EP 901 PG 11 WC Cell Biology SC Cell Biology GA XQ823 UT WOS:A1997XQ82300007 PM 9269898 ER PT J AU Hager, AJ Szostak, JW AF Hager, AJ Szostak, JW TI Isolation of novel ribozymes that ligate AMP-activated RNA substrates SO CHEMISTRY & BIOLOGY LA English DT Article DE ATP aptamer; catalytic RNA; in vitro selection; ligase; ribozyme ID TEMPLATE; SEQUENCES; COMPLEX; ATP AB Background: The protein enzymes RNA ligase and DNA ligase catalyze the ligation of nucleic acids via an adenosine-5'-5'-pyrophosphate 'capped' RNA or DNA intermediate, The activation of nucleic acid substrates by adenosine 5'-monophosphate (AMP) may be a vestige of 'RNA world' catalysis. AMP-activated ligation seems ideally suited for catalysis by ribozymes (RNA enzymes), because an RNA motif capable of tightly and specifically binding AMP has previously been isolated. Results: We used in vitro selection and directed evolution to explore the ability of ribozymes to catalyze the template-directed ligation of AMP-activated RNAs. We subjected a pool of 10(15) RNA molecules, each consisting of long random sequences flanking a mutagenized adenosine triphosphate (ATP) aptamer, to ten rounds of in vitro selection, including three rounds involving mutagenic polymerase chain reaction, Selection was for the ligation of an oligonucleotide to the 5'-capped active pool RNA species. Many different ligase ribozymes were isolated; these ribozymes had rates of reaction up to 0.4 ligations per hour, corresponding to rate accelerations of similar to 5 x 10(5) over the templated, but otherwise uncatalyzed, background reaction rate, Three characterized ribozymes catalyzed the formation of 3'-5'-phosphodiester bonds and were highly specific for activation by AMP at the ligation site. Conclusions: The existence of a new class of ligase ribozymes is consistent with the hypothesis that the unusual mechanism of the biological ligases resulted from a conservation of mechanism during an evolutionary replacement of a primordial ribozyme ligase by a more modern protein enzyme. The newly isolated ligase ribozymes may also provide a starting point for the isolation of ribozymes that catalyze the polymerization of AMP-activated oligonucleotides or mononucleotides, which might have been the prebiotic analogs of nucleoside triphosphates. C1 MASSACHUSETTS GEN HOSP,DEPT MOL BIOL,BOSTON,MA 02114. NR 19 TC 46 Z9 47 U1 2 U2 8 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 1074-5521 J9 CHEM BIOL JI Chem. Biol. PD AUG PY 1997 VL 4 IS 8 BP 607 EP 617 DI 10.1016/S1074-5521(97)90246-5 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XV884 UT WOS:A1997XV88400007 PM 9281527 ER PT J AU Bradley, J Forero, N Pho, H Escobar, B Kasinath, BS Anzueto, A AF Bradley, J Forero, N Pho, H Escobar, B Kasinath, BS Anzueto, A TI Progressive somnolence leading to coma in a 68-year-old man SO CHEST LA English DT Article ID ACYCLOVIR; NEUROTOXICITY C1 AUDIE L MURPHY MEM VET HOSP DIV,S TEXAS VET HLTH CARE SYST,SAN ANTONIO,TX. UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DIV NEPHROL,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DIV PULM DIS CRIT CARE MED,SAN ANTONIO,TX 78284. RP Bradley, J (reprint author), BROOKE ARMY MED CTR,SAN ANTONIO,TX, USA. NR 5 TC 4 Z9 4 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 SN 0012-3692 J9 CHEST JI Chest PD AUG PY 1997 VL 112 IS 2 BP 538 EP 540 DI 10.1378/chest.112.2.538 PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA XQ816 UT WOS:A1997XQ81600042 PM 9266897 ER PT J AU MacLellan, WR Schneider, MD AF MacLellan, WR Schneider, MD TI Death by design - Programmed cell death in cardiovascular biology and disease SO CIRCULATION RESEARCH LA English DT Review DE apoptosis; gene transfer; heart failure; ischemia ID WILD-TYPE P53; ENDONUCLEASE ACTIVATION; DILATED CARDIOMYOPATHY; MEDIATED APOPTOSIS; NECROSIS-FACTOR; HEART-FAILURE; MESSENGER-RNA; GENE CED-3; BCL-2; EXPRESSION AB Programmed cell death (apoptosis) is recognized, increasingly, as a contributing cause of cardiac myocyte loss with ischemia/reperfusion injury, myocardial infarction, and long-standing heart failure. Although the exact mechanisms initiating apoptosis in these in vivo settings remain unproven, insights into the molecular circuitry controlling apoptosis more widely suggest the potential to protect mammalian ventricular muscle from apoptosis through one or more of these pathways, by pharmacological means or, conceivably, gene transfer. C1 BAYLOR COLL MED,MOL CARDIOL UNIT,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT MED,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT CELL BIOL,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT PHYSIOL & MOL BIOPHYS,HOUSTON,TX 77030. BAYLOR COLL MED,HOUSTON VET AFFAIRS MED CTR,HOUSTON,TX 77030. FU NHLBI NIH HHS [R01 HL-47567, R01 HL-52555, P01 HL-49953] NR 101 TC 283 Z9 293 U1 0 U2 3 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7330 J9 CIRC RES JI Circ.Res. PD AUG PY 1997 VL 81 IS 2 BP 137 EP 144 PG 8 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA XN585 UT WOS:A1997XN58500001 PM 9242174 ER PT J AU Hajjar, RJ Schmidt, U Kang, JX Matsui, T Rosenzweig, A AF Hajjar, RJ Schmidt, U Kang, JX Matsui, T Rosenzweig, A TI Adenoviral gene transfer of phospholamban in isolated rat cardiomyocytes - Rescue effects by concomitant gene transfer of sarcoplasmic reticulum Ca2+-ATPase SO CIRCULATION RESEARCH LA English DT Article DE gene transfer; sarcoplasmic reticulum; phospholamban; Ca2+; Ca2+-ATPase ID HEART-FAILURE; IN-VIVO; DILATED CARDIOMYOPATHY; CARDIAC MYOCYTES; THYROID-HORMONE; CA2+ TRANSPORT; PROTEIN-LEVELS; MYOCARDIUM; EXPRESSION; MUSCLE AB Phospholamban forms an integral part of the cardiac sarcoplasmic reticulum (SR) and regulates the activity of SR Ca2+-ATPase (SERCA2a). A number of studies have suggested a decrease in SERCA2a relative to phospholamban in heart failure. To test the hypothesis that changes in the relative abundance of phospholamban to SERCA2a could account for the pathophysiological abnormalities in Ca2+ handling observed in failing myocardium, we created a recombinant adenovirus designed to overexpress phospholamban (Ad.RSV.PL). In neonatal rat cardiomyocytes, Ad.RSV.PL increased the expression of phospholamban in a concentration-dependent fashion, reaching 280+/-43% at a multiplicity of infection (MOI) of 10.0 plaque forming units (pfu)/cell at 48 hours. The relationship between Ca2+-ATPase activity and [Ca2+] was shifted rightward in membrane preparations from cardiomyocytes infected with Ad.RSV.PL. Intracellular Ca2+ transients measured in the neonatal cells infected with Ad.RSV.PL (MOI, 10 pfu/cell) were characterized by (1) a significant prolongation of the relaxation phase (344+/-26 versus 710+/-56 milliseconds, P<.01), (2) a decrease in peak [Ca2+](i) (967+/-43 versus 630+/-33 nmol/L, P<.01), and (3) an elevation in resting [Ca2+](i) (143+/-14 versus 213+/-17 nmol/L, P<.05). Similarly, the time course of shortening was prolonged in myocytes infected with Ad.RSV.PL. These effects were partially restored by simultaneous transduction with an adenovirus carrying SERCA2a. Cardiomyocytes infected with Ad.RSV.PL had an abnormal frequency response: a decrease in peak [Ca2+](i) and an increase in resting [Ca2+](i) with increasing frequency. These findings indicate that adenovirus-mediated gene transfer of phospholamban modifies intracellular Ca2+ handling and the frequency response in cardiomyocytes. Our results suggest that alterations in the ratio of phospholamban to SERCA2a could account for the abnormalities in Ca2+ handling observed in heart failure and that overexpression of SERCA2a can largely correct these abnormalities. C1 HARVARD UNIV, CARDIOVASC RES CTR, MASSACHUSETTS GEN HOSP E, SCH MED, CHARLESTOWN, MA 02129 USA. HARVARD UNIV, SCH MED, MASSACHUSETTS GEN HOSP, CARDIAC UNIT, CHARLESTOWN, MA 02129 USA. HARVARD UNIV, SCH MED, MASSACHUSETTS GEN HOSP, MED SERV, CHARLESTOWN, MA 02129 USA. HARVARD UNIV, SCH MED, MASSACHUSETTS GEN HOSP, DEPT PREVENT MED, CHARLESTOWN, MA 02129 USA. FU NHLBI NIH HHS [HL-54202, HL-50361, HL-57623] NR 41 TC 82 Z9 84 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7330 EI 1524-4571 J9 CIRC RES JI Circ.Res. PD AUG PY 1997 VL 81 IS 2 BP 145 EP 153 PG 9 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA XN585 UT WOS:A1997XN58500002 PM 9242175 ER PT J AU Lewandowski, ED Yu, X LaNoue, KF White, LT Doumen, C ODonnell, JM AF Lewandowski, ED Yu, X LaNoue, KF White, LT Doumen, C ODonnell, JM TI Altered metabolite exchange between subcellular compartments in intact postischemic rabbit hearts SO CIRCULATION RESEARCH LA English DT Article; Proceedings Paper CT 68th Annual Scientific Sessions of the American-Heart-Association CY NOV 13-16, 1995 CL ANAHEIM, CA SP Amer Heart Assoc, Brazilian Natl Res Council, Sao Paolo, CNR DE stunned myocardium; tricarboxylic acid cycle; mitochondria; reperfusion; nuclear magnetic resonance spectroscopy ID CITRIC-ACID CYCLE; C-13 NMR-SPECTROSCOPY; WORKING RAT HEARTS; REPERFUSED MYOCARDIUM; STUNNED MYOCARDIUM; GLOBAL-ISCHEMIA; GLUCOSE; OXIDATION; SUBSTRATE; RECOVERY AB To examine metabolic regulation in postischemic hearts, we examined oxidative recycling of C-13 within the glutamate pool (GLU) of intact rabbit hearts. Isolated hearts oxidized 2.5 mmol/L [2-C-13]acetate during normal conditions (n=6) or during reperfusion after 10 minutes of ischemia (n=5). C-13-Nuclear magnetic resonance spectra were acquired every 1 minute. Kinetic analysis of C-13 incorporation into GLU provided both tricarboxylic acid (TCA) cycle flux and the interconversion rate (F-1) between the TCA cycle intermediate, alpha-ketoglutarate (alpha-KG), and the largely cytosolic GLU. The rate-pressure product in postischemic hearts was 46% of normal (P<.05). No difference in substrate utilization occurred between groups, with acetate accounting for 92% of the carbon units entering the TCA cycle at the citrate synthase step. TCA cycle flux in postischemic hearts was normal (normal hearts, 10.7 mu mol.min(-1).g(-1); postischemic hearts, 9.4 mu mol.min(-1).g(-1)), whereas F-1 was 72% lower at 2.9+/-0.4 versus 10.2+/-2.5 mu mol.min(-1).g(-1) (mean+/-SE) in normal hearts (P<.05). From additional hearts perfused with 2.5 mmol/L [2-C-13]acetate plus supplemental 5 mmol/L glucose, any potential differences in endogenous carbohydrate availability were proved not to account for the reduced rate alpha-KG and GLU exchange, which remained depressed in postischemic hearts; However, specific activities of the transaminase enzyme, catalyzing chemical exchange of ol-KG and GLU, were the same, and transaminase flux was 100 mu mol.min(-1).g(-1) in postischemic hearts versus 68 mu mol.min(-1).g(-1) in normal hearts. Normal transaminase activity and the increased flux in postischemic hearts are contrary to the reduced F-1. The findings indicate reduced metabolite transport rates across the mitochondrial membranes of stunned myocardium, particularly through the reversible alpha-KG-malate carrier. C1 HARVARD UNIV,SCH MED,BOSTON,MA. PENN STATE UNIV,MILTON S HERSHEY MED CTR,DEPT PHYSIOL,HERSHEY,PA 17033. RP Lewandowski, ED (reprint author), MASSACHUSETTS GEN HOSP,NMR CTR,DEPT RADIOL,BLDG 149,13TH ST,CHARLESTOWN,MA 02129, USA. FU NHLBI NIH HHS [R01 HL-49244, R01 HL-56178] NR 44 TC 38 Z9 38 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 AUG PY 1997 VL 81 IS 2 BP 165 EP 175 PG 11 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA XN585 UT WOS:A1997XN58500004 PM 9242177 ER PT J AU Mahida, YR Galvin, AM Gray, T Makh, S McAlindon, ME Sewell, HF Podolsky, DK AF Mahida, YR Galvin, AM Gray, T Makh, S McAlindon, ME Sewell, HF Podolsky, DK TI Migration of human intestinal lamina propria lymphocytes, macrophages and eosinophils following the loss of surface epithelial cells SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE basement membrane; lymphocytes; macrophages; eosinophils; intestine ID INFLAMMATORY BOWEL-DISEASE; GROWTH-FACTOR-BETA; INTRAEPITHELIAL LYMPHOCYTES; FUNCTIONAL-CHARACTERIZATION; LYMPHOID-CELLS; MUCOSA; COLON; RAT; SUBPOPULATIONS; RECOGNITION AB Lymphocytes and macrophages are present in the normal intestinal lamina propria, separated from the epithelial monolayer by the basement membrane. There is evidence for movement of mononuclear cells through the lamina propria, entering from the systemic circulation and exiting via lymphatic channels. The goal of our studies was to investigate the capacity of cells to migrate out from the lamina propria into the lumen following the loss of surface epithelial cells. An in vitro model was therefore established in which normal human intestinal mucosal samples, denuded of the surface epithelium, were maintained in culture. Electron microscopy showed that during culture, large numbers (> 2 x 10(6)/g tissue per 24 h) of cells migrated out of the lamina propria via discrete 'tunnels' which were in continuity with pores (diameter <4 mu m) in the basement membrane. The emigrating cells were T cells (68.5 +/- 5.1%), macrophages (10.5 +/- 1.3%) and eosinophils (7.1 +/- 1.3%). Our studies have therefore demonstrated, for the first time, the capacity for large numbers of lymphocytes, macrophages and eosinophils to migrate out of the lamina propria, via basement membrane pores. We postulate that such emigration of cells occurs in vivo following the loss of surface epithelial cells due to injury, and could represent an important form of host defence against luminal microorganisms and also facilitate wound repair by enhancing restitution by neighbouring epithelial cells, via peptide factors. C1 UNIV NOTTINGHAM HOSP,QUEENS MED CTR,DIV IMMUNOL,NOTTINGHAM NG7 2UH,ENGLAND. UNIV NOTTINGHAM HOSP,QUEENS MED CTR,DIV PATHOL,NOTTINGHAM NG7 2UH,ENGLAND. UNIV NOTTINGHAM HOSP,QUEENS MED CTR,INST INFECT & IMMUN,NOTTINGHAM NG7 2UH,ENGLAND. HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,BOSTON,MA 02114. RP Mahida, YR (reprint author), UNIV NOTTINGHAM HOSP,QUEENS MED CTR,DIV GASTROENTEROL,NOTTINGHAM NG7 2UH,ENGLAND. FU NIDDK NIH HHS [DK41557, DK43351] NR 37 TC 69 Z9 70 U1 0 U2 2 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD AUG PY 1997 VL 109 IS 2 BP 377 EP 386 DI 10.1046/j.1365-2249.1997.4481346.x PG 10 WC Immunology SC Immunology GA XP310 UT WOS:A1997XP31000022 PM 9276536 ER PT J AU Lein, M Nowak, L Jung, K Koenig, F Lichtinghagen, R Schnorr, D Loening, SA AF Lein, M Nowak, L Jung, K Koenig, F Lichtinghagen, R Schnorr, D Loening, SA TI Analytical aspects regarding the measurement of metalloproteinases and their inhibitors in blood SO CLINICAL BIOCHEMISTRY LA English DT Article DE metalloproteinase-1; tissue inhibitor of metalloproteinase-1; preanalytical factors ID SANDWICH ENZYME-IMMUNOASSAY; TISSUE INHIBITOR; RHEUMATOID-ARTHRITIS; MATRIX-METALLOPROTEINASES; IV COLLAGENASES; SERUM; PLASMA; GELATINASE; DISEASE; CANCER AB Objective: Both in vitro and in vivo investigations have shown that the balance between matrix metalloproteinases (MMP) and the tissue inhibitors of metalloproteinases (TIMP) seems to be important in physiological and pathological processes which involve tissue remodeling and repair. Design and Methods: In order to investigate the analytical reliability of new commercial ELISA tests, BIOTRAK(TM) test kits (Amersham Int.) were used for the determination of metalloproteinase-1 (MMP-1), tissue inhibitor of metalloproteinase-1 (TIMP-1), and the MMP-1/TIMP-1 complex in blood. Results: The detection limits and the precision data were in the usual ranges of ELISA tests so that concentrations found in blood could be determined reliably. Since all three analytes were lower in heparin plasma than in serum or EDTA plasma, heparin plasma was selected as the specimen of choice. Measurement of diluted samples gave higher values than those of undiluted native plasma samples because the inhibitory effects of specific/unspecific inhibitors or other matrix components were apparently reduced. To obtain comparable data from different laboratories, the predilution of samples must be defined. We recommend to use diluted plasma samples of 1:5, 1:21, and 1:11 for the determination of MMP-1, TIMP-1, and the complex MMP-1/TIMP-1, respectively. The preliminary upper 95% reference limits measured under these conditions in healthy subjects (40 females. 40 males) were 14.4 mu g/L for MMP-1 in females, 20 mu g/L for MMP-1 in males, 1668 mu g/L for TIMP-1 and 116 mu g/L for the complex MMP-1/TIMP-1. Conclusion: The study has shown that the BIOTRAK(TM) test combinations for MMP-1, TIMP-1, and MMP-1/TIMP-1 complex allow a reliable measurement of the analyte concentrations in heparin plasma. In order to avoid preanalytical misinterpretations only heparin plasma samples in defined dilutions should be used. C1 HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138. HUMBOLDT UNIV BERLIN,UNIV HOSP CHARITE,DEPT UROL,BERLIN,GERMANY. UNIV MED SCH HANOVER,DEPT CLIN CHEM,HANNOVER,GERMANY. RP Lein, M (reprint author), MASSACHUSETTS GEN HOSP,WELLMAN LABS PHOTOMED WEL 224,55 FRUIT ST,BOSTON,MA 02114, USA. NR 27 TC 55 Z9 55 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0009-9120 J9 CLIN BIOCHEM JI Clin. Biochem. PD AUG PY 1997 VL 30 IS 6 BP 491 EP 496 DI 10.1016/S0009-9120(97)00097-0 PG 6 WC Medical Laboratory Technology SC Medical Laboratory Technology GA XY782 UT WOS:A1997XY78200007 PM 9316744 ER PT J AU Fenton, MA Shuster, TD Fertig, AM Taplin, ME Kolvenbag, G Bubley, GJ Balk, SP AF Fenton, MA Shuster, TD Fertig, AM Taplin, ME Kolvenbag, G Bubley, GJ Balk, SP TI Functional characterization of mutant androgen receptors from androgen-independent prostate cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID FLUTAMIDE WITHDRAWAL; LIGAND-BINDING; LNCAP CELLS; GENE; CARCINOMA; MUTATION; ANTIANDROGENS; MANAGEMENT; PROTEIN; DOMAIN AB Mutations in the androgen receptor (AR), that alter steroid hormone specificity have been identified in a series of androgen-independent prostate cancers, To address the functional properties of these mutant ARs that may have contributed to their selection in vivo, responses to a series of steroid hormones and antiandrogens were assessed, CV-1 cells mere cotransfected with wild-type or mutant ARs and a luciferase reporter plasmid regulated by an androgen-responsive element, Dose-response curves were analyzed for 5 alpha-dihydrotestosterone, the most active androgen in normal prostate, and androstenedione, a major androgen derived from the adrenals, Although the mutant ARs responded to both of these steroids, the responses were equivalent to or less than the wild-type AR, In contrast, responses to flutamide, a competitive antagonist of the mild-type ARI were markedly increased by three of the mutations, Similar responses mere observed with a second antiandrogen, nilutamide, Bicalutamide, another antiandrogen related to flutamide, remained an antagonist for these mutant ARs, Finally, flutamide was observed to be a weak partial agonist of the wild-type AR in this system, These results indicate that flutamide used in conjunction with androgen ablation therapy for prostate cancer may select for tumor cells with flutamide-inducible ARs. C1 BETH ISRAEL HOSP,DEACONESS MED CTR,DEPT MED,CANC BIOL PROGRAM,DIV HEMATOL ONCOL,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA 02215. UNIV MASSACHUSETTS,SCH MED,DIV HEMATOL ONCOL,WORCESTER,MA. ZENECA PHARMACEUT,WILMINGTON,DE 19803. FU NCI NIH HHS [CA65647, R29-CA51438]; NHLBI NIH HHS [HL07516] NR 31 TC 160 Z9 162 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 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD AUG PY 1997 VL 3 IS 8 BP 1383 EP 1388 PG 6 WC Oncology SC Oncology GA XP443 UT WOS:A1997XP44300018 PM 9815822 ER PT J AU Blumenthal, D AF Blumenthal, D TI The errors of our ways SO CLINICAL CHEMISTRY LA English DT Editorial Material C1 HARVARD UNIV,DEPT MED & HLTH CARE POLICY,CAMBRIDGE,MA 02138. RP Blumenthal, D (reprint author), MASSACHUSETTS GEN HOSP,HLTH POLICY RES & DEV UNIT,50 STANIFORD ST,BOSTON,MA 02114, USA. NR 2 TC 14 Z9 15 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD AUG PY 1997 VL 43 IS 8 BP 1305 EP 1305 PN 1 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA XP425 UT WOS:A1997XP42500001 PM 9267304 ER PT J AU Kulke, MH Vance, EA AF Kulke, MH Vance, EA TI Pneumocystis carinii pneumonia in patients receiving chemotherapy for breast cancer SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID CD4+ T-LYMPHOCYTOPENIA; OPPORTUNISTIC INFECTIONS; HIV-INFECTION; AIDS AB Pneumocystis carinii pneumonia (PCP) is uncommon in patients undergoing chemotherapy for breast cancer. Most previously described patients with breast cancer and PCP received treatment with corticosteroids, a known risk factor for PCP, We describe two patients with metastatic breast cancer who developed PCP after receiving therapy with high doses of cyclophosphamide with peripheral blood stem cell support. Both patients developed fevers of unclear etiology in the setting of recovery of the neutrophil count, Only one patient had pulmonary symptoms, P. carinii infection was documented in both cases by bronchoscopy, One patient died after prolonged ventilatory support for PCP. Steroid exposure did not appear to be a risk factor for the development of PCP in either patient. Patients receiving sequential high doses of chemotherapy with stem cell support may be at increased risk for PCP, The role of prophylaxis for PCP in this setting should be continually redefined as the type and intensity of chemotherapy, as well as methods of procurement of autologous stem cells, continue to change. C1 DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT MED,BOSTON,MA 02115. PFIZER INC,BETH ISRAEL HOSP,HARVARD MIT DIV HLTH SCI & TECHNOL,BOSTON,MA. RP Kulke, MH (reprint author), DANA FARBER CANC INST,DIV MED ONCOL,44 BINNEY ST,BOSTON,MA 02115, USA. NR 19 TC 41 Z9 41 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD AUG PY 1997 VL 25 IS 2 BP 215 EP 218 DI 10.1086/514542 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA XT820 UT WOS:A1997XT82000009 PM 9332513 ER PT J AU Falagas, ME Snydman, DR Griffith, J Werner, BG Freeman, R Rohrer, R Fairchild, R Fawaz, K Hoffman, MA Kaplan, M Gill, M Rubin, RH Dienstag, JL Doran, M ORourke, E Vacanti, J Jenkins, R Lewis, WD Hammer, S Martin, M Grady, GF Leszczynski, J Dougherty, N Katz, A Fausett, G Platt, R Cheeseman, SH Pasternack, M Gorbach, SL AF Falagas, ME Snydman, DR Griffith, J Werner, BG Freeman, R Rohrer, R Fairchild, R Fawaz, K Hoffman, MA Kaplan, M Gill, M Rubin, RH Dienstag, JL Doran, M ORourke, E Vacanti, J Jenkins, R Lewis, WD Hammer, S Martin, M Grady, GF Leszczynski, J Dougherty, N Katz, A Fausett, G Platt, R Cheeseman, SH Pasternack, M Gorbach, SL TI Clinical and epidemiological predictors of recurrent cytomegalovirus disease in orthotopic liver transplant recipients SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 35th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) CY SEP 17-22, 1995 CL SAN FRANCISCO, CA SP Amer Soc Microbiol ID GANCICLOVIR; PROPHYLAXIS AB Predictors of recurrent cytomegalovirus (CMV) disease after the first episode of successfully treated CMV disease in orthotopic liver transplant recipients were studied. Recurrent CMV disease was defined as disease diagnosed >14 days after the end of a minimum 8-day course of ganciclovir therapy for the first episode and was classified as early or late if it occurred within or after 90 days, respectively, after completion of ganciclovir treatment, Eleven (27%) of 41 patients had recurrent CMV disease (nine early recurrences and two late recurrences). Death was more likely to occur in patients with recurrent CMV disease than in those without it (55% vs. 13%, respectively; P = .006). Initial episodes of multiorgan CMV disease (P = .001) and CMV pneumonia (P = .012) were associated with early recurrence, Multivariate analysis showed that multiorgan CMV disease was independently associated with early recurrence (P = .003; odds ratio, 13.5; 95% confidence interval, 2.4-76.8), Recognition of risk factors for recurrent CMV disease may help identify patients for whom a more intensive therapeutic or diagnostic approach is needed. C1 TUFTS UNIV NEW ENGLAND MED CTR,DEPT MED,BOSTON,MA 02111. TUFTS UNIV NEW ENGLAND MED CTR,DEPT PATHOL,BOSTON,MA 02111. TUFTS UNIV NEW ENGLAND MED CTR,DEPT SURG,BOSTON,MA 02111. TUFTS UNIV,SCH MED,BOSTON,MA 02111. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. CHILDRENS HOSP,BOSTON,MA 02115. NEW ENGLAND DEACONESS HOSP,BOSTON,MA 02215. MASSACHUSETTS STATE LAB INST,BOSTON,MA. RI Snydman, David/O-3889-2014 OI Snydman, David/0000-0003-0119-3978 FU NIDDK NIH HHS [R10 DK31389] NR 7 TC 29 Z9 29 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD AUG PY 1997 VL 25 IS 2 BP 314 EP 317 DI 10.1086/514555 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA XT820 UT WOS:A1997XT82000027 PM 9332531 ER PT J AU Santarius, T Kirsch, M Rossi, ML Black, PM AF Santarius, T Kirsch, M Rossi, ML Black, PM TI Molecular aspects of neuro-oncology SO CLINICAL NEUROLOGY AND NEUROSURGERY LA English DT Review DE molecular biology; nervous system tumours; pathogenesis ID TUMOR-SUPPRESSOR GENE; PROGRAMMED CELL-DEATH; FACTOR RECEPTOR GENE; NEUROFIBROMATOSIS TYPE-1 GENE; HUMAN-MALIGNANT ASTROCYTOMA; DOMINANT-NEGATIVE MUTANTS; CENTRAL-NERVOUS-SYSTEM; GROWTH-FACTOR PDGF; 17P ALLELIC LOSS; GLIOBLASTOMA-MULTIFORME AB Detailed understanding of molecule events responsible for brain tumor growth is a prerequisite for the development of effective therapeutic modalities leading to improved prognosis and cure. Advances in molecular biology in the past decades have revolutionized our understanding of cancer, including brain tumors. We have learned that abnormal proliferation, inability of the cells to die and their potential to modify their tissue environment result from accumulation of genetic aberrations. This article reviews genetic mechanisms implicated in their pathogenesis of nervous system tumors, such as inactivation of tumor suppressor and replication error genes, generation of abnormal growth factor loops, alterations of apoptotic pathways and angiogenesis. (C) 1997 Elsevier Science B.V. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,BRAIN TUMOR CTR,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT SURG,DANA FARBER CANC INST,BOSTON,MA 02115. TECH UNIV DRESDEN,CARL GUSTAV CARUS KLINIKUM,NEUROCHIRURG KLIN,D-01307 DRESDEN,GERMANY. UNIV LIVERPOOL,WALTON CTR NEUROL & NEUROSURG,LIVERPOOL L69 3BX,MERSEYSIDE,ENGLAND. HARVARD UNIV,SCH MED,CHILDRENS HOSP,BOSTON,MA 02115. RP Santarius, T (reprint author), HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,NEUROSURG LABS,BOSTON,MA 02115, USA. RI Kirsch, Matthias/F-2824-2014 NR 141 TC 11 Z9 12 U1 1 U2 1 PU VAN GORCUM CO BV PI ASSEN PA PO BOX 43, 9400 AA ASSEN, NETHERLANDS SN 0303-8467 J9 CLIN NEUROL NEUROSUR JI Clin. Neurol. Neurosurg. PD AUG PY 1997 VL 99 IS 3 BP 184 EP 195 DI 10.1016/S0303-8467(97)00025-5 PG 12 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA YB337 UT WOS:A1997YB33700004 PM 9350399 ER PT J AU McGrory, BJ Burke, DW Moran, SJ AF McGrory, BJ Burke, DW Moran, SJ TI Posterior instability of the hip in an adult - A case report SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article AB Dislocation of the hip except as a congenital or developmental lesion is not common, and the onset of symptoms because of posterior instability of the hip in an adult has not been reported previously. An adult patient who had benign congenital hypotonia as an infant and who presented with generalized ligamentous laxity and hip pain associated with recurring posterior subluxation of the hip is the subject of this report. C1 UNIV VERMONT,DEPT ORTHOPAED SURG & REHABIL,BURLINGTON,VT. MAINE MED CTR,PORTLAND,ME 04102. ORTHOPAED ASSOCIATES PORTLAND PA,PORTLAND,ME 04104. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. MILES MEM HOSP,DAMARISCOTTA,ME. NR 14 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD AUG PY 1997 IS 341 BP 151 EP 154 PG 4 WC Orthopedics; Surgery SC Orthopedics; Surgery GA XQ565 UT WOS:A1997XQ56500023 PM 9269168 ER PT J AU Varghese, JC Hahn, PF Papanicolaou, N MayoSmith, WW Gaa, JA Lee, MJ AF Varghese, JC Hahn, PF Papanicolaou, N MayoSmith, WW Gaa, JA Lee, MJ TI MR differentiation of phaeochromocytoma from other adrenal lesions based on qualitative analysis of T2 relaxation times SO CLINICAL RADIOLOGY LA English DT Article ID CHEMICAL-SHIFT; MASSES; BENIGN; PHEOCHROMOCYTOMAS; SCINTIGRAPHY; DISTINCTION; GLAND; CT AB Aim: To determine the diagnostic accuracy of MR imaging in differentiating phaeochromocytoma from other adrenal lesions, Materials and methods: Sixty-seven adrenal masses (65 patients) including 17 phaeochromocytomas were imaged using T2-weighted pulse sequences on 0.6 T and 1.5 T GE MR units, The adrenal lesions mere qualitatively assessed by three observers and divided into three categories (benign adenomas, malignant lesions and phaeochromocytomas) based on lesion signal intensity relative to liver and cerebrospinal fluid, Results: Eleven phaeochromocytomas (65%) were correctly identified while the remaining six (35%) were misclassified, five as malignant lesions and one as a benign adenoma, because of atypical low signal intensity on T2-weighted MR images, Conversely, six non-phaeochromocytomas (three benign adenomas, two adrenal carcinomas and one metastasis) mere wrongly classified as phaeochromocytomas because of very high lesion signal intensity, The sensitivity of MR imaging for diagnosing phaeochromocytoma was 64.7%, specificity 88.0%, positive predictive value 64.7% and negative predictive value 88.0%, Conclusion: There is considerable overlap between the MR appearance of phaeochromocytoma and other adrenal lesions, A phaeochromocytoma cannot be excluded on the basis of a lack of high signal intensity on T2-weighted MR imaging. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138. NR 19 TC 47 Z9 53 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 0009-9260 J9 CLIN RADIOL JI Clin. Radiol. PD AUG PY 1997 VL 52 IS 8 BP 603 EP 606 DI 10.1016/S0009-9260(97)80252-8 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA XQ571 UT WOS:A1997XQ57100006 PM 9285420 ER PT J AU Otto, MW Fava, M Penava, SJ Bless, E Muller, RT Rosenbaum, JR AF Otto, MW Fava, M Penava, SJ Bless, E Muller, RT Rosenbaum, JR TI Life event, mood, and cognitive predictors of perceived stress before and after treatment for major depression SO COGNITIVE THERAPY AND RESEARCH LA English DT Article DE depression; dysfunctional attitudes; problem solving; perceived stress; negative life events ID DYSFUNCTIONAL ATTITUDES; UNIPOLAR DEPRESSION; SYMPTOMS; STATE; MODEL; PERSONALITY; DISORDERS AB Using regression models, we examined the influence of negative life events, depression severity dysfunctional attitudes, and problem-solving ability on the perceived stress of depressed outpatients before and after antidepressant treatment. The report of negative life events predicted she level of perceived stress in untreated patients, but was not a significant predictor after treatment Depression severity, dysfunctional attitudes, and problem-solving ability were associated with each other improved with treatment, and associated with perceived stress before and after treatment These findings are consistent with the hypothesis that less adaptive coping strategies are applied under conditions of mood disturbance, and that these strategies are in turn linked with increased stress. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP Otto, MW (reprint author), MASSACHUSETTS GEN HOSP,BEHAV THERAPY UNIT,WACC815,BOSTON,MA 02114, USA. NR 33 TC 18 Z9 18 U1 2 U2 2 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0147-5916 J9 COGNITIVE THER RES JI Cogn. Ther. Res. PD AUG PY 1997 VL 21 IS 4 BP 409 EP 420 DI 10.1023/A:1021980209878 PG 12 WC Psychology, Clinical SC Psychology GA XQ306 UT WOS:A1997XQ30600002 ER PT J AU Cullen, DJ Sweitzer, BJ Bates, DW Burdick, E Edmondson, A Leape, LL AF Cullen, DJ Sweitzer, BJ Bates, DW Burdick, E Edmondson, A Leape, LL TI Preventable adverse drug events in hospitalized patients: A comparative study of intensive care and general care units SO CRITICAL CARE MEDICINE LA English DT Article DE adverse drug events; intensive care unit; general care unit; medical unit; surgical unit; severity of illness; length of stay; costs; structured interviews ID RESIDENT ANESTHESIOLOGISTS; SLEEPINESS; ERRORS; SYSTEM AB Objectives: To compare the frequency and preventability of adverse drug events and potential adverse drug events in inten- sive care units (ICUs) and non-ICUs. To evaluate systems factors involving the individual caregivers, care unit teams, and patients involved in each adverse drug event by comparing ICUs with non-ICUs and medical ICUs with surgical ICUs. Design: Prospective cohort study. Participants included all 4,031 adult admissions to a stratified, random sample of 11 medical and surgical units in two tertiary care hospitals over a 6-month period, Units included two medical and three surgical ICUs and four medical and two surgical general care units. Setting: Two tertiary care hospitals: Eleven medical and surgical units, including two medical and three surgical ICUs. Patients: Adult admissions (n = 4,031). Interventions: None. Measurements and Main Results: Rate of preventable adverse drug events and potential adverse drug events, length of stay, charges, costs, and measures of the unit's environment. Incidents were detected by stimulated self-report by nurses and pharmacists and by daily review of all charts by nurse investigators. Incidents were subsequently classified by two independent reviewers as to whether they represented adverse drug events or potential adverse drug events and as to severity and preventability. Those individuals involved in the preventable adverse drug event and potential adverse drug event underwent detailed interviews by peer case-investigators. The rate of preventable adverse drug events and potential adverse drug events in ICUs was 19 events per 1000 patient days, nearly twice that rate of non-ICUs (p <.01). The medical ICU rate (25 events per 1000 patient days) was significantly (p <.05) higher than the surgical ICU rate (14 events per 1000 patient days). When adjusted for the number of drugs used in the previous 24 hrs or ordered since admission, there were no differences in rates between ICUs and non-ICUs. ICU acuity, length of stay, and severity of the adverse drug event were greater in ICUs than non-ICUs, but there were no differences between medical ICU and surgical ICU patients. Structured interviews indicated almost no differences between ICUs and non-ICUs for many characteristics of the patient, patient care team, systems, and individual caregivers. Conclusions: The rate of preventable and potential adverse drug events was twice as high in ICUs compared with non-ICUs. However, when adjusted for the number of drugs ordered, there was no greater likelihood for preventable adverse drug events and potential adverse drug events to occur in ICUs than in non-ICUs. Preventable adverse drug events and potential adverse drug events occurred in units that functioned normally and involved caregivers who were working under reasonably normal circumstances, not at the extremes of workload, stress, or a difficult environment. C1 HARVARD UNIV,SCH MED,DEPT ANAESTHESIA,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT MED,DIV GEN MED,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT HLTH POLICY & MANAGEMENT,BOSTON,MA 02115. HARVARD UNIV,DEPT PSYCHOL,BOSTON,MA 02115. RP Cullen, DJ (reprint author), MASSACHUSETTS GEN HOSP,DEPT ANAESTHESIA,BOSTON,MA 02114, USA. FU AHRQ HHS [R01-HS07107-01] NR 14 TC 287 Z9 295 U1 2 U2 10 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD AUG PY 1997 VL 25 IS 8 BP 1289 EP 1297 DI 10.1097/00003246-199708000-00014 PG 9 WC Critical Care Medicine SC General & Internal Medicine GA XQ994 UT WOS:A1997XQ99400014 PM 9267940 ER PT J AU Kirchhausen, T Bonifacino, JS Riezman, H AF Kirchhausen, T Bonifacino, JS Riezman, H TI Linking cargo to vesicle formation: receptor tail interactions with coat proteins SO CURRENT OPINION IN CELL BIOLOGY LA English DT Article ID FACTOR-II RECEPTOR; ENDOPLASMIC-RETICULUM; GOLGI MEMBRANES; CLATHRIN COATS; INTERNALIZATION; ENDOCYTOSIS; BINDING; SIGNAL; YEAST; LOCALIZATION AB How soluble cargo molecules concentrate into budding vesicles is the subject of intensive current research. Clathrin-based vesiculation from the plasma membrane and the trans-Golgi network constitutes the best described system that supports this sorting process. Soluble ligands bind to specific transmembrane receptors which have been shown to interact directly with clathrin adaptor complexes, components of clathrin coats. At the same time, these clathrin adaptors facilitate clathrin coat assembly and probably regulate the recruitment of the rest of the coat components. Recent studies have looked at both the interaction of receptor tails with adaptors and the assembly of the clathrin coat. Progress has also been made in elucidating how soluble cargo molecules may be concentrated for exit from the endoplasmic reticulum. C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. NICHHD,CELL BIOL & METAB BRANCH,NIH,BETHESDA,MD 20892. UNIV BASEL,BIOZENTRUM,CH-4056 BASEL,SWITZERLAND. RP Kirchhausen, T (reprint author), HARVARD UNIV,SCH MED,DEPT CELL BIOL,200 LONGWOOD AVE,BOSTON,MA 02115, USA. OI Riezman, Howard/0000-0003-4680-9422; Bonifacino, Juan S./0000-0002-5673-6370 NR 59 TC 338 Z9 340 U1 0 U2 2 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0955-0674 J9 CURR OPIN CELL BIOL JI Curr. Opin. Cell Biol. PD AUG PY 1997 VL 9 IS 4 BP 488 EP 495 DI 10.1016/S0955-0674(97)80024-5 PG 8 WC Cell Biology SC Cell Biology GA XM844 UT WOS:A1997XM84400005 PM 9261055 ER PT J AU Shoelson, SE AF Shoelson, SE TI SH2 and PTB domain interactions in tyrosine kinase signal transduction SO CURRENT OPINION IN CHEMICAL BIOLOGY LA English DT Article ID PHOSPHOTYROSINE INTERACTION DOMAIN; INSULIN-RECEPTOR SUBSTRATE-1; GROWTH-FACTOR RECEPTOR; PHOSPHATIDYLINOSITOL 3-KINASE; PHOSPHOINOSITIDE 3-KINASE; INHIBITORY PEPTIDES; PHOSPHATASE SH-PTP2; CRYSTAL-STRUCTURES; ACTIVATION MOTIF; BINDING DOMAIN AB Proteins with SH2 or phosphotyrosine binding (PTB) domains bind activated tyrosine kinase receptors and their substrates to propagate signals into cells. Both of the domains recognize phosphotyrosine. Selectivity in these interactions is conferred by short flanking peptide motifs. Therefore, potential exists for modulating tyrosine kinase signaling pathways by the discovery of compounds that selectively bind SH2 and PTB domains. Recent advances with small peptides and nonpeptide compounds suggest that this opportunity can be realized. (C) Current Biology Ltd ISSN 1367-5931. C1 Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. RP Shoelson, SE (reprint author), Harvard Univ, Sch Med, Dept Med, 1 Joslin Pl, Boston, MA 02215 USA. NR 64 TC 62 Z9 62 U1 0 U2 3 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON W1P 6LB, ENGLAND SN 1367-5931 J9 CURR OPIN CHEM BIOL JI Curr. Opin. Chem. Biol. PD AUG PY 1997 VL 1 IS 2 BP 227 EP 234 DI 10.1016/S1367-5931(97)80014-2 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA YP152 UT WOS:000071247900014 PM 9667855 ER PT J AU Brun, RP Kim, JB Hu, E Spiegelman, BM AF Brun, RP Kim, JB Hu, E Spiegelman, BM TI Peroxisome proliferator-activated receptor gamma and the control of adipogenesis SO CURRENT OPINION IN LIPIDOLOGY LA English DT Review ID BROWN ADIPOSE-TISSUE; UNCOUPLING PROTEIN GENE; ADIPOCYTE DIFFERENTIATION; FATTY-ACIDS; TRANSCRIPTION FACTOR; C/EBP-ALPHA; PPAR-GAMMA; EXPRESSION; ENHANCER; CELLS AB The adipose cell is now known to play a complex role in energy homeostasis, storing energy and signaling to other tissues concerning the state of energy balance, The past several years have seen an explosive increase in our knowledge of the transcriptional basis of adipocyte differentiation. This review describes the role of peroxisome proliferator-activated receptor gamma in this process, and describes how other transcription factors may affect adipogenesis by modulating the amount or activity of peroxisome proliferator-activated receptor gamma, Furthermore, peroxisome proliferator-activated receptor gamma and other adipogenic transcription factors provide a focus for beginning to understand how various hormones and metabolites influence the development of this tissue in vivo. RP Brun, RP (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT CELL BIOL,44 BINNEY ST,BOSTON,MA 02115, USA. NR 55 TC 86 Z9 90 U1 0 U2 3 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0957-9672 J9 CURR OPIN LIPIDOL JI Curr. Opin. Lipidology PD AUG PY 1997 VL 8 IS 4 BP 212 EP 218 DI 10.1097/00041433-199708000-00004 PG 7 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Peripheral Vascular Disease SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Cardiovascular System & Cardiology GA XP573 UT WOS:A1997XP57300004 PM 9253537 ER PT J AU Porter, FD Drago, J Xu, Y Cheema, SS Wassif, C Huang, SP Lee, E Grinberg, A Massalas, JS Bodine, D Alt, F Westphal, H AF Porter, FD Drago, J Xu, Y Cheema, SS Wassif, C Huang, SP Lee, E Grinberg, A Massalas, JS Bodine, D Alt, F Westphal, H TI Lhx2, a LIM homeobox gene, is required for eye, forebrain, and definitive erythrocyte development SO DEVELOPMENT LA English DT Article DE LIM homeobox; eye; forebrain; erythropoiesis; mouse ID EXPRESSION PATTERNS; VERTEBRATE LIMB; MOUSE; HOMEODOMAIN; PROTEIN; DOMAIN; INDUCTION; CELLS; ZINC; DIFFERENTIATION AB We investigated the function of Lhx2, a LIM homeobox gene expressed in developing B-cells, forebrain and neural retina, by analyzing embryos deficient in functional Lhx2 protein, Lhx2 mutant embryos are anophthalmic, have malformations of the cerebral cortex, and die in utero due to severe anemia, In Lhx2-/- embryos specification of the optic vesicle occurs; however, development of the eye arrests prior to formation of an optic cup, Deficient cellular proliferation in the forebrain results in hypoplasia of the neocortex and aplasia of the hippocampal anlagen, In addition to the central nervous system malformations, a cell non-autonomous defect of definitive erythropoiesis causes severe anemia in Lhx2-/- embryos, Thus Lhx2 is necessary for normal development of the eye, cerebral cortex, and efficient definitive erythropoiesis. C1 NIH,LAB MAMMALIAN GENES & DEV,BETHESDA,MD 20892. MONASH UNIV,DEPT ANAT,CLAYTON,VIC 3168,AUSTRALIA. HARVARD UNIV,CHILDRENS HOSP,SCH MED,HOWARD HUGHES MED INST,BOSTON,MA 02115. HARVARD UNIV,DEPT GENET,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. NIH,LAB GEN TRANSFER,BETHESDA,MD 20892. RP Porter, FD (reprint author), NIH,HERITABLE DISORDERS BRANCH,BLDG 10,BETHESDA,MD 20892, USA. OI Wassif, Christopher/0000-0002-2524-1420 NR 53 TC 323 Z9 326 U1 0 U2 3 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 AUG PY 1997 VL 124 IS 15 BP 2935 EP 2944 PG 10 WC Developmental Biology SC Developmental Biology GA XP688 UT WOS:A1997XP68800008 PM 9247336 ER PT J AU Schaapveld, RQJ Schepens, HTG Robinson, GW Attema, J Oerlemans, FTJJ Fransen, JAM Streuli, M Wieringa, B Hennighausen, L Hendriks, WJAJ AF Schaapveld, RQJ Schepens, HTG Robinson, GW Attema, J Oerlemans, FTJJ Fransen, JAM Streuli, M Wieringa, B Hennighausen, L Hendriks, WJAJ TI Impaired mammary gland development and function in mice lacking LAR receptor-like tyrosine phosphatase activity SO DEVELOPMENTAL BIOLOGY LA English DT Article ID EMBRYONIC STEM-CELLS; CREATINE-KINASE; TRANSGENIC MICE; EXTRACELLULAR-MATRIX; HOMOPHILIC BINDING; GENE-EXPRESSION; NERVOUS-SYSTEM; DOMAINS; BETA; ISOFORMS AB The LAR receptor-like protein tyrosine phosphatase is composed of two intracellular tyrosine phosphatase domains and a cell adhesion molecule-like extracellular region containing three immunoglubulin-like domains in combination with eight fibronectin type-III like repeats. This architecture suggests that LAR may function in cellular signalling by the regulation of tyrosine phosphorylation through cell-cell or cell-matrix interactions. We used gene targeting in mouse embryonic stem cells to generate mice lacking sequences encoding both LAR phosphatase domains, Northern blot analysis of various tissues revealed the presence of a truncated LAR mRNA lacking the cytoplasmic tyrosine phosphatase domains and indicated that this LAR mutation is not accompanied by obvious changes in the expression levels of one of the LAR-like receptor tyrosine phosphatases PTP delta or PTP sigma. LAR(-/-) mice develop and grow normally and display no appreciable histological tissue abnormalities. However, upon breeding we observed an abnormal neonatal death rate for pups from LAR(-/-) females. Mammary glands of LAR(-/-) females were incapable of delivering milk due to an impaired terminal differentiation of alveoli at late pregnancy. As a result, the glands failed to switch to a lactational state and showed a rapid involution postpartum. In wild-type mice, LAR expression is regulated during pregnancy reaching maximum levels around Day 16 of gestation. Taken together, these findings suggest an important role for LAR-mediated signalling in mammary gland development and function, (C) 1997 Academic Press. C1 UNIV NIJMEGEN,INST CELLULAR SIGNALLING,DEPT CELL BIOL & HISTOL,NL-6525 EK NIJMEGEN,NETHERLANDS. NIDDK,BIOCHEM & METAB LAB,NIH,BETHESDA,MD 20892. DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. RI Fransen, Jack/E-8924-2010; Robinson, Gertraud/I-2136-2012; Hendriks, Wiljan/A-5214-2013; Wieringa, Berend/A-5346-2011 OI Hendriks, Wiljan/0000-0001-9481-8281; Wieringa, Berend/0000-0001-9192-8020 NR 60 TC 105 Z9 106 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD AUG 1 PY 1997 VL 188 IS 1 BP 134 EP 146 DI 10.1006/dbio.1997.8630 PG 13 WC Developmental Biology SC Developmental Biology GA XQ251 UT WOS:A1997XQ25100012 PM 9245518 ER PT J AU Weir, GC BonnerWeir, S AF Weir, GC BonnerWeir, S TI Scientific and political impediments to successful islet transplantation SO DIABETES LA English DT Review ID DEPENDENT DIABETES-MELLITUS; BETA-CELL MASS; PANCREATIC-ISLETS; INSULIN INDEPENDENCE; TYPE-1; MICE; ALLOGRAFTS; IMMUNOSUPPRESSION; RECIPIENTS; LANGERHANS AB Islet transplantation is a treatment for diabetes that has the potential to normalize glucose levels and prevent the development of complications. In spite of the simplicity of the concept and the urgent need to provide such a treatment to patients, there has been a frustrating lack of progress. This perspective delves into the scientific and political impediments to success. The scientific barriers are the need to find a satisfactory source of insulin-producing tissue and the requirement to prevent this tissue from being destroyed by immune rejection and autoimmunity. The problems and potential of allografts, xenografts, and the development of cell lines are discussed. Multiple approaches to the prevention of immune destruction are considered, including immunobarrier devices, immunosuppression, development; of tolerance, and genetic manipulation. The political barriers discussed include the problems of high expectations, the controversy surrounding targeted research, the balance between basic and applied research, the roles of industry and academia, the concerns about xenotransplantation, and the difficulties in developing a planned approach to the problem. C1 BETH ISRAEL DEACONESS MED CTR,DEPT MED,BOSTON,MA. BRIGHAM & WOMENS HOSP,DEPT MED,BOSTON,MA 02115. HARVARD MED SCH,BOSTON,MA. RP Weir, GC (reprint author), JOSLIN DIABET CTR,DIV RES,1 JOSLIN PL,BOSTON,MA 02215, USA. FU NIDDK NIH HHS [DK-44523, DK-35449, DK-50657] NR 110 TC 116 Z9 120 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 AUG PY 1997 VL 46 IS 8 BP 1247 EP 1256 DI 10.2337/diabetes.46.8.1247 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XM400 UT WOS:A1997XM40000001 PM 9231647 ER PT J AU So, JBY Palmer, MT Shellito, PC AF So, JBY Palmer, MT Shellito, PC TI Postoperative perineal hernia SO DISEASES OF THE COLON & RECTUM LA English DT Article DE hernia; perineal; repair ID REPAIR AB dPURPOSE: Perineal hernia is an uncommon complication following abdominoperineal resection. The aim of the study was to evaluate the predisposing factors and the optimum method of repair. METHODS: A retrospective review of patients with postoperative perineal hernia at the Massachusetts General Hospital between 1963 and 1995 was performed. RESULTS: Twenty-one patients with perineal hernias were found. The original perineal operations were as follows. abdominoperineal resection in 13 patients, pelvic exenteration in 5 patients, cystourethrectomy in 2 patients, and perineal resection of the rectal stump in 1 patient. The incidence of symptomatic perineal hernia following abdominoperineal resection was estimated to be 0.62 percent. A total of 69 percent of patients had the original perineal wound left partially open, and in 10 percent it was left completely open. The peritoneal defect was not closed in 53 percent of patients, and only 21 percent had closure of the levator defect. Of the 19 patients who had hernia repair, 13 were repaired transperineally and 3 transabdominally and 3 required a combined abdominoperineal approach. The repair methods were as follows: simple closure of the pelvic defect (10 patients), mesh closure (5 patients), gluteus flap (1 patient), and retroflexion of the uterus (2 patients) or bladder (1 patient). Four patients had postoperative complications (mostly wound infections), and the recurrence rate was 16 percent. There was no difference in length of hospitalization among transperineal, transabdominal, and combined approaches. CONCLUSIONS: Primary closure of the perineal wound, with careful avoidance of wound infection is the most important consideration for avoiding a perineal hernia. Repair via the perineum with simple closure of the defect or a mesh is successful in most cases. C1 HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. RP So, JBY (reprint author), MASSACHUSETTS GEN HOSP,SURG SERV,BOSTON,MA 02114, USA. RI So, Jimmy/B-5761-2011 NR 18 TC 48 Z9 53 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0012-3706 J9 DIS COLON RECTUM JI Dis. Colon Rectum PD AUG PY 1997 VL 40 IS 8 BP 954 EP 957 DI 10.1007/BF02051204 PG 4 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA XQ774 UT WOS:A1997XQ77400012 PM 9269813 ER PT J AU Kebabian, JW Tarazi, FI Kula, NS Baldessarini, RJ AF Kebabian, JW Tarazi, FI Kula, NS Baldessarini, RJ TI Compounds selective for dopamine receptor subtypes SO DRUG DISCOVERY TODAY LA English DT Review ID SENSITIVE ADENYLATE CYCLASE; RAT-BRAIN; MOLECULAR-CLONING; ABSOLUTE-CONFIGURATION; AGONIST; EXPRESSION; POTENT; GENE; ANTAGONIST; BINDING AB Novel dopamine (DA) receptor proteins of relatively low natural abundance and uncertain physiology can be expressed selectively in genetically transfected cultured cells to facilitate screening of novel DA receptor ligands. Selective agonists or antagonists for most of the five major DA receptor types are emerging, but better D-4 and D-5 agonists, D-3 and D-5 antagonists, and more selective D-2 antagonists are needed. Clinical development of such compounds as diagnostic neuroradiopharmaceuticals or neuropsychiatric drugs remains empirical and somewhat unpredictable. The search for novel receptor-selective agents can be enhanced by better understanding of the physiology and pharmacology of DA neuroreceptors. C1 MASSACHUSETTS GEN HOSP, MCLEAN DIV, MAILMAN RES CTR, BELMONT, MA 02178 USA. HARVARD UNIV, SCH MED, DEPT PSYCHIAT, BELMONT, MA 02178 USA. HARVARD UNIV, SCH MED, NEUROSCI PROGRAM, BELMONT, MA 02178 USA. RP Kebabian, JW (reprint author), RES BIOCHEM INT, 1 STRATHMORE RD, NATICK, MA 01760 USA. NR 93 TC 51 Z9 52 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1359-6446 J9 DRUG DISCOV TODAY JI Drug Discov. Today PD AUG PY 1997 VL 2 IS 8 BP 333 EP 340 DI 10.1016/S1359-6446(97)01075-1 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA XM403 UT WOS:A1997XM40300006 ER PT J AU Eisenberg, LS Dirks, DD Gornbein, JA AF Eisenberg, LS Dirks, DD Gornbein, JA TI Subjective judgments of speech clarity measured by paired comparisons and category rating SO EAR AND HEARING LA English DT Article ID NATIONAL-ACOUSTIC-LABORATORIES; SOUND QUALITY JUDGMENTS; HEARING-AID SELECTION; FREQUENCY RESPONSES; LISTENING CONDITIONS; INTELLIGIBILITY; RELIABILITY; SENSITIVITY; LOUDNESS; STIMULI AB Objective: The purpose of this study was to compare listeners' subjective judgments of speech clarity via paired comparisons and category rating using stimulus conditions that varied in the relative spacing between stimulus items, producing either a wide or narrow range of performance. Design: Subjective judgments of speech clarity were measured via paired comparisons and category rating in 12 normal-hearing (Experiment 1) and eight hearing-impaired adults (Experiment 2). Sentences processed by six band-pass filters that increased monotonically in Articulation Index (AI) estimates constituted the stimuli to be judged. Using subsets of three filters from the group of six, subjective judgments were additionally obtained for stimulus conditions in which the performance ranges were wide (large differences in Al) and narrow (small differences in AI). Results: Speech clarity judgments obtained by paired comparisons and category rating were highly related to the Al estimates both for normal-hearing and hearing-impaired subjects. When the performance range was wide, both methods provided similar judgments for the normal-hearing subjects. For the hearing-impaired subjects, paired comparisons were more sensitive than category rating. When the performance range was narrow, paired comparisons were more sensitive than category rating in differentiating between filters for both groups of subjects. This difference was less obvious for the normal-hearing subjects when paired comparison data were converted to a scale comparable to the category ratings. Large between-subject variability was evident for the hearing-impaired subjects on the psychophysical scaling procedures, most notably for category rating. Conclusions: When judging the clarity among stimulus items where performance varied over a wide range, both category rating and paired comparisons provided comparable judgments for normal-hearing listeners. For conditions in which perceptual differences between stimulus items were restricted either by the choice of conditions or by the effects of sensorineural hearing loss, the method of paired comparisons was the more sensitive procedure. C1 UNIV CALIF LOS ANGELES,SCH MED,DIV HEAD & NECK SURG,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT BIOMATH,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. FU NIDCD NIH HHS [5 K08 DC 00083-04] NR 48 TC 22 Z9 22 U1 3 U2 5 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0196-0202 J9 EAR HEARING JI Ear Hear. PD AUG PY 1997 VL 18 IS 4 BP 294 EP 306 DI 10.1097/00003446-199708000-00004 PG 13 WC Audiology & Speech-Language Pathology; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Otorhinolaryngology GA XU406 UT WOS:A1997XU40600005 PM 9288475 ER PT J AU Merriam, GR Buchner, DM Prinz, PN Schwartz, RS Vitiello, MV AF Merriam, GR Buchner, DM Prinz, PN Schwartz, RS Vitiello, MV TI Potential applications of GH secretagogs in the evaluation and treatment of the age-related decline in growth hormone secretion SO ENDOCRINE LA English DT Article; Proceedings Paper CT Meeting on Assessment of the Growth Hormone/IGF-I Axis in Aging CY APR 14, 1997 CL BETHESDA, MD DE growth hormone (GH); GH-releasing hormone (GHRH); GH-releasing peptide (GHRP); insulin-like growth factor-I (IGF-I) ID FACTOR-I LEVELS; DEFICIENT CHILDREN; (GH)-RELEASING HORMONE; ELDERLY SUBJECTS; NORMAL MEN; OLD MEN; RESPONSES; ARGININE; ADULTS; STIMULATION AB The two classes of GH secretagogs-GH-releasing hormone (GHRH) and the GH-releasing peptides and their analogs (GHRP's)-retain their ability to endogenous GH secretion in healthy and frail elderly subjects. They have very limited utility in assessment of the state of the GH/IGF-I axis except to confirm an intact pituitary, but they are attractive potential alternatives to GH as therapeutic agents. There is wide interest in the possibility that elevating GH and IGF-I might increase muscle mass, physical strength and performance, and possibly sleep and cognition in aging, The GH secretagogs, like CH, can produce a sustained stimulation of this axis; in contrast to GH, they preserve feedback regulation at the pituitary level and stimulate a near-physiologic pulsatile pattern of GH release. GHRP's and their nonpeptide analogs are also active when given orally, a significant practical advantage. Short-term treatment studies have shown that GHRH and the GHRP's can enhance GH secretion and elevate IGF-I and IGFBP-3 levels; that GHRH may promote sleep; and that these agents are generally well tolerated, Longer-term studies assessing effects upon body composition and physical and psychological function are underway. C1 UNIV WASHINGTON, SCH MED, SEATTLE, WA USA. RP Merriam, GR (reprint author), VA PUGET SOUND HLTH CARE SYST, RES SERV 151, AMER LAKE DIV, BLDG 18S, ROOM 7, TACOMA, WA 98493 USA. OI Vitiello, Michael/0000-0002-9776-0473 NR 27 TC 11 Z9 11 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1355-008X EI 1559-0100 J9 ENDOCRINE JI Endocrine PD AUG PY 1997 VL 7 IS 1 BP 49 EP 52 DI 10.1007/BF02778062 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YJ962 UT WOS:A1997YJ96200007 PM 9449031 ER PT J AU Kronenberg, HM AF Kronenberg, HM TI Parathyroid hormone and osteocalcin - When friends become strangers SO ENDOCRINOLOGY LA English DT Editorial Material ID MESSENGER-RNA LEVELS; BONE; PROTEIN; GROWTH; CELLS RP Kronenberg, HM (reprint author), MASSACHUSETTS GEN HOSP,DEPT MED,ENDOCRINE UNIT,50 BLOSSOM ST,BOSTON,MA 02114, USA. NR 18 TC 6 Z9 6 U1 0 U2 1 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD AUG PY 1997 VL 138 IS 8 BP 3083 EP 3084 DI 10.1210/en.138.8.3083 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XL842 UT WOS:A1997XL84200001 PM 9231753 ER PT J AU Lein, M Brux, B Jung, K Henke, W Koenig, F Stephan, C Schnorr, D Loening, SA AF Lein, M Brux, B Jung, K Henke, W Koenig, F Stephan, C Schnorr, D Loening, SA TI Elimination of serum free and total prostate-specific antigen after radical retropubic prostatectomy SO EUROPEAN JOURNAL OF CLINICAL CHEMISTRY AND CLINICAL BIOCHEMISTRY LA English DT Article ID HALF-LIFE; CANCER; ALPHA-1-ANTICHYMOTRYPSIN; COMPLEX; PSA; CLEARANCE; KINETICS; ADENOCARCINOMA; ESTABLISHMENT; BIOCHEMISTRY AB Elimination kinetics of serum total and free prostate-specific antigen were studied for a ten days course after radical retropubic prostatectomy on 11 patients suffering from organ confined prostate cancer. Samples were taken before operation, immediately after finishing the operation and 1, 2, 3, 4, 5, 6 h after prostatectomy and then once a day for the following ten days. The measurements were performed with AxSym assays from Abbott Laboratories. The elimination of both total and free prostate-specific antigen followed a biphasic kinetics. In the fast phase, the average of the individual elimination half-lives of total and free prostate-specific antigen amounted to 6.3 h (SD = 6.1 h; range: 0.55 to 37.1 h) and 0.57 h (SD = 0.18 h; range: 0.22 to 0.89 h), respectively. In the slow phase, total prostate-specific antigen disappeared with an average half-life of 85.6 h (SD = 11 h; range: 47.2 to 261.7 h) and free prostate-specific antigen with an average half-life of 14.4 h (SD = 10.4 h; range: 2.4 to 30.3 h). These results might be significant for the use of free and total prostate-specific antigen and its ratio as a diagnostic and prognostic tool. C1 HUMBOLDT UNIV,KLINIKUM CHARITE,FORSCHUNGSABT KLIN UROL,UROL KLIN,D-10098 BERLIN,GERMANY. HUMBOLDT UNIV BERLIN,KLINIKUM CHARITE,INST PATHOL & KLIN BIOCHEM,BERLIN,GERMANY. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,WELLMAN LABS,BOSTON,MA. NR 31 TC 20 Z9 21 U1 0 U2 0 PU WALTER DE GRUYTER & CO PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 0939-4974 J9 EUR J CLIN CHEM CLIN JI Eur. J. Clin. Chem. Clin. Biochem. PD AUG PY 1997 VL 35 IS 8 BP 591 EP 595 PG 5 WC Biochemistry & Molecular Biology; Medical Laboratory Technology SC Biochemistry & Molecular Biology; Medical Laboratory Technology GA XX550 UT WOS:A1997XX55000003 PM 9298348 ER PT J AU SunderPlassmann, R Lialios, F Madsen, M Koyasu, S Reinherz, EL AF SunderPlassmann, R Lialios, F Madsen, M Koyasu, S Reinherz, EL TI Functional analysis of immunoreceptor tyrosine-based activation motif (ITAM)-mediated signal transduction: the two YxxL segments within a single CD3 xi-ITAM are functionally distinct SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE CD3 xi-immunoreceptor tyrosine-based activation motif; ZAP70; p56(lck); JCaM1.6; interleukin-2; CA(2+) ID CELL ANTIGEN RECEPTOR; TANDEM SH2 DOMAINS; ZETA-CHAIN; ZAP-70 KINASE; LYMPHOCYTES-T; PROTEIN; PHOSPHORYLATION; BINDING; SYK; INVOLVEMENT AB Functional analysis of the immunoreceptor tyrosine-based activation motif (ITAM) derived from the membrane-proximal ITAM of CD3 zeta demonstrates that mutations at either the tyrosine or leucine residues in the N-terminal YxxL segment of the ITAM abolish all signal transduction functions of this ITAM. In contrast, mutations at the tyrosine or leucine residues in the C-terminal YxxL segment abrogate signals for interleukin (IL)-2 production but do not prevent tyrosine phosphorylation of the N-terminal tyrosine of the ITAM, lck association with the ITAM, activation of phospholipase C-gamma l or calcium mobilization. Cross-linking of chimeric receptors containing a C-terminal YxxL leucine mutation induces tyrosine phosphorylation of ZAP70 but without stable binding to the phosphorylated ITAM. These results indicate that the two YxxL segments in an ITAM are functionally distinct and that both are essential for ZAP70 binding and IL-2 production. Furthermore, tyrosine phosphorylation of ZAP70 per se is not sufficient to trigger the downstream events leading to IL-2 production. Substitution of an alanine for the bulky side chain at the Y+1 position of the N-terminal YxxL segment reduces the receptor cross-linking requirement necessary to achieve cellular activation and the absolute dependence on lck in this process. Our results reveal that both the number of ITAM as well as the specific amino acid residues within a single ITAM determine the extent of chimeric receptor cross-linking required to trigger tyrosine phosphorylation-dependent signaling events. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. RP SunderPlassmann, R (reprint author), DANA FARBER CANC INST,IMMUNOBIOL LAB,44 BINNEY ST,BOSTON,MA 02115, USA. RI Koyasu, Shigeo/J-5583-2015 OI Koyasu, Shigeo/0000-0001-9585-3038 FU NIAID NIH HHS [AI19807] NR 48 TC 31 Z9 32 U1 0 U2 6 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 AUG PY 1997 VL 27 IS 8 BP 2001 EP 2009 DI 10.1002/eji.1830270826 PG 9 WC Immunology SC Immunology GA XQ080 UT WOS:A1997XQ08000025 PM 9295038 ER PT J AU Agematsu, K Nagumo, H Yang, FC Nakazawa, T Fukushima, K Ito, S Sugita, K Mori, T Kobata, T Morimoto, C Komiyama, A AF Agematsu, K Nagumo, H Yang, FC Nakazawa, T Fukushima, K Ito, S Sugita, K Mori, T Kobata, T Morimoto, C Komiyama, A TI B cell subpopulations separated by CD27 and crucial collaboration of CD27(+) B cells and helper T cells in immunoglobulin production SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE human; IgD; T cell-B cell collaboration; CD27 ID CD40 LIGAND; DECREASED EXPRESSION; TISSUE DISTRIBUTION; LYMPHOCYTES; MEMORY; ACTIVATION; SUBSETS; IGM; DIFFERENTIATION; SECRETION AB B cell immunoglobulin production is regulated by helper T cells through direct interaction and secreted cytokines. In the present study, we functionally analyzed CD27 in cord and peripheral blood B cells. Adult peripheral blood B cells were separated into CD27(+) and CD27(-) cells, which differed in their morphology. Cord blood B cells did not express CD27, and CD27 expression on peripheral blood B cells increased with age. Only CD27(+) B cells had the ability to produce immunoglobulin, which was increased by contact with a tumor necrosis factor-related transmembrane ligand, CD70. Adult peripheral blood CD27(+) B cells can be further subdivided into two discrete subtypes: IgD(-) CD27(+) and IgD(+) CD27(+) B cells. IgD(-) CD27(+) B cells produce IgG, IgM and IgA, whereas IgD(+) CD27(+) B cells predominantly produce IgM. The addition of activated CD4(+)CD45RO T cells expressing CD70 caused down-regulation of CD27 expression on activated B cells, and this down-modulation was completely blocked by anti-CD70 monoclonal antibody, indicating direct T-B cell contact via CD27/CD70. The triggering via CD27 and CD40 additively increased the immunoglobulin production under Staphylococcus aureus Cowan strain plus interleukin-2 stimulation. Taken together, our findings demonstrate that peripheral blood B cells are separated into subpopulations by CD27 and IgD expression and that CD27(+) B cells produce large amounts of immunoglobulin by interaction with the CD70 molecule. C1 SHINSHU UNIV,SCH MED,DEPT BLOOD TRANSFUS,MATSUMOTO,NAGANO 390,JAPAN. YAMANASHI MED UNIV,DEPT PEDIAT,KOFU,YAMANASHI,JAPAN. JUNTENDO UNIV,SCH MED,DEPT IMMUNOL,TOKYO 113,JAPAN. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,CAMBRIDGE,MA 02138. RP Agematsu, K (reprint author), SHINSHU UNIV,SCH MED,DEPT PEDIAT,ASAHI 3-1-1,MATSUMOTO,NAGANO 390,JAPAN. NR 34 TC 199 Z9 202 U1 0 U2 2 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 AUG PY 1997 VL 27 IS 8 BP 2073 EP 2079 DI 10.1002/eji.1830270835 PG 7 WC Immunology SC Immunology GA XQ080 UT WOS:A1997XQ08000034 PM 9295047 ER PT J AU Yano, S Falk, RE Natowicz, MR Williams, JC AF Yano, S Falk, RE Natowicz, MR Williams, JC TI Case of the month - A 3.5-year-old female with developmental delays, hepatomegaly, and coarse fades SO EUROPEAN JOURNAL OF PEDIATRICS LA English DT Article ID ACID STORAGE DISEASE; SALLA DISEASE; TRANSPORT; DISORDERS C1 UNIV SO CALIF,LOS ANGELES,CA 90089. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. EUNICE KENNEDY SHRIVER CTR MENTAL RETARDAT INC,BOSTON,MA. RP Yano, S (reprint author), CHILDRENS HOSP LOS ANGELES,DEPT PEDIAT,DIV MED GENET,LOS ANGELES,CA 90027, USA. NR 8 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-6199 J9 EUR J PEDIATR JI Eur. J. Pediatr. PD AUG PY 1997 VL 156 IS 8 BP 661 EP 663 DI 10.1007/s004310050687 PG 3 WC Pediatrics SC Pediatrics GA XQ809 UT WOS:A1997XQ80900019 PM 9266203 ER PT J AU Tang, MS Pawlyk, BS Kosaras, B Berson, EL Sidman, RL AF Tang, MS Pawlyk, BS Kosaras, B Berson, EL Sidman, RL TI ERG abnormalities in relation to histopathologic findings in vitiligo mutant mice SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE electroretinogram; retinitis pigmentosa; mouse mutant; retinal pigment epithelium; photoreceptor cell; retinal degeneration ID C57BL/6-MI(VIT)/MI(VIT) MOUSE MODEL; RETINAL DEGENERATION; MICROPHTHALMIA; MUTATIONS; LOCUS; GENE AB The vitiligo, mi(vit), mutation has several prenatal and perinatal effects on development of the retinal pigment epithelium, and later, leads to extensive, progressive degeneration of photoreceptor cells in the neural retina of homozygous affected mice. The aim of the present study was to determine by functional criteria how early can abnormalities be detected in the neural retina. Electroretinograms (ERGs) were correlated with histopathological findings in the same animals, Congenic homozygous mutants, heterozygotes, and homozygous wild-type mice were studied at 2, 3, 6, 24 and 56 weeks of age, the same animals being tested serially at the three older time points. The nontested eye of each animal was embedded in Epon and sectioned at 1 mu m for light microscopic study. ERG recordings from vitiligo homozygotes differed from heterozygous and wild-type mice, but the latter two groups did not differ from each other. As early as two weeks of age, homozygous mutants showed a significant reduction of rod dominated maximum ERG a-wave and b-wave amplitude. ERG b-wave sensitivity (sigma) was significantly reduced. and ERG implicit times were delayed for homozygous mutants at 3 (a-wave) and 6 (b-wave) weeks of age. This is the first study to report reduced and delayed ERG a-waves and b-waves in this animal model, like the early functional abnormalities in human retinitis pigmentosa, and also the first to show short and disoriented rod outer segments, beginning retinal separation from the pigment epithelium, and a few macrophage-like cells already present in the subretinal space at 2 weeks of age (in three of four homozygous mutant eyes examined). Given these early functional and structural abnormalities in the neural retina, it remains to be determined whether the mi gene targets the retinal pigment epithelial cell, the photoreceptor cell, or both. (C) 1997 Academic Press Limited. C1 HARVARD UNIV,NEW ENGLAND REG PRIMATE RES CTR,SCH MED,SOUTHBOROUGH,MA 01772. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BERMAN GUND LAB STUDY RETINAL DEGENERAT,BOSTON,MA 02114. FU NEI NIH HHS [EY06631] NR 20 TC 7 Z9 7 U1 0 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD AUG PY 1997 VL 65 IS 2 BP 215 EP 222 DI 10.1006/exer.1997.0327 PG 8 WC Ophthalmology SC Ophthalmology GA XQ896 UT WOS:A1997XQ89600007 PM 9268589 ER PT J AU Yamamoto, S Khani, SC Berson, EL Dryja, TP AF Yamamoto, S Khani, SC Berson, EL Dryja, TP TI Evaluation of the rhodopsin kinase gene in patients with retinitis pigmentosa SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE rhodopsin kinase; retinitis pigmentosa; visual transduction; polymorphism; retina; retinal degeneration ID STATIONARY NIGHT BLINDNESS; HETEROZYGOUS MISSENSE MUTATION; ROD CGMP PHOSPHODIESTERASE; BETA-SUBUNIT; ALPHA-SUBUNIT; PROTEIN AB We explored the possibility that defects in the rhodopsin kinase gene might cause retinitis pigmentosa (RP) by evaluating 160 unrelated cases with dominant RP and 151 unrelated cases with recessive RP. One of five missense changes was discovered in each of six cases of dominant RP, but none of the missense changes cosegregated with disease among relatives. Heterozygous missense changes were found in two cases of recessive RP, and a heterozygous frameshift mutation was found in one additional case of recessive RP. Although the same DNA sequence alterations could be found heterozygously in the only affected sibling of each index case of recessive RP, no defect could be found in the other allele. Hence, none of the changes found in the cases of dominant or recessive RP was proven to be a cause of RP. The data indicate that defects in the rhodopsin kinase gene causing RP are either rare or nonexistent. (C) 1997 Academic Press Limited. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,OCULAR MOL GENET INST,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BERMAN GUND LAB STUDY RETINAL DEGENERAT,BOSTON,MA 02114. SUNY BUFFALO,DEPT OPHTHALMOL,BUFFALO,NY 14215. FU NEI NIH HHS [EY00169, EY08683] NR 29 TC 8 Z9 9 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD AUG PY 1997 VL 65 IS 2 BP 249 EP 253 DI 10.1006/exer.1997.9998 PG 5 WC Ophthalmology SC Ophthalmology GA XQ896 UT WOS:A1997XQ89600011 PM 9268593 ER PT J AU Tsukada, J Misago, M Serino, Y Ogawa, R Morimoto, I Auron, PE Eto, S AF Tsukada, J Misago, M Serino, Y Ogawa, R Morimoto, I Auron, PE Eto, S TI Human T-cell leukemia virus type I tax transactivates the promoter of human prointerleukin 1 beta gene through association with two transcription factors, NF-IL6 and SPI-1. SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 UNIV OCCUPAT & ENVIRONM HLTH,SCH MED,DEPT INTERNAL MED 1,KITAKYUSHU,FUKUOKA 807,JAPAN. UNIV OCCUPAT & ENVIRONM HLTH,SCH HLTH SCI,KITAKYUSHU,FUKUOKA 807,JAPAN. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 2 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1997 VL 25 IS 8 BP 168 EP 168 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA XR330 UT WOS:A1997XR33000162 ER PT J AU Griffin, JD AF Griffin, JD TI Mechanisms of transformation by BCR/ABL. SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1997 VL 25 IS 8 BP 511 EP 511 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA XR330 UT WOS:A1997XR33000497 ER PT J AU Yin, A Miraglia, S Magee, K Zanjani, E Ogawa, M Buck, DW AF Yin, A Miraglia, S Magee, K Zanjani, E Ogawa, M Buck, DW TI AC133, a novel monoclonal antibody to human hematopoietic stem and progenitor cells SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 AMCORP CORP,SUNNYVALE,CA. UNIV NEVADA,RENO,NV 89557. RALPH H JOHNSON VET ADM MED CTR,CHARLESTON,SC. NR 0 TC 2 Z9 2 U1 0 U2 1 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1997 VL 25 IS 8 BP 523 EP 523 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA XR330 UT WOS:A1997XR33000508 ER PT J AU Krispel, L DAndrea, AD Frank, D Merchav, S AF Krispel, L DAndrea, AD Frank, D Merchav, S TI STAT-5 overexpresion enhances proliferation and inhibits the differentiation of murine erythroleukemia cells. SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 TECHNION ISRAEL INST TECHNOL,BRUCE RAPPAPORT FAC MED,IL-31096 HAIFA,ISRAEL. DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1997 VL 25 IS 8 BP 536 EP 536 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA XR330 UT WOS:A1997XR33000522 ER PT J AU Francis, JW Ren, JM Warren, L Brown, RH Finklestein, SP AF Francis, JW Ren, JM Warren, L Brown, RH Finklestein, SP TI Postischemic infusion of Cu/Zn superoxide dismutase or SOD:Tet451 reduces cerebral infarction following focal ischemia/reperfusion in rats SO EXPERIMENTAL NEUROLOGY LA English DT Article ID BLOOD-BRAIN-BARRIER; REPERFUSION INJURY; SPINAL-CORD; ISCHEMIA-REPERFUSION; ARTERY OCCLUSION; TRANSGENIC MICE; CARDIAC-ARREST; TETANUS TOXIN; CATALASE; PERMEABILITY AB Oxygen-free radicals play a major role in neuronal cell injury following cerebral ischemia/reperfusion. The free-radical scavenging enzyme, Cu/Zn superoxide dismutase (SOD-l), ameliorates various types of brain injury resulting from temporary CNS ischemia. We have compared the cerebroprotective properties of human SOD-1 (hSOD-1) with a novel recombinant SOD-1 hybrid protein, SOD:Tet451, composed of hSOD-1 linked to the neuronal binding fragment of tetanus toxin (TTxC). Following 2 h of temporary middle cerebral artery occlusion, rats infused with equivalent activities of either hSOD-1 or SOD:Tet451 for the initial 3 h of reperfusion showed reductions in cerebral infarct volume of 43 and 57%, respectively, compared to saline-treated controls (P < 0.01). Serum hSOD-1 concentrations in rats receiving SOD:Tet451 were sevenfold higher than those in rats receiving the native enzyme. Animals treated with SOD:Tet451 also demonstrated an extended persistence of hSOD-1 in the bloodstream during drug washout as compared to animals given free enzyme. Immunohistochemical examination of brain sections from an SOD:Tet451-treated ischemic rat showed positive immunoreactivity in the ipsilateral cerebral cortex using either anti-TTxC or anti-human SOD-l antibodies. Our results document that both hSOD-1 and SOD:Tet451 significantly reduce brain infarct volume in a model of transient focal ischemia/reperfusion in rats. Additionally, our findings suggest that the cerebroprotective effects of SOD-1 may be enhanced by neuronal targeting as seen with the hybrid protein SOD:Tet451. (C) 1997 Academic Press. C1 MASSACHUSETTS GEN HOSP, CNS, GROWTH FACTOR RES LAB, CHARLESTOWN, MA 02129 USA. RP Francis, JW (reprint author), MASSACHUSETTS GEN HOSP, CECIL B DAY LAB NEUROMUSCULAR RES, CHARLESTOWN, MA 02129 USA. FU NIA NIH HHS [1P01AG12992-01]; NINDS NIH HHS [1P01NS31248-04, P01 NS 10828] NR 47 TC 43 Z9 45 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD AUG PY 1997 VL 146 IS 2 BP 435 EP 443 DI 10.1006/exnr.1997.6547 PG 9 WC Neurosciences SC Neurosciences & Neurology GA XR256 UT WOS:A1997XR25600017 PM 9270054 ER PT J AU Gralnek, IM Jensen, DM Kovacs, TOG Jutabha, R Jensen, ME Cheng, S Gornbein, J Freeman, ML Machicado, GA Smith, J Sue, M Kominski, G AF Gralnek, IM Jensen, DM Kovacs, TOG Jutabha, R Jensen, ME Cheng, S Gornbein, J Freeman, ML Machicado, GA Smith, J Sue, M Kominski, G TI An economic analysis of patients with active arterial peptic ulcer hemorrhage treated with endoscopic heater probe, injection sclerosis, or surgery in a prospective, randomized trial SO GASTROINTESTINAL ENDOSCOPY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Society-for-Gastrointestinal-Endoscopy CY MAY 14-18, 1995 CL SAN DIEGO, CA SP Amer Soc Gastrointestinal Endoscopy ID UPPER GASTROINTESTINAL-TRACT; PURE ALCOHOL INJECTION; MULTIPOLAR ELECTROCOAGULATION; UNITED-STATES; THERAPY; THERMOCOAGULATION; COST; HEMOSTASIS; DISEASE; LASER AB Background: There are no published, detailed assessments of the direct costs of endoscopic hemostasis for actively bleeding peptic ulcers. We compared the direct costs of care for patients with active ulcer hemorrhage treated with endoscopic or medical-surgical therapies and correlated these costs with patient outcomes. Methods: In a prospective, randomized, controlled trial, 31 patients with active ulcer hemorrhage at emergency endoscopy were randomly assigned to heater probe, injection, or medical-surgical treatment. For further ulcer bleeding, heater probe and injection patients were re-treated endoscopically and medical-surgical patients were referred for surgery. Direct costs were estimated using fixed and variable costs for resources consumed and Medicare reimbursement rates for physician fees. Results: Compared to medical-surgical treatment, the heater probe and injection groups had significantly higher primary hemostasis rates (100% and 90% vs 8%) and lower rates of emergency surgery (0% and 10% vs 75%), blood transfusions, and median direct costs per patient ($4153 and $5247 vs $11,149). Furthermore, compared to medical-surgical treatment, the heater probe group had a significantly lower incidence of severe ulcer rebleeding (11% vs 75%). Conclusions: Heater probe and injection sclerosis are similarly efficacious treatments for active ulcer hemorrhage, and both treatments yield significantly lower direct costs of medical care and cost savings. C1 W LOS ANGELES VET AFFAIRS MED CTR,CURE DIGEST DIS RES CTR,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,DEPT BIOMATH,LOS ANGELES,CA 90024. HENNEPIN CTY MED CTR,MINNEAPOLIS,MN 55415. NORTHRIDGE HOSP MED CTR,NORTHRIDGE,CA. ALTON OCHSNER MED FDN & OCHSNER CLIN,NEW ORLEANS,LA 70121. WHITE MEM MED CTR,LOS ANGELES,CA. UNIV CALIF LOS ANGELES,SCH PUBL HLTH,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,CTR HLTH POLICY RES,LOS ANGELES,CA 90024. RP Gralnek, IM (reprint author), UNIV CALIF LOS ANGELES,SCH MED,DIV DIGEST DIS,CTR HLTH SCI,DEPT MED,CHS 44-138,10833 LECONTE AVE,LOS ANGELES,CA 90095, USA. RI smith, james/C-9922-2016 FU NIADDK NIH HHS [R0I-AM33273] NR 42 TC 46 Z9 46 U1 2 U2 2 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 AUG PY 1997 VL 46 IS 2 BP 105 EP 112 DI 10.1016/S0016-5107(97)70056-7 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA XU280 UT WOS:A1997XU28000001 PM 9283858 ER PT J AU Altiok, S Xu, M Spiegelman, BM AF Altiok, S Xu, M Spiegelman, BM TI PPAR gamma induces cell cycle withdrawal: inhibition of E2F/DP DNA-binding activity via down-regulation of PP2A SO GENES & DEVELOPMENT LA English DT Article DE PPAR gamma; E2F; DP; protein phosphatase 2A; cell cycle; adipogenesis ID LARGE-T-ANTIGEN; TRANSCRIPTION FACTOR E2F; RETINOBLASTOMA SUSCEPTIBILITY GENE; S-PHASE ENTRY; ADIPOCYTE DIFFERENTIATION; TRANSGENIC MICE; DP FAMILY; PROTEIN-ALPHA; OKADAIC ACID; IN-VIVO AB PPAR gamma is an adipose-selective nuclear hormone receptor that plays a key role in the control of adipocyte differentiation. Previous studies indicated that activation of ectopically expressed PPAR gamma induces differentiation when cells have ceased growth because of confluence. We show here that ligand activation of PPAR gamma is sufficient to induce growth arrest in fibroblasts and SV40 large T-antigen transformed, adipogenic HIB1B cells. Cell cycle withdrawal is accompanied by a decrease in the DNA-binding and transcriptional activity of the E2F/DP complex, which is attributable to an increase in the phosphorylation of these proteins, especially DP-1. This effect is a consequence of decreased expression of the catalytic subunit of the serine-threonine phosphatase PP2A. These data suggest an important role for PP2A in the control of E2F/DP activity and a new mode of cell cycle control in differentiation. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. FU NIDDK NIH HHS [R37 DK031405, DK31405, R01 DK031405] NR 85 TC 294 Z9 299 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 AUG 1 PY 1997 VL 11 IS 15 BP 1987 EP 1998 DI 10.1101/gad.11.15.1987 PG 12 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA XQ375 UT WOS:A1997XQ37500008 PM 9271121 ER PT J AU Schultze, JL AF Schultze, JL TI Vaccination as immunotherapy for B cell lymphoma SO HEMATOLOGICAL ONCOLOGY LA English DT Article DE lymphoma; idiotype; CD40 ID COLONY-STIMULATING FACTOR; ANTIGEN-PRESENTING CELL; MHC CLASS-I; BONE-MARROW TRANSPLANTATION; RESTRICTED TUMOR-ANTIGENS; ANTIIDIOTYPIC T-CELLS; IDIOTYPIC VACCINATION; IMMUNE-RESPONSE; ANTITUMOR IMMUNITY; DENDRITIC CELLS AB Current therapy does not cure the majority of patients with B cell non-Hodgkin's lymphoma (NHL) and further intensification does not benefit the patient. Therefore, new approaches are necessary. Immunotherapy has become again a major interest as a new treatment modality for B cell lymphoma since the discovery that the lymphoma specific Id can be presented to antigen-specific T cells. Vaccination of the tumour-bearing host is one of the major strategies to induce a T cell mediated anti-tumour immunity in vivo. For B cell lymphomas the lymphoma specific Id can be used as a tumour-specific antigen to stimulate T cells. Alternatively, the malignant B cells can be modified to become efficient antigen presenting cells (APCs) and present peptides from their own tumour-specific antigens to the autolagous T cells. Currently explored and future vaccination strategies for B cell lymphoma will be discussed here. (C) 1997 John Wiley & Sons, Ltd. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol,Dept Med, Boston, MA 02115 USA. RP Schultze, JL (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol,Dept Med, 44 Binney St, Boston, MA 02115 USA. EM schultze@mbcrr.harvard.edu RI Schultze, Joachim/D-7794-2011 OI Schultze, Joachim/0000-0003-2812-9853 NR 91 TC 10 Z9 10 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0278-0232 J9 HEMATOL ONCOL JI Hematol. Oncol. PD AUG PY 1997 VL 15 IS 3 BP 129 EP 139 DI 10.1002/(SICI)1099-1069(199708)15:3<129::AID-HON607>3.0.CO;2-N PG 11 WC Oncology; Hematology SC Oncology; Hematology GA ZL432 UT WOS:000073432300003 PM 9600112 ER PT J AU Fuller, TC Fuller, AA Golden, M Rodey, GE AF Fuller, TC Fuller, AA Golden, M Rodey, GE TI HLA alloantibodies and the mechanism of the antiglobulin-augmented lymphocytotoxicity procedure SO HUMAN IMMUNOLOGY LA English DT Article ID SENSITIZED DIALYSIS PATIENTS; MONOCLONAL-ANTIBODIES; ALLOGRAFT REJECTION; ANTIGENIC STRUCTURE; PUBLIC EPITOPES; CYTO-TOXICITY; CROSS-MATCH; TRANSPLANTATION; COMPLEMENT; BINDING AB HLA Class I alloantigens express multiple epitopes which can be defined serologically using human HLA alloantibodies (aAb). We have shown that the vast majority of HLA antisera exhibit the CYNAP phenomenon (complement-dependent cytotoxicity (CDC) negative, adsorption positive) which can be identified by conversion to direct CDC positive reactivity with the addition of an antihuman immunoglobulin (Ig) light chain (AHG) reagent. In this study, the immunochemical mechanisms responsible for the CYNAP phenomena and how AHG overrides CYNAP have been further characterized using affinity-purified HLA aAb, class-specific anti-IgH reagents and human Clq binding assays quantified by flow cytometry. We have found that CYNAP reactions are not the result of low affinity aAb or generally caused by non-complement fixing HLA aAb. Our experiments illustrate that only anti-human IgL AHG reagents can consistently augment CDC and override CYNAP; antiIgH have not effective. Two noncompeting HLA aAb of different epitopic specificity or one aAb in conjunction with the AHG-augmenting reagent results in striking synergy with a 200 to 400% increase in binding of Clq. We conclude from these and other experiments detailed in this article that an IgM aAb or either two adjacent, noncompeting IgG HLA aAb bound to spatially distinct epitopes on a single HLA molecule or a monospecific IgG HLA aAb in concert with the AHG binding to this HLA aAb, is required for efficient (bivalent) C1q binding and initiation of C-mediated lympholysis. In contrast, the CYNAP phenomenon usually occurs because monospecific HLA aAb directed against a single epitope cannot effect high affinity, bivalent interaction with Clq and activate complement that would ultimately lead to cytolysis. (C) American Society for Histocompatibility and Immunogenetics, 1997. Published by Elsevier Science Inc. C1 Univ Utah, Sch Med, H&I Lab, Dept Pathol, Salt Lake City, UT 84132 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Emory Univ, Sch Med, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. RP Fuller, TC (reprint author), Univ Utah, Sch Med, H&I Lab, Dept Pathol, 50 N Med Dr, Salt Lake City, UT 84132 USA. FU NHLBI NIH HHS [HL-18646] NR 47 TC 29 Z9 29 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD AUG-SEP PY 1997 VL 56 IS 1-2 BP 94 EP 105 DI 10.1016/S0198-8859(97)00174-2 PG 12 WC Immunology SC Immunology GA YN912 UT WOS:000071221200011 PM 9455498 ER PT J AU Walter, UM Ayer, LM Manning, AM Frenette, PS Wagner, DD Hynes, RO Wolitzky, BA Issekutz, AC AF Walter, UM Ayer, LM Manning, AM Frenette, PS Wagner, DD Hynes, RO Wolitzky, BA Issekutz, AC TI Generation and characterization of a novel adhesion function blocking monoclonal antibody recognizing both rat and mouse E-selectin SO HYBRIDOMA LA English DT Article; Proceedings Paper CT 27th Annual Meeting of the German-Society-for-Immunology CY SEP 26-28, 1996 CL HAMBURG, GERMANY SP Gernab Soc Immunol ID ENDOTHELIAL-CELLS; P-SELECTIN; POLYMORPHONUCLEAR LEUKOCYTES; MOLECULE-1; NEUTROPHILS; EXPRESSION; BINDING; INVIVO; IDENTIFICATION; INFLAMMATION AB The prerequisite for the recruitment of circulating leukocytes to sites of inflammation is adhesion to vascular endothelial cells. Selectins play a significant role in the initiation of this multistep process by mediating ''rolling'' of the leukocytes on the endothelium. Investigation of selectin-dependent cell interactions using function blocking monoclonal antibodies (MAb) provides insights into the mechanisms involved in leukocyte migration into inflammation. Until now most studies in inflammation models in rats have relied on cross-reactive or polyclonal antibodies against rat E-selectin. In an E-selectin knockout mouse, we aimed to generate an adhesion function blocking MAb to rat E-selectin by immunization with rat E-selectin transfected Chinese hamster ovary cells (RESEC). An IgG1 kappa MAb was identified that reacts with RESEC but not with untransfected Chinese hamster ovary cells, as well as with recombinant mouse E-selectin protein as assessed by ELISA. This MAb is designated RME-1. It does not cross-react with rat L-selectin or rat P-selectin or E-selectin expressed on human umbilical vein endothelium. Adhesion of the HL-60 myeloid cells to immobilized mouse E-selectin was completely inhibited by MAb RME-1 under static conditions and adhesion of rat polymorphonuclear leukocytes to recombinant mouse E-selectin was blocked under rotation conditions. This novel antibody thus recognizes a function-related epitope on rodent E-selectin. C1 DALHOUSIE UNIV,DEPT PEDIAT & MICROBIOL IMMUNOL,HALIFAX,NS B3J 3G9,CANADA. PHARMACIA & UPJOHN INC,KALAMAZOO,MI 49001. CTR BLOOD RES,BOSTON,MA 02115. MIT,HOWARD HUGHES MED INST,CAMBRIDGE,MA 02139. MIT,CTR CANC RES,DEPT BIOL,CAMBRIDGE,MA 02139. HOFFMANN LA ROCHE INC,NUTLEY,NJ 07110. RI Frenette, Paul/J-8272-2012 FU NHLBI NIH HHS [P01HL4184] NR 29 TC 38 Z9 38 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0272-457X J9 HYBRIDOMA JI Hybridoma PD AUG PY 1997 VL 16 IS 4 BP 355 EP 361 DI 10.1089/hyb.1997.16.355 PG 7 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Immunology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology GA XX228 UT WOS:A1997XX22800006 PM 9309426 ER PT J AU Jarvis, BW Lichenstein, H Qureshi, N AF Jarvis, BW Lichenstein, H Qureshi, N TI Diphosphoryl lipid A from Rhodobacter sphaeroides inhibits complexes that form in vitro between lipopolysaccharide (LPS)-binding protein, soluble CD14, and spectrally pure LPS SO INFECTION AND IMMUNITY LA English DT Article ID BINDING-PROTEIN; IDENTIFICATION; RECOGNITION; ANTAGONIZE; ENDOTOXINS; ATCC-17023 AB An early event in septic shock is the activation of macrophages by a complex consisting of lipopolysaccharide (LPS), LPS-binding protein (LBP), and the cell surface antigen CD14, The complexes that form between [H-3]ReLPS (ReLPS is deep-rough-chemotype hexacyl LPS from B. coli D31m4), soluble CD14 (sCD14), and LBP were analyzed by two independent methods, native (nondenaturing) gel electrophoresis and size-exclusion high-performance liquid chromatography (HPLC), This is the first reported use of HPLC to purify and study LPS-protein complexes, The binding of [H-3]ReLPS to LBP and sCD14 was inhibited by preincubation with diphosphoryl lipid A from Rhodobacter sphaeroides (RsDPLA), a potent LPS antagonist, In addition, [3H]ReLPS bound to LBP and to a truncated form of sCD14 [sCD14((1-152))] that contained the LPS binding domain. Binding to both proteins was blocked by RsDPLA. Thus, RsDPLA competes in a 1:1 ratio for the same or nearby binding sites on ReLPS complexes, Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of aggregated ReLPS eluting from the HPLC indicated that only LBP not sCD14, was bound to the aggregated ReLPS. This finding supports the binary model of LPS complex formation with LBP and sCD14. C1 WILLIAM S MIDDLETON MEM VET ADM MED CTR,LAB MYCOBACTERIOL,MADISON,WI 53705. UNIV WISCONSIN,DEPT BACTERIOL,MADISON,WI 53705. AMGEN INC,BOULDER,CO 80301. FU NIGMS NIH HHS [GM-50870] NR 24 TC 33 Z9 33 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD AUG PY 1997 VL 65 IS 8 BP 3011 EP 3016 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA XM714 UT WOS:A1997XM71400003 PM 9234747 ER PT J AU Ryan, ET Butterton, JR Zhang, TH Baker, MA Stanley, SL Calderwood, SB AF Ryan, ET Butterton, JR Zhang, TH Baker, MA Stanley, SL Calderwood, SB TI Oral immunization with attenuated vaccine strains of Vibrio cholerae expressing a dodecapeptide repeat of the serine-rich Entamoeba histolytica protein fused to the cholera toxin B subunit induces systemic and mucosal antiamebic and anti-V-cholerae antibody responses in mice SO INFECTION AND IMMUNITY LA English DT Article ID AMEBIC LIVER-ABSCESS; IMMUNE-RESPONSES; PROTECTION; INSERTION; ADHERENCE; GERBILS; CELLS; GENES; O139 AB Entamoeba histolytica is a significant cause of morbidity and mortality worldwide. The serine-rich E. histolytica protein (SREHP) is a surface-expressed trophozoite protein that includes multiple hydrophilic tandem repeats. A purified fusion protein between the dodecapeptide repeat of SREHP and cholera toxin B subunit (CTB) has previously been shown to be immunogenic in mice after oral inoculation when cholera toxin is coadministered as an immunoadjuvant. We engineered a live attenuated El Tor Vibrio cholerae vaccine strain, Peru2, to express the SREHP-12-CTB fusion protein to the supernatant from either a plasmid [Peru2 (pETR5.1)] or from a chromosomal insertion (ETR3). Vector strains were administered orally to germfree mice that were subsequently housed under nongermfree conditions; mice received one (day 0) or two (days 0 and 14) inoculations. No immunoadjuvant or cholera holotoxin was administered. Mice that received two inoculations of Peru2(pETR5.1) had the most pronounced antiamebic systemic and mucosal immunologic responses. Less marked, but significant, anti-SREHP serum immunoglobulin G antibody responses were also induced in mice that received either one or two oral inoculations of strain ETR3. Anti-V. cholerae responses were also induced, as measured by the induction of serum vibriocidal antibodies and by serum and mucosal anti-CTB antibody responses. These results suggest that V. cholerae vector strains can be successful delivery vehicles for the SREHP-12-CTB fusion protein, to induce mucosal and systemic antiamebic and anti-V. cholerae immune responses. The magnitude of these responses is proportional to the amount of SREHP-12-CTB produced by the vector strain. C1 MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA 02114. WASHINGTON UNIV,SCH MED,DEPT MED,ST LOUIS,MO 63110. WASHINGTON UNIV,SCH MED,DEPT MOL MICROBIOL,ST LOUIS,MO 63110. HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOL GENET,BOSTON,MA 02115. FU NIAID NIH HHS [KO8 AI01386, R01 AI030084, AI40725, AI30084, R01 AI040725] NR 43 TC 47 Z9 47 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD AUG PY 1997 VL 65 IS 8 BP 3118 EP 3125 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA XM714 UT WOS:A1997XM71400019 PM 9234763 ER PT J AU Nishizawa, K Koyasu, S AF Nishizawa, K Koyasu, S TI IL-2 and IL-7 differentially induce CD4(-)CD8(-)alpha beta TCR(+)NK1.1(+) large granular lymphocytes and IL-4-producing cells from CD4(-)CD8(-)alpha beta TCR(+)NK1.1(-) cells: Implications for the regulation of T(h)1- and t(h)2-type responses SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE cell sorter; large granular lymphocyte; NK; NKT; TCR repertoire ID ALPHA-BETA+ THYMOCYTES; ATHYMIC NUDE-MICE; CD4-CD8 T-CELLS; BONE-MARROW; CD8 THYMOCYTES; DEFICIENT MICE; RECEPTOR; CHAIN; TCR; EXPANSION AB Effector functions of CD4(-)CD8(-) double negative (DN) alpha beta TCR+ cells were examined. Among mouse DN alpha beta TCR+ thymocytes, NK1.1(+) cells expressing a canonical V(alpha)14/J(alpha)281 TCR but not NK1.1(-) cells produce IL-4 upon TCR cross-linking and IFN-gamma upon cross-linking of NK1.1 as well as TOP. Production of IL-4 but not IFN-gamma from DN alpha beta TCR(+)NK1.1(+) cells was markedly suppressed by IL-2. Whereas V(alpha)14/J(alpha)281 TCR+ cells express NK1.1(+), these cells are not the precursor of DN alpha beta TCR(+)NK1.1(+)CD16(+)B220(+) large granular lymphocytes (LGL). IL-2 induces rapid proliferation and generation of NK1.1(+) LGL from DN alpha beta TCR(+)NK1.1(-) but not from DN alpha beta TCR(+)NK1.1(+) cells. LGL cells exhibit NK activity and produce IFN-gamma but not IL-4 upon cross-linking of surface TCR or NK1.1 molecules. In contrast to IL-2, IL-7 does not induce LGL cells or NK activity from DN alpha beta TCR(+)NK1.1(-) cells but induces the ability to produce high levels of IL-4 upon TCR cross-linking. Our results show that DN alpha beta TCR+ T cells have several distinct subpopulations, and that IL-2 and IL-7 differentially regulate the functions of DN alpha beta TCR+ T cells by inducing different types of effector cells. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,IMMUNOBIOL LAB,BOSTON,MA 02115. KEIO UNIV,SCH MED,DEPT IMMUNOL,SHINJUKU KU,TOKYO 160,JAPAN. RI Koyasu, Shigeo/J-5583-2015 OI Koyasu, Shigeo/0000-0001-9585-3038 FU NIAID NIH HHS [R01 AI33017] NR 46 TC 13 Z9 13 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD AUG PY 1997 VL 9 IS 8 BP 1123 EP 1129 DI 10.1093/intimm/9.8.1123 PG 7 WC Immunology SC Immunology GA XP912 UT WOS:A1997XP91200007 PM 9263009 ER PT J AU Pontius, AA AF Pontius, AA TI Impact of literacy training on spatial representation in southwest Ethiopia SO INTERNATIONAL JOURNAL OF INTERCULTURAL RELATIONS LA English DT Article DE pre-literates; spatial representation; shapes vs. relations; face drawing; block designs; ecocultural cognition ID ECOLOGY AB In order to study the impact of literacy training on visual-spatial cognitive performance, the Kohs Block Design and the ''Draw-a-person-with-face-in-front (DAPF)'' lest were administered to two distinct populations of agricultural pastoralists in Southwest Ethiopia. The Karo have no literacy training while the Hamar subjects had had several years of schooling. As expected, Hamar subjects (who were literate) produced a larger percentage (43.1%) of correct block constructions as cornpared to the Karo who produced only 16.7% correct block constructions. Error analysis, however, revealed that the Karo produced a larger proportion (27.08%) of ''nonrandom'' error types (errors, which nevertheless preserved essential spatial attributes, the shapes of the target design, while neglecting its spatial relations) than did the literate Hamar subjects (9.03%). Similarly 57.6% of face drawings by nonliterate Karo subjects and only 8.3% of Hamar drawings were classified as resembling the ''neolithic'' protype (also neglecting spatial relations). Results support the hypothesis that literacy influences spatial-relational cognitive skills. (C) 1997 Elsevier Science Ltd. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CAMBRIDGE,MA 02138. NR 10 TC 3 Z9 3 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0147-1767 J9 INT J INTERCULT REL JI Int. J. Intercult. Relat. PD AUG PY 1997 VL 21 IS 3 BP 299 EP 304 DI 10.1016/S0147-1767(97)00002-3 PG 6 WC Psychology, Social; Social Sciences, Interdisciplinary; Sociology SC Psychology; Social Sciences - Other Topics; Sociology GA XW215 UT WOS:A1997XW21500002 ER PT J AU Teicher, BA Kakeji, Y Northey, D AF Teicher, BA Kakeji, Y Northey, D TI Lisofylline as an adjuvant to high dose cytotoxic therapy SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE lisofylline; high dose therapy; hematopoietic protection ID NECROSIS-FACTOR-ALPHA; COLONY-STIMULATING FACTOR; ALKYLATING-AGENTS; PENTOXIFYLLINE; MICE; INVIVO; LONIDAMINE; MODULATORS; RADIATION; CARBOGEN AB Lisofylline, a dimethylxanthine derivative, has been shown to block the induction of hematopoietic growth inhibitors produced in response to cytotoxic anticancer therapy. In the current study, mice bearing established EMT-6 mammary carcinoma were treated with high dose cyclophosphamide, melphalan, BCNU, 5-fluorouracil or with total body radiation alone or with peripheral blood cells. The effect of lisofylline and/or G-CSF on leukocyte recovery was examined. Lisofylline was as effective as G-CSF in accelerating the recovery of white blood cells and granulocytes after treatment with high dose chemotherapy or total body radiation. Lisofylline alone or along with G-CSF was effective in protecting animals from the weight loss caused by high dose melphalan but not from weight loss caused by other cytotoxic therapies. Administration of lisofylline did not alter the killing of bone marrow CFU-GM by single doses of cyclophosphamide, melphalan or BCNU. However, administration of lisofylline increased the killing of EMT-6 tumor cells taken from the same animals. Administration of lisofylline had no effect on EMT-6 tumor growth. However, treatment with lisofylline along with high dose cyclophosphamide: melphalan, BCNU or 5-fluorouracil significantly increased the tumor growth delay produced by these agents. Overall, in the high dose therapy/EMT-6 mammary carcinoma model, lisofylline selectively enhanced hematopoietic recovery and increased tumor response to cytotoxic therapy. C1 JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. RP Teicher, BA (reprint author), DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. NR 22 TC 2 Z9 2 U1 0 U2 0 PU INT JOURNAL ONCOLOGY PI ATHENS PA C/O PROFESSOR D A SPANDIDOS, EDITORIAL OFFICE, 1, S MERKOURI ST, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD AUG PY 1997 VL 11 IS 2 BP 265 EP 272 PG 8 WC Oncology SC Oncology GA XL048 UT WOS:A1997XL04800009 PM 21528210 ER PT J AU Aiello, LP AF Aiello, LP TI Vascular endothelial growth factor - 20th-century mechanisms, 21st-century therapies SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID RETINAL NEOVASCULARIZATION; RETINOPATHY; CELLS; DEGENERATION; INHIBITION RP Aiello, LP (reprint author), HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,1 JOSLIN PL,BOSTON,MA 02215, USA. NR 19 TC 61 Z9 68 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD AUG PY 1997 VL 38 IS 9 BP 1647 EP 1652 PG 6 WC Ophthalmology SC Ophthalmology GA XU430 UT WOS:A1997XU43000001 PM 9286253 ER PT J AU Smith, SW Mankiletow, A Harris, WH AF Smith, SW Mankiletow, A Harris, WH TI Vastus-psoas release for acetabular exposure in revision hip surgery SO JOURNAL OF ARTHROPLASTY LA English DT Article DE revision total hip arthroplasty; vastus-psoas release; acetabular exposure AB A technique is presented for wide exposure of the acetabulum for revision total hip arthroplasty surgery in the presence of a solidly fixed, modular, or monoblock femoral component without the need for trochanteric osteotomy. The technique involves release of the proximal portion of the vastus lateralis, vastus inter-medius, and vastus medialis muscles and the iliopsoas tendon from the femur and placement of the femoral head/neck posterior to the acetabulum. The exposure afforded by this release usually precludes the need for trochanteric osteotomy: and/or removal of a well-fixed femoral component in revision surgery that is being done for isolated loosening of acetabular components, thereby decreasing operative time, morbidity, and the risks of complication of trochanteric osteotomy. C1 MASSACHUSETTS GEN HOSP,DEPT ORTHOPAED SURG,ORTHOPAED BIOMECH LAB,BOSTON,MA 02114. NR 8 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 SN 0883-5403 J9 J ARTHROPLASTY JI J. Arthroplast. PD AUG PY 1997 VL 12 IS 5 BP 568 EP 571 DI 10.1016/S0883-5403(97)90181-9 PG 4 WC Orthopedics SC Orthopedics GA XR226 UT WOS:A1997XR22600013 PM 9268798 ER PT J AU Gallagher, PG Tse, WT Scarpa, AL Lux, SE Forget, BG AF Gallagher, PG Tse, WT Scarpa, AL Lux, SE Forget, BG TI Structure and organization of the human ankyrin-1 gene - Basis for complexity of pre-mRNA processing SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN ERYTHROCYTE ANKYRIN; DOMINANT HEREDITARY SPHEROCYTOSIS; POLYMERASE CHAIN-REACTION; MESSENGER-RNA; REGULATORY DOMAIN; ANION-EXCHANGER; MAJOR ANKYRIN; MEMBRANE-SKELETON; HEMOLYTIC-ANEMIA; PLASMA-MEMBRANE AB Ankyrin-1 (ANK-1) is an erythrocyte membrane protein that is defective in many patients with hereditary spherocytosis, a common hemolytic anemia. In the red cell, ankyrin-1 provides the primary linkage between the membrane skeleton and the plasma membrane, To gain additional insight into the structure and function of this protein and to provide the necessary tools for further genetic studies of hereditary spherocytosis patients, we cloned the human ANK-1 chromosomal gene, Characterization of the ANK-1 gene genomic structure revealed that the erythroid transcript is composed of 42 exons distributed over similar to 160 kilobase pairs of DNA. Comparison of the genomic structure with the protein do mains reveals a near-absolute correlation between the tandem repeats encoding the membrane-binding domain of ankyrin with the location of the intron/exon boundaries in the corresponding part of the gene, Erythroid stage-specific, complex patterns of alternative splicing were identified in the region encoding the regulatory domain of ankyrin-1. Novel brain-specific transcripts were also identified in this region, as well as in the ''hinge'' region between the membrane-binding and spectrin-binding domains, Utilization of alternative polyadenylation signals was found to be the basis for the previously described, stage-specific 9.0- and 7.2-kilobase pair transcripts of the ANK-1 gene. C1 YALE UNIV,SCH MED,DEPT GENET,NEW HAVEN,CT 06520. YALE UNIV,SCH MED,DEPT INTERNAL MED,NEW HAVEN,CT 06520. CHILDRENS HOSP,DIV HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PEDIAT,BOSTON,MA 02115. RP Gallagher, PG (reprint author), YALE UNIV,SCH MED,DEPT PEDIAT,333 CEDAR ST,POB 208064,NEW HAVEN,CT 06520, USA. NR 85 TC 48 Z9 49 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 AUG 1 PY 1997 VL 272 IS 31 BP 19220 EP 19228 DI 10.1074/jbc.272.31.19220 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XP063 UT WOS:A1997XP06300020 PM 9235914 ER PT J AU Ubeda, M Habener, JF AF Ubeda, M Habener, JF TI The large subunit of the DNA replication complex C (DSEB/RF-C140) cleaved and inactivated by caspase-3 (CPP32/YAMA) during Fas-induced apoptosis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DIFFERENTIATION-SPECIFIC ELEMENT; SMALL NUCLEAR RIBONUCLEOPROTEIN; 70-KDA PROTEIN-COMPONENT; DEATH GENE CED-3; CELL-DEATH; POLY(ADP-RIBOSE) POLYMERASE; ANGIOTENSINOGEN GENE; ICE/CED-3 PROTEASE; MAMMALIAN HOMOLOG; EXPRESSION AB We report the identification of the large subunit of the DNA replication factor, DSEB/RF-C140, as a new substrate for caspase-3 (CPP32/YAMA), or a very closely related protease activated during Fas-induced apoptosis in Jurkat T cells, DSEB/RF-C140 is a multifunctional DNA-binding protein with sequence homology to poly-(ADP-ribose) polymerase (PARP), This similarity includes a consensus DEVD/G cleavage site for caspase-3. Cleavage of DSEB/RF-C140 is predicted to occurs between Asp(706) and Gly(707), generating 87-kDa and 53-kDa fragments. An antiserum raised against the amino-terminal domain of DSEB/RF-C140 detects a new 87-kDa protein in Jurkat T cells in which apoptosis is activated by a monoclonal antibody to Fas, This cleavage occurs shortly after PARR cleavage, In vitro translated DSEB/RF-C140 is specifically cleaved into the predicted fragments when incubated with a cytoplasmic extract from Fas antibody-treated cells, Proteolytic cleavage was prevented by substituting Asp(706) by an alanine in the DEVD706/G caspase-3 cleavage site, The cleavage of DSEB/RF-C140 is prevented by iodoacetamide and the specific caspase-3 inhibitor, tetrapeptide aldehyde Ac-DEVD-CHO, but not by the specific ICE (interleukin-1-converting enzyme) inhibitors: CrmA and Ac-YVAD-CHO, indicating that the protease responsible for the cleavage of DSEB/RF-C140 during Fas induced apoptosis in Jurkat cells is caspase-3, or a closely related protease, This conclusion is reinforced by the fact that recombinant caspase-3 but not caspase-1 reproduced the ''in vivo'' cleavage, Inasmuch as the cleavage of DSEB/ RF-C140 separates its DNA binding from its association domain, required for replication complex formation, we propose that such a cleavage will impair DNA replication, Recent in vitro mutagenesis support this proposal (Uhlmann, F., Cai, J., Gibbs, E., O'Donnel, M., and Hurwitz, J. (1997) J. Biol. Chem. 272, 10058-10064). C1 MASSACHUSETTS GEN HOSP,HOWARD HUGHES MED INST,MOL ENDOCRINOL LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. FU NIDDK NIH HHS [R37 DK30457] NR 49 TC 30 Z9 30 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 1 PY 1997 VL 272 IS 31 BP 19562 EP 19568 DI 10.1074/jbc.272.31.19562 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XP063 UT WOS:A1997XP06300067 PM 9235961 ER PT J AU Ramamurti, BS Orr, TE Bragdon, CR Lowenstein, JD Jasty, M Harris, WH AF Ramamurti, BS Orr, TE Bragdon, CR Lowenstein, JD Jasty, M Harris, WH TI Factors influencing stability at the interface between a porous surface and cancellous bone: A finite element analysis of a canine in vivo micromotion experiment SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH LA English DT Article; Proceedings Paper CT 23rd Annual Meeting of the Society-for-Biomaterials CY APR 30-MAY 04, 1997 CL NEW ORLEANS, LA SP Soc Biomat DE porous coating; implant motion; bone ingrowth; press fit; friction coefficient ID COATED IMPLANTS; INGROWTH; TITANIUM; FIXATION; RABBITS; METAL; FIT AB Several factors contribute to the success of stable bony ingrowth into the porous coated surfaces of orthopaedic implants used in hip arthroplasty. Despite having good bony apposition, bony ingrowth might not occur if the relative motion between bone and implant is large. Therefore, determining the Limiting micromotion value that inhibits stable bony ingrowth is important. From a previous canine in vivo micromotion study performed at our laboratory, this Limiting value was found to be 20 mu m. Initially, cementless orthopaedic implants are stabilized only by frictional forces at the bone-implant interface. Therefore, other parameters such as the coefficient of friction and the compressive force normal to the interface should be considered as important factors which stabilize the interface along with micromotion. The purpose of this analytical study was to elucidate how the stability at the bone-implant interface is influenced by various factors, namely, motion of the implant, the coefficient of friction, the degree of press fit, and the modulus of the surrounding cancellous bone in determining the stability of the bone-implant interface. Nonlinear and Linear finite element models which simulated the immediate postsurgical condition and the end point of the canine in vivo micromotion experiment, respectively, were used to this end. From the results of the finite element models it was possible to identify the displacement magnitude for which the implant slipped relative to the bone as the motion of the implant was increased incrementally. This was done for combinations of the coefficient of friction, press fit, and Young's modulus of cancellous bone. This was used as an indicator of the limiting implant motion value beyond which bony ingrowth will be inhibited. The stress distribution in the surrounding cancellous bone bed was also obtained from the results of the finite element analyses for different press-fit conditions. The results of the study indicated that under slight press-fit conditions, the implant slipped relative to bone for implant motions as low as 20 mu m. For higher degrees of press fit and reasonable values for the coefficient of friction, no slip occurred for implant motions as much as 100 mu m. Although higher degrees of press fit were theoretically conducive to better implant stability, the concomitant high stresses in the adjacent cancellous bone will tend to compromise the integrity of the press fit. This was also evident when the results of an analytical model with a lower degree of press fit correlated well with those of the canine in vivo experiment in which a higher press fit was used, suggesting a possibility of achieving a less than desired press fit during the process of implantation. Through this study the importance of factors other than implant motion was emphasized. The results of the study suggest that the limiting value of implant motion that inhibits bone ingrowth might vary with the degree of press fit for reasonable coefficients of friction. (C) 1997 John Wiley & Sons, Inc. C1 MASSACHUSETTS GEN HOSP,ORTHOPAED BIOMECH LAB,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT ORTHOPAED SURG,HIP & IMPLANT UNIT,BOSTON,MA 02114. NR 23 TC 57 Z9 59 U1 1 U2 9 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9304 J9 J BIOMED MATER RES JI J. Biomed. Mater. Res. PD AUG PY 1997 VL 36 IS 2 BP 274 EP 280 DI 10.1002/(SICI)1097-4636(199708)36:2<274::AID-JBM17>3.0.CO;2-G PG 7 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA XP499 UT WOS:A1997XP49900017 PM 9261690 ER PT J AU Chen, W Li, YP AF Chen, W Li, YP TI Generation of immortalized osteoblast precursor cell lines for gene transfection studies. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 FORSYTH DENT CTR,DEPT CYTOKINE BIOL,BOSTON,MA 02115. NR 0 TC 3 Z9 3 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1997 VL 12 SU 1 BP 22 EP 22 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62700023 ER PT J AU Zhao, W Byrne, MH Boyce, BF Krane, SM AF Zhao, W Byrne, MH Boyce, BF Krane, SM TI Bone resorption stimulated by parathyroid hormone is strikingly diminished in collagenase-resistant mutant mice. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1997 VL 12 SU 1 BP 29 EP 29 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62700029 ER PT J AU Schipani, E Lanske, B Hunzelman, J Luz, A Kovacs, CS Lee, K Pirro, A Kronenberg, HM Juppner, H AF Schipani, E Lanske, B Hunzelman, J Luz, A Kovacs, CS Lee, K Pirro, A Kronenberg, HM Juppner, H TI Targeted expression of constitutively active PTH/PTHrP receptors delays endochondral bone formation and rescues PTHrP-less mice. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. GSF MUNICH,INST PATHOL,D-85758 NEUHERBERG,GERMANY. NR 0 TC 2 Z9 2 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1997 VL 12 SU 1 BP 30 EP 30 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62700031 ER PT J AU Hosokawa, Y Yoshimoto, K Bronson, R Wang, T Schmidt, EV Arnold, A AF Hosokawa, Y Yoshimoto, K Bronson, R Wang, T Schmidt, EV Arnold, A TI Chronic hyperparathyroidism in transgenic mice with parathyroid-targeted overexpression of cyclin D1/PRAD1. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. TUFTS UNIV NEW ENGLAND MED CTR,BOSTON,MA 02111. NR 0 TC 0 Z9 0 U1 0 U2 2 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1997 VL 12 SU 1 BP 31 EP 31 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62700030 ER PT J AU Kovacs, CS Lanske, B Byrne, M Krane, SM Kronenberg, HM AF Kovacs, CS Lanske, B Byrne, M Krane, SM Kronenberg, HM TI Interstitial collagenase expression is reduced in the tibias of PTH/PTHrP receptor gene-ablated fetal mice. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1997 VL 12 SU 1 BP 53 EP 53 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62700053 ER PT J AU Chung, U Lanske, B Carolan, P Lee, K Segre, G Li, E Kronenberg, H AF Chung, U Lanske, B Carolan, P Lee, K Segre, G Li, E Kronenberg, H TI A novel chimeric approach reveals cell-autonomous effects of the PTH/PTHrP receptor on chondrocyte differentiation. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1997 VL 12 SU 1 BP 56 EP 56 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62700056 ER PT J AU Pao, CLH Lee, K Seidman, JG Seidman, CE Segre, GV AF Pao, CLH Lee, K Seidman, JG Seidman, CE Segre, GV TI Hyperparathyroidism promotes bone resorption but retards cartilage resorption in calcium-sensing receptor-deficient mice. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,HOWARD HUGHES MED INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1997 VL 12 SU 1 BP 57 EP 57 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62700057 ER PT J AU Lee, K Carolan, P Koike, T Tanabe, S Segre, GV AF Lee, K Carolan, P Koike, T Tanabe, S Segre, GV TI Osteoblast precursors and proliferating chondrocytes are target cells for Indian hedgehog in developing endochondral bone. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1997 VL 12 SU 1 BP 63 EP 63 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62700062 ER PT J AU Corral, DA Amling, M Priemel, M Neff, L Chung, U Kronenberg, HM Baron, R Karsenty, G AF Corral, DA Amling, M Priemel, M Neff, L Chung, U Kronenberg, HM Baron, R Karsenty, G TI Reversible ablation of osteoblasts: An animal model of osteoporosis. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 UNIV TEXAS,MD ANDERSON CANC CTR,HOUSTON,TX. UNIV HAMBURG,HAMBURG,GERMANY. YALE UNIV,NEW HAVEN,CT 06520. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 2 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1997 VL 12 SU 1 BP 69 EP 69 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62700069 ER PT J AU Li, YC Pirro, AE Amling, M Baron, R Bronson, R Demay, MB AF Li, YC Pirro, AE Amling, M Baron, R Bronson, R Demay, MB TI Vitamin D receptor knock-out mice develop hypocalcemia, hyperparathyroidism, rickets, osteomalacia and alopecia SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,ENDOCRINE UNIT,BOSTON,MA 02114. YALE UNIV,SCH MED,NEW HAVEN,CT 06511. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1997 VL 12 SU 1 BP 81 EP 81 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62700081 ER PT J AU Koike, T Carolan, P Tanabe, S Colvin, J Ornitz, D Segre, GV Lee, K AF Koike, T Carolan, P Tanabe, S Colvin, J Ornitz, D Segre, GV Lee, K TI FGF and its receptor are potent negative regulators of skeletal growth. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. WASHINGTON UNIV,SCH MED,DEPT MOL BIOL & PHARMACOL,ST LOUIS,MO 63110. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1997 VL 12 SU 1 BP 89 EP 89 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62700089 ER PT J AU Bergwitz, C Luck, M Jusseaume, SA Juppner, H Gardella, TJ AF Bergwitz, C Luck, M Jusseaume, SA Juppner, H Gardella, TJ TI Agonist selectivity of the PTH-2 receptor is determined by two residues in the membrane-spanning core region of the receptor. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT MED,ENDOCRINE UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1997 VL 12 SU 1 BP 120 EP 120 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62700120 ER PT J AU Karperien, M FarihSips, H Hendriks, J Papapoulos, SE Lanske, B AbouSamra, AB Lowik, CWGM Defize, LHK AF Karperien, M FarihSips, H Hendriks, J Papapoulos, SE Lanske, B AbouSamra, AB Lowik, CWGM Defize, LHK TI Characterization of the PTH/PTHRP receptor gene promoter in vitro and in vivo: Regulation by retinoic acid and BMP2. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 UNIV LEIDEN HOSP,NL-2300 RC LEIDEN,NETHERLANDS. NETHERLANDS INST DEV BIOL,UTRECHT,NETHERLANDS. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1997 VL 12 SU 1 BP 122 EP 122 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62700123 ER PT J AU Carolan, PJ Lee, K Koike, T Lanske, B Tanabe, S Kronenberg, HM Segre, GV AF Carolan, PJ Lee, K Koike, T Lanske, B Tanabe, S Kronenberg, HM Segre, GV TI Effects of PTHrP on chondrocyte differentiation, responsiveness to IGF-I, and regulation of patched mRNA expression are mediated by protein kinase A. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1997 VL 12 SU 1 BP 125 EP 125 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62700125 ER PT J AU Hentunen, TA Koop, BA Reddy, SV Boyce, BF Devlin, RD Dallas, M Goldring, SR Windle, JJ Roodman, GD AF Hentunen, TA Koop, BA Reddy, SV Boyce, BF Devlin, RD Dallas, M Goldring, SR Windle, JJ Roodman, GD TI Development of an osteoclast (OCL) precursor cell line from mice transgenic for both SV40 T antigen and BCL-X-L. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX 78284. VA HOSP,SAN ANTONIO,TX 78284. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,BOSTON,MA 02215. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1997 VL 12 SU 1 BP 137 EP 137 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62700137 ER PT J AU Palanisamy, N Chaganti, RSK Arnold, A AF Palanisamy, N Chaganti, RSK Arnold, A TI Novel chromosomal abnormalities in parathyroid adenomas identified by comparative genomic hybridization (CGH). SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 MEM SLOAN KETTERING CANC CTR,NEW YORK,NY 10021. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1997 VL 12 SU 1 BP 159 EP 159 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62700158 ER PT J AU Stock, JL Avioli, LV Baylink, DJ Chesnut, C Genant, HK Maricic, MJ Silverman, SL Schaffer, AV Feinblatt, J AF Stock, JL Avioli, LV Baylink, DJ Chesnut, C Genant, HK Maricic, MJ Silverman, SL Schaffer, AV Feinblatt, J TI Calcitonin-salmon nasal spray reduces the incidence of new vertebral fractures in postmenopausal women: Three-year interim results of the proof study. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 WASHINGTON UNIV,SCH MED,ST LOUIS,MO. MEM HLTH CARE,WORCESTER,MA. LOMA LINDA UNIV,LOMA LINDA,CA 92350. UNIV WASHINGTON,MED CTR,SEATTLE,WA 98195. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. UNIV ARIZONA,HLTH SCI CTR,TUCSON,AZ. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. NOVARTIS PHARMACEUT,E HANOVER,NJ. NR 0 TC 1 Z9 1 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1997 VL 12 SU 1 BP 187 EP 187 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62700186 ER PT J AU Greenspan, SL Bouxsein, ML Melton, ME Kolodny, AH Clair, JH Delucca, PT Stek, M Faulkner, KG Orwoll, ES AF Greenspan, SL Bouxsein, ML Melton, ME Kolodny, AH Clair, JH Delucca, PT Stek, M Faulkner, KG Orwoll, ES TI Precision and discriminatory ability of calcaneal bone assessment technologies SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article; Proceedings Paper CT 2nd Annual Scientific Meeting of the Society-for-Clinical-Densitometry CY JAN 18-21, 1996 CL COLORADO SPRINGS, CO SP Soc Clin Densitometry ID X-RAY ABSORPTIOMETRY; BAND ULTRASOUND ATTENUATION; HIP FRACTURE; POSTMENOPAUSAL WOMEN; MINERAL DENSITY; RISK-FACTORS; QUANTITATIVE ULTRASOUND; SKELETAL SITES; ELDERLY WOMEN; OS CALCIS AB To determine if measuring skeletal status at the calcaneus is a potentially valuable technique for diagnosing osteoporosis, we examined five calcaneal assessment techniques in 53 young normal women and 108 postmenopausal women with osteoporosis and compared these measurements to dual-energy X-ray absorptiometry (DEXA)) at the calcaneus, hip, and spine. The five instruments, including single-energy X-ray absorptiometry (SEXA) and four quantitative ultrasound (QUS) instruments, were evaluated for precision, ability to discriminate osteoporotic from young normal subjects, and correlation to the other instruments, The coefficient of variation (%CV) for instrument, positioning, interobserver, and short-term precision of the five calcaneal instruments ranged from 1.34-7.76%, 1.63-7.00%, 1.84-9.44%, and 1.99-7.04%, respectively, The %CVs for positioning, interobserver, and short-term precision were similar for calcaneal DEXA, calcaneal SEXA, and stiffness (as measured by Achilles), The %CVs for instrument precision were similar between calcaneal DEXA and SEXA. The ability of the five calcaneal instruments to discriminate osteoporotic from young normal subjects was similar based on the analysis of area under the receiver operating characteristic curves (range 0.88-0.93) and equivalent to DEXA of the calcaneus and hip (0.88-0.93), The correlations between the measurements of five calcaneal instruments were strong (0.80 less than or equal to r less than or equal to 0.91,p < 0.001), These data suggest that although the precision is variable? the calcaneal QUS and SEXA instruments can discriminate between osteoporotic patients and young normal controls and appear to be a useful technique for assessment of osteoporosis. C1 MERCK & CO INC, W POINT, PA 19486 USA. BETH ISRAEL DEACONESS MED CTR, OSTEOPOROSIS PREVENT & TREATMENT CTR, BOSTON, MA USA. BETH ISRAEL DEACONESS MED CTR, ORTHOPAED BIOMECH LAB, BOSTON, MA USA. OREGON OSTEOPOROSIS CTR, PORTLAND, OR USA. PORTLAND VA MED CTR, BONE & MINERAL RES UNIT, PORTLAND, OR USA. OREGON HLTH SCI UNIV, PORTLAND, OR 97201 USA. OI Orwoll, Eric/0000-0002-8520-7355 NR 41 TC 141 Z9 143 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1997 VL 12 IS 8 BP 1303 EP 1313 DI 10.1359/jbmr.1997.12.8.1303 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XN797 UT WOS:A1997XN79700020 PM 9258762 ER PT J AU Chen, S McDougall, S IidaKlein, A Lee, S Hahn, TJ AF Chen, S McDougall, S IidaKlein, A Lee, S Hahn, TJ TI ECM-mediated regulation of PTH/PTHrP receptor expression in rat chondrocytes. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 UNIV CALIF LOS ANGELES,SCH MED,W LOS ANGELES VET AFFAIRS MED CTR,CTR GERIATR RES EDUC & CLIN,LOS ANGELES,CA 90073. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1997 VL 12 SU 1 BP F275 EP F275 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62700764 ER PT J AU Galson, DL Anusaksathein, O Hong, CY Doppalapudi, VA Flannery, M Manning, C Owen, C Goldring, SR AF Galson, DL Anusaksathein, O Hong, CY Doppalapudi, VA Flannery, M Manning, C Owen, C Goldring, SR TI A novel isoform of the human calcitonin receptor contains an 85 BP insert that generates a unique IC4 domain. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,BOSTON,MA 02115. BETH ISRAEL DEACONESS MED CTR,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1997 VL 12 SU 1 BP F388 EP F388 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62700878 ER PT J AU Lee, SK Galson, D Goldring, SR Lorenzo, JA AF Lee, SK Galson, D Goldring, SR Lorenzo, JA TI A murine monocyte-macrophage cell line (J774A.1) expresses calcitonin receptor mRNA after phorbol 12-myristate 13-acetate (PMA) treatment SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 VA CONNECICUT HEALTHCARE SYST,NEWINGTON,CT. UNIV CONNECTICUT,CTR HLTH,FARMINGTON,CT 06030. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,BETH ISRAEL DEACONESS MED CTR,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1997 VL 12 SU 1 BP F393 EP F393 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62700881 ER PT J AU Lim, T Lee, S Chen, S McDougall, S IidaKlein, A Hahn, TJ AF Lim, T Lee, S Chen, S McDougall, S IidaKlein, A Hahn, TJ TI The alpha v beta 3 vitronectin receptor: Second messenger generation and cell phenotype regulation in mammalian chondrocytes. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 UNIV CALIF LOS ANGELES,SCH MED,W LOS ANGELES VET AFFAIRS MED CTR,CTR GERIATR RES EDUC & CLIN,LOS ANGELES,CA 90073. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1997 VL 12 SU 1 BP F274 EP F274 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62700763 ER PT J AU McDougall, S Chen, S Glackin, C Fang, MA AF McDougall, S Chen, S Glackin, C Fang, MA TI The role of basic fibroblast growth factor and EGR-1 in regulating alpha 2(I) collagen and twist gene expression in osteoblasts. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 UNIV CALIF LOS ANGELES,SCH MED,W LOS ANGELES VET AFFAIRS MED CTR,CTR GERIATR RES EDUC & CLIN,LOS ANGELES,CA 90073. CITY HOPE NATL MED CTR,DUARTE,CA 91010. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1997 VL 12 SU 1 BP F215 EP F215 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62700704 ER PT J AU Menaa, C Roodman, GD AF Menaa, C Roodman, GD TI Increased sensitivity to 1,25-(OH)(2)D-3 of osteoclast precursors in Paget's disease is not due to differences in expression levels of the 1,25-D receptor. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1997 VL 12 SU 1 BP F418 EP F418 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62700907 ER PT J AU Peters, JH Lee, S McDougall, S Hahn, TJ AF Peters, JH Lee, S McDougall, S Hahn, TJ TI Rat chondrocytes interact with multiple segments of fibronectin. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 UNIV CALIF LOS ANGELES,SCH MED,W LOS ANGELES VET AFFAIRS MED CTR,GRECC,LOS ANGELES,CA 90073. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1997 VL 12 SU 1 BP F273 EP F273 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62700761 ER PT J AU Sneddon, WB Demay, MB AF Sneddon, WB Demay, MB TI Definition of an element required for 1,25-dehydroxyvitamin D-3-dependent transactivation of the rat osteocalcin gene. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,ENDOCRINE UNIT,BOSTON,MA 02114. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1997 VL 12 SU 1 BP F204 EP F204 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62700694 ER PT J AU Tanabe, S Lee, K Salusky, IB Carolan, PJ Koike, T Segre, GV AF Tanabe, S Lee, K Salusky, IB Carolan, PJ Koike, T Segre, GV TI 1,25-dihydroxy-vitamin D retards the pace of growth-plate chondrocyte differentiation. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. UNIV CALIF LOS ANGELES,SCH MED,DEPT PEDIAT,LOS ANGELES,CA 90024. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1997 VL 12 SU 1 BP F416 EP F416 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62700906 ER PT J AU Choi, SJ Devlin, RD Reddy, SV Roodman, GD AF Choi, SJ Devlin, RD Reddy, SV Roodman, GD TI Cloning and identification of a novel inhibitor of osteoclast formation and bone resorption derived from an osteoclast library. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1997 VL 12 SU 1 BP P217 EP P217 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62700211 ER PT J AU Giannoukos, G Chilco, P AbouSamra, A AF Giannoukos, G Chilco, P AbouSamra, A TI Characterization of an osteoblast-specific enhancer within the rat PTH/PTHrP receptor gene promoter. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1997 VL 12 SU 1 BP P212 EP P212 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62700206 ER PT J AU Imanishi, Y Tahara, H Salusky, IB Goodman, WG Gaz, RD Brandi, ML Sarfati, E Drueke, TB Smith, AP Yoshimoto, K Arnold, A AF Imanishi, Y Tahara, H Salusky, IB Goodman, WG Gaz, RD Brandi, ML Sarfati, E Drueke, TB Smith, AP Yoshimoto, K Arnold, A TI Distinct molecular pathogeneses in different categories of benign hyperparathyroidism. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 UNIV CALIF LOS ANGELES,MED CTR,LOS ANGELES,CA 90024. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. HOP ST LOUIS,PARIS,FRANCE. UNIV FLORENCE,FLORENCE,ITALY. HOP NECKER ENFANTS MALAD,PARIS,FRANCE. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1997 VL 12 SU 1 BP P314 EP P314 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62700309 ER PT J AU Ju, J Leigh, S Byrne, M vanderRest, M Liu, V Krane, S AF Ju, J Leigh, S Byrne, M vanderRest, M Liu, V Krane, S TI A new marker for measuring bone resorption using an ELISA for a 14 amino acid peptide (residues 620-633) derived from the collagen alpha 1(I) chain. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 METRA BIOSYST,MT VIEW,CA. COLLAGEN CORP,PALO ALTO,CA. INST BIOL STRUCT,GRENOBLE,FRANCE. HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1997 VL 12 SU 1 BP P307 EP P307 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62700300 ER PT J AU Komatsu, Y Segre, GV AF Komatsu, Y Segre, GV TI PTH/PTHrP receptor signaling of adenylyl cyclase and phospholipase C pathways is selectively inhibited by coexpression of minigene encoding intracellular domain of the receptor SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1997 VL 12 SU 1 BP P247 EP P247 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62700240 ER PT J AU Rubin, LP Kovacs, CS Tsal, SW Pinar, H Torday, JS Kronenberg, HM AF Rubin, LP Kovacs, CS Tsal, SW Pinar, H Torday, JS Kronenberg, HM TI The parathyroid hormone-related protein (PTHrP) knockout mouse shows delayed lung development. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,BOSTON,MA 02115. BROWN UNIV,PROVIDENCE,RI 02912. UNIV MARYLAND,BALTIMORE,MD 21201. NR 0 TC 1 Z9 1 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1997 VL 12 SU 1 BP P245 EP P245 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62700239 ER PT J AU Fuleihan, GE Klerman, B Brown, E Czeisler, CA AF Fuleihan, GE Klerman, B Brown, E Czeisler, CA TI N-Tx diurnal rhythm is truly endogenous. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 BRIGHAM & WOMENS HOSP,DIV ENDOCRINE HYPERTENS,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DIV BIOSTAT,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1997 VL 12 SU 1 BP S613 EP S613 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62701608 ER PT J AU Glowacki, J Yates, K LesieurBrooks, A Bleiberg, I Cheleuitte, D AF Glowacki, J Yates, K LesieurBrooks, A Bleiberg, I Cheleuitte, D TI Confounding influences of culture conditions on cytokine secretion by cultured primary human bone marrow cells SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1997 VL 12 SU 1 BP S337 EP S337 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62701333 ER PT J AU Kearns, AE Simays, W Demay, MB AF Kearns, AE Simays, W Demay, MB TI Osteoblast silencer activities in the first intron of the rat osteocalcin gene. SO JOURNAL OF BONE AND MINERAL RESEARCH 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 BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1997 VL 12 SU 1 BP S303 EP S303 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62701298 ER PT J AU Landis, WJ Block, D Hodgens, KJ Kronenberg, H Lanske, B AF Landis, WJ Block, D Hodgens, KJ Kronenberg, H Lanske, B TI PTH/PTHrP-receptor knock-out mice demonstrate altered epiphyseal cartilage and endochondral bone formation. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 CHILDRENS HOSP,DEPT ORTHOPED SURG,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1997 VL 12 SU 1 BP S371 EP S371 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62701366 ER PT J AU Liu, B Guo, J Lanske, B Kronenberg, HM Bringhurst, FR AF Liu, B Guo, J Lanske, B Kronenberg, HM Bringhurst, FR TI Expression of the PTH/PTHRP receptor by osteoclast progenitors is not required for PTH-dependent osteoclastogenesis. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. NR 0 TC 1 Z9 1 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1997 VL 12 SU 1 BP S272 EP S272 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62701267 ER PT J AU Maunstadt, M Keutmann, HT Jusseaume, S Takasu, H Juppner, H Gardella, TJ AF Maunstadt, M Keutmann, HT Jusseaume, S Takasu, H Juppner, H Gardella, TJ TI Studies on a putative PTH2 receptor-selective ligand in bovine hypothalamus. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1997 VL 12 SU 1 BP S368 EP S368 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62701363 ER PT J AU McClung, MR Neer, R Genant, HK Fraser, WD Barbier, A Picot, C AF McClung, MR Neer, R Genant, HK Fraser, WD Barbier, A Picot, C TI Tiludronate in the treatment of metabolic bone diseases - A summary of safety data. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. ROYAL LIVERPOOL HOSP,LIVERPOOL L7 8XP,MERSEYSIDE,ENGLAND. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1997 VL 12 SU 1 BP S477 EP S477 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62701473 ER PT J AU Otsuka, Y Takemura, M Segre, GV AF Otsuka, Y Takemura, M Segre, GV TI Highly conserved residues of the third cytoplasmic domain of the PTH/PTHrP receptor are critical for activating phospholipase C. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1997 VL 12 SU 1 BP S364 EP S364 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62701359 ER PT J AU Qian, F AbouSamra, A AF Qian, F AbouSamra, A TI Mapping of the phosphorylation sites of PTH/PTHrP receptor. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1997 VL 12 SU 1 BP S365 EP S365 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62701361 ER PT J AU Rubin, D Chen, J Zon, L Fishman, M Bergwitz, C Juppner, H AF Rubin, D Chen, J Zon, L Fishman, M Bergwitz, C Juppner, H TI Functional properties and tissue distribution of a parathyroid hormone type 2 receptor (PTH2R) in the zebrafish (Danio rerio). SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,ENDOCRINE UNIT,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CVRC,CHARLESTOWN,MA. HARVARD UNIV,SCH MED,CHILDRENS HOSP BOSTON,HHMI,BOSTON,MA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1997 VL 12 SU 1 BP S369 EP S369 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62701365 ER PT J AU Takasu, H Guo, J Bringhurst, FR AF Takasu, H Guo, J Bringhurst, FR TI Human and rat PTH/PTHrP receptors display different signal selectivity for hPTH(1-31) and hPTH(1-30) in stably transfected LLC-PK1 cells. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1997 VL 12 SU 1 BP S367 EP S367 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62701362 ER PT J AU Yamaguchi, DT Ma, D Huang, J Kim, T Ajmera, A AF Yamaguchi, DT Ma, D Huang, J Kim, T Ajmera, A TI Inhibition of gap junction communication in osteoblastic cells by electromagnetic fields is dependent on intracellular pH. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 W LOS ANGELES VET AFFAIRS MED CTR,GRECC,LOS ANGELES,CA 90073. W LOS ANGELES VET AFFAIRS MED CTR,RES SERV,LOS ANGELES,CA 90073. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1997 VL 12 SU 1 BP S248 EP S248 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62701243 ER PT J AU Feliers, D Woodruff, K Abboud, S AF Feliers, D Woodruff, K Abboud, S TI Role of insulin-like growth factor binding protein (IGFBP)-4 in decreasing bone formation in multiple myeloma (MM). SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1997 VL 12 SU 1 BP T410 EP T410 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62700405 ER PT J AU Kovacs, CS Kronenberg, HM AF Kovacs, CS Kronenberg, HM TI PTHrP regulates placental calbindin-D-9K expression: Evidence from the PTHrP gene ''knockout'' model. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1997 VL 12 SU 1 BP T441 EP T441 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62700435 ER PT J AU Peterson, WJ Yamaguchi, DT AF Peterson, WJ Yamaguchi, DT TI Down-regulation of DNA synthesis during osteogenesis in vitro: The effect of cell density and the extracellular matrix. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 W LOS ANGELES VET AFFAIRS MED CTR,GRECC,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA 90073. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1997 VL 12 SU 1 BP T397 EP T397 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62700391 ER PT J AU Akins, CW AF Akins, CW TI Mini-CABG: A step forward or a step backward? The ''con'' point of view SO JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA LA English DT Article DE MIDCAB; minimally invasive coronary artery surgery; CABG; angioplasty; cardiac surgery ID CORONARY RP Akins, CW (reprint author), MASSACHUSETTS GEN HOSP,CARDIAC SURG UNIT,WHITE 503,BOSTON,MA 02114, USA. NR 19 TC 4 Z9 4 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 1053-0770 J9 J CARDIOTHOR VASC AN JI J. Cardiothorac. Vasc. Anesth. PD AUG PY 1997 VL 11 IS 5 BP 669 EP 672 DI 10.1016/S1053-0770(97)90024-0 PG 4 WC Anesthesiology; Cardiac & Cardiovascular Systems; Respiratory System; Peripheral Vascular Disease SC Anesthesiology; Cardiovascular System & Cardiology; Respiratory System GA XQ052 UT WOS:A1997XQ05200025 PM 9263105 ER PT J AU Willsey, DB Peterfreund, RA AF Willsey, DB Peterfreund, RA TI Compartment syndrome of the upper arm after pressurized infiltration of intravenous fluid SO JOURNAL OF CLINICAL ANESTHESIA LA English DT Article DE complications, compartment syndrome AB Perioperative management of the acute trauma patient requires constant surveillance for the unexpected. We describe a case of upper extremity compartment syndrome resulting from pressurized infusion of crystalloid through an intravenous catheter placed in the emergency ward. Early recognition, diagnosis, and intervention with surgical fasciotomy averted potential complications and morbidity. (C) 1997 Elsevier Science Inc. C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA & CRIT CARE,BOSTON,MA 02114. NR 9 TC 18 Z9 18 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0952-8180 J9 J CLIN ANESTH JI J. Clin. Anesth. PD AUG PY 1997 VL 9 IS 5 BP 428 EP 430 DI 10.1016/S0952-8180(97)00073-1 PG 3 WC Anesthesiology SC Anesthesiology GA XN172 UT WOS:A1997XN17200017 PM 9257213 ER PT J AU Ohta, K Pang, XP Berg, L Hershman, JM AF Ohta, K Pang, XP Berg, L Hershman, JM TI Growth inhibition of new human thyroid carcinoma cell lines by activation of adenylate cyclase through the beta-adrenergic receptor SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article; Proceedings Paper CT 69th Annual Meeting of the American-Thyroid-Association CY NOV 13-17, 1996 CL SAN DIEGO, CA SP Amer Thyroid Assoc ID MOLECULAR-CLONING; THYROTROPIN RECEPTOR; TRANSCRIPTION; EXPRESSION; DIFFERENTIATION; HOMEODOMAIN; SEQUENCE; PROTEIN; BINDING; TTF-1 AB In normal thyroid cells, the TSH-adenylate cyclase system plays a pivotal role in controlling growth and differentiation. However, the role of this system in the growth of thyroid carcinoma is not well understood. To investigate this subject, we have established four new human thyroid carcinoma cell lines, designated BHP 2-7, 7-13, 10-3, and 18-21, from different patients. Northern gel analysis revealed that all of these cell lines expressed Pax-8 messenger ribonucleic acid; additionally, only BHP 18-21 cells expressed TTF-1 messenger ribonucleic acid. These cells were treated with various concentrations of 8-bromo-cAMP, forskolin, TSH, and adrenergic receptor agonist (norepinephrine, epinephrine, and isoproterenol), Cell proliferation was assessed by [H-3]thymidine incorporation and cell number. In these human thyroid carcinoma cell lines, the addition of 8-bromo-cAMP reduced [H-3]thymidine incorporation at a concentration of 10 mu mol/L. Forskolin (0.1-10 mu mol/L) significantly induced cAMP accumulation, decreased [H-3]thymidine incorporation, and reduced cell number in a dose-dependent manner. Conversely, TSH (0.01-1 mU/mL) did not affect the accumulation of cAMP or cell growth. We found that adrenergic receptor agonists induced the accumulation of cAMP and inhibited cell growth. The rank of potency was isoproterenol > epinephrine >> norepinephrine. The binding studies of [H-3]CGP-12177, a specific beta-adrenergic agonist, revealed that these new thyroid carcinoma cells had beta-adrenergic receptors. These results indicate that cAMP inhibits the growth of some human thyroid carcinoma cells, and that cAMP production is regulated through beta-adrenergic receptor-mediated pathways, but not through TSH receptor-mediated pathways. C1 W LOS ANGELES VET AFFAIRS MED CTR, DIV ENDOCRINOL 111D, ENDOCRINE RES LAB, LOS ANGELES, CA 90073 USA. UNIV CALIF LOS ANGELES, SCH MED, LOS ANGELES, CA 90073 USA. FU NCI NIH HHS [CA-61863] NR 28 TC 54 Z9 54 U1 1 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD AUG PY 1997 VL 82 IS 8 BP 2633 EP 2638 DI 10.1210/jc.82.8.2633 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP098 UT WOS:A1997XP09800043 PM 9253346 ER PT J AU Welt, CK Martin, KA Taylor, AE LambertMesserlian, GM Crowley, WF Smith, JA Schoenfeld, DA Hall, JE AF Welt, CK Martin, KA Taylor, AE LambertMesserlian, GM Crowley, WF Smith, JA Schoenfeld, DA Hall, JE TI Frequency modulation of follicle-stimulating hormone (FSH) during the luteal-follicular transition: Evidence for FSH control of inhibin B in normal women SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GONADOTROPIN-RELEASING-HORMONE; HUMAN MENSTRUAL-CYCLE; MESSENGER-RIBONUCLEIC-ACID; SUBUNIT GENE-EXPRESSION; RAT GRANULOSA-CELLS; PULSE FREQUENCY; LUTEINIZING-HORMONE; OVARIAN FOLLICLES; CORPUS-LUTEUM; DIMERIC INHIBIN AB To isolate the impact of GnRH pulse frequency on FSH secretion and to examine the effect of differing levels of FSH on inhibin B secretion during the luteal-follicular transition, exogenous GnRH was administered to GnRH-deficient women using one of two regimens, and the results were compared to those in normal women. In the GnRH-deficient women, the GnRH pulse frequency was increased from every 4 h in the late luteal phase to every 90 min on the day of menses to mimic normal cycling women (physiological frequency transition; n = 8 studies) or the GnRH pulse frequency was kept constant at a late luteal phase frequency of every 4 h through the first 6 days of the subsequent early follicular phase of cycle 2 (slow frequency transition: n = 6 studies). The differential rise in FSH secretion induced in these studies allowed us to examine the subsequent contribution of varying levels of FSH to inhibin B secretion. A physiological regimen of GnRH during the luteal-follicular transition resulted in a rise in FSH and inhibin B levels that did not differ from that in nor mal cycling women and a normal follicular phase length. On the other hand, maintaining a luteal frequency of GnRH for 6 days into the subsequent early follicular phase produced FSH levels significantly lower than those in the physiological transition (P < 0.05), with the greatest difference seen on the day after menses (9.1 +/- 1.0 us. 16.4 +/- 1.4 IU/L for the slow and physiological transition groups, respectively; P < 0.005), but no difference in LH. This slower rise of FSH secretion in the slow frequency group was associated with significantly lower inhibin B levels (43.3 +/- 21.5 vs. 140.0 +/- 24.4 pg/mL, mean days 1, 3, and 5; P < 0.02), a later doubling of estradiol from baseline (day 9.6 +/- 0.9 vs. day 5.6 +/- 0.1; P < 0.02), and a longer follicular phase length (16.0 +/- 1.4 us. 11.6 +/- 0.9 days; P < 0.05) compared with those in the physiological transition group. In conclusion, during the luteal-follicular transition, the GnRH pulse frequency contributes to but is not solely responsible for the FSH rise that initiates folliculogenesis. Alteration of FSH dynamics induced by changes in GnRH pulse frequency in GnRH-deficient women provides evidence that FSH stimulates inhibin B production in the human. Timely follicular development indicated by both estradiol and inhibin B secretion appears to be dependent on the pattern of increase in FSH during the luteal-follicular transition. C1 MASSACHUSETTS GEN HOSP, DEPT MED, REPROD ENDOCRINE SCI CTR, BOSTON, MA 02114 USA. WOMEN & INFANTS HOSP RHODE ISL, DEPT PATHOL & LAB MED, PROVIDENCE, RI 02905 USA. RP Welt, CK (reprint author), MASSACHUSETTS GEN HOSP, DEPT MED, NATL CTR INFERTIL RES, BOSTON, MA 02114 USA. OI Messerlian, Geralyn/0000-0002-9440-3411; Welt, Corrine/0000-0002-8219-5504 FU NCRR NIH HHS [M01-RR-01066]; NICHD NIH HHS [U54 HD029164, P30 HD028138, R01-HD-15080, U54-HD-29164] NR 53 TC 91 Z9 94 U1 1 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD AUG PY 1997 VL 82 IS 8 BP 2645 EP 2652 DI 10.1210/jc.82.8.2645 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP098 UT WOS:A1997XP09800045 PM 9253348 ER PT J AU Tao, XJ Tilly, KI Maravei, DV Shifren, JL Krajewski, S Reed, JC Tilly, JL Isaacson, KB AF Tao, XJ Tilly, KI Maravei, DV Shifren, JL Krajewski, S Reed, JC Tilly, JL Isaacson, KB TI Differential expression of members of the bcl-2 gene family in proliferative and secretory human endometrium: Glandular epithelial cell apoptosis is associated with increased expression of bax SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID UTERINE LUMINAL EPITHELIUM; MENSTRUAL-CYCLE; IN-VIVO; IMMUNOHISTOCHEMICAL ANALYSIS; TNF-ALPHA; DEATH; PROTEIN; PROTOONCOGENE; PROGESTERONE; NEURONS AB Glandular epithelial cells of the human endometrium initiate apoptosis in the secretory phase of the cycle. To better understand the regulation of apoptosis in this paradigm of endocrine-regulated cell turnover, Re studied the expression of the cell death regulatory genes, bax, bcl-2, and bcl-x, in human proliferative and secretory endometria relative to the absence or presence of apoptosis. As assessed by immunohistochemistry, levels of BAX protein were modest in proliferative endometrium and increased dramatically in the secretory phase when apoptosis was most prevalent. Expression of BAX was predominantly localized to epithelial cells of the functionalis layer of the secretory endometrium. In contrast, BCL-2 immunoreactivity was maximal during the proliferative phase and decreased in the secretory phase. Moreover, BCL-2 was topographically concentrated in the basalis layer. Immunoreactive BCL-X protein was observed mostly in glandular epithelial cells of the human endometrium. Compared with proliferative endometrium, secretory endometrium showed stronger BCL-X staining, especially in the functionalis layer. By Western blotting we confirmed that both proliferative and secretory endometrium expressed the long or antiapoptosis form as well as the short or proapoptosis form of the BCL-X protein. Taken together, our results demonstrate a coordinated pattern of expression of bcl-2 gene family members in human endometrium during the menstrual cycle, with a shift toward greater levels of the proapoptosis protein, BAX, occurring in glandular epithelial cells during the secretory phase of the cycle. Therefore, we conclude that cyclic changes in endometrial growth and regression may be precisely regulated by shifts in the ratio or balance of BCL-2 and related proteins in glandular epithelial cells. C1 HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, VINCENT CTR REPROD BIOL, BOSTON, MA 02114 USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, DIV REPROD ENDOCRINOL & INFERTIL, BOSTON, MA 02114 USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, DEPT OBSTET & GYNECOL, BOSTON, MA 02114 USA. BURNHAM INST, LA JOLLA, CA 92037 USA. FU NIA NIH HHS [R01-AG-12279]; NICHD NIH HHS [R01-HD-34226] NR 42 TC 103 Z9 114 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD AUG PY 1997 VL 82 IS 8 BP 2738 EP 2746 DI 10.1210/jc.82.8.2738 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP098 UT WOS:A1997XP09800061 PM 9253363 ER PT J AU Hebert, JR Ockene, IS Hurley, TG Luippold, R Well, AD Harmatz, MG AF Hebert, JR Ockene, IS Hurley, TG Luippold, R Well, AD Harmatz, MG TI Development and testing of a seven-day dietary recall SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE dietary fats; nutrition assessment; nutrition surveys; cognition; recall; serum cholesterol ID FOOD FREQUENCY QUESTIONNAIRE; WITHIN-SUBJECT VARIATION; NUTRITIONAL EPIDEMIOLOGY; NUTRIENT INTAKE; VALIDITY; TRIAL; REPRODUCIBILITY; VARIABILITY; CHOLESTEROL; NUMBER AB Using multiple 24-hr recalls (24HR) we tested the Seven Day Dietary Recall (7DDR) developed to assess nutrient exposures, especially lipids, in dietary interventions and other clinical trials requiring measurement of effect over moderate time periods. A total of 261 individuals in three studies completed a 7DDR at the end of a 3- to 5-week period during which 3 to 7 24HR were telephone-administered on randomly selected days. One of these studies ansi data from one additional study (total n = 678) allowed us to test the ability of the 7DDR to predict serum lipid changes in an intervention setting. In correlation and linear regression analyses, high levels of agreement between 7DDR and 24HR were obtained. For total energy: r = 0.67 and b = 0.69, and for total fat intake (g/day): r = 0.67 and b = 0.80. When 7 days of 24HR were available agreement tended to be higher. For total energy: r = 0.69 and b = 0.95, and for total fat (g/day): r = 0.71 and b = 1.04. Data derived from the 7DDR and fit to the Keys and Hegsted equations closely predicted actual changes in total serum cholesterol (within 15% and 10%, respectively). The 7DDR is a relatively easily administered, sensitive method to assess short-term changes in dietary fat consumption in individuals. (C) 1997 Elsevier Science Inc. C1 UNIV MASSACHUSETTS,SCH MED,DIV CARDIOVASC MED,WORCESTER,MA 01655. UNIV MASSACHUSETTS,DEPT PSYCHOL,AMHERST,MA 01003. ARIZONA DEPT HLTH SERV,OFF NUTR,PHOENIX,AZ 85007. FALLON CLIN INC,WORCESTER,MA. DANA FARBER CANC INST,DEPT CANC EPIDEMIOL & CANC CONTROL,BOSTON,MA 02115. UNIV MASSACHUSETTS,SCH MED,DEPT PSYCHIAT,WORCESTER,MA 01655. UNIV MASSACHUSETTS,MED CTR,DIV PREVENT & BEHAV MED,WORCESTER,MA. RP Hebert, JR (reprint author), UNIV MASSACHUSETTS,SCH MED,DIV PREVENT & BEHAV MED,55 LAKE AVE N,WORCESTER,MA 01655, USA. FU NHLBI NIH HHS [HL 52745, HL 44492] NR 53 TC 48 Z9 48 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD AUG PY 1997 VL 50 IS 8 BP 925 EP 937 DI 10.1016/S0895-4356(97)00098-X PG 13 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA XU619 UT WOS:A1997XU61900008 PM 9291878 ER PT J AU Noyes, R Moroz, G Davidson, JRT Liebowitz, MR Davidson, A Siegel, J Bell, J Cain, JW Curlik, SM Kent, TA Lydiard, RB Mallinger, AG Pollack, MH Rapaport, M Rasmussen, SA Hedges, D Schweizer, E Uhlenhuth, EH AF Noyes, R Moroz, G Davidson, JRT Liebowitz, MR Davidson, A Siegel, J Bell, J Cain, JW Curlik, SM Kent, TA Lydiard, RB Mallinger, AG Pollack, MH Rapaport, M Rasmussen, SA Hedges, D Schweizer, E Uhlenhuth, EH TI Moclobemide in social phobia: A controlled dose-response trial SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID PSYCHOPHARMACOLOGICAL TREATMENT; DOUBLE-BLIND; PLACEBO; PHENELZINE; CLONAZEPAM; DISORDERS; ATENOLOL; PHARMACOTHERAPY; COMORBIDITY; ALPRAZOLAM AB Although the monoamine oxidase inhibitor phenelzine has proven efficacious in social phobia, the risk of hypertensive crises has reduced its acceptability. The reversible monoamine oxidase inhibitor moclobemide has less potential for such reactions, but its efficacy in this disorder remains unproven. A double-blind, placebo-controlled study was undertaken to assess the efficacy and safety of fixed doses of moclobemide. After a 1-week placebo run-in, subjects with social phobia were randomly assigned to placebo or one of five doses (75 mg, 150 mg, 300 mg, 600 mg, or 900 mg daily) of moclobemide for 12 weeks. Although a trend toward greater efficacy of higher doses of moclobemide was observed at 8 weeks, no differences in response to various doses of the drug and placebo were observed at 12 weeks. At 12 weeks, 35% of subjects on 900 mg of moclobemide and 33% of those on placebo were at least much improved. Moclobemide was well tolerated, insomnia being the only dose-related adverse event observed with the drug. In this dose-response trial, moclobemide did not demonstrate efficacy at 12 weeks. Some other controlled studies have found moclobemide and brofaromine, another reversible monoamine oxidase inhibitor, efficacious in social phobia. Possible reasons for inconsistent findings are discussed. C1 HOFFMANN LA ROCHE,DEPT CLIN SCI,NUTLEY,NJ. DUKE UNIV,MED CTR,DEPT PSYCHIAT,DURHAM,NC 27710. COLUMBIA UNIV,COLL PHYS & SURG,DEPT PSYCHIAT,NEW YORK,NY. UNIV COLORADO,SCH MED,DENVER,CO. UNIV TEXAS,SW MED CTR,DALLAS,TX. TEMPLE UNIV,COLL MED,PHILADELPHIA,PA 19122. UNIV TEXAS,MED BRANCH,GALVESTON,TX 77550. MED UNIV S CAROLINA,CHARLESTON,SC 29425. UNIV PITTSBURGH,SCH MED,PITTSBURGH,PA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. UNIV CALIF SAN DIEGO,LA JOLLA,CA 92093. BROWN UNIV,BUTLER HOSP,PROVIDENCE,RI 02912. UNIV UTAH,SCH MED,SALT LAKE CITY,UT. UNIV PENN,SCH MED,PHILADELPHIA,PA 19104. UNIV NEW MEXICO,SCH MED,ALBUQUERQUE,NM 87131. RP Noyes, R (reprint author), UNIV IOWA,COLL MED,MED EDUC BLDG,IOWA CITY,IA 52242, USA. OI Kent, Thomas/0000-0002-9877-7584 NR 47 TC 104 Z9 105 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD AUG PY 1997 VL 17 IS 4 BP 247 EP 254 DI 10.1097/00004714-199708000-00002 PG 8 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA XL995 UT WOS:A1997XL99500002 PM 9241002 ER PT J AU Ford, JD Fisher, P Larson, L AF Ford, JD Fisher, P Larson, L TI Object relations as a predictor of treatment outcome with chronic posttraumatic stress disorder SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article ID COLLABORATIVE RESEARCH-PROGRAM; PERSONALITY-DISORDERS; VIETNAM VETERANS; DYNAMIC PSYCHOTHERAPY; CASE FORMULATION; DEPRESSION; SEVERITY; IMPACT; DISSOCIATION; RELIABILITY AB The role of object relations as a predictor of outcome was evaluated in inpatient posttraumatic stress disorder( PTSD) treatment. Cohort outcome at discharge on psychometric indices was mixed, with limited evidence of reliable or clinically significant change. Treatment was associated with an overall reduction in utilization of inpatient psychiatric and residential domiciliary services. However, moderate (vs. low) levels of object relations were predictive of reliable change outcome, independent of demographics, Axis II diagnosis, symptomatic severity, or early childhood or war zone trauma exposure. The findings suggest that consideration should be given both to the manner in which patients seeking treatment for PTSD are screened and matched with a range of treatment or rehabilitation services and to how treatment outcome is conceptualized beyond symptom reduction. Rehabilitation of chronic posttraumatic symptomatology and associated psychosocial impairment may be facilitated by assessment, treatment design, and client-treatment matching on the basis of multidimensional psychological indices. C1 DARTMOUTH COLL, SCH MED, HANOVER, NH 03755 USA. OREGON SOCIAL LEARNING CTR, EUGENE, OR 97401 USA. PORTLAND VET AFFAIRS MED CTR, PORTLAND, OR USA. RP Ford, JD (reprint author), DEPT VET AFFAIRS, EXECUT DIV, NATL CTR PTSD, VET AFFAIRS MED CTR 116D, WHITE RIVER JCT, VT 05009 USA. NR 72 TC 40 Z9 41 U1 4 U2 10 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X EI 1939-2117 J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD AUG PY 1997 VL 65 IS 4 BP 547 EP 559 PG 13 WC Psychology, Clinical SC Psychology GA XM674 UT WOS:A1997XM67400003 PM 9256555 ER PT J AU Li, GQ Salhany, KE Rook, AH Lessin, SR AF Li, GQ Salhany, KE Rook, AH Lessin, SR TI The pathogenesis of large cell transformation in cutaneous T-cell lymphoma is not associated with t(2;5)(p23;q35) chromosomal translocation SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; NON-HODGKINS-LYMPHOMA; MYCOSIS-FUNGOIDES; DISEASE; RECEPTOR; PROTEIN; GENE; CLASSIFICATION; EXPRESSION; AMERICAN AB In 20%-50% of the advanced cutaneous T-cell lymphomas (CTCL), malignant T cells undergo large cell transformation (LCT). The malignant T cells of LCT in CTCL can share morphologic and immunophenotypic similarities with CD30 (Ki-1)-positive anaplastic lar-ge cell lymphoma (ALCL), suggesting a common mechanism of pathogenesis. The t(2;5) (p23;q35) translocation, resulting in the fusion of the nucleophosmin (NPM) gene and the anaplastic lymphoma kinase (ALK) gene, is associated with primary CD30+ ALCL. To determine whether acquisition of this chromosomal translocation is involved in the pathogeneis of LCT in CTCL, we examined 12 tumor samples from 9 CTCL patients, including 8 with LCT-CTCL and one with concurrent CTCL and Hodgkin's disease, for the presence of the t(2;5) translocation. Numerous CD30+ large cells were present in 4 LCT-CTCL consistent with secondary CD30+ ALCL; CD30 was expressed by <10% of the large cells in another case and was negative in the other 3 lymphomas. Using primers spanning the NPM/ALK fusion junction, PCR amplification following reverse transcription (RT) of mRNA failed to show the products of NPM/ALK fusion in all samples tested. Thus, the t(2;5) (p23;q35) translocation does not appear to be involved in the molecular pathogenesis of LCT in CTCL, including CD30+ cases. (C) Munksgaard 1997. C1 UNIV PENN,MED CTR,DEPT DERMATOL,PHILADELPHIA,PA 19104. UNIV PENN,MED CTR,DEPT PATHOL & LAB MED,PHILADELPHIA,PA 19104. VET AFFAIRS MED CTR,PHILADELPHIA,PA. FU NCI NIH HHS [R29 CA-55017, R01 CA-58841]; NIAMS NIH HHS [T32 AR-07565] NR 35 TC 18 Z9 18 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD AUG PY 1997 VL 24 IS 7 BP 403 EP 408 DI 10.1111/j.1600-0560.1997.tb00814.x PG 6 WC Dermatology; Pathology SC Dermatology; Pathology GA XP876 UT WOS:A1997XP87600003 PM 9274957 ER PT J AU Perrin, JM AF Perrin, JM TI The implications of welfare reform for developmental and behavioral pediatrics SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Editorial Material ID CHILDREN RP Perrin, JM (reprint author), MASSACHUSETTS GEN HOSP,WACC 715,BOSTON,MA 02114, USA. NR 9 TC 1 Z9 1 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0196-206X J9 J DEV BEHAV PEDIATR JI J. Dev. Behav. Pediatr. PD AUG PY 1997 VL 18 IS 4 BP 264 EP 266 PG 3 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA XQ553 UT WOS:A1997XQ55300007 PM 9276834 ER PT J AU Jellinek, MS AF Jellinek, MS TI Cyclic vomiting SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Editorial Material C1 MASSACHUSETTS GEN HOSP,CHILD PSYCHIAT SERV,BOSTON,MA 02114. RP Jellinek, MS (reprint author), HARVARD UNIV,SCH MED,BOSTON,MA 02115, USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0196-206X J9 J DEV BEHAV PEDIATR JI J. Dev. Behav. Pediatr. PD AUG PY 1997 VL 18 IS 4 BP 269 EP 269 PG 1 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA XQ553 UT WOS:A1997XQ55300010 ER PT J AU Verma, RC Wu, HM Duerinckx, AJ Landowski, L Schiepers, C Rooholamini, SA AF Verma, RC Wu, HM Duerinckx, AJ Landowski, L Schiepers, C Rooholamini, SA TI Picture archiving and communication system-asynchronous transfer mode network in a midsized hospital SO JOURNAL OF DIGITAL IMAGING LA English DT Article; Proceedings Paper CT 14th Symposium for Computer Applications in Radiology CY JUN 21-24, 1997 CL MAYO CLIN, ROCHESTER, MN SP Soc Comp Applicat Radiol HO MAYO CLIN DE PACS; LAN; WAN; ATM AB This article describes the pathway to full implementation of a hospital information system-picture archiving and communication system-wide area network (HIS-PACS-WAN) in a 300-bed acute care hospital, and the linking of th at system to two other off-site medical centers. The PACS included direct digital capture of computed tomography (CT), magnetic resonance (MR) imaging, nuclear medicine, and ultrasonography images into an Olicon archive. Plain radiographs and fluoroscopy images were digitized manually and archived into an Olicon system. The active archive included current images on each Olicon workstation and the juke box. Long-term archiving of the images on removable optical discs, which would be loaded manually by an operator every time a request for one of these studies appeared on the operator's monitor, also was implemented. Ability to store, retrieve, and display simultaneously the physician's report of each procedure along with the images was an ultimate goal. The WAN is to be used for teleradiology and teleconferencing among the three medical centers involved in this study as well as other off-site locations. Phase I included the design and installation of the local area network (LAN) in the Department of Radiology at Olive View-UCLA Medical Center. This included the clinics and the inpatient and hospital-wide fiber-optic network and its linkage to the local telephone company. Phase II involved linkage of the Olicon workstations to imaging equipment. This implementation has been delayed significantly because of inadequate needs assessment, absence of planning for forward-compatibility to imaging equipment, and incompatibilities in DICOM conformance among vendors. Every PACS project must include an in-depth needs analysis, which should be updated yearly because of rapid turnover of technology. Although this analysis should have a heavy emphasis on clinical needs, it must incorporate the hospital-wide needs for an integrated information systems network. Integration of PACS, HIS, RIS, and a dictation/transcription system is a complex task that requires a full-time, clinically oriented project officer for successful completion. Copyright (C) 1997 by W.B. Saunders Company. C1 W LOS ANGELES VET AFFAIRS MED CTR,SERV RADIOL,LOS ANGELES,CA 90073. RP Verma, RC (reprint author), OLIVE VIEW UCLA MED CTR,DEPT RADIOL SCI,2C 176,14445 OLIVE VIEW DR,SYLMAR,CA 91342, USA. NR 0 TC 2 Z9 2 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0897-1889 J9 J DIGIT IMAGING JI J. Digit. Imaging PD AUG PY 1997 VL 10 IS 3 SU 1 BP 99 EP 102 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA XR542 UT WOS:A1997XR54200034 PM 9268851 ER PT J AU Teslow, TN AF Teslow, TN TI The laser film digitizer: Density, contrast, and resolution SO JOURNAL OF DIGITAL IMAGING LA English DT Article; Proceedings Paper CT 14th Symposium for Computer Applications in Radiology CY JUN 21-24, 1997 CL MAYO CLIN, ROCHESTER, MN SP Soc Comp Applicat Radiol HO MAYO CLIN DE quality assurance; image quality; laser film digitizer; film densitometry; PACS; laser scanner; digital radiography ID TEST PATTERN; DISPLAYS AB This work evaluates differences in density linearity, contrast, and resolution of digital images acquired from a laser film scanner. A calibrated photographic step tablet tested linearity of diffuse optical density (OD). It was digitized within center openings of a dark and light film. The 14- x 17-inch films were scanned into 1024 x 1280 picture elements of 8 bits. A photographic tapered resolution guide evaluated the scanner's detail resolution. A single characteristic curve adequately represents the rate of change of OD per pixel value, but two piecewise linear functions are better. One ranges in light OD and a second in dark OD. Contrast shows a steeper slope in a light film rather than a dark film, yet a greater difference exists between two identical digitizers. The resolution test diminishes at 1.3 line pairs per mm (LP/mm), which compares to a Nyquist limit of 1.44 LP/mm. Such density, contrast, and resolution tests yield a benchmark to assure quality operations. Copyright (C) 1997 by W.B. Saunders Company. C1 DEPT VET AFFAIRS MED CTR,RADIOTHERAPY SERV,HOUSTON,TX. RP Teslow, TN (reprint author), BAYLOR COLL MED,DEPT RADIOL,1 BAYLOR PLAZA,HOUSTON,TX 77030, USA. NR 9 TC 3 Z9 4 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0897-1889 J9 J DIGIT IMAGING JI J. Digit. Imaging PD AUG PY 1997 VL 10 IS 3 SU 1 BP 128 EP 132 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA XR542 UT WOS:A1997XR54200040 PM 9268857 ER PT J AU Protopapas, Z Siegel, EL Scanlon, M Mazan, W Reiner, BI Ghabrekidan, H Warner, J Pomerantz, SM Gitlin, JN AF Protopapas, Z Siegel, EL Scanlon, M Mazan, W Reiner, BI Ghabrekidan, H Warner, J Pomerantz, SM Gitlin, JN TI Experience with comparative picture archiving and communication system baseline data collection at four Veterans Affairs Medical Centers: Methodology, lessons learned, and suggestions for improvement SO JOURNAL OF DIGITAL IMAGING LA English DT Article; Proceedings Paper CT 14th Symposium for Computer Applications in Radiology CY JUN 21-24, 1997 CL MAYO CLIN, ROCHESTER, MN SP Soc Comp Applicat Radiol HO MAYO CLIN C1 VET AFFAIRS MED CTR,DEPT DIAGNOST RADIOL,BALTIMORE,MD 21201. UNIV MARYLAND,SCH MED,BALTIMORE,MD 21201. VET AFFAIRS MED CTR,PHILADELPHIA,PA. JOHNS HOPKINS SCH MED,BALTIMORE,MD. NR 2 TC 2 Z9 2 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0897-1889 J9 J DIGIT IMAGING JI J. Digit. Imaging PD AUG PY 1997 VL 10 IS 3 SU 1 BP 161 EP 164 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA XR542 UT WOS:A1997XR54200051 PM 9268868 ER PT J AU Yellen, G AF Yellen, G TI Single channel seeks permeant ion for brief but intimate relationship SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Editorial Material ID K+ CHANNELS; POTASSIUM CHANNEL; EXTERNAL K+; INACTIVATION; CONDUCTANCE; ACTIVATION; OCCUPANCY; CATIONS; PORE C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP Yellen, G (reprint author), HARVARD UNIV,SCH MED,DEPT NEUROBIOL,BOSTON,MA 02114, USA. OI Yellen, Gary/0000-0003-4228-7866 NR 21 TC 19 Z9 19 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD AUG PY 1997 VL 110 IS 2 BP 83 EP 85 DI 10.1085/jgp.110.2.83 PG 3 WC Physiology SC Physiology GA XP999 UT WOS:A1997XP99900001 PM 9236202 ER PT J AU Mudgal, CS Jupiter, JB AF Mudgal, CS Jupiter, JB TI Nora's lesion - Bizarre parosteal osteochondromatous proliferation SO JOURNAL OF HAND SURGERY-BRITISH AND EUROPEAN VOLUME LA English DT Article AB Isolated primary bony lesions of the digits are infrequent, A phalangeal lesion in the hand is most likely to be benign, Rarely, however, primary benign tumour-like conditions affecting the handmay radiologically mimic an osteochondroma and histologically mimic a malignancy, We describe a case of bizarre parosteal osteochondromatous proliferation (Nora's lesion, BPOP), which may do both and mislead the unsuspecting surgeon, The aim of this paper is to present our experience with this case, review existing literature and promote awareness among hand surgeons of a condition that can often be misdiagnosed. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 5 TC 3 Z9 3 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0266-7681 J9 J HAND SURG-BRIT EUR JI J. Hand Surg.-Br. Eur. Vol. PD AUG PY 1997 VL 22B IS 4 BP 469 EP 471 DI 10.1016/S0266-7681(97)80269-0 PG 3 WC Orthopedics; Surgery SC Orthopedics; Surgery GA XQ206 UT WOS:A1997XQ20600008 ER PT J AU DiSalvo, TG Koelling, TM MullerEhmsen, J Schmidt, U Semigran, MJ Dec, GW AF DiSalvo, TG Koelling, TM MullerEhmsen, J Schmidt, U Semigran, MJ Dec, GW TI Sex and left ventricular volume predict survival in heart transplant candidates with peak oxygen uptake between ten and fourteen milliliters per kilogram per minute SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Article ID SKELETAL-MUSCLE; CARDIAC TRANSPLANTATION; AMBULATORY PATIENTS; EJECTION FRACTION; EXERCISE CAPACITY; FAILURE SECONDARY; CONSUMPTION; MORTALITY; PROGNOSIS; CARDIOMYOPATHY AB Background: The purpose of this study was to identify predictors of survival in patients referred for heart transplantation evaluation who had a peak oxygen uptake of 10 to 14 ml/kg/min measured during initial cardiopulmonary exercise testing. Methods: Seventy-two patients were identified retrospectively from a database of 304 patients who underwent heart transplantation evaluations at our center from 1985 to 1995. All 72 patients underwent right-sided heart catheterization and first-pass right and left ventricular radionuclide ventriculography during cardiopulmonary exercise testing. Results: There were 14 women and 58 men in the study (mean age 52 +/- 9 years, 80% male, 79% New York Heart Association class III/IV, left ventricular ejection fraction of 0.24 +/- 0.9, and left ventricular end-diastolic volume index of 144 +/- 59 mi). During a mean follow-up of 19 +/- 23 months, two women and 32 men (47%) reached the combined end point of death (n = 20) or pretransplantation admission for inotropic or mechanical support (n 14). For the entire cohort, analysis of clinical, ventriculographic, and exercise parameters identified female sex, younger age, and age/ sex-adjusted peak oxygen uptake as independent predictors of survival. In men only, age, left ventricular end-diastolic volume index, and age/sex adjusted peak oxygen uptake were independent predictors of survival. Conclusions: Among patients referred for heart transplantation evaluation with a peak oxygen uptake between 10 to 14 ml/kg/min, younger age, female sex, and higher age/sex-adjusted peak oxygen uptake predict longer survival to the combined end point of death or pretransplantation admission for inotropic or mechanical support. These measures may be useful in additional risk stratification of such patients. RP DiSalvo, TG (reprint author), MASSACHUSETTS GEN HOSP,HEART FAILURE & CARDIAC TRANSPLANTAT CTR,BIGELOW 628,32 FRUIT ST,BOSTON,MA 02114, USA. NR 26 TC 2 Z9 2 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD AUG PY 1997 VL 16 IS 8 BP 869 EP 877 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA XU621 UT WOS:A1997XU62100010 PM 9286779 ER PT J AU Hershow, RC Riester, KA Lew, J Quinn, TC Mofenson, LM Davenny, K Landesman, S Cotton, D Hanson, IC Hillyer, GV Tang, HB Thomas, DL AF Hershow, RC Riester, KA Lew, J Quinn, TC Mofenson, LM Davenny, K Landesman, S Cotton, D Hanson, IC Hillyer, GV Tang, HB Thomas, DL TI Increased vertical transmission of human immunodeficiency virus from hepatitis C virus-coinfected mothers SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT XIth International Conference on AIDS CY JUL 07-13, 1996 CL VANCOUVER, CANADA ID MATERNAL-INFANT TRANSMISSION; INTRAVENOUS-DRUG-USERS; NON-B-HEPATITIS; NON-A; DISEASE PROGRESSION; INFECTION; HIV; RISK; ASSOCIATION; ANTIBODIES AB To determine if hepatitis C virus (HCV) infection affects vertical transmission of human immunodeficiency virus (HIV), 487 HIV-infected pregnant women in the prospective, multicenter, Women and Infants Transmission Study had HCV antibody (anti-HCV by second-generation ELISA) and HCV RNA (by quantitative polymerase chain reaction) measured in peripartum maternal plasma; 161 (33%) were anti-HCV-positive, HIV vertical transmission occurred from 42 HCV-infected mothers (26.1%) versus 53 HCV-uninfected mothers (16.3%; odds radio [OR], 1.82; P = .01). In a logistic regression model that included maternal drug use, a potential confounder, HCV infection was marginally associated with perinatal HIV transmission (OR, 1.64; P = .05), whereas drug use was not, Women who transmitted HIV had higher levels of HCV RNA (median, 721,254 copies/mL) than those who did not (337,561 copies/mL; P = .01), Maternal HCV infection is associated with increased HIV vertical transmission. Further studies are needed to ascertain if HCV directly affects perinatal HIV transmission or is a marker for another factor, such as maternal drug use. C1 UNIV ILLINOIS,COLL MED,CHICAGO,IL 60612. NEW ENGLAND RES INST,WATERTOWN,MA. MASSACHUSETTS GEN HOSP,DEPT MED,INFECT DIS UNIT,BOSTON,MA 02114. NICHHD,PEDIAT ADOLESCENT & MATERNAL AIDS BRANCH,NIH,ROCKVILLE,MD. NIDA,NIH,ROCKVILLE,MD. JOHNS HOPKINS UNIV,SCH MED,DIV INFECT DIS,BALTIMORE,MD 21205. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. SUNY HLTH SCI CTR,DIV INFECT DIS,BROOKLYN,NY 11203. COLUMBIA UNIV COLL PHYS & SURG,DEPT PEDIAT,NEW YORK,NY 10032. BAYLOR COLL MED,DEPT PEDIAT,HOUSTON,TX 77030. UNIV PUERTO RICO,SAN JUAN,PR 00936. RP Hershow, RC (reprint author), UNIV ILLINOIS,SCH PUBL HLTH,ROOM 504,2121 W TAYLOR ST,CHICAGO,IL 60612, USA. OI Mofenson, Lynne/0000-0002-2818-9808 FU NIAID NIH HHS [AI-34842, AI-34840, AI-34856] NR 44 TC 60 Z9 61 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD AUG PY 1997 VL 176 IS 2 BP 414 EP 420 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA XW859 UT WOS:A1997XW85900013 PM 9237706 ER PT J AU Oh, MD Merrill, DP Sutton, L Hirsch, MS AF Oh, MD Merrill, DP Sutton, L Hirsch, MS TI Sequential versus simultaneous combination antiretroviral regimens for the treatment of human immunodeficiency virus type 1 infection in vitro SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT XIth International Conference on AIDS CY JUL 07-13, 1996 CL VANCOUVER, CANADA ID RECOMBINANT INTERFERON-ALPHA; SIMULTANEOUS ZIDOVUDINE; DIDANOSINE THERAPY; REPLICATION; INVITRO; CD4 AB Two-, three-, and four-drug antiretroviral combinations in either simultaneous or sequential regimens were evaluated for their ability to suppress human immunodeficiency virus (HIV) type 1 replication in vitro. Zidovudine, lamivudine, saquinavir, and nevirapine were used at IC(90)s, IC(99)s, or IC(greater than or equal to 99)s in a CD4-positive human lymphoblastoid cell line (H9 cells) acutely infected with HIV-1. In sequential regimens, drugs were added at weekly intervals. In simultaneous regimens, all drugs were added on day 0. Increasing the number of drugs in a combination regimen both increased the degree of viral inhibition and delayed the time of breakthrough viral replication. Simultaneous regimens provided more profound and earlier viral inhibition than did sequential regimens. However, sequential addition provided relatively more durable viral inhibition than did simultaneous regimens when drug concentrations were low. The relative effectiveness of different HIV-1 therapeutic strategies depends on both the numbers and concentrations of the drugs used. C1 HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA 02114. FU NCI NIH HHS [CA-12464] NR 15 TC 5 Z9 5 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD AUG PY 1997 VL 176 IS 2 BP 510 EP 514 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA XW859 UT WOS:A1997XW85900027 PM 9237720 ER PT J AU Wolfsdorf, JI Laffel, LMB Crigler, JF AF Wolfsdorf, JI Laffel, LMB Crigler, JF TI Metabolic control and renal dysfunction in type I glycogen storage disease SO JOURNAL OF INHERITED METABOLIC DISEASE LA English DT Article ID URINARY ALBUMIN EXCRETION; UNCOOKED CORNSTARCH; CHILDREN; GLUCOSE; ABNORMALITIES; DEXTROSE; THERAPY; GROWTH AB This study was undertaken to determine the effect on renal function of continuous glucose therapy from early childhood. Twenty-three subjects, median age 13.9 years, range 5.9-26.9 years, with type I glycol:en storage disease (GSDI) treated with continuous glucose therapy from a median age of 1.3 years, range 0.1-12.9 years, had 24h monitoring of metabolites and glucoregulatory hormones on their home feeding regimen to assess metabolic control at approximately yearly intervals for a median duration of 8 years. During the most recent evaluation, 24h urinary albumin excretion rate (AER), kidney size, and creatinine clearance (Ccr) were measured. CCr was unrelated to age and was increased (>2.33 ml/s per 1.73 m(2)) in 10/23 (43%). Mean kidney length exceeded 2SD in 16/23 (70%). AER was normal in all five subjects <10 years and was increased (>10 mu g/min) in 8/23 (35%), all >10 years of age. AER was significantly greater in subject of similar age who started continuous glucose therapy later in childhood and was significantly higher in subjects with lower mean 24h plasma glucose concentrations and higher mean 24h blood lactate concentrations, both at the time of assessment of renal function and over the preceding 5 years. GSDI subjects with persistently elevated concentrations of blood lactate, serum lipids and uric acid are at increased risk of nephropathy. Optimal dietary therapy instituted early in life may delay, prevent, or slow the progression of renal disease. C1 HARVARD UNIV,SCH MED,DEPT PEDIAT,JOSLIN DIABET CTR,BOSTON,MA 02115. RP Wolfsdorf, JI (reprint author), CHILDRENS HOSP,DEPT MED,DIV ENDOCRINOL,300 LONGWOOD AVE,BOSTON,MA 02115, USA. FU NCRR NIH HHS [MO1RR02172] NR 36 TC 25 Z9 26 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0141-8955 J9 J INHERIT METAB DIS JI J. Inherit. Metab. Dis. PD AUG PY 1997 VL 20 IS 4 BP 559 EP 568 DI 10.1023/A:1005346824368 PG 10 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA XP410 UT WOS:A1997XP41000012 PM 9266393 ER PT J AU Torii, H Luster, AD Ozawa, H Granstein, RD AF Torii, H Luster, AD Ozawa, H Granstein, RD TI Production of eotaxin by murine Langerhans cells. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 CORNELL UNIV MED COLL,DEPT DERMATOL,NEW YORK,NY. MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 1997 VL 109 IS 2 BP 77 EP 77 PG 1 WC Dermatology SC Dermatology GA XM195 UT WOS:A1997XM19500098 ER PT J AU Bodennec, J Brichon, G Koul, O ElBabili, M Zwingelstein, G AF Bodennec, J Brichon, G Koul, O ElBabili, M Zwingelstein, G TI A two-dimensional thin-layer chromatography procedure for simultaneous separation of ceramide and diacylglycerol species SO JOURNAL OF LIPID RESEARCH LA English DT Article DE sea bass gills; fatty alcohols; phospholipids; cholesterol; triacylglycerols; signal transduction ID SPHINGOMYELIN METABOLISM; CELLS; DIGLYCERIDE; APOPTOSIS; SIGNAL; LIPIDS; GILLS AB We have developed a novel, simple, and rapid, two-dimensional thin-layer chromatography method to separate 1,2-, 1,3-diacylglycerols and ceramides containing alpha-hydroxy and normal fatty acids from other neutral lipids on one 10 x 10 cm precoated silica gel plate. The three solvent systems used in succession leave the phospholipids at the origin and separate neutral lipids of interest into component species. We have applied this method to incorporation of 9,10[H-3]myristic acid into lipids of gills from sea bass and obtained results that are similar and comparable to those obtained by described methods. C1 UNIV LYON 1,INST MICHEL PACHA,F-83500 LA SEYNE SUR MER,FRANCE. EUNICE KENNEDY SHRIVER CTR MENTAL RETARDAT INC,WALTHAM,MA 02254. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA 02215. NR 20 TC 12 Z9 14 U1 0 U2 1 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 AUG PY 1997 VL 38 IS 8 BP 1702 EP 1706 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XU911 UT WOS:A1997XU91100020 PM 9300792 ER PT J AU Rosowsky, A Fu, HN Pai, N Mellors, J Richman, DD Hostetler, KY AF Rosowsky, A Fu, HN Pai, N Mellors, J Richman, DD Hostetler, KY TI Synthesis and in vitro activity of long-chain 5'-O-[(alkoxycarbonyl)phosphinyl]-3'-azido-3'-deoxythymidines against wild-type and AZT- and foscarnet-resistant strains of HIV-1 SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; REVERSE-TRANSCRIPTASE; PHOSPHONOFORMATE FOSCARNET; CYTOMEGALOVIRUS RETINITIS; ANTIVIRAL ACTIVITY; TRISODIUM PHOSPHONOFORMATE; CONTROLLED TRIAL; HERPES-SIMPLEX; AIDS PATIENTS; REPLICATION AB Lipophilic esters of 3'-azido-3'-deoxy-5'-O-(carboxyphosphinyl)thymidine (PFA-AZT) were synthesized and tested for antiretroviral activity in CD4(+) HT4-6C cells infected with either wild-type HIV-1(LAI), a PFA-resistant strain encoding a single-point mutation in reverse transcriptase (E89K), or an AZT-resistant clinical isolate (A018-post). Arbuzov condensation of 1-octadecyl, 1-eicosanyl, and 1-docosanyl chloroformate with trimethyl phosphite yielded the corresponding dimethyl long-chain alkyl triesters of PFA. Selective removal of one methyl group from the triesters with sodium iodide yielded monosodium salts, whereas treatment with bromotrimethylsilane cleaved both methyl groups while leaving the long-chain alkyl group intact. Neutralization of the resulting [(alkyloxy)carbonyl]phosphonic acids with 2 equiv of sodium methoxide afforded disodium salts of the phosphonic acid moiety. Similar chemistry was used to obtain the mono- and disodium salts of the cholesterol ester of PFA. Reaction of the triesters with phosphorous pentachloride, followed by coupling with AZT and O-demethylation with sodium iodide, afforded 3'-azido-3'-deoxy-5'-O-[[(1-octadecyloxy)carbonyl]phosphinyl]thymidine (9a), 3'-azido-3'-deoxy-5'-O-[[(1-eicosanyloxy)carbonyl]phosphinyl]thymidine (9b), 3'-azido-3'-deoxy-5'-O-[[(1-docosanyloxy)carbonyl]phosphinyl]thymidine (9c), and 3'-azido-3'-deoxy-5'-O-[[(3 beta-cholest-5-enyloxy)carbonyl]phosphiny]thymidine (9d). Concentrations of 9a-d found to inhibit replication of wild-type HTV-1(LAI) by 50% (EC50 values) as measured in a plaque reduction assay were in the 0.1-0.3 mu M range as compared with 0.013 mu M for AZT and 133 mu M for PFA. The concentration at which toxicity was observed in 50% of the host cells (TC50 values) as measured by a visual grading scale of cellular morphology was 10 mu M for 9a and 9d, 32 mu M for 9b, and 320 mu M for 9c. Thus, the TC50/EC50 ratio or selectivity index (SI) was 100 for 9a, 230 for 9b, and 1000 for 9c but only 33 for 9d, suggesting that the straight-chained fatty alcohol esters were more therapeutically selective. Similar TC50 and SI values were obtained for rapidly dividing CEM lymphoblasts as for HT4-6C cells. In assays against E89K, 9a-c had mean EC50 values of 0.13, 0.009, and 0.17 mu M, whereas the EC50 Of PFB was > 1000 mu M and that of AZT was 0.009 mu M; thus, E89K was highly resistant to PFA but not cross-resistant to either AZT or the lipophilic PFA-AZT conjugates. In viral replication assays against the A018C-post isolate, the mean EC50 values of 9a-c were 0.30, 0.53, and 0.77 mu M as compared with 2.9 mu M for AZT and 65 mu M for PFA; thus, the virus recovered from a patient pretreated with AZT was not cross-resistant to either PFA or 9a-c. A notable feature of these results was that, in addition to being >1000-fold more potent than PFA against the PFA-resistant mutant, the lipophilic PFA-AZT conjugates were more potent than PFA, as well as AZT, against AZT-resistant HIV-1. C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOL PHARMACOL,BOSTON,MA 02115. UNIV PITTSBURGH,DEPT MED,PITTSBURGH,PA 15213. VET AFFAIRS MED CTR,PITTSBURGH,PA 15213. UNIV CALIF SAN DIEGO,DEPT MED,LA JOLLA,CA 92093. UNIV CALIF SAN DIEGO,DEPT PATHOL,LA JOLLA,CA 92093. VET AFFAIRS MED CTR,SAN DIEGO,CA 92121. RP Rosowsky, A (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. FU NIAID NIH HHS [P01-AI 27670, R01-AI 25715, R01-AI 29164] NR 41 TC 17 Z9 17 U1 1 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD AUG 1 PY 1997 VL 40 IS 16 BP 2482 EP 2490 DI 10.1021/jm970172f PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA XP087 UT WOS:A1997XP08700008 PM 9258355 ER PT J AU Wilens, TE Biederman, J Mick, E Faraone, SV Spencer, T AF Wilens, TE Biederman, J Mick, E Faraone, SV Spencer, T TI Attention deficit hyperactivity disorder (ADHD) is associated with early onset substance use disorders SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article ID PSYCHIATRIC COMORBIDITY; ALCOHOLISM ONSET; RISK-FACTORS; ADULTS; ABUSE; BOYS; AGE; PSYCHOPATHOLOGY; PATTERNS; CHILDREN AB We evaluated the association between attention deficit hyperactivity disorder (ADHD) and the age of onset of psychoactive substance use disorders (PSUD) in adults with ADHD. We hypothesized that ADHD and psychiatric comorbidity would be risk factors for early onset PSUD. We compared 120 referred adults having a clinical diagnosis of childhood-onset ADHD with 268 non-ADHD adults. All diagnoses were obtained using DSM-III-R based structured psychiatric interviews. We used group comparisons of age at onset and Cox proportional hazard models to examine the development of PSUD over time. ADHD was associated with earlier onset of PSUD independently of psychiatric comorbidity. Conduct and juvenile bipolar disorders conferred a significantly increased risk for early onset PSUD independently of ADHD. Psychiatric disorders commonly emerged before the onset of PSUD in both groups. Persistent ADHD with and without psychiatric comorbidity was associated with adolescent onset PSUD. In addition, comorbidity with conduct and juvenile bipolar disorders predicted very early onset PSUD in both ADHD and non-ADHD individuals. These findings confirm and extend previous findings documenting important associations between PSUD and psychiatric comorbidity including persistent ADHD. C1 HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. RP Wilens, TE (reprint author), MASSACHUSETTS GEN HOSP,PEDIAT PSYCHOPHARMACOL CLIN,ACC 725,BOSTON,MA 02114, USA. OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [R01 MH41314-02, K20 MH01175-01] NR 43 TC 183 Z9 184 U1 2 U2 5 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD AUG PY 1997 VL 185 IS 8 BP 475 EP 482 DI 10.1097/00005053-199708000-00001 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA XR353 UT WOS:A1997XR35300001 PM 9284860 ER PT J AU Nitsch, RM Deng, A Wurtman, RJ Growdon, JH AF Nitsch, RM Deng, A Wurtman, RJ Growdon, JH TI Metabotropic glutamate receptor subtype mGluR1 alpha stimulates the secretion of the amyloid beta-protein precursor ectodomain SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE amyloid; Alzheimer's disease; metabotropic glutamate receptor; alpha-secretase processing ID LONG-TERM POTENTIATION; ALZHEIMERS-DISEASE; KINASE-C; SYNAPTIC TRANSMISSION; RAT-BRAIN; HIPPOCAMPAL SLICES; MESSENGER-RNA; ACTIVATION; EXPRESSION; PEPTIDE AB To examine the effects of glutamatergic neurotransmission on amyloid processing, we stably expressed the metabotropic glutamate receptor subtype la (mGluR1 alpha) in HEK 293 cells. Both glutamate and the selective metabotropic agonist 1-amino-1,3-cyclopentanedicarboxylic acid (ACPD) rapidly increased phosphatidylinositol (PI) turnover four- to fivefold compared with control cells that were transfected with the expression vector alone. Increased PI turnover was effectively blocked by the metabotropic antagonist alpha-methyl-4-carbophenylglycine (MCPG), indicating that heterologous expression of mGluR1 alpha resulted in efficient coupling of the receptors to G protein and phospholipase C activation. Stimulation of mGluR1 alpha with glutamate, quisqualate, or ACPD rapidly increased secretion of the APP ectodomain (APPs); these effects were blocked by MCPG. The metabotropic receptors were coupled to APP processing by protein kinases and by phospholipase A(2) (PLA(2)), and melittin, a peptide that stimulates PLA(2), potently increased APPs secretion. These data indicate that mGluR1 alpha can be involved in the regulation of APP processing. Together with previous findings that muscarinic and serotonergic receptor subtypes can increase the secretion of the APP ectodomain, these observations support the concept that proteolytic processing of APP is under the control of several major neurotransmitters. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. MIT,DEPT BRAIN & COGNIT SCI,CAMBRIDGE,MA 02139. RP Nitsch, RM (reprint author), UNIV HAMBURG,CTR MOL NEUROBIOL,MARTINISTR 52,D-20246 HAMBURG,GERMANY. NR 56 TC 68 Z9 71 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 1997 VL 69 IS 2 BP 704 EP 712 PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA XL154 UT WOS:A1997XL15400029 PM 9231730 ER PT J AU Hsu, DW Louis, DN Efird, JT HedleyWhyte, ET AF Hsu, DW Louis, DN Efird, JT HedleyWhyte, ET TI Use of MIB-1 (Ki-67) immunoreactivity in differentiating grade II and grade III gliomas SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE astrocytoma; glioma; immunocytochemistry; Ki-67; MIB-1; proliferative index ID MONOCLONAL-ANTIBODY KI-67; HUMAN-BRAIN TUMORS; PROLIFERATING CELLS; NUCLEAR ANTIGEN; PROGNOSTIC-SIGNIFICANCE; GROWTH FRACTION; LABELING INDEX; ASTROCYTOMAS; IDENTIFICATION; SURVIVAL AB The grading of glial tumors has traditionally relied on histological assessment, but the distinction between grade II and grade III gliomas is still a subject of debate. We examined the value of the monoclonal antibody MLB-1 (Ki-67) labeling index (LI) in the differentiation between grade II and grade III gliomas by either the 1993 WHO grading scheme or the St. Anne-Mayo grading scale. The MIB-1 LI in the most densely labeled areas from 80 diffuse cerebral hemispheric gliomas was determined. The tumors included 16 grade II, 31 grade III and 33 grade IV gliomas by the WHO scale. The mean LIs (%) were 0.88 +/- 0.29 for grade II, 8.75 +/- 1.71 for grade III, and 9.12 +/- 1.55 for grade IV gliomas. Analysis of variance indicated a significant difference in mean LIs between grades II and III and grades II and IV (p less than or equal to 0.0001), but not between grades III and N. Seven tumors were classified differently by the 2 systems (grade III by WHO, but grade 2 by St. Anne-Mayo), and all had MIB-1 LI over 3%. Univariate analysis showed that MIB-1 LI with a cut-off point at 1.5% was a significant prognostic factor (p less than or equal to 0.0005). High tumor grade (WHO, p less than or equal to 0.0002; St. Anne-Mayo, p less than or equal to 0.0006) and patient age >50 (p less than or equal to 0.0001) were also significant factors for shorter survival. Using Cox Regression Multivariate Analysis, MIB-1 LI>1.5% was a significant independent predictor of shorter disease survival when paired with tumor grade (p less than or equal to 0.032), patient age (p less than or equal to 0.0065), or gender (p less than or equal to 0.0007). We conclude that the MLB-1 immunoreactivity is useful in distinguishing grade II from grade III gliomas, and maybe more sensitive in assigning aggressive gliomas to grade III than the St. Anne-Mayo grading system. C1 MASSACHUSETTS GEN HOSP,NEUROSURG SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RP Hsu, DW (reprint author), MASSACHUSETTS GEN HOSP,DEPT PATHOL,DIV NEUROPATHOL,WARREN 3,BOSTON,MA 02114, USA. NR 33 TC 79 Z9 81 U1 0 U2 1 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD AUG PY 1997 VL 56 IS 8 BP 857 EP 865 DI 10.1097/00005072-199708000-00003 PG 9 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA XQ552 UT WOS:A1997XQ55200003 PM 9258255 ER PT J AU Naisbitt, S Kim, E Weinberg, RJ Rao, A Yang, FC Craig, AM Sheng, M AF Naisbitt, S Kim, E Weinberg, RJ Rao, A Yang, FC Craig, AM Sheng, M TI Characterization of guanylate kinase-associated protein, a postsynaptic density protein at excitatory synapses that interacts directly with postsynaptic density-95 synapse-associated protein 90 SO JOURNAL OF NEUROSCIENCE LA English DT Article DE postsynaptic density; excitatory synapse; PSD-95/SAP90; immunogold electron microscopy; glutamate receptor; guanylate kinase domain; MAGUK ID TUMOR-SUPPRESSOR GENE; NMDA RECEPTOR SUBUNITS; PSD-95 FAMILY; HUMAN HOMOLOG; DROSOPHILA; GLUTAMATE; INTERNEURONS; NEOCORTEX; SAP90; DLG AB The structure of central synapses is poorly understood at the molecular level. A recent advance came with the identification of the postsynaptic density-95 (PSD-95)/synapse-associated protein 90 family of proteins as important mediators of the synaptic clustering of certain classes of ion channels. By yeast two-hybrid screening, a novel protein termed guanylate kinase-associated protein (GKAP) has been isolated that binds to the GK-like domain of PSD-95 (Kim et al., 1997). Here we present a detailed characterization of GKAP expression in the rat brain and report the cloning of a novel GKAP splice variant. By Northern blot, GKAP mRNAs (4, 6.5, and 8 kB) are expressed predominantly in the rat brain. By in situ hybridization, GKAP is expressed widely in neurons of cortex and hippocampus and in the Purkinje and granule cells of the cerebellum. On brain immunoblots, two prominent bands of 95 and 130 kDa are detected that correspond to products of short and long N-terminal splice variants of GKAP. Two independent GKAP antibodies label somatodendritic puncta in neocortical and hippocampal neurons in a pattern consistent with synaptic elements. Immunogold electron microscopy reveals GKAP to be predominantly postsynaptic and present at asymmetric synapses and in dendritic spines. The distribution of GKAP immunogold particles is uniform in the lateral plane of the PSD but peaks in the perpendicular axis similar to-20 nm from the postsynaptic membrane. In cultured hippocampal neurons GKAP immunoreactive puncta colocalize with the AMPA receptor subunit Glu receptor 1 but not with the GABA(A) receptor subunits beta 2 and beta 3. Thus GKAP is a widely expressed neuronal protein localized specifically in the PSD of glutamatergic synapses, consistent with its direct interaction with PSD-95 family proteins. C1 MASSACHUSETTS GEN HOSP,HOWARD HUGHES MED INST WELLMAN 423,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT NEUROBIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. PUSAN NATL UNIV,DEPT PHARMACOL,KUMJEONG KU,PUSAN 609735,SOUTH KOREA. UNIV N CAROLINA,DEPT CELL BIOL & ANAT,CHAPEL HILL,NC 27599. UNIV ILLINOIS,DEPT CELL & STRUCT BIOL,URBANA,IL 61801. RI Kim, Eunjoon/C-1566-2011; Craig, Ann Marie/M-2054-2014 FU NINDS NIH HHS [NS35050, NS29879] NR 28 TC 92 Z9 93 U1 0 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD AUG 1 PY 1997 VL 17 IS 15 BP 5687 EP 5696 PG 10 WC Neurosciences SC Neurosciences & Neurology GA XU918 UT WOS:A1997XU91800004 PM 9221768 ER PT J AU Fleming, JT Squire, MD Barnes, TM Tornoe, C Matsuda, K Ahnn, J Fire, A Sulston, JE Barnard, EA Sattelle, DB Lewis, JA AF Fleming, JT Squire, MD Barnes, TM Tornoe, C Matsuda, K Ahnn, J Fire, A Sulston, JE Barnard, EA Sattelle, DB Lewis, JA TI Caenorhabditis elegans levamisole resistance genes lev-1, unc-29, and unc-38 encode functional nicotinic acetylcholine receptor subunits SO JOURNAL OF NEUROSCIENCE LA English DT Article DE acetylcholine receptor; levamisole resistance genes; receptor mutations; Caenorhabditis elegans; evolution; nematode, unc-29; unc-38; lev-1; transmembrane domain mutation; Xenopus oocyte expression; GFP; confocal microscopy; receptor localization ID GATED ION CHANNELS; MULTIPLE SEQUENCE ALIGNMENT; GREEN FLUORESCENT PROTEIN; NEMATODE ASCARIS-SUUM; C-ELEGANS; ALPHA-SUBUNIT; DELTA-SUBUNIT; CHOLINERGIC RECEPTOR; MOLECULAR-CLONING; BINDING-SITE AB We show that three of the eleven genes of the nematode Caenorhabditis elegans that mediate resistance to the nematocide levamisole and to other cholinergic agonists encode nicotinic acetylcholine receptor (nAChR) subunits. unc-38 encodes an alpha subunit while lev-1 and unc-29 encode non-alpha subunits. The nematode nAChR subunits show conservation of many mammalian nAChR sequence features, implying an ancient evolutionary origin of nAChR proteins. Expression in Xenopus oocytes of combinations of these subunits that include the unc-38 alpha subunit results in levamisole-induced currents that are suppressed by the nAChR antagonists mecamylamine, neosurugatoxin, and d-tubocurarine but not alpha-bungarotoxin. The mutant phenotypes reveal that unc-38 and unc-29 subunits are necessary for nAChR function, whereas the lev-1 subunit is not. An UNC-29-GFP fusion shows that UNC-29 is expressed in body and head muscles. Two dominant mutations of lev-1 result in a single amino acid substitution or addition in or near transmembrane domain 2, a, region important to ion channel conductance and desensitization. The identification of viable nAChR mutants in C. elegans provides an advantageous system in which receptor expression and synaptic targeting can be manipulated and studied in vivo. C1 MRC CTR,MOL BIOL LAB,CAMBRIDGE CB2 2QH,ENGLAND. MRC CTR,MOL NEUROBIOL UNIT,CAMBRIDGE CB2 2QH,ENGLAND. UNIV CAMBRIDGE,DEPT ZOOL,BABRAHAM INST,MOL SIGNALLING LAB,CAMBRIDGE CB2 3EJ,ENGLAND. CARNEGIE INST WASHINGTON,DEPT EMBRYOL,BALTIMORE,MD 21210. UNIV TEXAS,OCCUPAT & SAFETY PROGRAMS,DIV LIFE SCI,SAN ANTONIO,TX 78249. MASSACHUSETTS GEN HOSP,DEPT PEDIAT HEMATOL ONCOL,BOSTON,MA 02114. FU NIGMS NIH HHS [R01 GM037706, GM 08194, GM 37706] NR 95 TC 185 Z9 199 U1 1 U2 3 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD AUG 1 PY 1997 VL 17 IS 15 BP 5843 EP 5857 PG 15 WC Neurosciences SC Neurosciences & Neurology GA XU918 UT WOS:A1997XU91800018 PM 9221782 ER PT J AU Carroll, RS Black, PM Zhang, JP Kirsch, M Percec, I Lau, N Guha, A AF Carroll, RS Black, PM Zhang, JP Kirsch, M Percec, I Lau, N Guha, A TI Expression and activation of epidermal growth factor receptors in meningiomas SO JOURNAL OF NEUROSURGERY LA English DT Article DE meningioma; epidermal growth factor receptor; Northern blot analysis; immunohistochemistry; Western blot analysis ID PROTEIN-TYROSINE KINASES; HUMAN-BRAIN-TUMORS; SIGNAL-TRANSDUCTION; SHC PROTEINS; EGF-RECEPTOR; FACTOR-ALPHA; PTB DOMAIN; FACTOR-I; CELLS; RAS AB Previous studies have demonstrated expression of epidermal growth factor receptors (EGFRs) in human cerebral meningiomas. However, the activation status of the EGFRs and whether they activate cytoplasmic mitogenic signaling pathways are not known. In this study, using Northern blot analysis and the polymerase chain reaction, the authors report expression of epidermal growth factor, transforming growth factor-alpha, and EGFR messenger RNA in 27 meningioma specimens. Using Western blot and immunohistochemical analyses of the meningioma samples, the authors demonstrate that the EGFRs expressed by these meningiomas are activated. These activated EGFRs interact with and phosphorylate Shc, an SH2 domain-containing adapter protein that is important in transducing mitogenic signals from EGFRs to the nucleus via activation of the Ras signaling pathway. These results support the concept that activation of EGFRs in human meningiomas by autocrine/paracrine stimulation may contribute to their proliferation. C1 BRIGHAM & WOMENS HOSP,BRAIN TUMOR RES CTR,BOSTON,MA 02115. DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. MT SINAI HOSP,SAMUEL LUNENFELD RES INST,PROGRAMME MOL BIOL & CANC,TORONTO,ON M5G 1X5,CANADA. UNIV TORONTO,TORONTO HOSP,DIV NEUROSURG & SURG ONCOL,TORONTO,ON,CANADA. RP Carroll, RS (reprint author), BRIGHAM & WOMENS HOSP,NEUROSURG LABS,221 LONGWOOD AVE,ROOM 121,BOSTON,MA 02115, USA. RI Kirsch, Matthias/F-2824-2014 NR 70 TC 57 Z9 62 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD AUG PY 1997 VL 87 IS 2 BP 315 EP 323 DI 10.3171/jns.1997.87.2.0315 PG 9 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA XN706 UT WOS:A1997XN70600024 PM 9254099 ER PT J AU Scremin, OU Li, MG Jenden, DJ AF Scremin, OU Li, MG Jenden, DJ TI Cholinergic modulation of cerebral cortical blood flow changes induced by trauma SO JOURNAL OF NEUROTRAUMA LA English DT Article; Proceedings Paper CT 13th Annual Houston Conference on Biomedical Engineering Research CY FEB 09, 1996 CL HOUSTON, TX DE cerebrovascular circulation; brain injuries; acetylcholine; physostigmine; scopolamine ID COMPRESSION CONTUSION TRAUMA; PERCUSSION BRAIN INJURY; SEVERE HEAD-INJURY; CHOLINESTERASE INHIBITOR; INTRACRANIAL-PRESSURE; WORKING MEMORY; AGED RATS; LONG-TERM; RESPONSES; ACETYLCHOLINE AB These experiments tested the role of cholinergic mechanisms in the changes of cerebral cortical blood flow (CBF) induced by brain trauma. CBF was measured with Iodo-C-14-antipyrine autoradiography, in 128 cerebral cortex regions of both hemispheres, distributed in eight coronal slices. The effects of a 6.3-mm diameter craniotomy over the left motor-sensory cortex with no weight drop, and of trauma (drop weight of 20 g from 30 cm height on left motor-sensory cortex through a 6.3 mm circular craniotomy) on CBF were studied at 2 and 24 h after the interventions. A group of control animals that received no intervention was also set up. Animals were treated with the cholinesterase inhibitor physostigmine salicylate (3.3 mu g/kg/min i.v. infusion started 60 min before CBF measurements), the cholinergic blocker scopolamine hydrobromide (1 mg/kg i.v. pulse, 18 min before CBF measurements), or with the drugs vehicle (saline). A focus of decreased CBF at the site of impact was observed 2 h after trauma, extending caudally as far as the occipital cortex. CBF on the contralateral cerebral cortex was also decreased. Both phenomena reversed partially at 24 h. This spontaneous recovery of CBF was blocked by scopolamine. Physostigmine reversed the decrease in CBF of the traumatized cortex, partially around the contused area and completely in more distant regions. The cerebral cortex contralateral to the trauma showed significantly higher CBF 24 h after trauma when compared to intact controls or craniotomy that peaked at the area symmetrical to the center of trauma. This phenomenon was also enhanced by physostigmine and completely blocked by scopolamine. These results suggest a prominent role of cholinergic mechanisms in the vascular adjustments that accompany cerebral trauma. C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT PHYSIOL,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT PHARMACOL & BIOMATH,LOS ANGELES,CA. RP Scremin, OU (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,RES DEPT,BLDG 115,ROOM 317,11301 WILSHIRE BLVD,LOS ANGELES,CA 90073, USA. NR 62 TC 17 Z9 17 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD AUG PY 1997 VL 14 IS 8 BP 573 EP 586 DI 10.1089/neu.1997.14.573 PG 14 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA XU894 UT WOS:A1997XU89400008 PM 9300567 ER PT J AU Babich, JW Tompkins, RG Graham, W Barrow, SA Fischman, AJ AF Babich, JW Tompkins, RG Graham, W Barrow, SA Fischman, AJ TI Localization of radiolabeled chemotactic peptide at focal sites of Escherichia coli infection in rabbits: Evidence for a receptor-specific mechanism SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE agonist; antagonists; peptide; chemotactic infection ID ACUTE BACTERIAL-INFECTION; CHEMOATTRACTANT RECEPTORS; POLYCLONAL IGG; LEUKOCYTES; ANALOGS; BIODISTRIBUTION; METABOLISM; RATS AB The infection imaging properties of a high-affinity Tc-99m-labeled chemotactic peptide receptor agonist (N-formyl-methionyl-leucylphenylalanine-lysine; N-For-MLFK) were compared with a low-affinity agonist (N-Acetyl-MLFK; N-Ac-MLFK), a moderate-affinity antagonist (N-isobutyloxycarbonyl-MLFK; N-iBoc-MLFK) and nonspecific inflammation imaging agents, Methods: All peptides were prepared by solid-phase methods and purified by high-performance liquid chromatography, The products were assayed in vitro for N-formyl-methionyl-leucyl-phenylalanine receptor binding and superoxide production, Three types of studies were performed in rabbits with Escherichia coli infection: (Study A) Four groups of six animals were coinjected with Tc-99m-N-For-MLFK-hydrazinonicotinamide (N-For-MLFK-HYNIC) plus In-111-immunoglobulin G, In-111-red blood cells or In-111-diethylene triamine pentaacetic acid. (Study B) Three groups of six rabbits were coinjected with In-111-leukocytes plus Tc-99m-N-For-MLFK-HYNIC, Tc-99m-N-Ac-MLFK-HYNIC or Tc-99m-N-iBoc-MLFK-HYNIC. (Study C) Two groups of six rabbits were injected with Tc-99m-N-For-MLFK-HYNIC and In-111-leukocytes with and without an excess of antagonist. in ail three studies, the radiopharmaceuticals were injected 24 hr after infection and dual photon (Tc-99m and In-111) gamma camera images were acquired at 2-3 and 16-18 hr later. Target-to-background (T/B) ratios were calculated for regions of interest drawn over the infected and contralateral normal tissue. Results: N-For-MLFK, N-Ac-MLFK and N-iBoc-MLFK had EC(50)s for receptor binding of 2.0, 830 and 150 nM, respectively. The corresponding EC(50)s for superoxide production were 20.0, approximate to 10(3) and > 10(4). Study A demonstrated that the T/B for Tc-99m-N-For-MLFK-HYNIC was higher than for any of the nonspecific imaging agents (p < 0.001), and In-111-immunoglobulin G had a higher T/B ratio than In-111-diethylenetriamine pentaacetic acid (p < 0.01) or In-111-red blood cells (p = NS). Study B showed that Tc-99m-N-For-MLFK-HYNIC had a higher T/B ratio than the other peptides (p < 0.001). In-111-leukocytes and Tc-99m-N-iBoc-MLFK-HYNIC had comparable T/B ratios, which were higher than for Tc-99m-N-Ac-MLFK-HYNIC (p < 0.05). Study C demonstrated that coinjection with an antagonist resulted in a significant reduction in the TIE ratio for Tc-99m-N-For-MLFK-HYNIC (p < 0.001), but did not affect the T/B ratio far In-111-leukocytes. Conclusion: Nonspecific mechanisms contribute minimally to the localization of Tc-99m-chemotactic peptide analogs at sites of infection and the majority of the accumulation appears to be receptor mediated, Also, chemotactic peptide receptor antagonists can be used for infection imaging, These results provide important new insights for future radiopharmaceutical development. C1 MASSACHUSETTS GEN HOSP,DIV NUCL PHYS,DEPT RADIOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT SURG,TRAUMA SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,SHRINERS BURNS INST,BOSTON,MA 02114. FU NIGMS NIH HHS [5P50 GM21700]; PHS HHS [R01 A131094] NR 28 TC 42 Z9 43 U1 1 U2 4 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD AUG PY 1997 VL 38 IS 8 BP 1316 EP 1322 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA XP424 UT WOS:A1997XP42400042 PM 9255175 ER PT J AU Li, KK Ung, F McKenna, MJ Keith, DA AF Li, KK Ung, F McKenna, MJ Keith, DA TI Combined middle cranial fossa and preauricular approach to the temporomandibular joint: Report of a case SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID MANDIBULAR CONDYLE; DISLOCATION; IMPLANT C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OTOLARYNGOL HEAD & NECK SURG,BOSTON,MA. HARVARD UNIV,SCH DENT MED,MASSACHUSETTS GEN HOSP,DEPT ORAL & MAXILLOFACIAL SURG,BOSTON,MA 02115. NR 10 TC 3 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD AUG PY 1997 VL 55 IS 8 BP 851 EP 852 DI 10.1016/S0278-2391(97)90348-7 PG 2 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA XQ334 UT WOS:A1997XQ33400015 PM 9251615 ER PT J AU Faraone, SV Biederman, J Wozniak, J Mundy, E Mennin, D ODonnell, D AF Faraone, SV Biederman, J Wozniak, J Mundy, E Mennin, D ODonnell, D TI Is comorbidity with ADHD a marker for juvenile-onset mania? SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE bipolar disorder; attention-deficit hyperactivity disorder; comorbidity; children; adolescents ID DEFICIT HYPERACTIVITY DISORDER; GENETIC-RELATIONSHIP; TOURETTES SYNDROME; ADOLESCENT MANIA; CHILDREN; FAMILY; PROBANDS AB Objective: To compare the characteristics and correlates of mania in referred adolescents and to determine whether attention-deficit hyperactivity disorder (ADHD) is a marker of very early onset mania. Method: From 637 consecutive admissions, 68 children (less than or equal to 12 years) and 42 adolescents (>13 years) who satisfied criteria for mania were recruited. These were compared with the 527 nonmanic referrals and 100 normal controls. Results: With the exception of comorbidity with ADHD, there were more similarities than differences between the children and adolescents with mania in course and correlates. There was an inverse relationship between the rates of comorbid ADHD and age of onset of mania: higher in manic children, intermediate in adolescents with childhood-onset mania, and lower in adolescents with adolescent-onset mania. Conclusions: ADHD is more common in childhood-onset compared with adolescent-onset cases of bipolar disorder, suggesting that in some cases, ADHD may signal a very early onset of bipolar disorder. Clinical similarities between the child- and adolescent-onset cases provide evidence for the clinical validity of childhood-onset mania. C1 MASSACHUSETTS GEN HOSP,CHILD PSYCHIAT SERV,PEDIAT PSYCHOPHARMACOL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,MASSACHUSETTS MENTAL HLTH CTR,INST PSYCHIAT EPIDEMIOL & GENET,DEPT PSYCHIAT,BOSTON,MA. COMMONWEALTH RES CTR,BOSTON,MA. OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [R01 MH50657-02, R01 MH41314-07] NR 23 TC 178 Z9 183 U1 1 U2 7 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 AUG PY 1997 VL 36 IS 8 BP 1046 EP 1055 DI 10.1097/00004583-199708000-00012 PG 10 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA XM571 UT WOS:A1997XM57100012 PM 9256584 ER PT J AU McNay, AT Ostad, A Moy, RL AF McNay, AT Ostad, A Moy, RL TI Surgical Pearl: Modified rhombic flap SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article C1 UNIV CALIF LOS ANGELES,W LOS ANGELES VET ADM MED CTR,DIV DERMATOL,LOS ANGELES,CA 90024. NR 8 TC 3 Z9 3 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD AUG PY 1997 VL 37 IS 2 BP 256 EP 258 DI 10.1016/S0190-9622(97)80134-X PN 1 PG 3 WC Dermatology SC Dermatology GA XT275 UT WOS:A1997XT27500015 PM 9270513 ER PT J AU Lehmann, KG Ferris, ST HeathLange, SJ AF Lehmann, KG Ferris, ST HeathLange, SJ TI Maintenance of hemostasis after invasive cardiac procedures: Implications for outpatient catheterization SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID PERIPHERAL VASCULAR COMPLICATIONS; CONVENTIONAL MANUAL COMPRESSION; ARTERIAL PUNCTURE SITES; RANDOMIZED TRIAL; CORONARY ANGIOPLASTY; STENT IMPLANTATION; GUIDING CATHETERS; BRACHIAL APPROACH; ANGIOGRAPHY; DEVICE AB Objectives. This study investigated the efficacy of four different methods of arterial puncture site management during recovery from invasive cardiac procedures, The primary goals were less patient discomfort and improved clinical outcome, Background The increasing use of outpatient catheterization, large interventional devices and potent periprocedural anticoagulation regimens has made the reduction of groin complications a high priority, Despite these trends, there are no randomized trials comparing commonly used techniques in treating the catheter entry site for the first few hours after the procedure, Methods. Four-hundred consecutive patients undergoing catheterization laboratory procedures were randomly assigned to one of four dressing techniques applied after achieving hemostasis: a sandbag placed over the site; a pressure dressing constructed from surgical gauze and elastic tape; a commercially available compression device; and no use of compressive dressing, Of these 400 patients, 171 would have been eligible for outpatient procedures in the absence of geographic constraints, The dressings were removed, and ambulation was encouraged 5 h after sheath removal. Uniform initial compression times, patient instructions, nursing follow-up and a structured interview and physical examination at 24 h were used, Results. The level of patient discomfort before and after dressing removal, as well as site tenderness at 24-h follow-up, was statistically similar in all four groups, Hematomas (typically small) and areas of ecchymosis were observed in 58 and 122 patients, respectively, but both their frequency and size were equally represented in each group, Important adverse events were confined to bleeding, rated as mild in 5.8%, moderate in 0.8% and severe in 0.6% of patients, Again, all four groups were statistically similar, Comparable findings were observed in the subgroup of patients eligible for outpatient procedures, Conclusions, Despite an increase in inconvenience and expense, none of the three compression techniques that were investigated improved patient satisfaction or outcome, Therefore, the routine use of compression dressings after invasive cardiac procedures cannot be recommended. (C) 1997 by the American College of Cardiology. C1 UNIV WASHINGTON,SCH MED,SEATTLE,WA 98108. RP Lehmann, KG (reprint author), VET AFFAIRS PUGET SOUND HLTH CARE SYST,SECT CARDIOL 111C,1660 S COLUMBIAN WAY,SEATTLE,WA 98108, USA. NR 35 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD AUG PY 1997 VL 30 IS 2 BP 444 EP 451 DI 10.1016/S0735-1097(97)00156-3 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA XN171 UT WOS:A1997XN17100017 PM 9247517 ER PT J AU Barry, MJ Fowler, FJ Bin, L Oesterling, JE AF Barry, MJ Fowler, FJ Bin, L Oesterling, JE TI A nationwide survey of practicing urologists: Current management of benign prostatic hyperplasia and clinically localized prostate cancer SO JOURNAL OF UROLOGY LA English DT Article DE prostate; prostatic hypertrophy; practice guidelines; physician's practice patterns; prostatic neoplasms ID PELVIC LYMPHADENECTOMY; PRACTICE TRENDS; UNITED-STATES; BONE-SCAN; ANTIGEN; DIAGNOSIS AB Purpose: Our aim was to define the spectrum of urological care for benign prostatic hyperplasia (BPH) and clinically localized prostate cancer. Materials and Methods: In 1995 a random sample of 394 American urologists was surveyed with a response rate of 67%. Results: Respondents reported seeing a median of 240 BPH patients during the preceding 12 months, and they had prescribed alpha-blockers for 70 and finasteride for 15. They had performed a median of 25 transurethral prostatectomies but few other operations for BPH. Almost all urologists routinely used digital rectal examinations and prostate specific antigen tests for BPH diagnosis. The next most common studies were American Urological Association symptom scores and uroflowmetry. Pressure-flow studies were rarely done. Respondents reported seeing a median of 35 new patients with prostate cancer during the last year, and performing a median of 90 prostate biopsies and 13 radical prostatectomies. Respondents had referred a median of 10 patients for external beam radiotherapy but few patients received brachytherapy or cryotherapy. Urologist staging practices varied considerably. Conclusions: These data provide a picture of current practice regarding the management of BPH and prostate cancer. C1 HARVARD UNIV, SCH MED, BOSTON, MA 02115 USA. UNIV MASSACHUSETTS, SURVEY RES CTR, BOSTON, MA 02125 USA. UNIV MICHIGAN, MED CTR, DEPT UROL, ANN ARBOR, MI 48109 USA. RP Barry, MJ (reprint author), MASSACHUSETTS GEN HOSP, MED PRACTICES EVALUAT CTR, BOSTON, MA 02114 USA. FU AHRQ HHS [HS 08397] NR 22 TC 49 Z9 50 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 EI 1527-3792 J9 J UROLOGY JI J. Urol. PD AUG PY 1997 VL 158 IS 2 BP 488 EP 491 DI 10.1016/S0022-5347(01)64510-5 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA XL143 UT WOS:A1997XL14300041 PM 9224330 ER PT J AU LaMuraglia, GM Adili, F Karp, SJ vanEps, RGS Watkins, MT AF LaMuraglia, GM Adili, F Karp, SJ vanEps, RGS Watkins, MT TI Photodynamic therapy inactivates extracellular matrix-basic fibroblast growth factor: Insights to its effect on the vascular wall SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID CHLOROALUMINUM SULFONATED PHTHALOCYANINE; EXPERIMENTAL INTIMAL HYPERPLASIA; SMOOTH-MUSCLE; NEOINTIMAL HYPERPLASIA; ENDOTHELIAL-CELLS; INJURY; INHIBITION; RAT; PROLIFERATION; PREVENTION AB Purpose: Photodynamic therapy (PDT), the light activation of photosensitizer dyes for the production of oxygen and other free radical moieties without the generation of heat, has been shown to inhibit the development of experimentally induced intimal hyperplasia. The host response to PDT, a form of vascular injury that results in complete vascular wall cell eradication, is devoid of inflammation and proliferation and promotes favorable vascular wall healing. These effects do not result in intimal hyperplasia and are suggestive of PDT-induced changes in the extracellular matrix (ECM). As a model to better understand the biologic consequences of PDT on the vascular wall matrix proteins, the effect of PDT was studied on the powerful matrix-resident mitogen basic fibroblast factor (bFGP) in vitro. Methods: PDT (5 to 200 J/cm(2), 100 mW/cm(2), 675 nm) was used with the photosensitizer chloroaluminum sulfonated phthalocyanine (5 mu g/ml) to inactivate bFGF in vitro while 100 J/cm(2) of irradiation was administered 24 hours after 5 mg/ml of the photosensitizer was used in vivo. PDT was used on bFGF in solution and on endothelial cell-derived ECM. Enzyme-linked immunosorbent assay was used to quantitate bFGF in solution after PDT treatment or after extraction from the ECM by collagenase and heparin. Functional activity of matrix-associated bFGF was assessed by smooth muscle cell mitogenesis by H-3-thymidine incorporation. To demonstrate the in vivo relevance of these observations, immunohistochemical analysis of PDT-treated rat carotid arteries was undertaken. Results: PDT eliminated detectable levels of bFGF in solution. PDT of ECM significantly reduced matrix-bound bFGF (1.0 +/- 0.6 vs 27.5 +/- 1.3 pg/ml; p < 0.0001). This reduction in bFGF after PDT of the ECM was associated with a decrease in vascular smooth muscle cell mitogenesis (52.4% +/- 4.6%; p < 0.0001) when plated on PDT-treated matrix compared with nontreated matrix. Quantitative replenishment of exogenous bFGF to PDT-treated matrix restored proliferation to baseline levels. PDT of rat carotid arteries demonstrated a loss of bFGF staining compared with control nontreated arteries. Conclusions: PDT inactivation of matrix-resident bFGF and possibly other bioactive molecules can provide a mechanism by which PDT suppresses smooth muscle cell proliferation in the vessel wall. This free radical-mediated alteration of matrix may contribute to favorable vascular healing when PDT is used for the inhibition of injury-induced intimal hyperplasia. C1 BOSTON UNIV,SCH MED,DIV VASC SURG,BOSTON VET ADM MED CTR,BOSTON,MA 02118. RP LaMuraglia, GM (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DIV VASC SURG,WELLMAN LABS PHOTOMED,BOSTON,MA 02114, USA. FU NHLBI NIH HHS [HL48152, HL02583] NR 32 TC 27 Z9 27 U1 2 U2 2 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD AUG PY 1997 VL 26 IS 2 BP 294 EP 301 DI 10.1016/S0741-5214(97)70192-7 PG 8 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA XT824 UT WOS:A1997XT82400016 PM 9279318 ER PT J AU Chen, SH Kramer, MF Schaffer, PA Coen, DM AF Chen, SH Kramer, MF Schaffer, PA Coen, DM TI A viral function represses accumulation of transcripts from productive-cycle genes in mouse ganglia latently infected with herpes simplex virus SO JOURNAL OF VIROLOGY LA English DT Article ID EPSTEIN-BARR-VIRUS; TRIGEMINAL GANGLIA; MESSENGER-RNA; TYPE-1 TRANSCRIPTS; IN-VIVO; INDUCED REACTIVATION; DELETION MUTANTS; THYMIDINE KINASE; EXPRESSION; MICE AB Latent infections of neurons by herpes simplex virus form reservoirs of recurrent viral infections that resist cure, In latently infected neurons, viral gene expression is severely repressed; only the latency-associated transcripts (LATs) are expressed abundantly. Using sensitive reverse transcriptase PCR assays, we analyzed the effects of a deletion mutation in the UT locus on viral gene expression in latently infected mouse trigeminal ganglia, The deletion mutation, which reduced expression of the major LATs 10(5)-fold, resulted in a similar to 5-fold increase in accumulation of transcripts from the immediate-early gene encoding ICP4, an essential transactivator of viral gene expression, The LAT deletion also resulted in a > 10-fold increase in the accumulation of transcripts from the early gene encoding thymidine kinase, whose expression during productive infection stringently depends on ICP4, and positively affected the correlation of the levels of these transcripts with the levels of ICP4 transcripts. We also detected transcripts antisense to ICP4, RNA which were in substantial excess to ICP4 transcripts in ganglia latently infected with wild-type virus. In contrast to its effects on productive cycle transcripts, the LAT deletion reduced the accumulation of these antisense transcripts similar to 15-fold. Thus, a viral function associated with the LAT locus represses the accumulation of transcripts from at least two productive-cycle genes in latently infected mouse ganglia, We discuss possible mechanisms and consequences of this repression. C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOL PHARMACOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,COMM VIROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MICROBIOL & MOL GENET,BOSTON,MA 02115. FU NIAID NIH HHS [P01 AI24010]; NINDS NIH HHS [P01 NS35138] NR 69 TC 122 Z9 124 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD AUG PY 1997 VL 71 IS 8 BP 5878 EP 5884 PG 7 WC Virology SC Virology GA XK153 UT WOS:A1997XK15300021 PM 9223477 ER PT J AU Yasugi, T Vidal, M Sakai, H Howley, PM Benson, JD AF Yasugi, T Vidal, M Sakai, H Howley, PM Benson, JD TI Two classes of human papillomavirus type 16 E1 mutants suggest pleiotropic conformational constraints affecting E1 multimerization, E2 interaction, and interaction with cellular proteins SO JOURNAL OF VIROLOGY LA English DT Article ID DNA-POLYMERASE-ALPHA; BOVINE PAPILLOMAVIRUS; REPLICATION PROTEIN; TRANSIENT REPLICATION; COMPLEX-FORMATION; BINDING DOMAIN; T-ANTIGEN; ORIGIN; ACTIVATION; SEQUENCES AB Random mutagenesis of human papillomavirus type 16 (HPV16) E1 was used to generate E1 missense mutants defective for interaction with either hUBC9 or 16E1-BP, two cDNAs encoding proteins that have been identified by their ability to interact with HPV16 E1 in two-hybrid assays, hUBC9, the human counterpart of Saccharomyces cerevisiae UBC9, is a ubiquitin-conjugating enzyme known to be involved in cell cycle progression, 16E1-BP encodes a protein of no known function but does contain an ATPase signature motif, Eight hUBC9 or 16E1-BP interaction-defective HPV16 E1 missense mutants were identified and characterized for origin dependent transient DNA replication, ATPase activity, and various protein-protein interaction phenotypes, Six of these mutant E1 proteins were significantly impaired for replication, Among these, two classes of replication-defective HPV16 E1 missense mutants were observed. One class, represented by the S330R replication-defective mutant (containing an S-to-R change at position 330), remained competent for all protein-protein interactions tested, with the exception of hUBC9 association, Furthermore, this mutant, unlike the other replication-defective HPV16 E1 missense mutants, had a strong dominant negative replication phenotype in transient-replication assays. The other class, represented by five of the missense mutants, was defective for multiple protein-protein interactions, usually including, but not limited to, the interaction defect for which each mutant was originally selected, In many cases, a single missense mutation in one region of HPV16 E1 had pleiotropic effects, even upon activities thought to be associated with other domains of HPV16 E1, This suggests that E1 proteins are not modular but may instead be composed of multiple structurally and/or functionally interdependent domains. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,CTR CANC,CHARLESTOWN,MA 02129. NR 58 TC 43 Z9 44 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD AUG PY 1997 VL 71 IS 8 BP 5942 EP 5951 PG 10 WC Virology SC Virology GA XK153 UT WOS:A1997XK15300028 PM 9223484 ER PT J AU Rowe, CL Fleming, JO Nathan, MJ Sgro, JY Palmenberg, AC Baker, SC AF Rowe, CL Fleming, JO Nathan, MJ Sgro, JY Palmenberg, AC Baker, SC TI Generation of coronavirus spike deletion variants by high-frequency recombination at regions of predicted RNA secondary structure SO JOURNAL OF VIROLOGY LA English DT Article ID INTERTYPIC POLIOVIRUS RECOMBINANTS; MURINE HEPATITIS-VIRUS; QUASI-SPECIES NATURE; NEUROTROPIC CORONAVIRUS; MONOCLONAL-ANTIBODIES; CROSSOVER REGIONS; SEQUENCE-ANALYSIS; C VIRUS; GLYCOPROTEIN; PROTEIN AB Coronavirus RNA evolves in the central nervous systems (CNS) of mice during persistent infection. This evolution can be monitored by detection of a viral quasispecies of spike deletion variants (SDVs) (C. L. Rowe, S. C. Baker, M. J. Nathan, and J. O. Fleming, J. Virol. 71:2959-2969, 1997). We and others have Pound that the deletions cluster in the region from 1,200 to 1,800 nucleotides from the 5' end of the spike gene sequence, termed the ''hypervariable'' region. To address how SDVs might arise, we generated the predicted folding structures of the positive- and negative-strand senses of the entire 4,139-nt spike RNA sequence. We found that a prominent, isolated stem-loop structure is coincident with the hypervariable region in each structure, To determine if this predicted stem-loop is a ''hot spot'' for RNA recombination, Re assessed whether this region of the spike is more frequently deleted than three other selected regions of the spike sequence in a population of viral sequences isolated from the CNS of acutely and persistently infected mice. Using differential colony hybridization of cloned spike reverse transcription-PCR products, we detected SDVs in which the hot spot was deleted but did not detect SDVs in which other regions of the spike sequence were exclusively deleted. Furthermore, sequence analysis and mapping of the crossover sites of 25 distinct patterns of SDVs showed that the majority of crossover sites clustered to two regions at the base of the isolated stem-loop, which we designated as high-frequency recombination sites 1 and 2. Interestingly, the majority of the left and right crossover sites of the SDVs were directly across from or proximal to one another, suggesting that these SDVs are likely generated by intramolecular recombination. Overall, our results are consistent with there being an important role for the spike RNA secondary structure as a contributing factor in the generation of SDVs during persistent infection. C1 LOYOLA UNIV,STRITCH SCH MED,DEPT MICROBIOL & IMMUNOL,MAYWOOD,IL 60153. LOYOLA UNIV,STRITCH SCH MED,PROGRAM MOL BIOL,MAYWOOD,IL 60153. UNIV WISCONSIN,DEPT NEUROL,MADISON,WI 53792. UNIV WISCONSIN,DEPT MED MICROBIOL,MADISON,WI 53792. WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI 53792. UNIV WISCONSIN,INST MOL VIROL,MADISON,WI 53706. UNIV WISCONSIN,DEPT ANIM HLTH & BIOMED SCI,MADISON,WI 53706. FU NIAID NIH HHS [AI32065] NR 52 TC 19 Z9 21 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD AUG PY 1997 VL 71 IS 8 BP 6183 EP 6190 PG 8 WC Virology SC Virology GA XK153 UT WOS:A1997XK15300058 PM 9223514 ER PT J AU Cohen, RM Feldman, GM Fernandez, PC AF Cohen, RM Feldman, GM Fernandez, PC TI The balance of acid, base and charge in health and disease SO KIDNEY INTERNATIONAL LA English DT Article ID RENAL TUBULAR-ACIDOSIS; LACTIC-ACIDOSIS; METABOLIC CONSEQUENCES; CITRATE EXCRETION; PROXIMAL COLON; DISTAL COLON; OXALATE; PH; KETOACIDOSIS; BICARBONATE C1 DEPT VET AFFAIRS MED CTR,RENAL SECT,PHILADELPHIA,PA 19104. ALLEGHENY UNIV HLTH SCI,GRAD HOSP,DIV NEPHROL,PHILADELPHIA,PA 19102. UNIV PENN,SCH MED,DIV NEPHROL,PHILADELPHIA,PA 19104. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DIV NEPHROL,RICHMOND,VA 23298. FU NIDDK NIH HHS [DK-07006] NR 69 TC 22 Z9 22 U1 0 U2 2 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD AUG PY 1997 VL 52 IS 2 BP 287 EP 293 DI 10.1038/ki.1997.334 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA XP205 UT WOS:A1997XP20500001 PM 9263983 ER PT J AU Kelly, K AF Kelly, K TI Sleeping with the mayor: A true story - Jiler,J SO LIBRARY JOURNAL LA English DT Book Review RP Kelly, K (reprint author), MASSACHUSETTS GEN HOSP,TREADWELL LIB,BOSTON,MA 02114, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU BOWKER MAGAZINE GROUP CAHNERS MAGAZINE DIVISION PI NEW YORK PA 249 W 17TH ST, NEW YORK, NY 10011 SN 0363-0277 J9 LIBR J JI Libr. J. PD AUG PY 1997 VL 122 IS 13 BP 112 EP 112 PG 1 WC Information Science & Library Science SC Information Science & Library Science GA XQ846 UT WOS:A1997XQ84600232 ER PT J AU Kelly, K AF Kelly, K TI Homeopathic self-care: The quick and easy guide for the whole family - Ullman,R, ReichenbergUllman,J SO LIBRARY JOURNAL LA English DT Book Review RP Kelly, K (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU BOWKER MAGAZINE GROUP CAHNERS MAGAZINE DIVISION PI NEW YORK PA 249 W 17TH ST, NEW YORK, NY 10011 SN 0363-0277 J9 LIBR J JI Libr. J. PD AUG PY 1997 VL 122 IS 13 BP 120 EP 120 PG 1 WC Information Science & Library Science SC Information Science & Library Science GA XQ846 UT WOS:A1997XQ84600279 ER PT J AU Baciu, PC Goetinck, PF AF Baciu, PC Goetinck, PF TI Characterization of a novel serine/threonine kinase that specifically interacts with the cytoplasmic domain of syndecan-4 SO MATRIX BIOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CUTANEOUS BIOL RES CTR,CHARLESTOWN,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GUSTAV FISCHER VERLAG PI JENA PA VILLENGANG 2, D-07745 JENA, GERMANY SN 0945-053X J9 MATRIX BIOL JI Matrix Biol. PD AUG PY 1997 VL 16 IS 3 BP 119 EP 119 DI 10.1016/S0945-053X(97)90041-X PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XW551 UT WOS:A1997XW55100007 ER PT J AU Wray, NP Peterson, NJ Souchek, J Ashton, CM Hollingsworth, JC AF Wray, NP Peterson, NJ Souchek, J Ashton, CM Hollingsworth, JC TI Application of an analytic model to early readmission rates within the Department of Veterans Affairs SO MEDICAL CARE LA English DT Article DE quality of care; disease-outcome pairs; database analysis; administrative databases; readmission ID HOSPITAL DISCHARGE DATA; QUALITY; OUTCOMES; CARE; COMPLICATIONS; MORTALITY; DATABASES; ACCURACY; PAYMENT; BIAS AB OBJECTIVES. Adverse outcome rates are increasingly used as yardsticks for the quality of hospital care. However, the validity of many outcome studies has been undermined by the application of one outcome to all patients in large, diagnostically diverse populations, many of which lack evidence of a link between antecedent process of care and the rate of the outcome, the underlying assumption of the analysis. METHODS. TO address this analytic problem, the authors developed a model that improves the ability to identify quality problems because it selects diseases for which there are processes of care known to affect the outcome of interest. Thus, for these diseases, the outcome is most likely to be causally related to the antecedent care. In this study of hospital readmissions, risk-adjusted models were created for 17 disease categories with strong links between process and outcome. Using these models, we identified outlier hospitals. RESULTS. The authors hypothesized that if the model improved on identifying hospitals with quality of care problems, then outlier status would not be random. That is, hospitals found to have extreme rates in one year would be more likely to have extreme rates in subsequent years, and hospitals with extreme rates in one condition would be more likely to have extreme rates in related disease categories. It was hypothesized further that the correlation of outlier status across time and across diseases would be stronger in the 17 disease categories selected by the model than in 10 comparison disease categories with weak links between process and outcome. CONCLUSIONS. The findings support all these hypotheses. Although the present study shows that the model selects disease;outcome pairs where hospital outlier status is not random, the causal factors leading to outlier status could include (1) systematic unmeasured patient variation, (2) practice pattern variation that, although stable with time, is not indicative of substandard care, or (3) true quality-of-care problems. Primary data collection must be done to determine which of these three factors is most causally related to hospital outlier status. C1 BAYLOR COLL MED,DEPT MED,HOUSTON,TX 77030. RP Wray, NP (reprint author), HOUSTON VA MED CTR,VA HLTH SERV RES & DEV FIELD PROGRAM,2002 HOLCOMBE BLVD,HOUSTON,TX 77030, USA. NR 27 TC 16 Z9 16 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0025-7079 J9 MED CARE JI Med. Care PD AUG PY 1997 VL 35 IS 8 BP 768 EP 781 PG 14 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA XP851 UT WOS:A1997XP85100003 PM 9268250 ER PT J AU Leaf, DA Kleinman, MT Hamilton, M Barstow, TJ AF Leaf, DA Kleinman, MT Hamilton, M Barstow, TJ TI The effect of exercise intensity on lipid peroxidation SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Article DE lipid peroxidation; physical activity ID OXIDATIVE STRESS; PENTANE AB This study characterizes exercise-induced lipid peroxidation during graded aerobic exercise in seven healthy men and women (36.4 +/- 3 yr). Levels of ethane and pentane in expired breath during cardiopulmonary exercise stress testing were measured at rest, lactic acidosis threshold (LAT), maximal exercise ((V) over dot O-2max), and recovery. Serum malonaldehyde (MDA) levels were measured at rest before exercise and 5 min after maximal exercise. Expired ethane and pentane flux levels were increased above resting levels at LAT, continued to rise at (V) over dot O-2max, then declined during recovery. Serum MDA levels were not significantly different before and after maximal exercise. Substantial exercise-induced lipid peroxidation (by expired ethane and pentane) apparently occurred in healthy individuals at LAT and continued to increase at (V) over dot O-2max, yet rapidly attenuated during post-exercise recovery. These findings indicate that in healthy individuals physical exercise induced lipid peroxidation transiently and that there was a removal of lipid peroxidation byproducts during recovery. C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT MED,LOS ANGELES,CA 90073. UNIV CALIF IRVINE,DEPT COMMUNITY & ENVIRONM MED,IRVINE,CA 92717. UNIV CALIF LOS ANGELES,SCH MED,DEPT MED,DIV CARDIOL,LOS ANGELES,CA 90095. HARBOR UCLA MED CTR,DEPT MED,DIV RESP & CRIT CARE PHYSIOL MED,TORRANCE,CA 90509. RP Leaf, DA (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,DIV GEN INTERNAL MED,DEPT MED,WILSHIRE & SAWTELLE BLVDS,LOS ANGELES,CA 90073, USA. NR 21 TC 74 Z9 77 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD AUG PY 1997 VL 29 IS 8 BP 1036 EP 1039 DI 10.1097/00005768-199708000-00008 PG 4 WC Sport Sciences SC Sport Sciences GA XR035 UT WOS:A1997XR03500008 PM 9268960 ER PT J AU Haake, DA Summers, TA McCoy, AM Schwartzman, W AF Haake, DA Summers, TA McCoy, AM Schwartzman, W TI Heat shock response and groEL sequence of Bartonella henselae and Bartonella quintana SO MICROBIOLOGY-UK LA English DT Article DE heat shock; Bartonella henselae; Bartonella quintana; GroEL ID SP-NOV; BACILLARY ANGIOMATOSIS; BRUCELLA-ABORTUS; COMB-NOV; ROCHALIMAEA; BACILLIFORMIS; PROTEINS; CELLS; PROPOSALS; PELIOSIS AB Transmission of Bartonella species from edoparasites to the mammalian host involves adaptation to thermal and other forms of stress. in order to better understand this process, the heat shock response of Bartonella henselae and Bartonella quintana was studied. Cellular proteins synthesized after shift to higher temperatures were intrinsically labelled with [S-35]methionine and analysed by gel electrophoresis and fluorography. The apparent molecular masses of three of the major heat shock proteins produced by the two Bartonella species were virtually identical, migrating at 70, 60 and 10 kDa. A fourth major shock protein was larger in B. quintana (20 kDa) than in B. henselae (17 kDa). The maximum heat shock response in B. quintana and B. henselae was observed at 39 degrees C and 42 degrees C, respectively. The groEL genes of both Bartonella species were amplified, sequenced and compared to other known groEL genes. The phylogenetic tree based on the groEL alignment places B. quintana and B. henselae in a monophyletic group with Bartonella bacilliformis. the deduced amino acid sequences of Bartonella GroEL homologues contain signature sequences that are uniquely shared by members of the Gram-negative alpha-purple subdivision of bacteria, which live within eukaryotic cells. Recombinant His(6)-GroEL fusion proteins were expressed in Escherichia coli to generate specific rabbit antisera. The GroEL antisera were used to confirm the identity of the 60 kDa Bartonella heat shock protein. These studies provide a foundation for evaluating the role of the heat shock response in the pathogenesis of Bartonella infection. C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT IMMUNOL & MICROBIOL,LOS ANGELES,CA 90095. VET AFFAIRS MED CTR,DIV INFECT DIS,SEPULVEDA,CA 91343. RP Haake, DA (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,DIV INFECT DIS,11301 WILSHIRE BLVD,LOS ANGELES,CA 90073, USA. NR 36 TC 13 Z9 15 U1 0 U2 1 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING, BERKS, ENGLAND RG7 1AE SN 1350-0872 J9 MICROBIOL-UK JI Microbiology-(UK) PD AUG PY 1997 VL 143 BP 2807 EP 2815 PN 8 PG 9 WC Microbiology SC Microbiology GA XQ875 UT WOS:A1997XQ87500032 PM 9274034 ER PT J AU Soslow, RA Zukerberg, LR Harris, NL Warnke, RA AF Soslow, RA Zukerberg, LR Harris, NL Warnke, RA TI BCL-1 (PRAD-1 cyclin D-1) overexpression distinguishes the blastoid variant of mantle cell lymphoma from B-lineage lymphoblastic lymphoma SO MODERN PATHOLOGY LA English DT Article DE BCL-1; blastoid/blastic variant of mantle cell lymphoma; CD99; cyclin D-1; lymphoblastic lymphoma; mantle cell lymphoma; PRAD-1; TdT ID EWINGS-SARCOMA; LYMPHOCYTIC LYMPHOMA; INTERMEDIATE DIFFERENTIATION; CENTROCYTIC LYMPHOMA; MONOCLONAL-ANTIBODY; SURFACE-ANTIGEN; MIC2 EXPRESSION; ONCOGENE; GENE; LEUKEMIA AB The blastoid variant of mantle cell lymphoma (MCL-BV) can occur de novo or can represent a morphologic transformation of MCL associated with aggressive clinical disease. Its cytologic appearance is very similar to that of lymphoblastic lymphoma (LBL) because of its characteristic nuclear features and high proliferative rate. To assess the usefulness of antibodies to cyclin D-1 (BCL-1/PRAD-1), CD99 (12E7), CD34, and TdT in distinguishing between MCL-BV and LBL in formalin-fixed, paraffin-embedded tissue, we studied from the Stanford data base 10 cases originally diagnosed as B-lineage LBL, 5 MCL-BVs, 2 cases thought likely to represent MCL-BV, and 2 blastic lymphomas whose morphology and immunophenotype were indeterminate. Six (60%) of 10 LBLs stained with CD99, as opposed to none of 7 MCL-BVs. Four (40%) of 10 LBLs reacted with CD34, as compared with none of 7 MCL-BVs. Eight (89%) of nine LBLs were positive for TdT, but all of the four MCL-BVs tested were negative. In contrast, the anti-cyclin D-1 antibody stained the nuclei of all of the MCL-BVs and none of the LBLs tested. On the basis of our evaluation, the probable MCL-BV cases were considered to be definite MCL-BV. Of the indeterminate cases, one was considered to be LBL, whereas we felt that the other represented MCL-BV. We conclude that staining formalin-fixed, paraffin-embedded, high-grade lymphomas with anti-cyclin D-1 antibody is useful in confirming the diagnosis of MCL-BV, whereas positive reactions with CD99, CD34, and particularly TdT are more characteristic of LBL. C1 STANFORD UNIV,MED CTR,DEPT PATHOL,STANFORD,CA 94305. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. FU NCI NIH HHS [CA34233] NR 50 TC 21 Z9 24 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD AUG PY 1997 VL 10 IS 8 BP 810 EP 817 PG 8 WC Pathology SC Pathology GA XR364 UT WOS:A1997XR36400009 PM 9267824 ER PT J AU NevelMcGarvey, CA Levin, RM Hudson, AP AF NevelMcGarvey, CA Levin, RM Hudson, AP TI Transcription of mitochondrial and mitochondria-related nuclear genes in rabbit bladder following partial outlet obstruction SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE outlet obstruction; bladder; mitochondria; transcription; RNA ID URINARY-BLADDER; EXPRESSION; REGIONS; ACID AB Using the rabbit model, we showed that partial outlet obstruction of the urinary bladder causes significant changes in the status and expression of the mitochondrial (mt) genetic system in bladder smooth muscle immediately after obstruction is initiated. Here we investigate quantitatively the severity of the mt genetic response to partial outlet obstruction in both short-and long-term obstructed rabbits. Based on previous functional studies, bladders with mass < 6 fold greater than control were considered compensated; bladders with mass > 6 fold that of control were considered decompensated. Analyses of DNA from compensated rabbit bladders showed that relative mt genome copy number decreased to 30% of control values. Transcript analyses for these samples showed that mt RNA levels increased 3 fold to compensate for lower template copy number. Analysis of decompensated bladders demonstrated that mt genome copy number increased to approximately 90% of control levels; mt transcripts progressively decreased in these samples by as much as 30 fold. In contrast, transcription of a mt-related nuclear gene decreased 3-9 fold in compensated bladders but increased 10-30 fold in decompensated bladders. Activity for the cytochrome oxidase complex, and for the mt enzyme citrate synthase, decreased steadily with increasing bladder hypertrophy. These data suggest that bladder dysfunction following partial outlet obstruction is mediated partly by a significant loss in mt and mt-related nuclear gene coordination. C1 DEPT VET AFFAIRS MED CTR, MED RES SERV, PHILADELPHIA, PA 19104 USA. MED COLL PENN & HAHNEMANN UNIV, SCH MED, DEPT MICROBIOL & IMMUNOL, PHILADELPHIA, PA 19102 USA. UNIV PENN, SCH MED, DEPT SURG, DIV UROL, PHILADELPHIA, PA 19104 USA. FU PHS HHS [33559, 44689, 26508] NR 28 TC 11 Z9 11 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0300-8177 EI 1573-4919 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD AUG PY 1997 VL 173 IS 1-2 BP 95 EP 102 PG 8 WC Cell Biology SC Cell Biology GA XU450 UT WOS:A1997XU45000011 PM 9278259 ER PT J AU HannaRose, W Licht, JD Hansen, U AF HannaRose, W Licht, JD Hansen, U TI Two evolutionarily conserved repression domains in the Drosophila Kruppel protein differ in activator specificity SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TRANSCRIPTIONAL REPRESSION; GENE-EXPRESSION; EUKARYOTIC PROMOTERS; FUNCTIONAL-ANALYSIS; BINDING PROTEIN; MAMMALIAN-CELLS; TFIID COMPLEX; DNA; HUNCHBACK; SEQUENCE AB To identify biologically functional regions in the product of the Drosophila melanogaster gene Kruppel, we cloned the Kruppel homolog from Drosophila virilis, Both the previously identified amino (N)-terminal repression region and the DNA-binding region of the D. virilis Kruppel protein are greater than 96% identical to those of the D. melanogaster Kruppel protein, demonstrating a selective pressure to maintain the integrity of each region during 60 million to 80 million years of evolution, An additional region in the carboxyl (C) terminus of Kruppel that was most highly conserved was examined further, A 42-amino-acid stretch within the conserved C-terminal region also encoded a transferable repression domain. The short, C-terminal repression region is a composite of three subregions of distinct amino acid composition, each containing a high proportion of either basic, proline, or acidic residues, Mutagenesis experiments demonstrated, unexpectedly, that the acidic residues contribute to repression function, Both the N-terminal and C-terminal repression regions were tested for the ability to affect transcription mediated by a variety of activator proteins, The N-terminal repression region was able to inhibit transcription in the presence of multiple activators. However, the C-terminal repression region inhibited transcription by only a subset of the activator proteins, The different activator specificities of the two regions suggest that they repress transcription by different mechanisms and may play distinct biological roles during Drosophila development. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV MOL GENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOL GENET,BOSTON,MA 02115. CUNY MT SINAI SCH MED,BROOKDALE CTR MOL BIOL,NEW YORK,NY 10029. CUNY MT SINAI SCH MED,DEPT MED,NEW YORK,NY 10029. FU NCI NIH HHS [T32-CA09361, CA-01272] NR 59 TC 20 Z9 21 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD AUG PY 1997 VL 17 IS 8 BP 4820 EP 4829 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XM783 UT WOS:A1997XM78300062 PM 9234738 ER PT J AU Treilleux, I Peloux, N Brown, M Sergeant, A AF Treilleux, I Peloux, N Brown, M Sergeant, A TI Human estrogen receptor (ER) gene promoter-P1: Estradiol-independent activity and estradiol inducibility in ER+ and ER- cells SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID BREAST-CANCER-CELLS; MESSENGER-RIBONUCLEIC-ACID; THYROID-HORMONE RECEPTOR; RESPONSE ELEMENT; PROGESTERONE-RECEPTOR; MCF-7 CELLS; STEROID-RECEPTORS; GROWTH-FACTOR; EXPRESSION; RNA AB Estrogen receptor (ER) is expressed at a low level in normal tissues such as breast and uterus but at a high level in breast and endometrial carcinomas. A proximal element (ERF-1) located between positions +133 and +204 relative to the promoter P1 major initiation site has been recently identified in ER+ cells and contributes to the differential promoter activity between ER+ and ER- cells, In this study, MCF7 and HeLa cells were transfected with chloramphenicol acetyltransferase constructs containing ER gene promoter P1 sequences. We show here that the sequences lying between nucleotides +13 to +212 are also essential for transcription at the ER gene promoter P1 in ER- cells, which do not express ERF-1. Interestingly, on gel shift experiments, a complex specific to ER- cells forms in the region spanning nucleotides +123 to +210. We also show that promoter P1 is responsive to estradiol in cells expressing endogenous (MCF7) or exogenous ER. We further demonstrate, using mutational analysis and gel retardation assays, that the three half-estrogen response elements located between nucleotides -420 and -892 are responsible for the estradiol inducibility of promoter P1. Because estradiol has a mitogenic effect on both breast and endometrial epithelial cells, our data would give an insight into the role of estrogens in the occurence of breast and endometrial carcinomas. C1 ECOLE NORMALE SUPER LYON, MOL VIROL LAB, INSERM, U412, F-69364 LYON 07, FRANCE. DANA FARBER CANC INST, DIV NEOPLAST DIS MECHANISMS, BOSTON, MA 02115 USA. RP Treilleux, I (reprint author), CTR LEON BERARD, DEPT ANAT & CYTOL PATHOL, 28 RUE LAENNEC, F-69373 LYON 08, FRANCE. RI Myles, Brown/B-6906-2008; OI Brown, Myles/0000-0002-8213-1658 NR 65 TC 31 Z9 31 U1 0 U2 3 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 AUG PY 1997 VL 11 IS 9 BP 1319 EP 1331 DI 10.1210/me.11.9.1319 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XN623 UT WOS:A1997XN62300012 ER PT J AU Helmlinger, G Netti, PA Lichtenbeld, HC Melder, RJ Jain, RK AF Helmlinger, G Netti, PA Lichtenbeld, HC Melder, RJ Jain, RK TI Solid stress inhibits the growth of multicellular tumor spheroids SO NATURE BIOTECHNOLOGY LA English DT Article DE tumor growth; apoptosis; proliferation ID RESIDUAL STRAINS; BLOOD-FLOW; CELL; RAT; RESISTANCE; RADIATION; TISSUE; DRUG; APOPTOSIS; DORMANCY AB In normal tissues, the processes of growth, remodeling, and morphogenesis are tightly regulated by the stress field; conversely, stress may be generated by these processes. We demonstrate that solid stress inhibits tumor growth iii vitro, regardless of host species, tissue of origin, or differentiation state. The inhibiting stress for multicellular tumor spheroid growth in agarose matrices was 45 to 120 mm Hg. This stress, which greatly exceeds blood pressure in tumor vessels, is sufficient to induce the collapse of vascular or lymphatic vessels in tumors in vivo and can explain impaired blood flow, poor lymphatic drainage, and suboptimal drug delivery previously reported in solid tumors. The stress-induced growth inhibition of plateau-phase spheroids was accompanied, at the cellular level, by decreased apoptosis with no significant changes in proliferation. A concomitant increase In the cellular packing density was observed, which may prevent cells from undergoing apoptosis via a cell-volume or cell-shape transduction mechanism. These results suggest that solid stress controls tumor growth at both the macroscopic and cellular levels, and thus influences tumor progression and delivery of therapeutic agents. C1 HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02114. OI NETTI, PAOLO/0000-0002-2435-7181 FU NCI NIH HHS [R35-CA-56591] NR 42 TC 329 Z9 335 U1 6 U2 45 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD AUG PY 1997 VL 15 IS 8 BP 778 EP 783 DI 10.1038/nbt0897-778 PG 6 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA XM707 UT WOS:A1997XM70700031 PM 9255794 ER PT J AU Haber, D Harlow, E AF Haber, D Harlow, E TI Tumour-suppressor genes: evolving definitions in the genomic age SO NATURE GENETICS LA English DT Editorial Material ID RETINOBLASTOMA RP Haber, D (reprint author), MASSACHUSETTS GEN HOSP,CTR CANC,CHARLESTOWN,MA 02129, USA. NR 8 TC 118 Z9 121 U1 0 U2 0 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD AUG PY 1997 VL 16 IS 4 BP 320 EP 322 DI 10.1038/ng0897-320 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA XM909 UT WOS:A1997XM90900003 PM 9241260 ER PT J AU Westphal, CH Rowan, S Schmaltz, C Elson, A Fisher, DE Leder, P AF Westphal, CH Rowan, S Schmaltz, C Elson, A Fisher, DE Leder, P TI atm and p53 cooperate in apoptosis and suppression of tumorigenesis, but not in resistance to acute radiation toxicity SO NATURE GENETICS LA English DT Article ID CYCLE CHECKPOINT PATHWAY; ATAXIA-TELANGIECTASIA; CELLULAR-RESPONSES; CANCER-THERAPY; DNA-DAMAGE; MICE; INSTABILITY; GENE AB Mutations in atm and p53 cause the human cancer-associated diseases ataxia-telangiectasia(1) and Li-Fraumeni syndrome(2,3), respectively. The two genes are believed to interact in a number of pathways(4-6), including regulation of DNA damage-induced cell-cycle checkpoints(7), apoptosis and radiation sensitivity(8), and cellular proliferation(9). Atm-null mice(10-12), as well as those null for p53(13,14), develop mainly T-cell lymphomas, supporting the view that these genes have similar roles in thymocyte development. To study the interactions of these two genes on an organismal level, we bred mice heterozygous for null alleles of both atm and p53 to produce all genotypic combinations. Mice doubly null for atm and p53 exhibited a dramatic acceleration of tumour formation relative to singly null mice, indicating that both genes collaborate in a significant manner to prevent tumorigenesis. With respect to their roles in apoptosis, loss of atm rendered thymocytes only partly resistant to irradiation-induced apoptosis, whereas additional loss of p53 engendered complete resistance. This implies that the irradiation-induced atm and p53 apoptotic pathways are not completely congruent. Finally-and in contrast to prior predictions(4,6)-atm and p53 do not appear to interact in acute radiation toxicity, suggesting a separate atm effector pathway for this DNA damage response and having implications for the prognosis and treatment of human tumours. C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,HOWARD HUGHES MED INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PEDIAT HEMATOL ONCOL,BOSTON,MA 02115. CHILDRENS HOSP BOSTON,BOSTON,MA 02115. WEIZMANN INST SCI,DEPT MOL GENET,IL-76100 REHOVOT,ISRAEL. FU NCI NIH HHS [CA69531]; NIAMS NIH HHS [AR43369] NR 28 TC 181 Z9 184 U1 0 U2 6 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD AUG PY 1997 VL 16 IS 4 BP 397 EP 401 DI 10.1038/ng0897-397 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA XM909 UT WOS:A1997XM90900026 PM 9241281 ER PT J AU Navia, BA Gonzalez, RG AF Navia, BA Gonzalez, RG TI Functional imaging of the AIDS dementia complex and the metabolic pathology of the HIV-1-infected brain SO NEUROIMAGING CLINICS OF NORTH AMERICA LA English DT Article ID IMMUNODEFICIENCY-VIRUS-INFECTION; PROTON MR SPECTROSCOPY; EMISSION COMPUTED-TOMOGRAPHY; HIV-SEROPOSITIVE INDIVIDUALS; NECROSIS-FACTOR-ALPHA; CEREBRAL BLOOD-FLOW; NEURONAL LOSS; ABSOLUTE QUANTITATION; NEOCORTICAL DAMAGE; FRONTAL-CORTEX AB The AIDS-dementia complex remains one of the more common neurologic disorders associated with human immunodeficiency virus (HIV) infection. Despite several advances that have been made in elucidating some of its clinical and biological features, pathogenesis is not well understood, and effective treatments are scarce. This article reveals the results of these studies and discusses how these different approaches have already enabled clinicians to study further the effects of HIV infection on brain function and to explore the functional anatomy of this important clinical syndrome. C1 TUFTS UNIV NEW ENGLAND MED CTR,DEPT NEUROL,BOSTON,MA 02111. TUFTS UNIV NEW ENGLAND MED CTR,DEPT PSYCHIAT,BOSTON,MA 02111. MASSACHUSETTS GEN HOSP,DEPT RADIOL,NEURORADIOL SECT,BOSTON,MA 02114. TUFTS UNIV,SCH MED,DEPT NEUROL,MEDFORD,MA 02155. TUFTS UNIV,SCH MED,DEPT PSYCHIAT,MEDFORD,MA 02155. HARVARD UNIV,SCH MED,BOSTON,MA. NR 84 TC 18 Z9 18 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 1052-5149 J9 NEUROIMAG CLIN N AM JI Neuroimaging Clin. N. Am. PD AUG PY 1997 VL 7 IS 3 BP 431 EP & PG 16 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA XV825 UT WOS:A1997XV82500003 PM 9376962 ER PT J AU Payami, H Schellenberg, GD Zareparsi, S Kaye, J Sexton, GJ Head, MA Matsuyama, SS Jarvik, LF Miller, B McManus, DQ Bird, TD Katzman, R Heston, L Norman, D Small, GW AF Payami, H Schellenberg, GD Zareparsi, S Kaye, J Sexton, GJ Head, MA Matsuyama, SS Jarvik, LF Miller, B McManus, DQ Bird, TD Katzman, R Heston, L Norman, D Small, GW TI Evidence for association of HLA-A2 allele with onset age of Alzheimer's disease SO NEUROLOGY LA English DT Article ID APOLIPOPROTEIN-E; TYPE-4 ALLELE; GENE; LONGEVITY; LOCUS; MEN; FREQUENCY; EPSILON-4; LINKAGE; MARKER AB Our earlier studies had suggested a possible association between the HLA-A2 allele and Alzheimer's disease (AD). In the present study are tested the hypothesis that A2 is associated with earlier AD onset. We performed two independent studies: a collaborative study with 111 patients and a confirmatory study with 96 patients. We found similar patterns of reduced age at onset as a function of A2 in both data sets. Overall, A2 was associated with a significant S-year shift to earlier onset. The effects of A2 and epsilon 4 on age at onset appeared additive. Our results suggest A2, or a closely linked gene, modulates onset age of AD. Association with A2 would suggest an immune/inflammatory response mechanism for AD. C1 OREGON HLTH SCI UNIV,VET AFFAIRS MED CTR,DEPT NEUROL,PORTLAND,OR 97201. OREGON HLTH SCI UNIV,VET AFFAIRS MED CTR,DEPT PUBL HLTH & PREVENTAT MED SURG & MED,PORTLAND,OR 97201. OREGON HLTH SCI UNIV,VET AFFAIRS MED CTR,DEPT MED TRANSPLANTAT MED,PORTLAND,OR 97201. OREGON HLTH SCI UNIV,VET AFFAIRS MED CTR,LAB IMMUNOGENET & TRANSPLANTAT,PORTLAND,OR 97201. UNIV WASHINGTON,VET AFFAIRS PEUGEOT SOUND HLTH CARE SYST,DIV NEUROL,SEATTLE,WA 98195. UNIV WASHINGTON,VET AFFAIRS PEUGEOT SOUND HLTH CARE SYST,DEPT PSYCHIAT,SEATTLE,WA 98195. VET AFFAIRS MED CTR,SEATTLE,WA 98108. UNIV CALIF SAN DIEGO,DEPT NEUROSCI,SAN DIEGO,CA 92103. SO ILLINOIS UNIV,DEPT NEUROL,SPRINGFIELD,IL. UNIV CALIF LOS ANGELES,W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA. UNIV CALIF LOS ANGELES,DEPT PSYCHIAT & BIOBEHAV SCI,LOS ANGELES,CA 90024. HARBOR UCLA MED CTR,DEPT NEUROL,LOS ANGELES,CA. RP Payami, H (reprint author), OREGON HLTH SCI UNIV,VET AFFAIRS MED CTR,DEPT MOL & MED GENET,CDW 2,745 SW GAINES RD,PORTLAND,OR 97201, USA. OI Kaye, Jeffrey/0000-0002-9971-3478 FU NIA NIH HHS [U24 AG021886, AG0513C, AG08017, AG10123] NR 35 TC 68 Z9 69 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0028-3878 J9 NEUROLOGY JI Neurology PD AUG PY 1997 VL 49 IS 2 BP 512 EP 518 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA XR937 UT WOS:A1997XR93700033 PM 9270587 ER PT J AU Wen, PY Feske, SK Teoh, SK Stieg, PE AF Wen, PY Feske, SK Teoh, SK Stieg, PE TI Cerebral hemorrhage in a patient taking fenfluramine and phentermine for obesity SO NEUROLOGY LA English DT Article C1 BRIGHAM & WOMENS HOSP,DEPT NEUROSURG,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT NEUROSURG,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT RADIOL,BOSTON,MA. RP Wen, PY (reprint author), BRIGHAM & WOMENS HOSP,DEPT NEUROL,75 FRANCIS ST,BOSTON,MA 02115, USA. NR 7 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0028-3878 J9 NEUROLOGY JI Neurology PD AUG PY 1997 VL 49 IS 2 BP 632 EP 633 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA XR937 UT WOS:A1997XR93700063 PM 9270617 ER PT J AU Hobert, O Mori, I Yamashita, Y Honda, H Ohshima, Y Liu, YX Ruvkun, G AF Hobert, O Mori, I Yamashita, Y Honda, H Ohshima, Y Liu, YX Ruvkun, G TI Regulation of interneuron function in the C-elegans thermoregulatory pathway by the ttx-3 LIM homeobox gene SO NEURON LA English DT Article ID NEMATODE CAENORHABDITIS-ELEGANS; NUCLEOTIDE-GATED CHANNEL; TEMPERATURE RECEPTORS; CHEMOSENSORY NEURONS; HOMEODOMAIN PROTEIN; LARVAL DEVELOPMENT; NERVOUS-SYSTEM; MOTOR-NEURONS; CELL LINEAGE; DROSOPHILA AB Neural pathways, which couple temperature-sensing neurons to motor and autonomic outputs, allow animals to navigate away from and adjust metabolism rates in response to the temperature extremes often encountered. ttx-3 is required for the specification of the AIY interneuron in the C. elegans neural pathway that mediates thermoregulation. ttx-3 null mutant animals exhibit the same thermotactic behavioral defect as that seen with laser ablation of AIY in wild type, suggesting that AIY does not signal in this mutant. ttx-3 encodes a LIM homeodomain protein. A ttx-3-GFP fusion gene is expressed specifically in the adult AIY interneuron pair, which connects to thermosensory neurons. In ttx-3 mutant animals, the AIY interneuron is generated but exhibits patterns of abnormal axonal outgrowth. Thus, the TTX-3 LIM homeodomain protein is likely to regulate the expression of target genes required late in AIY differentiation for the function of this interneuron in the thermoregulatory pathway. The ttx-3-dependent thermosensory pathway also couples to the temperature-modulated dauer neuroendocrine signaling pathway, showing that ttx-3 specifies AIY thermosensory information processing of both motor and autonomic outputs. C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02114. KYUSHU UNIV,FAC SCI,DEPT BIOL,FUKUOKA 81281,JAPAN. RP Hobert, O (reprint author), MASSACHUSETTS GEN HOSP,DEPT MOL BIOL,BOSTON,MA 02114, USA. OI Hobert, Oliver/0000-0002-7634-2854 NR 45 TC 173 Z9 181 U1 0 U2 7 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0896-6273 J9 NEURON JI Neuron PD AUG PY 1997 VL 19 IS 2 BP 345 EP 357 DI 10.1016/S0896-6273(00)80944-7 PG 13 WC Neurosciences SC Neurosciences & Neurology GA XU146 UT WOS:A1997XU14600013 PM 9292724 ER PT J AU Baynes, K Tramo, MJ Reeves, AG Gazzaniga, MS AF Baynes, K Tramo, MJ Reeves, AG Gazzaniga, MS TI Isolation of a right hemisphere cognitive system in a patient with anarchic (alien) hand sign SO NEUROPSYCHOLOGIA LA English DT Article DE tactile anemia; agraphia; corpus callosum; disconnection syndrome ID CORPUS-CALLOSUM; BRAIN BISECTION; INTERHEMISPHERIC-TRANSFER; LEXICAL ACCESS; LANGUAGE; DISCONNECTION; SECTION; INFARCTION; CAPACITY; LESION AB We report evidence of isolated conceptual knowledge in the right hemisphere of a woman with chronic anarchic hand sign after ischemic infarction of the central four-fifths of the corpus callosum. Limited visual information was available to the right hemisphere, access to medial temporal structures subserving memory was disrupted and disconnection from left hemisphere language structures was complete. Still, the right hemisphere could build mental representations of objects via tactile input and use them in cross-modal matching. These representations were not accessed consistently in auditory comprehension or naming tasks. This functional specificity and its pathoanatomical correlates demonstrate that the study of anarchic hand sign can illuminate not just motor control issues but may inform our understanding of the representation and lateralization of conceptual knowledge as well. C1 HARVARD UNIV,SCH MED,DEPT NEUROBIOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,AUDITORY NEUROL UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,COGNIT BEHAV NEUROL UNIT,BOSTON,MA 02114. DARTMOUTH COLL SCH MED,DEPT MED,NEUROL SECT,HANOVER,NH 03756. DARTMOUTH COLL,PROGRAM COGNIT NEUROSCI,HANOVER,NH 03756. RP Baynes, K (reprint author), UNIV CALIF DAVIS,CTR NEUROSCI,DAVIS,CA 95616, USA. FU NIDCD NIH HHS [R29 DC00811]; NIMH NIH HHS [MH18012]; NINDS NIH HHS [NS 22626] NR 53 TC 12 Z9 12 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PD AUG PY 1997 VL 35 IS 8 BP 1159 EP 1173 DI 10.1016/S0028-3932(97)00019-5 PG 15 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA XM391 UT WOS:A1997XM39100012 PM 9256381 ER PT J AU Hollister, RD Page, KJ Hyman, BT AF Hollister, RD Page, KJ Hyman, BT TI Distribution of the messenger RNA for the extracellularly regulated kinases 1, 2 and 3 in rat brain: Effects of excitotoxic hippocampal lesions SO NEUROSCIENCE LA English DT Article DE MAP kinase; NFT; Alzheimer's disease; excitotoxicity; immunohistochemistry; tau ID ACTIVATED PROTEIN-KINASE; ALZHEIMER-LIKE STATE; TAU-PROTEIN; TYROSINE PHOSPHORYLATION; GENE FAMILY; DISEASE; IDENTIFICATION; LOCALIZATION; STIMULATION; SUBUNITS AB Neurofibrillary tangles in Alzheimer's disease are composed of hyperphosphorylated forms of the microtubule-associated protein tau. Based on biochemical criteria, several enzymes have emerged as potential tan protein kinases, including the extracellularly regulated kinases 1, 2 and 3. In situ hybridization was used to map the messenger RNA distribution of extracellularly regulated kinase 1, 2 and 3 in the adult rat brain and their response to excitotoxic hippocampal lesions was examined. Extracellularly regulated kinase I messenger RNA was uniformly expressed by glia, but was also present in the dentate gyrus and some other neuronal populations. Extracellularly regulated kinase 2 was exclusively neuronal and concentrated within the cortical laminae and the CA subfields of the hippocampal formation. Extracellularly regulated kinase 3 messenger RNA expression was similar to extracellularly regulated kinase 2 and was also present in neurons but the level of expression was lower. Extracellularly regulated kinases 2 and 3 messenger RNA expression was lost following excitotoxic injury, further supporting a neuronal localization. Extracellularly regulated kinase I messenger RNA expression appeared unaltered, suggesting a non-neuronal localization and lack of responsiveness to lesion at the level of transcription. By contrast, messenger RNA of sgk, a recently described serine/threonine kinase, was up-regulated by glial cells following excitotoxic injury. In Based on their messenger RNA distribution, cellular localization and response to lesion, it is clear that each kinase may function differently in various signaling pathways. Extracellularly regulated kinase 2, however, is the only kinase with the proper messenger RNA distribution to contribute to neurofibrillary tangle formation in Alzheimer's disease. (C) 1997 IBRO. Published by Elsevier Science Ltd. C1 MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02115. FU NIA NIH HHS [AG11337] NR 34 TC 28 Z9 28 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD AUG PY 1997 VL 79 IS 4 BP 1111 EP 1119 DI 10.1016/S0306-4522(97)00014-6 PG 9 WC Neurosciences SC Neurosciences & Neurology GA XJ265 UT WOS:A1997XJ26500013 PM 9219970 ER PT J AU Xiao, YH Weaver, DT AF Xiao, YH Weaver, DT TI Conditional gene targeted deletion by Cre recombinase demonstrates the requirement for the double-strand break repair Mre11 protein in murine embryonic stem cells SO NUCLEIC ACIDS RESEARCH LA English DT Article ID SACCHAROMYCES-CEREVISIAE; ESCHERICHIA-COLI; DNA-REPAIR; YEAST; RAD50 AB Repair of DNA damage resulting in double-strand breaks (DSBs) is controlled by gene products executing homologous recombination or end-joining pathways, The MRE11 gene has previously been implicated in DSB repair in the yeast Saccharomyces cerevisiae, Here we have developed a methodology to study the roles of the murine Mre11 homolog in pluripotent embryonic stem cells. Using a gene targeting approach, a triple LoxP site cassette was inserted into a region of MRE11 genomic DNA flanking conserved phosphodiesterase motifs, The addition of Cre recombinase activity promotes deletions of three types that can be scored. We find that deletion at phosphodiesterase motif III encoded in the N-terminus of Mre11 is acheived in the presence of a wild-type MRE11 allele, However, when the wild-type MRE11 allele is inactivated by gene targeted insertion of a neo marker, only Cre recombination events that allow expression of wild-type Mre11 protein are observed. Therefore, Mre11 is required for normal cell proliferation, This methodology introduces a means to study important regions of essential genes in cell culture models. C1 HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOL GENET,BOSTON,MA 02115. DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. NR 33 TC 222 Z9 226 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD AUG 1 PY 1997 VL 25 IS 15 BP 2985 EP 2991 DI 10.1093/nar/25.15.2985 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XP995 UT WOS:A1997XP99500006 PM 9224597 ER PT J AU Veronikis, DK McClure, GB Nichols, DH AF Veronikis, DK McClure, GB Nichols, DH TI The Vecchietti operation for constructing a neovagina: Indications, instrumentation, and techniques SO OBSTETRICS AND GYNECOLOGY LA English DT Article AB The Vecchietti method is a surgical technique for the treatment of vaginal agenesis that constructs a dilation-type neovagina in 7-9 days. We have performed the Vecchietti operation on six patients. The method was applied to create a primary neovagina, to lengthen a surgically foreshortened vagina, and to reconstruct an obliterated neovagina with or without the presence of a uterus. Two patients underwent the conventional transabdominal approach, and four, laparoscopy. Follow-up was 7-39 months, and neovaginal depth was 8.0-10.6 cm. The anatomic and functional results in all patients were excellent. (C) 1997 by The American College of Obstetricians and Gynecologists. C1 MASSACHUSETTS GEN HOSP,DIV UROGYNECOL & RECONSTRUCT PELV SURG,VINCENT MEM OBSTET & GYNECOL SERV,BOSTON,MA. NR 7 TC 41 Z9 41 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD AUG PY 1997 VL 90 IS 2 BP 301 EP 304 DI 10.1016/S0029-7844(97)00231-7 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA XM912 UT WOS:A1997XM91200029 PM 9241312 ER PT J AU Ciulla, TA Pesavento, RD AF Ciulla, TA Pesavento, RD TI Epiretinal fibrosis SO OPHTHALMIC SURGERY AND LASERS LA English DT Review ID PRERETINAL MACULAR FIBROSIS; RETINAL-DETACHMENT SURGERY; VITREOUS SURGERY; PREMACULAR FIBROPLASIA; PROGNOSTIC FACTORS; MEMBRANES; PUCKER; VITRECTOMY; FEATURES; GLIOSIS C1 TUFTS MED SCH,NEW ENGLAND EYE CTR,OPHTHALM CONSULTANTS BOSTON,BOSTON,MA 02114. INDIANA UNIV,SCH MED,DEPT OPHTHALMOL,RETINA SECT,INDIANAPOLIS,IN 46202. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BOSTON,MA. NR 72 TC 7 Z9 8 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0022-023X J9 OPHTHALMIC SURG LAS JI Ophthalmic Surg. Lasers PD AUG PY 1997 VL 28 IS 8 BP 670 EP 679 PG 10 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA XQ346 UT WOS:A1997XQ34600008 PM 9268999 ER PT J AU Husain, D Miller, JW Kenney, AG Michaud, N Flotte, TJ Gragoudas, ES AF Husain, D Miller, JW Kenney, AG Michaud, N Flotte, TJ Gragoudas, ES TI Photodynamic therapy and digital angiography of experimental iris neovascularization using liposomal benzoporphyrin derivative SO OPHTHALMOLOGY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; TUMOR-BEARING MICE; RING-A BPD; RUBEOSIS-IRIDIS; MODEL; PHOTOSENSITIZER; PHTHALOCYANINE AB Purpose: To study the efficacy of liposomal benzoporphyrin derivative (BPD) (Verteporfin) for the angiographic visualization and photodynamic therapy (PDT) of experimental iris neovascularization. Methods: Experimental iris neovascularization was induced in eight cynomolgus monkey eyes by occluding all the branch retinal veins with a dye-yellow (577-nm) laser, Iris angiography was done with sodium fluorescein, indocyanine green (ICG), and liposomal BPD to compare the visualization of normal and neovascular vessels by these three dyes. PDT was performed using an intravenous infusion of liposomal BPD (0.375-0.75 mg/kg), followed by irradiation with 689-nm light from a diode laser/slit-lamp delivery system using 600 mW/cm(2) irradiance and 150 J/cm(2) fluence. The effect of treatment was followed by iris photography and angiography, and the findings were confirmed by histopathology using light and electron microscopy. Results: Iris fluorescein angiography (FA) showed superficial tortuous and leaky new vessels. Liposomal BPD and ICG angiography of the same eye demonstrated deeper dilated and tortuous iris vessels, with minimal dye leakage. PDT of the iris with irradiation, performed within 20 minutes of the start of dye infusion (0.75 mg/kg), resulted in angiographic and histologic occlusion of iris vessels examined at 24 hours. Three to nine days after PDT, histopathologic examination showed regression of the iris neovascular membrane, with some open vessels, Conclusions: Liposomal BPD and ICG provided angiographic visualization of deeper normal and neovascular iris vessels. PDT using liposomal BPD leads to effective early closure to experimental iris neovascularization. C1 HARVARD UNIV,RETINA SERV,LASER RES LAB,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BOSTON,MA 02114. HARVARD UNIV,WELLMAN LABS PHOTOMED,DEPT DERMATOL,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BOSTON,MA 02114. NR 30 TC 31 Z9 35 U1 1 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD AUG PY 1997 VL 104 IS 8 BP 1242 EP 1250 PG 9 WC Ophthalmology SC Ophthalmology GA XP841 UT WOS:A1997XP84100017 PM 9261310 ER PT J AU Taravella, MJ Johnson, DW Petty, JG Keyser, RB Foster, CS Lundberg, BE AF Taravella, MJ Johnson, DW Petty, JG Keyser, RB Foster, CS Lundberg, BE TI Infectious posterior scleritis caused by Pseudallescheria boydii - Clinicopathologic findings SO OPHTHALMOLOGY LA English DT Article ID KERATITIS AB Purpose: The purpose of the study is to describe an unusual case of infectious posterior scleritis after excision of a pterygium, Methods: The case history of a patient in whom anterior and posterior scleritis developed after excision of a pterygium is reviewed, Histopathologic findings are presented, Results: Pathologic examination results of a scleral biopsy site and the eye showed extensive involvement of the posterior sclera with fungi that on culture grew Pseudallescheria boydii. The development of posterior scleral thickening and intrascleral abscesses gave the clinical impression of autoimmune posterior scleritis or possible tumor, Ultrasonography and computed tomography scan of the eye and orbit proved particularly helpful in following progression of scleral involvement, Conclusions: Pseudallescheria boydii is capable of causing an infectious posterior scleritis, which can mimic autoimmune posterior scleritis. The use of systemic immunosuppressive agents contributed to this unusual clinical presentation, Progression of posterior scleritis in the face of apparent adequate immunosuppressive therapy always should suggest the possibility of tumor or infection. C1 UNIV COLORADO,HLTH SCI CTR,DEPT OPHTHALMOL,DENVER,CO. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BOSTON,MA. UNIV COLORADO,HLTH SCI CTR,DEPT MED,DIV INFECT DIS,DENVER,CO 80262. NR 10 TC 9 Z9 10 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD AUG PY 1997 VL 104 IS 8 BP 1312 EP 1316 PG 5 WC Ophthalmology SC Ophthalmology GA XP841 UT WOS:A1997XP84100026 PM 9261319 ER PT J AU Kaiser, PK Pineda, R AF Kaiser, PK Pineda, R TI A study of topical nonsteroidal anti-inflammatory drops and no pressure patching in the treatment of corneal abrasions SO OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of American-Academy-of-Ophthalmology CY OCT 29-NOV 02, 1995 CL ATLANTA, GA SP Amer Acad Ophthalmol ID LASER PHOTOREFRACTIVE KERATECTOMY; ANTIINFLAMMATORY DRUGS; DICLOFENAC SODIUM; DISCOMFORT; EFFICACY; AGENTS; PAIN AB Objective: To evaluate the effectiveness of an ophthalmic nonsteroidal anti-inflammatory drug (NSAID) in the treatment of noninfected, non-contact lens-related, traumatic corneal abrasions and no pressure patch, Design: A single-center, randomized, double-masked, placebo-controlled study. Participants: One hundred patients with noninfected, non-contact lens-related, traumatic or foreign body removal-related corneal abrasions less than 36 hours in duration. Intervention: All patients received a cycloplegic drop and erythromycin or polymyxin B (Polysporin Ophthalmic Ointment, Burroughs Wellcome, Research Triangle Park, NC), Patients were then randomized to receive either ketorolac tromethamine 0.5% ophthalmic solution or control vehicle drops, Main Outcome Measures: The main outcome measures were six subjective symptoms monitored daily, evaluation of corneal abrasion, and determination of adverse events, Long-term complications were determined 3 to 8 months after randomization, Results: Twelve patients were excluded from the study, One day after randomization, patients receiving ketorolac tromethamine 0.5% ophthalmic solution noted significantly decreased levels of pain (P < 0.002), photophobia (P < 0.009), and foreign body sensation (P < 0.003) as compared with the control vehicle group, In addition, the time to resumption of normal activities was shorter in the group who received ketorolac tromethamine 0.5% ophthalmic solution (P < 0.001). There was no statistical difference in the amount of tearing, healing time, acuity changes, or complication rates between the two groups, Conclusions: Ketorolac tromethamine 0.5% ophthalmic solution provides increased patient comfort without clinical adverse effects when used as adjunctive therapy in the treatment of noninfected, non-contact lens-related, traumatic corneal abrasions. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BOSTON,MA. RP Kaiser, PK (reprint author), CLEVELAND CLIN FDN,DIV OPHTHALMOL A31,9500 EUCLID AVE,CLEVELAND,OH 44195, USA. NR 23 TC 41 Z9 43 U1 1 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD AUG PY 1997 VL 104 IS 8 BP 1353 EP 1359 PG 7 WC Ophthalmology SC Ophthalmology GA XP841 UT WOS:A1997XP84100034 PM 9261326 ER PT J AU Todd, R Gallagher, GT Kaban, LB AF Todd, R Gallagher, GT Kaban, LB TI Mass in the infratemporal fossa SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTICS LA English DT Editorial Material ID PERIPHERAL AMELOBLASTOMA C1 HARVARD UNIV,SCH DENT MED,DEPT ORAL & MAXILLOFACIAL SURG,BOSTON,MA 02115. RP Todd, R (reprint author), MASSACHUSETTS GEN HOSP,DEPT ORAL & MAXILLOFACIAL SURG,FRUIT ST,BOSTON,MA 02114, USA. NR 12 TC 3 Z9 3 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 1079-2104 J9 ORAL SURG ORAL MED O JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. PD AUG PY 1997 VL 84 IS 2 BP 116 EP 118 DI 10.1016/S1079-2104(97)90054-8 PG 3 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA XR145 UT WOS:A1997XR14500006 PM 9269009 ER PT J AU Ebb, DH Weinstein, HJ AF Ebb, DH Weinstein, HJ TI Diagnosis and treatment of childhood acute myelogenous leukemia SO PEDIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID ACUTE MYELOID-LEUKEMIA; BONE-MARROW TRANSPLANTATION; ACUTE NONLYMPHOBLASTIC LEUKEMIA; ACUTE NONLYMPHOCYTIC LEUKEMIA; CHILDRENS-CANCER-GROUP; TOTAL-BODY IRRADIATION; HIGH-DOSE CYTARABINE; ACUTE PROMYELOCYTIC LEUKEMIA; CELL-SURFACE ANTIGENS; DOWNS-SYNDROME AB Acute myelogenous leukemia (AML) accounts for about 20% of the acute leukemias seen in children. In contrast to childhood acute lymphoblastic leukemia (ALL), there has only been a modest improvement in the cure rate of children with AML during the past two decades. Approximately 40% of children treated with chemotherapy alone are long-term survivors. The outcome is somewhat better for those children who are given bone marrow transplants from histocompatible sibling donors early in the first remission. During the last decade, however, new insights into the molecular basis of AML has increased our understanding of the pathogenesis and biology of this group of leukemias and are beginning to provide us with new therapeutic strategies. C1 HARVARD UNIV,SCH MED,DEPT PEDIAT,CAMBRIDGE,MA 02138. RP Ebb, DH (reprint author), MASSACHUSETTS GEN HOSP,PEDIAT HEMATOL ONCOL UNIT,BLAKE 255,55 FRUIT ST,BOSTON,MA 02114, USA. NR 93 TC 13 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 0031-3955 J9 PEDIATR CLIN N AM JI Pediatr. Clin. N. Am. PD AUG PY 1997 VL 44 IS 4 BP 847 EP & DI 10.1016/S0031-3955(05)70533-2 PG 17 WC Pediatrics SC Pediatrics GA XT840 UT WOS:A1997XT84000005 PM 9286288 ER PT J AU Grier, HE AF Grier, HE TI The Ewing family of tumors - Ewing's sarcoma and primitive neuroectodermal tumors SO PEDIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID ROUND-CELL TUMORS; TERM FOLLOW-UP; COMBINATION CHEMOTHERAPY; PROGNOSTIC-SIGNIFICANCE; CHIMERIC TRANSCRIPTS; MULTIMODAL THERAPY; PEDIATRIC-ONCOLOGY; SURGICAL RESECTION; RADIATION-THERAPY; COMBINED-MODALITY AB Many new developments in the Ewing family of tumors have occurred during the last decade. The addition of new drugs in the treatment of the disease has improved outcome, and biologic discoveries have increased our basic understanding of these tumors greatly. C1 CHILDRENS HOSP,DANA FARBER CANC INST,DEPT PEDIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. NR 84 TC 152 Z9 157 U1 0 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0031-3955 J9 PEDIATR CLIN N AM JI Pediatr. Clin. N. Am. PD AUG PY 1997 VL 44 IS 4 BP 991 EP & DI 10.1016/S0031-3955(05)70541-1 PG 15 WC Pediatrics SC Pediatrics GA XT840 UT WOS:A1997XT84000013 PM 9286296 ER PT J AU Pontius, AA AF Pontius, AA TI Lack of sex differences among East Ecuadorian school children on geometric figure rotation and face drawings SO PERCEPTUAL AND MOTOR SKILLS LA English DT Article AB No difference was shown on two spatial tasks, the Geometric Figure Rotation Task and the Draw-A-Person-With-Face-In-Front for 24 boys and 24 girls (ages 9-10) in eastern Ecuador, where girls still engage in women's traditional tasks, e.g., sewing, needle work, weaving, and knotting, which involve spatial representation. C1 MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02114. RP Pontius, AA (reprint author), HARVARD UNIV,SCH MED,55 FRUIT ST,BOSTON,MA 02114, USA. NR 13 TC 0 Z9 0 U1 0 U2 0 PU PERCEPTUAL MOTOR SKILLS PI MISSOULA PA PO BOX 9229, MISSOULA, MT 59807 SN 0031-5125 J9 PERCEPT MOTOR SKILL JI Percept. Mot. Skills PD AUG PY 1997 VL 85 IS 1 BP 72 EP 74 PG 3 WC Psychology, Experimental SC Psychology GA XU999 UT WOS:A1997XU99900013 PM 9293560 ER PT J AU Cahalin, LP Semigran, MJ Dec, GW AF Cahalin, LP Semigran, MJ Dec, GW TI Inspiratory muscle training in patients with chronic heart failure awaiting cardiac transplantation: Results of a pilot clinical trial SO PHYSICAL THERAPY LA English DT Article DE breathing exercise; cardiac transplantation; exercise; heart failure ID OBSTRUCTIVE PULMONARY-DISEASE; LEFT-VENTRICULAR DYSFUNCTION; SKELETAL-MUSCLE; EXERCISE; ABNORMALITIES; DYSPNEA; REHABILITATION; INTENSITY; COPD AB Background and Purpose. Persons with chronic heart failure (HF) have poor ventilatory muscle strength, and this weakness is associated with dyspnea. The purpose of this study was to examine the effects of inspiratory muscle training (IMT) on ventilatory muscle strength and dyspnea in patients with chronic HF. Subjects. Fourteen patients (mean age [+/-SD]=52+/-8.5 years) with end-stage cardiomyopathy and chronic HF (mean left ventricular ejection fraction=23%+/-13% and New York Heart Association class=3.6+/-0.6) participated in the study. Methods. Inspiratory muscle training was performed at 20% of maximal inspiratory pressure (MIP) for 5 to 15 minutes, three times a day, for 8 weeks. Dyspnea was evaluated at rest: and during exercise. Results. Both MIP and maximal expiratory pressure (MEP) were greater after 2 weeks of IMT (51+/-21 to 63+/-23 cm H2O and 85+/-22 to 96+/-19 cm H2O, representing 24% and 13% improvement). Dyspnea scores at rest and during exercise decreased after 2 weeks (2.0+/-0.7 to 1.3+/-0.5 and 3.6+/-0.5 to 2.6+/-0.6, representing 29% and 28% improvement) and plateaued throughout the remainder of IMT. Baseline MEP was related to the percentage of change in MEP after IMT (r= -.72), and several measures of pulmonary function were related to the degree of improvement in dyspnea after IMT (r=-.57 to -.82) and in MIP after IMT (r=.71). Conclusion and Discussion. Improvements in MIP, MEP, and dyspnea were found after 2 weeks of IMT. Greater pulmonary function was associated with greater improvement in dyspnea and ventilatory muscle strength after IMT. These improvements may decrease the dependency and impairment associated with chronic HF. C1 MASSACHUSETTS GEN HOSP,HEART FAILURE & TRANSPLANTAT SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138. MASSACHUSETTS GEN HOSP,CARDIAC UNIT,BOSTON,MA 02114. RP Cahalin, LP (reprint author), BOSTON UNIV,SARGENT COLL ALLIED HLTH PROFESS,635 COMMONWEALTH AVE,BOSTON,MA 02215, USA. NR 38 TC 18 Z9 18 U1 0 U2 5 PU AMER PHYSICAL THERAPY ASSOC PI ALEXANDRIA PA 1111 N FAIRFAX ST, ALEXANDRIA, VA 22314 SN 0031-9023 J9 PHYS THER JI Phys. Ther. PD AUG PY 1997 VL 77 IS 8 BP 830 EP 838 PG 9 WC Orthopedics; Rehabilitation SC Orthopedics; Rehabilitation GA XP460 UT WOS:A1997XP46000007 PM 9256871 ER PT J AU Morrow, NS Garrick, T AF Morrow, NS Garrick, T TI Effects of intermittent tail shock or water avoidance on proximal colonic motor contractility in rats SO PHYSIOLOGY & BEHAVIOR LA English DT Article DE proximal colon; tail shock; water avoidance; defecation; bowel dysfunction; feeding ID CORTICOTROPIN-RELEASING FACTOR; IRRITABLE BOWEL SYNDROME; GASTROINTESTINAL TRANSIT; PSYCHOLOGICAL STRESS; RESTRAINT STRESS; EMOTIONAL-STRESS; NEUROPEPTIDE-Y; MOTILITY; CRF; COLD AB Changes in proximal colonic mechanical activity and defecation during exposure to three different types of experimental stressors were examined in rats chronically implanted with 2 force transducers on the proximal colon. To validate the integrity of the recording system, meal-induced changes in proximal colonic contractility were initially measured in all rats 1-2 days prior to stress induction. Different groups of ad lib fed rats were then exposed to tail shock, re-exposure to the shock chamber or water avoidance for 1 h over the next 1-2 days. Two types of phasic colonic contractions, long (0-3/min) and short (6-8/min) duration, were analyzed separately using a computer. Long duration contractions were significantly elevated 21-71% over fasting basal values from 61-120 min following a meal. No other consistent changes during the prandial or postprandial period were observed. Tail shock significantly suppressed proximal colonic contractility from pre-shock values and increased fecal output and fluid content when compared to ad lib fed rats that were not shocked. Fecal output increased but proximal colonic contractility did not change when previously shocked rats were re-exposed to the tail shock chamber but not shocked. In rats exposed to water avoidance, proximal colonic contractility was minimally suppressed but defecation was significantly greater than home cage control animals. These results indicate that proximal colonic contractile activity is differentially altered by exposure to different environmental stressors and may be a contributing factor in stress-induced bowel dysfunction. (C) 1997 Elsevier Science Inc. C1 UNIV CALIF LOS ANGELES,DEPT PSYCHIAT,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,DEPT BIOBEHAV SCI,LOS ANGELES,CA 90024. RP Morrow, NS (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,DIGEST DIS RES CTR,11301 WILSHIRE BLVD,RM 203,LOS ANGELES,CA 90073, USA. FU NIDDK NIH HHS [DK 41301] NR 32 TC 19 Z9 19 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0031-9384 J9 PHYSIOL BEHAV JI Physiol. Behav. PD AUG PY 1997 VL 62 IS 2 BP 233 EP 239 DI 10.1016/S0031-9384(97)00108-X PG 7 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA XN410 UT WOS:A1997XN41000003 PM 9251963 ER PT J AU Zhang, H Wang, J Nickel, U Allen, RD Goodman, HM AF Zhang, H Wang, J Nickel, U Allen, RD Goodman, HM TI Cloning and expression of an Arabidopsis gene encoding a putative peroxisomal ascorbate peroxidase SO PLANT MOLECULAR BIOLOGY LA English DT Article DE 14-3-3 protein; Arabidopsis; ascorbate peroxidase; oxidative stress; peroxisome ID SIGNALING PROTEINS; 14-3-3 PROTEINS; FAMILY; PLANTS; OXYGEN; STRESS; RECOGNITION; SUPEROXIDE; THALIANA; ENZYMES AB An Arabidopsis 14-3-3 protein, AFT1, was used as a 'bait' in the two-hybrid system to identify its interacting proteins. One of the candidate proteins, APX3, was identified as a putative peroxisomal membrane-bound ascorbate peroxidase. Ascorbate peroxidases are important defense enzymes that protect plant cells from oxidative stress damage. DNA blot analysis indicates that APX3 is encoded by a single-copy gene in the Arabidopsis genome. RNA blot analyses show that APX3 transcript levels increase slightly in response to cold, UV light, and treatments with hydrogen peroxide and paraquat. The activity of APX3 in Arabidopsis may be controlled in two ways: its enzymatic activity through protein-protein interactions and its transcription by transcriptional or posttranscriptional regulation. C1 HENDRIX COLL,DEPT BIOL,CONWAY,AR 72032. MASSACHUSETTS GEN HOSP,DEPT MOL BIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02114. RP Zhang, H (reprint author), TEXAS TECH UNIV,DEPT BIOL SCI,LUBBOCK,TX 79409, USA. NR 29 TC 66 Z9 81 U1 0 U2 7 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-4412 J9 PLANT MOL BIOL JI Plant Mol.Biol. PD AUG PY 1997 VL 34 IS 6 BP 967 EP 971 DI 10.1023/A:1005814109732 PG 5 WC Biochemistry & Molecular Biology; Plant Sciences SC Biochemistry & Molecular Biology; Plant Sciences GA XU457 UT WOS:A1997XU45700014 PM 9290648 ER PT J AU Eavey, RD AF Eavey, RD TI Transplantation of chondrocytes utilizing a polymer-cell construct to produce tissue-engineered cartilage in the shape of a human ear - Discussion SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Editorial Material RP Eavey, RD (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,243 CHARLES ST,BOSTON,MA 02114, USA. NR 3 TC 3 Z9 4 U1 1 U2 8 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 AUG PY 1997 VL 100 IS 2 BP 303 EP 304 DI 10.1097/00006534-199708000-00002 PG 2 WC Surgery SC Surgery GA XN996 UT WOS:A1997XN99600002 ER PT J AU Li, YY Kang, JX Leaf, A AF Li, YY Kang, JX Leaf, A TI Differential effects of various eicosanoids on the production or prevention of arrhythmias in cultured neonatal rat cardiac myocytes SO PROSTAGLANDINS LA English DT Article DE eicosanoids; neonatal; rat myocytes; arrhythmia ID POLYUNSATURATED FATTY-ACIDS; LONG-CHAIN; LYSOPHOSPHATIDYLCHOLINE; REPERFUSION AB To identify the arrhythmogenic and the antiarrhythmic eicosanoids, cultured, spontaneously beating, neonatal rat cardiac myocytes were used to examine the effects of various eicosanoids added to the medium superfusing the cells at different concentrations on the contraction of the myocytes. Superfusion of the myocytes with the prostaglandins (PGD(2), PGE(2), PGF(2 alpha)) or the thromboxane (TXA(2))-mimetic, U 46619, induced reversible tacharrhythmias characterized by an increased beating rate, chaotic activity and contractures. These effects are concentration-dependent. PGF(2 alpha) and U 46619 were much more potent than PGD(2) or PGE(2) in the production of tachyarrhythmias. Prostacyclin (PGI(2)) induced a marked reduction in the contraction rate of the cells with a slight increase in the amplitude of the contractions and showed a protective effect against the arrhythmias induced by PGF(2 alpha) and TXA(2) (U 46619). PGE(1) exerted a dose-dependent dual effect on the contraction of the myocytes. At low concentrations (<2 mu M), PGE(1) reduced the contraction rate of the cells with an increase in the amplitude of the contractions and effectively terminated the tachyarrhythmias induced by arrhythmogemic agents, such as isoproterenol, ouabain and U 46619. At higher concentrations (>5 mu M), PGE, caused cell contractures and chaotic activity In contrast, the lipoxygenase products [leukotriene (LT) B-4, LTC4, LTD4 & LTE4] of arachidonic acid (AA) had no significant effect on the myocyte contractions. C1 MASSACHUSETTS GEN HOSP,DEPT MED,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02114. FU NIDDK NIH HHS [R01-DK 38165] NR 24 TC 78 Z9 79 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0090-6980 J9 PROSTAGLANDINS JI Prostaglandins PD AUG PY 1997 VL 54 IS 2 BP 511 EP 530 DI 10.1016/S0090-6980(97)00122-6 PG 20 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YB699 UT WOS:A1997YB69900001 PM 9380795 ER PT J AU Lenderking, WR Testa, MA Katzenstein, D Hammer, S AF Lenderking, WR Testa, MA Katzenstein, D Hammer, S TI Measuring quality of life in early HIV disease: the modular approach SO QUALITY OF LIFE RESEARCH LA English DT Article; Proceedings Paper CT International State-of-the-Art Meeting on HIV CY OCT 01-02, 1996 CL PARIS, FRANCE DE quality of life; HIV infection; antiviral therapy; CD4; modular approach; symptoms ID IMMUNODEFICIENCY-VIRUS INFECTION; PLACEBO-CONTROLLED TRIAL; OF-LIFE; FUNCTIONAL STATUS; ANTIHYPERTENSIVE THERAPY; STATUS QUESTIONNAIRE; MEDICAL OUTCOMES; PERCEIVED HEALTH; RELIABILITY; ZIDOVUDINE AB Rationale: to examine the reliability and validity of the General Health Self-assessment, a modular questionnaire for self-assessment of quality of life (QoL) in human immunodeficiency virus (HIV) clinical trials and to describe the baseline Got. of participants in a large HIV clinical trial. Design: the domains assessed include health perceptions, physical, psychological and role/social functioning, health care utilization and symptom distress. Method: 1,694 subjects with early HIV infection enrolled in the AIDS Clinical Trials Group Protocol 175 completed the scale at baseline. Results: the domains demonstrated reliability, construct and discriminant validity. A worse Gel, was associated with recent hospitalization and symptomatic status. Prior antiretroviral therapy was associated with higher health perceptions and wellbeing. The presence of symptom distress was related to lower QoL on the other scales. There was no relationship between QoL scales and the baseline CD4 count. Women showed a lower QoL than men on all scales, while ethnicity was related to differences in health perceptions and physical and psychological functioning. Conclusions: the General Health Self-assessment shows excellent potential as a measure of QoL for HIV-infected patients in clinical trials. Further research is necessary to determine the responsiveness of the scale to clinical and immunological changes in HIV-infected individuals. C1 HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,STAT & DATA ANAL CTR,QOL SECT,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02114. STANFORD UNIV,MED CTR,DIV INFECT DIS,CTR AIDS RES,STANFORD,CA 94305. DEACONESS HOSP,DIV INFECT DIS,BOSTON,MA 02115. RP Lenderking, WR (reprint author), PHASE 5 TECHNOL INC,20 WALNUT ST,WELLESLEY,MA 02181, USA. FU AHRQ HHS [R01-HS07767-03]; PHS HHS [N01-A195030] NR 38 TC 61 Z9 63 U1 0 U2 3 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 AUG PY 1997 VL 6 IS 6 BP 515 EP 530 DI 10.1023/A:1018408115729 PG 16 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA XX980 UT WOS:A1997XX98000007 PM 9330552 ER PT J AU Berzon, RA Leplege, AP Lohr, KN Lenderking, WR Wu, AW AF Berzon, RA Leplege, AP Lohr, KN Lenderking, WR Wu, AW TI Summary and recommendations for future research SO QUALITY OF LIFE RESEARCH LA English DT Editorial Material C1 HOP BICETRE,INSERM,LE KREMLIN BICETR,FRANCE. RES TRIANGLE INST,RES TRIANGLE PK,NC 27709. PHASE 5 TECHNOL,WELLESLEY HILLS,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,BALTIMORE,MD. RP Berzon, RA (reprint author), BAYER PHARMACEUT DIV,W HAVEN,CT, USA. NR 0 TC 8 Z9 8 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 AUG PY 1997 VL 6 IS 6 BP 601 EP 605 DI 10.1023/A:1018472402525 PG 5 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA XX980 UT WOS:A1997XX98000014 PM 9330559 ER PT J AU Palayoor, ST Bump, EA Teicher, BA Coleman, CN AF Palayoor, ST Bump, EA Teicher, BA Coleman, CN TI Apoptosis and clonogenic cell death in PC3 human prostate cancer cells after treatment with gamma radiation and suramin SO RADIATION RESEARCH LA English DT Article ID HAMSTER FIBROSARCOMA CELLS; FIBROBLAST GROWTH-FACTOR; PROTEIN KINASE-C; T-LYMPHOMA CELLS; IN-VITRO; PHASE-I; PROLIFERATION; INHIBITION; DRUG; IRRADIATION AB Suramin is a novel cytostatic/cytotoxic agent that is currently undergoing clinical trials in the treatment of hormone- and chemo-refractory tumors. Its unusual mechanism of action and its activity against prostate cancer raise the possibility that it could be particularly suitable for combined-modality treatment of prostate cancer. PC3 human prostate cancer tells were used as an in vitro model to test the possible interaction between suramin and ionizing radiation. Treatment with gamma radiation resulted in detachment of PC3 cells from the monolayer, and the detached cells exhibited internucleosomal DNA fragmentation characteristic of apoptosis. Low concentrations of suramin (50-100 mu g/ml, 35-70 mu M) increased spontaneous as well as radiation-enhanced apoptosis. However, suramin inhibited spontaneous and radiation-enhanced apoptosis at 300 mu g/ml (210 mu M), a concentration that is more commonly used in the clinic. At this concentration suramin inhibited DNA fragmentation induced by chemotherapeutic drugs as well. The effect of suramin on inhibition of DNA fragmentation was reversible if the suramin was removed 24 h after irradiation. Despite inhibition of radiation-induced apoptosis by 300 mu g/ml suramin (from 5% to 2.9% at 48 h), clonogenic cell death was enhanced by the combination of suramin and radiation. The effects of radiation and suramin on cIonogenic cell survival appeared to be additive by isobologram analysis at clinically relevant radiation doses. Continuous exposure to a lower concentration of suramin (100 mu g/ml) during the clonogenic assay period was as effective in decreasing clonogenic survival as 48 h exposure to 300 mu g/ml suramin in decreasing clonogenic survival. Our data indicate that, when used in combination with radiation, suramin may be effective at concentrations that are lower than those required for efficacy as a single agent. (C) 1997 bg Radiation Research Society. C1 DANA FARBER CANC INST,BOSTON,MA 02115. RP Palayoor, ST (reprint author), HARVARD UNIV,SCH MED,JOINT CTR RADIAT THERAPY,330 BROOKLINE AVE,BOSTON,MA 02215, USA. FU NCI NIH HHS [CA 42391, CA 46776] NR 65 TC 25 Z9 25 U1 0 U2 1 PU RADIATION RESEARCH SOC PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD AUG PY 1997 VL 148 IS 2 BP 105 EP 114 DI 10.2307/3579566 PG 10 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA XP963 UT WOS:A1997XP96300001 PM 9254728 ER PT J AU Palmer, WE Levine, SM Dupuy, DE AF Palmer, WE Levine, SM Dupuy, DE TI Knee and shoulder fractures: Association of fracture detection and marrow edema on MR images with mechanism of injury SO RADIOLOGY LA English DT Article DE fractures, MR; knee, fractures; shoulder, injuries ID ANTERIOR CRUCIATE LIGAMENT; PREVALENCE; TEARS; CLASSIFICATION; ABNORMALITIES; LESIONS; SIGN AB PURPOSE: To assess the value of magnetic resonance (MR) imaging for enabling the classification of fracture mechanisms and to compare marrow edema caused by compressive forces with that caused by tensile forces. MATERIALS AND METHODS: In 62 knees or shoulders, 78 fractures were identified prospectively on MR images or plain radiographs; compressive or tensile forces were determined retrospectively to have caused impaction or distraction fractures, respectively. Edema was measured on T1-weighted images. Frequencies of fracture detection on MR images or plain radiographs were compared. RESULTS: Forty-nine(63%) and 29 (37%) fractures were attributed to compressive and tensile forces, respectively. Edema measured 31 mm +/- 10 in impaction fractures and 2.5 mm +/- 2.4 in distraction fractures (P < .001). MR images and plain radiographs of 63 fractures were compared. On MR images, distraction fractures, including four of seven Segond fractures, were missed more often than impaction fractures (P < .008). Fractures overlooked on MR images were associated with less edema (P < .003). CONCLUSION: On MR images, impaction fractures demonstrate prominent marrow edema, and distraction fractures demonstrate minimal edema. Impaction fractures are more often missed on plain radiographs, and distraction fractures are more often missed on MR images. Segond fractures should be suspected if MR images show lateral capsular ligamentous injury in the knee; in these cases, evaluation with plain radiography is warranted. RP Palmer, WE (reprint author), HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,DEPT RADIOL,15 PARKMAN ST,WACC SUITE 515,BOSTON,MA 02114, USA. OI Dupuy, Damian/0000-0003-0524-5982 NR 22 TC 34 Z9 34 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD AUG PY 1997 VL 204 IS 2 BP 395 EP 401 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA XL644 UT WOS:A1997XL64400019 PM 9240526 ER PT J AU Enochs, WS Petherick, P Bogdanova, A Mohr, U Weissleder, R AF Enochs, WS Petherick, P Bogdanova, A Mohr, U Weissleder, R TI Paramagnetic metal scavenging by melanin: MR imaging SO RADIOLOGY LA English DT Article DE magnetic resonance (MR), experimental; melanoma; skin, neoplasms ID ELECTRON-SPIN RESONANCE; PROTON RELAXATION; MELANOTIC MELANOMA; SYNTHETIC MELANINS; SPECTROSCOPY; IONS; IDENTIFICATION; MANGANESE; AFFINITY; LESIONS AB PURPOSE: To quantitate the binding of metals to synthetic melanin in vitro, which is believed to be the reason why melanotic melanomas are hyperintense on T1-weighted magnetic resonance (MR) images, and to test whether such binding by natural melanin can be detected in cultured melanoma cells in vivo with MR imaging. MATERIALS AND METHODS: Seven synthetic metallomelanins were prepared and their metal contents and relaxivities determined. Melanotic PC1A and amelanotic B16 melanoma cells were incubated with increasing concentrations of iron. MR images of synthetic melanin and cell phantoms were obtained. RESULTS: The iron-binding capacities and relaxivities of the different synthetic metallomelanins varied considerably, which reflects the heterogeneous structure of melanin and the complexity of its binding of metals. Nevertheless, the MR signal intensities of the synthetic melanin and cell phantoms show marked increases that scale, respectively, with increasing iron content and iron concentration in the incubation medium. CONCLUSION: Melanotic melanomas are hyperintense on T1-weighted images because of paramagnetic metal scavenging. This observation has implications for the interpretation of MR images, the improved detection of melanomas, and the development of imaging marker genes. C1 MASSACHUSETTS GEN HOSP,CTR MOL IMAGING RES,DEPT RADIOL,CHARLESTOWN,MA 02129. FU NCI NIH HHS [1RO1 CA59649-01] NR 37 TC 141 Z9 154 U1 1 U2 8 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD AUG PY 1997 VL 204 IS 2 BP 417 EP 423 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA XL644 UT WOS:A1997XL64400022 PM 9240529 ER PT J AU Weissleder, R Simonova, M Bogdanova, A Bredow, S Enochs, WS Bogdanov, A AF Weissleder, R Simonova, M Bogdanova, A Bredow, S Enochs, WS Bogdanov, A TI MR imaging and scintigraphy of gene expression through melanin induction SO RADIOLOGY LA English DT Article DE genes; magnetic resonance (MR), experimental; melanoma; radionuclide imaging ID HUMAN TYROSINASE; MELANOGENESIS; FIBROBLASTS; RESONANCE; CDNA AB PURPOSE: To determine whether an expression vector that encodes for human tyrosinase, the key enzyme in the melanin production pathway, can be used to image gene expression with magnetic resonance (MR) imaging and scintigraphy. MATERIALS AND METHODS: Mouse fibroblasts and human embryonal kidney cells were transfected with an expression vector that contained a complete complementary DNA sequence that encodes the human tyrosinase gene (pcDNA3tyr). Transfected cells were assayed for messenger RNA presence, melanin staining, and indium-lll binding; scintigraphy and MR imaging were performed. RESULTS: Transfected cells contained tyrosinase messenger RNA and stained positively for melanin. Transfected cells had a higher In-111 binding capacity than nontransfected cells, a difference readily detectable with scintigraphy. MR imaging showed transfected cells to have markedly higher signal intensity after gene transfer than nontransfected cells. CONCLUSION Gene transfer and expression in cell culture can be detected with MR imaging and scintigraphy. The proposed strategy of using an imaging marker gene may have a substantial effect on the noninvasive imaging of gene therapy. RP Weissleder, R (reprint author), MASSACHUSETTS GEN HOSP,CTR MOL IMAGING RES,DEPT RADIOL,BLDG 149,5403 13TH ST,CHARLESTOWN,MA 02129, USA. FU NINDS NIH HHS [1RO1 NS35258-01] NR 25 TC 138 Z9 151 U1 1 U2 5 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD AUG PY 1997 VL 204 IS 2 BP 425 EP 429 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA XL644 UT WOS:A1997XL64400023 PM 9240530 ER PT J AU Gervais, DA Petersein, A Lee, MJ Hahn, PF Saini, S Mueller, PR AF Gervais, DA Petersein, A Lee, MJ Hahn, PF Saini, S Mueller, PR TI US-guided thoracentesis: Requirement for postprocedure chest radiography in patients who receive mechanical ventilation versus patients who breathe spontaneously SO RADIOLOGY LA English DT Article DE pleura, fluid; pneumothorax; thoracentesis ID COMPLICATIONS; PNEUMOTHORAX; THORACOCENTESIS; RISK AB PURPOSE: To identify a population of patients who may not need chest radiography after diagnostic thoracentesis by assessing and comparing the pneumothorax rates in patients with mechanical ventilation (intubation) versus spontaneously breathing patients (no intubation). MATERIALS AND METHODS: A retrospective review of all radiographs, clinical records, and ultrasound (US) scans obtained in 434 patients who underwent US-guided thoracentesis was performed. Three hundred forty-two patients were not intubated and 92 were intubated. Nine patients were excluded because of preexisting pneumothorax. The size of the effusion, the needle size used, and whether a pneumothorax occurred after the procedure were determined. RESULTS: Results demonstrated that only 10 pneumothoraces occurred (six in intubated and four in nonintubated patients). None of the nonintubated patients with pneumothorax and two of the six intubated patients with pneumothorax needed chest tubes. The difference in the pneumothorax rate between intubated and nonintubated patients was statistically significant (P <.01). CONCLUSION: Spontaneously breathing patients who undergo diagnostic thoracentesis do not need postprocedure chest radiography. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIOL,BOSTON,MA 02114. CHILDRENS HOSP,DEPT RADIOL,BOSTON,MA 02115. FREE UNIV BERLIN,KLINIKUM BENJAMIN FRANKLIN,RADIOL KLIN & POLIKLIN,D-12200 BERLIN,GERMANY. BEAUMONT HOSP,DEPT RADIOL,DUBLIN 9,IRELAND. ROYAL COLL SURGEONS IRELAND,DUBLIN 2,IRELAND. NR 17 TC 24 Z9 25 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD AUG PY 1997 VL 204 IS 2 BP 503 EP 506 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA XL644 UT WOS:A1997XL64400037 PM 9240544 ER PT J AU Carey, K AF Carey, K TI A panel data design for estimation of hospital cost functions SO REVIEW OF ECONOMICS AND STATISTICS LA English DT Article ID MARKET-STRUCTURE; COMPETITION; INDUSTRY; QUALITY AB This paper estimates a multiple-output hospital cost function using a panel data technique that allows for correlation between unobservable individual effects and observable determinants of behavior. Analysis of 1733 facilities for the period of 1987-1991 yields estimates that differ widely from those obtained from a more standard cross-sectional procedure. While the latter method results in negative and stable measures of ray economies of scale, the panel model indicates positive economies of scale that fall slightly over time. RP Carey, K (reprint author), US DEPT VET AFFAIRS,WASHINGTON,DC, USA. NR 38 TC 44 Z9 45 U1 3 U2 6 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 SN 0034-6535 J9 REV ECON STAT JI Rev. Econ. Stat. PD AUG PY 1997 VL 79 IS 3 BP 443 EP 453 DI 10.1162/003465300556850 PG 11 WC Economics; Social Sciences, Mathematical Methods SC Business & Economics; Mathematical Methods In Social Sciences GA XP330 UT WOS:A1997XP33000012 ER PT J AU Strauss, GM Lynch, TJ Elias, AD Jacobs, C Herbst, R Leong, T Lynch, C Kwiatkowski, DJ Carey, RW Grossbard, ML Skarin, AT AF Strauss, GM Lynch, TJ Elias, AD Jacobs, C Herbst, R Leong, T Lynch, C Kwiatkowski, DJ Carey, RW Grossbard, ML Skarin, AT TI Ifosfamide/carboplatin/etoposide/paclitaxel in advanced lung cancer: Update and preliminary survival analysis SO SEMINARS IN ONCOLOGY LA English DT Article; Proceedings Paper CT Fox-Chase-Cancer-Center and Free-University-Hospital Investigators Workshop and Consensus Conference on Paclitaxel CY MAR 12-16, 1997 CL PR SP Fox Chase Canc Ctr, Free Univ Hosp ID COOPERATIVE-ONCOLOGY-GROUP; PHASE-II; COMBINATION CHEMOTHERAPY; CARBOPLATIN; ETOPOSIDE; IFOSFAMIDE; PACLITAXEL; TAXOL; EXPERIENCE; CISPLATIN C1 DANA FARBER CANC INST,DEPT BIOSTAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BRIGHAM & WOMENS HOSP,DIV HEMATOL ONCOL,BOSTON,MA. MASSACHUSETTS GEN HOSP,HEMATOL ONCOL UNIT,BOSTON,MA 02114. RP Strauss, GM (reprint author), DANA FARBER CANC INST,DIV MED ONCOL,44 BINNEY ST,BOSTON,MA 02115, USA. NR 33 TC 2 Z9 2 U1 0 U2 2 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 AUG PY 1997 VL 24 IS 4 SU 12 BP 73 EP 80 PG 8 WC Oncology SC Oncology GA XZ836 UT WOS:A1997XZ83600018 ER PT J AU Palmer, WE AF Palmer, WE TI MR arthrography of the rotator cuff and labral-ligamentous complex SO SEMINARS IN ULTRASOUND CT AND MRI LA English DT Article ID GLENOHUMERAL LIGAMENTS; SHOULDER INSTABILITY; CT ARTHROGRAPHY; GLENOID LABRUM; STABILITY; TEARS RP Palmer, WE (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIOL,15 PARKMAN ST,WACC 515,BOSTON,MA 02114, USA. NR 18 TC 17 Z9 18 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0887-2171 J9 SEMIN ULTRASOUND CT JI Semin. Ultrasound CT MRI PD AUG PY 1997 VL 18 IS 4 BP 278 EP 290 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA XT117 UT WOS:A1997XT11700004 PM 9285996 ER PT J AU Collins, CL Wasa, M Souba, WW Abcouwer, SF AF Collins, CL Wasa, M Souba, WW Abcouwer, SF TI Regulation of glutamine synthetase in human breast carcinoma cells and experimental tumors SO SURGERY LA English DT Article; Proceedings Paper CT 58th Annual Meeting of the Society-of-University-Surgeons CY FEB 13-15, 1997 CL TAMPA, FL SP Soc Univ Surgeons ID HEPATOMA-CELLS; MUSCLE-CELLS; DEXAMETHASONE; METABOLISM; EXPRESSION; CANCER; LIVER AB Background. Acute deprivation of extracellular glutamine causes up-regulation of glutamine synthetase (GS) expression try a mechanism involving an increase in GS protein stability. This study examines GS expression in a highly glutamine-dependent and tumorigenic human breast cancer cell line, TSE cells, in response to acute and chronic glutamine deprivation in culture and during tumor formation. Methods. TSE cells were subjected to acute glutamine deprivation, adapted to growth in low glutamine concentrations, and subcutaneously injected into nude mice. GS protein and mRNA levels were assayed by Western and Northern blotting, and intracellular glutamine levels were evaluated by using a colorimetric assay. Results. GS protein levels increased but GS mRNA levels were unchanged in response to acute glutamine deprivation. Chronic glutamine deprivation in vitro and tumor growth in vivo caused an increase in both GS protein and mRNA levels. Large tumors exhibited lower intracellular glutamine, higher GS protein, and relatively unchanged GS mRNA levels relative to small tumors. Conclusions. TSE tumors exhibit up-regulation of GS protein and mRNA levels and declines in intracellular glutamine content, suggesting that growth in vivo causes a chronic and progressive glutamine deprivation. Up-regulation of GS expression may contribute to adaptation to a nutrient-poor intratumor environment. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,DIV SURG ONCOL,BOSTON,MA 02114. OI Abcouwer, Steven F/0000-0003-2580-1288 FU NIDDK NIH HHS [P30-DK40561] NR 23 TC 21 Z9 22 U1 0 U2 1 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 AUG PY 1997 VL 122 IS 2 BP 451 EP 463 DI 10.1016/S0039-6060(97)90039-8 PG 13 WC Surgery SC Surgery GA XU463 UT WOS:A1997XU46300078 PM 9288153 ER PT J AU Pekary, AE Chopra, IJ Berg, L Hershman, JM AF Pekary, AE Chopra, IJ Berg, L Hershman, JM TI Sphingomyelinase and phospholipase A(2) regulate type I deiodinase expression in FRTL-5 cells SO THYROID LA English DT Article ID TUMOR-NECROSIS-FACTOR; RAT-THYROID CELLS; FACTOR-ALPHA; IODOTHYRONINE DEIODINASE; SIGNAL-TRANSDUCTION; INTERFERON-GAMMA; ARACHIDONIC-ACID; CERAMIDE; IDENTIFICATION; INTERLEUKIN-1 AB We have previously reported (Mol. Cell. Endocrinol. (1994) 101, R31-R35) that the proinflammatory cytokines, tumor necrosis factor-alpha (TNF), interleukin-1 beta (IL-1 beta), and interferon-gamma (IFN-gamma), have a marked inhibitory effect on the expression and activity of type I iodothyronine deiodinase (D1) in FRTL-5 rat thyroid cells, while the antiinflammatory cytokine, transforming growth factor-beta(1) (TGF-beta(1)) had no effect. These three proinflammatory cytokines utilize a number of intracellular second messenger systems including the pathways beginning with activation of sphingomyelinase and phospholipase A(2). We have studied the time-dependent and dose-dependent effects of sphingomyelinase, ceramide, phospholipase A(2) (PLA(2)), and arachidonic acid on the expression and activity of D1 in FRTL-5 cells. Sphingomyelinase (0.3 U/mL) inhibited D1 activity 55% and reduced D1 mRNA levels 70% to 90% by 8 hours. Similar treatment with 10 U/mL PLA(2) inhibited D1 activity 54%. Treatment with 15 mu M 5,8,11-eicosatriynoic acid (ETI), a nonmetabolizable analog of arachidonic acid, or 15 mu M ceramide for 3 hours reduced D1 activity with a half-time of disappearance (t(1/2)) of 4.2 hours and 3.7 hours, respectively, but ETI and ceramide did not alter the D1 immunoreactivity or mRNA levels. Treatment for 8 hours with cycloheximide (5 or 10 mu g/mL) had no effect on the D1 mRNA level, but blocked the TNF-induced reduction of this mRNA. We conclude that proinflammatory cytokines inhibit D1 expression and activity in FRTL-5 cells, in part, by activation of sphingomyelinase and PLA(2) that results in (1) competitive inhibition of D1 activity by the enzymatic products ceramide and arachidonic acid and (2) reduction of D1 mRNA stability by protein synthesis-dependent mechanisms. C1 UNIV CALIF LOS ANGELES,DEPT MED,DIV ENDOCRINOL,LOS ANGELES,CA 90024. RP Pekary, AE (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,ENDOCRINOL RES LAB,11301 WILSHIRE BLVD,BLDG 114,ROOM 200,LOS ANGELES,CA 90073, USA. NR 36 TC 10 Z9 10 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1050-7256 J9 THYROID JI Thyroid PD AUG PY 1997 VL 7 IS 4 BP 647 EP 654 DI 10.1089/thy.1997.7.647 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XU747 UT WOS:A1997XU74700020 PM 9292957 ER PT J AU Ferrigno, P AF Ferrigno, P TI Pictures in cell biology - Splicing factors before your eyes SO TRENDS IN CELL BIOLOGY LA English DT Article RP Ferrigno, P (reprint author), DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02130, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0962-8924 J9 TRENDS CELL BIOL JI Trends Cell Biol. PD AUG PY 1997 VL 7 IS 8 BP 304 EP 304 PG 1 WC Cell Biology SC Cell Biology GA XM268 UT WOS:A1997XM26800003 ER PT J AU Maass, N Zhang, M Sager, R Jonat, W AF Maass, N Zhang, M Sager, R Jonat, W TI Transcriptional regulation of protease-inhibitor maspin in breast epithelial- and breast cancer-cell lines. SO TUMORDIAGNOSTIK & THERAPIE LA German DT Article DE breast cancer; protease inhibitor; maspin; PEA-3; AP-1; transcription factors ID DOWN-REGULATION; C-FOS; BINDING; GENE; PROMOTER; PEA3; AP-1; ACTIVATION; CONTAINS; PROTEINS AB Background: Maspin (mammary serpin) is a novel serine protease-inhibitor with tumor suppressor activity in human mammary epithelial cells. The maspin gene is expressed in normal mammary epithelial cells but down-regulated in a series of tumor derived breast cell lines. Maspin's decreased expression with increased level of malignancy and its loss in metastatic cells is regulated at the transcriptional level. Methods and Results: We have cloned and sequenced the maspin promoter region to investigate its regulation in normal and tumor cells. By chloramphenicol-transferase-(CAT) assay and deletion analysis the PEA-3 and AP-1 sites were identified within the maspin promoter that are active in regulating maspin expression in normal mammary epithelial cells but inactive in tumor cells. The PEA-3 site alone is sufficient to activate transcription in a heterologous promoter, while the AP-1 site cooperates with PEA-3 in activation. The enhancing function by PEA-3 and AP-1 promoter elements is decreased with malignancy (primary tumor cells 21NT) and is abolished in metastatic cells (MDA-MB231). Gel retardation experiments (EMSA) confirm the presence of PEA-3 binding proteins which differ qualitatively and quantitatively in a comparison of normal mammary epithelial cells and mammary carcinoma cells. Conclusions: Our data demonstrate that the loss of maspin expression during tumor progression is regulated at the transcriptional level and results most likely from the absence of transactivation through the PEA-3 and AP-1 sites. The study of the maspin promoter not only helps to understand the mechanism of gene regulation, but also offers an opportunity for reexpression of maspin in tumors by therapeutical intervention. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MOL BIOL & CANC GENET,BOSTON,MA 02115. RP Maass, N (reprint author), CHRISTIAN ALBRECHTS UNIV KIEL,GEBURTSHILFE & GYNAKOL ABT,KLIN GYNAKOL & GEBURTSHILFE,D-24105 KIEL,GERMANY. RI Jonat, Walter/E-3024-2010; Maass, Nicolai/F-2639-2014 NR 29 TC 4 Z9 4 U1 0 U2 0 PU GEORG THIEME VERLAG PI STUTTGART PA P O BOX 30 11 20, D-70451 STUTTGART, GERMANY SN 0722-219X J9 TUMORDIAGN THER JI Tumordiagnos. Ther. PD AUG PY 1997 VL 18 IS 4 BP 89 EP 96 PG 8 WC Oncology SC Oncology GA XZ694 UT WOS:A1997XZ69400001 ER PT J AU Roper, JM AF Roper, JM TI Trauma and addiction experiences of African American women - Commentary SO WESTERN JOURNAL OF NURSING RESEARCH LA English DT Editorial Material RP Roper, JM (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,11301 WILSHIRE BLVD,LOS ANGELES,CA 90073, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 SN 0193-9459 J9 WESTERN J NURS RES JI West. J. Nurs. Res. PD AUG PY 1997 VL 19 IS 4 BP 462 EP 463 PG 2 WC Nursing SC Nursing GA XQ149 UT WOS:A1997XQ14900008 ER PT J AU Chae, SJ Cooper, DKC AF Chae, SJ Cooper, DKC TI Legal implications of xenotransplantation SO XENOTRANSPLANTATION LA English DT Review DE guidelines; regulations; public health; law; xenotransplantation; tort; animal rights AB Xenotransplantation (XTx) offers a possible solution to the severe shortage of organs for transplantation, but it will raise new legal questions. There are currently no legal impediments to XTx in the United States nor do animals possess common law or constitutional rights that would prevent it. The law remains indefinite regarding what constitutes a human being, allowing the possibility that legal arguments will be raised regarding the legal status of transgenic animals expressing human tissues or cells. As successful XTx will eliminate the organ shortage, Congress or state legislatures will have to reconsider the need for the current centralized system of allocation and distribution of organs, for this could be replaced by a commercial system based on market forces. The most significant legal issue relating to XTx is probably the potential threat to the public health and safety through the transmission of an infectious disease. The Public Health Service has recently issued draft guidelines which make recommendations about how XTx procedures might be performed, These guidelines currently have no legal authority but offer insight into how XTx might be regulated if it becomes a clinical reality, Existing federal laws, however, empower federal agencies to regulate XTx, in part because of the potential risk to the public health. Additionally, tort liability will impose legal pressure on transplant centers to minimize the level of risk that the general public might face. The most difficult questions facing legislatures and the Public Health Service may well prove to be these raised by the behavior of individual patients or their social contacts who do not comply with the guidelines/regulations relating to long-term monitoring for infectious complications. C1 UNIV CHICAGO,SCH LAW,CHICAGO,IL 60637. RP Chae, SJ (reprint author), HARVARD UNIV,TRANSPLANTAT BIOL RES CTR,SCH MED,MASSACHUSETTS GEN HOSP,MGH E,BLDG 149,13TH ST,BOSTON,MA 02129, USA. NR 5 TC 6 Z9 6 U1 0 U2 2 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD AUG PY 1997 VL 4 IS 3 BP 132 EP 139 DI 10.1111/j.1399-3089.1997.tb00176.x PG 8 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA XU585 UT WOS:A1997XU58500002 ER PT J AU Banerjee, PT Kaynor, GC Muthukumar, S Denaro, M Shimada, H Zhu, SC Rosa, MD Sachs, DH LeGuern, C AF Banerjee, PT Kaynor, GC Muthukumar, S Denaro, M Shimada, H Zhu, SC Rosa, MD Sachs, DH LeGuern, C TI A polycistronic retrovirus vector for expression of swine MHC class II DR alpha/beta heterodimers SO XENOTRANSPLANTATION LA English DT Article DE gene therapy; polycistronic retrovirus vector; retrovirus; swine MHC ID CELL-SURFACE EXPRESSION; BONE-MARROW CELLS; MINIATURE SWINE; INVARIANT CHAIN; INTERNAL INITIATION; MEDIATED TRANSFER; RENAL-ALLOGRAFTS; MESSENGER-RNA; GENE-TRANSFER; STEM-CELLS AB A recombinant polycistronic retroviral vector was generated to express multimeric proteins from a single transcript by using internal ribosomal entry sites which allow independent initiation of translation from internal cistrons. In addition, an enhancerless SV40 origin of replication was incorporated into the recombinant plasmids between the retroviral long terminal repeat sequences to facilitate the testing of expression of multiple proteins in a transient COS cell transfection assay. With the ultimate goal of utilizing these vector types for the induction of transplantation tolerance via retrovirus-mediated gene transfer (LeGuern et al. J Mol Med 1995:73:269 [1]; Sachs Transplant Sci 1993:3:59 [2]) we have incorporated miniature swine MHC class II DRA and DRB cDNAs which encode for the SLA-DR alpha and SLA-DR beta polypeptide chains, respectively, into the retroviral construct. The proviral DNA integrated within the producer clone genome, was found to be stable over a 3-month period and no loss of expression of DR heterodimers was observed on the cell surface of either the retrovirus producer cells or the retrovirally transduced fibroblast cell line. High titers (>1 x 10(6) CFU/ml) of recombinant particles, devoid of replication competent helper viruses, were obtained. Such vectors represent the first successful attempt to express multimeric proteins at the cell surface of transduced cells. C1 MASSACHUSETTS GEN HOSP,TRANSPLANTAT BIOL RES CTR,BOSTON,MA 02114. RP Banerjee, PT (reprint author), BIOTRANSPLANT INC,CHARLESTOWN,MA 02129, USA. NR 42 TC 11 Z9 11 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD AUG PY 1997 VL 4 IS 3 BP 161 EP 173 DI 10.1111/j.1399-3089.1997.tb00180.x PG 13 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA XU585 UT WOS:A1997XU58500006 ER PT J AU Auchincloss, H AF Auchincloss, H TI Literature update SO XENOTRANSPLANTATION LA English DT Review RP Auchincloss, H (reprint author), MASSACHUSETTS GEN HOSP,SURG SERV,TRANSPLANTAT UNIT,WHITE 510 B,BOSTON,MA 02114, USA. NR 121 TC 0 Z9 0 U1 0 U2 2 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD AUG PY 1997 VL 4 IS 3 BP 194 EP 200 DI 10.1111/j.1399-3089.1997.tb00183.x PG 7 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA XU585 UT WOS:A1997XU58500009 ER PT J AU Das Gupta, R Kolodner, R AF Das Gupta, R Kolodner, R TI Identification of postmeiotic segregation (pms) mutants as novel alleles of mismatch repair (MMR) genes. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 1971 BP A1194 EP A1194 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305602458 ER PT J AU Fishman, MC AF Fishman, MC TI Genetic dissection of endothelial assembly in the zebrafish SO FASEB JOURNAL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 3471 BP A1450 EP A1450 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305603956 ER PT J AU Hirai, S Katoh, M Terada, M Kyriakis, JM Zon, LI Rana, A Avruch, J Ohno, S AF Hirai, S Katoh, M Terada, M Kyriakis, JM Zon, LI Rana, A Avruch, J Ohno, S TI MST/MLK2, a member of the mixed lineage kinase family, directly phosphorylates and activates SEK1, an activator of JNK/SAPK SO FASEB JOURNAL LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. MGH E, Diabet Unit, Charlestown, MA USA. Natl Canc Ctr, Res Inst, Div Genet, Tokyo 104, Japan. Yokohama City Univ, Sch Med, Dept Mol Biol, Yokohama, Kanagawa 232, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 1816 BP A1168 EP A1168 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305602304 ER PT J AU Hruska-Hageman, A Mohideen, MPK Nilsen-Hamilton, M AF Hruska-Hageman, A Mohideen, MPK Nilsen-Hamilton, M TI Three highly homologous promoters are differentially regulated in response to serum and growth factors SO FASEB JOURNAL LA English DT Meeting Abstract C1 Iowa State Univ, Ames, IA 50011 USA. Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 2065 BP A1210 EP A1210 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305602552 ER PT J AU Kolodner, R AF Kolodner, R TI Mismatch repair and inherited cancer susceptibility SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 2589 BP A1301 EP A1301 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305603078 ER PT J AU Livingston, D Scully, R Chen, J Plug, A Xiao, Y Weaver, D Feunteun, J Ashley, T AF Livingston, D Scully, R Chen, J Plug, A Xiao, Y Weaver, D Feunteun, J Ashley, T TI Association of BRCA1 with RAD51 in meiotic and mitotic cells. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Yale Univ, New Haven, CT USA. Inst Gustave Roussy, Villejuif, France. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 920 BP A1015 EP A1015 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305601404 ER PT J AU Lowe, JB Thall, AD Rogers, CE Smith, PL Askari, S Cheng, G von Andrian, UH Petryniak, B AF Lowe, JB Thall, AD Rogers, CE Smith, PL Askari, S Cheng, G von Andrian, UH Petryniak, B TI Exploring mammalian oligosaccharide function through targeted ablation of glycosyltransferase genes SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Michigan, Sch Med, Howard Hughes Med Inst, Ann Arbor, MI 48109 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 3433 BP A1443 EP A1443 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305603919 ER PT J AU Martin, KA Wyatt, R Robinson, J Bota, D Sodroski, J Gerard, NP Gerard, C AF Martin, KA Wyatt, R Robinson, J Bota, D Sodroski, J Gerard, NP Gerard, C TI Molecular characterization of the rhesus macaque CCR5 gene SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Childrens Hosp, Sch Med,Beth Israel Hosp, Ina Sue Perlmutter Lab,Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 2750 BP A1328 EP A1328 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305603236 ER PT J AU Richardson, A Heydari, AR AF Richardson, A Heydari, AR TI Mammals: Aging and response to stress. SO FASEB JOURNAL LA English DT Meeting Abstract C1 UTHSCSA, Audie L Murphy Div, S Texas Vet Hlth Care Syst, GRECC, San Antonio, TX 78284 USA. UTHSCSA, Dept Physiol, San Antonio, TX 78284 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 2527 BP A1289 EP A1289 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305603014 ER PT J AU Rock, KL Criau, A Gaczynska, M Akopian, T Fenteany, G Goldberg, A Farber, D AF Rock, KL Criau, A Gaczynska, M Akopian, T Fenteany, G Goldberg, A Farber, D TI How peptides are generated for MHC class I antigen presentation. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 20 BP A860 EP A860 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305600507 ER PT J AU Spiegelman, BM Brun, R Mueller, E Sarraf, P AF Spiegelman, BM Brun, R Mueller, E Sarraf, P TI PPAR-gamma and the transcriptional basis of adipogenesis SO FASEB JOURNAL LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 130 BP A880 EP A880 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305600617 ER PT J AU Symes, A Stahl, N Servidei, T Gearan, T Yancopoulos, G Fink, JS AF Symes, A Stahl, N Servidei, T Gearan, T Yancopoulos, G Fink, JS TI The protein tyrosine phosphatase SHP-2 negatively regulates ciliary neurotrophic factor induction of gene expression SO FASEB JOURNAL LA English DT Meeting Abstract C1 Uniformed Serv Univ Hlth Sci, Dept Pharmacol, Bethesda, MD 20814 USA. Massachusetts Gen Hosp, Mol Neurobiol Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Mol Neurooncol Lab, Boston, MA 02114 USA. Regeneron Pharmaceut Inc, Tarrytown, NY 10591 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 2799 BP A1336 EP A1336 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305603287 ER PT J AU Tanzi, RE AF Tanzi, RE TI Gene defects and their pathogenic mechanisms in familial Alzheimer's disease SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 3466 BP A1449 EP A1449 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305603952 ER PT J AU Vadlamudi, RK Joung, I Shin, J AF Vadlamudi, RK Joung, I Shin, J TI P62 - A new class of ubiquitin binding protein binds to RNA and associates with active ribosomes SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Tumor Virol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 3197 BP A1403 EP A1403 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305603686 ER PT J AU Vadlamudi, RK Lee, YH Mozell, RL Shin, J AF Vadlamudi, RK Lee, YH Mozell, RL Shin, J TI Immediate early response and genomic structure of a novel ubiquitin binding protein p62 SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Tumor Virol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 3115 BP A1389 EP A1389 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305603601 ER PT J AU Wong, H Yang, D Hill, JS Nikazy, J Schotz, MC AF Wong, H Yang, D Hill, JS Nikazy, J Schotz, MC TI Lipoprotein lipase subunit arrangement SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Los Angeles, CA USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 139 BP A882 EP A882 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305600625 ER PT J AU Yanagisawa, S Sheen, J AF Yanagisawa, S Sheen, J TI Maize Dof proteins: Involvement in tissue-specific and light-regulated gene expression SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Tokyo, Grad Sch Arts & Sci, Dept Life Sci Chem, Tokyo, Japan. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 1227 BP A1067 EP A1067 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305601713 ER PT J AU Weaver, DT Alt, FW AF Weaver, DT Alt, FW TI V(D)J recombination - From RAGs to stitches SO NATURE LA English DT Editorial Material C1 CHILDRENS HOSP,HOWARD HUGHES MED INST,BOSTON,MA 02115. RP Weaver, DT (reprint author), CTR BLOOD RES,200 LONGWOOD AVE,BOSTON,MA 02115, USA. NR 11 TC 14 Z9 14 U1 0 U2 0 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD JUL 31 PY 1997 VL 388 IS 6641 BP 428 EP 429 DI 10.1038/41225 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XN553 UT WOS:A1997XN55300026 PM 9242399 ER PT J AU Klima, U Guerrero, JL Levine, RA Vlahakes, GJ AF Klima, U Guerrero, JL Levine, RA Vlahakes, GJ TI A new, biventricular working heterotopic heart transplant model - Anatomic and physiologic considerations SO TRANSPLANTATION LA English DT Article ID OF-WISCONSIN SOLUTION; RAT-HEART; PRESERVATION; ISCHEMIA; ATROPHY AB Background. Current heterotopic heart transplant models have nonworking left ventricles that atrophy and are not suitable for some studies. We developed and characterized a new heterotopic model with working left and right ventricles. Methods. Hemodynamics were compared in the working and nonworking models. The influence of the length of the donor's aorta on coronary arterial oxygenation was tested. The influence of the recipient's arterial pressure on developed left ventricular systolic pressure and the effects of alpha- and beta-adrenergic stimulation were examined in both models. The nonworking and working models were compared in chronic transplant preparations to investigate possible ventricular atrophy. Results. In this model, coronary arterial oxygen tension was influenced by the length of the donor's aorta. With a short donor aorta (0.5 cm in the porcine model), normal coronary arterial oxygenation is maintained. Left ventricular systolic pressure was greater in the working compared with the nonworking models. Left ventricular systolic pressure did not respond to alpha-adrenergic stimulation but did respond to beta-adrenergic and combined stimulation, which indicates its relationship to donor heart output. Left ventricular systolic pressure correlated with and was determined by recipient arterial pressure. Ventricular atrophy occurred in the nonworking model, but ventricular weight was maintained at sham control levels in this new working model. Conclusion. These results demonstrate the surgical anatomic considerations of a new heterotopic heart transplant model in which the left and right ventricles work. Its hemodynamic performance is related to recipient hemodynamics, and the model responds to adrenergic stimulation. In chronic studies, ventricular mass is maintained, thus allowing this model to overcome a significant shortcoming of existing heterotopic heart transplant models. C1 MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 21 TC 7 Z9 9 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD JUL 27 PY 1997 VL 64 IS 2 BP 215 EP 222 DI 10.1097/00007890-199707270-00006 PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA XN869 UT WOS:A1997XN86900006 PM 9256176 ER PT J AU Sher, LS Cosenza, CA Michel, J Makowka, L Miller, CM Schwartz, ME Busuttil, R McDiarmid, S Burdick, JF Klein, AS Esquivel, C Klintmalm, G Levy, M Roberts, JP Lake, JR Kalayoglu, M DAlessandro, AM Gordon, RD Stieber, AC Shaw, BW Thistlethwaite, JR Whittington, P Wiesner, RH Porayko, M Bynon, JS Eckhoff, DE Freeman, RB Rohrer, RJ Lewis, WD Marsh, JW Peters, M Powelson, J Cosimi, AB AF Sher, LS Cosenza, CA Michel, J Makowka, L Miller, CM Schwartz, ME Busuttil, R McDiarmid, S Burdick, JF Klein, AS Esquivel, C Klintmalm, G Levy, M Roberts, JP Lake, JR Kalayoglu, M DAlessandro, AM Gordon, RD Stieber, AC Shaw, BW Thistlethwaite, JR Whittington, P Wiesner, RH Porayko, M Bynon, JS Eckhoff, DE Freeman, RB Rohrer, RJ Lewis, WD Marsh, JW Peters, M Powelson, J Cosimi, AB TI Efficacy of tacrolimus as rescue therapy for chronic rejection in orthotopic liver transplantation - A report of the US Multicenter Liver Study Group SO TRANSPLANTATION LA English DT Article ID BILE-DUCT SYNDROME; HEPATIC ALLOGRAFT-REJECTION; FK-506; KIDNEY AB Background. A study was performed by 17 different U.S. liver transplantation centers to determine the safety and efficacy of conversion from cyclosporine to tacrolimus for chronic allograft rejection. Methods. Ninety-one patients were converted to tacrolimus a mean of 319 days after liver transplantation. The indication for conversion was ongoing chronic rejection confirmed by biochemical and histologic criteria. Patients were followed for a mean of 251 days until the end of the study. Results. Sixty-four patients (70.3%) were alive with their initial hepatic allograft at the conclusion of the study period and were defined as the responder group. Twenty-seven patients (29.7%) failed to respond to treatment, and 20 of them required a second liver graft. The actuarial graft survival for the total patient group was 69.9% and 48.5% at 1 and 2 years, respectively. The actuarial patient survival at 1 and 2 years was 84.4% and 81.2%, respectively. Two significant positive prognostic factors were identified. Patients with a total bilirubin of less than or equal to 10 mg/dl at the time of conversion had a significantly better graft and patient survival than patients converted with a total bilirubin >10 mg/dl (P=0.00002 and P=0.00125, respectively). The time between liver transplantation and conversion also affected graft and patient survival. Patients converted to tacrolimus less than or equal to 90 days after transplantation bad a 1-year actuarial graft and patient survival of 51.9% and 65.9%, respectively, compared with 73.2% and 87.7% for those converted >90 days after transplantation. The mean total bilirubin level for the responder group was 7.1 mg/dl at the time of conversion and decreased significantly to a mean of 3.4 mg/dl at the end of the study (P=0.0018). Thirteen patients (14.3%) died during the study. Sepsis was the major contributing cause of death in most of these patients. Conclusions. Our results suggest that conversion to tacrolimus for chronic rejection after orthotopic liver transplantation represents an effective therapeutic option. Conversion to tacrolimus before development of elevated total bilirubin levels showed a significant impact on long-term outcome. C1 UNIV CALIF LOS ANGELES,LOS ANGELES,CA. STANFORD UNIV,MED CTR,PALO ALTO,CA 94304. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. MT SINAI MED CTR,NEW YORK,NY 10029. JOHNS HOPKINS MED INST,BALTIMORE,MD 21205. BAYLOR UNIV,MED CTR,DALLAS,TX. UNIV WISCONSIN HOSP & CLIN,MADISON,WI 53792. EMORY UNIV HOSP,ATLANTA,GA 30322. UNIV NEBRASKA,MED CTR,OMAHA,NE 68182. UNIV CHICAGO,CHICAGO,IL 60637. MAYO CLIN,ROCHESTER,MN. UNIV ALABAMA,BIRMINGHAM,AL. NEW ENGLAND DEACONESS HOSP,NEW ENGLAND MED CTR,BOSTON,MA 02215. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. UNIV PITTSBURGH,PITTSBURGH,PA. WASHINGTON UNIV,ST LOUIS,MO. RP Sher, LS (reprint author), ST VINCENTS MED CTR,COMPREHENS LIVER DIS & TREATMENT CTR,INST PLAZA,2200 W 3RD ST,SUITE 400,LOS ANGELES,CA 90057, USA. RI Marsh, Wallis/C-6796-2013 OI Marsh, Wallis/0000-0002-8143-9511 NR 19 TC 46 Z9 49 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD JUL 27 PY 1997 VL 64 IS 2 BP 258 EP 263 DI 10.1097/00007890-199707270-00014 PG 6 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA XN869 UT WOS:A1997XN86900014 PM 9256184 ER PT J AU Sawada, T Wu, Y Sachs, DH Iacomini, J AF Sawada, T Wu, Y Sachs, DH Iacomini, J TI CD4(+) T cells are able to reject class I disparate allografts SO TRANSPLANTATION LA English DT Article ID SKIN-GRAFT REJECTION; CELLULAR BASIS; LYMPHOCYTES-T; MICE; SUBSETS; INVIVO; SPECIFICITY; FAS; KB AB The ability of CD4(+) T cells to reject class I mismatched skin allografts remains controversial. In this study, we compare the ability of CD4(+) T cells to reject class I disparate skin grafts differing by either a single class I allelic disparity or only 3 amino acids encoded by the H-2K locus. We demonstrate that skin grafts across a full H-2K allelic disparity, but not across a disparity of only three amino acids are efficiently rejected by CD4(+) T cells. This observation is consistent with the possibility that peptides derived from allogeneic class I molecules generated through the major histocompatibility complex (MHC) class II antigen processing pathway can be recognized by host CD4 T cells and lead to rejection of class I mismatched skin grafts. The availability of peptides derived from allogeneic MHC class I molecules for presentation by host MHC class II may determine the efficiency of rejection of class I mismatched allografts by CD4(+) T cells. Thus, class I mismatched allografts can be rejected by CD4(+) T cells provided that host and donor MHC class I molecules are sufficiently disparate to activate CD4(+) effectors. C1 MASSACHUSETTS GEN HOSP,TRANSPLANTAT BIOL RES CTR,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02129. FU NHLBI NIH HHS [HL48049] NR 28 TC 27 Z9 27 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD JUL 27 PY 1997 VL 64 IS 2 BP 335 EP 340 DI 10.1097/00007890-199707270-00027 PG 6 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA XN869 UT WOS:A1997XN86900027 PM 9256197 ER PT J AU Faraone, SV Gottesman, II Tsuang, MT AF Faraone, SV Gottesman, II Tsuang, MT TI Fifty years of the Nuremberg Code: A time for retrospection and introspection SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Editorial Material C1 HARVARD UNIV,SCH MED,MASSACHUSETTS MENTAL HLTH CTR,DEPT PSYCHIAT,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD INST PSYCHIAT EPIDEMIOL & GENET,CAMBRIDGE,MA. UNIV VIRGINIA,DEPT PSYCHOL,CHARLOTTESVILLE,VA 22903. UNIV VIRGINIA,DEPT MED GENET,CHARLOTTESVILLE,VA 22903. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,CAMBRIDGE,MA 02138. BROCKTON W ROXBURY VET AFFAIRS MED CTR,PSYCHIAT SERV,BROCKTON,MA. RI G, I/D-8042-2011; OI Faraone, Stephen/0000-0002-9217-3982 NR 15 TC 2 Z9 2 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD JUL 25 PY 1997 VL 74 IS 4 BP 345 EP 347 DI 10.1002/(SICI)1096-8628(19970725)74:4<345::AID-AJMG1>3.0.CO;2-O PG 3 WC Genetics & Heredity SC Genetics & Heredity GA XP268 UT WOS:A1997XP26800001 PM 9259366 ER PT J AU Kula, NS Baldessarini, RJ Kebabian, JW Bakthavachalam, V Xu, LX AF Kula, NS Baldessarini, RJ Kebabian, JW Bakthavachalam, V Xu, LX TI RBI-257: A highly potent dopamine D-4 receptor-selective ligand SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE dopamine; dopamine D-4 receptor; RBI-257; U-101,958 ID SITES AB RBI-257 (1-[4-iodobenzyl]-4-[N-(3-isopropoxy-2-pyridinyl)-N-methyl]-aminopiperidine), the p-iodobenzyl analog of U-101,958 (1- benzyl-4-[N-(3-isopropoxy-2-pyridinyl)-N-methyl]-aminopiperidine had a lower dissociation constant (K-i = 0.3 vs. 2.7 nM) and higher selectivity than U-101,958 at dopamine D-4 receptors, over dopamine D-2 and D-3 receptors in transfected cell membranes and D-2-like sites in rat forebrain. Dopamine D-4 receptor affinity of iodo-isomers of RBI-257 ranked: para > meta > ortho. RBI-257 had much lower affinity at D-1 and D-5 dopamine receptors in transfected cells, as well as dopamine D-1-like receptors, alpha(1), alpha(2) or beta(1,2) adrenoceptors, sigma(1,2) receptors and 5-HT1A or 5-HT2A receptors, and transporters for dopamine, norepinephrine or serotonin in rat forebrain tissue. RBI-257 may be a useful probe or radioligand for brain dopamine D-4 receptors. (C) 1997 Elsevier Science B.V. C1 HARVARD UNIV,SCH MED,CONSOLIDATED DEPT PSYCHIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,MCLEAN DIV,MAILMAN RES CTR,BELMONT,MA 02178. RES BIOCHEM INT,NATICK,MA 01760. FU NIDA NIH HHS [DA-48312]; NIMH NIH HHS [MH-47370, MH-34006] NR 14 TC 34 Z9 34 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD JUL 23 PY 1997 VL 331 IS 2-3 BP 333 EP 336 DI 10.1016/S0014-2999(97)01065-0 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA XQ959 UT WOS:A1997XQ95900031 PM 9274997 ER PT J AU Molnar, GM Crozat, A Kraeft, SK Dou, QP Chen, LB Pardee, AB AF Molnar, GM Crozat, A Kraeft, SK Dou, QP Chen, LB Pardee, AB TI Association of the mammalian helicase MAH with the pre-mRNA splicing complex SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article; Proceedings Paper CT Colloquium on Genetics and the Origin of Species CY JAN 30-FEB 01, 1997 CL NATL ACAD SCIENCES BECKMAN CTR, IRVINE, CA SP Natl Acad Sciences HO NATL ACAD SCIENCES BECKMAN CTR ID DNA-BINDING PROTEIN; THYMIDINE KINASE PROMOTER; GLUTATHIONE-S-TRANSFERASE; SINGLE-STRANDED-DNA; SACCHAROMYCES-CEREVISIAE; ESCHERICHIA-COLI; RNA HELICASE; PURIFICATION; YEAST; SEQUENCE AB Conversion of pre-mRNAs into mature mRNAs includes several consecutive enzymatic modification steps that are carried out in the spliceosomes. Helicases have been shown to contribute to these catalytic processes both in yeast and in mammalian cells, Our results identify the mammalian protein MAH (matrix-associated helicase) as a new helicase present in the spliceosome complex, Sequence comparison describes MAH as the first higher eukaryotic member of the helicase superfamily I, with demonstrated enzymatic activity. Because MAH does not bind small nuclear ribonucleoproteins (snRNPs), it appears to be a non-snRNP binding factor of the splicing complex, In conclusion, our data suggest the involvement of MAH in processing of pre-mRNAs in mammalian cells. C1 DANA FARBER CANC INST,DEPT CELL GROWTH & REGULAT,BOSTON,MA 02115. DANA FARBER CANC INST,DEPT CELLULAR & MOL BIOL,BOSTON,MA 02115. OI Crozat, Anne/0000-0002-2539-8479 FU NIGMS NIH HHS [GM 24571] NR 47 TC 32 Z9 32 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 JUL 22 PY 1997 VL 94 IS 15 BP 7831 EP 7836 DI 10.1073/pnas.94.15.7831 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XM428 UT WOS:A1997XM42800023 PM 9223272 ER PT J AU Zavacki, AM Lehmann, JM Seol, W Willson, TM Kliewer, SA Moore, DD AF Zavacki, AM Lehmann, JM Seol, W Willson, TM Kliewer, SA Moore, DD TI Activation of the orphan receptor RIP14 by retinoids SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article; Proceedings Paper CT Colloquium on Genetics and the Origin of Species CY JAN 30-FEB 01, 1997 CL NATL ACAD SCIENCES BECKMAN CTR, IRVINE, CA SP Natl Acad Sciences HO NATL ACAD SCIENCES BECKMAN CTR ID THYROID-HORMONE RECEPTOR; X RECEPTOR; RESPONSE ELEMENTS; NUCLEAR RECEPTOR; BETA-GENE; ACID; SUPERFAMILY; IDENTIFICATION; CELLS; RAR AB Retinoids are crucial regulators of a wide variety of processes in both developing and adult animals, These effects are thought to be mediated by the retinoic acid (RA) receptors and the retinoid X receptors (RXRs), We have identified an additional retinoid activated receptor that is neither a retinoic acid receptors nor an RXR. RXR-interacting protein 14 (RIP14), a recently described orphan member of the nuclear receptor superfamily, can be activated by either all-trans-RA (tRA) or the synthetic retinoid TTNPB {[E]-4-[2-(5, 6, 7, 8-tetrahydro-5, 5, 8, 8-tetramethyl-2-naphthalenyl)propen-1-yl]benzoic acid}, RIP14 binds to DNA as a heterodimer with RXR. In the presence of either tRA or TTNPB, the addition of 9-cis-RA or the RXR-specific agonist LG1069 {4-[1-(3, 5, 5, 8, 8-pentamethyl-5, 6, 7, 8-tertrahydro-2-naphthyl)ethenyl]benzoic acid} results in additional activation. Mutations of the ligand-dependent transcriptional activation functions indicate that TTNPB activates the RIP14 component of the RIP14-RXR heterodimer, that 9-cis-RA and LG1069 activate RXR, and that tRA activates via both RIP14 and RXR. Despite the very effective activation of RIP14 by tRA or TTNPB, relatively high concentrations of these compounds are required, and no evidence for direct binding of either compound was obtained using several approaches. These results suggest that RIP14 is the receptor for an as-yet-unidentified retinoid metabolite. C1 MASSACHUSETTS GEN HOSP,DEPT MOL BIOL,BOSTON,MA 02114. GLAXO WELLCOME INC,RES & DEV,DEPT MOL ENDOCRINOL,RES TRIANGLE PK,NC 27709. GLAXO WELLCOME INC,RES & DEV,DEPT MED CHEM,RES TRIANGLE PK,NC 27709. FU NIDDK NIH HHS [F32 DK09641] NR 36 TC 77 Z9 79 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 JUL 22 PY 1997 VL 94 IS 15 BP 7909 EP 7914 DI 10.1073/pnas.94.15.7909 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XM428 UT WOS:A1997XM42800037 PM 9223286 ER PT J AU McDevitt, MA Fujiwara, Y Shivdasani, RA Orkin, SH AF McDevitt, MA Fujiwara, Y Shivdasani, RA Orkin, SH TI An upstream, DNase I hypersensitive region of the hematopoietic-expressed transcription factor GATA-1 gene confers developmental specificity in transgenic mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article; Proceedings Paper CT Colloquium on Genetics and the Origin of Species CY JAN 30-FEB 01, 1997 CL NATL ACAD SCIENCES BECKMAN CTR, IRVINE, CA SP Natl Acad Sciences HO NATL ACAD SCIENCES BECKMAN CTR DE cis-elements; erythropoiesis ID EMBRYONIC STEM-CELLS; ERYTHROID DEVELOPMENT; BINDING PROTEINS; GLOBIN GENE; DIFFERENTIATION; PROMOTER; EOSINOPHILS; PROGENITORS; LINEAGES; RESCUE AB The transcription factor GATA-1, which is expressed in several hematopoietic lineages and multipotential progenitors, is required for the development of red blood cells and platelets. To identify control elements of the mouse GATA-1 gene, se analyzed DNase I hypersensitivity of the locus in erythroid chromatin and the expression of GATA-1/Escherichia coli beta-galaclosidase (lacZ) transgenes in mice, Transgenes with 2.7 kb of promoter sequences are expressed infrequently and only within adult (definitive) erythroid cells, We show that inclusion of an upstream hypersensitive site (HS I) markedly enhances the frequency of expressing transgenic lines and activates expression in primitive erythroid cells. This pattern recapitulates the proper pattern of GATA-1 expression during development, By breeding a GATA-1/lacZ transgene into a GATA-1(-) background, we also have shown that the activation or maintenance of GATA-1 expression does not require the presence of GATA-1 itself, thereby excluding simple models of positive autoregulation, The transgene cassette reported here should be useful in directing expression of foreign sequences at the onset of hematopoiesis in the embryo and mag assist in the identification of upstream regulators of the GATA-1 gene. C1 HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CHILDRENS HOSP,BOSTON,MA 02115. HARVARD UNIV,SCH MED,HOWARD HUGHES MED INST,BOSTON,MA 02115. RP McDevitt, MA (reprint author), HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115, USA. FU NHLBI NIH HHS [T32 HL007623, T32HL07623] NR 49 TC 76 Z9 77 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 JUL 22 PY 1997 VL 94 IS 15 BP 7976 EP 7981 DI 10.1073/pnas.94.15.7976 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XM428 UT WOS:A1997XM42800049 PM 9223298 ER PT J AU Gu, YS Jin, SF Gao, YJ Weaver, DT Alt, FW AF Gu, YS Jin, SF Gao, YJ Weaver, DT Alt, FW TI Ku70-deficient embryonic stem cells have increased ionizing radiosensitivity, defective DNA end-binding activity, and inability to support V(D)J recombination SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article; Proceedings Paper CT Colloquium on Genetics and the Origin of Species CY JAN 30-FEB 01, 1997 CL NATL ACAD SCIENCES BECKMAN CTR, IRVINE, CA SP Natl Acad Sciences HO NATL ACAD SCIENCES BECKMAN CTR ID STRAND-BREAK-REPAIR; DEPENDENT PROTEIN-KINASE; PRE-B CELLS; RAY-SENSITIVE MUTANTS; HUMAN KU AUTOANTIGEN; RADIATION SENSITIVITY; CATALYTIC SUBUNIT; SCID DEFECT; GENE; ANTIGEN AB V(D)J recombination requires both lymphoid-specific and generally expressed enzymatic activities, All three known generally expressed activities involved in V(D)J recombination are also involved in DNA double-strand break repair (DSBR), Two of these are components of the DNA-dependent protein kinase (DNA-PK) and include Ku80 and DNA-PK catalytic subunit (DNA-PKcs); the third, XRCC4, is a protein of unknown function, The Ku70 protein is an additional component of DNA-PK; Ku70 forms a heterodimer with Ku80 to generate the DNA end-binding component of the enzyme, To test putative functions for Ku70, we have used gene-targeted mutation to generate a murine embryonic stem cell line which lacks Ku70 expression, We find that the Ku70(-/-) cells produce no detectable Ku70 and very little Ku80, suggesting a direct interrelationship between their levels, Correspondingly, these cells lack the nonspecific DNA end-binding activity associated with Ku. Significantly, the Ku70(-/-) embryonic stem cells have markedly increased sensitivity to gamma-irradiation relative to Ku70(+/-) or wild-type embryonic stem cells. Furthermore, the Ku70(-/-) cells lack the ability to effectively rejoin signal and coding ends liberated in transiently introduced V(D)J recombination substrates by enforced RAG-1 and RAG-2 expression. We conclude that the Ku70 gene product is involved in DSBR and V(D)J recombination and confirm that the Ku70 gene can Toe classified as a member of the x-ray cross-complementation group 6 (XRCC6). Potential differences between the Ku70(-/-) and Ku80(-/-) V(D)J recombination defects are discussed. C1 CHILDRENS HOSP, HOWARD HUGHES MED INST, BOSTON, MA 02115 USA. HOWARD HUGHES MED INST, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, CTR BLOOD RES, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DEPT GENET, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DANA FARBER CANC INST, DIV TUMOR IMMUNOL, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DEPT MICROBIOL & MOL GENET, BOSTON, MA 02115 USA. FU NCI NIH HHS [CA42335]; NIAID NIH HHS [AI20047, AI315714, R01 AI020047, R37 AI020047] NR 60 TC 299 Z9 309 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 JUL 22 PY 1997 VL 94 IS 15 BP 8076 EP 8081 DI 10.1073/pnas.94.15.8076 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XM428 UT WOS:A1997XM42800068 PM 9223317 ER PT J AU Li, CJ Ueda, Y Shi, B Borodyansky, L Huang, LL Li, YZ Pardee, AB AF Li, CJ Ueda, Y Shi, B Borodyansky, L Huang, LL Li, YZ Pardee, AB TI Tat protein induces self-perpetuating permissivity for productive HIV-1 infection SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article; Proceedings Paper CT Colloquium on Genetics and the Origin of Species CY JAN 30-FEB 01, 1997 CL NATL ACAD SCIENCES BECKMAN CTR, IRVINE, CA SP Natl Acad Sciences HO NATL ACAD SCIENCES BECKMAN CTR ID HUMAN-IMMUNODEFICIENCY-VIRUS; GROWTH-FACTOR; T-LYMPHOCYTES; EXPRESSION; APOPTOSIS; TYPE-1; CELLS; INDUCTION; ADHESION; DISEASE AB We report that human immunodeficiency virus type I (HIV-1) has evolved a self-perpetuating mechanism to actively generate cells permissive for productive and cytopathic infection, Only activated T cells can be productively infected, which leads to their rapid depletion (2 x 10(9)/day in an infected individual), Establishment of productive HIV-1 infection therefore requires continual activations from the large pool of quiescent T cells, Tat protein, which is secreted by infected cells, activated uninfected quiescent T cells in vitro and in vivo. These Tat-activated uninfected cells became highly permissive for productive HIV-1 infection, Activation of primary T cells by Tat protein involved integrin receptors and was associated with activation of mitogen-activated protein kinases, including ERK1 and JNK kinase, Accordingly, these primary T cells progressed from G(0) to the late G(1) phase of the cell cycle. C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOL PHARMACOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HUMAN RETROVIROL,BOSTON,MA 02115. RP Li, CJ (reprint author), HARVARD UNIV,SCH MED,DIV CELL GROWTH & REGULAT,44 BINNEY ST,BOSTON,MA 02115, USA. FU NIAID NIH HHS [AI-35576] NR 31 TC 96 Z9 96 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 JUL 22 PY 1997 VL 94 IS 15 BP 8116 EP 8120 DI 10.1073/pnas.94.15.8116 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XM428 UT WOS:A1997XM42800075 PM 9223324 ER PT J AU Kawamata, T Dietrich, WD Schallert, T Gotts, JE Cocke, RR Benowitz, LI Finklestein, SP AF Kawamata, T Dietrich, WD Schallert, T Gotts, JE Cocke, RR Benowitz, LI Finklestein, SP TI Intracisternal basic fibroblast growth factor enhances functional recovery and up-regulates the expression of a molecular marker of neuronal sprouting following focal cerebral infarction SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article; Proceedings Paper CT Colloquium on Genetics and the Origin of Species CY JAN 30-FEB 01, 1997 CL NATL ACAD SCIENCES BECKMAN CTR, IRVINE, CA SP Natl Acad Sciences HO NATL ACAD SCIENCES BECKMAN CTR DE growth-associated protein 43; cerebral ischemia; growth factors ID ADULT-RAT BRAIN; NEOCORTICAL DAMAGE; ISCHEMIA; INJURY; SYNAPTOGENESIS; CELLS AB Focal cerebral infarction (stroke) due to unilateral occlusion of the middle cerebral artery in mature rats produces deficits in sensorimotor function of the contralateral limbs that recover partially over time. We found that biweekly intracisternal injection of basic fibroblast growth factor (bFGF; 0.5 mu g/injection), a potent neurotrophic polypeptide, markedly enhanced recovery of sensorimotor function of the contralateral limbs during the first month after stroke without apparent adverse side effects, Immunostaining for growth-associated protein 43 (GAP-43), a molecular marker of axonal sprouting, showed a selective increase in GAP-43 immunoreactivity in the intact sensorimotor cortex contralateral to cerebral infarcts following bFGF treatment, These results show that bFGF treatment can enhance functional recovery after stroke, and that the mechanism may include stimulation of neuronal sprouting in the intact brain. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,CNS,GROWTH FACTOR RES LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. UNIV MIAMI,SCH MED,DEPT NEUROL,CEREBRAL VASC DIS RES CTR,MIAMI,FL 33101. UNIV TEXAS,DEPT PSYCHOL,AUSTIN,TX 78712. CHILDRENS HOSP,MED CTR,DEPT NEUROSURG,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. FU NINDS NIH HHS [F32 NS010828, P01 NS010828, NS10828, P50 NS010828] NR 32 TC 220 Z9 235 U1 1 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 JUL 22 PY 1997 VL 94 IS 15 BP 8179 EP 8184 DI 10.1073/pnas.94.15.8179 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XM428 UT WOS:A1997XM42800086 PM 9223335 ER PT J AU Giambarella, U Murayama, Y Ikezu, T Fujita, T Nishimoto, I AF Giambarella, U Murayama, Y Ikezu, T Fujita, T Nishimoto, I TI Potential CRE suppression by familial Alzheimer's mutants of APP independent of adenylyl cyclase regulation SO FEBS LETTERS LA English DT Article ID AMYLOID PRECURSOR PROTEIN; LONG-TERM-MEMORY; MANNOSE 6-PHOSPHATE RECEPTOR; ALPHA-SUBUNITS; KINASE-II; GENE-TRANSCRIPTION; MICE; EXPRESSION; MUTATION; DISEASE AB In familial Alzheimer's disease (FAD), mutations to I, F, and G have been discovered at V642 in the neuron-specific version of the amyloid precursor protein APP(695). It has been found that expression of each FAD mutant suppresses the transcriptional activity of the cAMP response element CRE in a G alpha(o)-dependent manner in a COS cell clone NK1 [Ikezu et al, (1996) EMBO J. 15, 2468-2475], Here we show that adenylyl cyclase (AC) inhibition is probably not the prerequisite for this pathway, First, expression of each FAD mutant in NK1 cells had no effect on AC activity stimulated by cholera toxin and by mutationally activated G alpha(s), although the same expression completely repressed the stimulated CRE, Second, a transfected activating mutant of G alpha(o) inhibited CRE without detectable suppression of AC, whereas similarly transfected activating G alpha(i2) inhibited both AC and CRE, Third, FAD mutant-induced inhibition occurred for CRE activity stimulated by dibutyryl cAMP. These data suggest that CRE suppression by FAD mutants of APP could occur independently of AC. (C) 1997 Federation of European Biochemical Societies. C1 HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,CHARLESTOWN,MA 02129. KEIO UNIV,SCH MED,DEPT PHARMACOL & NEUROSCI,SHINJUKU KU,TOKYO 160,JAPAN. UNIV TOKYO,SCH MED,DEPT MED 4,BUNKYO KU,TOKYO 112,JAPAN. MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,SHRINERS HOSP CRIPPLED CHILDREN,CAMBRIDGE,MA 02139. NR 34 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD JUL 21 PY 1997 VL 412 IS 1 BP 97 EP 101 DI 10.1016/S0014-5793(97)00753-9 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA XN709 UT WOS:A1997XN70900021 PM 9257698 ER PT J AU Leech, CA Habener, JF AF Leech, CA Habener, JF TI Insulinotropic glucagon-like peptide-1-mediated activation of non-selective cation currents in insulinoma cells is mimicked by maitotoxin SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PANCREATIC BETA-CELLS; MEDIATED CALCIUM ENTRY; PEPTIDE-I; SECRETING CELLS; INTRACELLULAR CALCIUM; ACINAR-CELLS; CA2+ INFLUX; G-PROTEIN; RECEPTOR; CHANNELS AB Maitotoxin (MTX) activates a Ca2+-dependent non-selective cation current (ICa-NS) in insulinoma cells whose time course is identical to non selective cation currents activated by incretin hormones such as glucagon-like peptide-1 (GLP-1), which stimulate glucose-dependent insulin secretion by activating cAMP signaling pathways, We investigated the mechanism of activation of ICa-NS in insulinoma cells using specific pharmacological reagents, and these studies further support an identity between MTX- and GLP-1-activated currents, ICa-NS is inhibited by extracellular application of genistein, econazole, and SKF 96365. This inhibition by genistein suggests that tyrosine phophorylation may play a role in the activation of ICa-NS. ICa-NS is not inhibited by incubation of cells in glucose-free solution, by extracellular tetrodotoxin, nimodipine, or tetraethylammonium, or by intracellular dialysis with 4-aminopyridine, ATP, ryanodine, or heparin, ICa-NS is also not significantly inhibited by staurosporine, which does, however, partially inhibit the MTX-induced rise of intracellular Ca2+ concentration, These effects of staurosporine suggest that protein kinase C may not be involved in the activation of ICa-NS but that it may regulate intracellular Ca2+ release, Alternatively, ICa-NS may have a small component that is carried through separate divalent cation-selective channels that are inhibited by staurosporine. ICa-NS is neither activated nor inhibited by dialysis with KF, KF + AlF3 or GTP gamma S (guanosine 5'-O-(3-thiotriphosphate)), suggesting that GTP-binding proteins do not play a major role in the activation of this current. RP Leech, CA (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,HOWARD HUGHES MED INST,LAB MOL ENDOCRINOL,BOSTON,MA 02114, USA. NR 46 TC 50 Z9 51 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 18 PY 1997 VL 272 IS 29 BP 17987 EP 17993 DI 10.1074/jbc.272.29.17987 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XL735 UT WOS:A1997XL73500015 PM 9218425 ER PT J AU Gabai, VL Meriin, AB Mosser, DD Caron, AW Rits, S Shifrin, VI Sherman, MY AF Gabai, VL Meriin, AB Mosser, DD Caron, AW Rits, S Shifrin, VI Sherman, MY TI Hsp70 prevents activation of stress kinases - A novel pathway of cellular thermotolerance SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HEAT-SHOCK PROTEINS; TUMOR-CELLS; PHOSPHORYLATION; NECROSIS; CASCADE; OVEREXPRESSION; ACCUMULATION; DENATURATION; FIBROBLASTS; AGGREGATION AB Harmful conditions including heat shock, oxidative stress, UV, and so forth cause programmed cell death, whose triggering requires activation of the Jun N-terminal kinase, JNK, High levels of Hsp72, a heat-inducible member of Hsp70 family, protect cells against a variety of stresses by a mechanism that is unclear at present. Here we report that elevated levels of Hsp72. inhibit a signal transduction pathway leading to programmed cell death by preventing stress-induced activation of JNK. Stress-induced activation of another stress-kinase, p38 (HOG1), is also blocked when the level of Hsp72 is increased, Similarly, addition of a purified recombinant Hsp72 to a crude cell lysate reduced p38 kinase activation, while depletion of the whole family of Hsp70 proteins with a monoclonal antibody enhanced such activation, In addition, we have found that accumulation of abnormal proteins in cells upon incubation with amino acid analogs causes activation of JNK and p38 kinases, which can be prevented by overproduction of Hsp72, Taken together, these data suggest that, in regulation of JNK and p38 kinases, Hsp70 serves as a ''sensor'' of the build-up of abnormal proteins after heat shock and other stresses, The inhibitory effect of an increased level of Hsp70 on JNK appears to be a major contributor to acquired thermotolerance in mammalian cells. C1 BOSTON BIOMED RES INST,BOSTON,MA 02114. MED RADIOL RES CTR,OBNINSK 249020,RUSSIA. BIOTECHNOL RES INST,MONTREAL,PQ H4P 2R2,CANADA. DANA FARBER CANC INST,BOSTON,MA 02115. RI Gabai, Vladimir/I-1650-2013 FU PHS HHS [R01] NR 35 TC 389 Z9 430 U1 1 U2 16 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 JUL 18 PY 1997 VL 272 IS 29 BP 18033 EP 18037 DI 10.1074/jbc.272.29.18033 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XL735 UT WOS:A1997XL73500022 PM 9218432 ER PT J AU Kim, TW Pettingell, WH Jung, YK Kovacs, DM Tanzi, RE AF Kim, TW Pettingell, WH Jung, YK Kovacs, DM Tanzi, RE TI Alternative cleavage of Alzheimer-associated presenilins during apoptosis by a caspase-3 family protease SO SCIENCE LA English DT Article ID DISEASE; NEURODEGENERATION; DEATH AB Most cases of early-onset familiar Alzheimer's disease (FAD) are caused by mutations in the genes encoding the presenilin 1 (PS1) and PS2 proteins, both of which undergo regulated endoproteolytic processing. During apoptosis, PS1 and PS2 were shown to be cleaved at sites distal to their normal cleavage sites by a caspase-3 family protease. In cells expressing PS2 containing the asparagine-141 FAD mutant, the ratio of alternative to normal PS2 cleavage fragments was increased relative to wild-type PS2-expressing cells, suggesting a potential role for apoptosis-associated cleavage of presenilins in the pathogenesis of Alzheimer's disease. C1 HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,DEPT NEUROL,GENET & AGING UNIT,CHARLESTOWN,MA 02129. KWANGJU INST SCI & TECHNOL,DEPT LIFE SCI,KWANGJU,SOUTH KOREA. OI Jung, Yong-Keun/0000-0002-9686-3120 NR 40 TC 307 Z9 316 U1 0 U2 2 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUL 18 PY 1997 VL 277 IS 5324 BP 373 EP 376 DI 10.1126/science.277.5324.373 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XL358 UT WOS:A1997XL35800047 PM 9219695 ER PT J AU Haluska, FG Thiele, C Goldstein, A Tsao, H Benoit, EP Housman, D AF Haluska, FG Thiele, C Goldstein, A Tsao, H Benoit, EP Housman, D TI Lack of phospholipase A(2) mutations in neuroblastoma, melanoma and colon-cancer cell lines SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID HUMAN COLORECTAL-CANCER; INTESTINAL NEOPLASIA; DYSPLASTIC NEVUS; MAJOR MODIFIER; MOM1 LOCUS; GENE; DELETIONS; CANDIDATE; MAPS AB A candidate murine tumor-suppressor gene, Mom1, has been identified as the secretory phospholipase A2 (GDB nomenclature: PLA2G2A) gene. Evidence suggests that PLA2G2A functions as a tumor-suppressor because mice lacking PLA2G2A expression demonstrate increased colonic polyposis, The human homologue of PLA2G2A has been mapped to chromosome 1p36, a region frequently implicated in the pathogenesis of neuroblastoma, colon cancer and melanoma. We identified 2 alterations in the PLA2G2A gene in a single neuroblastoma cell line out of 20 examined; however, we found no mutations in 24 melanoma cell lines, 12 lymphoblastoid cell lines from patients having chromosome 1-linked familial melanoma and 10 colon cancer cell lines, Secretory phospholipase A2 is unlikely to play a significant role in the pathogenesis of these tumors. (C) 1997 Wiley-Liss, Inc. C1 MIT,CTR CANC RES,CAMBRIDGE,MA 02139. NCI,CELL & MOL BIOL SECT,PEDIAT BRANCH,NIH,BETHESDA,MD. NIH,GENET EPIDEMIOL BRANCH,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,DEPT DERMATOL,BOSTON,MA 02115. RP Haluska, FG (reprint author), MASSACHUSETTS GEN HOSP,DEPT HEMATOL ONCOL,COX BLDG,ROOM 640,100 BLOSSOM ST,BOSTON,MA 02114, USA. NR 20 TC 18 Z9 18 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUL 17 PY 1997 VL 72 IS 2 BP 337 EP 339 DI 10.1002/(SICI)1097-0215(19970717)72:2<337::AID-IJC22>3.0.CO;2-B PG 3 WC Oncology SC Oncology GA XH810 UT WOS:A1997XH81000022 PM 9219842 ER PT J AU Campbell, EG Weissman, JS Blumenthal, D AF Campbell, EG Weissman, JS Blumenthal, D TI Relationship between market competition and the activities and attitudes of medical school faculty SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID CARE AB Context.-Growth in health care market competition and the concomitant increasing dependence of academic health centers on clinical revenues may require medical school faculty to increase patient care activity, perhaps at the expense of research and teaching. However, the relationship between health care market competitiveness and the activities and attitudes of medical school faculty has not been established. Objective.-To examine the relationship between market competitiveness and the activities and attitudes of medical school faculty members. Design.-Mailed survey of 3394 life-science faculty in the 50 universities that received the most funding from the National Institutes of Health in 1993. Setting.-Medical schools in research-intensive universities. Participants.-A total of 2167 faculty responded to the survey (response rate, 64%). We analyzed the responses of 1671 medical school research faculty located in markets of differing health care competitiveness, ranging from least competitive (stage 1) to most competitive (stage 4) markets. Main Outcome Measures.-The number of publications in refereed journals in the last 3 years, the average number of hours per week of teaching contact, whether faculty in clinical departments had patient care responsibilities, and measures of departmental community, cooperation, and conflict. Results.-Clinical researchers in stage 1 and 2 markets published more scientific articles than those in stage 3 markets (14.5 vs 12.6, P=.04) or in stage 4 markets (14.5 vs 12.0, P=.03). Among 96 young faculty (professional age less than or equal to 10 years) in clinical departments, 11 (44%) of those in stage 1 and 2 markets had patient care duties compared with 32 (56.1%) of young faculty members in stage 3 markets (P=.04) and 12 (85.7%) of those in stage 4 markets (P=.01). The percentage of senior faculty in clinical departments (n=691) with patient care responsibilities did not differ significantly by market stage. Compared with faculty in less competitive markets, faculty in stage 4 markets perceived lower levels of departmental cooperation and higher levels of conflict. Conclusions.-Increased competitiveness of health care markets seems to hinder the capacity of academic health centers to conduct clinical research and to foster the careers of young clinical faculty. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT HLTH CARE POLICY,BOSTON,MA 02115. RP Campbell, EG (reprint author), MASSACHUSETTS GEN HOSP,HLTH POLICY RES & DEV UNIT,DIV GEN INTERNAL MED,50 STANIFORD ST,9TH FLOOR,BOSTON,MA 02114, USA. FU NHGRI NIH HHS [HG00724-01] NR 20 TC 81 Z9 81 U1 0 U2 3 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 JUL 16 PY 1997 VL 278 IS 3 BP 222 EP 226 DI 10.1001/jama.278.3.222 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA XK108 UT WOS:A1997XK10800028 PM 9218669 ER PT J AU Sands, KE Bates, DW Lanken, PN Graman, PS Hibberd, PL Kahn, KL Parsonnet, J Panzer, R Orav, EJ Snydman, DR Black, E Schwartz, JS Moore, R Johnson, BL Platt, R AF Sands, KE Bates, DW Lanken, PN Graman, PS Hibberd, PL Kahn, KL Parsonnet, J Panzer, R Orav, EJ Snydman, DR Black, E Schwartz, JS Moore, R Johnson, BL Platt, R TI Epidemiology of sepsis syndrome in 8 academic medical centers SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID RESPIRATORY-DISTRESS SYNDROME; SEPTIC SHOCK; DEFINITIONS; METHYLPREDNISOLONE; ANTIBODY; SURVIVAL; TRIAL AB Context.-Sepsis syndrome is a leading cause of mortality in hospitalized patients, However, few studies have described the epidemiology of sepsis syndrome in a hospitalwide population. Objective.-To describe the epidemiology of sepsis syndrome in the tertiary care hospital setting. Design.-Prospective, multi-institutional, observational study including 5-month follow-up. Setting.-Eight academic tertiary care centers. Methods.-Each center monitored a weighted random sample of intensive care unit (ICU) patients, non-ICU patients who had blood cultures drawn, and all patients who received a novel therapeutic agent or who died in an emergency department or ICU. Sepsis syndrome was defined as the presence of either a positive blood culture or the combination of fever, tachypnea, tachycardia, clinically suspected infection, and any 1 of 7 confirmatory criteria. Estimates of total cases expected annually were extrapolated from the number of cases, the period of observation, and the sampling fraction. Results.-From January 4, 1993, to April 2, 1994, 12 759 patients were monitored and 1342 episodes of sepsis syndrome were documented. The extrapolated, weighted estimate of hospitalwide incidence (mean +/- 95% confidence limit) of sepsis syndrome was 2.0 +/- 0.16 cases per 100 admissions, or 2.8 +/- 0.17 per 1000 patient-days. The unadjusted attack rate for sepis syndrome between individual centers differed by as much as 3-fold, but after adjustment for institutional differences in organ transplant populations, variation from the expected number of cases was reduced to 2-fold and was not statistically significant overall. Patients in ICUs accounted for 59% of total extrapolated cases, non-ICU patients with positive blood cultures for 11%, and non-ICU patients with negative blood cultures for 30%. Septic shock was present at onset of sepsis syndrome in 25% of patients. Blood-stream infection was documented in 28%, with gram-positive organisms being the most frequent isolates. Mortality was 34% at 28 days and 45% at 5 months. Conclusions.-Sepsis syndrome is common in academic hospitals, although the overall rates vary considerably with the patient population. A substantial fraction of cases occur outside ICUs, An understanding of the hospitalwide epidemiology of sepsis syndrome is vital for rational planning and treatment of hospitalized patients with sepsis syndrome, especially as new and expensive therapeutic agents become available. C1 BRIGHAM & WOMENS HOSP,DEPT MED,CHANNING LAB,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT MED,DIV GEN MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA. HOSP UNIV PENN,DIV PULM & CRIT CARE,PHILADELPHIA,PA 19104. HOSP UNIV PENN,LEONARD DAVIS INST HLTH ECON,PHILADELPHIA,PA 19104. UNIV ROCHESTER,SCH MED,DEPT MED,INFECT DIS UNIT,ROCHESTER,NY. UNIV ROCHESTER,SCH MED,DEPT MED,GEN MED GERIATR UNIT,ROCHESTER,NY. MASSACHUSETTS GEN HOSP,DEPT MED,DIV INFECT DIS,BOSTON,MA 02114. UNIV CALIF LOS ANGELES,MED CTR,DIV GEN INTERNAL MED & HLTH SERV RES,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,MED CTR,DIV INFECT DIS,LOS ANGELES,CA 90024. DARTMOUTH HITCHCOCK MED CTR,INFECT DIS SECT,LEBANON,NH 03766. TUFTS UNIV NEW ENGLAND MED CTR,DEPT PATHOL & MED,DIV INFECT DIS,BOSTON,MA 02111. TUFTS UNIV,SCH MED,BOSTON,MA 02111. JOHNS HOPKINS MED INST,PHARMACOEPIDEMIOL PROGRAM,BALTIMORE,MD 21205. RI Snydman, David/O-3889-2014 OI Snydman, David/0000-0003-0119-3978 NR 29 TC 252 Z9 266 U1 0 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 JUL 16 PY 1997 VL 278 IS 3 BP 234 EP 240 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA XK108 UT WOS:A1997XK10800031 PM 9218672 ER PT J AU Burdi, D Aveline, BM Wood, PD Stubbe, J Redmond, RW AF Burdi, D Aveline, BM Wood, PD Stubbe, J Redmond, RW TI Generation of a tryptophan radical in high quantum yield from a novel amino acid analog using near-UV visible light SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID REDUCTASE PROTEIN R2; RIBONUCLEOTIDE REDUCTASE; ESCHERICHIA-COLI; FLASH-PHOTOLYSIS; CHEMISTRY; DERIVATIVES; TYROSINE; PEPTIDES; IDENTIFICATION; PHOTOCHEMISTRY AB Escherichia coli ribonucleotide reductase (RMC) catalyzes the conversion of nucleotides to deoxynucleotides. An initial step in this process has been postulated to be a coupled proton and electron transfer between the essential tyrosyl radical (.Y122) on the R2 subunit and a cysteine residue (C439) on the R1 subunit, the site of nucleotide reduction. One of our long-term goals is to generate the cysteinyl radical on R1 in the absence of R2 using a photoreactive peptide that binds to the R2 binding site of R1. Toward this end, the synthesis of an N-hydroxypyridine-2-thione derivative of tryptophan, designed to generate a tryptophan radical with a quantum of near-UV/visible light, is described. Laser flash photolysis (lambda(exc) = 355 nm) of this derivative gave rise to a transient absorption spectrum which showed a ground state depletion centered at its absorption maximum near 370 nm and a broad absorption band at 490 nm. The latter band partially decayed with a lifetime of similar to 3 mu s to leave an underlying band at 510 nm with a much longer lifetime, We have assigned the transient at 490 nm to the 2-pyridylthiyl radical and the transient at 510 nm to the neutral tryptophan radical, The addition of methyl methacrylate, a known thiyl radical quencher, suppressed the transient at 490 nm while the addition of trifluoroacetic acid caused a shift in the tryptophan radical absorbance to 560 nm consistent with protonation to form the corresponding cation radical. Using comparative actinometry, the quantum yields for N-O bond cleavage and tryptophan radical formation were found to be 1.0 +/- 0.1, This selective method for generating tryptophan radical, when incorporated into the appropriate peptide, may make this a useful probe for the study of electron transfer between the R1 and R2 subunits of RNR and may be generally applicable to other systems. C1 HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,DEPT DERMATOL,WELLMAN LABS PHOTOMED,BOSTON,MA 02114. MIT,DEPT CHEM,CAMBRIDGE,MA 02139. NR 41 TC 15 Z9 15 U1 1 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD JUL 16 PY 1997 VL 119 IS 28 BP 6457 EP 6460 DI 10.1021/ja9706918 PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA XL343 UT WOS:A1997XL34300001 ER PT J AU Rind, DM Kohane, IS Szolovits, P Safran, C Chueh, HC Barnett, GO AF Rind, DM Kohane, IS Szolovits, P Safran, C Chueh, HC Barnett, GO TI Maintaining the confidentiality of medical records shared over the Internet and the World Wide Web SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID CONSENT; LEGAL AB The Boston Electronic Medical Record Collaborative is working to develop a system that will use the World Wide Web to transfer computer-based patient information to clinicians in emergency departments. Maintaining adequate confidentiality of these records while still facilitating patient care is paramount to this effort. This paper describes an explicit protocol that would make it possible to electronically identify patients and providers, secure permission for release of records, and track information that is transmitted. It is hoped that other, similar efforts now underway will be able to use and build on this model. Comment on this proposal is invited from all parties with an interest in confidentiality. The system will be used only with ''scrubbed'' data-data from which all identifiers have been removed-until it is generally agreed that the confidentiality methods proposed here are appropriate and sufficient. C1 CHILDRENS HOSP,INFORMAT PROGRAM,BOSTON,MA 02115. MIT,COMP SCI LAB,CAMBRIDGE,MA 02139. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RP Rind, DM (reprint author), BETH ISRAEL MED CTR,CTR CLIN COMP,350 LONGWOOD AVE,BOSTON,MA 02115, USA. RI Kohane, Isaac Kohane/K-3716-2012; OI Kohane, Isaac Kohane/0000-0003-2192-5160; Szolovits, Peter/0000-0001-8411-6403 FU AHRQ HHS [HS08749]; NLM NIH HHS [U01 LM 05877] NR 23 TC 59 Z9 60 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 JUL 15 PY 1997 VL 127 IS 2 BP 138 EP 141 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA XK158 UT WOS:A1997XK15800010 PM 9230004 ER PT J AU Humphries, DE Sullivan, BM Aleixo, MD Stow, JL AF Humphries, DE Sullivan, BM Aleixo, MD Stow, JL TI Localization of human heparan glucosaminyl N-deacetylase/N-sulphotransferase to the trans-Golgi network SO BIOCHEMICAL JOURNAL LA English DT Article ID BREFELDIN-A; TRANSMEMBRANE DOMAIN; SULFATE PROTEOGLYCANS; MOLECULAR-CLONING; SULFOTRANSFERASE; BIOSYNTHESIS; DNA; EXPRESSION; RETENTION; PROTEIN AB In order to determine the intracellular location of heparan N-deacetylase/N-sulphotransferase, cDNAs encoding human heparan glucosaminyl N-deacetylase/N-sulphotransferase were cloned from human umbilical vein endothelial cells, The deduced amino acid sequence was identical to that of the human heparan N-sulphotransferase cloned previously [Dixon, Loftus, Gladwin, Scambler, Wasmuth and Dixon (1995) Genomics 26, 239-244]. RNA blot analysis indicated that two heparan N-sulphotransferase transcripts of approx, 8.5 and 4 kb were produced in all tissues. Expression was most abundant in heart, liver and pancreas, A cDNA encoding a Flag-tagged human heparan N-sulphotransferase (where Flag is an epitope with the sequence DYKDDDDK) was transfected into mouse LTA cells, Immunofluorescence detection using anti-Flag monoclonal antibodies demonstrated that the enzyme was localized to the trans-Golgi network, A truncated Flag-tagged heparan N-sulphotransferase was also retained in the Golgi, indicating that, as for many other Golgi enzymes, the N-terminal region of heparan N-sulphotransferase is sufficient for retention in the Golgi apparatus. C1 MASSACHUSETTS GEN HOSP, RENAL UNIT, BOSTON, MA 02130 USA. HARVARD UNIV, SCH MED, DEPT PATHOL, BOSTON, MA 02130 USA. UNIV QUEENSLAND, CTR MOL & CELLULAR BIOL, BRISBANE, QLD 4072, AUSTRALIA. RP HARVARD UNIV, SCH MED,DEPT MED,DEPT VET AFFAIRS MED CTR,RES 151, 150 S HUNTINGTON AVE, BOSTON, MA 02130 USA. OI Stow, Jennifer/0000-0002-5409-9101 FU NIDDK NIH HHS [DK42881] NR 39 TC 32 Z9 33 U1 0 U2 4 PU PORTLAND PRESS LTD PI LONDON PA CHARLES DARWIN HOUSE, 12 ROGER STREET, LONDON WC1N 2JU, ENGLAND SN 0264-6021 EI 1470-8728 J9 BIOCHEM J JI Biochem. J. PD JUL 15 PY 1997 VL 325 BP 351 EP 357 PN 2 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XK730 UT WOS:A1997XK73000010 PM 9230113 ER PT J AU Pillay, SS YurgelunTodd, DA Bonello, CM Lafer, B Fava, M Renshaw, PF AF Pillay, SS YurgelunTodd, DA Bonello, CM Lafer, B Fava, M Renshaw, PF TI A quantitative magnetic resonance imaging study of cerebral and cerebellar gray matter volume in primary unipolar major depression: Relationship to treatment response and clinical severity SO BIOLOGICAL PSYCHIATRY LA English DT Article DE morphometry; depression; gray matter; cerebral volume; cerebellar volume; fluoxetine response ID AFFECTIVE-DISORDER; ATROPHY; SCHIZOPHRENIA; TOMOGRAPHY; NUCLEI; LIFE AB The authors investigated whether there were differences in cerebral and cerebellar gray and white matter volumes in depressed patients compared to controls, and whether this was associated with treatment response to fluoxetine. Brain magnetic resonance images were obtained from 38 unipolar depressed patients and 20 age, gender, and educationally matched comparison subjects, Patients were divided into groups of ''responders'' and ''nonresponders'' based on change in 17-item Hamilton Depression Rating Scale (HDRS) after an 8-week standardized trial of fluoxetine, 20 mg/day, There were no group mean differences in cerebral or cerebellar tissue volumes between patients and controls, or responders and nonresponders, For nonresponders to fluoxetine treatment, cerebral and cerebellar gray matter volume, and total cerebellar tissue volume decreased as baseline HDRS increased The results suggest an association between gray matter volume and severity of illness in nonresponders to fluoxetine treatment. (C) 1997 Society of Biological Psychiatry. C1 MCLEAN HOSP,PSYCHOPHARMACOL SERV,BELMONT,MA 02178. MASSACHUSETTS GEN HOSP,CLIN PSYCHOPHARMACOL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,CONSOLIDATED DEPT PSYCHIAT,BOSTON,MA. RP Pillay, SS (reprint author), MCLEAN HOSP,BRAIN IMAGING CTR,115 MILL ST,BELMONT,MA 02178, USA. RI Lafer, Beny/C-1055-2012; Lafer, Beny/F-9390-2015 OI Lafer, Beny/0000-0002-6132-9999; Lafer, Beny/0000-0002-6132-9999 NR 31 TC 43 Z9 43 U1 3 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUL 15 PY 1997 VL 42 IS 2 BP 79 EP 84 DI 10.1016/S0006-3223(96)00335-6 PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA XG238 UT WOS:A1997XG23800001 PM 9209723 ER PT J AU Seidman, LJ Goldstein, JM Goodman, JM Koren, D Turner, WM Faraone, SV Tsuang, MT AF Seidman, LJ Goldstein, JM Goodman, JM Koren, D Turner, WM Faraone, SV Tsuang, MT TI Sex differences in olfactory identification and Wisconsin Card Sorting performance in schizophrenia: Relationship to attention and verbal ability SO BIOLOGICAL PSYCHIATRY LA English DT Article DE schizophrenia; sex; olfaction; executive functions; prefrontal; neuropsychology ID NEUROPSYCHOLOGICAL PERFORMANCE; ALZHEIMERS-DISEASE; DEFICITS; DYSFUNCTION; GENDER; BRAIN; IMPAIRMENTS; METABOLISM; DAMAGE; CORTEX AB We investigated the hypothesis that different prefrontal brain systems (i.e., dorsal vs. ventral) and sex contribute differentially to cognitive deficit in schizophrenia. Performance was assessed among clinically stable, chronic schizophrenic outpatients and matched normal control subjects on olfactory identification [on the University of Pennsylvania Smell Identification Test (UPSIT)] and on executive functions [using the Wisconsin Card Sorting Test (WCST)]. Patients were impaired on both tests compared to controls, and male schizophrenics were impaired on the WCST compared to female schizophrenics. The pattern of results suggests that gender differences on the UPSIT are mildly accentuated in schizophrenia. The data support our previous study indicating that UPSIT performance is largely independent of the executive or attentional deficits typically associated with schizophrenia, with the exception of verbal ability. Further research with larger samples is required to test the hypothesis that there is a severely impaired subgroup of male patients with diffuse prefrontal dysfunctions. (C) 1997 Society of Biological Psychiatry. C1 HARVARD UNIV,INST PSYCHIAT EPIDEMIOL & GENET,DEPT PSYCHIAT,MASSACHUSETTS MENTAL HLTH CTR,BROCKTON,MA 02401. BROCKTON W ROXBURY VET AFFAIRS MED CTR,BROCKTON,MA. BOSTON UNIV,SCH MED,PROGRAM BEHAV NEUROSCI,BOSTON,MA 02118. UNIV HAIFA,DEPT PSYCHOL,IL-31999 HAIFA,ISRAEL. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PSYCHIAT,BOSTON,MA. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. RP Seidman, LJ (reprint author), HARVARD UNIV,NEUROPSYCHOL LAB S530,MASSACHUSETTS MENTAL HLTH CTR,NEUROPSYCHOL LAB,BOSTON,MA 02115, USA. OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [MH41874-03, K21 MH00976, MH43518-03] NR 69 TC 97 Z9 98 U1 3 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUL 15 PY 1997 VL 42 IS 2 BP 104 EP 115 DI 10.1016/S0006-3223(96)00300-9 PG 12 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA XG238 UT WOS:A1997XG23800005 PM 9209727 ER PT J AU Cardoso, AA Seamon, MJ Afonso, HM Ghia, P Boussiotis, VA Freeman, GJ Gribben, JG Sallan, SE Nadler, LM AF Cardoso, AA Seamon, MJ Afonso, HM Ghia, P Boussiotis, VA Freeman, GJ Gribben, JG Sallan, SE Nadler, LM TI Ex vivo generation of human anti-pre-B leukemia-specific autologous cytolytic T cells SO BLOOD LA English DT Article ID TUMOR-CELLS; CLONES; LINES; VIRUS; ACTIVATION; MELANOMA; LYMPHOMA; TARGET; PROLIFERATION; INTERLEUKIN-2 AB In contrast to other neoplasms, antigen-specific autologous cytolytic T cells have not been detected in patients with human pre-B-cell leukemias. The absence of efficient B7 family (B7-1/CD80;B7-2/CD86)-mediated costimulation has been shown to be a major defect in tumor cells' capacity to function as antigen-presenting cells. We show here the generation of autologous anti-pre-B-cell leukemia-specific cytolytic T-cell lines from the marrows of 10 of 15 patients with pre-B-cell malignancies. T-cell costimulation via CD28 is an absolute requirement for the generation of these autologous cytolytic T cells (CTL). Although costimulation could be delivered by either bystander B7 transfectants or professional antigen-presenting cells (indirect costimulation), optimal priming and CTL expansion required that the costimulatory signal was expressed by the tumor cell (direct costimulatory. These anti-pre-B-cell leukemia-specific CTL lysed both unstimulated and CD40-stimulated tumor cells from each patient studied but did not lyse either K562 or CD40-stimulated allogeneic B cells. Cytolysis was mediated by the induction of tumor cell apoptosis by CD8(+) T cells via the perforin-granzyme pathway. Although we were able to generate anti-leukemia-specific CTL from the bone marrow, we were unable to generate such CTL from the peripheral blood of these patients. These studies show that antigen-specific CTL can be generated from the bone marrow of patients with pre-B-cell leukemias and these findings should facilitate the design of adoptive T-cell-mediated immunotherapy trials for the treatment of patients with B-cell precursor malignancies. (C) 1997 by The American Society of Hematology. C1 DANA FARBER CANC INST,DEPT PEDIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA. BRIGHAM & WOMENS HOSP,DEPT MED,BOSTON,MA 02115. RP Cardoso, AA (reprint author), DANA FARBER CANC INST,DEPT MED ONCOL,D-740,44 BINNEY ST,BOSTON,MA 02115, USA. RI Ghia, Paolo/K-7138-2016 OI Ghia, Paolo/0000-0003-3750-7342 FU NCI NIH HHS [P01-CA66996-01, P01-CA68484-02] NR 34 TC 105 Z9 106 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 JUL 15 PY 1997 VL 90 IS 2 BP 549 EP 561 PG 13 WC Hematology SC Hematology GA XL774 UT WOS:A1997XL77400007 PM 9226154 ER PT J AU Urashima, M Chen, BP Chen, S Pinkus, GS Bronson, RT Dedera, DA Hoshi, Y Teoh, G Ogata, A Treon, SP Chauhan, D Anderson, KC AF Urashima, M Chen, BP Chen, S Pinkus, GS Bronson, RT Dedera, DA Hoshi, Y Teoh, G Ogata, A Treon, SP Chauhan, D Anderson, KC TI The development of a model for the homing of multiple myeloma cells to human bone marrow SO BLOOD LA English DT Article ID SCID-HU MOUSE; INTERLEUKIN-6 TRANSGENIC MICE; PLASMA-CELLS; ADHESION MOLECULES; STROMAL CELLS; TUMOR-CELLS; EXPRESSION; GROWTH; LINES; SECRETION AB Prior in vitro studies have suggested a role of adhesion molecules, bone marrow stromal cells (BMSCs), and cytokines in the regulation of human multiple myeloma (MM) cell growth and survival. Although in vivo models have been developed in severe combined immunodeficient (SCID) mice that support the growth of human MM within the murine BM microenvironment, these xenograft models do not permit a study of the role of adhesion proteins in human MM cell-human BMSC interactions. We therefore established an in vivo model of human MM using SCID mice implanted with bilateral human fetal bone grafts (SCID-hu mice). For the initial tumor innoculum, human MM derived cell lines (1 x 10(4) or 5 x 10(4) ARH-77, OCI-My5, U-266, or RPMI-8226 cells) were injected directly into the BM cavity of the left bone implants in irradiated SCID-hu mice. MM cells engrafted and proliferated in the left human fetal bone implants within SCID-hu mice as early as 4 weeks after injection of as few as 1 x 10(4) MM cells, To determine whether homing of tumor cells occurred, animals were observed for up to 12 weeks after injection and killed to examine for tumor in the right bone implants. Of great interest, metastases to the right bone implants were observed at 12 weeks after the injection of 5 x 10(4) MM cells, without spread of human MM cells to murine BM. Human MM cells were identified on the basis of characteristic histology and monoclonal human Ig, Importantly, monoclonal human Ig and human interleukin-6 (IL-6), but not human IL-1 beta or tumor necrosis factor-alpha, were detectable in sera of SCID-hu mice injected with MM cells, In addition, specific monoclonal Ig light chain deposition was evident within renal tubules, This in vivo model of human MM provides for the first time a means for identifying adhesion molecules that are responsible for specific homing of human MM cells to the human, as opposed to murine, BM microenvironment. Moreover, induction of human IL-6 suggests the possibility that regulation of MM cell growth by this cytokine might also be investigated using this in vivo model. (C) 1997 by The American Society of Hematology. C1 DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02215. BRIGHAM & WOMENS HOSP,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. SYSTEMIX INC,PALO ALTO,CA. TUFTS UNIV,SCH VET MED,DIV LABS,BOSTON,MA 02111. JIKEI UNIV,SCH MED,DEPT PEDIAT,TOKYO,JAPAN. FU NCI NIH HHS [CA 50947] NR 52 TC 124 Z9 127 U1 2 U2 6 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JUL 15 PY 1997 VL 90 IS 2 BP 754 EP 765 PG 12 WC Hematology SC Hematology GA XL774 UT WOS:A1997XL77400029 PM 9226176 ER PT J AU Zietman, AL Prince, EA Nakfoor, BM Park, JJ AF Zietman, AL Prince, EA Nakfoor, BM Park, JJ TI Androgen deprivation and radiation therapy: Sequencing studies using the Shionogi in vivo tumor system SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE Shionogi tumor; radiation; androgen deprivation ID PROSTATE-CANCER; CARCINOMA AB Purpose: To test the relative effect of neoadjuvant and adjuvant androgen deprivation on the radiation response of an androgen dependent tumor, Methods and Materials: The transplantable, androgen dependent, Shionogi adenocarcinoma was grown as allografts in the hind limbs of NCr/Sed (nu/nu) athymic nude mice, Bilateral orchiectomy was the chosen form of androgen deprivation, Groups of tumors were irradiated to graded tumor doses and then studied for durable tumor control. The radiation response was expressed as the radiation dose required to control 50% of the tumors (TCD50). The sequence of radiation and orchiectomy was studied, Results: When radiation was combined with orchiectomy the Shionogi tumor was significantly more likely to be controlled than when radiation was used alone, Orchiectomy 12 days prior to radiation (neoadjuvant therapy) produced a significantly greater decline in the TCD50 than when orchiectomy was used 1 day or 12 days after radiation (adjuvant therapy). If, before radiation, tumors were allowed to regrow after orchiectomy to their original size in an androgen independent fashion then the advantage was largely lost, Those tumors responding well to neoadjuvant orchiectomy (> 50% volume decrease) were significantly more likely to be eradicated by radiation than those with a lesser response, Conclusion: When using combinations of androgen deprivation and radiation in the treatment of the Shionogi tumor, sequence and timing of the therapies are crucial to maximize the erect. (C) 1997 Elsevier Science Inc. RP Zietman, AL (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,EDWIN STEELE LAB,BOSTON,MA 02114, USA. NR 14 TC 93 Z9 97 U1 1 U2 2 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 JUL 15 PY 1997 VL 38 IS 5 BP 1067 EP 1070 DI 10.1016/S0360-3016(97)00309-X PG 4 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA XR730 UT WOS:A1997XR73000020 PM 9276373 ER PT J AU DellItalia, LJ Meng, QC Balcells, E Wei, CC Palmer, R Hageman, GR Durand, J Hankes, GH Oparil, S AF DellItalia, LJ Meng, QC Balcells, E Wei, CC Palmer, R Hageman, GR Durand, J Hankes, GH Oparil, S TI Compartmentalization of angiotensin II generation in the dog heart - Evidence for independent mechanisms in intravascular and interstitial spaces SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE angiotensin-converting enzyme inhibitors; left ventricular function; angiotensins; heart; heart hypertrophy ID CARDIAC-HYPERTROPHY; ADENOSINE-DEAMINASE; FORMING CHYMASE; EXPRESSION; SYSTEM; QUANTITATION; INCREASES; MYOCYTES; PATHWAYS; PEPTIDES AB Angiotensin-converting enzyme inhibitors have beneficial effects that are presumably mediated by decreased angiotensin II (ANG II) production. In this study, we measure for the first time ANG I and ANG II levels in the interstitial fluid (ISF) space of the heart. ISF and aortic plasma ANG I and II levels were obtained at baseline, during intravenous infusion of ANG I (5 mu M, 0.1 ml/min, 60 min), and during ANG I + the angiotensin-converting enzyme inhibitor captopril (cap) (2.5 mM, 0.1 ml/min, 60 min) in six anesthetized open-chested dogs, ISF samples were obtained using microdialysis probes inserted into the left ventricular myocardium (3-4 probes/dog). ANC I increased mean arterial pressure from 102+/-3 (SEM) to 124+/-3 mmHg (P < 0.01); addition of cap decreased MAP to 95+/-3 mmHg (P < 0.01). ANG I infusion increased aortic plasma ANG I and ANG II (pg/ml) (ANG I = 101+/-129 to 370+/-158 pg/ml, P < 0.01; and ANG II = 22+/-40 to 466+/-49, P < 0.01); addition of cap further increased ANG I(1,790+/-158, P < 0.01) and decreased ANG II (33+/-49, P < 0.01), ISF ANG I and ANG II levels (pg/ml) were > 100-fold higher than plasma levels, and did not change from baseline (8,122+/-528 and 6,333+/-677), during ANG 1(8,269+/-502 and 6,139+/-695) or ANG I + cap (8,753+/-502 and 5,884+/-695), The finding of very high ANG I and ANG II levels in the ISF vs, intravascular space that are not affected by IV ANG I or cap suggests that ANG II production and/or degradation in the heart is compartmentalized and mediated by different enzymatic mechanisms in the interstitial and intravascular spaces. C1 UNIV ALABAMA,BIRMINGHAM VET AFFAIRS MED CTR,BIRMINGHAM,AL 35294. UNIV ALABAMA,DEPT MED,DIV CARDIOVASC DIS,BIRMINGHAM,AL 35294. UNIV ALABAMA,DEPT PHYSIOL & BIOPHYS,BIRMINGHAM,AL 35294. AUBURN UNIV,COLL VET MED,AUBURN,AL 36849. FU NHLBI NIH HHS [2T32HLO7457-16A1, R01 HL54816]; NICHD NIH HHS [HD SCOR HL 17667] NR 37 TC 141 Z9 142 U1 1 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL 15 PY 1997 VL 100 IS 2 BP 253 EP 258 DI 10.1172/JCI119529 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA XN372 UT WOS:A1997XN37200003 PM 9218500 ER PT J AU Chung, DC Smith, AP Louis, DN GraemeCook, F Warshaw, AL Arnold, A AF Chung, DC Smith, AP Louis, DN GraemeCook, F Warshaw, AL Arnold, A TI A novel pancreatic endocrine tumor suppressor gene locus on chromosome 3p with clinical prognostic implications SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE islet cell tumor; pancreatic endocrine tumor; chromosome 3p25; VHL gene; tumor suppressor gene ID HIPPEL-LINDAU DISEASE; CELL LUNG-CANCER; PARATHYROID ADENOMAS; RENAL-CARCINOMA; RECEPTOR GENE; MUTATIONS; IDENTIFICATION; TUMORIGENESIS; POLYMORPHISM; REGION AB The molecular pathogenesis of pancreatic endocrine tumors is largely unknown, Such tumors are more likely to develop in individuals with the von Hippel-Lindau (VHL) syndrome, We sought to determine whether allelic loss of the recently identified VHL tumor suppressor gene on chromosome 3p25-26 occurs in the more common sporadic forms of these tumors. Allelic loss on chromosome 3p was identified in 33% of 43 patients with endocrine tumors of the pancreas. The smallest common region of allelic loss, however, centered not at the VHL locus, but rather at 3p25, centromeric to VHL, Furthermore, no mutations of the VHL gene were identified in these tumors. Loss of alleles on chromosome 3p was associated with clinically malignant disease, whereas tumors with retained 3p alleles were more likely to be benign. Thus, the VHL gene does not appear to play a pathogenic role in the development of sporadic pancreatic endocrine tumors, Instead, a locus at chromosome 3p25 may harbor a novel pancreatic endocrine tumor suppressor gene, and allelic loss of this chromosomal region may serve as a molecular marker that helps distinguish benign from clinically malignant disease. C1 MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP Chung, DC (reprint author), MASSACHUSETTS GEN HOSP,LAB ENDOCRINE ONCOL,JACKSON 1020,55 FRUIT ST,BOSTON,MA 02114, USA. FU NCI NIH HHS [CA 55909]; NIDDK NIH HHS [DK11794, DK01410-1] NR 50 TC 97 Z9 99 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL 15 PY 1997 VL 100 IS 2 BP 404 EP 410 DI 10.1172/JCI119547 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA XN372 UT WOS:A1997XN37200021 PM 9218518 ER PT J AU Tanabe, S Heesen, M Yoshizawa, I Berman, MA Luo, Y Bleul, CC Springer, TA Okuda, K Gerard, N Dorf, ME AF Tanabe, S Heesen, M Yoshizawa, I Berman, MA Luo, Y Bleul, CC Springer, TA Okuda, K Gerard, N Dorf, ME TI Functional expression of the CXC-chemokine receptor-4/fusin on mouse microglial cells and astrocytes SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PROTEIN-COUPLED RECEPTORS; CENTRAL-NERVOUS-SYSTEM; CHROMOSOMAL LOCALIZATION; SIGNAL-TRANSDUCTION; MOLECULAR-CLONING; HUMAN HOMOLOG; NPY BINDING; HIV-1; INFECTION; CULTURES AB The mRNA for the seven-transmembrane-spanning G protein-coupled receptor fusin/CXCR-4 is expressed in primary mouse astrocyte cultures and the transformed mouse microglial cell line, N9. Cell surface expression of fusin in these cells was confirmed by staining with a polyclonal anti-fusin Ab. The functional capacity of this chemokine receptor was examined by evaluating the calcium responses following stimulation of glial cells with the CXC-chemokine, stromal-derived cell factor-la (SDF-1 alpha). Both astrocytes and microglial cells mobilized calcium following stimulation with chemically synthesized SDF-1 alpha. SDF-1 alpha- and carbachol-mediated calcium responses of astrocytes were partially inhibited by treatment with pertussis toxin (PTx), suggesting receptor coupling to a combination of G alpha(i) and other G proteins. In contrast, the calcium responses of microglial cells to SDF-1 alpha were completely PTx sensitive, while responses to carbachol stimulation were PTx resistant. The ability of SDF-1 alpha to induce glial cell migration was also examined. Synthetic SDF-1 alpha was a potent chemoattractant for mouse microglial cells at ligand concentrations of 10 to 500 ng/ml; peak responses were noted at 100 ng/ml. In contrast, astrocytes did not migrate toward a gradient of SDF-1 alpha. The failure of SDF-1 alpha to induce astrocyte migration was specific, as another chemokine, macrophage inflammatory protein-1 alpha, triggered astrocyte chemotaxis. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. BETH ISRAEL DEACONESS MED CTR,PULM UNIT,BOSTON,MA 02115. YOKOHAMA CITY UNIV,SCH MED,DEPT BACTERIOL,KANAZAWA KU,YOKOHAMA,KANAGAWA 232,JAPAN. FU NCI NIH HHS [CA67416]; NINDS NIH HHS [NS31152] NR 43 TC 140 Z9 141 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 JUL 15 PY 1997 VL 159 IS 2 BP 905 EP 911 PG 7 WC Immunology SC Immunology GA XJ674 UT WOS:A1997XJ67400046 PM 9218610 ER PT J AU Reid, RR Prodeus, AP Khan, W Hsu, T Rosen, FS Carroll, MC AF Reid, RR Prodeus, AP Khan, W Hsu, T Rosen, FS Carroll, MC TI Endotoxin shock in antibody-deficient mice - Unraveling the role of natural antibody and complement in the clearance of lipopolysaccharide SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CBA-N MICE; B-CELLS; RHEUMATOID-FACTOR; STREPTOCOCCUS-PNEUMONIAE; GENETIC-CONTROL; LYMPHOCYTE-B; AUTOANTIBODIES; INFECTION; SPECIFICITIES; MECHANISMS AB While the significance of natural Ab is not entirely clear, one proposed role is clearance of bacterial Ags, To determine whether natural Ab was involved in clearance of endotoxin, we have examined novel strains of mice with either a total or selective deficiency in Ig, Recombinase-activating gene-2 (RAC-2(-/-))-deficient mice, which have no serum Ig due to arrested development of B cells at the pro-B stage, demonstrate increased sensitivity to endotoxin that correlates with an impaired clearance, When RAC-2(-/-) mice are reconstituted with pooled sera from normal mice, both survival and clearance of circulating endotoxin are enhanced, To further define the nature of the protective Ab, Bruton's tyrosine kinase (Btk) deficient mice were characterized in the high dose LPS model. Like RAG-2(-/-) mice, they are highly sensitive to endotoxin and have an impaired clearance of LPS, Reconstitution of Btk(-/-) mice, which have reduced levels of IgG3 and IgM, with purified normal mouse IgM dramatically enhances their ability to clear endotoxin compared with mock (saline)-reconstituted littermates. The cellular source of natural anti-LPS IgM was identified as the peritoneal-residing B-1 cell by enzyme-linked immunospot (ELISPOT) assay, Taken together, these studies demonstrate the important role of natural Ab and complement in the clearance of pathogenic substances from the circulation. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. CHILDRENS HOSP,HOWARD HUGHES MED INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. FU NIAID NIH HHS [AI-36389]; NICHD NIH HHS [HD 1746]; NIGMS NIH HHS [P50 GM-52585] NR 34 TC 124 Z9 126 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 15 PY 1997 VL 159 IS 2 BP 970 EP 975 PG 6 WC Immunology SC Immunology GA XJ674 UT WOS:A1997XJ67400054 PM 9218618 ER PT J AU Fischer, MB Prodeus, AP NicholsonWeller, A Ma, MH Murrow, J Reid, RR Warren, HB Lage, AL Moore, FD Rosen, FS Carroll, MC AF Fischer, MB Prodeus, AP NicholsonWeller, A Ma, MH Murrow, J Reid, RR Warren, HB Lage, AL Moore, FD Rosen, FS Carroll, MC TI Increased susceptibility to endotoxin shock in complement C3- and C4-deficient mice is corrected by C1 inhibitor replacement SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NITRIC-OXIDE SYNTHASE; SEPTIC SHOCK; HAGEMAN-FACTOR; PATHOGENESIS; RESPONSES; SEPSIS; INACTIVATION; ACTIVATION; COMPONENT; INFECTION AB Endotoxin shock is a life-threatening syndrome associated with a Gram-negative infection and mediated by a systemic inflammatory response, As a major effector of inflammation, the complement system has been implicated in both the pathogenesis and the protection from endotoxin shock, To clarify the role of complement in endotoxin shock, we have used mice totally deficient in either complement component C3 or C4, We found that both the C3- and C4-deficient mice were significantly more sensitive to endotoxin than wild-type controls, The endotoxin-challenged complement-deficient mice failed to clear endotoxin efficiently from the circulation and this led to excess consumption of C1 inhibitor protein (C1 INH), a major regulator of both complement and the contact system of blood coagulation, Replacement of C1 INH rescued the endotoxin-challenged complement-deficient mice from shock and death, These findings suggest a novel therapy for treatment of endotoxemia with C1 INH protein. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. BETH ISRAEL HOSP,BOSTON,MA 02115. CTR ANIM RESOURCES & COMPARAT MED,BOSTON,MA 02115. FU NIAID NIH HHS [AI-36389]; NICHD NIH HHS [HD-1746]; NIGMS NIH HHS [P50 GM-52585] NR 33 TC 72 Z9 74 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 JUL 15 PY 1997 VL 159 IS 2 BP 976 EP 982 PG 7 WC Immunology SC Immunology GA XJ674 UT WOS:A1997XJ67400055 PM 9218619 ER PT J AU Brezinski, ME Tearney, GJ Boppart, SA Swanson, EA Southern, JF Fujimoto, JG AF Brezinski, ME Tearney, GJ Boppart, SA Swanson, EA Southern, JF Fujimoto, JG TI Optical biopsy with optical coherence tomography: Feasibility for surgical diagnostics SO JOURNAL OF SURGICAL RESEARCH LA English DT Article ID EXPERIENCE; REMOVAL AB Background: Optical coherence tomography (OCT) is a recently developed compact technology which uses infrared light to perform cross-sectional imaging on a micrometer scale. Since OCT provides imaging at a resolution comparable to conventional histology and does not require direct contact with the tissue surface, a role in real-time surgical diagnostics represents a logical extension. In this work, we test the feasibility of OCT for surgical diagnostics by demonstrating imaging in tissue relevent to microsurgical intervention, a previously undescribed observation. Materials and methods: Over 50 sites on nervous, reproductive, and microvascular specimens from 10 patients were examined postmortem with OCT. After imaging, tissue was registered with microinjections of dye, under visible light laser guidance, followed by routine histologic processing to confirm the identity of microstructure. Results: The 16 +/- 1 mu m resolution allowed subsurface microstructure to be identified at unprecedented resolution. Structures identified included fascicles of peripheral nerves, the internal elastic membrane of microvessels, and the granular layer of the cerebellum. conclusions: The ability of OCT to provide micrometer-scale definition of tissue microstructure suggests a role in surgical diagnostics. Future in vivo investigations are merited to establish its utility for morbidity reduction associated with surgical intervention. (C) 1997 Academic Press. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. MIT,DEPT ELECT ENGN & COMP SCI,CAMBRIDGE,MA 02139. MIT,ELECT RES LAB,CAMBRIDGE,MA 02139. LINCOLN LAB,LEXINGTON,MA 02173. RP Brezinski, ME (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. RI Boppart, Stephen/C-7338-2009 FU NEI NIH HHS [NIH-9-R01-EY11289-10]; NIGMS NIH HHS [NIH-5-R01-GM35459-09] NR 23 TC 64 Z9 64 U1 1 U2 7 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD JUL 15 PY 1997 VL 71 IS 1 BP 32 EP 40 DI 10.1006/jsre.1996.4993 PG 9 WC Surgery SC Surgery GA XR040 UT WOS:A1997XR04000006 PM 9271275 ER PT J AU Metlay, JP Schulz, R Li, YH Singer, DE Marrie, TJ Coley, CM Hough, LJ Obrosky, DS Kapoor, WN Fine, MJ AF Metlay, JP Schulz, R Li, YH Singer, DE Marrie, TJ Coley, CM Hough, LJ Obrosky, DS Kapoor, WN Fine, MJ TI Influence of age on symptoms at presentation in patients with community-acquired pneumonia SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 18th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 04-06, 1995 CL SAN DIEGO, CA SP Soc Gen Internal Med ID BACTEREMIC PNEUMOCOCCAL PNEUMONIA; FUNCTIONAL STATUS; REQUIRING HOSPITALIZATION; ADULTS; MANIFESTATIONS; DIAGNOSIS; THERAPY; PROXY AB Background: Advanced age has become a well-recognized risk factor for death in patients with pneumonia. It may also be associated with reduced symptom reporting, raising the possibility that diagnosis and treatment may be delayed in older patients. Objective: To evaluate the association between age and the presenting symptoms in patients with community-acquired pneumonia. Methods: This study was conducted at inpatient and outpatient facilities at 3 university hospitals, 1 community hospital, and 1 staff-model health maintenance organization. Patients included adults (age greater than or equal to 18 years) with clinical and radiographic evidence of pneumonia, who were able to complete a baseline interview. The presence of 5 respiratory symptoms and 13 nonrespiratory symptoms were recorded during a baseline patient interview. A summary symptom score was computed as the total number of symptoms at presentation. Results: The 1812 eligible study patients were categorized into 4 age groups: 18 through 44 years (43%), 45 through 64 years (25%), 65 through 74 years (17%), and 75 years or older (15%). For 17 of the 18 symptoms, there were significant decreases in reported prevalence with increasing age (P<.01). In a linear regression analysis, controlling for patient demographics, comorbidity, and severity of illness at presentation, older age remained associated with lower symptom scores (P<.001). Conclusions: Respiratory and nonrespiratory symptoms are less commonly reported by older patients with pneumonia, even after controlling for the increased comorbidity and illness severity in these older patients. Recognition of this phenomenon by clinicians and patients is essential given the increased mortality in elderly patients with pneumonia. C1 MONTEFIORE UNIV HOSP,PITTSBURGH,PA 15213. UNIV PITTSBURGH,MED CTR,GRAD SCH PUBL HLTH,DIV GEN INTERNAL MED,DEPT MED,PITTSBURGH,PA 15213. UNIV PITTSBURGH,MED CTR,GRAD SCH PUBL HLTH,DEPT PSYCHIAT,PITTSBURGH,PA 15213. UNIV PITTSBURGH,MED CTR,GRAD SCH PUBL HLTH,DEPT BIOSTAT,PITTSBURGH,PA 15213. MASSACHUSETTS GEN HOSP,DEPT MED,GEN INTERNAL MED UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. DALHOUSIE UNIV,HALIFAX,NS,CANADA. VICTORIA GEN HOSP,DEPT MED & MICROBIOL,HALIFAX,NS B3H 2Y9,CANADA. FU AHRQ HHS [R01 HS06468] NR 30 TC 196 Z9 204 U1 1 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JUL 14 PY 1997 VL 157 IS 13 BP 1453 EP 1459 DI 10.1001/archinte.157.13.1453 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA XJ665 UT WOS:A1997XJ66500008 PM 9224224 ER PT J AU Tsang, AP Visvader, JE Turner, CA Fujiwara, Y Yu, CN Weiss, MJ Crossley, M Orkin, SH AF Tsang, AP Visvader, JE Turner, CA Fujiwara, Y Yu, CN Weiss, MJ Crossley, M Orkin, SH TI FOG, a multitype zinc finger protein, acts as a cofactor for transcription factor GATA-1 in erythroid and megakaryocytic differentiation SO CELL LA English DT Article ID DNA-BINDING PROTEIN; HEMATOPOIETIC-CELLS; MAMMALIAN-CELLS; EXPRESSION; GENE; ASSOCIATION; NF-E2; MICE; LINEAGES; CLONING AB The hematopoietic transcription factor GATA-1 is essential for development of the erythroid and megakaryocytic lineages. Using the conserved zinc finger DNA-binding domain of GATA-1 in the yeast two-hybrid system, we have identified a novel, multitype zinc finger protein, friend of GATA-1 (FOG), which binds GATA-1 but not a functionally inactive mutant lacking the amino (N) finger. FOG is coexpressed with GATA-1 during embryonic development and in erythroid and megakaryocytic cells. Furthermore, FOG and GATA-1 synergistically activate transcription from a hematopoietic-specific regulatory region and cooperate during both erythroid and megakaryocytic cell differentiation. These findings indicate that FOG acts as a cofactor for GATA-1 and provide a paradigm for the regulation of cell type-specific gene expression by GATA transcription factors. C1 CHILDRENS HOSP,DIV HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PEDIAT,BOSTON,MA 02115. CHILDRENS HOSP,HOWARD HUGHES MED INST,BOSTON,MA 02115. RI Crossley, Merlin/D-7888-2011; Weiss, Mitchell/A-1245-2013 OI Crossley, Merlin/0000-0003-2057-3642; FU NIGMS NIH HHS [T32-GM07753-18, T32 GM007753] NR 51 TC 527 Z9 540 U1 1 U2 8 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD JUL 11 PY 1997 VL 90 IS 1 BP 109 EP 119 DI 10.1016/S0092-8674(00)80318-9 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XL362 UT WOS:A1997XL36200013 PM 9230307 ER PT J AU Feschenko, MS Sweadner, KJ AF Feschenko, MS Sweadner, KJ TI Phosphorylation of Na,K-ATPase by protein kinase C at Ser(18) occurs in intact cells but does not result in direct inhibition of ATP hydrolysis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROXIMAL TUBULE CELLS; NA+-K+-ATPASE; NA+,K+-ATPASE ACTIVITY; CATALYTIC SUBUNIT; ALPHA-SUBUNIT; STIMULATION; INSULIN; KIDNEY; SITE; IDENTIFICATION AB Na,K-ATPase activity has been demonstrated to be regulated by a variety of hormones in different tissues. It is known to be directly phosphorylated on its alpha-subunit, but the functional effects of protein kinases remain controversial, We have developed a sensitive, antibody-based assay for detection of the level of phosphorylation of the alpha 1-isoform of rat Na,K-ATPase at the serine residue that is most readily phosphorylated by protein kinase C (PKC) in vitro, Ser(18), By stimulation of endogenous PKC and inhibition of phosphatase activity, it was possible to consistently obtain a very high stoichiometry of phosphorylation (close to 0.9) in several types of intact cells, This demonstrates the accessibility and competency of the site for endogenous phosphorylation. The cells used were derived from rat (NRK 52E, C6, L6, and primary cultures of cerebellar granule cells, representing epithelial cells, glia, muscle cells, and neurons). In the presence of the phosphatase inhibitor calyculin A, full phosphorylation was preserved during subsequent assays of enzyme activity in vitro. Assay of the hydrolysis of ATP in NRK and C6 cells, however, indicated that there was no significant effect of phosphorylation on the V-max of the Na,K-ATPase or on the apparent affinity for Na+, Any regulatory effect of PHC on sodium pump activity thus must be lost upon disruption or permeabilization of the cells and is not a direct consequence of enzyme alteration by covalent phosphorylation of Ser(18). C1 MASSACHUSETTS GEN HOSP, CTR NEUROSCI, LAB MEMBRANE BIOL, CHARLESTOWN, MA 02129 USA. FU NINDS NIH HHS [NS 27653] NR 41 TC 91 Z9 91 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 11 PY 1997 VL 272 IS 28 BP 17726 EP 17733 DI 10.1074/jbc.272.28.17726 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XK165 UT WOS:A1997XK16500067 PM 9211924 ER PT J AU Li, SL Valente, AJ Zhao, SJ Clark, RA AF Li, SL Valente, AJ Zhao, SJ Clark, RA TI PU.1 is essential for p47(phox) promoter activity in myeloid cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CHRONIC GRANULOMATOUS-DISEASE; RESPIRATORY BURST OXIDASE; COLONY-STIMULATING FACTOR-1; CCAAT DISPLACEMENT PROTEIN; TRANSCRIPTION FACTOR PU.1; TUMOR-NECROSIS-FACTOR; RNA-POLYMERASE-II; NADPH OXIDASE; CD11B PROMOTER; GENE PROMOTER AB Expression of the phagocyte cytosolic protein p47(phox), a component of NADPH oxidase, is restricted mainly to myeloid cells. To study the cis elements and trans acting factors responsible for its gene expression, we have cloned and characterized the p47(phox) promoter, A predominant transcriptional start site was identified 21 nucleotides upstream of the translation initiation codon, To identify the gene promoter sequences, transient transfections of HL-60 human myeloid cells were performed with a series of 5'-deletion p47(phox)-luciferase reporter constructs that extended as far upstream as -3050 bp relative to the transcriptional start site, The -224 and -86 constructs had the strongest p47(phax) promoter activity, whereas the -46 construct showed a major reduction in activity and the -36 construct a complete loss of activity. DNase I footprint analysis identified a protected region from -57 to -53. This region containing a consensus PU.1 site bound specifically both PU,I present in nuclear extracts from myeloid cells and PU.1 synthesized in vitro. Mutations of this site eliminated PU.1 binding and abolished the ability of the p47(phox) promoter to direct expression of the reporter gene, The p47(phox) promoter was active in all myeloid cell Lines tested (HL-60, THP-1, U937, PLB-985), but not in non-myeloid cells (HeLa, HEK293). Finally, PU.1 transactivated the p47(phox)-luciferase constructs in HeLa cells, We conclude that, similar to certain other myeloid specific genes, p47(phox) promoter activity in myeloid cells requires PU.1. C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. S TEXAS VET HLTH CARE SYST,AUDIE L MURPHY DIV,SAN ANTONIO,TX 78284. FU NHLBI NIH HHS [HL52665]; NIAID NIH HHS [AI20866, R01 AI020866, R37 AI020866] NR 70 TC 56 Z9 56 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 JUL 11 PY 1997 VL 272 IS 28 BP 17802 EP 17809 DI 10.1074/jbc.272.28.17802 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XK165 UT WOS:A1997XK16500077 PM 9211934 ER PT J AU Jacquot, S Kobata, T Iwata, S Schlossman, SF Morimoto, C AF Jacquot, S Kobata, T Iwata, S Schlossman, SF Morimoto, C TI CD27/CD70 interaction contributes to the activation and the function of human autoreactive CD27(+) regulatory T cells SO CELLULAR IMMUNOLOGY LA English DT Article ID MIXED-LYMPHOCYTE-REACTION; TUMOR-NECROSIS-FACTOR; HELPER-INDUCER; ANTIGEN; SUBSET; EXPRESSION; FAMILY; LIGAND; PARTICIPATION; COSTIMULATION AB CD27, a tumor necrosis factor receptor family member, is a costimulatory molecule for T and B cell activation. We demonstrate here that CD27 signaling is critical for T cell activation in the autologous mixed lymphocyte reaction (aMLR) and for aMLR-induced generation of regulatory T cells that suppress pokeweed mitogen-driven immunoglobulin G synthesis by B cells. Moreover, CD27, expressed on CD45RA(+) CD4(+) T cells, is directly involved in the suppressor function of aMLR-activated CD4(+) T cells, probably by interfering with the interaction between CD70, the CD27 ligand, expressed on CD45RO(+) CD4(+) helper T cells, and CD27, expressed on B cells. CD8(+) T cells, which are required in this system to obtain suppression, on the other hand, do not need CD27 engagement to exert their suppressor function. (C) 1997 Academic Press. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. RI Iwata, Satoshi/A-8819-2011 FU NIAID NIH HHS [AI 12 069, AI 29 530]; NIAMS NIH HHS [AR 33 713] NR 38 TC 8 Z9 8 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD JUL 10 PY 1997 VL 179 IS 1 BP 48 EP 54 DI 10.1006/cimm.1997.1150 PG 7 WC Cell Biology; Immunology SC Cell Biology; Immunology GA XR091 UT WOS:A1997XR09100007 PM 9259771 ER PT J AU Bonassar, LJ Trippel, SB AF Bonassar, LJ Trippel, SB TI Interaction of epidermal growth factor and insulin-like growth factor-1 in the regulation of growth plate chondrocytes SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID FACTOR-I; ARTICULAR CHONDROCYTES; HYPOPHYSECTOMIZED RATS; RABBIT CHONDROCYTES; CELL-PROLIFERATION; CARTILAGE EXPLANTS; DNA-SYNTHESIS; HORMONE; RECEPTOR; COLLAGEN AB The action of growth factors on the cells of the epiphyseal growth plate is an important mechanism in the regulation of skeletal growth. Insulin-like growth factor-I (IGF-I) is known to play a central role in the regulation of bone growth. In contrast, the role, if any, of epidermal growth factor (EGF) is not yet clear. In these studies, we tested the hypothesis that EGF interacts with IGF-I in the regulation of growth plate chondrocyte mitotic and metabolic activities. Chondrocytes isolated from bovine radioulnar growth plates and incubated in suspension culture were analyzed for their responsiveness to EGF with respect to synthesis of DNA, proteins, and proteoglycans, responsiveness to IGF-I, and ability to specifically bind [I-125]-IGF-I. Treatment of growth plate chondrocytes with maximally effective concentrations (10-100 ng/ml) of EGF produced a 16-27% increase in specific binding of [I-125]IGF-I. Scatchard analysis indicated that this increase in specific binding was due to an increase in the number of receptors/cell with no change in receptor affinity. EGF stimulated protein synthesis by 30-35%. Pretreatment with EGF increased the responsiveness of chondrocytes to IGF-I, resulting in 90 and 60% augmentation of IGF-I-stimulated mitotic activity and proteoglycan synthesis, respectively. Given the prominent role of IGF-I in skeletal development and the presence of EGF in the growth plate, this study suggests an important role for interactions between these growth factors in the regulation of skeletal growth. (C) 1997 Academic Press. C1 HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, ORTHOPAED RES LABS, BOSTON, MA 02114 USA. RI Bonassar, Lawrence/C-2103-2016 OI Bonassar, Lawrence/0000-0003-1094-6433 FU NIAMS NIH HHS [AR31068] NR 28 TC 22 Z9 27 U1 0 U2 1 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 EI 1090-2422 J9 EXP CELL RES JI Exp. Cell Res. PD JUL 10 PY 1997 VL 234 IS 1 BP 1 EP 6 DI 10.1006/excr.1997.3574 PG 6 WC Oncology; Cell Biology SC Oncology; Cell Biology GA XL843 UT WOS:A1997XL84300001 PM 9223364 ER PT J AU Reppas, JB Niyogi, S Dale, AM Sereno, MI Tootell, RBH AF Reppas, JB Niyogi, S Dale, AM Sereno, MI Tootell, RBH TI Representation of motion boundaries in retinotopic human visual cortical areas SO NATURE LA English DT Article ID SENSORY STIMULATION; MACAQUE MONKEY; HUMAN BRAIN; MT; NEURONS; CORTEX; SEGREGATION; PERCEPTION; LESIONS; FMRI AB Edges are important in the interpretation of the retinal image. Although luminance edges have been studied extensively, much less is known about how or where the primate visual system detects boundaries defined by differences in surface properties such as texture, motion or binocular disparity. Here we use functional magnetic resonance imaging (fMRI) to localize human visual cortical activity related to the processing of one such higher-order edge type: motion boundaries. We describe a robust fMRI signal that is selective for motion segmentation. This boundary-specific signal is present, and retinotopically organized, within early visual areas, beginning in the primary visual cortex (area V1). Surprisingly, it is largely absent from the motion-selective area MT/V5 and far extrastriate visual areas. Changes in the surface velocity defining the motion boundaries affect the strength of the fMRI signal. In parallel psychophysical experiments, the perceptual salience of the boundaries shows a similar dependence on surface velocity. These results demonstrate that information for segmenting scenes by relative motion is represented as early as V1. C1 MASSACHUSETTS GEN HOSP,NUCL MAGNET RESONANCE CTR,CHARLESTOWN,MA 02129. MIT,DEPT BRAIN & COGNIT SCI,PERCEPTUAL SCI GRP,CAMBRIDGE,MA 02139. UNIV CALIF SAN DIEGO,DEPT COGNIT SCI,LA JOLLA,CA 92093. RP Reppas, JB (reprint author), HARVARD UNIV,SCH MED,DEPT NEUROBIOL,220 LONGWOOD AVE,BOSTON,MA 02115, USA. RI Dale, Anders/A-5180-2010; Sereno, Martin/F-7657-2012 OI Sereno, Martin/0000-0002-7598-7829 NR 30 TC 88 Z9 88 U1 0 U2 6 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD JUL 10 PY 1997 VL 388 IS 6638 BP 175 EP 179 DI 10.1038/40633 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XK109 UT WOS:A1997XK10900050 PM 9217157 ER PT J AU Eder, JP Nguyen, P Koch, JS Nikrui, N AF Eder, JP Nguyen, P Koch, JS Nikrui, N TI A 67 year-old woman with a progressive movement disorder and a left-upper-quadrant mass - Hodgkin's disease, nodular-sclerosis type. Paraneoplastic cerebellar degeneration. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID NEUROLOGICAL SYNDROMES; STAGING LAPAROTOMY; RARE PRESENTATION; CANCER; ANTIGENS; SPLEEN C1 BETH ISRAEL HOSP,BOSTON,MA 02215. HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138. RP Eder, JP (reprint author), DANA FARBER CANC INST,BOSTON,MA 02115, USA. NR 41 TC 3 Z9 3 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 JUL 10 PY 1997 VL 337 IS 2 BP 115 EP 122 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA XJ822 UT WOS:A1997XJ82200008 ER PT J AU Kieburtz, K Shoulson, I McDermott, M Fahn, S Lang, A Olanow, W Penney, J Wooten, GF Kurlan, R Gardiner, I Petzinger, G Brin, M Dillon, S Shannon, K Jaglin, JA Trosch, R Mistura, K Harrison, M RostRuffner, E Tanner, C Singer, C Weiner, W Sheldon, C Grimes, JD Gray, P Hurtig, H Hauser, R Gauger, L Rajput, A Rudnitzky, R Dobson, J Panisset, M Gauthier, S Amyot, D Perlmutter, J Hubble, J Barter, R Suchowersky, O Lew, M Welsh, M Marek, K Fussell, B Sethi, K Ligon, K Rao, J Rudolph, A Casaceli, C Day, D Johnston, K Baker, D Cherne, C Watts, A Tariot, PN Griggs, RC Hall, WJ Peters, G Corrigan, M Bryan, W Schwartz, J Neidert, G Lai, PY AF Kieburtz, K Shoulson, I McDermott, M Fahn, S Lang, A Olanow, W Penney, J Wooten, GF Kurlan, R Gardiner, I Petzinger, G Brin, M Dillon, S Shannon, K Jaglin, JA Trosch, R Mistura, K Harrison, M RostRuffner, E Tanner, C Singer, C Weiner, W Sheldon, C Grimes, JD Gray, P Hurtig, H Hauser, R Gauger, L Rajput, A Rudnitzky, R Dobson, J Panisset, M Gauthier, S Amyot, D Perlmutter, J Hubble, J Barter, R Suchowersky, O Lew, M Welsh, M Marek, K Fussell, B Sethi, K Ligon, K Rao, J Rudolph, A Casaceli, C Day, D Johnston, K Baker, D Cherne, C Watts, A Tariot, PN Griggs, RC Hall, WJ Peters, G Corrigan, M Bryan, W Schwartz, J Neidert, G Lai, PY TI Safety and efficacy of pramipexole in early Parkinson disease - A randomized dose-ranging study SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID RATING-SCALE AB Context.-Monotherapy with dopamine agonists may be useful in early Parkinson disease. Objective.-To evaluate dose-response relationships for tolerability, safety, and efficacy of the synthetic dopamine agonist pramipexole. Design.-Multicenter, multidosage, parallel-group, double-blind, placebo-controlled, randomized clinical trial. Setting.-University or academically based movement disorder clinics. Patients.-A total of 264 patients with early Parkinson disease (PD) who were not requiring or receiving levodopa or other dopamine agonists were enrolled. Intervention.-Subjects were randomized to 1 of 5 treatment groups: pramipexole doses of 1.5 mg/d, 3.0 mg/d, 4.5 mg/d, and 6.0 mg/d, or matching placebo. A 6-week dosage escalation period was followed by a 4-week maintenance period and a 1-week period during which active treatment was withdrawn. Main Outcome Measures.-The primary measure of tolerability was the proportion of subjects completing the study on the assigned treatment. The primary measure of efficacy was the change from baseline to 10 weeks in the total score on the Unified Parkinson's Disease Rating Scale (UPDRS). Results.-Pramipexole was generally safe and well tolerated in this 10-week study. The proportion of subjects completing the study on the originally assigned dosage was 98% for placebo and 81% for the 1.5-mg/d, 92% for the 3.0-mg/d, 78% for the 4.5-mg/d, and 67% for the 6.0-mg/d treatment groups. There was a trend toward increased frequency of adverse experiences, particularly somnolence, in the 6.0-mg/d group. After 10 weeks of treatment, pramipexole-treated subjects showed a 20% improvement in total UPDRS scores, with mean improvements in scores ranging from 5.9 to 7.0 units among active treatment groups, compared with 0.9 units for the placebo group (P<.005 for each comparison with placebo). There was also evidence that the treatment effects were more pronounced in subjects with worse UPDRS scores at baseline. Conclusions.-Pramipexole is safe and effective as short-term monotherapy in patients with early PD who are not receiving levodopa. Further study is warranted to determine the long-term impact of pramipexole on the progression of disability in PD and its value in comparison with levodopa therapy and other dopamine agonists. C1 COLUMBIA UNIV,NEW YORK,NY. TORONTO HOSP,TORONTO,ON M5T 2S8,CANADA. MT SINAI HOSP,NEW YORK,NY 10029. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. UNIV VIRGINIA,HLTH SCI CTR,CHARLOTTESVILLE,VA. RUSH PRESBYTERIAN ST LUKES MED CTR,CHICAGO,IL 60612. SINAI HOSP DETROIT,W BLOOMFIELD,MI. PARKINSONS INST,SUNNYVALE,CA. UNIV MIAMI,SCH MED,MIAMI,FL. OTTAWA CIVIC HOSP,OTTAWA,ON K1Y 4E9,CANADA. UNIV PENN,GRAD HOSP,PHILADELPHIA,PA 19104. UNIV S FLORIDA,TAMPA,FL. UNIV SASKATCHEWAN,SASKATOON,SK,CANADA. UNIV IOWA,IOWA CITY,IA. DOUGLAS HOSP,MCGILL CTR STUDIES AGING,MONTREAL,PQ,CANADA. WASHINGTON UNIV,SCH MED,ST LOUIS,MO. UNIV KANSAS,MED CTR,KANSAS CITY,KS 66103. UNIV CALGARY,FOOTHILLS HOSP,CALGARY,AB,CANADA. UNIV SO CALIF,LOS ANGELES,CA. YALE UNIV,SCH MED,NEW HAVEN,CT. MED COLL GEORGIA,AUGUSTA,GA 30912. LOUISIANA STATE UNIV,MED CTR,NEW ORLEANS,LA. RP Kieburtz, K (reprint author), UNIV ROCHESTER,MED CTR,DEPT NEUROL,601 ELMWOOD AVE,BOX 673,ROCHESTER,NY 14642, USA. RI Day, Donal/C-5020-2015 OI Day, Donal/0000-0001-7126-8934 NR 18 TC 178 Z9 178 U1 1 U2 10 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 JUL 9 PY 1997 VL 278 IS 2 BP 125 EP 130 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA XH667 UT WOS:A1997XH66700032 ER PT J AU SmithHall, J Pons, S Patti, ME Burks, DJ Yenush, L Sun, J Kahn, CR White, MF AF SmithHall, J Pons, S Patti, ME Burks, DJ Yenush, L Sun, J Kahn, CR White, MF TI The 60 kDa insulin receptor substate functions like an IRS protein (pp60(IRS3)) in adipose cells SO BIOCHEMISTRY LA English DT Article ID STIMULATES TYROSINE PHOSPHORYLATION; PHOSPHATIDYLINOSITOL 3-KINASE; SIGNALING COMPLEXES; REGULATORY SUBUNIT; GLUCOSE-TRANSPORT; ASSOCIATION; SUBSTRATE; 3'-KINASE; TRANSLOCATION; ACTIVATION AB The 60 kDa insulin receptor substrate in rat adipocytes that binds to the PI-3 kinase displays several functional characteristics in common with the IRS proteins; so we propose the name pp60(IRS3) to distinguish it from other tyrosine phosphorylated proteins of similar size. During insulin stimulation, p85 associated with pp60(IRS3) more rapidly than with IRS-I or IRS-2. In mice lacking IRS-1, p85 associated more strongly with pp60(IRS3) than with IRS-2, suggesting that pp60(IRS3) provides an alternate pathway in these cells. Synthetic peptides containing two phosphorylated YMPM motifs displace pp60(IRS3) and IRS-I from alpha p85 immune complexes, suggesting that pp60(IRS3), like IRS-1, engages both SH2 domains in p85. Moreover, pp60(IRS3) binds to immobilized peptides containing a phosphorylated NPXY motif, suggesting that it contains a PTB domain with similar specificity to that in IRS-1. The clotting of pp60(IRS3) will reveal a new member of the IRS protein family which mediates insulin receptor signals in a narrow range of tissues. C1 JOSLIN DIABET CTR,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02215. INDIANA UNIV,SCH MED,DEPT PHYSIOL & BIOPHYS,INDIANAPOLIS,IN 46202. RI Pons , Sebastian/K-7794-2014; Yenush, Lynne/J-8815-2014 OI Pons , Sebastian/0000-0003-1027-0621; Yenush, Lynne/0000-0001-8589-7002 FU NIDDK NIH HHS [DK33201, DK38712] NR 46 TC 55 Z9 56 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUL 8 PY 1997 VL 36 IS 27 BP 8304 EP 8310 DI 10.1021/bi9630974 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XK094 UT WOS:A1997XK09400014 PM 9204876 ER PT J AU Tishkoff, DX Boerger, AL Bertrand, P Filosi, N Gaida, GM Kane, MF Kolodner, RD AF Tishkoff, DX Boerger, AL Bertrand, P Filosi, N Gaida, GM Kane, MF Kolodner, RD TI Identification and characterization of Saccharomyces cerevisiae EXO1, a gene encoding an exonuclease that interacts with MSH2 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cancer; hereditary nonpolyposis colorectal carcinoma; mutagenesis; mutS ID MUTATION AVOIDANCE; DNA; PROTEIN; REPAIR; DELETION; HOMOLOG; CANCER; POMBE AB A two-hybrid screen was used to identify Saccharomyces cerevisiae genes encoding proteins that interact with MSH2, One gene was found to encode a homologue of Schizosaccharomyces pombe EXO1, a double-stranded DNA-specific 5'-3' exonuclease. S. cerevisiae EXO1 interacted with both S. cerevisiae and human MSH2 in two-hybrid and coimmunoprecipitation experiments. exo1 mutants showed a mutator phenotype, and epistasis analysis was consistent with EXO1 functioning in the MSH2-dependent mismatch repair pathway. exo1 mutations were lethal in combination with rad27 mutations, and overexpression of EXO1 suppressed both the temperature sensitive and mutator phenotypes of rad27 mutants. C1 DANA FARBER CANC INST,DIV HUMAN CANC GENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOL PHARMACOL,BOSTON,MA 02115. FU NCI NIH HHS [CA06516, P30 CA006516]; NIAID NIH HHS [AI28691, P30 AI028691]; NIGMS NIH HHS [GM50006, R01 GM050006] NR 35 TC 281 Z9 284 U1 1 U2 18 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 JUL 8 PY 1997 VL 94 IS 14 BP 7487 EP 7492 DI 10.1073/pnas.94.14.7487 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XJ876 UT WOS:A1997XJ87600066 PM 9207118 ER PT J AU DaSilva, AJ Li, ZW DeVera, C Canto, E Findell, P Rudd, CE AF DaSilva, AJ Li, ZW DeVera, C Canto, E Findell, P Rudd, CE TI Cloning of a novel T-cell protein FYB that binds FYN and SH2-domain-containing leukocyte protein 76 and modulates interleukin 2 production SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TYROSINE KINASE; ANTIGEN RECEPTOR; ZETA-CHAIN; ACTIVATION; DOMAIN; PHOSPHORYLATION; COSTIMULATION; PROTOONCOGENE; P56(LCK); P59(FYN) AB T cell receptor zeta (TcR zeta)/CD3 ligation initiates a signaling cascade that involves src kinases p56(lck) and zeta-associated protein 70, leading to the phosphorylation of substrates such as TcR zeta, Vav, SH2-domain-containing leukocyte protein 76 (SLP-76), cbl, and p120/130. FYN binding protein (FYB or p120/130) associates with p59(fyn), the TcR zeta/CD3 complex, and becomes tyrosine-phosphorylated in response to receptor ligation. In this study, we report the cDNA cloning of human and murine FYB and show that it is restricted in expression to T cells and myeloid cells and possesses an overall unique hydrophilic sequence with several tyrosine-based motifs, proline-based type I and type II SH3 domain binding motifs, several putative lysine/glutamic acid-rich nuclear localization motifs, and a SH3-like domain. In addition to binding the src kinase p59(fyn), FYB binds specifically to the hematopoietic signaling protein SLP-76, an interaction mediated by the SLP-76 SH2 domain. In keeping with this, expression of FYB augmented interleukin 2 secretion from a T cell hybridoma, DC27.10, in response to TcR zeta/CD3 ligation. FYB is therefore a novel hematopoietic protein that acts as a component of the FYN and SLP-76 signaling cascades in T cells. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. ROCHE BIOSCI,PALO ALTO,CA 94304. NR 37 TC 212 Z9 216 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 JUL 8 PY 1997 VL 94 IS 14 BP 7493 EP 7498 DI 10.1073/pnas.94.14.7493 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XJ876 UT WOS:A1997XJ87600067 PM 9207119 ER PT J AU Dong, ZM GutierrezRamos, JC Coxon, A Mayadas, TN Wagner, DD AF Dong, ZM GutierrezRamos, JC Coxon, A Mayadas, TN Wagner, DD TI A new class of obesity genes encodes leukocyte adhesion receptors SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MOLECULE-1; MICE; EXPRESSION; MOUSE AB Obesity is a complex disease, and multiple genes contribute to the trait. The description of five genes (ob, db, tub, A(y), and fat) responsible for distinct syndromes of spontaneous monogenic obesity in mice has advanced our knowledge of the genetics of obesity. However, many other genes involved in the expression of this disease remain to be determined. We report here the identification of an additional class of genes involved in the regulation of adipose tissue mass. These genes encode receptors mediating leukocyte adhesion. Mice deficient in intercellular adhesion molecule-1 became spontaneously obese in old age on normal mouse chow or at a young age when provided with a diet rich in fat. Mice deficient in the counterreceptor for intercellular adhesion molecule-1, the leukocyte integrin alpha M beta 2 (Mac-1), showed a similar obesity phenotype. Since all mice consumed approximately the same amount of food as controls, the leukocyte function appears to be in regulating lipid metabolism and/or energy expenditure. Our results indicate that (i) leukocytes play a role in preventing excess body fat deposition and (ii) defects in leukocyte adhesion receptors can result in obesity. C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. FU NHLBI NIH HHS [R01 HL041002, R01HL41002] NR 25 TC 78 Z9 80 U1 0 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 JUL 8 PY 1997 VL 94 IS 14 BP 7526 EP 7530 DI 10.1073/pnas.94.14.7526 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XJ876 UT WOS:A1997XJ87600073 PM 9207125 ER PT J AU Bruijn, LI Beal, MF Becher, MW Schulz, JB Wong, PC Price, DL Cleveland, DW AF Bruijn, LI Beal, MF Becher, MW Schulz, JB Wong, PC Price, DL Cleveland, DW TI Elevated free nitrotyrosine levels, but not protein-bound nitrotyrosine or hydroxyl radicals, throughout amyotrophic lateral sclerosis (ALS)-like disease implicate tyrosine nitration as an aberrant in vivo property of one familial ALS-linked superoxide dismutase 1 mutant SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE nitration; peroxidation ID MOTOR-NEURON DISEASE; NITRIC-OXIDE SYNTHASE; TRANSGENIC MICE; NF-L; MOUSE MODEL; INJURY; GENE; MUTATIONS; SUBUNIT; PEROXYNITRITE AB Mutations in superoxide dismutase 1 (SOD1; EC 1.15.1.1) are responsible for a proportion of familial amyotrophic lateral sclerosis (ALS) through acquisition of an as-yet-unidentified toxic property or properties. Two proposed possibilities are that toxicity may arise from imperfectly folded mutant SOD1 catalyzing the nitration of tyrosines [Beekman, J. S., Carson, M., Smith, C. D. & Koppenol, W. H. (1993) Nature (London) 364, 584] through use of peroxynitrite or from peroxidation arising from elevated production of hydroxyl radicals through use of hydrogen peroxide as a substrate [Wiedau-Pazos, M., Goto, J. J., Rabizadeh, S., Gralla, E. D., Roe, J. A., Valentine, J. S. & Bredesen, D. E. (1996) Science 271, 515-518]. To test these possibilities, levels of nitrotyrosine and markers for hydroxyl radical formation were measured in two lines of transgenic mice that develop progressive motor neuron disease from expressing human familial ALS-linked SOD1 mutation G37R Relative to normal mice or mice expressing high levels of wild-type human SOD1, 3-nitrotyrosine levels were elevated by 2- to 3-fold in spinal cords coincident with the earliest pathological abnormalities and remained elevated in spinal cord throughout progression of disease. However, no increases in protein-bound nitrotyrosine were found during any stage of SOD1-mutant-mediated disease in mice or at end stage of sporadic or SOD1-mediated familial human ALS. When salicylate trapping of hydroxyl radicals and measurement of levels of malondialdehyde were used, there was no evidence throughout disease progression in mice for enhanced production of hydroxyl radicals or lipid peroxidation, respectively. The presence of elevated nitrotyrosine levels beginning at the earliest stages of cellular pathology and continuing throughout progression of disease demonstrates that tyrosine nitration is one in vivo aberrant property of this ALS-linked SOD1 mutant. C1 UNIV CALIF SAN DIEGO,LUDWIG INST CANC RES,LA JOLLA,CA 92093. UNIV CALIF SAN DIEGO,DEPT MED,LA JOLLA,CA 92093. UNIV CALIF SAN DIEGO,DEPT NEUROSCI,LA JOLLA,CA 92093. JOHNS HOPKINS UNIV,SCH MED,DEPT PATHOL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,NEUROPATHOL LAB,BALTIMORE,MD 21205. MASSACHUSETTS GEN HOSP,NEUROL SERV,NEUROCHEM LAB,BOSTON,MA 02114. RI Schulz, Jorg/D-9786-2012 OI Schulz, Jorg/0000-0002-8903-0593 FU NINDS NIH HHS [NS 27036, R01 NS027036, R37 NS027036] NR 48 TC 219 Z9 221 U1 1 U2 6 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 JUL 8 PY 1997 VL 94 IS 14 BP 7606 EP 7611 DI 10.1073/pnas.94.14.7606 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XJ876 UT WOS:A1997XJ87600087 PM 9207139 ER PT J AU Cruz, L Urbanc, B Buldyrev, SV Christie, R GomezIsla, T Havlin, S McNamara, M Stanley, HE Hyman, BT AF Cruz, L Urbanc, B Buldyrev, SV Christie, R GomezIsla, T Havlin, S McNamara, M Stanley, HE Hyman, BT TI Aggregation and disaggregation of senile plaques in Alzheimer disease SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID AMYLOID-BETA-PROTEIN; PRECURSOR; PEPTIDE AB We quantitatively analyzed, using laser scanning confocal microscopy, the three-dimensional structure of individual senile plaques in Alzheimer disease. We carried out the quantitative analysis using statistical methods to. gain insights about the processes that govern A beta peptide deposition. Our results show that plaques are complex porous structures with characteristic pore sizes. We interpret plaque morphology in the context of a new dynamical model based on competing aggregation and disaggregation processes in kinetic steady-state equilibrium with an additional diffusion process allowing A beta deposits to diffuse over the surface of plaques. C1 BOSTON UNIV,CTR POLYMER STUDIES,BOSTON,MA 02215. BOSTON UNIV,DEPT PHYS,BOSTON,MA 02215. MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114. BAR ILAN UNIV,DEPT PHYS,IL-52900 RAMAT GAN,ISRAEL. BAR ILAN UNIV,GONDA GOLDSCHMIED CTR,IL-52900 RAMAT GAN,ISRAEL. RI Urbanc, Brigita/G-5839-2011; Cruz Cruz, Luis/B-2685-2013; Buldyrev, Sergey/I-3933-2015 OI Urbanc, Brigita/0000-0001-9159-7698; FU NIA NIH HHS [AG05134, AG08487, P50 AG005134, R01 AG008487] NR 32 TC 77 Z9 79 U1 1 U2 5 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 JUL 8 PY 1997 VL 94 IS 14 BP 7612 EP 7616 DI 10.1073/pnas.94.14.7612 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XJ876 UT WOS:A1997XJ87600088 PM 9207140 ER PT J AU Jain, RK AF Jain, RK TI Delivery of molecular and cellular medicine to solid tumors SO ADVANCED DRUG DELIVERY REVIEWS LA English DT Article DE tumor microcirculation; angiogenesis; blood flow; vascular permeability; diffusion and convection; receptor-ligand binding; interstitial pressure; lymphatics; cell adhesion and deformation; cancer detection and treatment ID INTERSTITIAL FLUID PRESSURE; NATURAL-KILLER-CELLS; GROWTH-FACTOR-BETA; POSITRON EMISSION TOMOGRAPHY; HUMAN ADENOCARCINOMA LS174T; INDUCED LEUKOCYTE ADHESION; BLOOD-FLOW; MICROVASCULAR PERMEABILITY; MONOCLONAL-ANTIBODIES; NEOPLASTIC TISSUES AB To reach cancer cells in a tumor, a blood-borne therapeutic molecule or cell must make its way into the blood vessels of the tumor and across the vessel wall into the interstitium, and finally migrate through the interstitium. Unfortunately, tumors often develop in ways that hinder each of these steps. Our research goals are to analyze each of these steps experimentally and theoretically, and then integrate the resulting information in a unified theoretical framework. This paradigm of analysis and synthesis has allowed us to obtain a better understanding of physiological barriers in solid tumors, and to develop novel strategies to exploit and/or to overcome these barriers for improved cancer detection and treatment. (C) 1997 Elsevier Science B.V. RP HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, DEPT RADIAT ONCOL, BOSTON, MA 02114 USA. NR 150 TC 100 Z9 103 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-409X EI 1872-8294 J9 ADV DRUG DELIVER REV JI Adv. Drug Deliv. Rev. PD JUL 7 PY 1997 VL 26 IS 2-3 BP 71 EP 90 DI 10.1016/S0169-409X(97)00027-6 PG 20 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA XM179 UT WOS:A1997XM17900002 ER PT J AU Johnson, RP AF Johnson, RP TI Upregulation of Fas ligand by simian immunodeficiency virus - A nef-arious mechanism of immune evasion? SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Editorial Material ID CYTOTOXIC LYMPHOCYTES-T; EPSTEIN-BARR-VIRUS; HIV-1 INFECTION; QUANTITATIVE-ANALYSIS; PERIPHERAL-BLOOD; CELL RECOGNITION; VIRAL-INFECTION; LYMPH-NODES; APOPTOSIS; RESPONSES C1 HARVARD UNIV,SCH MED,INFECT DIS UNIT,MASSACHUSETTS GEN HOSP,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,AIDS RES CTR,MASSACHUSETTS GEN HOSP,CHARLESTOWN,MA 02129. RP Johnson, RP (reprint author), HARVARD UNIV,NEW ENGLAND REG PRIMATE RES CTR,SCH MED,DIV IMMUNOL,POB 9102,SOUTHBOROUGH,MA 01772, USA. FU NCRR NIH HHS [K26 RR000168, RR 00168, P51 RR000168]; NIAID NIH HHS [AI35365, U01 AI035365, P01 AI035365] NR 50 TC 7 Z9 7 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUL 7 PY 1997 VL 186 IS 1 BP 1 EP 5 DI 10.1084/jem.186.1.1 PG 5 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA XK466 UT WOS:A1997XK46600001 PM 9207006 ER PT J AU Suzuki, H Shinkai, Y Granger, LG Alt, FW Love, PE Singer, A AF Suzuki, H Shinkai, Y Granger, LG Alt, FW Love, PE Singer, A TI Commitment of immature CD4(+)8(+) thymocytes to the CD4 lineage requires CD3 signaling but does not require expression of clonotypic T cell receptor (TCR) chains SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID NATURAL-KILLER-CELLS; POSITIVE SELECTION; INTERMEDIATE STEPS; INSTRUCTIVE MODEL; CD8+ THYMOCYTES; DEFICIENT MICE; DIFFERENTIATION; COMPLEX; LYMPHOCYTES; ACTIVATION AB As a consequence of positive selection in the thymus, immature CD4(+)8(+) double-positive, [DP] thymocytes selectively terminate synthesis of one coreceptor molecule and, as a result, differentiate into either CD4(+) or CD8(+) T cells. The decision by individual DP thymocytes to terminate synthesis of one or the other coreceptor molecule is referred to as lineage commitment. Previously, we reported that the intrathymic signals that induced commitment to the CD4 versus CD8 T cell lineages were markedly asymmetric. Notably, CD8 commitment appeared to require lineage-specific signals, whereas CD4 commitment appeared to occur in the absence of lineage-specific signals by default. Consequently, it was unclear whether CD4 commitment, as revealed by selective termination of CD8 coreceptor synthesis, occurred in all DP thymocytes, or whether CD4 commitment occurred only in T cell receptor (TCR)-CD3-signaled DP thymocytes. Here, we report that selective termination of CD8 coreceptor synthesis does not occur in DP thymocytes spontaneously. Rather, CD4 commitment in DP thymocytes requires signals transduced by either CD3 or zeta chains, which can signal CD4 commitment even in the absence of clonotypic TCR chains. C1 NCI,EXPT IMMUNOL BRANCH,BETHESDA,MD 20892. HOWARD HUGHES MED INST,BOSTON,MA 02115. CHILDRENS HOSP,DEPT GENET & PEDIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. NICHHD,LAB MAMMALIAN GENES & DEV,BETHESDA,MD 20892. RI Suzuki, Harumi/L-1271-2013; Shinkai, Yoichi/N-3909-2014 OI Suzuki, Harumi/0000-0003-3616-9361; Shinkai, Yoichi/0000-0002-6051-2484 NR 34 TC 13 Z9 13 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUL 7 PY 1997 VL 186 IS 1 BP 17 EP 23 DI 10.1084/jem.186.1.17 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA XK466 UT WOS:A1997XK46600003 PM 9206993 ER PT J AU BlockGalarza, J Chase, KO Sapp, E Vaughn, KT Vallee, RB DiFiglia, M Aronin, N AF BlockGalarza, J Chase, KO Sapp, E Vaughn, KT Vallee, RB DiFiglia, M Aronin, N TI Fast transport and retrograde movement of huntingtin and HAP 1 in axons SO NEUROREPORT LA English DT Article DE anterograde transport; Huntington's disease; retrograde transport ID PROTEIN; BRAIN; DISEASE; ORGANELLES; NEURONS; EXPRESSION AB HUNTINGTIN, the protein product of the Huntington's disease gene, associates with vesicle membranes and microtubules in neurons. Analysis of axonal transport with a stop-flow, double crush ligation approach in rat sciatic nerve showed that full length huntingtin (350 kDa) and an N-terminal cleavage product (50 kD) were increased within 6-12 h on both the proximal and distal sides of the crush site when compared with normal unligated nerve. The huntingtin associated protein HAP 1 and the retrograde motor protein dynein also accumulated on both sides of the crush, whereas the vesicle docking protein SNAP-25 was elevated only proximally. The cytoskeletal protein alpha-tubulin was unaffected. The rapid anterograde accumulation of huntingtin and HAP 1 is compatible with their axonal transport on vesicular membranes. Retrograde movement of both proteins, as seen by accumulation distal to the nerve crush, may be necessary for their degradation at the soma or for a function in retrograde membrane trafficking. C1 UNIV MASSACHUSETTS,SCH MED,DEPT MED,WORCESTER,MA 01655. UNIV MASSACHUSETTS,SCH MED,DEPT CELL BIOL,WORCESTER,MA 01655. HARVARD UNIV,SCH MED,CHARLESTOWN,MA. MASSACHUSETTS GEN HOSP,LAB CELLULAR NEUROBIOL,CHARLESTOWN,MA. WORCESTER FDN EXPT BIOL INC,SHREWSBURY,MA 01545. FU NIGMS NIH HHS [GM47434]; NINDS NIH HHS [NS 16367, NS31579] NR 26 TC 105 Z9 108 U1 0 U2 5 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD JUL 7 PY 1997 VL 8 IS 9-10 BP 2247 EP 2251 DI 10.1097/00001756-199707070-00031 PG 5 WC Neurosciences SC Neurosciences & Neurology GA XL180 UT WOS:A1997XL18000032 PM 9243620 ER PT J AU Hoglund, S Ohagen, A Goncalves, J Panganiban, AT Gabuzda, D AF Hoglund, S Ohagen, A Goncalves, J Panganiban, AT Gabuzda, D TI Ultrastructure of HIV-1 genomic RNA SO VIROLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; MOLONEY MURINE LEUKEMIA; CIS ELEMENTS; IN-VITRO; DIMERIZATION; SEQUENCE; IDENTIFICATION; VIRIONS; SIGNAL AB The HIV-1 RNA genome is a dimer which consists of two identical strands of RNA linked near their 5' ends by a dimer linkage structure (DLS). We have structurally characterized full-length HIV-1 genomic RNA isolated from HIV-I virions by electron microscopy. As in other retroviruses, the HIV-I RNA genome contains a central dimer linkage structure and additional loop structures within each monomer subunit. in contrast to the DLS of other retroviruses, the DLS region of HIV-1 contains a loop of 323 +/- 44 nucleotides. The free 5' ends of the two RNA strands were not visualized, suggesting that the 5' end regions are involved in interstrand complementary base pairing. Computer modeling identified a single stable structure that was consistent with the electron microscopy data. In this model, the two RNA strands are linked at their 5' ends by two contact points derived from ''kissing-loop'' interactions between r-u5 and SL1 stem-loops and their counterparts on the second strand. These interactions may contribute to the formation of stable HIV-I RNA dimers in vivo. (C) 1997 Academic Press. C1 DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. UNIV WISCONSIN,SCH MED,MCARDLE LAB CANC RES,MADISON,WI 53706. RP Hoglund, S (reprint author), BIOMED CTR,DEPT BIOCHEM,BOX 576,S-75123 UPPSALA,SWEDEN. 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; FU NIAID NIH HHS [AI36186, AI34733] NR 39 TC 83 Z9 83 U1 0 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD JUL 7 PY 1997 VL 233 IS 2 BP 271 EP 279 DI 10.1006/viro.1997.8585 PG 9 WC Virology SC Virology GA XJ073 UT WOS:A1997XJ07300003 PM 9217051 ER PT J AU Scaglioni, PP Melegari, M Wands, JR AF Scaglioni, PP Melegari, M Wands, JR TI Biologic properties of hepatitis B viral genomes with mutations in the precore promoter and precore open reading frame SO VIROLOGY LA English DT Article ID FULMINANT-HEPATITIS; CORE PROMOTER; E-ANTIGEN; ENHANCED REPLICATION; VIRUS; REGION; MUTANT; VARIANTS; DNA; ENCAPSIDATION AB It is now well recognized that mutations in the hepatitis B virus (HBV) genome occur during the natural course of chronic viral infection. Regions of the viral genome that are frequently affected by such mutations, rearrangements, and/or deletions generally involve the precore promoter, precore, and core as well as the preS gene regions. However, little is known regarding the biologic consequences of these mutations on the functional properties of the variant viral strains with respect to effects on viral replication. In this study, we investigated the functional significance of precore promoter and precore gene mutations that reduce or abolish the synthesis of hepatitis B e antigen (HBeAg). We found that precore promoter mutations diminished the expression of HBeAg but did not affect the synthesis of pregenomic RNA. However, these precore mutations were associated with a modest increase in HBV replication. In contrast, a naturally occurring mutant that carries a termination codon in position 28 of the precore open reading frame demonstrated increased encapsidation of pregenomic mRNA into nucleocapsid particles. Consequently, this variant viral strain demonstrated a substantial increase in the level of viral replication compared to ''wild-type'' HBV and other precore promoter mutant viral strains. These studies suggest that substitutions in the precore promoter and precore gene not only alter the synthesis of HBeAg but also affect the level of viral replication. (C) 1997 Academic Press. C1 HARVARD UNIV,CTR CANC,MOL HEPATOL LAB,MED SCH,MASSACHUSETTS GEN HOSP,CHARLESTOWN,MA 02129. OI Scaglioni, Pier Paolo/0000-0002-6036-5138 FU NCI NIH HHS [CA-35711]; NIAAA NIH HHS [AA-02169] NR 41 TC 121 Z9 141 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD JUL 7 PY 1997 VL 233 IS 2 BP 374 EP 381 DI 10.1006/viro.1997.8594 PG 8 WC Virology SC Virology GA XJ073 UT WOS:A1997XJ07300012 PM 9217060 ER PT J AU Roth, CM Reiken, SR LeDoux, JM Rajur, SB Lu, XM Morgan, JR Yarmush, ML AF Roth, CM Reiken, SR LeDoux, JM Rajur, SB Lu, XM Morgan, JR Yarmush, ML TI Targeted antisense modulation of inflammatory cytokine receptors SO BIOTECHNOLOGY AND BIOENGINEERING LA English DT Article DE antisense; receptor targeted delivery; acute phase response; IL-6; gp130; HepG2 cells ID GROWTH-FACTOR RECEPTOR; ACUTE-PHASE RESPONSE; ASIALOGLYCOPROTEIN RECEPTOR; INTERLEUKIN-6 RECEPTOR; SIGNAL-TRANSDUCTION; TYROSINE KINASE; HEPATOMA-CELLS; GENE-TRANSFER; EXPRESSION; DELIVERY AB Antisense technology is potentially a powerful means by which to selectively control gene expression. We have used antisense oligonucleotides to modulate the response of the hepatoma cell line, HepG2, to the inflammatory cytokine, IL-6, by inhibiting the expression of its multifunctional signal transducer, gp130. HepG2 cells respond to IL-6 by upregulating acute phase proteins, such as haptoglobin, by five- to tenfold. Gp130 is central to this response, as the upregulation of haptoglobin is almost completely blocked by the addition of high concentrations (similar to 100 mu g/mL) of a monoclonal antibody to gp130. Antisense oligodeoxynucleotides complementary to the mRNA encoding gp130 inhibited the upregulation of haptoglobin by IL-6-stimulated HepG2 cells by about 50%. However, a nonsense sequence also inhibited haptoglobin secretion by about 20%. To improve the specificity and efficiency of action, we targeted the antisense oligonucleotides to HepG2 cells using a conjugate of asialoglycoprotein-poly-L-lysine. The targeted antisense reduced the binding of IL-6 to HepG2 cells, virtually eliminating high affinity binding. In addition, it inhibited haptoglobin upregulation by over 70%. Furthermore, the dose of targeted antisense required for biological effect was reduced by about an order of magnitude as compared with unconjugated antisense. These results demonstrate the potential of antisense oligonucleotides as a means to control the acute phase response as well as the need for a greater understanding of the mechanism and dynamics of antisense molecules as they are developed toward therapeutic application. (C) 1997 John Wiley & Sons, Inc. C1 MASSACHUSETTS GEN HOSP,CTR ENGN MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,SURG SERV,BOSTON,MA 02114. SHRINERS BURN INST,BOSTON,MA 02114. OI Morgan, Jeffrey/0000-0002-7546-3443; Roth, Charles/0000-0002-4924-0721 NR 53 TC 10 Z9 10 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0006-3592 J9 BIOTECHNOL BIOENG JI Biotechnol. Bioeng. PD JUL 5 PY 1997 VL 55 IS 1 BP 72 EP 81 DI 10.1002/(SICI)1097-0290(19970705)55:1<72::AID-BIT9>3.0.CO;2-U PG 10 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA XB902 UT WOS:A1997XB90200009 PM 18636446 ER PT J AU Pisegna, JR Leyton, J Coelho, T Hida, T Jakowlew, S Birrer, M Fridkin, M Gozes, I Moody, TW AF Pisegna, JR Leyton, J Coelho, T Hida, T Jakowlew, S Birrer, M Fridkin, M Gozes, I Moody, TW TI PACAP hybrid: A new PACAP receptor antagonist SO LIFE SCIENCES LA English DT Article DE PACAP; PACAP antagonist; receptor; splice variants ID CYCLASE-ACTIVATING POLYPEPTIDE; VASOACTIVE INTESTINAL POLYPEPTIDE; LUNG-CANCER CELLS; ADENYLATE-CYCLASE; FUNCTIONAL EXPRESSION; MOLECULAR-CLONING; STRUCTURAL REQUIREMENTS; I RECEPTOR; PEPTIDE; VIP AB The effects of pituitary adenylate cyclase activating polypeptide (PACAP) hybrid, a synthetic antagonist, was investigated on NIH/3T3 cells containing PACAP receptor (R) splice variants (SVs). PACAPhybrid inhibited I-125-PACAP-27 binding to NIH/3T3 cells stably expressing PACAP-R basic, SV- 1, SV-2 or SV-3 with an IC50 of 1000 nM. PACAPhybrid antagonized the ability of PACAP-27 to elevate cAMP regardless of the PACAP-R SV used. PACAP was more efficacious at increasing cytosolic Ca2+ in NIH/3T3 cells containing PACAP-R SV-2 than PACAP-R basic, SV-1 or SV-3. PACAPhybrid antagonized the increase in cytosolic Ca2+ caused by PACAP-27 regardless of the PACAP-R SV used. PACAP was more potent at elevating c-fos mRNA using NIH/3T3 cells transfected with PACAP-R SV-2 than PACAP-R basic, SV-1 or SV-3. PACAPhybrid antagonized the increase in c-fos mRNA caused by PACAP-27. These data suggest that PACAPhybrid is a useful PACAP receptor antagonist for PACAP-R SVs. C1 NCI,BIOMARKERS & PREVENT RES BRANCH,ROCKVILLE,MD 20850. UNIV CALIF LOS ANGELES,W LOS ANGELES VET AFFAIRS MED CTR,CURE,CTR DIGEST DIS,LOS ANGELES,CA 90073. WEIZMANN INST SCI,DEPT ORGAN CHEM,IL-76100 REHOVOT,ISRAEL. SACKLER SCH MED,DEPT CLIN BIOCHEM,TEL AVIV,ISRAEL. NR 30 TC 15 Z9 15 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0024-3205 J9 LIFE SCI JI Life Sci. PD JUL 3 PY 1997 VL 61 IS 6 BP 631 EP 639 DI 10.1016/S0024-3205(97)00438-4 PG 9 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA XK788 UT WOS:A1997XK78800006 PM 9250719 ER PT J AU Carabello, BA Crawford, FA AF Carabello, BA Crawford, FA TI Valvular heart disease SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID AORTIC-VALVE REPLACEMENT; LEFT-VENTRICULAR FUNCTION; CORONARY-ARTERY DISEASE; CHRONIC MITRAL REGURGITATION; LONG-TERM SURVIVAL; ASYMPTOMATIC PATIENTS; EJECTION PERFORMANCE; SYMPTOMATIC PATIENTS; NATURAL-HISTORY; WALL STRESS C1 MED UNIV S CAROLINA,GAZES CARDIAC RES INST,CHARLESTON,SC 29425. MED UNIV S CAROLINA,DEPT SURG,DIV CARDIOTHORAC SURG,CHARLESTON,SC 29425. RALPH H JOHNSON DEPT VET AFFAIRS,CHARLESTON,SC 29425. RP Carabello, BA (reprint author), MED UNIV S CAROLINA,DIV CARDIOL,DEPT MED,171 ASHLEY AVE,CHARLESTON,SC 29425, USA. NR 99 TC 165 Z9 171 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 JUL 3 PY 1997 VL 337 IS 1 BP 32 EP 41 DI 10.1056/NEJM199707033370107 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA XH186 UT WOS:A1997XH18600007 PM 9203430 ER PT J AU Gleason, PP Kapoor, WN Stone, RA Lave, JR Obrosky, DS Schulz, R Singer, DE Coley, CM Marrie, TJ Fine, MJ AF Gleason, PP Kapoor, WN Stone, RA Lave, JR Obrosky, DS Schulz, R Singer, DE Coley, CM Marrie, TJ Fine, MJ TI Medical outcomes and antimicrobial costs with the use of the American Thoracic Society guidelines for outpatients with community-acquired pneumonia SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID RESPIRATORY-TRACT INFECTIONS; REQUIRING HOSPITALIZATION; ANTIBIOTIC-TREATMENT; INITIAL MANAGEMENT; CLINICAL-PRACTICE; UNITED-STATES; ETIOLOGY; ADULTS; EPIDEMIOLOGY; PERSPECTIVE AB Context.-The American Thoracic Society (ATS) published guidelines based on expert opinion and published data-but not clinically derived or validated-for treating adult outpatients with community-acquired pneumonia, Objective.-To compare medical outcomes and antimicrobial costs for patients whose antimicrobial therapy was consistent or inconsistent with ATS guidelines, Design.-Multicenter, prospective cohort study. Setting.-Emergency departments, medical clinics, and practitioner offices affiliated with 3 university hospitals, 1 community teaching hospital, and 1 health maintenance organization, Participants.-A total of 864 immunocompetent, adult outpatients with community-acquired pneumonia, 546 aged 60 years or younger with no comorbidity and 318 older than 60 years or with 1 comorbidity or more. Main Outcome Measures.-Patients' antimicrobial therapy was classified as being consistent or inconsistent with the ATS guidelines, Mortality, subsequent hospitalization, medical complications, symptom resolution, return to work and usual activities, health-related quality of life, and antimicrobial costs were compared among those treated consistently or inconsistently with the guidelines, Results.-Outpatients aged 60 years or younger with no comorbidity who were prescribed therapy consistent with ATS guidelines (ie, erythromycin with some exceptions) had 3-fold lower antimicrobial costs ($5.43 vs $18.51; P<.001) and no significant differences in medical outcomes, Outpatients older than 60 years or with 1 comorbidity or more who were prescribed therapy consistent with ATS guidelines (ie, second-generation cephalosporin, sulfamethoxazble-trimethoprim, or beta-lactam and beta-lactamase inhibitor with or without a macrolide) had 10-fold higher antimicrobial costs ($73.50 vs $7.50; P<.001); despite trends toward higher mortality and subsequent. hospitalization, no significant differences in medical outcomes were observed. Conclusion.-Our findings support the use of erythromycin as recommended by the ATS guidelines for outpatients aged 60 years or younger with no comorbidity, Although the antimicrobial therapy recommended in outpatients older than 60 years or with 1 comorbidity or more is more costly, this observational study provides no evidence of improved medical outcomes in the small subgroup who received ATS guideline-recommended therapy. C1 UNIV PITTSBURGH, SCH PHARM, DEPT PHARMACEUT SCI, PITTSBURGH, PA 15261 USA. UNIV PITTSBURGH, DEPT MED, DIV GEN INTERNAL MED, PITTSBURGH, PA USA. UNIV PITTSBURGH, DEPT BIOSTAT, PITTSBURGH, PA 15261 USA. UNIV PITTSBURGH, DEPT HLTH SERV ADM, PITTSBURGH, PA USA. UNIV PITTSBURGH, DEPT PSYCHIAT, GRAD SCH PUBL HLTH, PITTSBURGH, PA USA. UNIV PITTSBURGH, UNIV CTR SOCIAL & URBAN RES, PITTSBURGH, PA USA. UNIV PITTSBURGH, CTR RES HLTH CARE, PITTSBURGH, PA USA. MASSACHUSETTS GEN HOSP, GEN INTERNAL MED UNIT, BOSTON, MA 02114 USA. VICTORIA GEN HOSP, DEPT MED, DIV INFECT DIS, HALIFAX, NS B3H 2Y9, CANADA. DALHOUSIE UNIV, FAC MED, HALIFAX, NS, CANADA. FU AHRQ HHS [R01HS06468] NR 42 TC 149 Z9 156 U1 1 U2 5 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 JUL 2 PY 1997 VL 278 IS 1 BP 32 EP 39 DI 10.1001/jama.278.1.32 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA XG387 UT WOS:A1997XG38700033 PM 9207335 ER PT J AU Centeno, BA Warshaw, AL MayoSmith, W Southern, JF Lewandrowski, K AF Centeno, BA Warshaw, AL MayoSmith, W Southern, JF Lewandrowski, K TI Cytologic diagnosis of pancreatic cystic lesions - A prospective study of 28 percutaneous aspirates SO ACTA CYTOLOGICA LA English DT Article DE pancreatic diseases; cysts; aspiration biopsy ID FINE-NEEDLE ASPIRATION; ISLET-CELL TUMORS; DIFFERENTIAL-DIAGNOSIS; MUCINOUS CYSTADENOCARCINOMA; FLUID ANALYSIS; NEOPLASMS; CYSTADENOMA; PSEUDOCYSTS AB PURPOSE: To prospectively evaluate fine needle aspiration biopsy (FNAB) of pancreatic cystic lesions. STUDY DESIGN: We performed a blind, prospective study on percutaneous aspirates from 28 radiographically identified cysts, including 6 inflammatory cysts (5 pseudocysts and 1 abscess), 4 serous cystadenomas, 1 cystic islet cell tumor, 5 mucinous cystic neoplasms, 6 mucinous cystadenocarcinomas and 6 nonpancreatic cysts. RESULTS: Four of six (67%) cystadenocarcinomas were identified as malignant, and the other two, which lacked sufficient morphologic criteria for malignancy, as consistent with mucinous cystic neoplasm. Two of five mucinous cystic neoplasms were correctly classified. One, which contained atypical cells, did not appear to be mucinous on the ThinPrep, and one, which lacked an epithelial component, was suggested because of the presence of mucin in the background, The fifth one contained inflammatory cells only. One of four serous cystadenomas produced a diagnostic specimen. FNAB of the cystic islet cell tumor was nondiagnostic. Five of six inflammatory cysts (83%) were correctly diagnosed, whereas one case produced an acellular, nondiagnostic specimen. Six of 28 (23%) cases were nonpancreatic cysts, aspirated under the presumption that they were pancreatic cysts based on radiologic studies: only one case, a papillary cystadenocarcinoma of the stomach, was correctly diagnosed; the other five cases were nondiagnostic, and in two of these the assumption that the cysts were pancreatic in origin precluded an accurate classification. CONCLUSION: FNAB of pancreatic cystic lesions can differentiate mucinous from nonmucinous pancreatic cysts and provide definitive evidence of malignancy. In some cases, serous cystadenomas can be diagnosed. Pseudocysts can be suspected on the basis of an inflammatory smear lacking both epithelial cells and background mucin, but this finding is not specific. Nonpancreatic lesions constitute a significant percentage of cases aspirated as pancreatic cysts and present a major pitfall in cytologic interpretation. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,SURG SERV,CLIN LABS,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. NR 19 TC 60 Z9 61 U1 0 U2 0 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA P.O. DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 SN 0001-5547 J9 ACTA CYTOL JI Acta Cytol. PD JUL-AUG PY 1997 VL 41 IS 4 BP 972 EP 980 PG 9 WC Pathology SC Pathology GA XN684 UT WOS:A1997XN68400003 PM 9250287 ER PT J AU Ono, Y Tamiya, T Ichikawa, T Matsumoto, K Furuta, T Ohmoto, T Akiyama, K Seki, S Ueki, K Louis, DN AF Ono, Y Tamiya, T Ichikawa, T Matsumoto, K Furuta, T Ohmoto, T Akiyama, K Seki, S Ueki, K Louis, DN TI Accumulation of wild-type p53 in astrocytomas is associated with increased p21 expression SO ACTA NEUROPATHOLOGICA LA English DT Article DE p21; p53; astrocytoma; single-strand conformation polymorphism; immunohistochemistry ID CYCLIN-DEPENDENT KINASES; HUMAN BRAIN-TUMORS; P53-INDEPENDENT PATHWAY; CELL-CYCLE; GENE; WAF1/CIP1; MUTATIONS; INHIBITOR; INDUCTION; PROTEIN AB Approximately one quarter of human astrocytomas show immunohistochemical positivity for p53 protein but lack p53 gene mutations, which could reflect either an accumulation of wild-type p53 protein or an inadequate sensitivity of mutation detection. Since wild-type p53 up-regulates p21 expression, increased p21 expression in those astrocytomas with p53 accumulation in the absence of mutations would argue that the protein was wild type in these tumors. We therefore compared p21 expression with p53 gene and protein status in 48 primary human astrocytomas. Single-strand conformation polymorphism analysis and direct sequencing of the p53 gene showed mutations in 11 tumors (22.9%), while immunohistochemistry revealed positive staining in 19 cases (39.6%). Those tumors with p53 immunopositivity in the absence of p53 mutation had significantly increased p21 expression when compared to either mutant p53 or p53-immunonegative cases. Neither p53 nor p21 status correlated with proliferation indices, as assessed by Ki-67 immunohistochemistry. These results support the hypotheses that functionally wild-type p53 accumulates in some astrocytomas, and that alternative cell cycle checkpoints (such as the p16 pathway) may be more important than p21 in regulating proliferation in astrocytomas. C1 OKAYAMA UNIV,SCH MED,DEPT NEUROL SURG,OKAYAMA 700,JAPAN. OKAYAMA UNIV,SCH MED,INST MOL & CELLULAR BIOL,DEPT MOL BIOL,OKAYAMA 700,JAPAN. MASSACHUSETTS GEN HOSP,DEPT PATHOL,MOL NEUROONCOL LAB,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,NEUROSURG SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. FU NCI NIH HHS [CA57683] NR 39 TC 32 Z9 32 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0001-6322 J9 ACTA NEUROPATHOL JI Acta Neuropathol. PD JUL PY 1997 VL 94 IS 1 BP 21 EP 27 PG 7 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA XG013 UT WOS:A1997XG01300004 PM 9224526 ER PT J AU Arnsten, JH Gelfand, JM Singer, DE AF Arnsten, JH Gelfand, JM Singer, DE TI Determinants of compliance with anticoagulation: A case-control study SO AMERICAN JOURNAL OF MEDICINE LA English DT Article; Proceedings Paper CT 18th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 04-06, 1995 CL SAN DIEGO, CA SP Soc Gen Internal Med ID ATRIAL-FIBRILLATION; RANDOMIZED TRIAL; MEDICAL OUTCOMES; WARFARIN; ADHERENCE; RECOMMENDATIONS; PREVENTION; THERAPY AB BACKGROUND: The number of patients for whom long-term anticoagulation is indicated has increased dramatically over the past decade. Good patient compliance is necessary to safely realize the benefits of anticoagulation, yet barriers to compliance with anticoagulation therapy have not been studied. METHODS: We conducted a case-control study in the Anticoagulation Therapy Unit (ATU) at Massachusetts General Hospital. Forty-three patients who had been discharged from the ATU for noncompliance (cases) and 89 randomly selected compliant ATU controls were interviewed. Noncompliant cases had self-discontinued warfarin or were taking warfarin with inadequate monitoring of international normalized ratio (INR) levels. Telephone interviews assessed sociodemographic features, indication for anticoagulation, patient satisfaction, and health beliefs. RESULTS: Noncompliant cases were more likely to be younger (mean 53.7 years versus 68.7 years, P < 0.0001), male (odds ratio [OR] 3.5, 95% confidence interval [CI] 1.5, 8.2), and nonwhite (OR 6.4, 95% CI 1.9, 21.9), and less likely to have had a stroke or transient ischemic attack (OR 0.2, 95% CI 0.1, 0.7). In open-ended questioning, cases were more likely to report that they did not know why warfarin had been prescribed (OR 4.4, 95% CI 1.4, 14.2). Noncompliant cases were more likely not to have a regular physician (OR 11.1, 95% CI 3.6, 50.0); among patients with a regular physician, noncompliant cases were more likely to feel dissatisfied. Examination of health beliefs revealed that noncompliant cases felt more burdened by taking warfarin, and perceived fewer health benefits. CONCLUSIONS: Patients who are noncompliant with warfarin share distinctive clinical characteristics. Notably, younger, male patients who have not experienced a thromboembolic event are more likely to forego INR testing or to stop anticoagulation therapy completely. Improved patient education, physician involvement, and ease of monitoring may improve compliance, particularly among younger male patients. (C) 1997 by Excerpta Medica, Inc. C1 MASSACHUSETTS GEN HOSP, GEN INTERNAL MED UNIT, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA USA. HARVARD UNIV, SCH PUBL HLTH, DEPT EPIDEMIOL, BOSTON, MA 02115 USA. FU BHP HRSA HHS [5T32PE11001-07] NR 24 TC 88 Z9 90 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 EI 1555-7162 J9 AM J MED JI Am. J. Med. PD JUL PY 1997 VL 103 IS 1 BP 11 EP 17 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA XL324 UT WOS:A1997XL32400002 PM 9236480 ER PT J AU Sormanti, M August, J AF Sormanti, M August, J TI Parental bereavement: Spiritual connections with deceased children SO AMERICAN JOURNAL OF ORTHOPSYCHIATRY LA English DT Article ID DEATH AB Of a sample of 43 bereaved parents of pediatric cancer patients, 38 reported experiencing feelings of continued connection with their deceased child, Analysis of the data revealed several consistent themes in the experiences and in their impact on the parental bereavement process. Implications for research and clinical practices are discussed. C1 DANA FARBER CANC INST,BOSTON,MA 02115. RP Sormanti, M (reprint author), COLUMBIA UNIV,SCH SOCIAL WORK,622 W 113TH ST,NEW YORK,NY 10025, USA. NR 20 TC 21 Z9 21 U1 2 U2 4 PU AMER ORTHOPSYCHIATRIC ASSOC PI NEW YORK PA 330 SEVENTH AVE, 18TH FL, NEW YORK, NY 10001 SN 0002-9432 J9 AM J ORTHOPSYCHIAT JI Am. J. Orthopsychiatr. PD JUL PY 1997 VL 67 IS 3 BP 460 EP 469 DI 10.1037/h0080247 PG 10 WC Psychiatry; Social Work SC Psychiatry; Social Work GA XL633 UT WOS:A1997XL63300013 PM 9250346 ER PT J AU Miller, JW AF Miller, JW TI Vascular endothelial growth factor and ocular neovascularization - Comment SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Editorial Material ID EXPERIMENTAL CHOROIDAL NEOVASCULARIZATION; EXPERIMENTAL SUBRETINAL NEOVASCULARIZATION; EXPERIMENTAL IRIS NEOVASCULARIZATION; PROLIFERATIVE DIABETIC-RETINOPATHY; SUB-RETINAL NEOVASCULARIZATION; BRANCH VEIN OCCLUSION; PERMEABILITY FACTOR; PRERETINAL NEOVASCULARIZATION; PHOTODYNAMIC THERAPY; CORNEAL NEOVASCULARIZATION C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,LASER LAB,BOSTON,MA 02114. RP Miller, JW (reprint author), HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,RETINA SERV,243 CHARLES ST,BOSTON,MA 02114, USA. NR 97 TC 90 Z9 104 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 JUL PY 1997 VL 151 IS 1 BP 13 EP 23 PG 11 WC Pathology SC Pathology GA XH227 UT WOS:A1997XH22700004 PM 9212726 ER PT J AU Keates, S Keates, AC Mizoguchi, E Bhan, A Kelly, CP AF Keates, S Keates, AC Mizoguchi, E Bhan, A Kelly, CP TI Enterocytes are the primary source of the chemokine ENA-78 in normal colon and ulcerative colitis SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article; Proceedings Paper CT 96th Annual Meeting of the American-Gastroenterological-Association CY MAY 18-23, 1996 CL SAN FRANCISCO, CA SP Amer Gastroenterol Assoc DE inflammatory bowel disease; interleukin-8; chemotaxis; inflammation ID INTESTINAL EPITHELIAL-CELLS; ACTIVATING PEPTIDE ENA-78; INFLAMMATORY CYTOKINES; INTERLEUKIN-8 GENE; PROINFLAMMATORY CYTOKINES; SALMONELLA-TYPHIMURIUM; EXPRESSION; FAMILY; LYMPHOTACTIN; NEUTROPHILS AB Epithelial cell-derived neutrophil-activating protein-78 (ENA-78) is a neutrophil-directed C-X-C chemokine. We report that Caco-2 and T84 human intestinal epithelial cells produce ENA-78 after stimulation by interleukin (IL)-1 beta or tumor necrosis factor-alpha. Caco-2 cells show increased IL-8 production at 4-12 h and increased ENA-78 production at 8-24 h after cytokine stimulation. Immunohistochemical studies in normal human colon and in ulcerative colitis demonstrate ENA-78 immunoreactivity principally associated with crypt epithelial cells. Furthermore, human colonic tissues from patients with ulcerative colitis show elevated levels of ENA-78 mRNA (24-fold increase, P < 0.01) and protein (4-fold increase, P < 0.05) compared with normal controls. Thus ENA-78 is produced in normal colon and in ulcerative colitis and is predominantly of enterocyte origin. The kinetics of ENA-78 induction in human colon epithelial cell lines are delayed and prolonged compared with IL-8. We propose that ENA-78 and IL-8 serve complementary and sequential roles in neutrophil recruitment in ulcerative colitis. ENA-78 as an enterocyte-derived, neutrophil-activating chemokine may be especially important in neutrophil recruitment from the lamina propria into the epithelial layer. C1 HARVARD UNIV, BETH ISRAEL DEACONESS MED CTR, SCH MED, DIV GASTROENTEROL, BOSTON, MA 02215 USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, IMMUNOPATHOL DEPT, BOSTON, MA 02215 USA. FU NIDDK NIH HHS [DK-02128, DK-43551] NR 36 TC 71 Z9 71 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD JUL PY 1997 VL 273 IS 1 BP G75 EP G82 PG 8 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA XL328 UT WOS:A1997XL32800011 PM 9252512 ER PT J AU Kiraly, A Suto, G Guth, PH Tache, Y AF Kiraly, A Suto, G Guth, PH Tache, Y TI Mechanisms mediating gastric hyperemic and acid responses to central TRH analog at a cytoprotective dose SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE prostaglandins; capsaicin; calcitonin gene-related peptide antagonist; gastric mucosal blood flow; vagus ID GENE-RELATED PEPTIDE; THYROTROPIN-RELEASING-HORMONE; MUCOSAL BLOOD-FLOW; HYDROGEN GAS CLEARANCE; VAGAL-STIMULATION; NERVOUS-SYSTEM; RAT; SECRETION; CGRP; NEUROPEPTIDES AB Gastric hyperemic and acid responses to the stable thyrotropin-releasing hormone (TRH) analog RX-77368 injected intracisternally at a cytoprotective dose were investigated, as well as the underlying mechanisms of the responses. Gastric acid secretion (GAS), mucosal blood flow (GMBF; measured by the hydrogen gas clearance technique), and mucosal vascular resistance (GMVR) and mean arterial pressure (MAP) were assessed simultaneously for 30 min before and after RX-77368 (1.5 ng) administration in urethan-anesthetized rats. RX-77368 increased GMBF from 46.8 +/- 5.3 to 100.6 +/- 20.9 ml.min(-1).100 g(-1) and MAP from 70.3 +/- 2.1 to 84.3 +/- 5.9 mmHg and decreased GMVR from 1.50 +/- 0.33 to 0.84 +/- 0.08 mmHg.ml(-1).min.100 g, whereas GAS was not significantly altered (1.8 +/- 0.4 vs. 4.7 +/- 1.7 mu mol/30 min) in vehicle-pretreated rats. The GMBF, MAP, and GMVR responses to RX-77368 were not modified by indomethacin (5 mg/kg ip), whereas GAS was increased. In rats pretreated with capsaicin (125 mg/kg sc) or calcitonin gene-related peptide (CGRP) antagonist hCGRP-(8-37), intracisternal RX-77368 did not increase GMBF or decrease GMVR but did stimulate GAS. These data show that vagal stimulation by the TRH analog RX-77368 injected intracisternally at a nonacid secretory dose increases GMBF. Gastric hyperemia is mediated by CGRP contained in capsaicin-sensitive afferent fibers, whereas acid secretion is under the inhibitory influence of prostaglandins and CGRP. C1 W LOS ANGELES VET AFFAIRS MED CTR, DIGEST DIS RES CTR, CURE, LOS ANGELES, CA 90073 USA. UNIV CALIF LOS ANGELES, DEPT MED, LOS ANGELES, CA 90073 USA. UNIV CALIF LOS ANGELES, BRAIN RES INST, LOS ANGELES, CA 90073 USA. FU NIDDK NIH HHS [DK-30110, DK-41301]; NIMH NIH HHS [MH-00663] NR 36 TC 15 Z9 15 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD JUL PY 1997 VL 273 IS 1 BP G31 EP G38 PG 8 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA XL328 UT WOS:A1997XL32800005 PM 9252506 ER PT J AU Saghir, M Werner, J Laposata, M AF Saghir, M Werner, J Laposata, M TI Rapid in vivo hydrolysis of fatty acid ethyl esters, toxic nonoxidative ethanol metabolites SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE alcohol; pancreatitis; free fatty acid; omega-3 fatty acids ID GENE-TRANSCRIPTION; ADIPOSE-TISSUE; RAT; ORGANS; CELLS; N-3 AB Fatty acid ethyl esters (FAEE), esterification products of fatty acids and ethanol, are in use as fatty acid supplements, but they also have been implicated as toxic mediators of ethanol ingestion. We hypothesized that hydrolysis of orally ingested FAEE occurs in the gastrointestinal (GI) tract and in the blood to explain their apparent lack of toxicity. To study the in vivo inactivation of FAEE by hydrolysis to free fatty acids and ethanol, we assessed the hydrolysis of FAEE administered as an oil directly into the rat stomach and when injected within the core of low-density lipoprotein particles into the circulation of rats. Our studies demonstrate that FAEE are rapidly degraded to free fatty acids and ethanol in the GI tract at the level of the duodenum with Limited hydrolysis in the stomach. In addition, FAEE are rapidly degraded in the circulation, with a half-life of only 58 s. Thus the degradation of FAEE in the GI tract and in the blood provides an explanation for the apparent lack of toxicity of orally ingested FAEE. C1 MASSACHUSETTS GEN HOSP, DIV CLIN LABS, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, DEPT PATHOL, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, DEPT SURG, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02114 USA. FU NIDDK NIH HHS [R01DK-37454] NR 36 TC 32 Z9 33 U1 1 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD JUL PY 1997 VL 273 IS 1 BP G184 EP G190 PG 7 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA XL328 UT WOS:A1997XL32800024 PM 9252525 ER PT J AU Amsterdam, JD Fawcett, J Quitkin, FM Reimherr, FW Rosenbaum, JF Michelson, D HornigRohan, M Beasley, CM AF Amsterdam, JD Fawcett, J Quitkin, FM Reimherr, FW Rosenbaum, JF Michelson, D HornigRohan, M Beasley, CM TI Fluoxetine and norfluoxetine plasma concentrations in major depression: A multicenter study SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 3rd International Conference on Refractory Depression CY OCT 18-21, 1995 CL NAPA, CA ID ANTIDEPRESSANT RESPONSE; THERAPEUTIC RESPONSE; CLINICAL-RESPONSE; DOUBLE-BLIND; PHARMACOKINETICS; AMITRIPTYLINE; IMIPRAMINE AB Objective: Prior studies examining the relationship between fluoxetine plasma concentrations and response in major depression have either found no relationship between plasma concentration and response or suggested a curvilinear relationship with a therapeutic window. To elucidate this relationship, plasma concentrations of fluoxetine, norfluoxetine, fluxoetine plus norfluoxetine, and fluoxetine/norfluoxetine ratio were compared to therapeutic response. Method: A total of 839 patients (577 women, 262 men; mean age=40 years [SD=11]) with a DSM-III-R diagnosis of major affective disorder who were in the course of either major depression or bipolar disorder not otherwise specified and had a minimum baseline score of 16 on the 17-item Hamilton Depression Rating Scale were initially treated. Response was defined as follows: 1) nonresponders had less than a 50% reduction from baseline Hamilton depression score, 2) nonremitting responders had a 50% or more seduction from baseline Hamilton depression score but a final scole higher than 7, and 3) remitters had a final Hamilton depression score of 7 ol lower. Plasma fluoxetine and norfluoxetine concentrations were measured after 8 weeks of fixed-dose treatment at 20 mg/day. Results: Plasma concentration data were available from 615 patients. Plasma concentrations were similar In responders, both remitting and nonremitting (N=411), and nonresponders (N=204) for fluoxetine concentrations, for norfluoxetine concentrations, as well as for the sum of fluoxetine and norfluoxetine and for the ratio of fluoxetine to norfluoxetine. No apparent relationship was observed between plasma drug concentrations and clinical response. Conclusions: Plasma concentrations of fluoxetine and norfluoxetine do not appear to be related to clinical outcome and should not be used to make treatment decisions. C1 UNIV PENN,MED CTR,DEPRESS RES UNIT,PHILADELPHIA,PA 19104. RUSH PRESBYTERIAN ST LUKES MED CTR,CHICAGO,IL 60612. NEW YORK STATE PSYCHIAT INST & HOSP,NEW YORK,NY. UNIV UTAH,SCH MED,SALT LAKE CITY,UT. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. LILLY RES LABS,INDIANAPOLIS,IN. OI Beasley, Charles/0000-0001-8743-7691 NR 30 TC 82 Z9 83 U1 1 U2 6 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JUL PY 1997 VL 154 IS 7 BP 963 EP 969 PG 7 WC Psychiatry SC Psychiatry GA XG892 UT WOS:A1997XG89200012 PM 9210747 ER PT J AU Liu, HW Anand, A Bloch, K Christiani, D Kradin, R AF Liu, HW Anand, A Bloch, K Christiani, D Kradin, R TI Expression of inducible nitric oxide synthase by macrophages in rat lung SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID COLONY-STIMULATING FACTOR; PRESENTING CELL FUNCTION(S); ALVEOLAR MACROPHAGES; DENDRITIC CELLS; DOWN-REGULATION; ANTIGEN; MICE; POPULATIONS; MONOCYTES; RESPONSES AB Nitric oxide (NO) is a short-lived free radical that is secreted by pulmonary macrophages (Mo). An inducible isoform of NO synthase (iNOS) catalyses the production of NO and is activated by lipopolysaccharide and certain T-helper(h) 1 cytokines, including interferon-gamma and TNF-alpha. In the present study, iNOS(+) interstitial cells were demonstrated in the alveolar wall of normal Lewis rat lung. Enzymatic digests of normal lung showed that approximately one third of pulmonary ED1(+) interstitial Mo (IM) were iNOS(+) and secreted modest amounts of NO without ex vivo stimulation, whereas normal alveolar macrophages (AM) were iNOS(-) and showed no basal NO secretion. When incubated with heat-killed Listeria monocytogenes (HKL) in vitro, AM secreted larger amounts of NO than did IM. Recombinant murine CM-CSF stimulated production of NO by AM hut not by IM. However, when IM were costimulated with CM-CSF and IFN-gamma, they expressed a marked increase in NO production. Intratracheal challenge with HKL yielded decreased NO production by IM. We conclude that iNOS(+) IM are present in normal rat lung, where they regulate the pulmonary cell-mediated immune response to antigen. C1 MASSACHUSETTS GEN HOSP,IMMUNOPATHOL UNIT,DEPT PATHOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. FU NHLBI NIH HHS [HL-48385] NR 33 TC 32 Z9 32 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD JUL PY 1997 VL 156 IS 1 BP 223 EP 228 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA XJ865 UT WOS:A1997XJ86500036 PM 9230752 ER PT J AU Lee, SL Wang, WW Joseph, PM Hales, CA Fanburg, BL AF Lee, SL Wang, WW Joseph, PM Hales, CA Fanburg, BL TI Inhibitory effect of heparin on serotonin-induced hyperplasia and hypertrophy of smooth muscle cells SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID PRIMARY PULMONARY-HYPERTENSION; STIMULATE TYROSINE PHOSPHORYLATION; SWISS 3T3 CELLS; RAT; PROLIFERATION; GROWTH; ARTERY; PROGRESSION; SUPPRESSES; PROTEINS AB Serotonin (5-HT) produces both hyperplastic and hypertrophic effects on smooth muscle cell (SMC) in culture. Heparin is known to inhibit serum-induced hyperplasia of SMC but has not been previously tested on the stimulatory effect of 5-HT on SMC. Our present data show that at 24 h heparin inhibited by 50% the stimulation of H-3-thymidine incorporation into bovine pulmonary artery SMC and at 7 days totally reversed both cellular proliferation and enlargement of SMC produced by 1 mu M 5-HT. Heparin failed to alp ter 5-HT uptake by SMC, but inhibited the stimulation of tyrosine phosphorylation of GTPase-activating protein, a proposed intermediate in the 5-HT stimulatory process. Thus heparin inhibits both hyperplastic and hypertrophic effects of 5-HT on SMC, perhaps through the inhibition of a phosphorylated intermediate protein. C1 TUFTS UNIV,SCH MED,NEW ENGLAND MED CTR,DIV PULM,DEPT MED,BOSTON,MA 02111. TUFTS UNIV,SCH MED,NEW ENGLAND MED CTR,DIV CRIT CARE,DEPT MED,BOSTON,MA 02111. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA. FU NHLBI NIH HHS [R01 HL039150, HL39150, HL32723] NR 47 TC 10 Z9 11 U1 1 U2 2 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD JUL PY 1997 VL 17 IS 1 BP 78 EP 83 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA XK110 UT WOS:A1997XK11000011 PM 9224212 ER PT J AU Rieumont, MJ Kaufman, JA Geller, SC Yucel, EK Cambria, RP Fang, LST Bazari, H Waltman, AC AF Rieumont, MJ Kaufman, JA Geller, SC Yucel, EK Cambria, RP Fang, LST Bazari, H Waltman, AC TI Evaluation of renal artery stenosis with dynamic gadolinium-enhanced MR angiography SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article; Proceedings Paper CT 80th Scientific Assembly and Annual Meeting of the Radiology-Society-of-North-America CY NOV 27-DEC 02, 1994 CL CHICAGO, IL SP Radiol Soc N Amer ID MAGNETIC-RESONANCE ANGIOGRAPHY; ABDOMINAL-AORTA; SEQUENCES; DONORS AB OBJECTIVE. The purpose of this study was to compare dynamic gadolinium-enhanced three-dimensional spoiled gradient-recalled MR angiography with conventional arteriography in the evaluation of proximal renal artery stenosis (RAS). MATERIALS AND METHODS. MR angiography and conventional arteriographic examinations of 30 patients evaluated for RAS were analyzed retrospectively. Three-dimensional MR angiography was performed with an RF spoiled gradient-recalled imaging sequence acquired during the dynamic IV injection of gadolinium (0.2-0.3 mmol/kg). MR data and conventional arteriograms were independently evaluated for the number and location of renal arteries and the degree and location of stenoses. The patients had a mean age of 70 years old and a mean serum creatinine level of 2.9 mg/dl, reflecting a population in whom atherosclerotic RAS was the primary concern. RESULTS, Gadolinium-enhanced MR angiography revealed 100% of main renal arteries. For RAS of 50% or greater occlusion, the technique was 100% sensitive and 71% specific; the negative predictive value was 100%. The technique was 100% sensitive and 71% specific for RAS of 75% or greater occlusion. CONCLUSION. Dynamic gadolinium-enhanced three-dimensional spoiled gradient-recalled MR angiography has a high sensitivity for revealing proximal RAS and is a quick and reliable technique for obtaining helpful anatomic information. C1 BOSTON UNIV,MED CTR,DEPT RADIOL,BOSTON,MA 02118. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DIV VASC SURG,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DIV MED,BOSTON,MA 02114. RP Rieumont, MJ (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIOL,32 FRUIT ST,BOSTON,MA 02114, USA. NR 30 TC 70 Z9 71 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 JUL PY 1997 VL 169 IS 1 BP 39 EP 44 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA XG216 UT WOS:A1997XG21600010 PM 9207498 ER PT J AU Rhea, JT Rao, PM Novelline, RA McCabe, CJ AF Rhea, JT Rao, PM Novelline, RA McCabe, CJ TI A focused appendiceal CT technique to reduce the cost of caring for patients with clinically suspected appendicitis SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article AB OBJECTIVE. This investigation analyzed the potential impact on hospitalwide variable costs and total costs of introducing a focused helical CT technique for diagnosing appendicitis. MATERIALS AND METHODS, This investigation had three components. First, we retrospectively reviewed the records of 651 patients who had admitting diagnoses of appendicitis. Second, we determined variable costs and total costs for the components of these patients' care. Third, we projected change in costs if the focused appendiceal CT technique had been used to guide patient management. RESULTS, Using focused appendiceal CT in 100 patients would have decreased the number of nontherapeutic appendectomies by 13. The average length of stay for observation would have also decreased by 1 day because the diagnosis of an abnormal appendix or an alternative diagnosis would have been made more quickly. Savings in variable costs and total costs would have been $23,030 and $45,556 per 100 patients, respectively. CONCLUSION, Routine use of focused appendiceal CT would lower the costs of caring for patients with clinically suspected appendicitis. C1 MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. RP Rhea, JT (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,32 FRUIT ST,BOSTON,MA 02114, USA. NR 9 TC 54 Z9 55 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 JUL PY 1997 VL 169 IS 1 BP 113 EP 118 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA XG216 UT WOS:A1997XG21600021 PM 9207509 ER PT J AU Graf, O Boland, GW Warshaw, AL FernandezdelCastillo, C Hahn, PF Mueller, PR AF Graf, O Boland, GW Warshaw, AL FernandezdelCastillo, C Hahn, PF Mueller, PR TI Arterial versus portal venous helical CT for revealing pancreatic adenocarcinoma: Conspicuity of tumor and critical vascular anatomy SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID DYNAMIC CT; SPIRAL CT; RESECTABILITY; DIAGNOSIS AB OBJECTIVE. The purpose of this study was to determine the conspicuity of pancreatic adenocarcinoma and surrounding critical pancreatic vascular structures on helical CT scans obtained during the arterial and portal venous phases of enhancement. SUBJECTS AND METHODS. Forty patients with pancreatic adenocarcinomas underwent dual-phase helical CT (3-mm collimation; 1-mm overlapping reconstructions; 160 ml contrast medium injected at 4 ml/sec; scan delay: 18 sec for arterial phase, 60 sec for portal venous phase), Tissue enhancement and differences in tumor-to-pancreas contrast were compared. Quantitative evaluation was also done for the aorta, the superior mesenteric artery and vein, and the splenic and portal veins, RESULTS, Tumor conspicuity was significantly greater in the portal venous phase, when the tumor-to-pancreas contrast difference was 54 +/- 31 H, than in the arterial phase, when the difference was 31 +/- 29 H. Enhancement Values of critical pancreatic venous structures were significantly greater in the portal Venous phase than in the arterial phase. CONCLUSION, Arterial-phase helical CT in patients with pancreatic adenocarcinoma is of limited benefit: lesion conspicuity is suboptimal and depiction of venous anatomy is inferior to the depiction possible with venous-phase helical CT. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. NR 13 TC 70 Z9 84 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 JUL PY 1997 VL 169 IS 1 BP 119 EP 123 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA XG216 UT WOS:A1997XG21600022 PM 9207510 ER PT J AU Dupuy, DE Hangen, DH Zachazewski, JE Boland, AL Palmer, W AF Dupuy, DE Hangen, DH Zachazewski, JE Boland, AL Palmer, W TI Kinematic CT of the patellofemoral joint SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID COMPUTED-TOMOGRAPHY; LATERAL RELEASE; ABNORMALITIES; MOTION AB OBJECTIVE. The purpose of this study was to determine if kinematic CT can be applied to the patellofemoral joint using current slip-ring CT scanner design in patients with anterior knee pain and thus a suspected patellar tracking disorder. SUBJECTS AND METHODS. Twenty knees in 18 patients with anterior knee pain were evaluated with kinematic CT. A single 10-sec exposure of the patellofemoral joint was obtained during active flexion and extension. Static nonkinematic and loaded kinematic examinations were compared with unloaded kinematic studies in a subset of patients. The changes in lateral patellofemoral angle and lateral shift were measured. Video cine viewing of patellofemoral motion was used to subjectively grade image quality and patellofemoral abnormalities by consensus. RESULTS. Kinematic CT was successfully used in ail 20 knees. In nine knees studied with static nonkinematic and unloaded kinematic images, the lateral patellofemoral angle improved an average of 4 degrees on the kinematic images. In addition, lateral shift improved by an average of 3%, an improvement that was statistically significant (p = .01). In 10 knees studied with and without loading, the lateral patellofemoral angle decreased an average of 3% with loading. No significant change was seen in lateral shift. In all patients, cine viewing wets thought to be more useful than single images. Cine viewing was of good or diagnostic quality in all 20 knees studied. Lateral patellar translation during extension was detected in eight of 20 kinematic studies. Lateral patellar tilting also was detected in eight of 20 kinematic studies. Narrowing of the articular space was detected in 12 of 20 knees. Six knees were determined to be normal. CONCLUSION, Kinematic CT with slip-ring technology is a new technique that can be easily performed on the patellofemoral joint. This technique shows promise as a tool for determining the cause of anterior knee pain. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT ORTHOPED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PHYS THERAPY,BOSTON,MA 02114. RP Dupuy, DE (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,15 PARKMAN ST,LEVEL 5,STE 515,BOSTON,MA 02114, USA. OI Dupuy, Damian/0000-0003-0524-5982 NR 19 TC 25 Z9 26 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 JUL PY 1997 VL 169 IS 1 BP 211 EP 215 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA XG216 UT WOS:A1997XG21600040 PM 9207527 ER PT J AU Kubaska, SM Chew, FS AF Kubaska, SM Chew, FS TI Brain abscess in hereditary hemorrhagic telangiectasia SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID DISEASE C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 4 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 JUL PY 1997 VL 169 IS 1 BP 240 EP 240 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA XG216 UT WOS:A1997XG21600045 PM 9207532 ER PT J AU Marini, RP Callahan, RJ Jackson, LR Jyawook, S Esteves, MI Fox, JG Wilkinson, RA Strauss, HW AF Marini, RP Callahan, RJ Jackson, LR Jyawook, S Esteves, MI Fox, JG Wilkinson, RA Strauss, HW TI Distribution of technetium 99m-labeled red blood cells during isoflurane anesthesia in ferrets SO AMERICAN JOURNAL OF VETERINARY RESEARCH LA English DT Article; Proceedings Paper CT American-Association-for-Laboratory-Animal-Science National Meeting CY OCT, 1993 CL NASHVILLE, TN SP Amer Assoc Lab Anim Sci ID NITROUS-OXIDE; HALOTHANE; SEQUESTRATION; VOLUME AB Objective-To address the physiologic mechanism of isoflurane-associated reduction in hematologic variables in ferrets. Animals-6 young adult female ferrets. Procedure-Distribution of Tc-99m-labeled autologous erythrocytes was measured by serial in vivo imaging. Data were recorded in 4 ferrets, using a gamma camera, immediately prior to anesthesia, 15 minutes after 2% isoflurane anesthesia in O-2 via endotracheal tube, 1 minute prior to and throughout a 10-minute phenylephrine infusion, 20 and 40 minutes after termination of the phenylephrine infusion, and 45 minutes after termination of anesthesia. Blood indices were also measured at times that paralleled those for imaging, One ferret served as a conscious control (no anesthetic administration), and another as an isoflurane control (no phenylephrine administration). Results-In ferrets under anesthesia, splenic radioactivity increased from baseline of 10.2 +/- 2.0% to 38.4 +/- 3.2% (mean +/- SEM; P < 0.05) of the injected dose. Splenic radioactivity decreased to 13.4 +/- 3.8% of the injected dose during phenylephrine infusion and to near baseline for the recovery image. Splenic radioactivity in the conscious control remained constant throughout the study, whereas that of the anesthetized control was persistently increased throughout administration of isoflurane. Percentage reduction of the 15-minute sample values, compared with baseline values for all hematologic indices, was: RBC count, 33% (P < 0.05); hemoglobin concentration, 34% (P < 0.05); hematocrit, 35% (P < 0.05); and plasma protein concentration, 20% (P < 0.05). All RBC variables returned to within 7 to 14% of baseline by 45 minutes after termination of anesthesia. Conclusion-Isoflurane anesthesia causes splenic sequestration of RBC in ferrets that is partially reversed by phenylephrine infusion or termination of anesthesia. Thus, investigators and clinicians should be cautious when interpreting hematologic findings in isoflurane-anesthetized ferrets, and accordingly, fluid treatment and transfusion should be planned. C1 HARVARD UNIV,SCH MED,DEPT RADIOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT NUCL PHARM,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DIV NUCL MED,BOSTON,MA 02114. RP Marini, RP (reprint author), MIT,DIV COMPARAT MED,CAMBRIDGE,MA 02139, USA. FU NCRR NIH HHS [RR01046, RR07036] NR 23 TC 17 Z9 17 U1 0 U2 1 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 SN 0002-9645 J9 AM J VET RES JI Am. J. Vet. Res. PD JUL PY 1997 VL 58 IS 7 BP 781 EP 785 PG 5 WC Veterinary Sciences SC Veterinary Sciences GA XG913 UT WOS:A1997XG91300029 PM 9215458 ER PT J AU Kaltashov, IA Doroshenko, V Cotter, RJ Takayama, K Qureshi, N AF Kaltashov, IA Doroshenko, V Cotter, RJ Takayama, K Qureshi, N TI Confirmation of the structure of lipid A derived from the lipopolysaccharide of Rhodobacter sphaeroides by a combination of MALDI, LSIMS, and tandem mass spectrometry SO ANALYTICAL CHEMISTRY LA English DT Article ID FAST ATOM BOMBARDMENT; RHODOPSEUDOMONAS-SPHAEROIDES; FATTY-ACIDS; ATCC-17023 AB The chemical structure of nontoxic diphosphoryl lipid A from Rhodobacter sphaeroides was confirmed using a combination of LSIMS (on a two-sector mass spectrometer) and MALDI (on time-of-flight and ion trap mass spectrometers) in conjunction with tandem mass spectrometry in both positive and negative ion modes. Accurate molecular weight measurement accompanied by the analysis of fragment ion masses yielded the composition of fatty acyl groups. Tandem experiments (collisionally induced dissociation of both quasimolecular and oxonium ions) were also performed, revealing the precise location and nature of the fatty acyl groups on the disaccharide backbone. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT PHARMACOL,MIDDLE ATLANTIC MASS SPECTROMETRY LAB,BALTIMORE,MD 21205. WILLIAM S MIDDLETON MEM VET ADM MED CTR,MYCOBACTERIOL RES LAB,MADISON,WI 53705. UNIV WISCONSIN,COLL AGR & LIFE SCI,DEPT BACTERIOL,MADISON,WI 53706. FU NCRR NIH HHS [R01RR08912]; NIGMS NIH HHS [R01GM33967, GM50870] NR 16 TC 46 Z9 46 U1 2 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD JUL 1 PY 1997 VL 69 IS 13 BP 2317 EP 2322 DI 10.1021/ac9612943 PG 6 WC Chemistry, Analytical SC Chemistry GA XG497 UT WOS:A1997XG49700019 PM 9212704 ER PT J AU Kharasch, ED Russell, M Garton, K Lentz, G Bowdle, TA Cox, K AF Kharasch, ED Russell, M Garton, K Lentz, G Bowdle, TA Cox, K TI Assessment of cytochrome P450 3A4 activity during the menstrual cycle using alfentanil as a noninvasive probe SO ANESTHESIOLOGY LA English DT Article; Proceedings Paper CT 1996 Annual Meeting of the American-Society-of-Anesthesiologists CY OCT 18-25, 1996 CL NEW ORLEANS, LA SP Amer Soc Anesthesiologists DE anesthetics, intravenous, alfentanil, fentanyl, sufentanil; analgesics, opioid, alfentanil, fentanyl, sufentanil; enzymes, cytochrome P450 3A4; menstrual cycle, pharmacokinetics, variability, women ID ERYTHROMYCIN BREATH TEST; CYCLOSPORINE-A OXIDASE; HUMAN-LIVER; IN-VIVO; HUMAN HEPATOCYTES; PRIMARY CULTURES; RAT-LIVER; PHARMACOKINETICS; METABOLISM; GENDER AB Background: Gender-dependent differences in cytochrome P450 activity, drug metabolism, drug elimination, and their clinical consequences are increasingly apparent. P450 3A4 is the most abundant P450 isoform in the human liver and is responsible for metabolizing a vast and diverse assortment of therapeutic agents, including opioids, benzodiazepines, and local anesthetics. P450 3A4 activity is higher in women, influenced by steroid hormone levels, and is speculated to vary during the menstrual cycle. This investigation tested the hypothesis that P450 3A4 activity varies during the menstrual cycle. Alfentanil clearance was used as a metabolic probe for P450 3A4 activity. Methods: Alfentanil (20 mu g/kg bolus) was administered to nine nonsmoking, nonpregnant female volunteers (age, 26 +/- 5 yr) with normal menstrual cycles on three separate occasions during the same menstrual cycle: days 2 (menstrual phase), 13 (estrogen peak), and 21 (progesterone peak). Venous plasma alfentanil concentrations were determined by gas chromatography-mass spectrometry. Alfentanil clearance was determined by noncompartmental methods and by a three-compartment model with both pooled population and two-stage analysis. Results: There was no significant difference in any measure of alfentanil clearance. Noncompartmental clearances (mean +/- SD) were 3.62 +/- 0.76, 3.81 +/- 0.96, and 3.60 +/- 0.84 ml/kg/ min, respectively, on days 2, 13, and 21 of the menstrual cycle. Conclusions: Alfentanil clearances were not different on menstrual cycle days 2, 13, and 21, strongly suggesting no change in P450 3A4 activity. Menstrual cycle differences in alfentanil clearances do not contribute to interindividual variability in alfentanil disposition In women. If other P450 3A4 substrates are comparable, then menstrual cycle variability in their metabolism may not be a consideration in dosing or in the design of pharmacokinetic investigations. C1 VET AFFAIRS PUGET SOUND HLTH CARE SYST,ANESTHESIOL SERV,SEATTLE,WA. RP Kharasch, ED (reprint author), UNIV WASHINGTON,DEPT ANESTHESIOL,BOX 356540,SEATTLE,WA 98195, USA. FU NCRR NIH HHS [M01 RR00037] NR 54 TC 51 Z9 52 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD JUL PY 1997 VL 87 IS 1 BP 26 EP 35 DI 10.1097/00000542-199707000-00005 PG 10 WC Anesthesiology SC Anesthesiology GA XJ862 UT WOS:A1997XJ86200009 PM 9232131 ER PT J AU Humphrey, D Kwiatkowska, J Henske, EP Haines, JL Halley, D vanSlegtenhorst, M Kwiatkowski, DJ AF Humphrey, D Kwiatkowska, J Henske, EP Haines, JL Halley, D vanSlegtenhorst, M Kwiatkowski, DJ TI Cloning and evaluation of RALGDS as a candidate for the tuberous sclerosis gene TSC1 SO ANNALS OF HUMAN GENETICS LA English DT Article ID RAS; IDENTIFICATION; MUTATIONS AB RALGDS is a 115 kDa protein which was identified by its ability to enhance guanine nucleotide exchange for the ras family member ral. It also binds to activated ras and rap1, and appears to function as part of a signalling complex in downstream events following rap1 activation. Here we report the identification of full-length cDNA clones for human RALGDS, isolated front a brain cDNA library. The predicted protein has strong sequence homology to rat and murine isoforms of RALGDS in the N- and C-terminal regions, but an internal region (aa 250-380) shows relatively high divergence with only 42% identical amino acid residues. The human RALGDS gene is contained within a 30 kb region of 9q34, approximately 200 kb proximal to the ABO gene, within the current critical region for the tuberous sclerosis gene TSC1. Partial genomic structure was determined; it consists of at least 11 exons. Based upon analysis of Southern blots from 110 TSC patients, genomic DNA SSCP analysis, and RT-PCR analysis which demonstrated RNA expression of both alleles in patients from 9q34-linked TSC families using intragenic polymorphisms, we conclude that RALGDS is not likely to be TSC1. C1 BRIGHAM & WOMENS HOSP,DIV EXPT MED,BOSTON,MA 02115. ERASMUS UNIV ROTTERDAM,DEPT CLIN GENET,ROTTERDAM,NETHERLANDS. ACAD HOSP,ROTTERDAM,NETHERLANDS. MASSACHUSETTS GEN HOSP,NEUROGENET UNIT,BOSTON,MA 02114. RI Haines, Jonathan/C-3374-2012; Jura, Jolanta/F-8889-2015 FU NINDS NIH HHS [NS31535] NR 18 TC 6 Z9 7 U1 0 U2 3 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0003-4800 J9 ANN HUM GENET JI Ann. Hum. Genet. PD JUL PY 1997 VL 61 BP 299 EP 305 DI 10.1046/j.1469-1809.1997.6140299.x PN 4 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA YA617 UT WOS:A1997YA61700002 PM 9365783 ER PT J AU Zeitels, SM HIllman, RE Bunting, GW Vaughn, T AF Zeitels, SM HIllman, RE Bunting, GW Vaughn, T TI Reinke's edema: Phonatory mechanisms and management strategies SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article; Proceedings Paper CT Meeting of the American-Laryngological-Association CY MAY 04-05, 1996 CL ORLANDO, FL SP Amer Laryngol Assoc DE laryngoscopy; laser; microlaryngoscopy; microsurgery; phonosurgery; polypoid corditis; Reinke's edema; stroboscopy; vocal cord; vocal fold; voice ID SEVERE POLYPOID DEGENERATION; SURGICAL-TREATMENT; VOICE AB Reinke's edema (RE) has been associated typically with smoking and sometimes with vocal abuse, but aspects of the pathophysiology of RE remain unclear. To gain new insights into phonatory mechanisms associated with RE pathophysiology, we used an integrated battery of objective vocal function tests to analyze 20 patients (19 women) who underwent phonomicrosurgical resection. Preoperative stroboscopic examinations demonstrated that the superficial lamina propria is distended primarily on the superior vocal fold surface. Acoustically, these individuals have an abnormally low average speaking fundamental frequency (123 Hz), and they generate abnormally high average subglottal pressures (9.7 cm H2O). The presence of elevated aerodynamic driving pressures reflects difficulties in producing vocal fold vibration that are most likely the result of mass loading associated with RE, and possibly vocal hyperfunction. Furthermore, it is hypothesized that in the environment of chronic glottal mucositis secondary to smoking and reflux, the cephalad force on the vocal folds by the subglottal driving pressure contributes to the superior distention of the superficial lamina propria. Surgical reduction of the volume of the superficial lamina propria resulted in a significant elevation in fundamental frequency (154 Hz) and improvement in perturbation measures. In almost all instances, both the clinician and the patient perceived the voice as improved. However, these patients continued to generate elevated subglottal pressure (probably a sign of persistent hyperfunction) that was accompanied by visually observed supraglottal strain despite the normal-sized vocal folds. This finding suggests that persistent hyperfunctional Vocal behaviors may contribute to postsurgical RE recurrence if therapeutic strategies are not instituted to modify such behavior. C1 HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA. RP Zeitels, SM (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,243 CHARLES ST,BOSTON,MA 02114, USA. NR 37 TC 42 Z9 53 U1 0 U2 1 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD JUL PY 1997 VL 106 IS 7 BP 533 EP 543 PN 1 PG 11 WC Otorhinolaryngology SC Otorhinolaryngology GA XK481 UT WOS:A1997XK48100001 PM 9228851 ER PT J AU deVirgilio, C Toosie, K Arnell, T Lewis, RJ Donayre, CE Baker, JD Melany, M White, RA AF deVirgilio, C Toosie, K Arnell, T Lewis, RJ Donayre, CE Baker, JD Melany, M White, RA TI Asymptomatic carotid artery stenosis screening in patients with lower extremity atherosclerosis: A prospective study SO ANNALS OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 15th Annual Meeting of the Southern-California-Vascular-Surgical-Society CY SEP 15-17, 1996 CL DANA POINT, CA SP So Calif Vasc Surg Soc ID SURGERY; DISEASE AB Eighty-nine male veterans presenting to a vascular surgery clinic with symptomatic lower extremity atherosclerosis were prospectively screened by duplex scan for asymptomatic carotid artery stenosis (GAS). Their chief complaint was: claudication (90%), rest pain (6%), and ischemic ulcer or gangrene (4%). The mean ankle-brachial index (ABI) was 0.77. Twenty-five CAS > 50% were detected in 18 (20%) patients. Twelve CAS > 75% were detected in 11 (12%) patients. There was no difference between patients with and without CAS > 50% with regards to mean ABI, history of: angina, diabetes, hypertension, prior coronary artery bypass, or history of smoking. Carotid bruit was associated with ipsilateral CAS > 50% [p<0.0001, sensitivity (52%), specificity (88%), positive predictive value (41%), negative predictive value (92%)]. As a result of the screening, eight elective carotid endarterectomies have been performed to date in six (7%) patients with one transient twelfth cranial nerve paresis as the only postoperative complication. We conclude that: (1) male patients presenting with symptomatic lower extremity atherosclerosis have a 20% prevalence of asymptomatic CAS > 50%, (2) there is no correlation between the degree of lower extremity ischemia and CAS > 50%, (3) carotid bruit is significantly associated with CAS > 50%, but has a low sensitivity, and (4) routine CAS screening should be considered far all male patients with symptomatic lower extremity atherosclerosis regardless of whether a bruit is present. C1 W LOS ANGELES VET AFFAIRS MED CTR, DEPT SURG, LOS ANGELES, CA 90073 USA. W LOS ANGELES VET AFFAIRS MED CTR, DEPT RADIOL, LOS ANGELES, CA 90073 USA. UNIV CALIF LOS ANGELES, HARBOR MED CTR, DEPT EMERGENCY MED, TORRANCE, CA 90509 USA. NR 10 TC 26 Z9 27 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0890-5096 J9 ANN VASC SURG JI Ann. Vasc. Surg. PD JUL PY 1997 VL 11 IS 4 BP 374 EP 377 DI 10.1007/s100169900063 PG 4 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA XJ350 UT WOS:A1997XJ35000007 PM 9236993 ER PT J AU Lyon, JG Cariski, D Keisler, L Rosenbek, J Levine, R Kumpula, J Ryff, C Coyne, S Blanc, M AF Lyon, JG Cariski, D Keisler, L Rosenbek, J Levine, R Kumpula, J Ryff, C Coyne, S Blanc, M TI Communication Partners: Enhancing participation in life and communication for adults with aphasia in natural settings SO APHASIOLOGY LA English DT Article AB Communication partners is a novel aphasia treatment plan whose aim is to restore a sense of purpose, direction, and control to daily life for both patient and caregiver. Treatment involves the participation of a community volunteer who, once paired with an aphasic adult, acts as a Liaison in bridging clinical and real-life pursuits. Initially, treatment pairs are taught how to interact freely and effectively. Once comfortable in each other's company these partners embark on activities of the patient's choosing at home or in the community. Results from 10 treated pairs failed to yield significant differences on the Boston Diagnostic Aphasia Examination, Communication Abilities in Daily Living, or the Affect Balance Scale. However, all participants, i.e. patients, caregivers, and communication partners, noted statistically significant gains in the aphasic adult's well-being and communication on two investigator-constructed questionnaires. Other informal measures also supported the use of this treatment. The significance of these findings, as well as methodological considerations when undertaking this type of research, are discussed. C1 WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI. UNIV WISCONSIN,SCH MED,DEPT NEUROL,MADISON,WI. UNIV WISCONSIN,DEPT PSYCHOL,MADISON,WI 53706. UNIV WISCONSIN,DEPT COMMUN DISORDERS,MADISON,WI 53706. RP Lyon, JG (reprint author), LIVING APHASIA INC,6344 HILLSANDWOOD RD,MAZOMANIE,WI 53560, USA. NR 17 TC 106 Z9 107 U1 0 U2 13 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE SN 0268-7038 J9 APHASIOLOGY JI Aphasiology PD JUL PY 1997 VL 11 IS 7 BP 693 EP 708 DI 10.1080/02687039708249416 PG 16 WC Clinical Neurology SC Neurosciences & Neurology GA XJ639 UT WOS:A1997XJ63900005 ER PT J AU Edge, ASB Spiro, RG AF Edge, ASB Spiro, RG TI Structure of the O-linked oligosaccharides from a major thyroid cell surface glycoprotein SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE O-linked oligosaccharide; thyroid cell surface; alpha-linked galactose; glycoprotein ID ANTI-GAL ANTIBODY; CARBOHYDRATE UNITS; PLASMA-MEMBRANES; CHAINS; FETUIN AB A major glycoprotein at the surface of calf thyroid cells, GP-3 (M(r)20,000), contains the I-antigenic activity of calf thyroid which has been attributed to its poly-N-acetyllactosamine N-linked saccharide chains (Edge, A. S. B., and Spiro, R.G., J. Biol. Chem. 260, 15332-15338, 1985). The present study demonstrated that alkaline borohydride treatment of GP-3 results in the release of five neutral and five acidic saccharides that were found to represent over 30% of the saccharides of this carbohydrate-rich glycoprotein. Three of the oligosaccharides contained terminal alpha 1 --> 3-linked galactose residues which accounted for their affinity toward Bandeiraea simplicifolia I lectin, The saccharides could be grouped into several distinct categories on the basis of their internal sequence. A novel tetrasaccharide in GP-3 was shown to have the structure: Gal alpha 1 --> 3Gal beta 1 --> 6(Gal beta 1 --> 3)GalNAcH(2). An unsubstituted N-acetylgalactosamine unit and a Gal beta 1 --> 3GalNAc disaccharide were prominent O-linked constituents, with the disaccharide serving as a core unit for the attachment of sialic acid residues to form tetra-and trisaccharides, A branched core structure, Gal beta 1 --> 3(GlcNAc beta 1 --> 6)GalNAcH(2) was shared by 4 of the 10 saccharides, the most complete of which was assigned the sequence NeuAc alpha 2 --> 3Gal beta l --> 3(Gal alpha l --> 3Gal beta 1 -->4GlcNAc beta 1 -->6)GalNAcH(2). (C) 1997 Academic Press C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02215. JOSLIN DIABET CTR,BOSTON,MA 02215. FU NIDDK NIH HHS [DK17325] NR 41 TC 9 Z9 10 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD JUL 1 PY 1997 VL 343 IS 1 BP 73 EP 80 DI 10.1006/abbi.1997.0143 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA XH220 UT WOS:A1997XH22000010 PM 9210648 ER PT J AU Raskind, MA Sadowsky, CH Sigmund, WR Beitler, PJ Auster, SB AF Raskind, MA Sadowsky, CH Sigmund, WR Beitler, PJ Auster, SB TI Effect of tacrine on language, praxis, and noncognitive behavioral problems in Alzheimer disease SO ARCHIVES OF NEUROLOGY LA English DT Article AB Objective: To examine the effects of tacrine hydrochloride in patients with Alzheimer disease (AD) and detectable baseline deficits in discrete cognitive and noncognitive parameters who were enrolled in a previously reported multicenter, double-blind, 30-week trial. Design: An exploratory analysis using last observation carried forward. The study population included a placebo group (n=181) and all patients randomized to treatment with 160 mg/d of tacrine hydrochloride (n=238), regardless of highest dose achieved or duration of tacrine therapy. Study Population: Male and female subjects, at least 50 years of age, with mild to moderate AD and detectable baseline deficits in discrete cognitive and noncognitive parameters. Main Outcome Measures: Change from baseline to last observation carried forward in discrete subscale scores of the Alzheimer's Disease Assessment Scale (ADAS): cognitive (memory, language, praxis) and noncognitive (mood, behavior). Improvement was defined as a decrease of at least 1 point hom baseline; stabilization was defined as no change or a decrease from baseline. Results: Compared with the placebo group, the percentage of patients receiving tacrine whose conditions improved or stabilized was significantly greater for 8 of 11 ADAS-cognitive items (word recall, word recognition, orientation, language production, comprehension, word finding, following commands, ideational praxis) and for the ADAS-noncognitive items: cooperation, delusions, and pacing. Conclusions: Tacrine stabilizes or improves specific behavioral deficits and symptoms in AD. The previous demonstration of tacrine's effect on global cognitive function has been extended by suggesting an association between tacrine therapy and improvements in individual cognitive and noncognitive items of the ADAS. Effects of tacrine in clinical practice might be more accurately and efficiently assessed by measuring individual ADAS cognitive and noncognitive items relevant to individual patient pretreatment clinical status. C1 UNIV WASHINGTON,SCH MED,SEATTLE,WA. PALM BEACH NEUROL GRP,PALM BEACH,FL. WARNER LAMBERT PARKE DAVIS,PARKE DAVIS PHARMACEUT RES DIV,MORRIS PLAINS,NJ 07950. RP Raskind, MA (reprint author), VET AFFAIRS PUGET SOUND HLTH CARE SYST,MENTAL HLTH SERV 116,1600 S COLUMBIA WAY,SEATTLE,WA 98109, USA. RI Sigmund, Wolfgang/B-2856-2008 NR 9 TC 91 Z9 92 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD JUL PY 1997 VL 54 IS 7 BP 836 EP 840 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA XL131 UT WOS:A1997XL13100007 PM 9236571 ER PT J AU Growdon, JH Graefe, K Tennis, M Hayden, D Schoenfeld, D Wray, SH AF Growdon, JH Graefe, K Tennis, M Hayden, D Schoenfeld, D Wray, SH TI Pupil dilation to tropicamide is not specific for Alzheimer disease SO ARCHIVES OF NEUROLOGY LA English DT Article ID DOWNS-SYNDROME AB Background: The extent of pupil dilation after instillation of a dilute tropicamide solution was proposed as a noninvasive neurobiological diagnostic test for Alzheimer disease (AD). Pupils in patients with AD dilated 23% vs only 5% in control subjects. Objective: To determine whether pupil dilation in response to tropicamide distinguishes patients with AD from control subjects without dementia. Methods: There were 50 patients with AD and 51 control subjects; no participant had primary ocular pathological conditions or took drugs that affected cholinergic tone. All participants received 1 drop of 0.01% tropicamide in 1 eye and 1 drop of 0.9% saline solution in the other eye in random order. Pupil measurements were obtained using a pupil and corneal reflection tracking system (RK-426 PC system, ISCAN Inc, Burlington, Mass) that illuminated the eye with a low-level infrared source and measured pupil diameters, fixation, and light level every 16.7 milliseconds during each 30-second measurement. Pupil measurements were obtained from each eye at baseline and 5, 10, 15, and 30 minutes after drop instillation. Results: The increase in pupil size after tropicamide instillation was equal between patients with AD and control subjects. The mean (+/-SD) pupil diameter increased from 4.5+/-1.1 to 5.5+/-1.1 mm after 30 minutes in patients with AD and from 4.7+/-0.9 to 5.8+/-0.9 mm in control subjects. Anisocoria and the mean rate of dilation did not differ between patients with AD and control subjects. Eye color and corneal moisture did not affect these results. The extent of pupil dilation in patients with AD was not related to clinical estimates of dementia severity. Conclusion: Pupil dilation in response to instillation of 0.01% tropicamide is not useful as an antemortem diagnostic test for AD. RP Growdon, JH (reprint author), MASSACHUSETTS GEN HOSP,DEPT NEUROL,15 PARKMAN ST,BOSTON,MA 02114, USA. FU NIA NIH HHS [P50 AG05134] NR 14 TC 22 Z9 22 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 JUL PY 1997 VL 54 IS 7 BP 841 EP 844 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA XL131 UT WOS:A1997XL13100008 PM 9236572 ER PT J AU Guyer, DR Adamis, PA Bird, A Brancato, R Coscas, G Gragoudas, E Yannuzzi, LA OShaughnessy, D Slakter, JS Miller, JW Soubrane, G Buyse, M Melis, C DeRosa, JT Baes, P Bressler, N Bressler, S Alexander, J Cooper, R Javornik, N Orlock, D Hanutsaha, P Chang, A Mott, D Betts, F Smith, H Ward, C Lane, AM Bang, D Finn, S Harmon, D Dow, E Brucker, A DuPont, J Sorenson, J Napoli, J Daly, J Burke, K Bollenbacher, E Folk, J Reddy, C Boldt, C Kimura, AE Griffin, M Gitter, K Newell, K Johnson, M Blodi, B Elner, S Vine, A Jessup, L Jost, B Callanan, D Fish, GE Anderson, T Fogelman, K Klein, M Nolte, S Lewis, ML Rodriguez, B Mieler, W Pulido, J Newman, J Sjaarda, R Glaser, B Murphy, R Thompson, J Donahue, D Nanda, S Kingsley, R Shofner, J Orth, D Larsen, T Schachat, A Petty, B Nesbitt, P Schatz, H McDonald, HR Johnson, R DiAngelo, M Singerman, L Zegarra, H Lichterman, S Sternberg, P Johnson, J Tiedeman, JS Comway, BP Henofer, MJ Williams, G Cumming, K Burgess, D Williams, D Venverloh, S Ambler, J Moss, S Mitchell, P Wang, JJ Stur, M Tittl, M Vogelmuller, M BelfortMattos, R Bonomo, P Farah, ME Cunha, SL Takahashi, W Souza, EC Harvey, PT Fralick, RA Kraus, L Sjoelie, AK Moeller, F Engler, C Sander, B Immonen, I Jaakkola, A Hyyppa, T Koenig, F Beuchaboune, M Hansen, L Janknecht, P Guhlmann, M Kampik, A Scheider, A Ulbig, M Kiraly, A Richard, G Weckerle, P Holz, FG Volcker, HE Yassur, Y Loewenstein, A Rosenblatt, I Avanza, P Cardia, L Boscia, F Ferrari, TM Durante, G Papoff, G deJong, TVM vanSanten, CA CunhaVaz, J Silva, R Bauer, B Sjoeberg, U Agardh, E Matensson, E Pournaras, C Stepanian, E Zografos, L Piquet, B Owens, S Chisholm, I Hill, J Parish, K AF Guyer, DR Adamis, PA Bird, A Brancato, R Coscas, G Gragoudas, E Yannuzzi, LA OShaughnessy, D Slakter, JS Miller, JW Soubrane, G Buyse, M Melis, C DeRosa, JT Baes, P Bressler, N Bressler, S Alexander, J Cooper, R Javornik, N Orlock, D Hanutsaha, P Chang, A Mott, D Betts, F Smith, H Ward, C Lane, AM Bang, D Finn, S Harmon, D Dow, E Brucker, A DuPont, J Sorenson, J Napoli, J Daly, J Burke, K Bollenbacher, E Folk, J Reddy, C Boldt, C Kimura, AE Griffin, M Gitter, K Newell, K Johnson, M Blodi, B Elner, S Vine, A Jessup, L Jost, B Callanan, D Fish, GE Anderson, T Fogelman, K Klein, M Nolte, S Lewis, ML Rodriguez, B Mieler, W Pulido, J Newman, J Sjaarda, R Glaser, B Murphy, R Thompson, J Donahue, D Nanda, S Kingsley, R Shofner, J Orth, D Larsen, T Schachat, A Petty, B Nesbitt, P Schatz, H McDonald, HR Johnson, R DiAngelo, M Singerman, L Zegarra, H Lichterman, S Sternberg, P Johnson, J Tiedeman, JS Comway, BP Henofer, MJ Williams, G Cumming, K Burgess, D Williams, D Venverloh, S Ambler, J Moss, S Mitchell, P Wang, JJ Stur, M Tittl, M Vogelmuller, M BelfortMattos, R Bonomo, P Farah, ME Cunha, SL Takahashi, W Souza, EC Harvey, PT Fralick, RA Kraus, L Sjoelie, AK Moeller, F Engler, C Sander, B Immonen, I Jaakkola, A Hyyppa, T Koenig, F Beuchaboune, M Hansen, L Janknecht, P Guhlmann, M Kampik, A Scheider, A Ulbig, M Kiraly, A Richard, G Weckerle, P Holz, FG Volcker, HE Yassur, Y Loewenstein, A Rosenblatt, I Avanza, P Cardia, L Boscia, F Ferrari, TM Durante, G Papoff, G deJong, TVM vanSanten, CA CunhaVaz, J Silva, R Bauer, B Sjoeberg, U Agardh, E Matensson, E Pournaras, C Stepanian, E Zografos, L Piquet, B Owens, S Chisholm, I Hill, J Parish, K TI Interferon alfa-2a is ineffective for patients with choroidal neovascularization secondary to age-related macular degeneration - Results of a prospective randomized placebo-controlled clinical trial SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID INHIBITION; ALPHA-2A; THERAPY AB Background: Interferon alfa-2a has been shown to be effective as an antiangiogenic agent for several systemic human angiogenic disorders and has shown antiangiogenic activity in the laboratory. Objective: To evaluate the safety and efficacy of interferon alfa-2a for the treatment of choroidal neovascularization secondary to age-related macular degeneration. Methods: A randomized, placebo-controlled, parallel, multicenter double-blind trial was performed at 45 ophthalmic centers worldwide. Four hundred eighty-one patients were randomly assigned to 4 treatment groups: placebo or or interferon alfa-2a (Roferon-A), 1.5, 3.0, or 6.0 million international units (MIU). Visual acuity testing, clinical examination, fluorescein angiography, and indocyanine green angiography were evaluated, with the primary end point being a comparison of the number of patients who experienced a loss of 3 lines or more of vision at 1 year. Results: At 52 weeks, 40 (38%; 95% confidence interval, 29%-48%) of 105 placebo-treated patients had lost at least 3 lines of vision (with 12% unavailable for follow-up), compared with 142 (50%; 95% confidence interval, 44%-55%) of 286 in che 3 active treatment groups combined. The difference in proportions was not statistically significant. However, a pairwise comparison of these proportions for the placebo group vs the group that received interferon alfa-2a, 6 MIU (with 26% unavailable for follow-up), showed a statistically significant difference in favor of the placebo group (P=.02) and a nearly significant difference for the placebo vs the 1.5-MIU group (P=.05) (with 16% unavailable for follow-up), again favoring the placebo group. The 3-MIU group (with 22% unavailable for follow-up) did not show a statistically significant difference in pairwise comparison (P=.48), suggesting that a dose-response relationship was not evident. Conclusion: Interferon alfa-2a provides no benefit as a treatment for choroidal neovascularization secondary to age-related macular degeneration and may be associated with a poorer visual outcome when given at a dose of 6 MIU. However, the absence of a clear dose-response relationship raises the possibility that the observed differences result from chance. C1 COORDINATING CTR,NEW YORK,NY. INT INST DRUG DEV,BRUSSELS,BELGIUM. WILMER READING CTR,PHOTOG FLUORESCEIN ANGIOG READING CTR,BALTIMORE,MD. ICG READING CTR,NEW YORK,NY. HOFFMANN LA ROCHE INC,NUTLEY,NJ 07110. HOFFMANN LA ROCHE INC,STRASBOURG,FRANCE. UNIV PENN,SCHEIE EYE INST,PHILADELPHIA,PA 19104. VITREOUS RETINA MACULA CONSULTANTS NY,NEW YORK,NY. UNIV IOWA HOSP & CLIN,OPHTHALMOL CLIN,IOWA CITY,IA 52242. UNIV MICHIGAN,KELLOGG EYE CTR,ANN ARBOR,MI 48109. TEXAS RETINA ASSOCIATES,DALLAS,TX. CASEY EYE INST,PORTLAND,OR. BASCOM PALMER EYE INST,MIAMI,FL 33136. MED COLL WISCONSIN,INST EYE,MILWAUKEE,WI 53226. RETINA INST MARYLAND,TOWSON,MD. DEAN A MCGEE EYE INST,OKLAHOMA CITY,OK. IRWIN RETINA CTR,HARVEY,IL. JOHNS HOPKINS UNIV HOSP,WILMER EYE INST,BALTIMORE,MD. RETINA ASSOCIATES,CLEVELAND,OH. EMORY UNIV,CTR EYE,ATLANTA,GA 30322. UNIV VIRGINIA,CHARLOTTESVILLE,VA. ASSOCIATED RETINAL CONSULTANTS,ROYAL OAK,MI. BARNES HOSP,ST LOUIS,MO 63110. PRINCESS ALEXANDRA HOSP,WOOLLOONGABBA,QLD 4102,AUSTRALIA. WESTMEAD HOSP,WESTMEAD,NSW 2145,AUSTRALIA. AUGENKLIN,ABT A,VIENNA,AUSTRIA. ESCOLA PAULISTA MED,BR-04023 SAO PAULO,BRAZIL. UNIV SAO PAULO,SCH MED,SAO PAULO,BRAZIL. BONOMO OFTALMOL,SAO PAULO,BRAZIL. UNIV TORONTO,WELLESLEY HLTH CTR,EYE RES INST CANADA,TORONTO,ON,CANADA. AARHUS KOMMUNE HOSP,DK-8000 AARHUS,DENMARK. KAS HERLEV,HERLEV,DENMARK. HELSINKI EYE HOSP,HELSINKI,FINLAND. HOP BELLEVUE,ST ETIENNE,FRANCE. UNIV MUNICH,AUGENKLIN,D-8000 MUNICH,GERMANY. UNIV FREIBURG,AUGENKLIN & KLINIKUM,D-7800 FREIBURG,GERMANY. UNIV HAMBURG,KRANKENHAUS EPPENDORF,AUGENKLIN & POLIKLIN,D-2000 HAMBURG,GERMANY. UNIV HEIDELBERG,AUGENKLIN & POLIKLIN & KLINIKUM,HEIDELBERG,GERMANY. BEILINSON MED CTR,PETAH TIQWA,ISRAEL. UNIV MILAN,HOSP SAN RAFFAELE,DEPT OPHTHALMOL,MILAN,ITALY. INST CLIN OCULIST,BARI,ITALY. NETHERLANDS OPHTHALM RES INST,NL-1100 AC AMSTERDAM,NETHERLANDS. ACAD ZIEKENHUIS,ROTTERDAM,NETHERLANDS. UNIV COIMBRA HOSP,COIMBRA,PORTUGAL. UNIV LUND HOSP,S-22185 LUND,SWEDEN. HOP CANTONAL,GENOA,ITALY. HOP OPHTALM JULES GONIN,LAUSANNE,SWITZERLAND. SOUTHAMPTON EYE INST,SOUTHAMPTON,HANTS,ENGLAND. MOORFIELDS EYE HOSP,DEPT CLIN OPHTHALMOL,LONDON EC1V 2PD,ENGLAND. UNIV PARIS 12,CRETEIL HOSP INTERCOMMUNAL,OPHTHALMOL CLIN,CRETEIL,FRANCE. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,BOSTON,MA. RP Guyer, DR (reprint author), MANHATTAN EYE EAR & THROAT HOSP,LUESTER T MERTZ RETINAL RES LAB,210 E 64TH ST,NEW YORK,NY 10021, USA. RI Silva, Rufino/J-2817-2012 OI Silva, Rufino/0000-0001-8676-0833 NR 21 TC 115 Z9 116 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD JUL PY 1997 VL 115 IS 7 BP 865 EP 872 PG 8 WC Ophthalmology SC Ophthalmology GA XK907 UT WOS:A1997XK90700005 ER PT J AU Rumelt, S Harsh, GR Rubin, PAD AF Rumelt, S Harsh, GR Rubin, PAD TI Giant epidermoid involving 3 cranial bones SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID TEMPORAL BONE AB We describe a patient with an incidental finding of an expansile osteolytic lesion centered in the sphenoid involving 3 cranial bones-frontal, temporal, and sphenoid-and invading the brain parenchyma and orbit, Biopsy demonstrated an epidermoid. The lesion was excised through frontotemporal craniotomy. Despite the benign nature of the tumor, the epidermoid had a destructive pattern of growth. Complete resection was needed to adequately address the inflammatory mass effect of the large lesion. C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,DEPT OPHTHALM PLAST & ORBITAL SURG,BOSTON,MA 02114. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,DEPT NEUROSURG SERV,BOSTON,MA 02115. NR 9 TC 6 Z9 6 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD JUL PY 1997 VL 115 IS 7 BP 922 EP 924 PG 3 WC Ophthalmology SC Ophthalmology GA XK907 UT WOS:A1997XK90700018 PM 9230838 ER PT J AU Compton, CC AF Compton, CC TI Protocol for the examination of specimens from patients with carcinoma of the ampulla of Vater - A basis for checklists SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID PROGNOSTIC FACTORS; INTRADUCTAL CARCINOMA; DUCTAL ECTASIA; PANCREAS; ADENOCARCINOMA; CANCER; TUMORS; PANCREATICODUODENECTOMY; SURVIVAL; ADENOMA AB A protocol for the pathologic examination and reporting of specimens from patients with carcinoma of the ampulla of Vater has been developed by the Cancer Committee of the College of American Pathologists. The protocol incorporates all basic pathology data of diagnostic and prognostic significance appropriate for the treatment of patients with ampullary carcinoma. The purposes of the protocol are to serve as a basis for the development of checklists, as an outline for full narrative reporting, as a basis for research protocols, or as a guide for other types of synoptic or reporting formats. The protocol is stratified to accommodate the surgical procedures usually employed for carcinomas of the ampulla of Vater, including acquisition of cytologic specimens, incisional biopsy, excisional biopsy, and Whipple procedure (pancreaticoduodenectomy, partial or complete, with or without partial gastrectomy). Explanatory notes detailing specific procedures and rationales for documentation of specific pathologic data are included in the protocol. The protocol uses the staging system for carcinoma of the ampulla of Vater defined by the American joint Committee on Cancer and the International Union Against Cancer. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. NR 34 TC 5 Z9 5 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD JUL PY 1997 VL 121 IS 7 BP 673 EP 677 PG 5 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA XL323 UT WOS:A1997XL32300003 PM 9240900 ER PT J AU Rabban, JT Blair, JA Rosen, CL Adler, JN Sheridan, RL AF Rabban, JT Blair, JA Rosen, CL Adler, JN Sheridan, RL TI Mechanisms of pediatric electrical injury - New implications for product safety and injury prevention SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article; Proceedings Paper CT 29th Annual Meeting of the American-Burn-Association CY MAR 19-22, 1997 CL NEW YORK, NY SP Amer Burn Assoc ID CHILDREN; BURNS AB Objectives: To determine age-specific mechanisms of electrical injury in children, to examine product safety regulation of the major sources of electrical injury hazard, and to assess the adequacy of current prevention strategies. Design: Case series of 144 pediatric and adolescent electrical injuries in patients seen in the specialized burn center and tertiary care hospital between 1970 and 1995, examination of Consumer Product Safety Commission product recall reports for electrical injury hazards between 1973 and 1995, and review of the National Electric Code. Results: Eighty-six cases of electrical injuries resulted from low-voltage (<1000-V) exposures, all occurring within the home. In children aged 12 years and younger, household appliance electrical cords and extension cords caused more than 64 (63%) of 102 injuries, whereas wall outlets were responsible for only 14 (15%) of injuries. Fifty-eight cases resulted from high-voltage exposures, accounting for 38 (90%) of 42 injuries in children older than 12 years. No federal safety regulations for electrical cords exist, although voluntary standards have been adopted by many manufacturers. Among 383 consumer products identified by the Consumer Product Safety Commission to be electrical injury hazards, 119 were appliance cords, extension cards, or holiday stringed light sets. Several products numbered more than 1.5 million units in US household distribution prior to the investigation by the Consumer Product Safety Commission. Conclusions: Household electrical cords are the major electrocution hazard for children younger than 12 years, yet no federal safety mandates exist. Despite voluntary standards, noncompliant manufacturers can introduce vast numbers of unsafe cords onto the US household market every year. Conversion of existing voluntary safety guidelines into federally legislated standards may be the most effective intervention against pediatric electrocutions. C1 HARVARD UNIV,SCH MED,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT EMERGENCY MED,DIV EMERGENCY MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,SHRINERS BURNS INST,BOSTON,MA 02114. NR 28 TC 18 Z9 18 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD JUL PY 1997 VL 151 IS 7 BP 696 EP 700 PG 5 WC Pediatrics SC Pediatrics GA XL138 UT WOS:A1997XL13800010 PM 9232044 ER PT J AU Mutton, DL Scremin, AME Barstow, TJ Scott, MD Kunkel, CF Cagle, TG AF Mutton, DL Scremin, AME Barstow, TJ Scott, MD Kunkel, CF Cagle, TG TI Physiologic responses during functional electrical stimulation leg cycling and hybrid exercise in spinal cord injured subjects SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article ID INDIVIDUALS; PARAPLEGIA; DISEASE AB Objectives: (1) To determine if a hybrid exercise (leg plus arm) training program performed immediately after functional electrical stimulation (FES) leg cycle exercise (LCE) training would further improve aerobic capacity when compared with FES leg cycle training alone, and (2) to compare the submaximal responses occurring during both FES-LCE alone and hybrid exercise in the same SCI subjects. Design: Nonrandomized control trial whereby subjects act as their own control. Setting: Outpatient rehabilitation in a primary care hospital, Patients: A volunteer sample (n = 11) of men 20 to 50 years old with complete spinal cord injury, free from cardiovascular and metabolic disease with spasticity. Interventions: Three phases of exercise training: phase I, progressive FES-LCE to 30 minutes of exercise (n = 11); phase II, 35.2 +/- 16.2 sessions of FES-LCE (n = 11); phase III, 41.4 +/- 17.7 30-minute sessions of hybrid exercise in = 8), Main Outcome Measures: (1) Aerobic capacity-a further increase after hybrid exercise when compared with FES-LCE alone; (2) submaximal physiologic parameters (oxygen uptake [(V) over dot O-2], heart rate [HR], blood lactate [BLa-])-measurement of these during constant work rate exercise and a training effect, Results: (V) over dot O-2 (the body's ability to utilize oxygen) significantly improved (p < .05) after both FES-LCE and then further after hybrid training, Hybrid exercise training resulted in significantly (p < .05) greater work rates and (V) over dot O-2 values than both FES-LCE at baseline and training work rates, Conclusion: These subjects demonstrated that hybrid exercise performed twice a week provided sufficient intensity to improve aerobic capacity and provide a medium whereby patients with SCI can burn more calories than via FES-LCE alone. This has important implications for improving the health and fitness levels of individuals with SCI and may ultimately reduce their risk of cardiovascular disease. (C) 1997 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation. C1 W LOS ANGELES VET AFFAIRS MED CTR,PHYS MED & REHABIL SERV 117,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,DEPT MED,LOS ANGELES,CA 90024. HARBOR UCLA MED CTR,DEPT MED,DIV RESP & CRIT CARE PHYSIOL & MED,TORRANCE,CA 90509. UNIV SO CALIF,RANCHO LOS AMIGOS MED CTR,DOWNEY,CA 90242. ALBUQUERQUE VET AFFAIRS MED CTR,PHYS MED & REHABIL SERV,ALBUQUERQUE,NM. UNIV NEW MEXICO,DEPT ORTHOPED,ALBUQUERQUE,NM 87131. NR 25 TC 49 Z9 50 U1 2 U2 10 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD JUL PY 1997 VL 78 IS 7 BP 712 EP 718 DI 10.1016/S0003-9993(97)90078-2 PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA XK216 UT WOS:A1997XK21600006 PM 9228873 ER PT J AU Bischof, JC Ryan, CM Tompkins, RG Yarmush, ML Toner, M AF Bischof, JC Ryan, CM Tompkins, RG Yarmush, ML Toner, M TI Ice formation in isolated human hepatocytes and human liver tissue SO ASAIO JOURNAL LA English DT Article ID CRYOPRESERVATION; WATER; PERMEABILITY; TRANSPORT; SLICES; CELLS; RAT AB Cryopreservation of isolated cells and tissue slices of human liver is required to furnish extracorporeal bioartificial liver devices with a ready supply of hepatocytes, and to create in vitro drug metabolism and toxicity models. Although both the bioartificial liver and many current biotoxicity models are based on reconstructing organ functions from single isolated hepatocytes, tissue slices offer an in vitro system that may more closely resemble the in vivo situation of the cells because of cell-cell and cell-extracellular matrix interactions. However, successful cryopreservation of both cellular and tissue level systems requires an increased understanding of the fundamental mechanisms involved in the response of the liver and its cells to freezing stress. This study investigates the biophysical mechanisms of water transport and intracellular ice formation during freezing in both isolated human hepatocytes and whole liver tissue. The effects of cooling rate on individual cells were measured using a cryomicroscope. Biophysical parameters governing water transport (L-pg = 2.8 mu m/min-atm and E-Lp = 79 kcal/mole) and intracellular heterogeneous ice nucleation (Omega(het) = 1.08 X 10(9)m(-2)s(-1) and K-het = 1.04 X 10(9) K-5) were determined. These parameters were then incorporated into a theoretical Krogh cylinder model developed to simulate water transport and ice formation in intact liver tissue. Model simulations indicated that the cellular compartment of the Krogh model maintained more water than isolated cells under the same freezing conditions. As a result, intracellular ice nucleation occurred at lower cooling rates in the Krogh model than in isolated cells. Furthermore, very rapid cooling rates (1000 degrees C/min) showed a depression of heterogeneous nucleation and a shift toward homogeneous nucleation. The results of this study are in qualitative agreement with the findings of a previous experimental study of the response to freezing of intact human liver. C1 MASSACHUSETTS GEN HOSP,CTR ENGN MED & SURG SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,SHRINERS BURNS INST,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. FU NIDDK NIH HHS [DK 46270] NR 25 TC 18 Z9 18 U1 0 U2 5 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1058-2916 J9 ASAIO J JI Asaio J. PD JUL-AUG PY 1997 VL 43 IS 4 BP 271 EP 278 DI 10.1097/00002480-199707000-00003 PG 8 WC Engineering, Biomedical; Transplantation SC Engineering; Transplantation GA XL743 UT WOS:A1997XL74300003 PM 9242939 ER PT J AU BenoreParsons, M Ayoub, MA AF BenoreParsons, M Ayoub, MA TI Presence of RNase A causes aberrant DNA band shifts SO BIOTECHNIQUES LA English DT Article ID BINDING PROTEIN; RIBONUCLEASE AB RNase A, which is routinely added during DNA purification to reduce contaminating RNA, causes shifting of DNA bands in agarose gels. DNA band sizes on agarose gels increase as much as 10%-20% when RNase A is present. The low concentrations of RNase A typically used to purify DNA cause shifting of select DNA bands, in contrast to higher concentrations of RNase A where all bands are shifted and smeared. The binding of RNase A to the DNA is specific and the degree of the shift varies; not all DNA bands are retarded, and the deviation is more pronounced in certain buffers. Other proteins, such as bovine serum albumin or proteinase K, do not induce DNA band shift, suggesting the interaction is specific. The binding of RNase A to DNA is reversible. The formation of RNase:DNA complexes may affect experiments involving DNA:protein interactions such as gel shift, footprinting and filter binding assays. Researchers performing DNA characterization from miniprep protocols should be aware that RNase may cause the apparent sizes of DNA fragments to be altered and obscure the presence of very small cloned fragments. C1 HARVARD UNIV,JOSLIN DIABET CTR,BOSTON,MA 02115. RP BenoreParsons, M (reprint author), UNIV MICHIGAN,DEPT NAT SCI,4901 EVERGREEN RD,DEARBORN,MI 48128, USA. FU NIDDK NIH HHS [1R15 DK43949] NR 12 TC 8 Z9 10 U1 0 U2 2 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD JUL PY 1997 VL 23 IS 1 BP 128 EP 131 PG 4 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XK261 UT WOS:A1997XK26100027 PM 9232244 ER PT J AU Urashima, M Teoh, G Chauhan, D Hoshi, Y Ogata, A Treon, SP Schlossman, RL Anderson, KC AF Urashima, M Teoh, G Chauhan, D Hoshi, Y Ogata, A Treon, SP Schlossman, RL Anderson, KC TI Interleukin-6 overcomes p21 WAF1 upregulation and G1 growth arrest induced by dexamethasone and interferon-gamma in multiple myeloma cells SO BLOOD LA English DT Article ID MARROW STROMAL CELLS; MALIGNANT PLASMA-CELLS; GLUCOCORTICOID RECEPTOR; DOWN-REGULATION; C-JUN; LINES; EXPRESSION; APOPTOSIS; SECRETION; GENE AB Interleukin-6 (IL-6) is a growth factor for multiple myeloma (MM) cells and can inhibit MM cell apoptosis. Our recent studies show that IL-6 facilitates MM cell growth via phosphorylation of retinoblastoma protein (PRE); however, the effects of IL-6 on those cyclins, cyclin-dependent kinases (CDKs), and CDK inhibitors (CDIs) that are known to regulate phosphorylation of pRB have not been defined in MM cells. In the present report, we cultured MM cell lines and patient cells with IL-6 and/or dexamethasone (Dex) and characterized changes in cell cycle; expression and association of cyclins, CDKs, and CDIs; and phosphorylation of pRB. Dex induced G1 growth arrest in MM cells, whereas IL-6 facilitated G1 to S phase transition; moreover, the effect of Dex was blocked by IL-6. p21WAF1 (p21) protein was constitutively expressed in the majority of MM cells independent of the status of p53. Ifs expression was upregulated by Dex and downregulated by IL-6; again, IL-6 inhibited the increase in p21 triggered by Dex. These alterations in p21 expression in MM cells were associated with changes in p21 binding to CDK2, CDK4, and CDK6; CDK2, CDK4, and CDK6 kinase activities; and phosphorylation of pRB. In contrast, expression of G1 cell cycle regulatory proteins, including p27KIP1, cyclin D2, and cyclin E, was not altered in MM cells cultured with Dex and/or IL-6. Finally, interferon-gamma (IFN-gamma) also induced G1 growth arrest and upregulated p21 protein expression; as with Dex, affects of IFN-gamma were inhibited by IL-6. Our results therefore show that changes in cell cycle distribution in MM cells triggered by Dex, IL-6, and IFN-gamma correlate with changes in p21 protein expression and implicate p21 in the coupling of Dex-, IL-6-, and IFN-gamma-related signals to G1 cell cycle regulation in MM cells. (C) 1997 by The American Society of Hematology. C1 DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. JIKEI UNIV,SCH MED,DEPT PEDIAT,TOKYO,JAPAN. FU NCI NIH HHS [CA 50947] NR 47 TC 84 Z9 86 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JUL 1 PY 1997 VL 90 IS 1 BP 279 EP 289 PG 11 WC Hematology SC Hematology GA XH428 UT WOS:A1997XH42800033 PM 9207463 ER PT J AU Li, YP Andersen, J Zelent, A Rao, S Paietta, E Tallman, MS Wiernik, PH Gallagher, RE AF Li, YP Andersen, J Zelent, A Rao, S Paietta, E Tallman, MS Wiernik, PH Gallagher, RE TI RAR alpha 1/RAR alpha 2-PML mRNA expression in acute promyelocytic leukemia cells: A molecular and laboratory-clinical correlative study SO BLOOD LA English DT Article ID ACID RECEPTOR-ALPHA; RAR-ALPHA; RETINOIC ACID; T(15-17) TRANSLOCATION; FUSION GENE; PML; ISOFORMS; TRANSCRIPTS; PROTEINS; APL AB In addition to the major fusion gene PML-RAR alpha, the t(15;17) in acute promyelocytic leukemia (APL) produces the reciprocal fusion gene RAR alpha-FML. To determine the scope of RAR alpha-containing mRNA expression in APL cells, we tested PML-RAR alpha-positive APL cells for the presence of mRNAs initiated from two distinct RAR alpha gene promoters, alpha 1 and alpha 2. From the normal allele, both RAR alpha 1 and RAR alpha 2 mRNAs were expressed in all APL cases (N = 24), From the translocated allele, RAR alpha 1-PML mRNA was expressed in 77% and RAR alpha 2-PML mRNA in 28% of cases (N = 98). RAR alpha 2-PML mRNA was not observed in the absence of RAR alpha 1-PML mRNA, There was no association between RAR alpha 1-PML or RAR alpha 2-PML mRNA expression and the type of PML-RAR alpha mRNA formed by either 5' or 3' breaksites in the PML gene. RAR alpha 1-PML mRNAs and RAR alpha 2-PML mRNAs from 5' PML breaksite cases coded for full-length RAR alpha-PML proteins but RAR alpha 2-PML mRNAs from 3' PML breaksite cases encoded a truncated RAR alpha 2 peptide. RAR alpha 1-alpha 2-PML mRNA expression was not associated with differences in APL cell sensitivity to all-trans retinoic acid(tRA)-induced differentiation in vitro or in clinical outcome after tRA or chemotherapy induction therapy (protocol E2491), Our analysis indicated that RAR alpha 1/alpha 2-PML mRNA expression markedly differs from normal RAR alpha 1/alpha 2 mRNA expression, that the difference in RAR alpha 1-PML and RAR alpha 2-PML mRNA expression frequency is primarily related to the genomic separation of the RAR alpha 1 and RAR alpha P coding exons, and that variations in RAR alpha 1/alpha 2-PML mRNA expression likely have no clinically relevant function in APL cells. (C) 1997 by The American Society of Hematology. C1 MONTEFIORE MED CTR,ALBERT EINSTEIN CANC CTR,DEPT ONCOL,BRONX,NY 10467. DANA FARBER CANC INST,BOSTON,MA 02115. NORTHWESTERN UNIV,SCH MED,CHICAGO,IL. INST CANC RES,LEUKAEMIA RES FUND CTR,LONDON SW3 6JB,ENGLAND. RI Zelent, Arthur/B-3532-2009 FU NCI NIH HHS [CA21115, CA23318, CA56771] NR 21 TC 40 Z9 41 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JUL 1 PY 1997 VL 90 IS 1 BP 306 EP 312 PG 7 WC Hematology SC Hematology GA XH428 UT WOS:A1997XH42800036 PM 9207466 ER PT J AU Kay, NE Leong, T Kyle, RA Greipp, P Billadeau, D VanNess, B Bone, N Oken, MM AF Kay, NE Leong, T Kyle, RA Greipp, P Billadeau, D VanNess, B Bone, N Oken, MM TI Circulating blood B cells in multiple myeloma: Analysis and relationship to circulating clonal cells and clinical parameters in a cohort of patients entered on the Eastern Cooperative Oncology Group phase III E9486 clinical trial SO BLOOD LA English DT Article ID MONOCLONAL LYMPHOCYTES-B; PERIPHERAL-BLOOD; REARRANGEMENT; QUANTITATION; EXPRESSION; GAMMOPATHY; POPULATION; CHAIN AB Recent analyses of circulating blood B cells in myeloma have generated controversy concerning the exact levels of these cells and whether they may represent circulating clonal tumor B cells. Previous reports suggested that CD19(+) B cells are markedly increased in myeloma patients and that this population shares clonotypic rearrangements with the malignant plasma cell. We studied the numbers of CD19(+) B cells by flow cytometry in previously untreated newly diagnosed myeloma patients in Eastern Cooperative Oncology Group (ECOG) phase III trial E9486. There were 628 patients who were eligible for the clinical protocol E9486, but of these 521 were also entered on the companion laboratory study (E9487) and had CD19 data. In comparison with normal controls, the myeloma patients exhibited a marked heterogeneity in the number of circulating CD19(+) B cells as detected by flow cytometry. Approximately 20% of patients had significantly increased levels of circulating CD19(+) B cells. However, the total CD19(+) blood population from myeloma was not significantly different from the median of age-matched, normal controls. Analysis of CD19(+) blood cells in relationship to circulating clonal cells was done in 13 myeloma patients using a clonotypic, quantitative allele-specific oligonucleotide-polymerase chain reaction (PCR) assay. No correlation was found between the numbers of CD19(+) B cells (range, 5% to 51%) and PCR estimates of the number of clonal cells in the peripheral blood (range, .009% to 3.6%). Low CD19(+) B-cell level (<125 mu L) was associated with clinical stage III (P = .033). A significant relationship exists between higher levels (greater than or equal to 125/mu L) of CD19 cells and longer overall survival (P < .0001). In addition, high CD19 levels also predicted a clinical response and longer event-free survival. There was a strong inverse association between the level of CD19 values at diagnosis and infections within the first 2 months of diagnosis. Importantly, the number of deaths related to infections was significantly greater in the low versus high CD19 group (P < .0202). Also, CD19 is an independent prognostic factor in addition to plasma cell labeling indices, beta(2)-microglobulin, hemoglobin, and plasmablastic morphology. Patients with infections were more likely to have low levels of CD19(+) cells. In summary, higher CD19(+) cell levels are a favorable prognostic sign with no apparent relationship to circulating tumor cells. In addition, this analysis strongly suggests that low peripheral blood levels of CD19(+) cells are an adverse prognostic sign in myeloma. The CD19(+) cell levels in myeloma patients is an important parameter in the overall assessment of these patients. (C) 1997 by The American Society of Hematology. C1 UNIV KENTUCKY,MED CTR,DEPT MED,LEXINGTON,KY 40536. DANA FARBER CANC INST,DIV BIOSTAT,BOSTON,MA 02115. MAYO CLIN,DIV HEMATOL,ROCHESTER,MN. UNIV MINNESOTA,DEPT BIOCHEM,MINNEAPOLIS,MN 55455. UNIV MINNESOTA,INST HUMAN GENET,MINNEAPOLIS,MN 55455. VIRGINIA PIPER CANC INST,MINNEAPOLIS,MN. FU NCI NIH HHS [CA 18653, CA 28818, CA 15947] NR 23 TC 45 Z9 46 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 JUL 1 PY 1997 VL 90 IS 1 BP 340 EP 345 PG 6 WC Hematology SC Hematology GA XH428 UT WOS:A1997XH42800040 PM 9207470 ER PT J AU Denning, GM Leidal, KG Holst, VA Iyer, SS Pearson, DW Clark, JR Nauseef, WM Clark, RA AF Denning, GM Leidal, KG Holst, VA Iyer, SS Pearson, DW Clark, JR Nauseef, WM Clark, RA TI Calreticulin biosynthesis and processing in human myeloid cells: Demonstration of signal peptide cleavage and N-glycosylation SO BLOOD LA English DT Article ID CALCIUM-BINDING PROTEIN; ENDOPLASMIC-RETICULUM PROTEINS; MUSCLE SARCOPLASMIC-RETICULUM; RO/SS-A AUTOANTIGEN; HIGH-AFFINITY; GENE-EXPRESSION; MOLECULAR-CLONING; CA2+ BINDING; HL-60 CELLS; RAT-LIVER AB Calreticulin is a soluble endoplasmic reticulum protein comprising the major storage reservoir for inositol trisphosphate-releasable calcium. Although its highly conserved primary structure and a wide range of functions have been well described, less attention has been paid to its biosynthesis, particularly in human tissues. We report analyses of synthesis, proteolytic processing and glycosylation of human calreticulin, In both HL-60 and PLB-985 myeloid cell lines calreticulin was immunoprecipitated as a single 60-kD species without evidence of precursor forms. However, in vitro cell-free synthesis produced a 62-kD primary translation product, which in the presence of microsomal membranes, was processed by cotranslational signal peptide cleavage to a 60-kD species that comigrated with mature calreticulin produced in myeloid cells, Neither tunicamycin treatment of the cells nor endoglycosidase digestion of calreticulin resulted in any forms other than the 60-kD protein on sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis, suggesting that the potential site for N-glycosylation at asparagine-327 was unmodified, However, oxidative derivatization of carbohydrate components with digoxigenin showed that human calreticulin produced in either HL-60 cells or Sf9 insect cells is glycosylated, indicating that glycosylated and nonglycosylated human calreticulin have indistinguishable electrophoretic mobilities, Direct measurement by phenol-H2SO4 confirmed the presence of carbohydrate on recombinant human calreticulin, These data show that human myeloid calreticulin undergoes cotranslational signal peptide cleavage and posttranslational N-linked glycosylation, Although glycosylation of calreticulin has been shown in rat liver and bovine liver and brain, it has been reported to be lacking in other tissues including human lymphocytes. (C) 1997 by The American Society of Hematology. C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. DEPT VET AFFAIRS MED CTR,DEPT MED,IOWA CITY,IA 52242. UNIV IOWA,IOWA CITY,IA. S TEXAS VET HLTH CARE SYST,AUDIE L MURPHY DIV,DEPT MED,SAN ANTONIO,TX. FU BLRD VA [I01 BX000513] NR 49 TC 29 Z9 30 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JUL 1 PY 1997 VL 90 IS 1 BP 372 EP 381 PG 10 WC Hematology SC Hematology GA XH428 UT WOS:A1997XH42800043 PM 9207473 ER PT J AU Tang, DC Ebb, D Hardison, RC Rodgers, GP AF Tang, DC Ebb, D Hardison, RC Rodgers, GP TI Restoration of the CCAAT box or insertion of the CACCC motif activate delta-globin gene expression SO BLOOD LA English DT Article ID KRUPPEL-LIKE FACTOR; HUMAN BETA-GLOBIN; TRANSCRIPTION FACTOR; DNA INTERACTIONS; HEMOGLOBIN-F; FACTOR EKLF; CELLS; THALASSEMIA; SEQUENCE; POLYMERIZATION AB Hemoglobin A(2) (HbA(2)), which contains delta-globin as its non-alpha-globin, represents a minor fraction of the Hb found in normal adults. It has been shown recently that HbA(2) is as potent as HbF in inhibiting intracellular deoxy-HbS polymerization, and its expression is therefore relevant to sickle cell disease treatment strategies. To elucidate the mechanisms responsible for the low-level expression of the delta-globin gene in adult erythroid cells, we first compared promoter sequences and found that the delta-globin gene differs from the beta-globin gene in the absence of an erythroid Kruppel-like factor (EKLF) binding site, the alteration of the CCAAT box to CCAAC, and the presence of a GATA-1 binding site. Second, serial deletions of the human delta-globin promoter sequence fused to a luciferase (LUC) reporter gene were transfected into K562 cells. We identified both positive and negative regulatory regions in the 5' flanking sequence, Furthermore, a plasmid containing a single base pair (bp) mutation in the CCAAC box of the delta promoter, restoring the CCAAT box, caused a 5.6-fold and 2.4-fold (P < .05) increase of LUC activity in transfected K562 cells and MEL cells, respectively, in comparison to the wild-type delta promoter. A set of substitutions that create an EKLF binding site centered at -85 bp increased the expression by 26.8-fold and 6.5-fold (P < .05) in K562 and MEL cells, respectively. These results clearly demonstrate that the restoration of either an EKLF binding site or the CCAAT box can increase delta-globin gene expression, with potential future clinical benefit. (C) 1997 by The American Society of Hematology. C1 NIDDK,BIOL CHEM LAB,NIH,BETHESDA,MD 20892. MASSACHUSETTS GEN HOSP,DEPT PEDIAT,BOSTON,MA 02114. PENN STATE UNIV,DEPT BIOCHEM & MOL BIOL,UNIVERSITY PK,PA 16802. RI Hardison, Ross/G-1142-2010 OI Hardison, Ross/0000-0003-4084-7516 FU NIDDK NIH HHS [DK27635]; NLM NIH HHS [LM057733, LM05110] NR 28 TC 23 Z9 24 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 JUL 1 PY 1997 VL 90 IS 1 BP 421 EP 427 PG 7 WC Hematology SC Hematology GA XH428 UT WOS:A1997XH42800049 PM 9207479 ER PT J AU Chan, CY Molrine, DC Antin, JH Wheeler, C Guinan, EC Weinstein, HJ Phillips, NR McGarigle, C Harvey, S Schnipper, C Ambrosino, DM AF Chan, CY Molrine, DC Antin, JH Wheeler, C Guinan, EC Weinstein, HJ Phillips, NR McGarigle, C Harvey, S Schnipper, C Ambrosino, DM TI Antibody responses to tetanus toxoid and Haemophilus influenzae type b conjugate vaccines following autologous peripheral blood stem cell transplantation (PBSCT) SO BONE MARROW TRANSPLANTATION LA English DT Article DE peripheral blood stem cell transplantation; immunization, active; vaccines, conjugate; vaccines, protein ID BONE-MARROW TRANSPLANTATION; HIGH-DOSE CHEMOTHERAPY; COLONY-STIMULATING FACTOR; PROGENITOR CELLS; HEMATOPOIETIC ENGRAFTMENT; RECONSTITUTION; DISEASE; COLLECTIONS; CHILDREN; RECOVERY AB Accelerated granulocyte and platelet recovery following peripheral blood stem cell transplantation (PBSCT) are well documented, We hypothesize that functional immunity may also be enhanced in PBSCT and performed a phase II trial of immunizations in patients with lymphoma undergoing autologous transplantation with peripheral blood stem cells or bone marrow, Seventeen BMT and 10 PBSCT recipients were immunized at 3, 6, 12, and 24-months post-transplantation with Haemophilus influenza type b (HIB)-conjugate and tetanus toroid (TT) vaccines, IgG anti-HIB and anti-TT antibody concentrations were measured and compared between the two groups, Geometric mean IgG anti HIB antibody concentrations were significantly higher for PBSCT recipients compared to BMT recipients at 24 months post-transplantation (11.3 mu g/ml vs 0.93 mu g/ml, P = 0.051) and following the 24 month immunization (66.2 mu g/ml vs 1.30 mu g/ml, P = 0.006), Similar results were noted for IgG anti-TT antibody with significantly higher geometric mean antibody concentrations in the PBSCT group at 24 months post-transplantation (182 mu g/ml vs 21.6 mu g/ml, P = 0.039), Protective levels of total anti-HIB antibody were achieved earlier in PBSCT recipients compared with those of BMT recipients, PBSCT recipients had higher antigen-specific antibody concentrations following HIB and TT immunizations, These results suggest enhanced recovery of humoral immunity in PBSCT recipients and earlier protection against HIB with immunization. C1 DANA FARBER CANC INST,INFECT DIS LAB,BOSTON,MA 02115. DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DIV HEMATOL ONCOL,BOSTON,MA 02115. BETH ISRAEL HOSP,DIV HEMATOL ONCOL,BOSTON,MA 02215. FU NCI NIH HHS [CA01730, CA39542]; PHS HHS [A129623] NR 29 TC 8 Z9 8 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD JUL PY 1997 VL 20 IS 1 BP 33 EP 38 DI 10.1038/sj.bmt.1700843 PG 6 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA XK233 UT WOS:A1997XK23300006 PM 9232253 ER PT J AU Mendez, MF Cherrier, MM Perryman, KM AF Mendez, MF Cherrier, MM Perryman, KM TI Differences between Alzheimer's disease and vascular dementia on information processing measures SO BRAIN AND COGNITION LA English DT Article ID MULTIPLE LACUNAR INFARCTS; CLINICAL-DIAGNOSIS; REACTION-TIME; LESIONS AB This study evaluated information processing differences between 30 vascular dementia (VaD) patients, 30 Alzheimer's disease (AD) patients, and 30 normal elderly (NE) controls. They were administered a complex reaction time test, a continuous performance test (CPT), and a neuropsychological battery. Compared to NE, both dementia groups had significantly slower motor reaction times and made more errors on the CPT. Compared to AD patients, the VaD patients were slower in stimulus categorization time and had increasing omission errors and persistent commission errors throughout the CPT trial. VaD, which usually includes frontal-subcortical circuit injury, can impair mental speed and stimulus response initiation. (C) 1997 Academic Press. C1 UNIV CALIF LOS ANGELES,DEPT NEUROL,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,DEPT BIOBEHAV SCI,LOS ANGELES,CA 90024. RP Mendez, MF (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,NEUROBEHAV UNIT 691 116AF,13001 WILSHIRE BLVD,LOS ANGELES,CA 90073, USA. NR 36 TC 37 Z9 38 U1 2 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0278-2626 J9 BRAIN COGNITION JI Brain Cogn. PD JUL PY 1997 VL 34 IS 2 BP 301 EP 310 DI 10.1006/brcg.1997.0923 PG 10 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA XH668 UT WOS:A1997XH66800009 PM 9220093 ER PT J AU Hayashi, Y Ueki, K Waha, A Wiestler, OD Louis, DN vonDeimling, A AF Hayashi, Y Ueki, K Waha, A Wiestler, OD Louis, DN vonDeimling, A TI Association of EGFR gene amplification and CDKN2 (p16/MTS1) gene deletion in glioblastoma multiforme SO BRAIN PATHOLOGY LA English DT Article ID GROWTH-FACTOR-RECEPTOR; MALIGNANT GLIOMA; APOPTOSIS; PATHWAYS; TUMORS; CELLS AB Glioblastoma multiforme (GEM) can be divided into genetic subsets: approximately one-third of GEM, primarily in older adults, have EGFR amplification; another one-third, primarily in younger adults, have TP53 mutation, The majority of GEM also have homozygous deletions of the CDKN2 (p16/MTS1) gene, resulting in cell cycle deregulation and elevated proliferation indices, We evaluated the relationship between CDKN2 deletions and the GEM subsets as defined by EGFR amplification or TP53 mutation in 70 GBM. Twenty-eight cases (40%) had EGFR amplification, 21 (30%) had TP53 mutation, and 21 (30%) had neither change, CDKN2 deletions were present in 36 (51%) GEM. Of the 28 GEM with EGFR amplification, 20 (71%) had CDKN2 deletion (p = 0.0078), The remaining 16 cases with CDKN2 loss were divided between GEM with TP53 mutations (6 cases) and GEM with neither EGFR amplification nor TP53 mutation (10 cases), Thus, CDKN2 deletions occur twice as commonly in GEM with EGFR amplification (71%) than in GEM with TP53 mutation (29%), CDKN2 deletions occurred in GEM from patients somewhat older than those patients with GEM lacking CDKN2 deletion (mean age 53 vs, 48 years), Specifically among GEM with EGFR amplification, those with CDKN2 deletions also occurred in patients slightly older than those few GEM without CDKN2 deletions (mean age 55 vs, 51 years), The presence of CDKN2 deletions in most GEM with EGFR amplification and in generally older patients may provide one explanation for the potentially more aggressive nature of such tumors. C1 MASSACHUSETTS GEN HOSP EAST,MOL NEUROONCOL LAB,CHARLESTOWN,MA 02129. MASSACHUSETTS GEN HOSP EAST,DEPT PATHOL NEUROPATHOL,CHARLESTOWN,MA 02129. UNIV KLINIKEN BONN,INST NEUROPATHOL,D-53105 BONN,GERMANY. RI Waha, Andreas/J-2950-2014; von Deimling, Andreas/F-7774-2013 OI von Deimling, Andreas/0000-0002-5863-540X FU NCI NIH HHS [CA57683] NR 29 TC 105 Z9 107 U1 0 U2 0 PU INT SOC NEUROPATHOLOGY PI PITTSBURGH PA 200 LOTHROP ST A506, PITTSBURGH, PA 15213 SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD JUL PY 1997 VL 7 IS 3 BP 871 EP 875 DI 10.1111/j.1750-3639.1997.tb00890.x PG 5 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA XF769 UT WOS:A1997XF76900003 PM 9217972 ER PT J AU Stone, ME AF Stone, ME TI Reference services for the underserved - Zipkowitz,F SO BULLETIN OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Book Review RP Stone, ME (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU MEDICAL LIBRARY ASSOC PI CHICAGO PA STE 300, 6 N MICHIGAN AVE, CHICAGO, IL 60602 SN 0025-7338 J9 B MED LIBR ASSOC JI Bull. Med. Libr. Assoc. PD JUL PY 1997 VL 85 IS 3 BP 315 EP 315 PG 1 WC Information Science & Library Science SC Information Science & Library Science GA XU092 UT WOS:A1997XU09200018 ER PT J AU Lees, S Capel, M Hukins, DWL Mook, HA AF Lees, S Capel, M Hukins, DWL Mook, HA TI Effect of sodium chloride solutions on mineralized and unmineralized turkey leg tendon SO CALCIFIED TISSUE INTERNATIONAL LA English DT Article DE collagen; saline solutions; X-ray diffraction; neutron diffraction; equatorial diffraction spacing ID X-RAY-DIFFRACTION; BONE AB Previous studies showed that the equatorial diffraction spacing of the collagen molecules in mineralized tissues decreases when the tissue is dried and that the spacing in totally dried tissue is about the same (1.1 nm) whether mineralized or not. Here we report that spacing decreases were observed in both mineralized and unmineralized turkey leg tendon after soaking in various sodium chloride solutions up to 4.0 M concentration. The effect was seen by X-ray diffraction as well as by neutron diffraction. No effect was seen in turkey leg tendon soaked in 3.0 M ethylene glycol solution. The spacing in unmineralized tissue decreased from 1.459 +/- 0.011 nn in 0.15 M saline to 1.403 +/- 0.025 nm in 1.5 M saline, a change of 0.056 +/- 0.03 nm or 3.84%. In mineralized turkey leg tendon the corresponding spacings were 1.387 +/- 0.012 and 1.321 +/- 0.019 nm, a change of 0.046 +/- 0.02 nm or 3.4%. No significant dimensional change was noted in the thickness even though the equatorial diffraction spacing decreased by 3.4%. Electron microscopy showed the collagen fibrils within the mineralized turkey leg tendon to be surrounded by highly mineralized material, Presumably the composition of the extrafibrillar material is different from the intrafibrillar and therefore the extrafibrillar material is a different kind of composite. if it is assumed that the extrafibrillar material does not change dimensions significantly, then the collagen molecules in the fibrils can be mobile within the dimensionally stable cage-like structure. C1 BROOKHAVEN NATL LAB,UPTON,NY 11973. UNIV ABERDEEN,DEPT BIOMED PHYS & BIOENGN,ABERDEEN AB9 2ZD,SCOTLAND. OAK RIDGE NATL LAB,DIV SOLID STATE,OAK RIDGE,TN 37830. RP Lees, S (reprint author), FORSYTH DENT CTR,140 FENWAY,BOSTON,MA 02115, USA. NR 12 TC 3 Z9 4 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0171-967X J9 CALCIFIED TISSUE INT JI Calcif. Tissue Int. PD JUL PY 1997 VL 61 IS 1 BP 74 EP 76 DI 10.1007/s002239900298 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XE921 UT WOS:A1997XE92100017 PM 9192518 ER PT J AU GarciaClosas, M Kelsey, KT Wiencke, JK Xu, XP Wain, JC Christiani, DC AF GarciaClosas, M Kelsey, KT Wiencke, JK Xu, XP Wain, JC Christiani, DC TI A case-control study of cytochrome P450 1A1, glutathione S-transferase M1, cigarette smoking and lung cancer susceptibility (Massachusetts, United States) SO CANCER CAUSES & CONTROL LA English DT Article DE cytochrome P450; genotype; glutathione transferases; lung neoplasm; smoking; United States ID GSTM1 NULL GENOTYPE; SQUAMOUS-CELL CARCINOMA; GENETIC SUSCEPTIBILITY; JAPANESE POPULATION; CYP1A1 GENE; POLYMORPHISMS; RISK; MU; ASSOCIATION; INDUCIBILITY AB Cytochrome P450 1A1 (CYP1A1) and glutathione S-transferase M1 (GSTM1) genetic polymorphisms are involved in the activation and detoxification of chemical carcinogens found in tobacco smoke; thus they may influence host susceptibility to lung cancer, In this study at Massachusetts General Hospital (Boston, MA, USA) of 416 cases and 446 controls (mostly White) we evaluated the association between the CYP1A1 MspI and GSTM1 polymorphisms and lung cancer risk, and their interaction with cigarette smoke. The CYP1A1 MspI heterozygous genotype was present in 18 percent of cases and 16 percent of controls, and one percent of cases and controls were CYP1A1 MspI homozygous variant, The GSTM1 null genotype was detected in 54 percent of cases and 52 percent of controls, After adjusting for age, gender, pack-years of smoking, and years since quitting smoking, while neither the CYP1A1 MspI heterozygous genotype alone nor the GSTM1 null genotype alone were associated with a significant increase in lung cancer risk, having both genetic traits was associated with a twofold increase in risk (95 percent confidence interval [CI] = 1.0-3.4). Our data did not provide enough evidence for a substantial modification of the effect of pack-years on lung cancer risk by the CYP1A1 MspI and GSTM1 genotypes, However, limitations of our study preclude a conclusion about this potential interaction. C1 NCI,DIV CANC EPIDEMIOL & GENET,BETHESDA,MD 20892. HARVARD UNIV,SCH PUBL HLTH,DEPT ENVIRONM HLTH,OCCUPAT HLTH PROGRAM,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,BOSTON,MA 02115. UNIV CALIF SAN FRANCISCO,DEPT EPIDEMIOL & BIOSTAT,LAB MOL EPIDEMIOL,SAN FRANCISCO,CA 94143. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,THORAC SURG UNIT,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,PULM & CRIT CARE UNIT,BOSTON,MA. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. RI Kelsey, Karl/I-1252-2014 FU NIEHS NIH HHS [ES00002, ES/CA P01 06409] NR 41 TC 78 Z9 79 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD JUL PY 1997 VL 8 IS 4 BP 544 EP 553 DI 10.1023/A:1018481910663 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA XM629 UT WOS:A1997XM62900002 PM 9242469 ER PT J AU Colditz, GA Cannuscio, CC Frazier, AL AF Colditz, GA Cannuscio, CC Frazier, AL TI Physical activity and reduced risk of colon cancer: implications for prevention SO CANCER CAUSES & CONTROL LA English DT Review DE colon cancer; physical activity; prevention ID LARGE-BOWEL CANCER; COLORECTAL-CANCER; UNITED-STATES; BREAST-CANCER; OCCUPATIONAL EXERCISE; CIGARETTE-SMOKING; DIETARY FACTORS; PUBLIC-HEALTH; ADENOMA; WOMEN AB This paper reviews the consistency of the relation between increased physical activity and reduced risk of colon cancer, estimates the potential prevention benefit from increasing population levels of physical activity, and considers social strategies to increase activity levels. The published literature was reviewed systematically and supplemented by MEDLINE searches through March 1997. Studies that reported a measure of physical activity and outcomes of colon cancer or colorectal cancer were included. We excluded the first report of a study that was expanded subsequently by extended follow-up, and any study that did not report the methods for measurement of physical activity. Data were extracted including details on study size, methods of classifying physical activity, and outcomes. A consistent inverse relation was observed such that increased physical activity was associated with reduced risk of colon cancer. About a 50 percent reduction in incidence was observed among those with the highest level of activity across numerous studies that used different measures of activity (occupational or leisure-time activity). This association persisted in studies using multivariate analyses to control for diet and other known or suspected risk factors for colon cancer. Risk reduction was attenuated in those studies that combined colon and rectal cancer. This review indicates that greater attention should be placed on social strategies to increase physical activity as a means of preventing colon cancer. C1 BRIGHAM & WOMENS HOSP,DEPT MED,CHANNING LAB,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,CTR CANC PREVENT,BOSTON,MA 02115. DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT HLTH & SOCIAL BEHAV,BOSTON,MA 02115. RI Cannuscio, Carolyn/A-1123-2007; Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [KO7CA62252] NR 109 TC 184 Z9 188 U1 1 U2 13 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD JUL PY 1997 VL 8 IS 4 BP 649 EP 667 DI 10.1023/A:1018458700185 PG 19 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA XM629 UT WOS:A1997XM62900015 PM 9242482 ER PT J AU Collins, MM Fletcher, RH AF Collins, MM Fletcher, RH TI Research questions concerning prostate cancer screening SO CANCER CAUSES & CONTROL LA English DT Editorial Material ID RADICAL PROSTATECTOMY; COLORECTAL-CANCER; MORTALITY; ANTIGEN; TRIAL C1 MASSACHUSETTS GEN HOSP,MED SERV,DIV GEN MED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT AMBULATORY CARE & PREVENT,BOSTON,MA. HARVARD PILGRIM HLTH CARE,BOSTON,MA. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. NR 18 TC 1 Z9 1 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD JUL PY 1997 VL 8 IS 4 BP 668 EP 671 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA XM629 UT WOS:A1997XM62900016 ER PT J AU Mackey, MF Gunn, JR Ting, PP Kikutani, H Dranoff, G Noelle, RJ Barth, RJ AF Mackey, MF Gunn, JR Ting, PP Kikutani, H Dranoff, G Noelle, RJ Barth, RJ TI Protective immunity induced by tumor vaccines requires interaction between CD40 and its ligand, CD154 SO CANCER RESEARCH LA English DT Article ID CD8+ T-CELLS; DENDRITIC CELLS; INFILTRATING LYMPHOCYTES; ADOPTIVE IMMUNOTHERAPY; HUMAN MONOCYTES; EXPRESSION; GP39; ACTIVATION; MELANOMA; IL-12 AB Interactions between CD40 and its ligand, CD154 (CD40L, gp39), have been shown to play a central role in the regulation of humoral immunity. Recent evidence suggests that this ligand-receptor pair also plays an important role in the induction of cell-mediated immune responses, including those directed against viral pathogens, intracellular parasites, and alloantigens. The contribution of this ligand-receptor pair to the development of protective immunity against syngeneic tumors was evaluated by blocking the in vivo function of CD154 or by studying tumor resistance in mice genetically deficient in CD40 expression (CD40(-/-)). In the former ease, anti-CD154 monoclonal antibody treatment inhibited the generation of protective immune responses after the administration of three potent tumor vaccines: irradiated MCA 105, MCA 105 admixed with Corynebacterium parvum adjuvant, and irradiated B16 melanoma cells transduced with the gene for granulocyte macrophage colony-stimulating factor. Confirmation of the role of CD40/CD154 interactions in tumor immunity was provided by the overt tumor susceptibility in CD40-deficient mice as compared to that in CD40(+/+) mice. In this case, wild-type but not CD40-deficient mice could be readily protected against live TS/A tumor challenge by preimmunization with TS/A admired with C. parvum. These findings suggest a critical role for CD40/CD154 interactions in the induction of cellular immunity by tumor vaccines and may have important implications for future approaches to cell-based cancer therapies. C1 DARTMOUTH COLL,HITCHCOCK MED CTR,SECT GEN SURG,LEBANON,NH 03756. DARTMOUTH COLL,SCH MED,DEPT MICROBIOL,LEBANON,NH 03756. DARTMOUTH COLL,SCH MED,DEPT SURG,LEBANON,NH 03756. NORRIS COTTON CANC CTR,LEBANON,NH. OSAKA UNIV,DEPT MOL IMMUNOL,MICROBIAL DIS RES INST,SUITA,OSAKA 565,JAPAN. DANA FARBER CANC INST,DIV CLIN ONCOL,BOSTON,MA 02115. RI Kikutani, Hitoshi/C-9525-2009 FU NIAID NIH HHS [AI37075, AI26296] NR 42 TC 87 Z9 89 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 1 PY 1997 VL 57 IS 13 BP 2569 EP 2574 PG 6 WC Oncology SC Oncology GA XG575 UT WOS:A1997XG57500008 PM 9205055 ER PT J AU Brunicardi, FC Moldovan, S Gilman, S Livingston, E Passaro, E AF Brunicardi, FC Moldovan, S Gilman, S Livingston, E Passaro, E TI An Internet multicast symposium concerning the microcirculation of the islets of Langerhans SO CELL TRANSPLANTATION LA English DT Article DE Internet; MBone; pancreatic islet; microcirculation ID CELLULAR PERFUSION; CORROSION CASTS; HUMAN PANCREAS; MONKEY; MICROSCOPY; ORDER AB The Internet Globally-linked Computer System was used to conduct an international scientific symposium, The symposium was held at the VAMC-Long Beach and consisted of prepared lectures that were multicast over the Internet, The basic unit of hardware used for the Internet Multicast was the Silicon Graphics Indy Unix Workstation, which was equipped with a color video camera, The multicast required four additional pieces of software from the file transfer protocol, The multicast backbone protocol allowed for simultaneous audio and video signals (the presenter, the slides, and the videotape images of islet microcirculation studies) to be transmitted over the computer network, The faculty included 12 experts in microcirculation, who gave 15-min lectures that included a question and answer period, All lectures were received at 14 computer stations in six countries, Eleven of the faculty gave their lectures at the VAMC-Long Beach, and one gave her lecture at the Massachusetts Institute of Technology in Boston, MA. The presenter from Boston was able to receive and answer questions from the faculty at the VAMC-Long Beach, An estimated $12,000 was saved in travel, hotel, and food costs and an estimated 180 travel hours were saved by viewers who did not have to travel to the symposium, We have demonstrated that a scientific symposium can be conducted using the Internet, We propose that many of our future meetings will be organized over the computer network, This format of multiimage projections allows us to effectively communicate in a personal way with a reduction in expensive and time-consuming travel. (C) 1997 Elsevier Science Inc. C1 W LOS ANGELES VET AFFAIRS MED CTR,DEPT SURG,LOS ANGELES,CA 90073. VA EDUC CTR,LONG BEACH,CA. NR 24 TC 0 Z9 0 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PD JUL-AUG PY 1997 VL 6 IS 4 BP 439 EP 442 PG 4 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA XN786 UT WOS:A1997XN78600010 PM 9258519 ER PT J AU Clairmont, KB Boll, W Ericsson, M Kirchhausen, T AF Clairmont, KB Boll, W Ericsson, M Kirchhausen, T TI A role for the hinge/ear domain of the beta chains in the incorporation of AP complexes into clathrin-coated pits and coated vesicles SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Article DE coated pits; vesicles; endocytosis; adaptors; coat assembly ID PLASMA-MEMBRANE; ASSEMBLY POLYPEPTIDES; ADAPTER COMPLEXES; PROTEINS; BINDING; RECEPTORS; SUBUNIT; SIGNALS; GOLGI; RECONSTITUTION AB The clathrin-associated adaptor protein (AP) complexes drive the polymerization of clathrin in coated pits to form coated vesicles. It has previously been shown that the carboxyl-terminal hinge/ear domain of the beta 2 chain contains a binding site for clathrin and that removal of this domain from APs or from isolated beta 2 chains abrogates their ability to form clathrin coats in vitro. We show here that the hinge/ear domain is necessary for efficient incorporation of AP complexes into coated pits and coated vesicles in cells, a result that is consistent with the view that the beta chains indeed provide an important interaction between the AP complexes and clathrin. C1 HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. NR 40 TC 14 Z9 14 U1 2 U2 2 PU BIRKHAUSER VERLAG AG PI BASEL PA PO BOX 133 KLOSTERBERG 23, CH-4010 BASEL, SWITZERLAND SN 1420-682X J9 CELL MOL LIFE SCI JI Cell. Mol. Life Sci. PD JUL PY 1997 VL 53 IS 7 BP 611 EP 619 DI 10.1007/s000180050080 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XP609 UT WOS:A1997XP60900009 PM 9284964 ER PT J AU Tully, K Koke, K Garshick, E Lieberman, SL Tun, CG Brown, R AF Tully, K Koke, K Garshick, E Lieberman, SL Tun, CG Brown, R TI Maximal expiratory pressures in spinal cord injury using two mouthpieces SO CHEST LA English DT Article DE muscular disease; respiratory muscles; spinal disease AB Study objective: A technique for assessing expiratory muscle strength is the measurement of maximal expiratory pressure (PEmax). Previous studies have shown that a tube-style mouthpiece yields greater PEmax values than a flange-style mouthpiece because the latter technique is limited by the strength of the buccal muscles. In individuals with weak muscles of exhalation, this limitation may not apply because the strength of their buccal muscles may exceed that of the respiratory muscles. Design: A tube-style mouthpiece and flange-style mouthpiece were used to measure PEmax. The order of the mouthpiece used in testing was alternated between subjects and the greatest values obtained after three efforts were compared. Setting: Department of Veterans Affairs Medical Center. Participants: Fifty subjects with chronic spinal cord injury without acute medical illnesses recruited from veterans and the community. Results: The mean difference between PEmax(tube) and PEmax(flange) was 20.7+/-26.4 cm H2O (p=0.0001). Differences were negligible in those with the weakest muscles of exhalation but were substantial even in some quadriplegic subjects. Conclusion: Even in individuals with neuromuscular disorders, errors in assessment of expiratory strength occur when a flange-style mouthpiece is used, and we recommend that this technique be abandoned in the measurement of PEmax. C1 BROCKTON W ROXBURY VET AFFAIRS MED CTR,PULM & CRIT CARE MED SECT,REHABIL MED SERV,W ROXBURY,MA 02401. BROCKTON W ROXBURY VET AFFAIRS MED CTR,PULM & CRIT CARE MED SECT,MED SERV,W ROXBURY,MA 02401. HARVARD UNIV,SCH MED,BOSTON,MA. NR 6 TC 19 Z9 23 U1 1 U2 1 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 SN 0012-3692 J9 CHEST JI Chest PD JUL PY 1997 VL 112 IS 1 BP 113 EP 116 DI 10.1378/chest.112.1.113 PG 4 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA XJ885 UT WOS:A1997XJ88500023 PM 9228365 ER PT J AU Steudel, W Ichinose, F Huang, PL Hurford, WE Jones, RC Bevan, JA Fishman, MC Zapol, WM AF Steudel, W Ichinose, F Huang, PL Hurford, WE Jones, RC Bevan, JA Fishman, MC Zapol, WM TI Pulmonary vasoconstriction and hypertension in mice with targeted disruption of the endothelial nitric oxide synthase (NOS 3) gene SO CIRCULATION RESEARCH LA English DT Article DE targeted nitric oxide synthase 3 gene disruption; pulmonary vascular resistance; nitric oxide; mouse; acetylcholine ID RELAXING FACTOR; L-ARGININE; VASCULAR TONE; RAT LUNGS; METHYLENE-BLUE; VASODILATION; CIRCULATION; INHIBITION; RELEASE; NITROPRUSSIDE AB NO, synthesized in endothelial cells by endothelial NO synthase (NOS 3), is believed to be an important endogenous pulmonary vasodilator substance that contributes to the normal low pulmonary vascular resistance. To selectively investigate the role of NOS 3 in the pulmonary circulation, mice with targeted disruption of the NOS 3 gene were studied. Pulmonary hemodynamics were studied by measuring pulmonary artery pressure, left ventricular end-diastolic pressure, and lower thoracic aortic flow by using a novel open-chest technique. Transient partial occlusion of the inferior vena cava was used to assess the pulmonary artery pressure-flow relationship. Tension developed by isolated pulmonary artery segments after acetylcholine stimulation was measured in vitro. The histological appearance of NOS 3-deficient and wild-type murine lungs was compared. NOS 3-deficient mice (n=27), when compared with wild-type mice (n=32), had pulmonary hypertension (pulmonary artery pressure, 19.0+/-0.8 versus 16.4+/-0.6 mm Hg [mean+/-SE]; P<.05) that was due to an increased total pulmonary resistance (62+/-6 versus 33+/-2 mm Hg . min . g mL(-1); P<.001). In vitro, acetylcholine induced vasodilation in the main pulmonary arteries of wild-type but not NOS 3-deficient mice. The morphology of the lungs of NOS 3-deficient mice did not differ from that of wild-type mice. We conclude that NOS 3 is a key enzyme responsible for providing basal pulmonary NO release. Congenital NOS 3 deficiency produces mild pulmonary hypertension in mice. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ANAESTHESIA & CRIT CARE,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CARDIOVASC RES CTR,BOSTON,MA 02114. UNIV VERMONT,COLL MED,DEPT PHARMACOL,BURLINGTON,VT 05405. RI Hurford, William/G-6386-2013 OI Hurford, William/0000-0003-1201-0313 FU NHLBI NIH HHS [HL-42397]; NINDS NIH HHS [NS-10828, NS-33335] NR 33 TC 174 Z9 184 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7330 J9 CIRC RES JI Circ.Res. PD JUL PY 1997 VL 81 IS 1 BP 34 EP 41 PG 8 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA XH247 UT WOS:A1997XH24700005 PM 9201025 ER PT J AU Rosenzweig, KE Youmell, MB Palayoor, ST Price, BD AF Rosenzweig, KE Youmell, MB Palayoor, ST Price, BD TI Radiosensitization of human tumor cells by the phosphatidylinositol 3-kinase inhibitors Wortmannin and LY294002 correlates with inhibition of DNA-dependent protein kinase and prolonged G(2)-M delay SO CLINICAL CANCER RESEARCH LA English DT Article ID ATAXIA-TELANGIECTASIA GENE; STRAND BREAK REPAIR; SACCHAROMYCES-CEREVISIAE; IONIZING-RADIATION; V(D)J RECOMBINATION; CATALYTIC SUBUNIT; PRODUCT; PHOSPHORYLATES; HOMOLOG; DAMAGE AB Members of the phosphatidylinositol (PI) 3-kinase gene family, including the ataxia telangiectasia gene and the DNA-dependent protein kinase (DNA-PK), are involved in regulating cellular radiosensitivity. We have investigated two structurally unrelated PI 3-kinase inhibitors, wortmannin and LY294002, to determine whether they inhibit DNA-PK and increase cellular radiosensitivity. The PI 3-kinase inhibitors wortmannin and LY294002 were effective radiosensitizers of human tumor cells, with sensitizer enhancement ratios (at 10% survival) of 2.8 and 1.9, respectively, in SW480 cells. Wortmannin and LY294002 inhibited the kinase activity of purified DNA-PK and inactivated cellular DNA-PK kinase activity. Inhibition of cellular DNA-PK activity occurred at the same concentrations of wortmannin that caused radiosensitization, and this correlation was found in a range of tumor cell lines. However, cells deficient in either DNA-PK (scid cells) or the ataxia telangiectasia protein were also partly sensitized to radiation by wortmannin, indicating the involvement of more than one protein kinase in the mechanism of action of wortmannin. Wortmannin also affected the G(2)-M checkpoint. SW480 cells had a reversible G(2)-M delay of 20 h following irradiation. However, wortmannin-treated SW480 cells had a prolonged G(2)-M delay; more than 75% of cells were arrested in G(2) at 50 h postirradiation. This suggests the accumulation of significant unrepaired DNA damage following inhibition of PI 3-kinase family members. Therefore, PI 3-kinase inhibitors may represent a new class of radiosensitizers that inhibit the repair of DNA damage. C1 DANA FARBER CANC INST,JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. FU NCI NIH HHS [CA64585] NR 44 TC 182 Z9 187 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUL PY 1997 VL 3 IS 7 BP 1149 EP 1156 PG 8 WC Oncology SC Oncology GA XH784 UT WOS:A1997XH78400015 PM 9815794 ER PT J AU Singh, BN AF Singh, BN TI Amiodarone: The expanding antiarrhythmic role and how to follow a patient on chronic therapy SO CLINICAL CARDIOLOGY LA English DT Review DE class III antiarrhythmic drugs; ventricular tachycardia and fibrillation; sotalol; atrial fibrillation; heart failure; myocardial infarction; proarrhythmia; monitoring amiodarone therapy ID LOW-DOSE AMIODARONE; VENTRICULAR TACHYARRHYTHMIAS; INTRAVENOUS AMIODARONE; MYOCARDIAL-INFARCTION; ATRIAL-FIBRILLATION; DOUBLE-BLIND; TRIAL; DEFIBRILLATORS; TACHYCARDIA; RECURRENT AB Amiodarone was introduced as an antiarrhythmic compound in the early 1970s and was approved in the U.S. for the treatment of refractory ventricular arrhythmias in late 1984. Since that time the drug has become the most widely studied antiarrhythmic compound with expanding potential indications, including maintaining stability of sinus rhythm, secondary prevention in the survivors of myocardial infarction, and prolongation of survival in certain subsets of patients with congestive heart failure. Intravenous amiodarone was introduced in the U.S. in 1995 for the control of recurrent destabilizing ventricular tachycardia or ventricular fibrillation resistant to conventional therapy. The level of comfort in its use has risen considerably in the recent past. This has stemmed from the reasonably decisive evidence that class I agents increase mortality in patients with structural heart disease. In contrast, amiodarone either reduces mortality or its effect is neutral; this is consistent with its low to negligible proarrhythmic actions. The drug does not aggravate heart failure and it may even increase left ventricular ejection fraction and improve exercise capacity. Above all, it is becoming increasingly evident from wider experience and from controlled clinical trials that the side-effect profile of the drug is not as compelling an issue as it appeared to be when first used in much higher doses. Therefore, the overall objective of amiodarone therapy is to use the lowest dose that produces a defined therapeutic end point without causing serious side effects. Careful clinical surveillance in conjunction with monitoring of certain laboratory parameters and indices of efficacy at regular intervals permits the drug to be used effectively in a large number of patients who fail to respond to, or are intolerant of other antiarrhythmic compounds. Many experienced clinicians have begun to consider the use of amiodarone as first-line therapy in certain disorders of rhythm, especially in patients with severely compromised ventricular function. C1 UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA 90024. RP Singh, BN (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,CARDIOL SECT,11301 WILSHIRE BLVD 111E,LOS ANGELES,CA 90073, USA. NR 31 TC 40 Z9 41 U1 0 U2 1 PU CLINICAL CARDIOLOGY PUBL CO PI MAHWAH PA PO BOX 832, MAHWAH, NJ 07430-0832 SN 0160-9289 J9 CLIN CARDIOL JI Clin. Cardiol. PD JUL PY 1997 VL 20 IS 7 BP 608 EP 618 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA XH249 UT WOS:A1997XH24900004 PM 9220176 ER PT J AU Holmes, LB AF Holmes, LB TI Severe malformation of one foot from amniocentesis needle injury SO CLINICAL DYSMORPHOLOGY LA English DT Article DE amniocentesis; puncture injury ID MIDTRIMESTER AMNIOCENTESIS; HYDROCEPHALUS; COMPLICATION; DEFECTS; UPDATE AB An 11-year-old boy is described who was born with a poorly developed right foot. At 16 weeks gestation his mother had had amniocentesis without direct ultrasound guidance. After the insertion of the amniocentesis needle, she felt strong abdominal resistance, which disappeared with slight withdrawal of the needle. Then, real-time ultrasound was used to determine the position of the needle, which was reported to be up against the feet. Nine days later deep purple amniotic fluid was removed by amniocentesis. At birth there was a scab over an oozing hole in the lateral aspect of his right 'foot', a poorly formed structure with five digit-like structures at the tip. It seems most likely that the deformity was caused by tissue injury from needle puncture at 16 weeks gestation. C1 HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. RP Holmes, LB (reprint author), MASSACHUSETTS GEN HOSP,CHILDRENS SERV,GENET & TERATOL UNIT,BOSTON,MA 02114, USA. NR 23 TC 5 Z9 5 U1 0 U2 0 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0962-8827 J9 CLIN DYSMORPHOL JI Clin. Dysmorphol. PD JUL PY 1997 VL 6 IS 3 BP 273 EP 279 DI 10.1097/00019605-199707000-00013 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA XG903 UT WOS:A1997XG90300013 PM 9220200 ER PT J AU Graybill, JR AF Graybill, JR TI Can we agree on the treatment of candidiasis? Response SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material ID MULTIPLE-DOSE PHARMACOKINETICS; AMPHOTERICIN-B; ORAL SOLUTION; FLUCONAZOLE; ITRACONAZOLE; FLUCYTOSINE; CANDIDEMIA; MENINGITIS; LEUKEMIA; TRIAL RP Graybill, JR (reprint author), AUDIE L MURPHY MEM VET ADM MED CTR,7400 MERTON MINTER BLVD,SAN ANTONIO,TX 78284, USA. NR 21 TC 17 Z9 17 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUL PY 1997 VL 25 IS 1 BP 60 EP 62 DI 10.1086/514503 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA XL367 UT WOS:A1997XL36700011 PM 9243033 ER PT J AU Ring, D Barrick, WT Jupiter, JB AF Ring, D Barrick, WT Jupiter, JB TI Recalcitrant nonunion SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID REPAIR; CELLS AB One surgeon treated 13 patients with 14 long bone fractures that remained ununited for 10 or more years (average, 16 years) and after an average of three prior surgeries, The clavicle was involved in two cases, the humerus in five (one proximal, three diaphyseal, and one distal intraarticular), the femoral diaphysis in three, and the tibial diaphysis in four, The patients were observed for an average of 54 months, All of the fractures healed, and every patient in the series regained functional use of the involved limb without reports of pain, instability, or persistent swelling related to the site of nonunion, Three patients had persistent leg length discrepancies, and five had substantial residual stiffness of one or both adjacent joints, This experience has shown that despite the longevity of the nonunions, healing can be achieved using the basic concepts of the creation of a stable skeletal fixation in the presence of a well vascularized environment with the addition of autogenous bone graft, By the same token, the duration of the nonunion will lead to soft tissue maladaptation and contracture that at times compromise successful restoration of limb length or adjacent articular mobility. C1 MASSACHUSETTS GEN HOSP,DEPT ORTHOPED,HARVARD COMBINED ORTHOPAED RESIDENCY PROGRAM,BOSTON,MA 02114. TUFTS UNIV NEW ENGLAND MED CTR,DEPT ORTHOPED,TUFTS ORTHOPED RESIDENCY PROGRAM,BOSTON,MA 02111. MASSACHUSETTS GEN HOSP,ORTHOPAED HAND SURG SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 26 TC 33 Z9 34 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD JUL PY 1997 IS 340 BP 181 EP 189 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA XJ873 UT WOS:A1997XJ87300023 PM 9224254 ER PT J AU Tan, MH Mankin, HJ AF Tan, MH Mankin, HJ TI Blood transfusion and bone allografts - Effect on infection and outcome SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID COLORECTAL-CANCER SURGERY; POSTOPERATIVE INFECTION; BACTERIAL PERITONITIS; SEPTIC COMPLICATIONS; WOUND-INFECTION; IMMUNE FUNCTION; RECURRENCE; SURVIVAL; RISK; SUSCEPTIBILITY AB Intraoperative and postoperative blood replacement have been implicated in increased rates of wound infection, decreased rates of renal allograft transplant rejection, and increased rates of local recurrence and metastasis of certain kinds of tumors, all presumably on the basis of some alteration in the immune system. Because patients who have bone allograft surgery for tumors often require transfusion and because the procedure is associated with a high rate of failure (20%), infection (9%-10%), and local recurrence (10% for high grade tumors), the effect of transfusion (range, 0-4750 ml) was studied for 264 patients who had proximal humeral, proximal or distal femoral resections, and massive cadaveric allografts but who did not have adjuvant chemotherapy or radiation. An attempt was made to statistically correlate the tumor and allograft outcome and rate of infection with patient age and gender, anatomic site, diagnosis, stage, type of graft, number of subsequent procedures, surgical margins, perioperative transfusions, blood loss, duration of operative procedures, and number of pregnancies. Of the variables studied, only blood loss, transfusion, and duration of surgery had an effect on outcome and, more specifically, on infection rate and time to union. No effect was observed on metastasis, recurrence, or the ultimate outcome of the procedure. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CONNECT TISSUE ONCOL CTR,ORTHOPAED SERV GR606,BOSTON,MA 02114. NR 52 TC 12 Z9 12 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD JUL PY 1997 IS 340 BP 207 EP 214 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA XJ873 UT WOS:A1997XJ87300027 PM 9224258 ER PT J AU Goldberg, MA MayoSmith, WW Papanicolaou, N Fischman, AJ Lee, MJ AF Goldberg, MA MayoSmith, WW Papanicolaou, N Fischman, AJ Lee, MJ TI FDG PET characterization of renal masses: Preliminary experience SO CLINICAL RADIOLOGY LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; F-18 FLUORODEOXYGLUCOSE; RADIATION NECROSIS; MALIGNANT-LYMPHOMA; COLORECTAL TUMORS; GLUCOSE ANALOG; BRAIN-TUMORS; CANCER; 2--FLUORO-2-DEOXY-D-GLUCOSE; FLUORINE-18-FLUORODEOXYGLUCOSE AB Objective: This study was undertaken to evaluate the potential efficacy of fluorine-18 2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET) to detect renal tumours and to characterize indeterminate renal cysts. Subjects and methods: Twenty-six PET scans mere performed in 21 patients (14 PET scans in 10 patients with malignant renal tumours and 12 PET scans in 11 patients with Bosniak type 3 indeterminate renal cysts). Pathological proof was obtained in 18 of 21 patients (10 with solid neoplasms, eight with indeterminate cysts). Imaging was performed 1 h after injection of 5-10 mCi of FDG with IV administration of Lasix (10 mg) 20 mins after injection. Two consecutive 9.7-cm image segments mere scanned to cover the entire renal areas. Results: PET accurately depicted solid neoplasms as areas of increased uptake in nine of 10 patients. Bilateral renal cell carcinomas mere missed in one diabetic patient. All but one indeterminate renal cysts mere correctly classified as benign (photopenic areas), but an indeterminate cyst with a 4-mm papillary neoplasm was wrongly classified as benign. There mere no false positive PET interpretations. The mean tumour-to-kidney ratio was 3.0 for malignant lesions. Conclusion: We conclude that FDG PET scanning shows promise in the evaluation of indeterminate renal cysts. A positive PET scan in the appropriate clinical setting obviates the need for cyst aspiration. A negative PET scan in conjunction with a negative cyst aspiration offers confirmatory evidence of benignity. Our preliminary results are encouraging and further work is ongoing. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 33 TC 43 Z9 44 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 0009-9260 J9 CLIN RADIOL JI Clin. Radiol. PD JUL PY 1997 VL 52 IS 7 BP 510 EP 515 DI 10.1016/S0009-9260(97)80327-3 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA XK274 UT WOS:A1997XK27400003 PM 9240703 ER PT J AU Anzueto, A Peters, JI Tobin, MJ DelosSantos, R Seidenfeld, JJ Moore, G Cox, WJ Coalson, JJ AF Anzueto, A Peters, JI Tobin, MJ DelosSantos, R Seidenfeld, JJ Moore, G Cox, WJ Coalson, JJ TI Effects of prolonged controlled mechanical ventilation on diaphragmatic function in healthy adult baboons SO CRITICAL CARE MEDICINE LA English DT Article DE mechanical ventilation; lung pathology/morphology; diaphragmatic function ID LUNG INJURY; PRESSURE; MUSCLES; VOLUME; EDEMA AB Objective: To study diaphragmatic strength and endurance after a prolonged period of mechanical ventilation, Design: Prospective animal study, Setting: Animal research laboratory, Subjects: Seven uninjured adult baboons (Papio cynocephalus) were anesthetized with ketamine, sedated, paralyzed, and mechanically ventilated, Animals were monitored with pulmonary arterial and peripheral arterial catheters, Interventions: Mechanical Ventilation was provided for 11 days with an FIO2 of 0.21 and tidal Volume of 15 mL/kg, Pulmonary function tests, including lung volumes, arterial brood gases, and chest radiographs were also monitored, Nursing care procedures included frequent turning, chest physiotherapy, and endotracheal suction, Antacids and prophylactic antibiotics (intravenous penicillin, topical polymyxin B, and gentamicin sulfate) were administered, In three animals, fishhook electrodes were surgically placed around both phrenic nerves on both day 0 and after 11 days of mechanical ventilation for diaphragmatic stimulation, On day 0, the electrodes were removed after phrenic nerve stimulation studies were performed, After 11 days of mechanical ventilation, animals were electively killed and full autopsy performed. Measurements and Main Results: Hemodynamic and pulmonary function parameters were measured at baseline and every day during the 11 days of mechanical ventilation, Diaphragmatic strength and endurance were measured on days 0 and 11. Diaphragmatic endurance was determined by an inspiratory resistive loading protocol, There were no significant changes in hemodynamics, lung volumes, or gas exchange during the period of mechanical ventilation, On day 7,the chest radiographs showed patchy lobar atelectasis in six animals, which cleared by day 11 in ail but two of the animals, Lung pathology showed mild, focal pneumonitis, By day 11, maximum transdiaphragmatic pressure had decreased by 25% from day 0 and diaphragmatic endurance had decreased by 36%, Conclusions: Eleven days of mechanical ventilation and neuromuscular blockade in healthy baboons resulted in nonsignificant changes in hemodynamics, oxygenation, and/or lung function, However, significant impairment in diaphragmatic endurance and strength were seen, Based on these results, it is likely that prolonged mechanical ventilation by itself impairs diaphragmatic function independent of underlying lung disease. C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV PULM DIS CRIT CARE MED,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT PATHOL,SAN ANTONIO,TX 78284. SW FDN BIOMED RES,SAN ANTONIO,TX 78284. UNIV ARKANSAS MED SCI HOSP,LITTLE ROCK,AR 72205. LOYOLA UNIV,STRITCH SCH MED,DEPT MED,DIV PULM & CRIT CARE MED,CHICAGO,IL 60611. VET AFFAIRS EDWARD HINES JR HOSP,MAYWOOD,IL. RP Anzueto, A (reprint author), AUDIE L MURPHY MEM VET HOSP DIV,PULM DIS SECT,S TEXAS VET HLTH CARE SYST,SAN ANTONIO,TX 78284, USA. FU NHLBI NIH HHS [HL-23578] NR 18 TC 94 Z9 99 U1 0 U2 3 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 JUL PY 1997 VL 25 IS 7 BP 1187 EP 1190 DI 10.1097/00003246-199707000-00021 PG 4 WC Critical Care Medicine SC General & Internal Medicine GA XL366 UT WOS:A1997XL36600021 PM 9233746 ER PT J AU Niederman, R Zhang, J Kashket, S AF Niederman, R Zhang, J Kashket, S TI Short-chain carboxylic-acid-stimulated, PMN-mediated gingival inflammation SO CRITICAL REVIEWS IN ORAL BIOLOGY & MEDICINE LA English DT Review DE propionic acid; butyric acid; lactic acid; gingival inflammation; neutrophils; gene expression ID DENTAL PLAQUE EXTRACTS; GAS-LIQUID-CHROMATOGRAPHY; GLOBIN GENE-EXPRESSION; CHINESE-HAMSTER CELLS; VOLATILE FATTY-ACIDS; NF-KAPPA-B; SODIUM-BUTYRATE; PERIODONTAL-DISEASE; ANAEROBIC-BACTERIA; CREVICULAR FLUID AB This communication reviews the effects of short-chain carboxylic acids on human cells of importance to the periodontium. The central hypothesis is that these acids can alter both cell function and gene expression, and thus contribute to the initiation and prolongation of gingival inflammation. Short-chain carboxylic acids (CH3-(CH2)x-COOH, x < 3) are metabolic intermediates with a broad range of apparently paradoxical biological effects. For example, lactic acid (CH3-CHOH-COOH), a 3-carbon alpha-hydroxy-substituted acid, is widely recognized for its cariogenicity. Lactic acid, however, also occurs in tropical fruits, and is the active ingredient in a variety of anti-wrinkle creams developed by dermatologists. In marked contrast, the unsubstituted S-carbon propionic acid (CH3-CH2-COOH) is used as a food preservative and is the active principle For one class of non-steroidal anti-inflammatory agents. Interestingly, the addition of one carbon to propionic acid dramatically changes the biological effects. The unsubstituted 4-carbon butyric acid (CH3-CH2-CH2-COOH) is used by hematologists as a de-differentiating agent for the treatment of sickle cell anemia, but by oncologists as a differentiating, agent for cancer chemotherapy. Finally, acting either individually or in concert, these acids can increase vascular dilation. Clearly, these acids, while metabolically derived, have a number of very divergent activities which are cell-type-specific (Fig. 1). It may be telling that periodontal bacteria produce these acids in millimolar concentrations, and that these bacteria can be characterized by their acid production profiles. It is no less interesting that these acids occur in the gingival crevices of human subjects with severe periodontal disease at millimolar levels which are > 10-fold higher than those found in mildly diseased subjects, and are undetectable in healthy subjects. Further, when applied directly to healthy human gingiva, short-chain carboxylic acids stimulate a gingival inflammatory response and inflammatory cytokine release. At the cellular level, these acids inhibit proliferation of gingival epithelial and endothelial cells, and inhibit leukocyte apoptosis and function, but can stimulate leukocyte cytokine release. At the molecular level, these acids can stimulate neutrophil gene transcription, translation, and protein expression. Thus, the likelihood is high that these acids, in addition to their cariogenic activity, can promote and prolong gingival inflammation. Our challenge will be to identify the cell or cells of the periodontium which respond to short-chain carboxylic acids, to delineate their responses and the molecular mechanism(s) of these effects, and to categorize the aspects of the inflammatory components which damage and those which protect the host. With this information, it may be possible to begin to rationally identify and test pharmaceutical agents which diminish the harmful aspects, while enhancing the beneficial components, of the inflammatory response. C1 FORSYTH DENT CTR,DEPT CYTOKINE BIOL,BOSTON,MA 02115. FORSYTH DENT CTR,NUTR SECT,BOSTON,MA 02115. RP Niederman, R (reprint author), HARVARD UNIV,SCH DENT MED,DEPT PERIODONTOL,188 LONGWOOD AVE,BOSTON,MA 02115, USA. FU NIDCR NIH HHS [DE08415] NR 143 TC 60 Z9 63 U1 1 U2 3 PU INT AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 SN 1045-4411 J9 CRIT REV ORAL BIOL M JI Crit. Rev. Oral Biol. Med. PD JUL PY 1997 VL 8 IS 3 BP 269 EP 290 PG 22 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA XP895 UT WOS:A1997XP89500003 PM 9260044 ER PT J AU Podolsky, DK AF Podolsky, DK TI Inflammatory bowel disease 1997: where is the cutting edge? SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Editorial Material RP Podolsky, DK (reprint author), MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,GRJ 719-32 FRUIT ST,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. PD JUL PY 1997 VL 13 IS 4 BP 287 EP 288 DI 10.1097/00001574-199707000-00001 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA XN785 UT WOS:A1997XN78500001 ER PT J AU Mendez, MF Stanley, TM Medel, NM Li, ZP Tedesco, DT AF Mendez, MF Stanley, TM Medel, NM Li, ZP Tedesco, DT TI The vascular dementia of Fabry's disease SO DEMENTIA AND GERIATRIC COGNITIVE DISORDERS LA English DT Article DE Fabry's disease; dementia; vascular dementia; cerebrovascular disease ID ALPHA-GALACTOSIDASE-A; INVOLVEMENT; GENE AB Fabry's disease, a rare X-linked disorder of glycosphingolipid metabolism, can present as an insidious dementia in middle or later life. This genetic disorder produces a deficiency of a-galactosidase A which results in the deposition of glycosphingolipids in blood vessel walls in the brain as well as in the kidney, heart, peripheral nerves, and other organs. Among the cerebrovascular manifestations of this disorder is a vascular dementia from involvement of multiple small penetrating blood vessels, Fabry's disease is a consideration in the workup of an otherwise unexplained vascular dementia, particularly in males less than 65 years of age. C1 UNIV CALIF LOS ANGELES,DEPT NEUROL,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,DEPT PSYCHIAT,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,DEPT PATHOL,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,DEPT INTERNAL MED,LOS ANGELES,CA 90024. RP Mendez, MF (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,11301 WILSHIRE BLVD,LOS ANGELES,CA 90073, USA. NR 23 TC 39 Z9 41 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1420-8008 J9 DEMENT GERIATR COGN JI Dement. Geriatr. Cogn. Disord. PD JUL-AUG PY 1997 VL 8 IS 4 BP 252 EP 257 DI 10.1159/000106640 PG 6 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA XF934 UT WOS:A1997XF93400009 PM 9213072 ER PT J AU Phelan, SA Ito, M Loeken, MR AF Phelan, SA Ito, M Loeken, MR TI Neural tube defects in embryos of diabetic mice - Role of the Pax-3 gene and apoptosis SO DIABETES LA English DT Article ID PROGRAMMED CELL-DEATH; TUMOR ALVEOLAR RHABDOMYOSARCOMA; GLYCEMIC CONTROL; MESSENGER-RNA; MOUSE MUTANT; RAT EMBRYOS; PAIRED BOX; CONGENITAL-MALFORMATIONS; DIFFERENTIAL DISPLAY; DNA FRAGMENTATION AB Neural tube defects are among the most common of the malformations associated with diabetic embryopathy. To study the molecular mechanisms by which neural tube defects occur during diabetic pregnancy, we have developed a new experimental system using pregnant diabetic mice. In this system, the rate of neural tube defects is about three times higher in embryos of diabetic mice than in embryos of nondiabetic mice. Most of the defects affected presumptive midbrain and hindbrain structures and included open defects (i.e., exencephaly) and gross maldevelopment. By semiquantitative reverse transcription-polymerase chain reaction and in situ hybridization, we found that expression of Pax-3, a gene required for neural tube closure in the area of the midbrain and hindbrain, is significantly reduced in the embryos of diabetic mice. The same regions of the neural tube where Pax-3 had been underexpressed were found subsequently to contain high concentrations of cells undergoing apoptosis. Reduced expression of Pax-3 appears to be responsible for this apoptosis because apoptotic cells were also found at sites of neural tube defects in embryos carrying null mutation of the Pax-3 gene. Finally, mouse strains that carry null mutations in Pax-3 develop neural tube defects that resemble the malformations that occur in embryos of diabetic mice. These results suggest that Pax-3 is an important developmental control gene, expression of which is disturbed in embryos of diabetic mice, and that as a consequence, apoptosis of the neural tube occurs. This pathway may be responsible for many of the neural tube defects resulting from pregnancy. C1 HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,MOL BIOL SECT,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DIV MED SCI,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02215. FU NCI NIH HHS [CA50599]; NIDDK NIH HHS [DK36836, T32 DK07260] NR 73 TC 181 Z9 188 U1 0 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD JUL PY 1997 VL 46 IS 7 BP 1189 EP 1197 DI 10.2337/diabetes.46.7.1189 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XF832 UT WOS:A1997XF83200014 PM 9200655 ER PT J AU White, MF AF White, MF TI The insulin signalling system and the IRS proteins SO DIABETOLOGIA LA English DT Article; Proceedings Paper CT EASD/JDFI Workshop on Macrovascular Disease in Diabetes CY NOV, 1996 CL OXFORD, ENGLAND DE insulin action; insulin signalling; insulin receptor substrate proteins; signal transduction ID TYROSINE KINASE-ACTIVITY; GROWTH-FACTOR-I; SH2-CONTAINING PHOSPHOTYROSINE PHOSPHATASE; NECROSIS-FACTOR-ALPHA; NUCLEOTIDE-RELEASING-FACTOR; COOH-TERMINAL TRUNCATION; SRC HOMOLOGY-2 DOMAINS; RECEPTOR SUBSTRATE-1; PHOSPHATIDYLINOSITOL 3'-KINASE; INTACT-CELLS AB During the past few years, the insulin signalling system has emerged as a flexible network of interacting proteins. By utilizing the insulin receptor substrate (IRS)-proteins (IRS-1 and IRS-2), the insulin signal can be amplified or attenuated independently of insulin binding and tyrosine kinase activity, providing an extensible mechanism for signal transmission in multiple cellular backgrounds. By employing IRS-proteins to engage various signalling proteins, the insulin receptor avoids the stoichiometric constraints encountered by receptors which directly recruit SH2-proteins to their autophosphorylation sites. Finally, the shared use of IRS-proteins by multiple receptors is likely to reveal important connections between insulin and other hormones and cytokines which were previously unrecognized, or observed but unexplained. C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP White, MF (reprint author), JOSLIN DIABET CTR,DIV RES,1 JOSLIN PL,BOSTON,MA 02215, USA. NR 153 TC 205 Z9 214 U1 1 U2 6 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD JUL PY 1997 VL 40 SU 2 BP S2 EP S17 DI 10.1007/s001250051387 PG 16 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XJ515 UT WOS:A1997XJ51500002 PM 9248696 ER PT J AU Shivdasani, RA Fujiwara, Y McDevitt, MA Orkin, SH AF Shivdasani, RA Fujiwara, Y McDevitt, MA Orkin, SH TI A lineage-selective knockout establishes the critical role of transcription factor GATA-1 in megakaryocyte growth and platelet development SO EMBO JOURNAL LA English DT Article DE conditional gene inactivation; differentiation; GATA transcription factors; megakaryocytes; platelets ID ERYTHROID-DIFFERENTIATION; TARGETED MUTATION; MAMMALIAN-CELLS; STEM-CELLS; GENE; EXPRESSION; MICE; RECOMBINATION; PRECURSORS; DELETION AB Transcription factor GATA-1 is essential for red blood cell maturation and, therefore, for survival of developing mouse embryos, GATA-1 is also expressed in megakaryocytes, mast cells, eosinophils, multipotential hematopoietic progenitors and Sertoli cells of the testis, where its functions have been elusive, Indeed, interpretation of gene function in conventional knockout mice is often limited by embryonic lethality or absence of mature cells of interest, creating the need for alternate methods to assess gene function in selected cell lineages. Emerging strategies for conditional gene inactivation through site-specific recombinases rely on the availability of mouse strains with high fidelity of transgene expression and efficient, tissue-restricted DNA excision. In an alternate approach, we modified sequences upstream of the GATA-1 locus in embryonic stem cells, including a DNase I-hypersensitive region, This resulted in generation of mice with selective loss of megakaryocyte GATA-1 expression, yet sufficient erythroid cell levels to avoid lethal anemia, The mutant mice have markedly reduced platelet numbers, associated with deregulated megakaryocyte proliferation and severely impaired cytoplasmic maturation, These findings reveal a critical role for GATA-1 in megakaryocyte growth regulation and platelet biogenesis, and illustrate how targeted mutation of cis-elements can generate lineage-specific knockout mice. C1 DANA FARBER CANC INST,DEPT MED,BOSTON,MA 02115. CHILDRENS HOSP,DEPT MED,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HOWARD HUGHES MED INST,DEPT MED,BOSTON,MA 02115. NR 44 TC 469 Z9 479 U1 0 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD JUL 1 PY 1997 VL 16 IS 13 BP 3965 EP 3973 DI 10.1093/emboj/16.13.3965 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XJ990 UT WOS:A1997XJ99000022 PM 9233806 ER PT J AU Besecke, LM Guendner, MJ Sluss, PA Polak, AG Woodruff, TK Jameson, JL BauerDantoin, AC Weiss, J AF Besecke, LM Guendner, MJ Sluss, PA Polak, AG Woodruff, TK Jameson, JL BauerDantoin, AC Weiss, J TI Pituitary follistatin regulates activin-mediated production of follicle-stimulating hormone during the rat estrous cycle SO ENDOCRINOLOGY LA English DT Article ID GONADOTROPIN-RELEASING-HORMONE; MESSENGER-RIBONUCLEIC-ACID; GENE-EXPRESSION; BETA-SUBUNIT; LUTEINIZING-HORMONE; SECONDARY SURGE; FEMALE RAT; INHIBIN; SECRETION; CELLS AB Follistatin, an activin-binding protein, plays a key role in the modulation of activin-dependent functions. In the anterior pituitary, activin stimulates the synthesis and secretion of FSH. In the current study, we assessed the roles of locally produced activin and follistatin in the control of FSH gene expression and secretion. The anterior pituitary gland follistatin content was measured at frequent intervals during the rat estrous cycle. Follistatin protein levels were high before the primary gonadotropin surges, decreased by 50% on proestrous evening, and rebounded to a peak at midnight on proestrus before returning to presurge levels on estrus morning. Changes in pituitary follistatin protein content were preceded by parallel changes in pituitary follistatin messenger RNA (mRNA). The trough in follistatin protein content on proestrus coincided with a peak in circulating levels of free activin A (not bound to follistatin) and a sharp rise in FSH beta mRNA levels, suggesting that decreased pituitary follistatin leads to increased available activin. To quantitate the contribution of pituitary free activin to pituitary expression of FSH beta mRNA and the primary and secondary serum FSH surges, rats were infused through carotid catheters with saline or recombinant human follistatin (288-amino acid isoform; rhFS-288) at different times during the estrous cycle. Infusion of rhFS-288 on diestrus did not affect FSH production. In contrast, infusion of rhFS-288 during the secondary FSH surge decreased the peaks in FSH beta mRNA and serum FSH by 63% and 47%, respectively, relative to those in saline-infused control animals. Infusion of rhFS-288 during the primary FSH surge decreased serum FSK to a lesser degree (24%). These data indicate a physiological role for pituitary follistatin in the control of activin-mediated FSH synthesis and secretion during the rat estrous cycle. C1 NORTHWESTERN UNIV, SCH MED, DIV ENDOCRINOL METAB & MOL MED, CHICAGO, IL 60611 USA. MASSACHUSETTS GEN HOSP, REPROD ENDOCRINE UNIT, BOSTON, MA 02114 USA. OI Jameson, James/0000-0001-9538-4059 FU NICHD NIH HHS [P30-HD-28048, U54-HD-29164] NR 35 TC 61 Z9 62 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD JUL PY 1997 VL 138 IS 7 BP 2841 EP 2848 DI 10.1210/en.138.7.2841 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XF427 UT WOS:A1997XF42700028 PM 9202226 ER PT J AU Affenito, SG LammiKeefe, CJ Vogel, S Backstrand, JR Welch, GW Adams, CH AF Affenito, SG LammiKeefe, CJ Vogel, S Backstrand, JR Welch, GW Adams, CH TI Women with insulin-dependent diabetes mellitus (IDDM) complicated by eating disorders are at risk for exacerbated alterations in lipid metabolism SO EUROPEAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE lipid metabolism, alpha-tocopherol; carotenoid; glycosylated haemoglobin; insulin-dependent diabetes mellitus; eating disorders; bulimia nervosa; anorexia nervosa ID ANOREXIA-NERVOSA; BULIMIA-NERVOSA; MICRONUTRIENT; BINDING; VITAMIN; SERUM AB Objective: To examine lipid parameters that are affected in women with insulin-dependent diabetes mellitus (IDDM) who engaged in disordered eating behaviours. Design: Randomized, unmatched. Setting: Tertiary care. Subjects: Ninety women (18-46 y) with IDDM. Interventions: Classification of subjects based on severity of eating disorder: clinical (n=14), subclinical (n=13) and control (n=63). Blood was analysed for glycosylated haemoglobin (HbA(1c)) and serum for triglycerides and cholesterol. Carotenoid and tocopherol concentrations were analysed by high performance liquid chromatography (HPLC). Dietary intake was assessed by the National Cancer Institute food frequency questionnaire. Results: HbA(1c) was significantly increased im women demonstrating clinical and subclinical symptoms compared to control (10.4+/-2.6, 10.0+/-1.5 and 8.3+/-1.6%, respectively, P<0.05). Triglyceride concentrations were significantly increased in women with subclinical eating disorders compared to controls. In women who intentionally omitted or reduced insulin, triglyceride cholesterol and HbA(1c) were significantly increased compared to controls. Women with IDDM and eating disorders who exhibited bulimic behaviours consumed significantly more energy, total fat and cholesterol compared to controls and women with eating disorders who were restrained eaters. Conclusion: While IDDM is known to perturb lipid metabolism, these data demonstrate that eating disorders, in combination with IDDM, results in additional alterations in lipid metabolism. C1 UNIV CONNECTICUT, DEPT NUTR SCI, STORRS, CT 06269 USA. HARVARD UNIV, SCH MED, DEPT PSYCHIAT, BOSTON, MA 02215 USA. HARVARD UNIV, SCH MED, JOSLIN DIABET CTR, MENTAL HLTH UNIT, BOSTON, MA 02215 USA. RP Affenito, SG (reprint author), UNIV CONNECTICUT, SCH ALLIED HLTH, STORRS, CT 06269 USA. FU NCRR NIH HHS [M01RR06192] NR 36 TC 13 Z9 13 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0954-3007 EI 1476-5640 J9 EUR J CLIN NUTR JI Eur. J. Clin. Nutr. PD JUL PY 1997 VL 51 IS 7 BP 462 EP 466 DI 10.1038/sj.ejcn.1600429 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA XK155 UT WOS:A1997XK15500008 PM 9234029 ER PT J AU Hussain, MA AF Hussain, MA TI Sensing hypoglycemia: The ventromedial hypothalamus SO EUROPEAN JOURNAL OF ENDOCRINOLOGY LA English DT Editorial Material ID RESPONSES RP Hussain, MA (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,HOWARD HUGHES MED INST,LAB MOL ENDOCRINOL,BOSTON,MA 02114, USA. NR 11 TC 2 Z9 2 U1 0 U2 0 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0804-4643 J9 EUR J ENDOCRINOL JI Eur. J. Endocrinol. PD JUL PY 1997 VL 137 IS 1 BP 18 EP 19 DI 10.1530/eje.0.1370018 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XK498 UT WOS:A1997XK49800005 PM 9242195 ER PT J AU Meier, CA AF Meier, CA TI Molecular insights into the regulation of energy intake and expenditure SO EUROPEAN JOURNAL OF ENDOCRINOLOGY LA English DT Editorial Material C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DIV ENDOCRINE,BOSTON,MA. RP Meier, CA (reprint author), BRIGHAM & WOMENS HOSP,DIV GENET,DEPT MED,THORN 905,20 SHATTUCK ST,BOSTON,MA 02115, USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0804-4643 J9 EUR J ENDOCRINOL JI Eur. J. Endocrinol. PD JUL PY 1997 VL 137 IS 1 BP 20 EP 21 DI 10.1530/eje.0.1370020 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XK498 UT WOS:A1997XK49800006 PM 9242196 ER PT J AU Segu, VB Mahvi, DM Wilson, MA Hale, SJ Warner, TF Meredith, M Shenker, Y AF Segu, VB Mahvi, DM Wilson, MA Hale, SJ Warner, TF Meredith, M Shenker, Y TI Use of In-111 pentetreotide scintigraphy in the diagnosis of a midgut carcinoid causing Cushing's syndrome SO EUROPEAN JOURNAL OF ENDOCRINOLOGY LA English DT Article ID SOMATOSTATIN-RECEPTOR SCINTIGRAPHY; ECTOPIC ACTH SYNDROME; CORTICOTROPIN-RELEASING HORMONE; ENDOCRINE TUMORS; DIFFERENTIAL-DIAGNOSIS; LOCALIZATION; MANAGEMENT; ANALOGS AB A 57-year-old man presented with clinical features of hypercortisolism and was diagnosed with ACTH-dependent Cushing's syndrome. Biochemical testing showed partial suppression of urinary free cortisol with high dose dexamethasone. Initial computed tomography (GT) of the chest and abdomen, and magnetic resonance imaging of the pituitary were negative. In-111 pentetreotide scintigraphy with single photon emission computerized tomography revealed two 'hot' lesions in the abdomen which were then confirmed by subsequent directed thin-slice abdominal CT and small bowel barium study, At surgery, two segments of ileum, adjoining mesentery and lymph nodes were resected. Histopathology was consistent with a malignant carcinoid tumor of the ileum which stained intensely for ACTH. Plasma ACTH, and serum and urinary cortisol normalized postoperatively. To our knowledge, this is the first reported case of ileal carcinoid tumor causing Cushing's syndrome with premortem diagnosis. Another unique feature of this case is that In-111 pentetreotide scan provided the decisive clue to localization of the tumor. C1 UNIV WISCONSIN HOSP & CLIN, DEPT MED, SECT ENDOCRINOL DIABET & METAB, CTR CLIN SCI H4568, MADISON, WI 53792 USA. UNIV WISCONSIN HOSP & CLIN, DEPT SURG, MADISON, WI 53792 USA. UNIV WISCONSIN HOSP & CLIN, DEPT RADIOL, MADISON, WI 53792 USA. UNIV WISCONSIN HOSP & CLIN, DEPT PATHOL, MADISON, WI 53792 USA. WILLIAM S MIDDLETON MEM VET ADM MED CTR, MED SERV, MADISON, WI 53705 USA. NR 33 TC 7 Z9 7 U1 0 U2 1 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0804-4643 J9 EUR J ENDOCRINOL JI Eur. J. Endocrinol. PD JUL PY 1997 VL 137 IS 1 BP 79 EP 83 DI 10.1530/eje.0.1370079 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XK498 UT WOS:A1997XK49800016 PM 9242206 ER PT J AU Bidaud, C Salomon, R VanCamp, G Pelet, A Attie, T Eng, C Bonduelle, M Amiel, J NihoulFekete, C Willems, PJ Munnich, A Lyonnet, S AF Bidaud, C Salomon, R VanCamp, G Pelet, A Attie, T Eng, C Bonduelle, M Amiel, J NihoulFekete, C Willems, PJ Munnich, A Lyonnet, S TI Endothelin-3 gene mutations in isolated and syndromic Hirschsprung disease SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article DE Hirschsprung disease; Waardenburg syndrome; endothelin; neural crest cells; enteric nervous system; malformation ID SHAH-WAARDENBURG SYNDROME; RET PROTOONCOGENE; GERMLINE MUTATIONS; RECEPTOR; CHROMOSOME-10; GDNF AB Hirschsprung disease (HSCR, aganglionic megacolon) is a frequent congenital malformation regarded as a multigenic neurocristopathy. Four susceptibility genes have recently been identified in HSCR, namely the RET proto-oncogene, the glial cell line-derived neurotrophic factor (GDNF), the endothelin B receptor (EDNRB) and the endothelin-3 genes (EDN3). Homozygosity for EDN3 mutations has been previously shown to cause the Shah-Waardenburg syndrome, a combination of HSCR with features of the Waardenburg syndrome. Here, we report on heterozygous EDN3 missense mutations in isolated HSCR. The present data give further support to the role of the endothelin-signaling pathway in the development of neural crest-derived enteric neurons. They also suggest the possibility that either recessive or weakly penetrant dominant alleles could occur at the EDN3 locus, depending on the nature of the mutation. C1 HOP NECKER ENFANTS MALAD,DEPT GENET,INSERM,U393,UNITE RECH HANDICAPS GENET ENFANT,F-75743 PARIS 15,FRANCE. HOP NECKER ENFANTS MALAD,CLIN CHIRURG INFANTILE,F-75743 PARIS 15,FRANCE. UNIV ANTWERP,DEPT MED GENET,B-2020 ANTWERP,BELGIUM. HARVARD UNIV,SCH MED,DEPT MED,DANA FARBER CANC INST,DIV CANC EPIDEMIOL & CONTROL,BOSTON,MA. FREE UNIV BRUSSELS,DEPT MED GENET,B-1050 BRUSSELS,BELGIUM. RI Van Camp, Guy/F-3386-2013; OI Van Camp, Guy/0000-0001-5105-9000; Eng, Charis/0000-0002-3693-5145 NR 22 TC 67 Z9 70 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-4813 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD JUL-AUG PY 1997 VL 5 IS 4 BP 247 EP 251 PG 5 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA YA534 UT WOS:A1997YA53400013 PM 9359047 ER PT J AU Tomera, JF Harakal, C AF Tomera, JF Harakal, C TI Multiple linear regression analysis of blood pressure, hypertrophy, calcium and cadmium in hypertensive and non-hypertensive states SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE blood pressure; calcium; cadmium; cadmium-induced hypertension; hypertrophy; multiple linear regression analysis; renal hypertension ID SIGNAL-TRANSDUCTION MECHANISMS; SURFACE AREA BURN; MULTIVARIATE INFLUENCE; VECTORIAL ANALYSIS; INOSITOL 1,4,5-TRIPHOSPHATE; POLYINOSITOL PHOSPHATES; SKELETAL-MUSCLE; CROSS-TALK; TRAUMA; DIAPHRAGM AB High blood pressure causes heart disease and remains a major public health issue. This paper expands mathematically and mechanistically on environmental heavy metal exposure and heart disease. In rabbits, mean blood pressure was measured by direct puncture of the middle ear artery. Measurements of calcium and cadmium levels were made by flame atomic absorption spectrophotometry in tissue from hypertensive and non-hypertensive rabbits. Relationships between blood pressure, hypertrophy, calcium and cadmium were tested using multiple regression analysis. Multiple linear relationships occurred showing the dependence of: high blood pressure on hypertrophy, calcium and cadmium; hypertrophy on calcium, cadmium and high blood pressure; and calcium on cadmium, high blood pressure and hypertrophy. These data provide insight into the mechanism of elevated blood pressure on heavy metal and calcium accumulation, and cardiac hypertrophy. (C) 1997 Elsevier Science Ltd. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. SHRINERS BURN INST,LAB ANESTHESIA SERV,CLIN PHARMACOL LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT ANAESTHESIOL,BOSTON,MA 02114. TEMPLE UNIV,SCH MED,DEPT PHARMACOL,PHILADELPHIA,PA 19140. FU NHLBI NIH HHS [HL 14217] NR 26 TC 8 Z9 12 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD JUL PY 1997 VL 35 IS 7 BP 713 EP 718 DI 10.1016/S0278-6915(97)00042-2 PG 6 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA XU582 UT WOS:A1997XU58200011 PM 9301656 ER PT J AU Werner, J Laposata, M FernandezDelCastillo, C Saghir, M Iozzo, RV Lewandrowski, KB Warshaw, AL AF Werner, J Laposata, M FernandezDelCastillo, C Saghir, M Iozzo, RV Lewandrowski, KB Warshaw, AL TI Pancreatic injury in rats induced by fatty acid ethyl ester, a nonoxidative metabolite of alcohol SO GASTROENTEROLOGY LA English DT Article ID TRYPSINOGEN-ACTIVATION PEPTIDES; LOW-DENSITY-LIPOPROTEIN; ETHANOL-METABOLISM; CHOLESTERYL ESTERS; SERUM; IDENTIFICATION; ACETALDEHYDE; CONSUMPTION; PARTICLE; ENZYMES AB Background & Aims: The mechanism by which alcohol injures the pancreas remains unknown. Alcohol-intoxicated humans have high levels of fatty acid ethyl esters (FAEEs), nonoxidative products of ethanol metabolism, in blood, pancreas, and liver. The aims of this study were to determine whether FAEEs are toxic to the pancreas in vivo and, if so, to assess whether this injury is specific to the pancreas and to compare it to the injury observed in acute pancreatitis. Methods: FAEEs were infused into Sprague-Dawley rats. Levels of FAEEs in plasma and pancreas were measured, and pancreatic injury was assessed during a 48-hour period for edema formation and ectopic trypsinogen activation and by light and electron microscopy. Results: FAEEs induced highly significant increases in pancreatic edema, pancreatic trypsinogen activation, and vacuolization of acinar cells. These findings were specific to the pancreas and were not found in liver, lung, myocardium, skeletal muscle, or subcutaneous fat. Conclusions: FAEEs at concentrations found in human plasma produce a pancreatitis-like injury in rats, providing direct evidence that FAEEs can produce organ-specific toxicity. Thus, FAEEs may contribute to acute alcohol-induced damage to the pancreas. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,DIV CLIN LABS,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT PATHOL ANAT & CELL BIOL,PHILADELPHIA,PA 19107. OI Iozzo, Renato/0000-0002-5908-5112 FU NCI NIH HHS [R01 CA39481, R01 CA47282] NR 63 TC 140 Z9 140 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JUL PY 1997 VL 113 IS 1 BP 286 EP 294 DI 10.1016/S0016-5085(97)70106-9 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA XJ383 UT WOS:A1997XJ38300039 PM 9207289 ER PT J AU Shea, JA Asch, DA Johnson, RF Staroscik, RN Malet, PF Pollack, BJ Clarke, JR Green, PE Schwartz, JS Williams, SV AF Shea, JA Asch, DA Johnson, RF Staroscik, RN Malet, PF Pollack, BJ Clarke, JR Green, PE Schwartz, JS Williams, SV TI What predicts gastroenterologists' and surgeons' diagnosis and management of common bile duct stones? SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID ENDOSCOPIC RETROGRADE CHOLANGIOGRAPHY; LAPAROSCOPIC CHOLECYSTECTOMY; OPERATIVE CHOLANGIOGRAPHY; INTRAOPERATIVE CHOLANGIOGRAPHY; MULTIVARIATE-ANALYSIS; RANDOMIZED TRIAL; ROUTINE; EXPERIENCE; PHYSICIANS; INJURIES AB Background: Because the literature suggests numerous indicators of common bile duct stones, we undertook a systematic assessment of physicians' judgments of the clinical utility of eight indicators: patient age, history of jaundice, history of pancreatitis, levels of serum alanine aminotransferase, alkaline phosphatase, amylase, and total bilirubin, and common bile duct diameter on ultrasonography. Methods: Random samples of 1500 gastroenterologists and 1500 surgeons were sent a survey asking them to indicate the importance of each potential indicator of common bile duct stones, the likelihood of common bile duct stones for each of nine clinical vignettes, and whether they would order a preoperative ERCP. An abbreviated survey was sent to nonrespondents. Results: Although there was substantial variation in the importances assigned to each indicator, the most important indicators were serum total bilirubin and diameter of common bile duct on ultrasound. The best predictors of the decision to order an ERCP were perceived likelihood of stones and specialty. The average threshold for ordering an ERCP was 37%. Respondents did not differ from nonrespondents in the perceived importance of the eight indicators. Conclusions: The substantial variation among gastroenterologists and surgeons regarding the optimal approach to common bile duct stones has clinical implications. Patients will receive varying recommendations for care, depending on whom they see. C1 UNIV PENN,WHARTON SCH,DEPT SURG,DEPT MED,DIV GASTROENTEROL,PHILADELPHIA,PA 19104. UNIV PENN,LEONARD DAVIS INST HLTH ECON,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,CTR CLIN EPIDEMIOL & BIOSTAT,PHILADELPHIA,PA 19104. VET AFFAIRS MED CTR,PHILADELPHIA,PA. ALLEGHENY UNIV HLTH SCI,DEPT SURG,PHILADELPHIA,PA 19102. RP Shea, JA (reprint author), UNIV PENN,WHARTON SCH,DEPT SURG,DEPT MED,DIV GEN INTERNAL MED,RALSTON HOUSE 318,3615 CHESTNUT ST,PHILADELPHIA,PA 19104, USA. FU AHRQ HHS [HS06481] NR 45 TC 12 Z9 12 U1 0 U2 1 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 JUL PY 1997 VL 46 IS 1 BP 40 EP 47 DI 10.1016/S0016-5107(97)70208-6 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA XQ654 UT WOS:A1997XQ65400008 PM 9260704 ER PT J AU Eng, C AF Eng, C TI From bench to bedside ... but when? SO GENOME RESEARCH LA English DT Article ID CANCER SUSCEPTIBILITY GENE; MEDULLARY-THYROID CARCINOMA; NEOPLASIA TYPE 2A; RET PROTOONCOGENE; OVARIAN-CANCER; BREAST-CANCER; FAMILIAL BREAST; MUTATIONS; PHENOTYPE; DISEASE C1 UNIV CAMBRIDGE,CANC RES CAMPAIGN,HUMAN CANC GENET RES GRP,CAMBRIDGE,ENGLAND. RP Eng, C (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT ADULT ONCOL,HUMAN CANC GENET UNIT,BOSTON,MA 02115, USA. OI Eng, Charis/0000-0002-3693-5145 FU NIA NIH HHS [1P30AG13314-01] NR 29 TC 5 Z9 5 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 1054-9803 J9 GENOME RES JI Genome Res. PD JUL PY 1997 VL 7 IS 7 BP 669 EP 672 PG 4 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA XM094 UT WOS:A1997XM09400003 PM 9253596 ER PT J AU Johnson, SM Cheng, HM Pineda, R Nietland, PA AF Johnson, SM Cheng, HM Pineda, R Nietland, PA TI Magnetic resonance imaging of cyclodialysis clefts SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 14-15, 1995 CL SARASOTA, FL SP Assoc Res Vis & Ophthalmol AB Background: Our purpose was to determine whether cyclodialysis clefts call be imaged with magnetic resonance imaging (MRI), Methods: Surgical cyclodialysis clefts extending approximately 3 clock hours were created in four New Zealand white rabbits. Eyes were scanned with an ocular MRI coil. Images obtained after intravenous gadolinium. topical gadolinium, and gadolinium injected into the cleft were compared to images obtained without contrast. Two human eyes were also scanned for cyclodialysis clefts with MRI. Results. Direct injection of gadolinium into the suprachoroid space yielded definitive localization and delineation of the cyclodialysis cleft. Cyclodialysis clefts could also be imaged following enhancement with topical or intravenous gadolinium. Without contrast medium, the clefts could not be clearly identified in rabbits. In a patient with hypotony and choroidal effusion following cataract surgery, a cyclodialysis cleft and enhancement of the suprachoroidal space were found with intravenous administration of gadolinium. MRI from a patient with a trabeculo-suprachoroidal shunt also demonstrated gadolinium enhancement of the suprachoroidal space. Conclusion: Cyclodialysis clefts can be imaged using gadolinium-enhanced MRI in rabbits and humans. C1 KING KHALID EYE SPECIALIST HOSP,RIYADH 11462,SAUDI ARABIA. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,BOSTON,MA. FU NEI NIH HHS [EY08925] NR 6 TC 4 Z9 4 U1 0 U2 1 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 JUL PY 1997 VL 235 IS 7 BP 468 EP 471 DI 10.1007/BF00947068 PG 4 WC Ophthalmology SC Ophthalmology GA XL023 UT WOS:A1997XL02300011 PM 9248845 ER PT J AU Schorge, JO Molpus, KL Koelliker, D Nikrui, N Goodman, A Fuller, AF AF Schorge, JO Molpus, KL Koelliker, D Nikrui, N Goodman, A Fuller, AF TI Stage IB and IIA cervical cancer with negative lymph nodes: The role of adjuvant radiotherapy after radical hysterectomy SO GYNECOLOGIC ONCOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the New-England-Association-of-Gynecologic-Oncologists CY JUN 14-16, 1996 CL OGUNQUIT, ME SP New England Assoc Gynecol Oncol ID SQUAMOUS-CELL CARCINOMA; PELVIC LYMPHADENECTOMY; GYNECOLOGIC ONCOLOGY; PROGNOSTIC FACTORS; RADIATION-THERAPY; METASTASES; RECURRENCE; SIZE; RISK AB The records of 171 patients with lymph node-negative stage IB and IIA cervical cancer primarily treated with radical hysterectomy and pelvic lymphadenectomy from 1974 to 1992 were retrospectively reviewed to identify poor prognostic factors and evaluate the role of adjuvant pelvic radiotherapy. One hundred sixteen patients (68%) were treated with radical hysterectomy alone (RH) and 55 patients (32%) received adjuvant radiotherapy (RH + RT). Factors predictive of recurrence for the entire group of patients included lymph-vascular space invasion (LVSI) (P = 0.003) and grade 3 histology (P = 0.04). Patients receiving RH + RT were older and more likely to have outer third cervical wall invasion, LVSI, positive margins, greater than or equal to 2 cm pathologic tumor size, and > 4 cm clinical tumor size (all P < 0.05). Overall, 28 patients (16%) developed recurrent disease with no difference between RH and RH + RT groups. After controlling for confounding variables, patients with LVSI who received RH + RT were less likely to develop disease recurrence than patients receiving RH alone (P = 0.04). LVSI is an important prognostic variable in lymph node-negative stage IB and IIA cervical cancer. Although adjuvant pelvic radiotherapy may decrease the risk of recurrence in patients with LVSI, the majority of patients with negative lymph nodes may be treated with radical surgery alone. (C) 1997 Academic Press. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DIV GYNECOL ONCOL,VINCENT MEM OBSTET & GYNECOL SERV,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02114. NR 19 TC 53 Z9 59 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD JUL PY 1997 VL 66 IS 1 BP 31 EP 35 DI 10.1006/gyno.1997.4691 PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA XN023 UT WOS:A1997XN02300007 PM 9234917 ER PT J AU Bemporad, J Prince, JB Wilens, TE AF Bemporad, J Prince, JB Wilens, TE TI ADD: The media as a referral source SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; PSYCHIATRIC STATUS; CHILDHOOD-ONSET; ADULTS; COMORBIDITY; PREVALENCE; CHILDREN; METHYLPHENIDATE; POPULATION; PATTERNS C1 CORNELL UNIV,MED CTR,NEW YORK HOSP,DEPT PSYCHIAT,NEW YORK,NY 10021. HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. MCLEAN HOSP,BELMONT,MA 02178. NR 33 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 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD JUL-AUG PY 1997 VL 5 IS 2 BP 82 EP 90 DI 10.3109/10673229709034731 PG 9 WC Psychiatry SC Psychiatry GA XN402 UT WOS:A1997XN40200004 PM 9385025 ER PT J AU Burack, JH Back, AL Pearlman, RA AF Burack, JH Back, AL Pearlman, RA TI Provoking nonepileptic seizures: The ethics of deceptive diagnostic testing SO HASTINGS CENTER REPORT LA English DT Article ID PSYCHOGENIC SEIZURES; PSEUDOSEIZURES; EPILEPSY; PROVOCATION; SUGGESTION C1 UNIV CALIF BERKELEY,SCH PUBL HLTH,BERKELEY,CA 94720. UNIV WASHINGTON,SCH MED,DIV ONCOL,SEATTLE,WA 98195. UNIV WASHINGTON,SCH MED,DIV GERONTOL & GERIATR MED,SEATTLE,WA 98195. VET AFFAIRS PUGET SOUND HLTH CARE SYST,CTR CLIN,SEATTLE,WA. RP Burack, JH (reprint author), UNIV CALIF SAN FRANCISCO,DIV GEN INTERNAL MED,SAN FRANCISCO,CA 94143, USA. NR 25 TC 5 Z9 5 U1 1 U2 2 PU HASTINGS CENTER PI BRIARCLIFF MANOR PA 255 ELM ROAD, BRIARCLIFF MANOR, NY 10510 SN 0093-0334 J9 HASTINGS CENT REP JI Hastings Cent. Rep. PD JUL-AUG PY 1997 VL 27 IS 4 BP 24 EP 33 DI 10.2307/3528776 PG 10 WC Ethics; Health Care Sciences & Services; Medical Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Health Care Sciences & Services; Medical Ethics; Biomedical Social Sciences GA XR919 UT WOS:A1997XR91900009 PM 9271719 ER PT J AU Som, PM Curtin, HD Silvers, AR AF Som, PM Curtin, HD Silvers, AR TI A re-evaluation of imaging criteria to assess aggressive masticator space tumors SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK LA English DT Article DE masticator space; malignancy; parapharyngeal space; computed tomography; magnetic resonance imaging ID PARAPHARYNGEAL SPACE; NECK; CT; HEAD; RHABDOMYOSARCOMA; DIAGNOSIS; SARCOMAS; JAWS AB Purpose. To evaluate the correlation between the gross imaging evidence of an aggressive masticator space (MS) tumor and the presence of such a MS malignancy. Materials and Methods: Thirty patients were identified retrospectively who had a malignancy that either arose in or metastasized to the MS, had pathologic verification of the diagnosis, and had magnetic resonance (MR) and/or computed tomographic (CT) images. Specifically evaluated was the presence or absence of gross imaging evidence of mandibular erosion and the integrity of the medial MS fascia as evaluated by a smooth margin between this fascia and the parapharyngeal space fat. Results. Of the 30 tumors, 28 were high-grade malignancies and 2 were histiocytoses. Of these, 5 had mandibular erosion and violation of the MS fascia, 19 had bone erosion with an intact fascia, 4 had neither bone erosion nor fascial violation (3 of these patients were under the age of 20 years), and 2 had fascial violation with no bone erosion. Conclusions. In 76.7% of patients with a malignancy arising in the MS, on imaging the medial MS fascia was grossly intact. There were 4 patients with MS malignancy and neither violation of the medial MS fascia nor mandibular bone erosion. Thus, these imaging findings may not be good criteria to evaluate the presence of a high-grade MS malignancy, especially ii the patient is under the age of 20 years, in which age group MS sarcomas are more likely to arise. (C) 1997 John Wiley & Sons, Inc. C1 CUNY MT SINAI SCH MED, DEPT OTOLARYNGOL, NEW YORK, NY 10029 USA. MASSACHUSETTS EYE & EAR INFIRM, DEPT RADIOL, BOSTON, MA 02114 USA. RP Som, PM (reprint author), MT SINAI HOSP, DEPT RADIOL, 1 GUSTAVE LEVY PL, NEW YORK, NY 10029 USA. NR 49 TC 6 Z9 6 U1 0 U2 1 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1043-3074 J9 HEAD NECK-J SCI SPEC JI Head Neck-J. Sci. Spec. Head Neck PD JUL PY 1997 VL 19 IS 4 BP 335 EP 341 DI 10.1002/(SICI)1097-0347(199707)19:4<335::AID-HED12>3.0.CO;2-8 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA XG726 UT WOS:A1997XG72600012 PM 9213112 ER PT J AU Woodward, ER Eng, C McMahon, R Voutilainen, R Affara, NA Ponder, BAJ Maher, ER AF Woodward, ER Eng, C McMahon, R Voutilainen, R Affara, NA Ponder, BAJ Maher, ER TI Genetic predisposition to phaeochromocytoma: Analysis of candidate genes GDNF, RET and VHL SO HUMAN MOLECULAR GENETICS LA English DT Article ID MULTIPLE ENDOCRINE NEOPLASIA; TUMOR-SUPPRESSOR GENE; HIPPEL-LINDAU DISEASE; MEDULLARY-THYROID CARCINOMA; TYROSINE KINASE DOMAIN; HIRSCHSPRUNG DISEASE; GERMLINE MUTATIONS; POINT MUTATION; MEN 2A; PROTOONCOGENE AB Inherited predisposition to phaeochromocytoma (MIM No 171300) occurs in multiple endocrine neoplasia type 2 (MEN 2) (MIM No 171400), von Hippel-Lindau (VHL) disease (MIM No 199300), and neurofibromatosis type 1 (NF1) (MIM No 162200), In addition, familial phaeochromocytoma alone has also been reported and we and others have identified germline VHL mutations in five of six kindreds analysed previously, Germline mutations in the RET proto-oncogene, which encodes a receptor tyrosine kinase, and in the VHL tumour suppressor gene cause MEN 2 and VHL disease, respectively, To further investigate the genetics of phaeochromocytoma predisposition, we analysed three groups of patients with no evidence of VHL disease, MEN 2 or NF1: Group A, eight kindreds with familial phaeochromocytoma; Group B, two patients with isolated bilateral phaeochromocytoma; and Group C, six cases of multiple extra-adrenal phaeochromocytoma or adrenal phaeochromocytoma with a family history of neuroectodermal tumours, Germline missense VHL mutations were identified in three of eight kindreds with familial phaeochromocytoma, A germline VHL mutation was also characterised in one of the two patients with bilateral phaeochromocytoma, No VHL or RET mutations were detected in the final group of patients with multiple extra-adrenal phaeochromocytoma or adrenal phaeochromocytoma with a family history of neuroectodermal tumours, The absence of germline VHL and RET gene mutations in many of these families suggested that other phaeochromocytoma susceptibility loci may exist, Glial cell line-derived neurotrophic factor (GDNF) has been recently identified as a natural ligand for RET Thus, it seems plausible that GDNF is a good candidate gene to play a role in phaeochromocytoma susceptibility, We searched for germline mutations in GDNF in 16 cases of familial phaeochromocytoma (groups A, B and C) and looked for evidence of somatic change in GDNF in 28 sporadic phaeochromocytomas, 12 MEN 2 phaeochromocytomas and five VHL phaeochromocytomas, No GDNF mutations were identified in patients with familial phaeochromocytoma disease, but a c277C-->T (R93W) sequence variant was identified in one of 28 sporadic tumours, This candidate mutation was identified in the germline and tumour tissue but was not present in 104 control GDNF alleles, GDNF sequence variants including R93W have been suggested previously to represent low penetrance susceptibility mutations for Hirschsprung disease and the R93W was not identified in 376 control alleles studied by others, These findings suggest that although GDNF mutations do not appear to have a major role in the pathogenesis of familial or sporadic phaeochromocytomas, allelic variation at the GDNF locus may modify phaeochromocytoma susceptibility. C1 UNIV BIRMINGHAM,DEPT PAEDIAT & CHILD HLTH,DIV MED GENET,BIRMINGHAM B15 2TG,W MIDLANDS,ENGLAND. UNIV CAMBRIDGE,DEPT PATHOL,CAMBRIDGE CB2 1QP,ENGLAND. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC EPIDEMIOL & CONTROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,CHARLES A DANA DIV HUMAN CANC GENET,BOSTON,MA 02115. UNIV CAMBRIDGE,ADDENBROOKES HOSP,CRC,HUMAN CANC GENET RES GRP,CAMBRIDGE CB2 2QQ,ENGLAND. UNIV HELSINKI,DEPT PATHOL,FIN-00014 HELSINKI,FINLAND. ADDENBROOKES NHS TRUST,MOL GENET LAB,E ANGLIAN REG GENET SERV,CAMBRIDGE CB2 2QQ,ENGLAND. RI MAHER, EAMONN/A-9507-2008; OI MAHER, EAMONN/0000-0002-6226-6918; Eng, Charis/0000-0002-3693-5145 NR 35 TC 86 Z9 88 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JUL PY 1997 VL 6 IS 7 BP 1051 EP 1056 DI 10.1093/hmg/6.7.1051 PG 6 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA XH932 UT WOS:A1997XH93200011 PM 9215674 ER PT J AU Teicher, BA Ara, G Herbst, R Takeuchi, H Keyes, S Northey, D AF Teicher, BA Ara, G Herbst, R Takeuchi, H Keyes, S Northey, D TI PEG-hemoglobin: Effects on tumor oxygenation and response to chemotherapy SO IN VIVO LA English DT Article ID POLY(ETHYLENE GLYCOL)-MODIFIED PROTEINS; MELPHALAN ANTITUMOR-ACTIVITY; CYTOTOXIC CANCER THERAPIES; RAT MAMMARY-CARCINOMA; FLUOSOL-DA; POLYETHYLENE-GLYCOL; CYTO-TOXICITY; RADIATION-THERAPY; X-RAYS; REOXYGENATION AB Background: The study was undertaken to determine whether administration of PEG-hemoglobin could improve the oxygenation of a solid tumor prior to and after chemotherapy and to determine whether administration of PEG-hemoglobin could enhance the efficacy of chemotherapy in a solid tumor. Materials and Methods: Rats bearing the 13762 mammary carcinoma were untreated or treated with cyclophosphamide, melphalan, taxol or cisplatin. Tumor oxygenation was determined 24 hrs. after chemotherapy with or without administration of PEG-hemoglobin while the animals breathed air, 28% oxygen or carbogen. Mice bearing the EMT-6 murine mammary carcinoma were treated with single doses of chemotherapy with or without co-administration of PEG-hemoglobin and tumor cell and bone marrow CFU-GM survivals were determined Other EMT-6 tumor-bearing mice were treated with multiple doses of chemotherapy with or without PEG-hemoglobin and tumor growth delay was determined. Results: Administration of PEG-hemoglobin was effective in decreasing hypoxia in the 13762 mammary carcinoma both prior to and after chemotherapy administration Increasing the level of inspired oxygen further decreased the tumor hypoxia most effectively when the level of tumor cell killing by the chemotherapy was high. Administration of PEG-hemoglobin along with air breathing to mice bearing the EMT-6 tumor increased tumor cell killing by cyclophosphamide, BCNU, adriamycin and taxol without increasing toxicity to the bone marrow CFU-GM. PEG-Hemoglobin given prior to each dose of chemotherapy increased the tumor growth delay produced by cyclophosphamide, adriamycin, 5-fluorouracil, BCNU and taxol in a manner with increased level of inspired oxygen and with a concomitant decreased in lung metastases. Conclusions: Further investigation of PEG-hemoglobin as an oxygen delivery agent in oncology is warranted. C1 JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. RP Teicher, BA (reprint author), DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. NR 54 TC 21 Z9 21 U1 0 U2 1 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDNTIOU-KALAMOU RD KAPANDRITI, POB 22, ATHENS 19014, GREECE SN 0258-851X J9 IN VIVO JI In Vivo PD JUL-AUG PY 1997 VL 11 IS 4 BP 301 EP 311 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA XP730 UT WOS:A1997XP73000003 PM 9292296 ER PT J AU Williams, DM Grubbs, BG Pack, E Kelly, K Rank, RG AF Williams, DM Grubbs, BG Pack, E Kelly, K Rank, RG TI Humoral and cellular immunity in secondary infection due to murine Chlamydia trachomatis SO INFECTION AND IMMUNITY LA English DT Article ID DEFICIENT MICE; T-CELLS; MOUSE PNEUMONITIS; GAMMA-INTERFERON; HOST DEFENSE; GENITAL-INFECTION; ROLE INVIVO; AGENT; RESOLUTION; ANTIBODY AB A murine model of pneumonia due to the mouse pneumonitis agent (MoPn [murine Chlamydia trachomatis]) in mice deficient in CD4(+) T-cell function (major histocompatibility complex [MHC] class II function [class II-/-], CD8(+) T-cell function (beta(2)-microglobulin deficient, MHC class I deficient [Beta(2)m(-/-)]), B-cell function (C57BL/10J-Igh(tm1Cgn) [Igh(-/-)]), and gamma Interferon (IFN-gamma) (C57BL/6-Ifg(tm1) [Ifg(-/-)]) or interleukin-4 (C57/BLtm1Cgn129 [IL4(-/-)]) production was employed to determine if each of these mechanisms was critical to resistance against reinfection by C. trachomatis or if alternate compensatory mechanisms existed in their absence which could potentially be exploited in vaccine development. Resistance to reinfection with MoPn was heavily dependent on CD4(+) T cells. CD4 T-cell-deficient MHC class II-/- mice sere very susceptible to reinfection with MoPn, showing the critical importance of this cell to resistance. These mice lacked antibody production hut did produce IFN-gamma, apparently hy mechanisms involving NK and CD8(+) T cells. Neutralization of IFN-gamma in these mice led to a borderline increase in susceptibility showing a possible role (albeit small) of this cytokine in this setting, Tumor necrosis factor alpha (TNF-alpha) was also present at increased levels in these mice, Igh(-/-) B-cell-deficient mice which produce no antibody to MoPn were only modestly more susceptible to reinfection than immunized B-cell-intact controls, shelving that antibody, including lung immunoglobulin A, if not an absolute requirement for relatively successful host defense in this setting. Levels of lung IFN-gamma and TNF-alpha were elevated in Igh(-/-) miff compared to those in controls. IL-4(-/-) mice (deficient in Th2 function) could develop normal resistance to reinfection with MoPn. Conversely, normal mice rendered partially IFN-gamma deficient by antibody depletion were somewhat impair ed in their ability to develop acquired immunity to MoPn, again indicating a role for this cytokine in host defense against rechallenge. Of most importance, however, congenitally IFN-gamma-deficient Ifg(-/-) mice (which have elevated levels of other cytokines, including TNF-alpha and granulocyte-macrophage colony-stimulating fatter) are paradoxically more resistant to MoPn rechallenge than controls, showing that IFN-gamma if not an absolute requirement for acquired resistance and implying the presence of very effective compensatory host defense mechanism(s). In vivo depletion of TNF-alpha significantly increased MoPn levels in the lungs in these mice. Thus, resistance to reinfection in this model is flexible and multifactorial and is heavily dependent on CD4(+) T cells, with a probable role for IFN-gamma and TNF-alpha and a possible modest role for Th1-dependent antibody Since IFN-gamma was dispensable in host defense, the highly effective mechanism or mechanisms which can compensate for its absence (which include TNF-alpha) deserve further study. C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. UNIV ARKANSAS MED SCI HOSP,DEPT MICROBIOL & IMMUNOL,LITTLE ROCK,AR 72205. RP Williams, DM (reprint author), AUDIE L MURPHY MEM VET ADM MED CTR,DIV INFECT DIS,7400 MERTON MINTER BLVD,SAN ANTONIO,TX 78284, USA. FU NIAID NIH HHS [R01 AI026328] NR 35 TC 61 Z9 62 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUL PY 1997 VL 65 IS 7 BP 2876 EP 2882 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA XF631 UT WOS:A1997XF63100051 PM 9199462 ER PT J AU Ryan, ET Butterton, JR Smith, RN Carroll, PA Crean, TI Calderwood, SB AF Ryan, ET Butterton, JR Smith, RN Carroll, PA Crean, TI Calderwood, SB TI Protective immunity against Clostridium difficile toxin A induced by oral immunization with a live, attenuated Vibrio cholerae vector strain SO INFECTION AND IMMUNITY LA English DT Article ID ESCHERICHIA-COLI; B-SUBUNIT; HOSPITAL ENVIRONMENT; NUCLEOTIDE-SEQUENCE; SECRETION SYSTEM; OUTER-MEMBRANE; A GENE; VACCINE; INFECTION; BINDING AB Clostridium difficile causes pseudomembranous colitis through the action of Rho-modifying proteins, toxins A and B. Antibodies directed against C. difficile toxin A prevent or limit C. difficile-induced colitis. We engineered plasmid pETR14, containing the hlyB and hlyD genes of the Escherichia coli hemolysin operon, to express a fusion protein containing 720 amino acid residues from the nontoxic, receptor-binding, carboxy terminus of C. difficile toxin A and the secretion signal of E. coli hemolysin A. We introduced pETR14 into Vibrio cholerae and found that the toxin A-HlyA fusion protein was secreted by a number of V. cholerae strains and recognized by both monoclonal and polyclonal anti-C. difficile toxin A antibodies. We introduced pETR14 into an attenuated V. cholerae strain, O395-NT, and inoculated rabbits orally with this construct. Colonization studies disclosed that the V. cholerae vector containing pETR14 was recoverable from rabbit ilea up to 5 days after oral inoculation. Vaccination produced significant systemic anti-C. difficile toxin A immunoglobulin G and anti-V. cholerae vibriocidal antibody responses. Vaccination also produced significant protection against toxin A in an ileal loop challenge assay, as assessed by determination of both fluid secretion and histological changes. These results suggest that the hemolysin system off. coli can be used successfully in V. cholerae vector strains to effect secretion of large heterologous antigens and that a V. cholerae vector strain secreting a nontoxic, immunogenic portion of C. difficile toxin A fused to the secretion signal of E. coli HlyA induces protective systemic and mucosal immunity against this toxin. C1 MASSACHUSETTS GEN HOSP,DIV INFECT DIS,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,IMMUNOPATHOL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOL GENET,BOSTON,MA 02115. FU NIAID NIH HHS [KO8 AI01386, AI40725, KO8 AI01332, R01 AI040725] NR 63 TC 71 Z9 71 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUL PY 1997 VL 65 IS 7 BP 2941 EP 2949 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA XF631 UT WOS:A1997XF63100059 PM 9199470 ER PT J AU AlvaradoCabrero, I Navani, SS Young, RH Scully, RE AF AlvaradoCabrero, I Navani, SS Young, RH Scully, RE TI Tumors of the fimbriated end of the Fallopian tube: A clinicopathologic analysis of 20 cases, including nine carcinomas SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Article DE Fallopian tube; fimbriae; tumors; carcinoma ID METAPLASTIC PAPILLARY TUMOR; ENDOMETRIOID CARCINOMA; PERITONEI; LESION AB Twenty tumors that were primary in the tubal fimbriae are reported. They were found in patients aged 17 to 83 (average 57) years. All were of mullerian type. Nine tumors were benign (eight adenofibromas, one cystadenoma), of which seven were serous and two, endometrioid. Two rumors were borderline, a serous papillary cystic tumor of borderline malignancy and an endometrioid adenofibroma of borderline malignancy. Nine tumors were carcinomas, of which four were serous, three endometrioid, and two undifferentiated. Follow-up information was available for six patients with carcinoma. One with serous carcinoma was well at 1 year; a second had ascites with malignant cytologic features nine years postoperatively and is currently on chemotherapy. One patient with endometrioid carcinoma was alive without disease after 8 years, and the other died. of tumor at 6.5 years. One patient with undifferentiated carcinoma was alive without disease ar 5 years and the other died of disease at eight months. The occurrence of fallopian tube tumors that arise in the fimbriae has received scanty attention in the literature. A fimbrial origin for the tumors is often overlooked initially. Carcinomas confined to the fimbriae cannot be adequately staged according to the current staging system of the International Federation of Gynecology and Obstetrics. It is proposed that they be placed in a new category, Stage I(F), because the tumor cells are exposed directly to the peritoneal cavity even though they do not invade the tubal wall. Although experience is limited it appears that they may have a worse prognosis than Stage I tribal tumors that are nonfimbrial. C1 MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,JAMES HOMER WRIGHT PATHOL LABS,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. NR 29 TC 44 Z9 47 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0277-1691 J9 INT J GYNECOL PATHOL JI Int. J. Gynecol. Pathol. PD JUL PY 1997 VL 16 IS 3 BP 189 EP 196 DI 10.1097/00004347-199707000-00001 PG 8 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA YH437 UT WOS:A1997YH43700001 PM 9421082 ER PT J AU Pins, MR Young, RH Crum, CP Leach, IH Scully, RE AF Pins, MR Young, RH Crum, CP Leach, IH Scully, RE TI Cervical squamous cell carcinoma in situ with intraepithelial extension to the upper genital tract and invasion of tubes and ovaries: Report of a case with human papilloma virus analysis SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Article DE carcinoma in situ; squamous cell; cervix; ovary; uterus; Fallopian tube; metastasis; human papilloma virus; polymerase chain reaction; in situ hybridization ID METASTASES; NEOPLASIA; CANCER AB A 55-year-old woman, who was found to have malignant squamous cells on a routine cervical smear, underwent a conization biopsy, followed by hysterectomy with bilateral salpingo-oophorectomy. No gross tumor was present in the uterus, but both ovaries, which were of normal size, contained multiple cysts filled with light brown, soft material. Microscopic examination showed squamous cell carcinoma in situ of the cervix with contiguous spread to the endometrium, fallopian tubes, and ovaries; squamous cell carcinoma extensively replaced the endometrial and tubal epithelium, focally invaded the wall of the fallopian tubes, and involved the parenchyma of both ovaries. Although an invasive cervical carcinoma occasionally spreads to the ovary, this case illustrates that exceptionally an In situ tumor spreads along the epithelium of the upper genital tract and the ovarian surface and invades the ovary and tubes. The detection of human papillomavirus DNA in the cervical, endometrial, tubal, and ovarian tumors by the polymerase chain reaction suggests a role for human papilloma virus infection in this case. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,JAMES HOMER WRIGHT PATHOL LABS,BOSTON,MA. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,WOMENS & PERINATAL PATHOL DIV,BOSTON,MA 02115. UNIV NOTTINGHAM HOSP,QUEENS MED CTR,DEPT HISTOPATHOL,NOTTINGHAM NG7 2UH,ENGLAND. NR 21 TC 48 Z9 51 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0277-1691 J9 INT J GYNECOL PATHOL JI Int. J. Gynecol. Pathol. PD JUL PY 1997 VL 16 IS 3 BP 272 EP 278 DI 10.1097/00004347-199707000-00014 PG 7 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA YH437 UT WOS:A1997YH43700013 PM 9421094 ER PT J AU Mohammad, AR Bauer, RL Yeh, CK AF Mohammad, AR Bauer, RL Yeh, CK TI Spinal bone density and tooth loss in a cohort of postmenopausal women SO INTERNATIONAL JOURNAL OF PROSTHODONTICS LA English DT Article ID OSTEOPOROSIS; PERIODONTITIS AB Osteoporosis has been suggested to contribute to the edentulous condition. However, studies specifically designed to examine the relationship between tooth loss and osteoporosis are scarce, and reported results have been mixed. This study investigated the correlation between tooth loss and spinal bone density in a nonHispanic white female population. Forty-four subjects were recruited and divided into high and low spinal bone density groups based on whether the bone density was higher or lower than the age-adjusted population mean bone density. Missing teeth and periodontal status in these groups were assessed and analyzed. Tooth loss was not significantly different between subjects with low spinal bone density (4.90 +/- 0.89 teeth) and high spinal bone density (3.81 +/- 0.90 teeth). Tooth loss did not differ after age and periodontal adjustment. However, the loss of attachment levels (relative to the cementoenamel junction) was greater in the low spinal bone density subjects (3.42 +/- 0.30 mm) than in the high spinal bone density subjects (2.37 +/- 0.26 mm) (P<.05). The difference may have resulted from gingival recession (P<.05), because the gingival pocket depths were not significantly different between the two groups. In this study, total tooth loss was not directly associated with systemic bone density. However, periodontal disease was negatively associated with spinal bone density. Whether periodontal disease will ultimately lead to greater tooth loss in law spinal bone density group merits further investigation. C1 UNIV SO CALIF,SCH DENT,DEPT DENT MED & PUBL HLTH,LOS ANGELES,CA 90089. UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM HOSP DIV,S TEXAS VET HLTH CARE SYST,CTR GERIATR RES EDUC & CLIN,SAN ANTONIO,TX. UNIV TEXAS,HLTH SCI CTR,DEPT DENT DIAGNOST SCI,SAN ANTONIO,TX. NR 22 TC 41 Z9 43 U1 0 U2 1 PU QUINTESSENCE PUBL CO INC PI CAROL STREAM PA 551 KIMBERLY DR, CAROL STREAM, IL 60188-1881 SN 0893-2174 J9 INT J PROSTHODONT JI Int. J. Prosthodont. PD JUL-AUG PY 1997 VL 10 IS 4 BP 381 EP 385 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA XN376 UT WOS:A1997XN37600011 PM 9484049 ER PT J AU Morris, MM Dallow, KC Zietman, AL Park, J Althausen, A Heney, NM Shipley, WU AF Morris, MM Dallow, KC Zietman, AL Park, J Althausen, A Heney, NM Shipley, WU TI Adjuvant and salvage irradiation following radical prostatectomy for prostate cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 37th Annual Scientific Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology (ASTRO) CY OCT 08-11, 1995 CL MIAMI, FL SP Amer Soc Therapeut Radiol & Oncol DE prostatectomy; pT3N0 disease; salvage irradiation ID PATHOLOGICAL STAGE-C; RADIATION-THERAPY; ANTIGEN LEVELS; ADENOCARCINOMA; RADIOTHERAPY; CARCINOMA; ERRORS; BEAM AB Purpose: We performed a retrospective analysis to assess the durability of benefit derived from irradiation after prostatectomy for pT3NO disease, and the possibility of cure. Methods and Materials: We studied 88 patients who were irradiated after prostatectomy and had available prostate specific antigen (PSA) data, no known nodal or metastatic disease, no hormonal treatment, and follow-up of at least 12 months from surgery, Forty patients received adjuvant therapy for a high risk of local failure with undetectable PSA, Forty-eight patients received salvage therapy for elevated PSA levels, Mean follow up was 44 months from date of surgery and 31 months from irradiation, Biochemical failure was strictly defined as a confirmed rise in PSA of >10%, or as the ability to detect a previously undetectable PSA value. Results: After salvage irradiation, 69% of patients attained an undetectable PSA, Eighty-eight percent of adjuvant patients were biochemically and clinically free of disease (bNED) at 3 years from prostatectomy, Sixty-eight percent of those receiving salvage irradiation were bNED 3 years after surgery, On univariate analysis, treatment group (adjuvant or salvage), pre-operative PSA, and the status of seminal vesicles were significant prognostic factors, The extent of PSA elevation in the salvage group was also significant, We did not demonstrate a significant difference between those salvage patients referred for persistently elevated PSA as compared to those with a late rise in PSA, On multivariate analysis, the only significant predictor of outcome was treatment group, with adjuvant irradiation having better outcome than salvage. Conclusion: More than two-thirds of this group of patients remain biochemically disease free at 3 years following irradiation, attesting to a number of potential cures, For patients with stage pT3NO prostate cancer following radical prostatectomy, our data support the use of either routine postoperative adjuvant irradiation or close PSA follow-up with early salvage treatment. (C) 1997 Elsevier Science Inc. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT UROL,BOSTON,MA 02114. RP Morris, MM (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,GENITOURINARY ONCOL UNIT,FRUIT ST,BOSTON,MA 02114, USA. NR 23 TC 137 Z9 137 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JUL 1 PY 1997 VL 38 IS 4 BP 731 EP 736 DI 10.1016/S0360-3016(97)00080-1 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA XM436 UT WOS:A1997XM43600008 PM 9240639 ER PT J AU Shen, Z Fox, JG Dewhirst, FE Paster, BJ Foltz, CJ Yan, L Shames, B Perry, L AF Shen, Z Fox, JG Dewhirst, FE Paster, BJ Foltz, CJ Yan, L Shames, B Perry, L TI Helicobacter rodentium sp. nov, a urease-negative Helicobacter species isolated from laboratory mice SO INTERNATIONAL JOURNAL OF SYSTEMATIC BACTERIOLOGY LA English DT Article ID CAMPYLOBACTER-CINAEDI; GASTRIC-CARCINOMA; PYLORI INFECTION; BACTERIUM; IDENTIFICATION; LIVERS; MUCOSA; RISK AB A spiral-shaped bacterium with bipolar, single, nonsheathed flagella was isolated from the intestines of laboratory mice. The organism grew at 37 and 42 degrees C under microaerobic and anaerobic conditions, did not hydrolyze urea, was weakly positive for catalase and oxidase, reduced nitrate to nitrite, did not hydrolyze indoxyl acetate or hippurate, and was resistant to cephalothin and nalidixic acid. This is the first urease-negative, murine Helicobacter spp. isolated from intestines. Also, Helicobacter pullorum and this bacterium are unique among the genus Helicobacter in having nonsheathed flagella. The new bacterium appears to be part of the normal intestinal flora; although its pathogenic potential is unknown, this organism was also isolated from scid mice with diarrhea that were co-infected with Helicobacter bills. On the basis of 16S rRNA gene sequence analysis data and biochemical and phenotypic criteria, the new organism is classified as a novel helicobacter, for which we propose the name Helicobacter rodentium. The type strain is MIT 95-1707 (= ATCC 700285). C1 MIT,DIV COMPARAT MED,CAMBRIDGE,MA 02139. FORSYTH DENT CTR,DEPT MOL GENET,BOSTON,MA 02115. FU NCI NIH HHS [R01 CA67529]; NCRR NIH HHS [RR01046, RR07036] NR 28 TC 105 Z9 107 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0020-7713 J9 INT J SYST BACTERIOL JI Int. J. Syst. Bacteriol. PD JUL PY 1997 VL 47 IS 3 BP 627 EP 634 PG 8 WC Microbiology SC Microbiology GA XK390 UT WOS:A1997XK39000004 PM 9226892 ER PT J AU Biederman, J Faraone, SV Hatch, M Mennin, D Taylor, A George, P AF Biederman, J Faraone, SV Hatch, M Mennin, D Taylor, A George, P TI Conduct disorder with and without mania in a referred sample of ADHD children SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE ADHD; conduct disorder; mania; bipolar; children ID DEFICIT HYPERACTIVITY DISORDER; RISK-FACTORS; COMORBIDITY; ADOLESCENTS; RELIABILITY; CHILDHOOD; INTERVIEW; BEHAVIOR; FAMILY; ADVERSITY AB Objective: To test the hypothesis that dysphoric and non-dysphoric types of CD could be distinguished from one another in their patterns of familiality, adversity, and comorbidity. Methods: We examined 140 ADHD and 120 normal controls at baseline and 4 years later using assessments from multiple domains. We compared ADHD subgroups with and without conduct (CD) and bipolar (BPD) disorders on psychiatric outcomes at a 4-year follow-up, familial psychopathology and psychosocial functioning. Results: We found that ADHD children with both disorders had higher familial and personal risk for mood disorders than those with CD only, who had a higher personal risk for antisocial personality disorder. Among ADHD probands, having both CD and BPD was associated with poorer functioning and an increased risk for psychiatric hospitalization. Discussion: Although preliminary, our findings suggest that the distinction between dysphoric and non-dysphoric CD may be clinically meaningful. If confirmed, our findings could have important diagnostic and therapeutic implications for the management of antisocial youth. (C) 1997 Elsevier Science B.V. C1 HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PSYCHIAT,HARVARD INST PSYCHIAT,MASSACHUSETTS HLTH CTR,BOSTON,MA 02115. HARVARD UNIV,MASSACHUSETTS HLTH CTR,DEPT PSYCHIAT,SCH MED,BOSTON,MA 02115. RP Biederman, J (reprint author), MASSACHUSETTS GEN HOSP,PSYCHIAT SERV,PEDIAT PSYCHOPHARMACOL UNIT ACC 725,FRUIT ST,BOSTON,MA 02114, USA. OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [R01 MH41314-07] NR 48 TC 52 Z9 53 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD JUL PY 1997 VL 44 IS 2-3 BP 177 EP 188 DI 10.1016/S0165-0327(97)00043-8 PG 12 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA XK226 UT WOS:A1997XK22600010 PM 9241578 ER PT J AU Lore, CJ AF Lore, CJ TI Student mental health and funding constraints: A delicate balance SO JOURNAL OF AMERICAN COLLEGE HEALTH LA English DT Article DE cost benefits; managed care; mental health; psychiatric disorders; university students AB A wide range of serious psychiatric disorders that would be progressive if untreated was observed during the first 9 months of a 1-year psychotherapy fellowship at the student health center of a major New England university. This finding underscores the cost benefits, in both human and financial terms, of having a multidisciplinary mental health center staff on campus to provide timely, intensive, and comprehensive interventions. RP Lore, CJ (reprint author), MASSACHUSETTS GEN HOSP,CHELSEA MEM HLTH CTR,CHELSEA,MA 02150, USA. NR 8 TC 2 Z9 2 U1 1 U2 1 PU HELDREF PUBLICATIONS PI WASHINGTON PA 1319 EIGHTEENTH ST NW, WASHINGTON, DC 20036-1802 SN 0744-8481 J9 J AM COLL HEALTH JI J. Am. Coll. Health PD JUL PY 1997 VL 46 IS 1 BP 43 EP 46 PG 4 WC Education & Educational Research; Public, Environmental & Occupational Health SC Education & Educational Research; Public, Environmental & Occupational Health GA XL369 UT WOS:A1997XL36900007 PM 9248242 ER PT J AU Kradin, RL AF Kradin, RL TI The psychosomatic symptom and the self: A sirens' song SO JOURNAL OF ANALYTICAL PSYCHOLOGY LA English DT Article DE psychosomatics; symbol; hysteria; multiple chemical sensitivity; narcissism; self; . AB This paper examines the symbolic nature of the psychosomatic symptom. It is suggested that the psychosomatic symptom is an informationally rich symbolic derivative of the Self that serves to focus attention on developmental disturbances in the archetypal processes of constructing body image and interpreting dysphoric somatic sensations. Clinical examples are offered to illustrate the changing nature of the psychomatic symptom in society. The therapeutic Importance of monitoring affectual transactions in the transference-countertransference field is stressed. C1 HARVARD UNIV,SCH MED,BOSTON,MA. CG INST,BOSTON,MA. RP Kradin, RL (reprint author), MASSACHUSETTS GEN HOSP,DEPT PULM MED PATHOL & PSYCHIAT,COX 5 BLDG,BOSTON,MA 02114, USA. NR 41 TC 2 Z9 2 U1 0 U2 0 PU ROUTLEDGE PI LONDON PA 11 NEW FETTER LANE, LONDON, ENGLAND EC4P 4EE SN 0021-8774 J9 J ANAL PSYCHOL JI J. Anal. Psychol. PD JUL PY 1997 VL 42 IS 3 BP 405 EP 423 DI 10.1111/j.1465-5922.1997.00405.x PG 19 WC Psychology, Psychoanalysis SC Psychology GA XL136 UT WOS:A1997XL13600004 PM 9246928 ER PT J AU Taylor, AE McCourt, B Martin, KA Anderson, EJ Adams, JM Schoenfeld, D Hall, JE AF Taylor, AE McCourt, B Martin, KA Anderson, EJ Adams, JM Schoenfeld, D Hall, JE TI Determinants of abnormal gonadotropin secretion in clinically defined women with polycystic ovary syndrome SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article; Proceedings Paper CT 10th Congress of the International-Society-for-Endocrinology CY JUN 12-15, 1996 CL SAN FRANCISCO, CA SP Int Soc Endocrinol ID FOLLICLE-STIMULATING-HORMONE; LUTEINIZING-HORMONE; HYPERANDROGENIC WOMEN; INSULIN-RESISTANCE; MENSTRUAL-CYCLE; PULSE FREQUENCY; BODY-WEIGHT; OBESE WOMEN; DISEASE; SERUM AB Polycystic ovary syndrome (PCOS) is a heterogeneous disorder of reproductive age women characterized in its broadest definition by the presence of oligomenorrhea and hyperandrogenism and the absence of other disorders. Defects of gonadotropin secretion, including an elevated LH level, elevated LH to FSH ratio, and an increased frequency and amplitude of LH pulsations have been described, but the prevalence of these defects in a large, unbiased population of PCOS patients has not been determined. Sixty-one women with PCOS defined by oligomenorrhea and hyperandrogenism and 24 normal women in the early follicular phase had LH samples obtained every 10 min for 8-12 h. Pool LH levels from the frequent sampling studies were within the normal range in the 9 PCOS patients (14.8%) who were studied within 21 days after a documented spontaneous ovulation. Excluding these post-ovulatory patients, 75.0% of the PCOS patients had an elevated pool LH level (above the 95th percentile of the normal controls), and 94% had an elevated LH to FSH ratio. In the anovulatory PCOS patients, pool LH correlated positively with 17-OH progesterone (R = 0.30, P = 0.03), but not with estradiol, estrone, testosterone, androstenedione, or DHEA-S. Pool LH and LH to FSH ratio correlated positively with LH pulse frequency (R = 0.40, P = 0.004 for pool LH, and R = 0.39; P = 0.005 for LH/FSH). There was also a strong negative correlation between pool LH and body mass index (BMI) (R = -0.59, P < 10(-5)). The relationship between BMI and LH secretion in the PCOS patients appeared to be strongest with body fatness, as pool LH was correlated inversely with percent body fat, whether measured by skinfolds (R = -0.61, P < 10(-5)), bioimpedance (R = -0.55, P < 10(-4)), or dual energy x-ray absorptiometry (DEXA) (R = -0.70, P = 0.001; n = 18 for DEXA only). By DEXA, the only body region that was highly correlated with pool LH was the trunk (R = -0.71, P = 0.001). The relationship between body fatness and LH secretion occurred via a decrease in LH pulse amplitude (R = -0.63, P < 10(-5) for BMI; R = -0.58, P < 10(-4) for bioimpedance; and R = -0.64, P = 0.004 for whole body DEXA), with no significant change in pulse frequency with increasing obesity (R = -0.17, P = 0.23 for BMI). In conclusion: 1) the prevalence of gonadotropin abnormalities is very high in women with PCOS selected on purely clinical grounds, but is modified by recent spontaneous ovulation; 2) the positive relationship between LH pulse frequency and both pool LH and LH to FSH ratio supports the hypothesis that a rapid frequency of GnRH secretion may play a key etiologic role in the gonadotropin defect in PCOS patients; 3) pool LH and LII pulse amplitude are inversely related to body mass index and percent body fat in a continuous fashion; and 4) the occurrence of a continuous spectrum of gonadotropin abnormalities varying with body fat suggests that nonobese and obese patients with PCOS do not represent distinct pathophysiologic subsets of this disorder. RP Taylor, AE (reprint author), MASSACHUSETTS GEN HOSP, NATL CTR FERTIL RES, REPROD ENDOCRINE UNIT, BARTLETT HALL EXTENS, FRUIT ST, BOSTON, MA 02114 USA. FU NCRR NIH HHS [M-1-RR01066]; NICHD NIH HHS [P30-HD28138, U54-HD29164] NR 66 TC 248 Z9 261 U1 0 U2 5 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL PY 1997 VL 82 IS 7 BP 2248 EP 2256 DI 10.1210/jc.82.7.2248 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XH824 UT WOS:A1997XH82400039 PM 9215302 ER PT J AU Salgia, R Li, JL Ewaniuk, DS Pear, W Pisick, E Burky, SA Ernst, T Sattler, M Chen, LB Griffin, JD AF Salgia, R Li, JL Ewaniuk, DS Pear, W Pisick, E Burky, SA Ernst, T Sattler, M Chen, LB Griffin, JD TI BCR/ABL induces multiple abnormalities of cytoskeletal function SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE chronic myelogenic leukemia; cytoskeleton; cell motility; fibronectin; actin ID CHRONIC MYELOGENOUS LEUKEMIA; CHRONIC MYELOID-LEUKEMIA; FOCAL ADHESION PROTEIN; BCR-ABL; TYROSINE KINASE; CELL-LINE; PROGENITOR CELLS; MARROW STROMA; C-ABL; GROWTH AB The BCR/ABL oncogene causes human chronic myelogenous leukemia (CML). a myeloproliferative disease characterized by massive expansion of hematopoietic progenitor cells and cells of the granulocyte lineage, When transfected into murine hematopoietic cell lines, BCR/ABL causes cytokine-independence and enhances viability, There is also growing evidence that p210(BCR/ABL) affects cytoskeletal structure, p210(BCR/ABL) binds to actin. and several cytoskeletal proteins are tyrosine phosphorylated by this oncoprotein. Also, at least one aspect of cytoskeletal function is abnormal, in that the affinity of beta 1 integrins for fibronectin is altered in CML cells, However, isolated changes in beta 1 integrin function would be unlikely to explain the clinical phenotype of CML. We used time-lapse video microscopy to study cell motility and cell morphology on extracellular cell matrix protein-coated surfaces of a series of cell lines before and after transformation by BCR/ABL. BCR/ABL was associated with a striking increase in spontaneous motility, membrane ruffling, formation of long actin extensions (filopodia) and accelerated the rate of protrusion and retraction of pseudopodia on fibronectin-coated surfaces, Also, while untransformed cells were sessile for long periods, BCR/ABL-transformed cells exhibited persistent motility, except for brief periods during cell division, Using cell lines transformed by a temperature-sensitive mutant of BCR/ABL. these kinetic abnormalities of cytoskeletal function were shown to require BCR/ABL tyrosine kinase activity. Similar abnormalities of cytoskeletal function on fibronectin-coated surfaces were observed when hematopoietic progenitor cells purified by CD34 selection from patients with CML were compared with CD34 positive cells from normal individuals, Interestingly, alpha-interferon treatment was found to slowly revert the abnormal motility phenotype of BCR/ABL-transformed cells towards normal, The increase in spontaneous motility and other defects of cytoskeletal function described here will be useful biological markers of the functional effects of BCR/ABL in hematopoietic cells. C1 DANA FARBER CANC INST,DIV CELLULAR & MOL BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. UNIV PENN,INST MED & ENGN,DEPT PATHOL,STELLER CHANCE LABS,PHILADELPHIA,PA 19104. RP Salgia, R (reprint author), DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,DANA 730B,44 BINNEY ST,BOSTON,MA 02115, USA. OI Li, Jian-Liang/0000-0002-6487-081X FU NCI NIH HHS [CA-01730]; NIDDK NIH HHS [DK560654] NR 36 TC 135 Z9 139 U1 1 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL 1 PY 1997 VL 100 IS 1 BP 46 EP 57 DI 10.1172/JCI119520 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA XK426 UT WOS:A1997XK42600008 PM 9202056 ER PT J AU Koya, D Jirousek, MR Lin, YW Ishii, H Kuboki, K King, GL AF Koya, D Jirousek, MR Lin, YW Ishii, H Kuboki, K King, GL TI Characterization of protein kinase C beta isoform activation on the gene expression of transforming growth factor-beta, extracellular matrix components, and prostanoids in the glomeruli of diabetic rats SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE arachidonic acid release; PGE(2); TGF-beta 1; alpha 1(IV) collagen; fibronectin ID HIGH-GLUCOSE MEDIUM; MESANGIAL CELLS; DIACYLGLYCEROL MASS; PHORBOL ESTERS; MESSENGER-RNA; IV COLLAGEN; COMPLICATIONS; PROSTAGLANDIN; PATHOGENESIS; MEDIATION AB Induction of protein kinase C (PKC) pathway in the vascular tissues by hyperglycemia has been associated with many of the cellular changes observed in the complications of diabetes. Recently, we have reported that the use of a novel, orally effective specific inhibitor of PKC beta isoform (LY333531) normalized many of the early retinal and renal hemodynamics in rat models of diabetes, In the present study, we have characterized a spectrum of biochemical and molecular abnormalities associated with chronic changes induced by glucose or diabetes in the cultured mesangial cells and renal glomeruli that can be prevented by LY333531, Hyperglycemia increased diacylglycerol (DAG) level in cultured mesangial cells exposed to high concentrations of glucose and activated PKC alpha and beta 1 isoforms in the renal glomeruli of diabetic rats. The addition of PKC beta selective inhibitor (LY333531) to cultured mesangial cells inhibited activated PKC activities by high glucose without lowering DAG levels and LY333531 given orally in diabetic rats specifically inhibited the activation of PKC beta 1 isoform without decreasing PKC alpha isoform activation, Glucose-induced increases in arachidonic acid release, prostaglandin E-2 production, and inhibition of Na+-K+ ATPase activities in the cultured mesangial cells were completely prevented by the addition of LY333531, Oral feeding of LY333531 prevented the increased mRNA expression of TGF-beta 1 and extracellular matrix components such as fibronectin and alpha 1(IV) collagen in the glomeruli of diabetic rats in parallel with inhibition of glomerular PKC activity, These results suggest that the activation of PKC, predominately the beta isoform by hyperglycemia in the mesangial cells and glomeruli can partly contribute to early renal dysfunctions by alteration of prostaglandin production and Na+-K+ ATPase activity as well as the chronic pathological changes by the overexpression of TGF-beta 1 and extracellular matrix components genes. C1 JOSLIN DIABET CTR, DIV RES, BOSTON, MA 02215 USA. BRIGHAM & WOMENS HOSP, DEPT MED, BOSTON, MA 02215 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02215 USA. LILLY RES LABS, INDIANAPOLIS, IN 46285 USA. RI Koya, Daisuke /J-3257-2014 FU NEI NIH HHS [EY5110-12]; NIDDK NIH HHS [DK36836-10] NR 57 TC 377 Z9 389 U1 1 U2 4 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL 1 PY 1997 VL 100 IS 1 BP 115 EP 126 DI 10.1172/JCI119503 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA XK426 UT WOS:A1997XK42600015 PM 9202063 ER PT J AU Imanaka, H Hess, D AlHimyary, A Bigatello, LM Ritz, R Kacmarek, RM Hurford, WE AF Imanaka, H Hess, D AlHimyary, A Bigatello, LM Ritz, R Kacmarek, RM Hurford, WE TI Assessment of errors when expiratory condensate PCO2 is used as a proxy for mixed expired PCO2 during mechanical ventilation SO JOURNAL OF CLINICAL MONITORING LA English DT Article DE blood gas measurement; carbon dioxide production; mixed expired PCO2; pulmonary dead space ID CARBON-DIOXIDE; OXYGEN AB Objectives, We designed a series of experiments to determine whether expiratory water condensate (PconCO(2)) can be used as a proxy for mixed expired gas collection. Methods, in 18 adult mechanically ventilated patients with ARDS (40 samples), simultaneous collections of arterial blood, expiratory water trap condensate, mixed expired gas, and minute ventilation were used to calculate VCO2 and V-D/V-T. To assess the effect of temperature, a constant gas flow (PCO2 10-30 mm Hg) was bubbled through water at temperatures of 19.5-37 degrees C. Gas and water samples were collected, immediately analyzed for PCO2, and a temperature correction factor was calculated. A lung model was constructed using a 5 L anesthesia bag connected to a mechanical ventilator with a heated humidifier. Temperature at the Y-piece was set to approximate to 37 degrees C and CO2 was injected into the bag to establish an end-tidal PCO2 of 20-70 mm Hg. After equilibration, condensate was collected, PCO2 was measured, and the temperature-corrected PCO2 was compared to PECO2. The capnogram at points along the expiratory limb, circuit was used to evaluate mixing. Results, There was an over-estimation of PECO2 by PconCO(2) (p < 0.001) for the patient data, resulting in an underestimation of V-D/V-T (p < 0.001) and an overestimation of VCO2 (p < 0.001). The temperature correction factor for PCO2 in water was -0.010 (about half of the factor used for whole blood), The bias between temperature-corrected PconCO(2) and PECO2 was 0.3 +/- 3.2 mm Hg in the lung model. Mixing in the expiratory limb was poor, as evaluated by the capnogram. Conclusions. Even with temperature correction, we failed to precisely predict PECO2 from PconCO(2). For measurement of V-D/V-T and VCO2, we do not recommend methods that use PconCO(2). C1 MASSACHUSETTS GEN HOSP, BOSTON, MA 02114 USA. RI Hurford, William/G-6386-2013 OI Hurford, William/0000-0003-1201-0313 NR 8 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0748-1977 J9 J CLIN MONITOR JI J. Clin. Monit. PD JUL PY 1997 VL 13 IS 4 BP 215 EP 222 DI 10.1023/A:1007305902518 PG 8 WC Anesthesiology SC Anesthesiology GA XV999 UT WOS:A1997XV99900001 PM 9269614 ER PT J AU Yamauchi, H ONeill, A Gelman, R Carney, W Tenney, DY Hosch, S Hayes, DF AF Yamauchi, H ONeill, A Gelman, R Carney, W Tenney, DY Hosch, S Hayes, DF TI Prediction of response to antiestrogen therapy in advanced breast cancer patients by pretreatment circulating levels of extracellular domain of the HER-2/c-neu protein SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID C-ERBB-2 ANTIGEN LEVELS; ESTROGEN-RECEPTOR; CARCINOMA CELLS; TYROSINE KINASE; OVARIAN-CANCER; NEU-ONCOGENE; DNA-REPAIR; EXPRESSION; AMPLIFICATION; GROWTH AB Purpose: Overexpression of the HER-2/c-neu/c-erbB2-oncogene is associated with a worse prognosis in patients with breast cancer, perhaps due to an association of the HER-2 proto-oncogene protein with resistance to hormone and/or chemotherapy. Circulating levels of the extracellular domain (ECD) of the HER-2/c-neu-related protein (NRP) are elevated in 20% to 40% of patients with metastatic breast cancer. We investigated whether pretreatment levels of NRP predict response to hormone therapy (HT), Materials and Methods: Circulating NRP levels were determined in 94 patients who participated in a randomized trial of three different doses of the antiestrogen, droloxifene (DRO), as first-line HT for metastatic breast cancer, Results: NRP levels were elevated (greater than or equal to 5,000 U/mL) in 32 of 94 patients (34%), Only three of 32 patients (9%) with elevated NRP levels responded to DRO, compared with 35 of 62 (56%) with nonelevated NRP levels (P = .00001), Low pretreatment NRP level was the most powerful predictor of response to DRO (odds ratio of response, 22.4; P = .0001), Elevated pretreatment NRP levels were also associated with a shorter time to progression (TTP) and survival duration, Conclusion: Pretreatment circulating NRP levels predict a low likelihood of benefit from HT, specifically DRO, in patients with estrogen receptor (ER)-positive and/or progesterone receptor (PgR) positive or receptor-unknown metastatic breast cancer, even when adjusted for other known predictive factors, such as ER and/or PgR levels, site of disease, disease-free interval from primary treatment to recurrence, and prior adjuvant chemotherapy. These delta suggest that pretreatment NRP levels may be useful in deciding whether to treat a patient who otherwise appears to be likely to respond to HT. (C) 1997 by American Society of Clinical Oncology. C1 DANA FARBER CANC INST,DIV BIOSTAT,BOSTON,MA 02115. ONCOGENE SCI INC,CAMBRIDGE,MA. KLINGE PHARMA GMBH,MUNICH,GERMANY. GEORGETOWN UNIV,MED CTR,DEPT MED,LOMBARDI CANC CTR,WASHINGTON,DC 20007. FU NCI NIH HHS [CA64057] NR 53 TC 179 Z9 180 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL PY 1997 VL 15 IS 7 BP 2518 EP 2525 PG 8 WC Oncology SC Oncology GA XH442 UT WOS:A1997XH44200006 PM 9215820 ER PT J AU Saxman, SB Propert, KJ Einhorn, LH Crawford, ED Tannock, I Raghavan, D Loehrer, PJ Trump, D AF Saxman, SB Propert, KJ Einhorn, LH Crawford, ED Tannock, I Raghavan, D Loehrer, PJ Trump, D TI Long-term follow-up of a phase III intergroup study of cisplatin alone or in combination with methotrexate, vinblastine, and doxorubicin in patients with metastatic urothelial carcinoma: A cooperative group study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID COLONY-STIMULATING FACTOR; TRANSITIONAL CELL-CARCINOMA; M-VAC; RANDOMIZED TRIAL; TUMORS; MVAC; CHEMOTHERAPY; RELAPSE; THERAPY; CANCER AB Purpose: A previously reported randomized intergroup trial demonstrated that combination chemotherapy with methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) was superior to single-agent cisplatin in patients with advanced urothelial carcinoma, We conducted a long-term analysis of patients included in the intergroup trial to examine factors associated with long-term survival, Patients and Methods: Two-hundred fifty-five assessable patients with urothelial carcinoma were randomized to receive either single-agent cisplatin (70 mg/m(2) on day 1) or combination chemotherapy with methotrexate (30 mg/m(2) on days 1, 15, and 22), vinblastine (3 mg/m(2) on days 2, 15, and 22), doxorubicin (30 mg/m(2) on day 2), and cisplatin (70 mg/m(2) on day 2), Courses were repeated every 28 days, The association between patient characteristics and survival was assessed using Cox proportional hazards models. Results: With long-term follow-up evaluation, survival in the M-VAC arm continues to be superior to cisplatin (P = .00015, log-rank test), Predictors of survival include performance status, histology, and the presence of liver or bone metastasis. Only 3.7% of the patients randomized to M-VAC are alive and continuously disease-free at 6 years, Conclusion: Long-term follow-up evaluation of the intergroup trial confirms that M-VAC is superior to single-agent cisplatin in patients with advanced urothelial carcinoma; however, durable progression-free survival is rare. Patients with non-transitional-cell histology, poor performance status, and/or bone or visceral involvement fare poorly and are unlikely to benefit significantly from M-VAC chemotherapy. (C) 1997 by American Society of Clinical Oncology. C1 DANA FARBER CANC INST,BOSTON,MA 02115. UNIV COLORADO,DENVER,CO 80202. UNIV TORONTO,PRINCESS MARGARET HOSP,TORONTO,ON,CANADA. ROYAL PRINCE ALFRED HOSP,CAMPERDOWN,NSW,AUSTRALIA. UNIV PITTSBURGH,CTR CANC,PITTSBURGH,PA 15260. RP Saxman, SB (reprint author), INDIANA UNIV,SCH MED,DIV HEMATOL ONCOL,535 BARNHILL DR,ROOM RT 440,INDIANAPOLIS,IN 46202, USA. FU NCI NIH HHS [CA 49883, CA 23318, CA 18653] NR 15 TC 332 Z9 339 U1 1 U2 4 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL PY 1997 VL 15 IS 7 BP 2564 EP 2569 PG 6 WC Oncology SC Oncology GA XH442 UT WOS:A1997XH44200012 PM 9215826 ER PT J AU Morris, MM Powell, SN AF Morris, MM Powell, SN TI Irradiation in the setting of collagen vascular disease: Acute and late complications SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID RADIATION-INDUCED FIBROSIS; NASOPHARYNGEAL CARCINOMA; BREAST-CONSERVATION; SYSTEMIC-SCLEROSIS; THERAPY; INJURY AB Purpose: Based on reports of greater toxicity from radiation therapy, collagen vascular diseases (CVDs) have been considered a contraindication to irradiation, We assessed the complications of radiation therapy in patients with CVD, patients and Methods: A total of 209 patients with documented CVD were irradiated between 1960 and 1995, One hundred thirty-one had rheumatoid arthritis (RA), 25 had systemic lupus erythematosus (SLE); 17 had polymyositis or dermatomyositis; 16 had scleroderma; eight had ankylosing spondylitis; five had juvenile RA; three held discoid lupus erythematosus; and four had 4 mixed connective tissue disorders (MCTD), The mean follow-up duration of curative cases was more than 6 years, Doses ranged from 10 to 87.6 Gy, with a median of 45 Gy, Results: Overall, 263 sites were assessable in 209 patients, Significant (greater than or equal to grade 3) acute toxicity was seen in 10% of irradiated sites, Severe late effects were associated with significant acute reactions and with non-RA CVDs (6% v 21% at 5 years), No difference was seen in late effects according to timing of CVD onset, presence of concurrent vascular insults, radiation dose, or other technical factors, or by measures of disease activity, Conclusion: RA does not appear to have an elevated rate of late toxicity. While non-RA CVD is significantly associated with increased radiation late effects at standard doses, radiation-related mortality remains exceedingly rare, The choice of therapeutic modality in this radiosensitive group of patients should be made on a case-by-case basis. (C) 1997 by American Society of Clinical Oncology. RP Morris, MM (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,COX LL,100 BLOSSOM ST,BOSTON,MA 02114, USA. NR 18 TC 68 Z9 70 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL PY 1997 VL 15 IS 7 BP 2728 EP 2735 PG 8 WC Oncology SC Oncology GA XH442 UT WOS:A1997XH44200033 PM 9215847 ER PT J AU Burstein, HJ Janicek, MJ Skarin, AT AF Burstein, HJ Janicek, MJ Skarin, AT TI Hypertrophic osteoarthropathy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID RHEUMATOLOGIC MANIFESTATIONS C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP Burstein, HJ (reprint author), BRIGHAM & WOMENS HOSP,DANA FARBER CANC INST,BOSTON,MA 02115, USA. NR 6 TC 7 Z9 7 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL PY 1997 VL 15 IS 7 BP 2759 EP 2760 PG 2 WC Oncology SC Oncology GA XH442 UT WOS:A1997XH44200036 PM 9215850 ER PT J AU Goudsouzian, N Martyn, JA AF Goudsouzian, N Martyn, JA TI Potentiation of mivacurium by rocuronium is age- and time-dependent: A study in children, adolescents, and young and elderly adults SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article; Proceedings Paper CT 1996 Annual Meeting of the American-Society-of-Anesthesiologists CY OCT 18-25, 1996 CL NEW ORLEANS, LA SP Amer Soc Anesthesiologists ID NITROUS-OXIDE HALOTHANE; INFUSION REQUIREMENTS; ANESTHESIA; VECURONIUM; PHARMACOKINETICS; ATRACURIUM; BROMIDE; INFANTS; TUBOCURARINE; PHARMACOLOGY AB Potentiation occurs when the steroidal muscle relaxant, rocuronium, is coadministered with the benzylisoquinolinium relaxant, mivacurium. The effect of time and age on this interaction was evaluated in four predetermined groups: children, adolescents, young adults, and elderly adults (25 per group) by monitoring the ulnar nerve-evoked force of contraction of the adductor pollicis (twitch response). During recovery from paralysis induced by 600 mu g/kg of rocuronium, an infusion of mivacurium was started and maintained for at least 90 minutes to retain the twitch response at 1% to 9% of baseline tension (95 +/- 4% paralysis). Rocuronium at 600 mu g/kg induced greater than 95% paralysis in 57 of the 60 patients within 2.2 +/- 0.4 (mean +/- SE) minutes. The period of recovery from rocuronium-induced paralysis to 5% of baseline twitch height was longest in the elderly (30.9 +/- 2.9 minutes) and shortest in the adolescents (16.5 +/- 2.4 minutes). The mivacurium infusion requirements to maintain 95 +/- 4% paralysis was highest in children and progressively increased with time. in young and elderly adults, the infusion rates remained lower than that of children and did not change with time. The incidence of satisfactory spontaneous recovery within 20 minutes (train-of-four ratio >75%) was the highest in children, followed by adolescents and young adults, and was least in the elderly. The residual neuromuscular effect of rocuronium on the subsequent mivacurium infusion was most pronounced in the elderly, followed by young adults, then adolescents, and was least in children. C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA & CRIT CARE,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 28 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD JUL PY 1997 VL 37 IS 7 BP 649 EP 655 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA XM951 UT WOS:A1997XM95100013 PM 9243359 ER PT J AU Strissel, KJ Tessier, MJ Shams, NB Grabbe, S Gross, J Fini, ME AF Strissel, KJ Tessier, MJ Shams, NB Grabbe, S Gross, J Fini, ME TI Frog PNKT-4B cells express specific extracellular matrix-degrading enzymes and cytokines correlated with an invasive phenotype SO JOURNAL OF EXPERIMENTAL ZOOLOGY LA English DT Article ID FIBROBLAST GROWTH-FACTOR; INTERLEUKIN-1 RECEPTOR ANTAGONIST; LUCKE RENAL ADENOCARCINOMA; GENE-EXPRESSION; FACTOR-BETA; IV COLLAGENASE; HEAT-SHOCK; TEMPERATURE; RELEASE; IL-1 AB A temperature-dependent metastatic phenotype reported for a frog cell line, PNKT-4B, provided a means for studying potential mediators of cell-matrix interaction involved in metastatic invasion. Zymography revealed that these cells secreted enzyme species with properties and characteristics of mammalian metalloproteinases: collagenase, stromelysin, gelatinase A, and gelatinase B. These enzymes were produced by PNKT-4B cultures maintained at both invasive-permissive (28 degrees C), and invasion-restrictive (20 degrees C) temperatures. However, under the invasive-permissive culture condition cells produced more of the putative gelatinase B and A enzymes. In addition, an activated form of gelatinase A was produced only in invasion-permissive cultures. DNA synthesis bioassays (Mv1Lu cell line and mouse thymocytes) to detect growth promoting and/or inhibitory cytokines, revealed that PNKT-4B cultures kept at 28 degrees C released significantly higher levels of stimulatory (interleukin-1-like) and latent inhibitory (transforming growth factor-beta-like) substances into the medium compared to 20 degrees C cultures. Pre-absorption of media samples with heparin-sepharose indicated a second stimulatory cytokine as well. A corneal fibroblast bioassay that tests for mediators of collagenase synthesis, detected a stimulatory substance whose activity was greatly reduced in the presence of interleukin-1 receptor antagonist protein. Collagenase stimulatory activity present in 28 degrees C culture medium was significantly higher than equal samples from 20 degrees C cultures. These studies provide a molecular correlation between release of cytokines with properties of the metastatic phenotype seen in vivo. They further provide some of the first characterizations of frog MMPs and cytokines, which are likely to be involved in other tissue remodeling events. (C) 1997 Wiley-Liss, Inc. C1 MASSACHUSETTS GEN HOSP,CUTANEOUS BIOL RES CTR,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,DEPT DERMATOL,CHARLESTOWN,MA 02129. SCHEPENS EYE RES INST,BOSTON,MA 02114. TUFTS UNIV,SCH MED,DEPT OPHTHALMOL,BOSTON,MA 02111. RP Strissel, KJ (reprint author), TUFTS UNIV,NEW ENGLAND MED CTR,SCH MED,VIS RES LABS,750 WASHINGTON ST,BOX 450,BOSTON,MA 02111, USA. FU NEI NIH HHS [R01-EY08408, R01-EY09828]; NIAMS NIH HHS [T32-AR07908] NR 63 TC 0 Z9 0 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 0022-104X J9 J EXP ZOOL JI J. Exp. Zool. PD JUL 1 PY 1997 VL 278 IS 4 BP 201 EP 214 PG 14 WC Zoology SC Zoology GA XG183 UT WOS:A1997XG18300001 PM 9206030 ER PT J AU Silva, JA Ferrari, MM Leong, GB Weinstock, R AF Silva, JA Ferrari, MM Leong, GB Weinstock, R TI The role of mania in the genesis of dangerous delusional misidentification. SO JOURNAL OF FORENSIC SCIENCES LA English DT Article DE forensic science; forensic psychiatry; dangerousness; delusional misidentification; violence; aggression; mania; bipolar disorder; schizoaffective disorder ID CAPGRAS SYNDROME; SELF; INTERMETAMORPHOSIS; VIOLENCE AB The delusional misidentification syndromes are characterized by a misidentification delusion of the self and/or others. Delusional misidentification syndromes frequently occur in psychotic disorders such as schizophrenia, psychotic disorder due to general medical condition, or psychotic disorder not otherwise specified. On rare occasions these syndromes may be associated with manic states secondary to bipolar disorder, schizoaffective disorder, or general medical conditions. The delusional misidentification syndromes may also be associated with verbal and physical aggression. in this article we present three cases of dangerous delusional misidentification associated with mania. We will discuss the role that mania may have in the genesis of dangerous delusional misidentification. C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX. OHIO STATE UNIV,COLL MED,COLUMBUS,OH 43210. VET AFFAIRS OUTPATIENT CLIN,COLUMBUS,OH. UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. RP Silva, JA (reprint author), S TEXAS VET HLTH CARE SYST,PSYCHIAT SERV 116A,PSYCHIAT RES UNIT,7400 MERTON MINTER BLVD,SAN ANTONIO,TX 78284, USA. NR 39 TC 3 Z9 3 U1 1 U2 1 PU AMER SOC TESTING MATERIALS PI W CONSHOHOCKEN PA 100 BARR HARBOR DR, W CONSHOHOCKEN, PA 19428-2959 SN 0022-1198 J9 J FORENSIC SCI JI J. Forensic Sci. PD JUL PY 1997 VL 42 IS 4 BP 670 EP 674 PG 5 WC Medicine, Legal SC Legal Medicine GA XL348 UT WOS:A1997XL34800013 PM 9243830 ER PT J AU Metlay, JP Fine, MJ Schulz, R Marrie, TJ Coley, CM Kapoor, WN Singer, DE AF Metlay, JP Fine, MJ Schulz, R Marrie, TJ Coley, CM Kapoor, WN Singer, DE TI Measuring symptomatic and functional recovery in patients with community-acquired pneumonia SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT Joint Meeting of the Eastern Section of the American-Federation-for-Medical-Research / New England Section of the Society-of-General-Internal-Medicine CY OCT 05, 1996 CL BOSTON, MA SP Amer Federat Med Res, E Sect, Soc Gen Internal Med, New England Sect DE pneumonia; health status; outcomes assessment; questionnaires ID HOSPITALIZATION; ADULTS; PROXY AB OBJECTIVE: To determine the rates of resolution of symptoms and return to premorbid health status and assess the association of these outcomes with health care utilization in patients with community-acquired pneumonia. DESIGN: A prospective, multicenter cohort study. SETTING: Inpatient and outpatient facilities at three university hospitals, one community hospital, and one staff-model health maintenance organization. PATIENTS: Five hundred seventy-six adults (aged greater than or equal to 18 years) with clinical and radiographic evidence of pneumonia, judged by a validated pneumonia severity index to be at low risk of dying. MEASUREMENTS AND MAIN RESULTS: The presence and severity of five symptoms (cough, fatigue, dyspnea, sputum, and chest pain) were recorded through questionnaires administered at four time points: 0, 7, 30, and 90 days from the time of radiographic diagnosis of pneumonia, A summary symptom score was tabulated as the sum of the five individual severity scores. Patients also provided responses to the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) and reported the number of and reason for outpatient physician visits. Symptoms and health status 30 days before pneumonia onset (prepneumonia) were obtained at the initial interview. All symptoms, except pleuritic chest pain, were still commonly reported at 30 days, and the prevalence of each symptom at 90 days was still nearly twice prepneumonia levels. Physical health measures derived from the SF-36 Form declined significantly at presentation but continued to improve over all three follow-up time periods. Patients with elevated symptom scores at day 7 or day 30 were significantly more likely to report pneumonia-related ambulatory care visits at the subsequent day 30 or day 90 interviews, respectively, CONCLUSIONS: Disease-specific symptom resolution and recovery of the premorbid physical health status requires more than 30 days for many patients with pneumonia. Delayed resolution of symptoms is associated with increased utilization of outpatient physician visits. C1 HARVARD UNIV,SCH MED,BOSTON,MA. UNIV PITTSBURGH,DEPT MED,DIV GEN INTERNAL MED,PITTSBURGH,PA 15260. MASSACHUSETTS GEN HOSP,DEPT PSYCHOL,CTR RES HLTH CARE,BOSTON,MA 02114. VICTORIA GEN HOSP,DEPT MED & MICROBIOL,HALIFAX,NS B3H 2Y9,CANADA. DALHOUSIE UNIV,HALIFAX,NS,CANADA. RP Metlay, JP (reprint author), MASSACHUSETTS GEN HOSP,GEN INTERNAL MED UNIT,DEPT MED,50 STANIFORD ST,0TH FLOOR,BOSTON,MA 02114, USA. FU AHRQ HHS [R01 HS06468]; BHP HRSA HHS [5T32PE11001-08] NR 23 TC 58 Z9 61 U1 0 U2 2 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 1997 VL 12 IS 7 BP 423 EP 430 DI 10.1046/j.1525-1497.1997.00074.x PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA XK257 UT WOS:A1997XK25700005 PM 9229281 ER PT J AU Jupiter, JB Fernandez, DL AF Jupiter, JB Fernandez, DL TI Comparative classification for fractures of the distal end of the radius SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article AB As suggested by Muller, a useful classification system for distal radius fractures must consider the severity of the bone lesion and serve as a basis for treatment and for evaluation of out come. Although these fractures have long been considered to be Colles or Smith's fractures, they have been subjected to extensive scrutiny in order to define fracture morphology and treatment considerations. This review highlights a number of contemporary classification systems for distal radius fractures, including the systems of Older et al., the Comprehensive Classification of fractures, the Melone intra-articular classification system, and that of Fernandez. RP Jupiter, JB (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,ORTHOPAED HAND SERV,15 PARKMAN ST,SUITE 527,BOSTON,MA 02114, USA. NR 29 TC 43 Z9 44 U1 0 U2 2 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD JUL PY 1997 VL 22 IS 4 BP 563 EP 571 DI 10.1016/S0363-5023(97)80110-4 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA XP421 UT WOS:A1997XP42100001 PM 9260608 ER PT J AU Beissert, S Mohammad, T Torri, H Lonati, A Yan, ZM Morrison, H Granstein, RD AF Beissert, S Mohammad, T Torri, H Lonati, A Yan, ZM Morrison, H Granstein, RD TI Regulation of tumor antigen presentation by urocanic acid SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MURINE EPIDERMAL-CELLS; HERPES-SIMPLEX VIRUS; ULTRAVIOLET-RADIATION; HYPERSENSITIVITY RESPONSE; INDUCED IMMUNOSUPPRESSION; CONTACT HYPERSENSITIVITY; IMMUNE SUPPRESSION; LIGHT; HISTAMINE; MOUSE AB Urocanic acid (UCA) accumulates in the epidermis after deamination of histidine. UCA isomerizes from the trans to the cis form upon exposure to environmental UV radiation. Cis-UCA is immunosuppressive in several models. Topically applied cis-UCA was reported to enhance the cutaneous tumor yield in chronically UV-irradiated mice, suggesting involvement of cis-UCA in photocarcinogenesis. Since Langerhans cells (LC) are capable of presenting tumor-associated Ags (TAA) for primary and secondary tumor-immune responses, we examined the effects of trans- and cis-UCA on LC tumor Ag presentation in a model of immunity to the S1509a spindle cell tumor (H-2(a)). In this system, induction of immunity requires exposure of LC to granulocyte-macrophage CSF. Naive CAF, (H-2(a/d)) mice were immunized against S1509a by injection with granulocyte-macrophage CSF-exposed and TAA-pulsed epidermal cells (EC), as assessed by growth inhibition of inoculated tumor cells, Incubation of EC in cis-, but not trans-UCA completely inhibited Ag presentation in this system. Neither histamine antagonists nor indomethacin reversed these effects of cis-UCA. The ability of trans- and cis-UCA to modulate EC presentation of TAA for secondary immune responses was also examined. EC were pulsed with TAA in vitro and then injected into hind footpads of tumor-immune mice, After 24 h, footpad swelling was assessed as a measure of delayed-type hypersensitivity. Incubation with cis-, but again not trans-UCA before TAA exposure significantly inhibited elicitation of delayed-type hypersensitivity. These data indicate that cis-UCA may be an important regulator of LC Ag-presenting function in tumor-immune responses, and thus may play a role in photocarcinogenesis. C1 PURDUE UNIV,DEPT CHEM,W LAFAYETTE,IN 47907. HARVARD UNIV,MASSACHUSETTS GEN HOSP,DEPT DERMATOL,CUTANEOUS BIOL RES CTR,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,CHARLESTOWN,MA 02129. RP Beissert, S (reprint author), UNIV MUNSTER,DEPT DERMATOL,VON ESMARCH STR 56,D-48149 MUNSTER,GERMANY. FU NIAMS NIH HHS [AR40667] NR 38 TC 42 Z9 44 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 JUL 1 PY 1997 VL 159 IS 1 BP 92 EP 96 PG 5 WC Immunology SC Immunology GA XF564 UT WOS:A1997XF56400015 PM 9200443 ER PT J AU Lu, CF Springer, TA AF Lu, CF Springer, TA TI The alpha subunit cytoplasmic domain regulates the assembly and adhesiveness of integrin lymphocyte function-associated antigen-1 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INTERCELLULAR-ADHESION MOLECULE-1; DIVALENT-CATION REGULATION; POLYMERASE CHAIN-REACTION; OUT SIGNAL-TRANSDUCTION; BETA-SUBUNIT; MONOCLONAL-ANTIBODY; CELL-ADHESION; LIGAND-BINDING; CR3-DEPENDENT ADHESION; FIBRONECTIN RECEPTOR AB The integrin LFA-1 mediates activation-dependent leukocyte adhesion. The beta subunit cytoplasmic domain has been demonstrated previously to modulate the adhesiveness of LFA-1. To investigate whether the alpha subunit cytoplasmic domain is also involved in the regulation of LFA-1-adhesive function, we stably expressed cytoplasmic domain truncated forms of the a subunit in a Jurkat mutant (Jurkat-beta(2.7)) deficient in the endogenous LFA-1 alpha subunit and in K562 cells. Clones expressing similar levels of cell surface LFA-1 were tested for their ability to bind to immobilized ICAM-1. Truncation of the alpha subunit cytoplasmic domain before, but not after, the conserved GFFKR sequence motif resulted in constitutive ICAM-1 binding of both Jurkat-beta(2.7) and K562 transfectants. However, truncation after the GFFKR motif reduced sensitivity to stimulation by PMA or stimulatory Abs. Internal deletion of the GFFKR motif, or point mutations of the Gly (C), the two Phe (F), or the Arg (R) in the GFFKR motif to Ala (A) rendered LFA-1 constitutively active. Mutation of the Lys (K) did not affect LFA-1 adhesion to ICAM-1. These findings indicate that the GFFKR motif maintains the low adhesive state of LFA-1, possibly by restraining the receptor conformation. We further demonstrate that the alpha subunit cytoplasmic domain and the conserved GFFKR motif are also required for efficient formation of LFA-1 alpha beta heterodimers. C1 CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. FU NCI NIH HHS [CA 31798] NR 69 TC 119 Z9 121 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 JUL 1 PY 1997 VL 159 IS 1 BP 268 EP 278 PG 11 WC Immunology SC Immunology GA XF564 UT WOS:A1997XF56400035 PM 9200463 ER PT J AU Chen, L Chen, DS Block, E ODonnell, M Kufe, DW Clinton, SK AF Chen, L Chen, DS Block, E ODonnell, M Kufe, DW Clinton, SK TI Eradication of murine bladder carcinoma by intratumor injection of a bicistronic adenoviral vector carrying cDNAs for the IL-12 heterodimer and its inhibition by the IL-12 p40 subunit homodimer SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CELL STIMULATORY FACTOR; RECOMBINANT HUMAN INTERLEUKIN-12; LYMPHOCYTE MATURATION FACTOR; IMMUNOREGULATORY FUNCTIONS; ANTITUMOR IMMUNITY; INTERFERON-GAMMA; FACTOR NKSF; T-CELLS; CYTOKINE; MOUSE AB IL-12 is a heterodimeric immunoregulatory cytokine composed of covalently linked p40 and p35 subunits and exhibits antitumor activity in a variety of laboratory models. The efficacy of systemically administered cytokines for cancer therapy is often limited by toxicity. The gene therapy approach provides a mechanism to achieve temporary and high local concentrations of cytokines within a tumor with less risk of systemic toxicity. We constructed replication-defective adenoviruses containing the murine IL-12 p40 subunit (Ad.mp40) or a bicistronic vector containing cDNAs for the p40 and p35 subunits (Ad.mlL-12). Murine MB49 bladder cancer cells infected with Ad.mlL-12 secrete high concentrations of biologically active IL-12, while those infected with Ad.mp40 produce the p40 homodimer. Tumors injected with Ad.mlL-12 show rapid increases in IL-12 and lFN-gamma expression over 2 to 5 days and a return to baseline by 7 to 14 days. Injection of tumors with Ad.mlL-12 (1 x 10(9) plaque-forming units) results in a complete tumor regression in all mice, while those treated with control adenovirus succumb to their tumor. Efficacy is reduced when studies are performed in mice depleted of CD4(+) and CD8(+) cells or in nude mice. Mice cured of their tumor by Ad.mlL-12 demonstrate specific protective immunity upon rechallenge. Ad.mp40 does not exhibit antitumor activity and may antagonize the activity of rlL-12 or Ad.mlL-12. In summary, gene therapy strategies for cancer using adenoviral vectors containing IL-12 are highly effective with no significant toxicity in mice. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BETH ISRAEL DEACONESS MED CTR,DEPT UROL,BOSTON,MA 02115. FU NCI NIH HHS [KO7 CA23326, R29 CA 64230] NR 49 TC 129 Z9 132 U1 1 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 1 PY 1997 VL 159 IS 1 BP 351 EP 359 PG 9 WC Immunology SC Immunology GA XF564 UT WOS:A1997XF56400045 PM 9200473 ER PT J AU Grewal, IS Rutledge, BJ Fiorillo, JA Gu, L Gladue, RP Flavell, RA Rollins, BJ AF Grewal, IS Rutledge, BJ Fiorillo, JA Gu, L Gladue, RP Flavell, RA Rollins, BJ TI Transgenic monocyte chemoattractant protein-1 (MCP-1) in pancreatic islets produces monocyte-rich insulitis without diabetes - Abrogation by a second transgene expressing systemic MCP-1 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HISTAMINE-RELEASING FACTOR; ACTIVATING FACTOR; GROWTH-FACTOR; CELL-LINE; JE GENE; MICE; CYTOKINE; ALPHA; SUSCEPTIBILITY; PURIFICATION AB Monocyte chemoattractant protein-1 (MCP-1) is a CC chemokine that attracts monocytes and T lymphocytes in vitro; however, its in vivo functions are poorly understood, To address this question, we constructed transgenic mice expressing MCP-1 controlled by an insulin promoter. These mice developed a chronic insulitic infiltrate composed of F4/80(+) monocytes with minor populations of CD4(+), CD8(+), and B220(+) cells, Despite persistent transgene expression, the insulitis never progressed, and blood glucose levels remained normal, Thus, MCP-1 alone is sufficient to elicit a monocytic infiltrate, but not to activate elicited cells. These results differ from those obtained with another transgenic model using the mouse mammary tumor virus long terminal repeat, in which mice expressed substantial MCP-1 in several organs but had no infiltrates, However, mice expressing both transgenes had minimal insulitis, indicating that high systemic levels of MCP-1 prevented monocytes from responding to local MCP-1. Thus, the ability of MCP-1 to elicit monocytic infiltration depends on its being expressed at low levels in an anatomically restricted area. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT ADULT ONCOL,BOSTON,MA 02115. YALE UNIV,SCH MED,HOWARD HUGHES MED INST,NEW HAVEN,CT 06510. YALE UNIV,SCH MED,IMMUNOBIOL SECT,NEW HAVEN,CT 06510. PFIZER INC,CENT RES,GROTON,CT 06340. FU NCI NIH HHS [CA53091] NR 47 TC 123 Z9 125 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 1 PY 1997 VL 159 IS 1 BP 401 EP 408 PG 8 WC Immunology SC Immunology GA XF564 UT WOS:A1997XF56400051 PM 9200479 ER PT J AU Ingalls, RR Arnaout, MA Golenbock, DT AF Ingalls, RR Arnaout, MA Golenbock, DT TI Outside-in signaling by lipopolysaccharide through a tailless integrin SO JOURNAL OF IMMUNOLOGY LA English DT Article ID COMPLEMENT RECEPTOR TYPE-3; CR3 CD11B/CD18; MONOCLONAL-ANTIBODIES; HUMAN MONOCYTES; BINDING-SITE; ADHESION; BETA-2-INTEGRIN; ENDOTOXIN; CD18; RECOGNITION AB Ligand binding to integrins activates intracellular signaling pathways that coordinate and regulate a variety of cellular responses. There is evidence to suggest that the cytoplasmic tails play a key role in several of these signaling events, We sought to determine whether the beta(2) integrin complement receptor type 3 (CR3; CD11b/CD18), a receptor for LPS, could initiate an intracellular signal in the absence of its cytoplasmic domains, Expression of full length CR3 in a Chinese hamster ovary-K1 fibroblast line enabled serum-independent translocation of nuclear factor-kappa B in response to binding LPS. Unexpectedly, a cell line expressing a mutated form of CR3 deficient in the cytoplasmic domains was also competent for transmitting a signal in response to LPS. In contrast, phagocytosis of whole Cram-negative bacteria and iC3b-coated erythrocytes took place only with a full length receptor, Thus, while full length CR3 is necessary for productive phagocytic signals, LPS activation does not require the cytoplasmic domains, CR3 may function to activate cells by presenting LPS to a downstream signal transducer. C1 BOSTON UNIV,MED CTR,DEPT MED,DIV INFECT DIS,MAXWELL FINLAND LAB INFECT DIS,BOSTON,MA 02118. BOSTON UNIV,SCH MED,BOSTON,MA 02118. MASSACHUSETTS GEN HOSP,DEPT MED,DIV NEPHROL,LEUKOCYTE BIOL & INFLAMMAT PROGRAM,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. FU NIAID NIH HHS [AI38515]; NIDDK NIH HHS [DK50305]; NIGMS NIH HHS [GM54060] NR 32 TC 100 Z9 103 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 JUL 1 PY 1997 VL 159 IS 1 BP 433 EP 438 PG 6 WC Immunology SC Immunology GA XF564 UT WOS:A1997XF56400055 PM 9200483 ER PT J AU Agostini, HT Ryschkewitsch, CF Mory, R Singer, EJ Stoner, GL AF Agostini, HT Ryschkewitsch, CF Mory, R Singer, EJ Stoner, GL TI JC virus (JCV) genotypes in brain tissue from patients with progressive multifocal leukoencephalopathy (PML) and in urine from controls without PML: Increased frequency of JCV type 2 in PML SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 48th Annual Meeting of the American-Academy-of-Neurology CY MAR 23-30, 1996 CL SAN FRANCISCO, CA SP Amer Acad Neurol ID HUMAN-IMMUNODEFICIENCY-VIRUS; POLYMERASE CHAIN-REACTION; PROMOTER ENHANCER; BK-VIRUS; DNA; AIDS; REARRANGEMENTS; AMPLIFICATION; INDIVIDUALS; INFECTION AB Progressive multifocal leukoencephalopathy (PML) is caused by the human polyomavirus JC (JCV), and there are at least 4 different genotypes of JCV in the United States, Type 1 strains are of European origin, whereas type 2 and 3 strains are of Asian and African origin, respectively, JCV type 4 strains are derived from a type 1/3 recombinant, In this study, the genotype distribution of JCV strains found in brain tissue or cerebrospinal fluid of 50 PML patients was compared with JCV genotypes excreted in the urine of 103 control subjects, Type determination was based on the polymerase chain reaction-amplified partial sequence of the VP1 coding gene and the noncoding region left of ori, Brain tissues from patients with PML were infected with a significantly higher proportion of JCV type 2 strains than were urine samples from the control group (P = .004), This evidence indicates a biologic difference between JCV genotypes and suggests a difference in their potential to cause PML. C1 NINCDS,EXPT NEUROPATHOL LAB,NIH,BETHESDA,MD 20892. W LOS ANGELES VET AFFAIRS MED CTR,NEUROL SERV,LOS ANGELES,CA 90073. NR 37 TC 56 Z9 56 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUL PY 1997 VL 176 IS 1 BP 1 EP 8 DI 10.1086/514010 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA XH275 UT WOS:A1997XH27500001 PM 9207343 ER PT J AU Merrill, DP Manion, DJ Chou, TC Hirsch, MS AF Merrill, DP Manion, DJ Chou, TC Hirsch, MS TI Antagonism between human immunodeficiency virus type 1 protease inhibitors indinavir and saquinavir in vitro SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 36th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) CY SEP 15-18, 1996 CL NEW ORLEANS, LA ID ZIDOVUDINE; DIDANOSINE AB Human immunodeficiency virus type 1 (HIV-1) protease inhibitors are a promising class of antiretroviral agents that compromise enzymatic function through substrate mimicry. The in vitro susceptibility of a panel of HIV-1 clinical isolates demonstrating various drug resistance phenotypes to combinations of the HIV-1 protease inhibitors saquinavir and indinavir was determined. Antiviral effect was assessed by an HIV-1 p24 antigen reduction assay in phytohemagglutinin-stimulated peripheral blood mononuclear cells after harvesting of cell-free supernatant fluids at peak antigen production (days 4-7). Drug interactions were determined by median-dose-effect analysis, with the combination index (CI) calculated at several inhibitory concentrations (IC50, IC75, IC90, IC95, IC99). The interactive effects ranged from synergy at low efficacy doses to antagonism at higher doses against a pan-susceptible clinical isolate of HIV-1. Against a zidovudine-resistant isolate as well as a multidrug-resistant isolate, the combination of saquinavir and indinavir demonstrated antagonism at all doses. C1 HARVARD UNIV,INFECT DIS UNIT,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114. MEM SLOAN KETTERING CANC CTR,NEW YORK,NY 10021. RI Chou, Ting-Chao/B-4111-2009 OI Chou, Ting-Chao/0000-0002-3340-1594 FU NCI NIH HHS [CA-12464] NR 9 TC 29 Z9 29 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUL PY 1997 VL 176 IS 1 BP 265 EP 268 DI 10.1086/517263 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA XH275 UT WOS:A1997XH27500037 PM 9207379 ER PT J AU Moss, P Charmley, P Mulvihill, E Ziegler, S Raugi, GJ Kern, D Piepkorn, M Gelinas, R AF Moss, P Charmley, P Mulvihill, E Ziegler, S Raugi, GJ Kern, D Piepkorn, M Gelinas, R TI The repertoire of T cell antigen receptor beta-chain variable regions associated with psoriasis vulgaris SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE T lymphocytes; psoriasis; RT-PCR; repertoire; analysis ID LYMPHOCYTES-T; GENE USAGE; LESIONS; KERATINOCYTE; EXPRESSION; GUTTATE; IMMUNE; LINES; SKIN AB We investigated whether the pattern of T-cell receptors expressed by T cells in inflamed psoriatic skin differed substantially from the pattern seen in T cells from the peripheral blood. A bias or restriction in the repertoire of T-cell receptors found in the lesional skin of different patients might imply that specific subsets of T cells were causally associated with initiating or maintaining the lesions, By using a polymerase chain reaction-based assay of T-cell receptor beta-chain variable region mRNA, we found that the patterns of beta-chain mRNAs displayed in 14 samples of lesional skin or six samples of noninvolved skin were not significantly less diverse than the patterns found in matched peripheral blood samples. There was no evidence that the active lesions of multiple patients showed overexpression of T cells expressing one or a few T-cell receptor forms. The pattern of T-cell receptors displayed in clinically normal skin from normal control individuals showed about the same diversity as normal blood. While these results may not exclude either classical antigen or superantigen-based T-cell activation mechanisms in active plaques, the absence of a simple pattern of V beta usage in different patients suggests than other aspects of T-cell biology including trafficking, proliferation, co-stimulation, or responses to cytokines must also be considered. C1 DARWIN MOL CORP,DEPT MOL BIOL & IMMUNOL,BOTHELL,WA 98021. DARWIN MOL CORP,DEPT GEN,BOTHELL,WA 98021. VA PUGET SOUND HLTH CARE SYST,MED SERV,DERMATOL SECT,SEATTLE,WA. UNIV WASHINGTON,SCH MED,DEPT MED,DIV DERMATOL,SEATTLE,WA 98195. NR 34 TC 23 Z9 23 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 1997 VL 109 IS 1 BP 14 EP 19 DI 10.1111/1523-1747.ep12276338 PG 6 WC Dermatology SC Dermatology GA XF815 UT WOS:A1997XF81500003 PM 9204948 ER PT J AU Tsou, HC Ping, X Xie, X Yao, Y Schrager, C Gruener, A Christiano, AM Liaw, D Parsons, R Eng, C Peacocke, M AF Tsou, HC Ping, X Xie, X Yao, Y Schrager, C Gruener, A Christiano, AM Liaw, D Parsons, R Eng, C Peacocke, M TI The molecular basis of Cowden's syndrome SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. COLUMBIA UNIV,DEPT DERMATOL,NEW YORK,NY 10027. COLUMBIA UNIV,DEPT MED,NEW YORK,NY 10027. COLUMBIA UNIV,DEPT PATHOL,NEW YORK,NY 10027. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 1997 VL 109 IS 1 BP HB5 EP HB5 PG 1 WC Dermatology SC Dermatology GA XF815 UT WOS:A1997XF81500025 ER PT J AU Ramanathan, C Ackerman, JL AF Ramanathan, C Ackerman, JL TI ADRF differential cross polarization spectroscopy of synthetic calcium phosphates and bone mineral SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article ID DILUTE SPINS; NMR; SOLIDS; DYNAMICS AB An adiabatic demagnetization in the rotating frame (ADRF) differential cross polarization (DCP), or inversion recovery cross polarization (IRCP), technique has been developed to study synthetic calcium phosphates and bone mineral. ADRF of the protons followed by a remagnetization of the phosphorus-31 spins results in an equalization of the dipolar and phosphorus Zeeman nuclear spin temperatures, By shifting the phase of the phosphorus RF by 180 degrees during the forward cross polarization it is possible to invert the temperature of this reservoir and initiate reverse cross polarization. Transient Strombotne-Hahn oscillations were observed on inverting the temperature. The presence of these oscillations complicates the determination of a null point on the basis of cross polarization times. It is necessary to shift the phase of the RF only after a Zeeman spin temperature can be defined, and to use an RF field strength that is slightly smaller than the equivalent S-spin local dipolar field in order to produce a zero crossing after the transient oscillations have decayed. (C) 1997 Academic Press. C1 HARVARD UNIV,SCH MED,CHARLESTOWN,MA 02129. MIT,DIV HLTH SCI & TECHNOL,CAMBRIDGE,MA 02139. MIT,DEPT NUCL ENGN,CAMBRIDGE,MA 02139. RP Ramanathan, C (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,NMR CTR,BIOMAT LAB,CHARLESTOWN,MA 02129, USA. RI Ramanathan, Chandrasekhar/C-5207-2008; Ackerman, Jerome/E-2646-2015 OI Ramanathan, Chandrasekhar/0000-0002-7457-3608; Ackerman, Jerome/0000-0001-5176-7496 FU NIAMS NIH HHS [AR42258] NR 22 TC 9 Z9 9 U1 0 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD JUL PY 1997 VL 127 IS 1 BP 26 EP 35 DI 10.1006/jmre.1997.1173 PG 10 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA XQ510 UT WOS:A1997XQ51000003 PM 9245627 ER PT J AU Graybill, JR Bocanegra, R Lambros, C Luther, MF AF Graybill, JR Bocanegra, R Lambros, C Luther, MF TI Granulocyte colony stimulating factor therapy of experimental cryptococcal meningitis SO JOURNAL OF MEDICAL AND VETERINARY MYCOLOGY LA English DT Article DE cryptococcal meningitis; GCSF ID AMPHOTERICIN-B; MURINE CRYPTOCOCCOSIS; NEOFORMANS; MICE; PROTECTION; ANTIBODIES; AIDS AB Cryptococcal meningitis was induced in mice using intracerebral injection of Cryptococcus neoformans. Beginning either 3 days before or 1 day after infection, mice were treated with human recombinant granulocyte colony stimulating factor (hGCSF). In high doses hGCSF reduced the brain tissue burden of C. neoformans but had no effect on survival. The effect of hGCSF was dependent on size of the infecting dose and time of administration. A large innocula of C. neoformans, or when hGCSF was initiated after infection, there was no added benefit. Some groups of mice also received low doses of fluconazole beginning 1 day after infection. Fluconazole both prolonged survival and reduced brain tissue counts of C. neoformans. Combined cytokine/fluconazole therapy was superior to either agent given alone. These studies suggest that hGCSF can add to the efficacy of fluconazole therapy in murine cryptococcosis, and suggest that polymorphonuclear leucocytes contribute to host defence in cryptococcal meningitis. The relative potency of fluconazole appears greater than hGCSF. C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. NIAID,BETHESDA,MD 20892. RP Graybill, JR (reprint author), AUDIE L MURPHY MEM VET ADM MED CTR,DEPT MED,DIV INFECT DIS,7400 MERTON MINTER BLVD,SAN ANTONIO,TX 78284, USA. FU PHS HHS [N0I-A1-25141] NR 17 TC 28 Z9 28 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 0268-1218 J9 J MED VET MYCOL JI J. Med. Vet. Mycol. PD JUL-AUG PY 1997 VL 35 IS 4 BP 243 EP 247 PG 5 WC Mycology SC Mycology GA XW007 UT WOS:A1997XW00700003 PM 9292420 ER PT J AU Novoa, LJ Nagra, RM Nakawatase, T EdwardsLee, T Tourtellotte, WW Cornford, ME AF Novoa, LJ Nagra, RM Nakawatase, T EdwardsLee, T Tourtellotte, WW Cornford, ME TI Fulminant demyelinating encephalomyelitis associated with productive HHV-6 infection in an immunocompetent adult SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE human herpes virus 6; encephalomyelitis; demyelination ID HUMAN HERPESVIRUS-6 INFECTION; EXANTHEM-SUBITUM; ENCEPHALITIS; VIRUS AB Human herpesvirus 6 (HHV-6), the etiologic agent of roseola in young children, has been reported to be detectable in the brain of many neurologically normal adults, although regional localization to plaques of multiple sclerosis has also been demonstrated. Large amounts of this virus were present in multifocal demyelinating white matter lesions of fulminant encephalomyelitis with seizures in a 21-year-old woman with normal immune parameters. Brain biopsy after 3 weeks of neurologic deterioration revealed a viral etiology by light and electron microscopy; the virus was identified as HHV-6 by immunohistochemistry and by polymerase chain reaction (PCR) amplification in biopsy and autopsy specimens. (C) 1997 Wiley-Liss, Inc. C1 UNIV CALIF LOS ANGELES,LOS ANGELES CTY HARBOR MED CTR,DEPT PATHOL,TORRANCE,CA 90509. UNIV CALIF LOS ANGELES,LOS ANGELES CTY HARBOR MED CTR,DEPT NEUROL,TORRANCE,CA 90509. UNIV CALIF LOS ANGELES,SCH MED,BRAIN RES INST,NEUROL RES SERV,W LOS ANGELES VET ADM MED CTR,LOS ANGELES,CA 90024. NR 16 TC 63 Z9 65 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD JUL PY 1997 VL 52 IS 3 BP 301 EP 308 DI 10.1002/(SICI)1096-9071(199707)52:3<301::AID-JMV11>3.0.CO;2-L PG 8 WC Virology SC Virology GA XG228 UT WOS:A1997XG22800011 PM 9210040 ER PT J AU Schulder, M Black, PM Shrieve, DC Alexander, E Loeffler, JS AF Schulder, M Black, PM Shrieve, DC Alexander, E Loeffler, JS TI Permanent low-activity iodine-125 implants for cerebral metastases SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE brachytherapy; cancer; intracranial neoplasms; metastatic tumors; radiation therapy ID BRAIN METASTASES; STEREOTAXIC RADIOSURGERY; RADIATION-THERAPY; MALIGNANT GLIOMAS; IRRADIATION; MANAGEMENT; BRACHYTHERAPY AB Beginning in 1987, selected patients with metastatic brain tumors were treated with permanent implants of low-activity radioactive iodine-125 (I-125) seeds. These patients underwent craniotomy, gross total resection of the metastatic lesion, and placement of the seeds. In general, criteria for treatment included the presence of a recurrent tumor with a volume too large to permit radiosurgery, and a Karnofsky Performance Score of 70 or higher. Thirteen patients underwent 14 implant procedures: all received external whole-brain radiotherapy. Implant dose ranged from 43 Gy to 132 Gy, with a mean of 83 Gy. Survival after implantation ranged from 2 weeks to almost 9 years, with a median of 9 months. Clinical and radiographic local control was obtained in 9 patients. Two patients died of acute, postoperative complications within a month of implantation, so no information regarding tumor control is available for them. Late complications included a bone flap infection in one patient and a CSF leak in another; both were treated without further sequelae. These results demonstrate that permanent I-125 implants can result in good survival and quality of life, and occasionally can yield long-term survival. Potentially, it is a cost-effective treatment in that a separate procedure for stereotactic implantation or radiosurgery is not needed, as is the case with the use of temporary high-activity seeds. The permanent implantation itself adds less than 10 minutes to the craniotomy, and the risk of symptomatic radiation necrosis is low. We recommend consideration of this procedure in patients harboring large, recurrent metastatic tumors that require further surgery. C1 HARVARD UNIV,SCH MED,DEPT SURG NEUROSURG,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT RADIAT ONCOL,BOSTON,MA. BRIGHAM & WOMENS HOSP,BRAIN TUMOR CTR,BOSTON,MA 02115. CHILDRENS HOSP,BOSTON,MA 02115. DANA FARBER CANC INST,BOSTON,MA 02115. JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. NR 26 TC 20 Z9 23 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD JUL PY 1997 VL 33 IS 3 BP 213 EP 221 DI 10.1023/A:1005798027813 PG 9 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA XD897 UT WOS:A1997XD89700005 PM 9195493 ER PT J AU Matthews, RT Ferrante, RJ Jenkins, BG Browne, SE Goetz, K Berger, S Chen, IYC Beal, MF AF Matthews, RT Ferrante, RJ Jenkins, BG Browne, SE Goetz, K Berger, S Chen, IYC Beal, MF TI Iodoacetate produces striatal excitotoxic lesions SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE excitotoxicity; oxidative damage; Huntington's disease; peroxynitrite ID DISEASE GENE HOMOLOG; HUNTINGTONS-DISEASE; IMPAIRMENT; METABOLISM; INHIBITION; BRAIN; ACID AB Impairment of energy production may play a role in the pathogenesis of Huntington's disease (HD). It was recently shown that huntingtin can bind to and possibly inhibit the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH). We found that intrastriatal administration of the GAPDH inhibitor iodoacetate produces striatal lesions that are significantly attenuated by removal of the corticostriatal glutamatergic input, consistent with an excitotoxic mechanism. The lesions are accompanied by increased production of hydroxyl free radicals as assessed by conversion of salicylate to 2,3- and 2,5-dihydroxybenzoic acid. In vivo magnetic resonance imaging showed lesions on T-2-weighted scans, but there was only a small increase in lactate content, These results show that inhibition of GAPDH produces striatal lesions in vivo and suggest that inhibition of GAPDH could contribute to neuronal degeneration in HD. C1 MASSACHUSETTS GEN HOSP,NEUROL SERV,NEUROCHEM LAB,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT RADIOL,NMR CTR,BOSTON,MA 02114. HARVARD UNIV,CAMBRIDGE,MA 02138. BOSTON UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02118. VET ADM MED CTR,GERIATR RES EDUC CLIN CTR,BEDFORD,MA. FU NINDS NIH HHS [NS10828, NS16367, NS31579] NR 22 TC 38 Z9 38 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUL PY 1997 VL 69 IS 1 BP 285 EP 289 PG 5 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA XF431 UT WOS:A1997XF43100034 PM 9202321 ER PT J AU Levine, RL Turski, PA Turnipseed, WD Dulli, DA Grist, TM AF Levine, RL Turski, PA Turnipseed, WD Dulli, DA Grist, TM TI Vasodilatory responses and magnetic resonance angiography - Extracranial and intracranial intravascular flow data SO JOURNAL OF NEUROIMAGING LA English DT Article ID CAROTID-ARTERY STENOSIS; CEREBRAL BLOOD-FLOW; CEREBROVASCULAR REACTIVITY; PERFUSION RESERVE; OCCLUSION; DISEASE; ISCHEMIA; VASOCAPACITANCE; VASOREACTIVITY; ACETAZOLAMIDE AB This study measured the responses of both extracranial (internal carotid arteries) and intracranial (middle cerebral/angular, basilar arteries) intravascular arterial volume flow rates to acetazolamide using phase-contrast magnetic resonance angiography. Twenty-eight newly studied patients were subdivided into four groups: Group l-Nonocclusive, asymptomatic (n = 7, or 14 carotid and middle cerebral/angular artery sides); Group II-unilateral carotid transient ischemic attacks, nonhemodynamic (embolic), varying stenoses (n = 11); Group Ill-unilateral carotid transient ischemic attacks, hemodynamic, varying stenoses (n = 5); and Group lV-unilateral carotid occlusion, asymptomatic (n = 5). The data were separated into nonischemic and ischemic sides so as to illustrate group differences based on vasodilatory responses to acetazolamide. For example, the percent change in volume flow rates over baseline values for the ischemic-side middle cerebral arteries of Group III was significantly the lowest of all of the vasodilatory responses (-25 +/- 11% vs 40 +/- 14% for group II ischemic middle cerebral/angular artery sides, p = 0.008). Group III patients also had significantly lower standing blood pressures (p = 0.012), higher number of transient ischemic attacks (p = 0.008), and shorter duration of events (p = 0.013). Determinations of volume flow rate continue to assist in determining the degree of hemodynamic compromise of a particular vascular territory. C1 UNIV WISCONSIN,DEPT RADIOL,MADISON,WI 53705. UNIV WISCONSIN,DEPT SURG,MADISON,WI 53705. UNIV WISCONSIN,DEPT NEUROL,MADISON,WI 53705. RP Levine, RL (reprint author), WILLIAM S MIDDLETON MEM VET ADM MED CTR,DEPT NEUROL,2500 OVERLOOK TERRACE,MADISON,WI 53705, USA. NR 41 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1051-2284 J9 J NEUROIMAGING JI J. Neuroimaging PD JUL PY 1997 VL 7 IS 3 BP 152 EP 158 PG 7 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA XM018 UT WOS:A1997XM01800003 PM 9237434 ER PT J AU Platten, M MeyerPuttlitz, B Blumcke, I Waha, A Wolf, HK Nothen, MM Louis, DN Sampson, JR vonDeimling, A AF Platten, M MeyerPuttlitz, B Blumcke, I Waha, A Wolf, HK Nothen, MM Louis, DN Sampson, JR vonDeimling, A TI A novel splice site associated polymorphism in the tuberous sclerosis 2 (TSC2) gene may predispose to the development of sporadic gangliogliomas SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE ganglioglioma; polymorphism; risk factor; TSC7 gene ID HETEROZYGOSITY; PATHOLOGY; TISSUES; LOCUS AB The tuberous sclerosis 2 (TSC2) gene is thought to function as a growth suppressor in sporadic and TSC-associated hamartomas and tumors. Clusters of dysplastic glial cells are a common feature of cortical tubers and subependymal nodules in tuberous sclerosis patients. In an effort to identify TSC2 gene alterations in sporadic gliomas, we detected a novel polymorphism adjacent to the 3' splice site of intron 4. We evaluated the distribution of this variant allele in a series of 244 patients with glial tumors, including 55 gangliogliomas, 31 pilocytic astrocytomas (WHO grade I), 50 astrocytomas (WHO grades II and III), and 108 glioblastomas (WHO grade IV. The allelic distribution in the general population was estimated by examining 381 healthy blood donors. This rare allele appeared in the control population and in the patients with astrocytic gliomas with a virtually identical frequency (8.14%, and 8.20%, respectively), The frequency of the rare allele in gangliogliomas, however, was significantly higher (15.5%; p = 0.024). The fact that both gangliogliomas and cortical tubers in tuberous sclerosis contain neuronal and astrocytic elements and may resemble each other histologically suggests that the TSC2 gene map be involved in the development of these tumors. The rare allele of the TSC2 gene emerges as a candidate for a predisposing factor for the formation of sporadic gangliogliomas. C1 UNIV KLINIKEN BONN, INST NEUROPATHOL, D-53105 BONN, GERMANY. UNIV KLINIKEN MAINZ, INST PATHOL, MAINZ, GERMANY. UNIV BONN, INST HUMANGENET, D-5300 BONN, GERMANY. MASSACHUSETTS GEN HOSP, DEPT PATHOL NEUROPATHOL, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, NEUROSURG SERV, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA USA. UNIV WALES COLL MED, INST MED GENET, CARDIFF CF4 4XN, S GLAM, WALES. RI Platten, Michael/F-2902-2013; von Deimling, Andreas/F-7774-2013 OI von Deimling, Andreas/0000-0002-5863-540X NR 26 TC 25 Z9 25 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD JUL PY 1997 VL 56 IS 7 BP 806 EP 810 PG 5 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA XJ202 UT WOS:A1997XJ20200007 PM 9210877 ER PT J AU Paulus, W Baur, I Oberer, DM Breakefield, XO Reeves, SA AF Paulus, W Baur, I Oberer, DM Breakefield, XO Reeves, SA TI Regulated expression of the diphtheria toxin A gene in human glioma cells using prokaryotic transcriptional control elements SO JOURNAL OF NEUROSURGERY LA English DT Article DE diphtheria toxin; gene therapy; glioblastoma multiforme; Lac system; Tet system; tetracycline ID OPERATOR-REPRESSOR SYSTEM; EUKARYOTIC CELLS; MAMMALIAN-CELLS; MEDIATED APOPTOSIS; DNA FRAGMENTATION; LAC OPERATOR; IN-VITRO; PROMOTER; THERAPY; CANCER AB Because accurate regulation of toxin gene expression is critical for safe and effective gene therapy applications, the authors have examined the regulation of diphtheria toxin A (DTA) fragment expression in human glioma cell lines using two transcriptional control systems derived from Escherichia coli: the tetracycline (Tet) system and the lactose (Lac) system. The Tet system includes a tetracycline-controlled transactivator (tTA), a tTA-responsive minimum human cytomegalovirus (hCMV) promoter controlling the expression of the DTA gene, and tetracycline as an allosteric inhibitor. The Lac system includes the lac repressor (lacR), a lacR-regulated Rous sarcoma virus-long terminal repeat (RSV-LTR) promoter controlling the expression of the DTA gene, and isopropyl-thio-beta-D-galactoside (IPTG) as an allosteric inducer. Expression plasmids encoding either tTA or lacR were transfected into U-87MG and U-343MG glioma cells along with the responsive DTA plasmid. Cell killing was monitored by the ability of the toxin to abolish protein synthesis and was quantitated using a luciferase reporter gene. In the Tet system, tumor cell killing could be regulated by tetracycline up to 120-fold. In contrast, only a twofold IPTG-dependent regulation was obtained using the Lac system because of an incomplete repression of DTA expression in the uninduced state. Replacement of the RSV-LTR promoter with the heavy metal-inducible mouse metallothionein-1 promoter in the lacR-responsive unit, as well as the generation of a clonal glioma cell line expressing lacR, did not significantly enhance regulation of DTA in the Lac system. In conclusion, this study demonstrates that the Tet system is of potential use in gene therapy applications in which regulated expression of a therapeutic gene is an important issue. C1 HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,DEPT NEUROL,MOL NEUROONCOL LABS,NEUROL SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT NEUROL,MOL NEUROGENET UNIT,DEPT NEUROL,BOSTON,MA 02114. RP Paulus, W (reprint author), UNIV ERLANGEN NURNBERG,SCH MED,INST PATHOL,DIV NEUROPATHOL,KRANKENHAUSSTR 8-10,D-91054 ERLANGEN,GERMANY. FU NINDS NIH HHS [NS24279] NR 38 TC 22 Z9 22 U1 0 U2 2 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD JUL PY 1997 VL 87 IS 1 BP 89 EP 95 DI 10.3171/jns.1997.87.1.0089 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA XF331 UT WOS:A1997XF33100014 PM 9202271 ER PT J AU Khaw, BA Nakazawa, A ODonnell, SM Pak, KY Narula, J AF Khaw, BA Nakazawa, A ODonnell, SM Pak, KY Narula, J TI Avidity of technetium 99m glucarate for the necrotic myocardium: In vivo and in vitro assessment SO JOURNAL OF NUCLEAR CARDIOLOGY LA English DT Article DE myocardial infarct; radionuclide imaging; myosin; antibody; reperfusion; glucaric acid ID MYOSIN-SPECIFIC ANTIBODY; CARDIAC MYOSIN; LOCALIZATION; INFARCTION; TECHNETIUM-99M-GLUCARATE; INJURY AB Background. Similar to other Tc-99m-based infarct-avid agents, Tc-99m-glucarate localizes in myocardial infarcts, Whether severely ischemic viable myocytes sequester Tc-99m-glucarate is uncertain, To assess the infarct specificity, in vitro and in vivo studies were performed. Methods and Results. H9C2 embryonic rat cardiocytes cultured under normoxia (N) or hypoxia (H) for 24 hours in 7.5 mu Ci Tc-99m-glucarate were compared with necrotic cardiocytes, Mean H/N ratio (3.0 +/- 0.004, mean +/- SD) was significantly less than that of the necrotic/N ratio (39.9 +/- 6.5, p < 0.01), Reperfused myocardial infarction (MI) in 4 dogs confirmed by Tl-201 (0.5 to 1.0 mCi) scintigraphy mere imaged serially with simultaneously injected mixture of Tc-99m-glucarate and In-111-antimyosin Fab, Infarcts were detected scintigraphically within 4 to 10 minutes with Tc-99m-glucarate. In-111-antimyosin required more than 1 hour, Myocardial distribution at 5 hours showed a direct correlation between Tc-99m-glucarate and In-111-antimyosin uptake (r = 0.99, p < 0.0001), Both Tc-99m-glucarate (r = -0.777, p < 0.0001) and In-111-antimyosin (r = -0.775, p < 0.0001) were inversely related to Tl-201 distribution. Conclusions, The near perfect correlation between Tc-99m-glucarate and In-111-antimyosin uptake (r = 0.99) in reperfused canine MI and the insignificant glucarate uptake by viable cardiocytes in vitro attest to the avidity of Tc-99m-glucarate for the necrotic myocardium and favor its use as a specific early marker of myocyte necrosis in acute MI. C1 MASSACHUSETTS GEN HOSP,DIV NUCL MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CARDIAC UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. MOL TARGETING TECHNOL INC,MALVERN,PA. RP Khaw, BA (reprint author), NORTHEASTERN UNIV,BOUVE COLL PHARM,CTR CARDIOVASC TARGETING,205 MUGAR LIFE SCI BLDG,BOSTON,MA 02115, USA. FU NHLBI NIH HHS [1R43-HL54410-01] NR 20 TC 36 Z9 37 U1 0 U2 4 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 1071-3581 J9 J NUCL CARDIOL JI J. Nucl. Cardiol. PD JUL-AUG PY 1997 VL 4 IS 4 BP 283 EP 290 DI 10.1016/S1071-3581(97)90105-7 PG 8 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA XT041 UT WOS:A1997XT04100004 PM 9278874 ER PT J AU Fischman, AJ Thornton, AF Frosch, MP Swearinger, B Gonzalez, RG Alpert, NM AF Fischman, AJ Thornton, AF Frosch, MP Swearinger, B Gonzalez, RG Alpert, NM TI FDG hypermetabolism associated with inflammatory necrotic changes following radiation of meningioma SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE fluorine-18-FDG; PET; meningioma ID F-18 FLUORODEOXYGLUCOSE UPTAKE; TUMOR RECURRENCE; BRAIN-ABSCESS; PET; NECROSIS; SPECT; DIFFERENTIATION; TOMOGRAPHY; GLIOMA; TL-201 AB PET with F-18-fluoro-2-deoxy-D-glucose (FDG) is currently the noninvasive gold standard for distinguishing brain tumor recurrence from radiation necrosis. We present a case report that appears to contradict this doctrine. The patient had a history of atypical meningioma and was treated with surgical resection and postoperative proton-beam radiation therapy. Approximately 16 mo after completion of therapy, MRI demonstrated two new regions of enhancement, and an FDG-PET study was performed to further characterize these lesions. FDG-PET demonstrated an area of intense hypermetabolism, and wide surgical resection was performed. Histological examination of the surgical specimen revealed reactive changes and areas of necrosis. There was no evidence of either recurrent or radiation-induced tumor. C1 MASSACHUSETTS GEN HOSP,DEPT RADIAT MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT NEUROSURG,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RP Fischman, AJ (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,DIV NUCL MED,32 FRUIT ST,BOSTON,MA 02114, USA. NR 20 TC 25 Z9 25 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD JUL PY 1997 VL 38 IS 7 BP 1027 EP 1029 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA XK214 UT WOS:A1997XK21400013 PM 9225785 ER PT J AU Smith, RJ AF Smith, RJ TI Glutamine-supplemented nutrition SO JOURNAL OF PARENTERAL AND ENTERAL NUTRITION LA English DT Editorial Material ID PARENTERAL-NUTRITION C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP Smith, RJ (reprint author), JOSLIN DIABET CTR,1 JOSLIN PL,ROOM 520,BOSTON,MA 02215, USA. FU NIDDK NIH HHS [DK 43038] NR 11 TC 11 Z9 11 U1 0 U2 0 PU AMER SOC PARENTERAL & ENTERAL NUTRITION PI SILVER SPRING PA 8630 FENTON STREET SUITE 412, SILVER SPRING, MD 20910 SN 0148-6071 J9 JPEN-PARENTER ENTER JI J. Parenter. Enter. Nutr. PD JUL-AUG PY 1997 VL 21 IS 4 BP 183 EP 184 DI 10.1177/0148607197021004183 PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA XM333 UT WOS:A1997XM33300001 PM 9252941 ER PT J AU Waters, GS Caplan, D AF Waters, GS Caplan, D TI Working memory and on-line sentence comprehension in patients with Alzheimer's disease SO JOURNAL OF PSYCHOLINGUISTIC RESEARCH LA English DT Article ID MINI-MENTAL STATE; SHORT-TERM-MEMORY; INDIVIDUAL-DIFFERENCES; DEMENTIA; CAPACITY; NEUROPSYCHOLOGY AB We examined the ability of patients with dementia of the Alzheimer's type (DAT) and normal controls to perform a sentence acceptability judgment task that required determining the I referent for a reflexive pronoun. Performance on three different sentence types that differed in terms of syntactic complexity was assessed. Subjects performed the task alone and under two different dual-task conditions which required continuous, externally paced responses. DAT patients were move affected than controls by the dual-task conditions, but were not disproportionately impaired on the more complex sentence types. The failure of DAT patients to be disproportionately affected on the most complex sentence types in the dual-task conditions provides evidence for the separation of the processing resources that are used in sentence comprehension from those involved in other tasks. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,NEUROPSYCHOL LAB,BOSTON,MA 02114. RP Waters, GS (reprint author), MCGILL UNIV,SCH COMMUN SCI & DISORDERS,1266 PINE AVE W,MONTREAL,PQ H3G 1A8,CANADA. FU NIA NIH HHS [AG09661] NR 48 TC 30 Z9 30 U1 1 U2 1 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0090-6905 J9 J PSYCHOLINGUIST RES JI J. Psycholinguist. Res. PD JUL PY 1997 VL 26 IS 4 BP 377 EP 400 DI 10.1023/A:1025073902269 PG 24 WC Linguistics; Psychology, Experimental SC Linguistics; Psychology GA XL385 UT WOS:A1997XL38500001 PM 9232007 ER PT J AU Saxon, AJ McGuffin, R Walker, RD AF Saxon, AJ McGuffin, R Walker, RD TI An open trial of transdermal nicotine replacement therapy for smoking cessation among alcohol- and drug-dependent inpatients SO JOURNAL OF SUBSTANCE ABUSE TREATMENT LA English DT Article DE nicotine dependence; alcohol dependence; drug dependence; transdermal nicotine; smoking cessation ID FAGERSTROM TOLERANCE QUESTIONNAIRE; TOBACCO WITHDRAWAL; QUITTERS AB An open trial of transdermal nicotine replacement for smoking cessation was conducted Over a 7-month period, all patients admitted to the inpatient alcohol and drug treatment unit of the Seattle Veterans Affairs Medical Center (n = 207) were offered the opportunity to participate in an open trial of transdermal nicotine replacement for smoking cessation. Forty-nine (23.7%) elected to attempt cessation with transdermal nicotine during their inpatient treatment episodes. These subjects received no psychosocial treatments directed specifically at smoking cessation. They smoked a mean of 28.5 (SD = 16.4) cigarettes per day and obtained a mean score of 8.3 (SD = 1.9) on the Fagerstrom Test for Nicotine Dependence. Subjects remained on transdermal nicotine an average of 18.8 (SD = 8.2) days with desire to resume smoking the major reason for discontinuation. Seven subjects (14.3%) self-reported tobacco abstinence at 21 days, and 5 (10.2%) self-reported abstinence as outpatients at 6 weeks. These results show that a substantial proportion of alcohol-and drug-dependent patients entering inpatient treatment are willing to attempt alcohol and illicit drug cessation and tobacco cessation simultaneously and that transdermal nicotine holds promise as a treatment modality in this population. RP Saxon, AJ (reprint author), UNIV WASHINGTON,SCH MED,DEPT PSYCHIAT & BEHAV SCI,VA PUGET SOUND HLTH CARE SYST,SEATTLE,WA 98195, USA. NR 20 TC 36 Z9 36 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0740-5472 J9 J SUBST ABUSE TREAT JI J. Subst. Abus. Treat. PD JUL-AUG PY 1997 VL 14 IS 4 BP 333 EP 337 DI 10.1016/S0740-5472(97)00031-7 PG 5 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA YE196 UT WOS:A1997YE19600003 PM 9368209 ER PT J AU Qi, YY Hillman, RE AF Qi, YY Hillman, RE TI Temporal and spectral estimations of harmonics-to-noise ratio in human voice signals SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID VOCAL QUALITY; COMPUTATION; PERCEPTION; HOARSENESS; SPEECH AB The quantity, harmonic-to-noise ratio (HNR), has been used to estimate the level of noise in human voice signals. HNR estimation can be accomplished in two ways: (1) on a time-domain basis, in which HNR is computed directly from the acoustic waveform; and (2) on a frequency-domain basis, in which HNR is computed from a transformed representation of the waveform. An algorithm for computing HNR in the frequency domain was modified and tested in the work described here. The modifications were designed to reduce the influence of spectral leakage in the computation of harmonic energy, and to remove the necessity of spectral baseline shifting prescribed in one existing algorithm [G. de Krom, J. Speech Hear. Res. 36, 254-266 (1993)]. Frequency-domain estimations of HNR based on this existing algorithm and our modified algorithm were compared to time-domain estimations on synthetic signals and human pathological voice samples. Results indicated a highly significant, linear correlation between frequency- and time-domain estimations of HNR for our modified approach. (C) 1997 Acoustical Society of America. C1 MASSACHUSETTS EYE & EAR INFIRM,VOICE & SPEECH LAB,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,CAMBRIDGE,MA 02139. MASSACHUSETTS GEN HOSP,INST HLTH PROFESS,BOSTON,MA 02215. RP Qi, YY (reprint author), UNIV ARIZONA,DEPT SPEECH & HEARING SCI,TUCSON,AZ 85721, USA. FU NIDCD NIH HHS [DC00266, DC01440] NR 19 TC 58 Z9 63 U1 0 U2 1 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD JUL PY 1997 VL 102 IS 1 BP 537 EP 543 DI 10.1121/1.419726 PG 7 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA XL752 UT WOS:A1997XL75200057 PM 9228816 ER PT J AU Hirshfeld, DR Biederman, J Brody, L Faraone, SV Rosenbaum, JF AF Hirshfeld, DR Biederman, J Brody, L Faraone, SV Rosenbaum, JF TI Expressed emotion toward children with behavioral inhibition: Associations with maternal anxiety disorder SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE behavioral inhibition; anxiety disorder; expressed emotion ID PANIC DISORDER; FAMILY FACTORS; PARENTS; RISK; PSYCHOPATHOLOGY; AGORAPHOBIA; DEPRESSION; INTERVIEW; MOTHERS AB Objective: To examine the role of maternal psychopathology in influencing ''expressed emotion'' (EE) directed toward children with behavioral inhibition (BI) or psychiatric disorders. Method: Maternal EE was assessed via Five-Minute-Speech-Sample in two samples of children previously evaluated for child and maternal lifetime prevalence of DSM-III disorders and assessed via laboratory observations for BI. The authors previously reported that maternal EE was associated with BI and with the number of child behavior and mood disorders in these samples. The at-risk sample (N = 30) consisted of mothers with panic disorder and psychiatric controls and their 4- through 10-year-old children, The Kagan sample (N = 41) consisted of children selected at age 21 months as BI or uninhibited and followed through age 11. Results: Interaction effects were found: In mothers with anxiety disorders, but not those without, maternal criticism (a component of EE) was significantly associated with child BI, independently of the child's number of disorders. Similarly, in mothers with anxiety disorders only, maternal criticism was significantly associated with a high number of child disorders. Conclusions: The relationships between mothers who have anxiety disorders and their children who have BI or psychiatric disorders may be marked by criticism or dissatisfaction. If confirmed, these findings offer opportunities for appropriate interventions. C1 BOSTON UNIV,DEPT PSYCHOL,BOSTON,MA 02215. MASSACHUSETTS MENTAL HLTH CTR,COMMONWEALTH RES CTR,BOSTON,MA 02115. RP Hirshfeld, DR (reprint author), HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,PSYCHIAT SERV,RES UNIT,50 STANIFORD ST,4TH FLOOR,BOSTON,MA 02114, USA. OI Faraone, Stephen/0000-0002-9217-3982 NR 35 TC 89 Z9 90 U1 5 U2 10 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 JUL PY 1997 VL 36 IS 7 BP 910 EP 917 DI 10.1097/00004583-199707000-00012 PG 8 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA XF817 UT WOS:A1997XF81700012 PM 9204668 ER PT J AU Wilens, TE Biederman, J Abrantes, AM Spencer, TJ AF Wilens, TE Biederman, J Abrantes, AM Spencer, TJ TI Clinical characteristics of psychiatrically referred adolescent outpatients with substance use disorder SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE adolescent; substance abuse; psychopathology; comorbidity ID ILLICIT DRUG-USE; YOUNG ADULTHOOD; ANTISOCIAL BEHAVIORS; ANXIETY DISORDERS; COMORBIDITY; ABUSERS; ALCOHOL; DEPRESSION; PATTERNS; PROGRESSION AB Objective: There is increasing interest in the developmental relationship of psychopathology and substance use disorders (SUD) in youths. Because the bulk of literature is focused in inpatient or incarcerated youths, inferences and generalizations are limited in outpatient settings. The clinical characteristics of psychiatrically referred outpatients were studied to determine whether differences existed in the nature and severity of comorbid psychiatric disorders when substance abuse was involved. Method: All diagnoses were derived from structured psychiatric interviews completed on all youths on intake assessment. Adolescents with an identified SUD (n = 38) were compared with those without SUD (n = 321) on a number of variables including past and current psychopathology, cognitive and school functioning, and overall impairment. Results: Eleven percent of referred outpatients (mean age = 15.9 +/- 1.3 years) met full criteria for a SUD by parental report. Controlling for age, adolescents with SUD had higher risk for mood and disruptive behavioral disorders compared with psychiatric controls. In the majority of cases, the onset of psychopathology preceded the onset of SUD by at least 1 year. The group with SUD also had lower overall functioning and more school dysfunction and psychiatric hospitalizations than their non-SUD peers. Conclusions: Despite the small number of adolescents with SUD in this sample, these data indicate that SUD is common in outpatient psychiatry referrals. Youths with SUD appear to be at increased risk for more psychopathology and dysfunction in a number of domains. C1 HARVARD UNIV, SCH MED, BOSTON, MA USA. RP Wilens, TE (reprint author), MASSACHUSETTS GEN HOSP, PEDIAT PSYCHOPHARMACOL UNIT, CHILD PSYCHIAT SERV, ACC 725, BOSTON, MA 02114 USA. FU NIMH NIH HHS [MH-K2001175A03] NR 51 TC 77 Z9 77 U1 2 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JUL PY 1997 VL 36 IS 7 BP 941 EP 947 DI 10.1097/00004583-199707000-00016 PG 7 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA XF817 UT WOS:A1997XF81700016 PM 9204672 ER PT J AU Magro, CM Baden, LA Crowson, AN Bowden, PE Baden, HP AF Magro, CM Baden, LA Crowson, AN Bowden, PE Baden, HP TI A novel nonepidermolytic palmoplantar keratoderma: A clinical and histopathologic study of six cases SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID PALMAR-PLANTAR KERATODERMA; HYSTRIX CURTH-MACKLIN; EPIDERMOLYTIC HYPERKERATOSIS; MUTATIONS; GENE; KERATIN-1; DOMAIN; LOCUS AB Background: Some hereditary palmoplantar keratodermas (PPK) have been defined at the molecular level. Objective: Our purpose was to establish the cause of a hereditary PPK with unique histopathologic findings in the epidermis. Methods: Investigative studies included light and electron microscopy and determination of genomic DNA sequence. Results: Six patients with PPK were found to have unique changes in the epidermis characterized by orthokeratosis, parakeratosis, perinuclear vacuolization, and keratohyalin granules that varied in size and shape and were located in the cell periphery. Electron microscopy showed the perinuclear region contained many ribosomes and vacuoles and was surrounded by a tonofibril shell. Family involvement suggested a dominant disorder. However, no mutation of keratin genes 1, 6a, 9, or 16 was found. Conclusion: The histopathologic features of this unique PPK most closely resemble Curth-Macklin ichthyosis for which the genetic basis has not been established. Further genetic studies are needed. C1 HARVARD UNIV,CUTANEOUS BIOL RES CTR,MASSACHUSETTS GEN HOSP,MED SCH,DEPT DERMATOL,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,BETH ISRAEL HOSP,DEPT PATHOL,CAMBRIDGE,MA 02138. PATHOL SERV INC,CAMBRIDGE,MA. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT DERMATOL,BOSTON,MA 02115. MISERICORDIA GEN HOSP,DEPT LABS,WINNIPEG,MB,CANADA. MISERICORDIA GEN HOSP,CENT MED LABS,WINNIPEG,MB,CANADA. UNIV WALES COLL CARDIFF,COLL MED,DEPT DERMATOL,CARDIFF CF1 3NS,S GLAM,WALES. NR 25 TC 7 Z9 7 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 JUL PY 1997 VL 37 IS 1 BP 27 EP 33 DI 10.1016/S0190-9622(97)70208-1 PG 7 WC Dermatology SC Dermatology GA XJ179 UT WOS:A1997XJ17900002 PM 9216520 ER PT J AU Grevelink, JM White, VR Bonoan, R Denman, WT AF Grevelink, JM White, VR Bonoan, R Denman, WT TI Pulsed laser treatment in children and the use of anesthesia SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID PORT-WINE STAINS; TUNABLE DYE-LASER; 577 NM; THERAPY; EMLA AB Background: The rationale for choosing certain anesthetic options in children when they are being treated with pulsed lasers is unclear. Objective: Our purpose was to assess the safety and side effects of general anesthesia in the treatment of vascular lesions and to compare this to treatment outcome in the office setting. Methods: We carried out a retrospective chart review of 179 patients, with an age range of 5 weeks to 18 years, who received laser treatment and underwent different anesthetic modalities. The age of the patient and the size, location, and severity of the vascular lesion were also noted. Results: The factors determining the type of anesthesia to use included (1) the age of the patient, (2) the number of treatments, and (3) the size and location of the lesion. Our data showed minimal risk and sequelae of general anesthesia in the treatment of vascular lesions in children. Conclusion: Proper selection of anesthesia is a key factor in dealing with children. Office surgery can be performed safely when small lesions are treated. The use of general anesthesia in the treatment of port-wine stains in children does not appear to be accompanied by increased risk. C1 HARVARD UNIV,DEPT ANESTHESIA,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114. RP Grevelink, JM (reprint author), HARVARD UNIV,DERMATOL LASER CTR,MASSACHUSETTS GEN HOSP,SCH MED,275 CAMBRIDGE ST,SUITE 503,BOSTON,MA 02114, USA. NR 25 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 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD JUL PY 1997 VL 37 IS 1 BP 75 EP 81 DI 10.1016/S0190-9622(97)70214-7 PG 7 WC Dermatology SC Dermatology GA XJ179 UT WOS:A1997XJ17900008 PM 9216526 ER PT J AU Swanson, SJ Mentzer, SJ DeCamp, MM Bueno, R Richards, WG Ingenito, EP Reilly, JJ Sugarbaker, DJ AF Swanson, SJ Mentzer, SJ DeCamp, MM Bueno, R Richards, WG Ingenito, EP Reilly, JJ Sugarbaker, DJ TI No-cut thoracoscopic lung plication: A new technique for lung volume reduction surgery SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID OBSTRUCTIVE PULMONARY-DISEASE; THORACIC-SURGERY AB Background: Lung volume reduction surgery (LVRS) using a linear cutting stapler or laser ablation via median sternotomy or thoracoscopy is a current therapy for symptomatic emphysema. The primary causes of morbidity and mortality (as high as 20%) are existing comorbidities and prolonged air leaks secondary to visceral pleural division. We report a novel technique using minimally invasive techniques designed to achieve volume reduction while preserving the visceral pleura. A novel lung grasper and a knifeless stapler are used to permanently plicate lung tissue without cutting visceral pleura. Study Design: This prospective analysis involves a consecutive series of patients who had LVRS using this method. Between May 1995 and September 1996, 32 patients underwent 50 unilateral, staged bilateral, or bilateral thoracoscopic lung plication procedures. The indications for LVRS were standard; they included severe limiting dyspnea (forced expiratory volume in one second [FEV1] = 0.68 +/- 0.05), hyperinflated lungs with flattened diaphragms on chest x-ray, and diffuse emphysema seen on chest computed tomography scan. Ventilation and perfusion scanning was used to identify potential ventilation and perfusion mismatch target areas of lung for plication. Results: The right lung was plicated first in 25 of 32 patients (78%), and upper lobe plications predominated (77%), A mean of 9.3 +/- 0.8 staple firing were used for each unilateral plication procedure. There were no perioperative deaths. Two patients (4%) required axillary thoracotomies to repair air leaks. Mean chest tube duration was 6.3 +/- 0.5 days. Median hospital stay was 7 days (range 3-15). An Intensive Care Unit stay was required following 8 procedures (17%). Post-operative morbidity occurred in 18 (39%) of 46 procedures, including 5 cases of atrial fibrillation and 4 persistent (> 7 days) air leaks. A minimum 2 month followup was available for 22 patients (32 of 46 procedures), demonstrating a clear chest x-ray with significant improvement in ipsilateral diaphragmatic contour. Twelve patients had unilateral reduction, and 10 patients had bilateral reduction in either a staged (n = 7) or sequential at one operation (n = 3) fashion. Twenty-five (78%) of 32 procedures were associated with improved pulmonary function, with a mean increase in FEV1, in patients in this subgroup of procedures, of 43 +/- 7% for each ipsilateral plication at a mean followup of 3.8 +/- 0.5 months. For the entire group of 32 procedures, the mean improvement in measured FEV1 was 29 +/- 7%. Supplemental oxygen requirement was significantly reduced in 9 of 16 patients following plication. Conclusion: These data suggest that minimally invasive surgical techniques coupled with a no-cut lung plication can achieve significant lung volume reduction with favorable postoperative morbidity and mortality. Lung plication appears to hold promise as an alternative technique of LVRS. (C) 1997 by the American College of Surgeons. C1 BRIGHAM & WOMENS HOSP,DIV PULM CRIT CARE,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA. DANA FARBER CANC INST,BOSTON,MA 02115. RP Swanson, SJ (reprint author), BRIGHAM & WOMENS HOSP,DIV THORAC DIS,75 FRANCIS ST,BOSTON,MA 02115, USA. NR 15 TC 36 Z9 36 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 JUL PY 1997 VL 185 IS 1 BP 25 EP 32 DI 10.1016/S1072-7515(01)00877-8 PG 8 WC Surgery SC Surgery GA XG419 UT WOS:A1997XG41900005 PM 9208957 ER PT J AU Rosenfeld, KE Pearlman, RA AF Rosenfeld, KE Pearlman, RA TI Allocating medical resources: Recommendations for a professional response SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Editorial Material ID RACIAL-DIFFERENCES; UNITED-STATES; APPROPRIATENESS; SYSTEM C1 VET ADM MED CTR,SEATTLE,WA. RP Rosenfeld, KE (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,11301 WILSHIRE BLVD,LOS ANGELES,CA 90073, USA. NR 19 TC 2 Z9 2 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 JUL PY 1997 VL 45 IS 7 BP 886 EP 888 PG 3 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA XH933 UT WOS:A1997XH93300022 PM 9215345 ER PT J AU Simeone, LR Veves, A AF Simeone, LR Veves, A TI Screening techniques to identify the diabetic patient at risk of ulceration SO JOURNAL OF THE AMERICAN PODIATRIC MEDICAL ASSOCIATION LA English DT Article ID FOOT ULCERATION; PRESSURES; THRESHOLD; MELLITUS AB Foot problems are common in diabetic patients, with neuropathy and peripheral vascular disease being the main causative factors. Identification of high-risk feet can be accomplished by using basic clinical skills and simple equipment. Limb amputation is the most preventable of the long-term diabetes complications and a multidisciplinary approach can achieve a dramatic reduction of major limb amputations. C1 BETH ISRAEL DEACONESS MED CTR,JOSLIN FOOT CTR,DIV PODIAT,BOSTON,MA 02215. RP Simeone, LR (reprint author), HARVARD UNIV,SCH MED,DEPT SURG,CAMBRIDGE,MA 02138, USA. NR 24 TC 12 Z9 12 U1 0 U2 0 PU AMER PODIATRIC MED ASSN PI BETHESDA PA 9312 OLD GEORGETOWN ROAD, BETHESDA, MD 20814-1621 SN 0003-0538 J9 J AM PODIAT MED ASSN JI J. Am. Podiatr. Med. Assoc. PD JUL PY 1997 VL 87 IS 7 BP 313 EP 317 PG 5 WC Orthopedics SC Orthopedics GA XL325 UT WOS:A1997XL32500004 PM 9241973 ER PT J AU Boiselle, PM Shepard, JAO McLoud, TC Grillo, HC Wright, CD AF Boiselle, PM Shepard, JAO McLoud, TC Grillo, HC Wright, CD TI Postpneumonectomy syndrome: Another twist SO JOURNAL OF THORACIC IMAGING LA English DT Article DE bronchi, compression; bronchi, CT; lung, surgery; lung, CT ID RIGHT-PNEUMONECTOMY AB This report describes the clinical, radiographic, and surgical findings in a patient with a rare postoperative complication, the postpneumonectomy syndrome. To our knowledge, it is the first reported case of postpneumonectomy syndrome after left pneumonectomy in a patient with a left-sided aortic arch. C1 MASSACHUSETTS GEN HOSP,DEPT DIAGNOST RADIOL,BOSTON,MA 02114. NR 6 TC 6 Z9 7 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0883-5993 J9 J THORAC IMAG JI J. Thorac. Imaging PD JUL PY 1997 VL 12 IS 3 BP 209 EP 211 DI 10.1097/00005382-199707000-00007 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA XK878 UT WOS:A1997XK87800007 PM 9249679 ER PT J AU Bromley, B Benacerraf, B AF Bromley, B Benacerraf, B TI Adnexal masses during pregnancy: Accuracy of sonographic diagnosis and outcome SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article DE masses, adnexal; adnexa, masses; ovary; dermoid; endometrioma; cysts, ovarian ID OVARIAN MASSES; CYSTS AB We sought to determine the accuracy of sonographic diagnosis and perinatal outcome in pregnancies with maternal adnexal masses. All patients with a prenatal sonographic diagnosis of an adnexal mass measuring 4 cm or greater beyond 12 weeks of gestation were identified. Only masses associated with live fetuses, for which pathologic follow-up or direct visualization of the ovary was available at a single hospital, were included in the study. Sonographic evaluation of the pelvic mass was done prospectively at the time of the original scan and characterized on the basis of morphologic criteria. One hundred and twenty-five pregnant patients 21 to 47 years old with 131 lesions formed the study group. The pathologic diagnoses included 40 dermoids, 15 endometriomas, 14 cysts, 13 cystadenomas, nine tubal cysts, four fibroids, and one ovarian cancer. Six patients had complex pathologic lesions and five had unusual diagnoses. Twenty-four patients had normal ovaries on follow-up examination. Sonographically benign appearing lesions were seen in 89.3% of patients. Ninety-five percent of dermoids, 80% of endometriomas, and 71% of simple cysts were characterized correctly. Fourteen of the 131 lesions (10.7%) had sonographic characteristics suggestive of malignancy. One of these 14 patients (7%) had ovarian cancer. This represents a 0.8% malignancy rate among the total number of lesions. Twenty-four of the 125 patients (19%) underwent second trimester laparotomy at the discretion of their managing obstetricians, with no pregnancy losses. One patient had acute torsion of a dermoid at 39 weeks. Prenatal sonography can accurately characterize maternal adnexal lesions. C1 MASSACHUSETTS GEN HOSP,DEPT OBSTET & GYNECOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,BOSTON,MA 02115. NR 8 TC 64 Z9 67 U1 0 U2 0 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD JUL PY 1997 VL 16 IS 7 BP 447 EP 452 PG 6 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA XT751 UT WOS:A1997XT75100001 PM 9315194 ER PT J AU Barry, MJ AF Barry, MJ TI Does evaluation with the international prostate symptom score predict the outcome of transurethral resection of the prostate? Editorial comment SO JOURNAL OF UROLOGY LA English DT Editorial Material RP Barry, MJ (reprint author), MASSACHUSETTS GEN HOSP,MED PRACTICES EVALUAT CTR,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JUL PY 1997 VL 158 IS 1 BP 99 EP 99 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XC692 UT WOS:A1997XC69200025 ER PT J AU Hamdan, AD Aiello, LP Misare, BD Contreras, MA King, GL LoGerfo, FW Quist, WC AF Hamdan, AD Aiello, LP Misare, BD Contreras, MA King, GL LoGerfo, FW Quist, WC TI Vascular endothelial growth factor expression in canine peripheral vein bypass grafts SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID SMOOTH-MUSCLE CELLS; RNA DIFFERENTIAL DISPLAY; MESSENGER-RNA; INTIMAL HYPERPLASIA; GENE-EXPRESSION; ARTERIAL RECONSTRUCTIONS; DIABETIC-RETINOPATHY; ANGIOGENESIS; HYPOXIA; PROLIFERATION AB Purpose: Autologous veins used as arterial bypass grafts undergo initial loss of the endothelial cell (EC) lining, which is followed by reendothelialization. We characterized the expression of the EC-specific angiogenic mitogen, vascular endothelial growth factor (VEGF), in vascular grafts to help elucidate the molecular and cellular events after bypass procedures. Methods: Cephalic vein-femoral artery interposition grafts were placed in mongrel dogs. Vein grafts and arteries were harvested at either 48 hours or 4 weeks after bypass, the total RNA was isolated, and the VEGF mRNA expression was evaluated by Northern blot analysis. Tissue segments from each time period were evaluated by immunohistochemical analysis using anti-VEGF antibodies. Results: VEGF mRNA expression in vein grafts as compared with control veins was increased 2.5-fold 48 hours after bypass grafting (p = 0.02) but returned to initial control levels in grafts removed at 4 weeks. Distal arterial segments, which included the anastomotic site without attached vein graft, had a 21.4-fold increase in VEGF expres sion at 48 hours (p = 0.02) and a 6.6-fold increase at 4 weeks (p < 0.01) as compared with control arterial segments. Vessels subjected to arteriotomy or ischemia alone also demonstrated increased VEGF expression. Immunohistochemical analysis revealed VEGF protein within ECs and smooth muscle cells of the venous bypass graft, with maximal levels observed within intimal hyperplasia at the arterial anastomosis. Conclusions: After arterial reconstruction procedures using venous conduits, VEGF is significantly increased at 48 hours in the vein graft and arterial anastomosis. VEGE expression in the vein graft normalizes within 4 weeks but remains significantly elevated in the adjacent arterial segment. Increased VEGF production after arterial grafting may facilitate reendothelialization, thus partially accounting for optimal patency rates achieved with autologous vein grafts. C1 HARVARD UNIV,NEW ENGLAND DEACONESS HOSP,SCH MED,DIV VASC SURG,BOSTON,MA 02215. HARVARD UNIV,NEW ENGLAND DEACONESS HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02215. CHILDRENS HOSP,DEPT CARDIAC SURG,BOSTON,MA. JOSLIN DIABET CTR,BEETHAM EYE INST,BOSTON,MA. BRIGHAM & WOMENS HOSP,DEPT MED,BOSTON,MA 02115. FU NEI NIH HHS [EY10827]; NHLBI NIH HHS [HL-217906-13, T32-HL07734-01A1] NR 33 TC 15 Z9 15 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUL PY 1997 VL 26 IS 1 BP 79 EP 86 DI 10.1016/S0741-5214(97)70150-2 PG 8 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA XM927 UT WOS:A1997XM92700013 PM 9240325 ER PT J AU Melegari, M Scaglioni, PP Wands, JR AF Melegari, M Scaglioni, PP Wands, JR TI The small envelope protein is required for secretion of a naturally occurring hepatitis B virus mutant with pre-S1 deleted SO JOURNAL OF VIROLOGY LA English DT Article ID CHRONIC HBV INFECTION; TRANSMEMBRANE TOPOLOGY; AVIAN HEPADNAVIRUS; SURFACE-ANTIGEN; REPLICATION; VARIANTS; GENE; GLYCOPROTEIN; PARTICLES; SEQUENCE AB Naturally occurring deletions in the hepatitis B virus pre-S1 domain have been frequently found during persistent viral infection, In this study we have investigated the functional properties of a mutant viral genome that carries an in-frame deletion of 183 nucleotides in the pre-S1 region, This deletion removes the promoter of the small envelope gene, Transfection into human hepatocellular carcinoma cells of a replication-competent construct containing this deletion resulted in an increase of intermediate DNA replicative forms compared to those produced by wild-type hepatitis B virus. Northern blot analysis revealed that such cells lack the 2.1-kb transcripts encoding the small envelope protein and that hepatitis B surface antigen was absent as well, Furthermore, nucleocapsids containing the genome with pre-S1 deleted were not secreted, and the deleted large envelope protein was retained with the cytoplasm and exhibited a perinuclear pattern of distribution, However, coexpression with the small envelope protein was sufficient to restore virion secretion and to change the cellular distribution of the deleted large envelope protein, In addition, the creation of point mutations that prevent the synthesis of large or small envelope proteins also inhibited viral secretion and led to increased levels of hepatitis B virus intermediate replicative forms within the cell, These studies suggest that naturally occurring viral mutants with pre-S1 deletions involving the promoter region of the small envelope gene will generate a deleted large envelope protein that is retained in the endoplasmic reticulum, resulting in the accumulation of nucleocapsids containing viral DNA; transcomplementation With the wild-type small envelope protein will allow mutant virion secretion to occur. C1 HARVARD UNIV,MOL HEPATOL LAB,MASSACHUSETTS GEN HOSP,SCH MED,CANC CTR,CHARLESTOWN,MA 02129. OI Scaglioni, Pier Paolo/0000-0002-6036-5138 FU NCI NIH HHS [CA-35711]; NIAAA NIH HHS [AA-02169] NR 31 TC 60 Z9 61 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 1997 VL 71 IS 7 BP 5449 EP 5454 PG 6 WC Virology SC Virology GA XD829 UT WOS:A1997XD82900069 PM 9188617 ER PT J AU Feener, EP King, GL AF Feener, EP King, GL TI Vascular dysfunction in diabetes mellitus SO LANCET LA English DT Article ID GLYCATION; HEART; INHIBITION; COLLAGEN; DISEASE C1 HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02215. FU NIDDK NIH HHS [P30 DK036836] NR 35 TC 23 Z9 27 U1 0 U2 1 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD JUL PY 1997 VL 350 SU 1 BP SI9 EP SI13 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA XM265 UT WOS:A1997XM26500004 PM 9250277 ER PT J AU Nathan, DM Meigs, J Singer, DE AF Nathan, DM Meigs, J Singer, DE TI The epidemiology of cardiovascular disease in type 2 diabetes mellitus: How sweet it is ... or is it? SO LANCET LA English DT Article ID CORONARY-HEART-DISEASE; IMPAIRED GLUCOSE-TOLERANCE; RISK-FACTORS; FOLLOW-UP; MORTALITY; INSULIN; COMPLICATIONS; POPULATION; ONSET; PREVALENCE C1 MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RP Nathan, DM (reprint author), MASSACHUSETTS GEN HOSP,DIABET UNIT,MED EVALUAT UNIT,BULFINCH 408,BOSTON,MA 02114, USA. NR 58 TC 18 Z9 18 U1 0 U2 1 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD JUL PY 1997 VL 350 SU 1 BP SI4 EP SI9 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA XM265 UT WOS:A1997XM26500003 PM 9250276 ER PT J AU Nathan, DM AF Nathan, DM TI Diabetes and the heart - Foreword SO LANCET LA English DT Editorial Material RP Nathan, DM (reprint author), MASSACHUSETTS GEN HOSP,DIABET UNIT,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD JUL PY 1997 VL 350 SU 1 BP U2 EP U2 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA XM265 UT WOS:A1997XM26500001 ER PT J AU Merchant, SN Wang, PC Jang, CH Glynn, RJ Rauch, SD McKenna, MJ Nadol, JB AF Merchant, SN Wang, PC Jang, CH Glynn, RJ Rauch, SD McKenna, MJ Nadol, JB TI Efficacy of tympanomastoid surgery for control of infection in active chronic otitis media SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT Meeting of the Eastern Section of the American-Laryngological-Rhinological-and-Otological-Society CY JAN 31-FEB 02, 1997 CL BOSTON, MA SP Amer Laryngol Rhinol & Otol Soc, E Sect ID CHOLESTEATOMA SURGERY; MASTOIDECTOMY AB The efficacy of surgery in controlling infection in 272 tympanomastoidectomy procedures for chronic otitis media (COM) was assessed by means of a four-point rating scale that incorporated both symptoms and signs, such as the presence or absence of otorrhea and granulation tissue. Of the 272 procedures, 170 were performed for COM with cholesteatoma and 102 were for active COM with granulation tissue but no cholesteatoma. Forty-seven percent were primary procedures, and 53% were revisions. Minimum follow-up was 12 months for all cases, with a mean of 30 months. Adequate control of infection occurred in 248 (91%) of the 272 cases. Of the 24 cases (9%) that developed persistent infection, 10 were controlled with a combination of oral and topical antibiotics and/or delayed skin grafting in the office. Thus overall satisfactory control of infection was achieved in 258 of 272 cases (95%). The outcome was influenced by the diagnostic category of COM: COM with cholesteatoma did significantly better than COM with granulation tissue (P = 0.02). The outcome was not influenced by the following variables: primary versus revision surgery, canal wall-up versus canal wall-down surgery, and extent of disease. The results suggest that active COM with granulation tissue may be more difficult to control than COM with cholesteatoma. C1 HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02115. RP Merchant, SN (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,243 CHARLES ST,BOSTON,MA 02114, USA. NR 17 TC 32 Z9 32 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD JUL PY 1997 VL 107 IS 7 BP 872 EP 877 DI 10.1097/00005537-199707000-00007 PG 6 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA XJ298 UT WOS:A1997XJ29800007 PM 9217122 ER PT J AU Walker, RP Kazuko, E Gopalsami, C Bassali, J Lawrence, AM Paloyan, E AF Walker, RP Kazuko, E Gopalsami, C Bassali, J Lawrence, AM Paloyan, E TI Hyperparathyroidism associated with a chronic hypothyroid state SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT Meeting of the Middle-Section of the American-Laryngological-Rhinological-and-Otological-Society CY JAN 20-21, 1996 CL DEARBORN, MI SP Amer Laryngol Rhinol & Otol Soc Inc ID HASHIMOTOS THYROIDITIS; PARATHYROID ADENOMA; RADIATION; DISEASE; HYPERCALCEMIA; PREVALENCE; NEOPLASIA; SERUM AB Reports of the coexistence of hyperparathyroidism and thyroid disease have raised the issue of a possible etiologic relationship. The present study tests the hypothesis that chronic elevation of thyroid-stimulating hormone (TSH) is related to the development of hyperparathyroidism. Four groups of 60 female rats were treated as follows: group 1, control; group 2, propylthiouracil (PTU) 0.0025%; group 3, PTU 0.0025% plus thyroxine, 5 mu g two times per week; and group 4, only thyroxine. The animals' serum calcium, phosphorus, TSH, thyroxine, and parathyroid hormone (PTH) levels were evaluated at 0, 6, 12, and 18 months. Significant elevation of TSH was sustained throughout the 18 months in groups 2 and 3. The PTH levels were also significantly elevated in both group 2 and group 3 animals (P = 0.02), The histopathologic features of the parathyroids were evaluated at 18 months. In the group 2 (PTU only) animals, which had profound hypothyroid, 44% developed parathyroid adenomas. In the group 3 (PTU plus thyroxine) animals, who had mildly elevated TSH levels, 53% developed parathyroid adenomas. These findings are consistent with the hypothesis that prolonged TSH stimulation may lead to hyperparathyroidism in the rat model. C1 LOYOLA UNIV, MED CTR, DEPT BIOCHEM, MAYWOOD, IL 60153 USA. US DEPT VET AFFAIRS, VET AFFAIRS EDWARD HINES JR HOSP, RES SERV, HINES, IL 60141 USA. US DEPT VET AFFAIRS, VET AFFAIRS EDWARD HINES JR HOSP, EDUC SERV, HINES, IL 60141 USA. HINSDALE HOSP, HINSDALE, IL USA. RP Walker, RP (reprint author), LOYOLA UNIV, MED CTR, DEPT OTOLARYNGOL, 2160 S 1ST AVE, MAYWOOD, IL 60153 USA. NR 40 TC 3 Z9 3 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0023-852X EI 1531-4995 J9 LARYNGOSCOPE JI Laryngoscope PD JUL PY 1997 VL 107 IS 7 BP 903 EP 909 DI 10.1097/00005537-199707000-00013 PG 7 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA XJ298 UT WOS:A1997XJ29800013 ER PT J AU Bosch, I Crankshaw, CL PiwnicaWorms, D Croop, JM AF Bosch, I Crankshaw, CL PiwnicaWorms, D Croop, JM TI Characterization of functional assays of multidrug resistance P-glycoprotein transport activity SO LEUKEMIA LA English DT Editorial Material DE multidrug resistance; MDR; P-glycoprotein ID MYELOMA CELL-LINE; CANCER AB P-glycoprotein-mediated multidrug resistance has emerged as one of the most attractive targets to improve anticancer therapy. The P-glycoprotein functions as an energy-dependent, membrane transport pump capable of decreasing the intracellular concentration of a broad range of chemotherapeutic agents. Pharmaceuticals which inhibit P-glycoprotein transport activity are currently being evaluated in clinical trials. Characterization of P-glycoprotein functional activity is critical in determining if these multidrug resistance reversal agents improve therapeutic responses of tumors expressing P-glycoprotein. In this report, we directly compare and characterize assays using rhodamine 123, dimethyloxadicarbocyanine iodide (DIOC2), [H-3]daunorubicin and hexakis(2-methoxyisobutyl isonitrile)technetium(I) ([Tc-99m]Sestamibi) as P-glycoprotein transport probes to quantitate functional activity. The accumulation of certain substrates is concentration dependent and the parameters which determine probe accumulation are impacted by the level of P-glycoprotein expression. In addition, higher concentrations of reversal agents are required to inhibit multidrug resistance in cell lines expressing higher levels of P-glycoprotein. Furthermore, the concentration of reversal agents required to inhibit completely P-glycoprotein transport activity is higher than generally recognized. Thus, the level of P-glycoprotein expression may confound intersample comparisons unless sensitive probes are used in combination with saturating concentrations of potent reversal agents. These results highlight the importance of carefully characterizing assay systems under uniform conditions to quantitate P-glycoprotein function. C1 HARVARD UNIV,CHILDRENS HOSP,SCH MED,DANA FARBER CANC INST,DIV PEDIAT HEMATOL ONCOL,BOSTON,MA 02115. WASHINGTON UNIV,SCH MED,EDWARD MALLINCKRODT INST RADIOL,LAB MOL RADIOPHARMACOL,ST LOUIS,MO 63110. WASHINGTON UNIV,SCH MED,DEPT MOL BIOL & PHARMACOL,ST LOUIS,MO 63110. NR 20 TC 32 Z9 32 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0887-6924 J9 LEUKEMIA JI Leukemia PD JUL PY 1997 VL 11 IS 7 BP 1131 EP 1137 DI 10.1038/sj.leu.2400695 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA XK278 UT WOS:A1997XK27800035 PM 9205002 ER PT J AU Klingenspor, M Bodnar, J Xia, YR Welch, C Lusis, AJ Reue, K AF Klingenspor, M Bodnar, J Xia, YR Welch, C Lusis, AJ Reue, K TI Localization of profilin-1 (Pfn1) and a related sequence (Pfn1-rs) to mouse Chromosomes 11 and 15 respectively SO MAMMALIAN GENOME LA English DT Article ID CDNA C1 W LOS ANGELES VET AFFAIRS MED CTR,LIPID RES LAB,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,INST MOL BIOL,LOS ANGELES,CA 90095. UNIV CALIF LOS ANGELES,DEPT PATHOL,LOS ANGELES,CA 90095. UNIV CALIF LOS ANGELES,DEPT MICROBIOL & MOL GENET,LOS ANGELES,CA 90095. UNIV CALIF LOS ANGELES,DEPT MED,LOS ANGELES,CA 90095. RI Klingenspor, Martin/D-6930-2011; OI Klingenspor, Martin/0000-0002-4502-6664 FU NHLBI NIH HHS [HL28481] NR 10 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD JUL PY 1997 VL 8 IS 7 BP 539 EP 540 DI 10.1007/s003359900496 PG 2 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA XG180 UT WOS:A1997XG18000021 PM 9196007 ER PT J AU Dobens, LL Hsu, T Twombly, V Gelbart, WM Raftery, LA Kafatos, FC AF Dobens, LL Hsu, T Twombly, V Gelbart, WM Raftery, LA Kafatos, FC TI The Drosophila bunched gene is a homologue of the growth factor stimulated mammalian TSC-22 sequence and is required during oogenesis SO MECHANISMS OF DEVELOPMENT LA English DT Article DE TGF-alpha; oogenesis; Drosophila ID MEDIATED ENHANCER DETECTION; PROTEIN-TYROSINE KINASE; LEUCINE-ZIPPER MOTIF; DNA-BINDING; DORSOVENTRAL POLARITY; PATTERN-FORMATION; ADULT DROSOPHILA; EGF RECEPTOR; GERM-LINE; ENCODES AB A Drosophila melanogaster sequence homologous to the mammalian growth factor-stimulated TSC-22 gene was isolated in an enhancer trap screen for genes expressed in anterodorsal follicle cells during oogenesis. This sequence includes a 225 aa residue open reading frame that encompasses a leucine zipper motif immediately preceded by a highly conserved region (TSC box), similarly located but distinct from the basic domain of bZIP proteins. The gene encoding this sequence, bunched (bun), has been independently isolated and characterized with respect to its role in peripheral nervous system development and eye development (Treisman, J.E., Lai, Z.-C, and Rubin, G.M. (1995) Shortsighted acts in the decapentaplegic pathway in the Drosophila eye development and has homology to a mouse TGF-beta-responsive gene. Development 121, 2835-2845). In agreement with the expression of the enhancer detector insertion, in situ hybridization reveals that bun transcripts localize to the anterior dorsal follicle cells at stages 10-12 of oogenesis. Changes in bun enhancer trap expression in genetic backgrounds that disrupt the grk/Egfr signaling pathway suggest that bun is regulated by growth factor patterning of dorsal anterior follicle cell fates. Clonal analysis shows that bun is required for the proper elaboration of dorsal cell fates leading to the formation of the dorsal appendages. (C) 1997 Elsevier Science Ireland Ltd. C1 MASSACHUSETTS GEN HOSP,CUTANEOUS BIOL RES CTR,DEPT DERMATOL,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,MGH E,CHARLESTOWN,MA 02129. MED UNIV S CAROLINA,CTR MOL & STRUCT BIOL,CHARLESTON,SC 29425. EUROPEAN MOL BIOL LAB,D-69117 HEIDELBERG,GERMANY. RP Dobens, LL (reprint author), HARVARD UNIV,DEPT CELLULAR & MOL BIOL,16 DIVIN AVE,CAMBRIDGE,MA 02138, USA. RI Raftery, Laurel/H-1406-2012 OI Raftery, Laurel/0000-0003-4797-4163 NR 62 TC 49 Z9 52 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 J9 MECH DEVELOP JI Mech. Dev. PD JUL PY 1997 VL 65 IS 1-2 BP 197 EP 208 DI 10.1016/S0925-4773(97)00080-4 PG 12 WC Developmental Biology SC Developmental Biology GA XM198 UT WOS:A1997XM19800016 PM 9256356 ER PT J AU Rosenzweig, KE Arceci, RJ Tarbell, NJ AF Rosenzweig, KE Arceci, RJ Tarbell, NJ TI Diabetes insipidus secondary to Langerhans' cell histiocytosis: Is radiation therapy indicated? SO MEDICAL AND PEDIATRIC ONCOLOGY LA English DT Article DE diabetes insipidus; Langerhans' cell histiocytosis; histiocytosis X; radiation therapy; radiotherapy; pediatric oncology ID PITUITARY-STALK; CHILDREN; MR AB Langerhans' cell histiocytosis (LCH) is a proliferative disease of Langerhans' cells that has multiple clinical manifestations including diabetes insipidus (DI). This study reviews the effectiveness of hypothalamic-pituitary radiation therapy (HPRT) as a treatment of LCH-induced DI in the modern era. A retrospective review was done of 116 pediatric patients with LCH seen from 1975 to 1992. Seventeen of the 116 patients (15%) were diagnosed with complete or partial diabetes insipidus. Diagnosis was made either by water deprivation test or on clinical grounds. Fourteen patients received hy hypothalamic-pituitary irradiation as treatment for Di. The median interval from the onset of DI symptoms (polyuria and polydipsia) to treatment was 30 days. The median interval from the onset of diagnosis to treatment was 4 days. With a mean follow-up of 7.3 years (range, 2.4-14.3), only two patients had a complete response to therapy, as defined as no need for antidiuretic hormone (ADH) replacement therapy. No patient had a partial response, defined as a decrease in the dose of ADH replacement. Of the two responders, neither had a complete ADH deficiency, suggesting ''early'' disease. In addition, both received RT within 3 days. We feel that the standard treatment of RT to all patients with LCH-induced DI is no longer justified. Our series has shown no benefit in treating patients with a long history of DI. Rather, an improved rationale would be rapid initiation of hypothalamic-pituitary irradiation in patients with new symptoms of D1 and an abnormal water deprivation test. (C) 1997 Wiley-Liss, Inc. C1 CHILDRENS HOSP,DEPT RADIAT ONCOL,JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NR 19 TC 40 Z9 40 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 0098-1532 J9 MED PEDIATR ONCOL JI Med. Pediatr. Oncol. PD JUL PY 1997 VL 29 IS 1 BP 36 EP 40 DI 10.1002/(SICI)1096-911X(199707)29:1<36::AID-MPO7>3.0.CO;2-T PG 5 WC Oncology; Pediatrics SC Oncology; Pediatrics GA WX014 UT WOS:A1997WX01400007 PM 9142204 ER PT J AU Gastfriend, DR McLellan, AT AF Gastfriend, DR McLellan, AT TI Treatment matching - Theoretic basis and practical implications SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Review ID EMPIRICALLY DERIVED TYPOLOGY; AMBULATORY COCAINE ABUSERS; SUBSTANCE USE DISORDERS; ALCOHOL-CONSUMPTION; DRUG-USE; ANTISOCIAL PERSONALITY; GENDER DIFFERENCES; OPIATE DEPENDENCE; NATURAL-HISTORY; FAMILY HISTORY AB Substance abuse treatments are effective, however, cost containment is pressing providers to demonstrate selective efficacy, i.e. valid treatment matching. Studies exist to inform decisionmakers about how to best match patients to various treatments, either in terms of the theoretic modalities of treatment (e.g., dynamic psychotherapy or cognitive-behavioral therapy) or the settings in which care is delivered (e.g., inpatient versus outpatient). Data from comparative treatment studies indicate numerous patient characteristics that may be matched selectively to specific treatments. Complex matching algorithms with at least face validity are being adopted throughout the United States. Although technically difficult, treatment matching research in addictions has become sophisticated and ultimately promises a solid empirical foundation for clinical decision making. C1 HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, ADDICT SERV, BOSTON, MA 02115 USA. SPAULDING REHABIL HOSP, ADDICT REHABIL PROGRAM, BOSTON, MA USA. UNIV PENN, SCH MED, CTR STUDY ADDICT, PHILADELPHIA, PA 19104 USA. FU NIDA NIH HHS [DA08781] NR 136 TC 35 Z9 35 U1 9 U2 11 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0025-7125 J9 MED CLIN N AM JI Med. Clin. N. Am. PD JUL PY 1997 VL 81 IS 4 BP 945 EP + DI 10.1016/S0025-7125(05)70557-5 PG 0 WC Medicine, General & Internal SC General & Internal Medicine GA XJ841 UT WOS:A1997XJ84100008 PM 9222262 ER PT J AU Wong, DH Corbett, AH Kent, HM Stewart, M Silver, PA AF Wong, DH Corbett, AH Kent, HM Stewart, M Silver, PA TI Interaction between the small GTPase Ran/Gsp1p and Ntf2p is required for nuclear transport SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID SACCHAROMYCES-CEREVISIAE; PROTEIN IMPORT; BINDING-PROTEIN; MESSENGER-RNA; ACTIVATING PROTEIN; CYTOSOLIC FACTORS; GENE-PRODUCT; HNRNP A1; YEAST; IDENTIFICATION AB Bidirectional movement of proteins and RNAs across the nuclear envelope requires Ran, a Ras-like GTPase, A genetic screen of the yeast Saccharomyces cerevisiae was performed to isolate conditional alleles of GSP1, a gene that encodes a homolog of Ran, Two temperature-sensitive alleles, gsp1-1 and gsp1-2, were isolated. The mutations in these two alleles map to regions that are structurally conserved between different members of the Ras family, Each mutant strain exhibits various nuclear transport defects, Both biochemical and genetic experiments indicate a decreased interaction between Ntf2p, a factor which is required for protein import, and the mutant GSP1 gene products, Overexpression of NTF2 can suppress the temperature sensitive phenotype of gsp1-1 and gsp1-2 and partially rescue nuclear transport defects. However, overexpression of a mutant allele of NTF2 with decreased binding to Gsp1p cannot rescue the temperature sensitivity of gsp1-1 and gsp1-2. Taken together, these data demonstrate that the interaction between Gsp1p and Ntf2p is critical for nuclear transport. C1 DANA FARBER CANC INST, DIV CELLULAR & MOL BIOL, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DEPT BIOL CHEM & MOL PHARMACOL, BOSTON, MA 02115 USA. MRC, MOL BIOL LAB, CAMBRIDGE CB2 2QH, ENGLAND. FU Wellcome Trust NR 81 TC 88 Z9 89 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUL PY 1997 VL 17 IS 7 BP 3755 EP 3767 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XF220 UT WOS:A1997XF22000028 PM 9199309 ER PT J AU Aktas, H Cai, H Cooper, GM AF Aktas, H Cai, H Cooper, GM TI Ras links growth factor signaling to the cell cycle machinery via regulation of cyclin D1 and the Cdk inhibitor p27(KIP1) SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID DEPENDENT KINASE INHIBITOR; PROTEIN-KINASE; G1 PHASE; POTENTIAL MEDIATOR; MAMMALIAN-CELLS; FACTOR-BETA; 3T3 CELLS; TGF-BETA; G(1); ARREST AB Activation of growth factor receptors by ligand binding initiates a cascade of events leading to cell growth and division. Progression through the fell cycle is controlled by cyclin-dependent protein kinases (Cdks), but the mechanisms that link growth factor signaling to the cell cycle machinery have not been established, We report here that Ras proteins play a key role in integrating mitogenic signals with cell cycle progression through G(I). Ras is required for cell cycle progression and activation of both Cdk2 and Cdk4 until similar to 2 h before the G(I)/S transition, corresponding to the restriction point, Analysis of Cdk-cyclin complexes indicates that Res signaling is required both for induction of cyclin D1 and for downregulation of the Cdk inhibitor p27(KIP1). Constitutive expression of cyclin D1 circumvents the requirement for Bas signaling in cell proliferation, indicating that regulation of cyclin D1 is a critical target of the Res signaling cascade. C1 DANA FARBER CANC INST,DIV MOL GENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. FU NCI NIH HHS [R01 CA18689] NR 52 TC 326 Z9 333 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUL PY 1997 VL 17 IS 7 BP 3850 EP 3857 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XF220 UT WOS:A1997XF22000038 PM 9199319 ER PT J AU Dynlacht, BD Moberg, K Lees, JA Harlow, E Zhu, L AF Dynlacht, BD Moberg, K Lees, JA Harlow, E Zhu, L TI Specific regulation of E2F family members by cyclin-dependent kinases SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TRANSCRIPTION FACTOR E2F; DNA-BINDING ACTIVITY; S-PHASE ENTRY; RETINOBLASTOMA PROTEIN; CELL-CYCLE; FIBROBLASTS LEADS; IN-VIVO; P107; EXPRESSION; APOPTOSIS AB The transcription factor E2F-1 interacts stably with cyclin A via a small domain near its amino terminus and is negatively regulated by the cyclin A-dependent kinases, Thus, the activities of E2F, a family of transcription factors involved in cell proliferation, are regulated by at least two types of cell growth regulators: the retinoblastoma protein family and the cyclin-dependent kinase family. To investigate further the regulation of E2F by cyclin-dependent kinases, we have extended our studies to include additional cyclins and E2F family members, Using purified components in an in vitro system, we show that the E2F-1-DP-1 heterodimer, the functionally active form of the E2F activity, is not a substrate for the active cyclin D-dependent kinases but is efficiently phosphorylated by the cyclin B-dependent kinases, which do not form stable complexes with the E2F-1-DP-1 heterodimer. Phosphorylation of the E2F-1-DP-1 heterodimer by cyclin B-dependent kinases, however, did not result in down-regulation of its DNA-binding activity, as is readily seen after phosphorylation by cyclin A-dependent kinases, suggesting that phosphorylation per se is not sufficient to regulate E2F DNA-binding activity, Furthermore, heterodimers containing E2F-4, a family member lacking the cyclin A binding domain found in E2F-1, are not efficiently phosphorylated or functionally down-regulated by cyclin A-dependent kinases, However, addition of the E2F-1 cyclin A binding domain to E2F-1 conferred cyclin A-dependent kinase-mediated down-regulation of the E2F-4-DP-1 heterodimer. Thus, both enzymatic phosphorylation and stable physical interaction are necessary for the specific regulation of E2F family members by cyclin-dependent kinases. C1 MIT,DEPT BIOL,CTR CANC RES,CAMBRIDGE,MA 02139. MASSACHUSETTS GEN HOSP,CTR CANC,ONCOL MOL LAB,CHARLESTOWN,MA 02129. RP Dynlacht, BD (reprint author), HARVARD UNIV,DEPT MOL & CELLULAR BIOL,16 DIVIN AVE,CAMBRIDGE,MA 02138, USA. NR 54 TC 86 Z9 89 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUL PY 1997 VL 17 IS 7 BP 3867 EP 3875 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XF220 UT WOS:A1997XF22000040 PM 9199321 ER PT J AU Peshavaria, M Henderson, E Sharma, A Wright, CVE Stein, R AF Peshavaria, M Henderson, E Sharma, A Wright, CVE Stein, R TI Functional characterization of the transactivation properties of the PDX-1 homeodomain protein SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID INSULIN GENE-TRANSCRIPTION; LOOP-HELIX PROTEINS; DNA-BINDING; BETA-CELLS; MAMMALIAN-CELLS; ISLET HORMONES; II GENE; EXPRESSION; ENHANCER; PANCREAS AB Pancreas formation is prevented in mice carrying a null mutation in the PDX-1 homeoprotein, demonstrating a key role for this factor in development, PDX-1 can also bind to and activate transcription from cis-acting regulatory sequences in the insulin and somatostatin genes, which are expressed in pancreatic islet beta and delta cells, respectively, In this study, we compared the functional properties of PDX-1 with those of the closely related Xenopus homeoprotein XIHbox8. Analysis of chimeras between PDX-1, XIHbox8, and the DNA-binding domain of the Saccharomyces cerevisiae transcription factor GAL4 revealed that their transactivation domain was contained within the N-terminal region (amino acids 1 to 79), Detailed mutagenesis of this region indicated that transactivation is mediated by three highly conserved sequences, spanning amino acids 13 to 22 (subdomain A), 32 to 38 (subdomain B), and 60 to 73 (subdomain C), These sequences were also required by PDX-1 to synergistically activate insulin enhancer-mediated transcription with another key insulin gene activator, the E2A-encoded basic helix-loop-helix E2-5 and E47 proteins, These results indicated that N-terminal sequences conserved between the mammalian PDX-1 and Xenopus XIHbox8 proteins are important in transcriptional activation, Stable expression of the PDX-1 Delta ABC mutant in the insulin- and PDX-1-expressing beta TC3 cell line resulted in a threefold reduction in the rate of endogenous insulin gene transcription, Strikingly, the level of the endogenous PDX-1 protein was reduced to very low levels in these cells, These results suggest that PDX-1 is not absolutely essential for insulin gene expression in beta TC3 cells, We discuss the possible significance of these findings for insulin gene transcription in islet beta cells. C1 VANDERBILT UNIV,MED CTR,DEPT PHYSIOL & MOL BIOPHYS,NASHVILLE,TN 37232. VANDERBILT UNIV,MED CTR,DEPT CELL BIOL,NASHVILLE,TN 37232. JOSLIN DIABET CTR,BOSTON,MA 02215. FU NICHD NIH HHS [R01 HD 28062]; NIDDK NIH HHS [DK42502, R01 DK50203] NR 67 TC 75 Z9 81 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUL PY 1997 VL 17 IS 7 BP 3987 EP 3996 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XF220 UT WOS:A1997XF22000052 PM 9199333 ER PT J AU Shearman, LP Weaver, DR AF Shearman, LP Weaver, DR TI Haloperidol regulates neurotensin gene expression in striatum of c-fos-deficient mice SO MOLECULAR BRAIN RESEARCH LA English DT Article DE c-fos; neurotensin; haloperidol; immediate-early gene; striatum; knockout mouse; gene expression regulation ID N MESSENGER-RNA; ELEMENT-BINDING PROTEIN; DOPAMINE RECEPTOR GENE; AMP RESPONSE ELEMENT; NEUROMEDIN-N; RAT STRIATUM; NUCLEUS-ACCUMBENS; MUTANT MICE; STRIATOPALLIDAL NEURONS; NULL MUTATION AB The immediate-early gene c-fos has been proposed to play a role in induction of neurotensin/neuromedin N (NT/N) gene expression in the striatum following acute haloperidol (HAL) treatment. We utilized mice with targeted disruption of the c-fos gene to directly test this hypothesis. A robust increase in NT/N gene expression was observed in the dorsolateral striatum (DLSt) in both wild-type (WT) and c-fos-deficient mice 4-6 h after a single injection of HAL (1 or 4 mg/kg) indicating that products of the c-fos gene are not absolutely required for induction of NT/N mRNA. The basal expression of preprotachykinin, preproenkephalin and preprocholecystokinin mRNAs did not differ between WT and c-fos knockout mice. HAL treatment first increased striatal NT/N mRNA on postnatal day (PD) 10. HAL-induced NT/N mRNA levels were significantly lower in c-fos knockout mice than in WT mice on PD 10 and 15. These findings indicate that reliance on c-fos may be greater earlier in development and that redundant molecular pathways can lead ro induction of NT/N mRNA in mouse striatum. (C) 1997 Elsevier Science B.V. C1 MASSACHUSETTS GEN HOSP,DEPT CHRONOBIOL,LAB DEV CHRONOBIOL,SERV PEDIAT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. FU NICHD NIH HHS [HD29470] NR 55 TC 6 Z9 6 U1 0 U2 1 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 JUL PY 1997 VL 47 IS 1-2 BP 275 EP 285 DI 10.1016/S0169-328X(97)00058-2 PG 11 WC Neurosciences SC Neurosciences & Neurology GA XH214 UT WOS:A1997XH21400031 PM 9221926 ER PT J AU Brent, R AF Brent, R TI Looms to weave genomic nets SO NATURE GENETICS LA English DT Editorial Material C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02114. RP Brent, R (reprint author), HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,DEPT MOL BIOL,50 BLOSSOM ST,BOSTON,MA 02114, USA. NR 7 TC 5 Z9 5 U1 0 U2 0 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JUL PY 1997 VL 16 IS 3 BP 216 EP 217 DI 10.1038/ng0797-216 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA XG609 UT WOS:A1997XG60900006 PM 9207780 ER PT J AU Bamshad, M Lin, RC Law, DJ Watkins, WS Krakowiak, PA Moore, ME Franceschini, P Lala, R Holmes, LB Gebuhr, TC Bruneau, BG Schinzel, A Seidman, JG Seidman, CE Jorde, LB AF Bamshad, M Lin, RC Law, DJ Watkins, WS Krakowiak, PA Moore, ME Franceschini, P Lala, R Holmes, LB Gebuhr, TC Bruneau, BG Schinzel, A Seidman, JG Seidman, CE Jorde, LB TI Mutations in human TBX3 alter limb, apocrine and genital development in ulnar-mammary syndrome SO NATURE GENETICS LA English DT Article ID CONSERVED PROTEIN MOTIF; MOUSE BRACHYURY; EEC-SYNDROME; GENE FAMILY; HOMOLOG; DROSOPHILA; EXPRESSION; CLONING; HAND C1 HOWARD HUGHES MED INST,DEPT GENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. UNIV MICHIGAN,DEPT HUMAN GENET,ANN ARBOR,MI 48109. UNIV UTAH,HLTH SCI CTR,DEPT HUMAN GENET,SALT LAKE CITY,UT 84112. UNIV TURIN,IST DISCIPLINE PEDIAT,SERV GENET CLIN,TURIN,ITALY. OSPED INFANTILE R MARGHERETA,DIV ENDOCRINOL PEDIAT,TURIN,ITALY. MASSACHUSETTS GEN HOSP,GENET & TERATOL UNIT,BOSTON,MA 02114. UNIV ZURICH,INST MED GENET,CH-8001 ZURICH,SWITZERLAND. BRIGHAM & WOMENS HOSP,DIV CARDIOVASC,BOSTON,MA 02115. RP Bamshad, M (reprint author), UNIV UTAH,HLTH SCI CTR,DEPT PEDIAT,SALT LAKE CITY,UT 84112, USA. OI Bruneau, Benoit/0000-0002-0804-7597 FU NHGRI NIH HHS [5-P30-HG00199, HG00209]; PHS HHS [M01-00064] NR 40 TC 360 Z9 370 U1 1 U2 5 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 JUL PY 1997 VL 16 IS 3 BP 311 EP 315 DI 10.1038/ng0797-311 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA XG609 UT WOS:A1997XG60900031 PM 9207801 ER PT J AU Sykes, M Szot, GL Swenson, KA Pearson, DA AF Sykes, M Szot, GL Swenson, KA Pearson, DA TI Induction of high levels of allogeneic hematopoietic reconstitution and donor-specific tolerance without myelosuppressive conditioning SO NATURE MEDICINE LA English DT Article ID MONOCLONAL-ANTIBODIES; T-CELLS; MARROW TRANSPLANTATION; CLONAL DELETION; HOST DISEASE; ENGRAFTMENT; MICE; ANTIGENS; EXPRESSION; LEUKEMIA AB Donor-specific tolerance induced by bone marrow transplantation (BMT) would allow organ allografting without chronic immunosuppressive therapy. However, the toxicity(1) of conditioning regimens used to achieve marrow engraftment has precluded the clinical use of BMT for tolerance induction. We have developed a BMT strategy that achieves alloengraftment without toxic or myelosuppressive host conditioning. B6 mice received depleting anti-CD4 and anti-CD8 monoclonal antibodies, local thymic irradiation, and a high-dose (174 x 10(6)) of major histocompatibility (MHC)-mismatched B10.A bone marrow cells (BMCs) divided over days 0 through 4. High levels of donor cells were observed among white blood cells (WBCs) of all lineages. Permanent, multilineage mixed chimerism; donor-specific skin-graft tolerance; and in vitro tolerance were observed in most animals. Large numbers of donor class IIhigh cells were detected in thymuses of long-term chimeras, and their presence was associated with intrathymic deletion of donor-reactive host thymocytes. The treatment was not associated with significant myelosuppression, toxicity, or graft-versus-host disease (GVHD). Thus, high levels of allogeneic stem-cell engraftment can be achieved without myelosuppressive host conditioning. As stem-cell mobilization(2) and in vitro culture techniques' have increased the feasibility of administering high doses of hematopoietic cells to humans, this approach brings hematopoietic cell transplantation closer to clinical use for the induction of central deletional T-cell tolerance. RP Sykes, M (reprint author), HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,TRANSPLANTAT BIOL RES CTR,SURG SERV,MGH E,BOSTON,MA 02129, USA. FU NHLBI NIH HHS [R01-HL-49915, R01-HL-18646] NR 30 TC 251 Z9 254 U1 0 U2 2 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 JUL PY 1997 VL 3 IS 7 BP 783 EP 787 DI 10.1038/nm0797-783 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA XG767 UT WOS:A1997XG76700041 PM 9212108 ER PT J AU Hyman, BT GomezIsla, T AF Hyman, BT GomezIsla, T TI The natural history of Alzheimer neurofibrillary tangles and amyloid deposits SO NEUROBIOLOGY OF AGING LA English DT Editorial Material ID DISEASE RP Hyman, BT (reprint author), MASSACHUSETTS GEN HOSP,NEUROL SERV,FRUIT ST,BOSTON,MA 02114, USA. NR 8 TC 13 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL-AUG PY 1997 VL 18 IS 4 BP 386 EP 387 DI 10.1016/S0197-4580(97)00054-7 PG 2 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA XZ921 UT WOS:A1997XZ92100009 PM 9330968 ER PT J AU Ball, M Braak, H Coleman, P Dickson, D Duyckaerts, C Gambetti, P Hansen, L Hyman, B Jellinger, K Markesbery, W Perl, D Powers, J Price, J Trojanowski, JQ Wisniewski, H Phelps, C Khachaturian, Z AF Ball, M Braak, H Coleman, P Dickson, D Duyckaerts, C Gambetti, P Hansen, L Hyman, B Jellinger, K Markesbery, W Perl, D Powers, J Price, J Trojanowski, JQ Wisniewski, H Phelps, C Khachaturian, Z TI Consensus recommendations for the postmortem diagnosis of Alzheimer's disease SO NEUROBIOLOGY OF AGING LA English DT Article DE plaques; tangles; amyloid; A beta; Tau; neurodegenerative disease AB This report summarizes the consensus recommendations of a panel of neuropathologists from the United States and Europe to improve the postmortem diagnostic criteria for Alzheimer's disease. The recommendations followed from a two-day workshop sponsored by the National Institute on Aging (NIA) and the Ronald and Nancy Reagan Institute of the Alzheimer's Association to reassess the original NIA criteria for the postmortem diagnosis of Alzheimer's disease published in 1985 (2). The consensus recommendations for improving the neuropathological criteria for the postmortem diagnosis of Alzheimer's disease are reported here, and the ''position papers'' by members of the Working Group that accompany this report elaborate on the research findings and concepts upon which these recommendations were based. Further, commentaries by other experts in the field also are included here to provide additional perspectives on these recommendations. Finally, it is anticipated that future meetings of the Working Group will reassess these recommendations and the implementation of postmortem diagnostic criteria for Alzheimer's disease. (C) 1997 Elsevier Science Inc. C1 OREGON HLTH SCI UNIV,PORTLAND,OR 97201. UNIV FRANKFURT,D-6000 FRANKFURT,GERMANY. UNIV ROCHESTER,MED CTR,ROCHESTER,NY 14642. ALBERT EINSTEIN COLL MED,BRONX,NY 10467. HOP LA PITIE SALPETRIERE,PARIS,FRANCE. UNIV HOSP CLEVELAND,CLEVELAND,OH 44106. UNIV CALIF SAN DIEGO,LA JOLLA,CA 92093. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. LUDWIG BOLTZMANN INST,VIENNA,AUSTRIA. UNIV KENTUCKY,LEXINGTON,KY 40506. MT SINAI SCH MED,NEW YORK,NY. WASHINGTON UNIV,SCH MED,ST LOUIS,MO 63130. INST BASIC RES DEV DISABIL,STATEN ISL,NY. UNIV PENN,SCH MED,HUP,DEPT PATHOL & LAB MED,WORKING GRP CHAIR,PHILADELPHIA,PA 19104. NR 5 TC 46 Z9 46 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL-AUG PY 1997 VL 18 IS 4 SU 1 BP S1 EP S2 PG 2 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA YA778 UT WOS:A1997YA77800001 ER PT J AU Hyman, BT AF Hyman, BT TI The neuropathological diagnosis of Alzheimer's disease: Clinical-pathological studies SO NEUROBIOLOGY OF AGING LA English DT Article; Proceedings Paper CT Working Group Meeting on the Consensus Recommendations for the Postmortem Diagnosis of Alzheimers Disease CY NOV 13-14, 1996 CL NIH, BETHESDA, MD SP NIA, Ronald & Nancy Reagan Res Inst Alzheimers Assoc HO NIH DE Alzheimer's disease; clinical-pathological correlations; neurofibrillary tangles; senile plaques ID APOLIPOPROTEIN-E EPSILON-4; NEUROFIBRILLARY TANGLES; SENILE PLAQUES; HIPPOCAMPAL-FORMATION; DOWNS-SYNDROME; CEREBRAL-CORTEX; E GENOTYPE; PATTERN; DEGENERATION; INDIVIDUALS AB The neuropathological diagnosis of Alzheimer's disease currently relies on quantitative or semiquantitative criteria of senile or neuritic plaques that are adjusted for age and for the presence absence of a clinical history of dementia. Based on clinical-pathological correlation studies, I will argue that neuropathological assessment should stand independently of clinical history and instead should describe brain lesions in the context of the topography and natural history of the disease. Only probabalistic estimates about the presence or absence of dementia can be made from a neuropathological examination, especially in the setting of Alzheimer disease lesions plus other pathological alterations such as Lewy bodies or infarcts. Moreover, I will argue that any neurofibrillary tangles or smile plaques are inherently pathological entities: even if clinically silent and so ''incidental'' neuropathological findings. Because the intensity and location of neurofibrillary tangles, rather than senile plaques, appears to correlate most closely with clinical symptoms, I suggest using a staging system that highlights this information rather than using absolute numerical cut-offs for diagnostic purposes. (C) 1997 Elsevier Science Inc. RP Hyman, BT (reprint author), MASSACHUSETTS GEN HOSP, DEPT NEUROL, 149 13TH ST CNY 6405, CHARLESTOWN, MA 02129 USA. FU NIA NIH HHS [P50AG05134, AG08487] NR 40 TC 50 Z9 53 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL-AUG PY 1997 VL 18 IS 4 SU 1 BP S27 EP S32 DI 10.1016/S0197-4580(97)00066-3 PG 6 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA YA778 UT WOS:A1997YA77800005 PM 9330982 ER PT J AU Albert, SM Sane, M Marder, K Jacobs, DM Brandt, J Albert, M Stern, Y AF Albert, SM Sane, M Marder, K Jacobs, DM Brandt, J Albert, M Stern, Y TI Participation in clinical trials and long-term outcomes in Alzheimer's disease SO NEUROLOGY LA English DT Article; Proceedings Paper CT 48th Annual Meeting of the American-Academy-of-Neurology CY MAR 23-30, 1996 CL SAN FRANCISCO, CA SP Amer Acad Neurol ID DEMENTIA AB The objective of this study was to determine whether participation in clinical trials affects long-term outcomes in Alzheimer's disease (AD). Participation in clinical trials for persons with dementia is often justified on the grounds that patients benefit from the medical oversight typical of trials, even when experimental agents do not demonstrate short-term benefits. This claim has not been rigorously assessed. Of 215 community-resident subjects enrolled in a prospective study of outcomes in AD, 101 participated in randomized clinical trials (RCTs) during the first 2 years of follow-up. These subjects were compared with subjects who met eligibility requirements for RCTs but did not participate (N = 57) and with subjects who were ineligible (N = 57), over a total of 3.5 years of follow-up. Survival analyses assessed risk of death, nursing home placement, and incident functional deficit end points, adjusting for baseline differences. Subjects who participated in RCTs were younger and more highly educated. Mortality, risk of hospitalization, number of medical examinations conducted by study physicians, and onset of severe functional deficit did not differ between the groups, but risk of nursing home admission was significantly lower among RCT participants compared with eligible nonparticipants and ineligible subjects (16.8% versus 36.8% and 31.6%, respectively [p = 0.01]). The difference in risk of nursing home placement may represent a long-term, drug-related benefit to patients, a selection effect (caregivers of patients who participate in RCTs differ from caregivers of patients who do not), or a positive effect on caregivers (greater contact with a medical service may be associated with better care-giving outcomes). Further research is required to assess these effects. C1 COLUMBIA UNIV,DEPT NEUROL,NEW YORK,NY 10032. JOHNS HOPKINS UNIV,DEPT PSYCHIAT & BEHAV SCI,BALTIMORE,MD. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. RP Albert, SM (reprint author), COLUMBIA UNIV,GERTRUDE H SERGIEVSKY CTR,630 W 168TH ST,P&S BOX 16,NEW YORK,NY 10032, USA. OI Brandt, Jason/0000-0001-7381-6244; Albert, Steven/0000-0001-6786-9956 FU NIA NIH HHS [AG-07232, AG-07370, AG-08702] NR 17 TC 40 Z9 40 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUL PY 1997 VL 49 IS 1 BP 38 EP 43 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA XK353 UT WOS:A1997XK35300007 PM 9222167 ER PT J AU Litvan, I Agid, Y Sastrj, N Jankovic, J Wenning, GK Goetz, CG Verny, M Brandel, JP Jellinger, K Chaudhuri, KR McKee, A Lai, EC Pearce, RKB Bartko, JJ AF Litvan, I Agid, Y Sastrj, N Jankovic, J Wenning, GK Goetz, CG Verny, M Brandel, JP Jellinger, K Chaudhuri, KR McKee, A Lai, EC Pearce, RKB Bartko, JJ TI What are the obstacles for an accurate clinical diagnosis of Pick's disease? A clinicopathologic study SO NEUROLOGY LA English DT Article; Proceedings Paper CT 5th International Conference on Alzheimers Disease and Related Disorders CY JUL 24-29, 1996 CL OSAKA, JAPAN ID PROGRESSIVE SUPRANUCLEAR PALSY; FRONTAL-LOBE DEGENERATION; NON-ALZHEIMER TYPE; CORTICOBASAL DEGENERATION; INTERRATER RELIABILITY; COGNITIVE IMPAIRMENT; PARKINSONS-DISEASE; DEMENTIA; CRITERIA; VALIDITY AB Several studies have evaluated the reliability and validity of the clinical diagnosis of Alzheimer's disease (AD) using well-defined neuropathologic criteria, but none has attempted to evaluate the diagnostic accuracy of Pick's disease. We determined the accuracy of the clinical diagnosis of Pick's by presenting 105 autopsy-confirmed cases of Pick's (n = 7) and related disorders (non-Pick's, n = 98) as clinical vignettes in randomized order to six neurologists who, were unaware of the autopsy findings. The group of raters had moderate to fair agreement for the diagnosis of Pick's as measured by the kappa statistics. The sensitivity for the diagnosis of Pick's for the first visit (mean, 53 months after onset) and last visit (mean, 78 months after onset) was low (range, 0 to 71%), but specificity was near-perfect. Median positive predictive values at both visits were 83 to 85%. False-negative misdiagnoses mainly involved AD. False-positive diagnoses were rare and occurred with corticobasal degeneration (first visit) and with dementia with Lewy bodies (last visit). Pick's was also misdiagnosed by primary neurologists. The best clinical predictors for the early diagnosis of Pick's included ''frontal'' dementia, early ''cortical'' dementia with severe frontal lobe disturbances, absence of apraxia, and absence of gait disturbance at onset. However, the first neurologic evaluation in some of the Pick's cases took place in advanced stages of the disease. Our findings suggest that this disorder is underdiagnosed in clinical practice. Although the low sensitivity for the clinical diagnosis of Pick's is disappointing, our data suggest that when clinicians suspect Pick's, their diagnosis is almost always correct. Absence of awareness of the main features of this disorder and of specificity of the frontal lobe syndrome may partially explain the low detection of Pick's disease. C1 HOP LA PITIE SALPETRIERE,INSERM,U289,PARIS,FRANCE. BAYLOR COLL MED,DEPT NEUROL,HOUSTON,TX 77030. UNIV LONDON,NEUROL INST,DEPT CLIN NEUROL,LONDON,ENGLAND. RUSH MED COLL,DEPT NEUROL,CHICAGO,IL 60612. HOP LA PITIE SALPETRIERE,RAYMOND ESCOUROLLE NEUROPATHOL LAB,INSERM,U360,PARIS,FRANCE. LUDWIG BOLTZMANN INST CLIN NEUROBIOL,VIENNA,AUSTRIA. INST PSYCHIAT,DEPT NEUROL,LONDON SE5 8AF,ENGLAND. MASSACHUSETTS GEN HOSP,DEPT NEUROPATHOL,BOSTON,MA 02114. PARKINSONS DIS SOC BRAIN BANK RES CTR,LONDON,ENGLAND. NIMH,DIV EPIDEMIOL & RES STUDIES,BETHESDA,MD 20892. RP Litvan, I (reprint author), NINCDS,NEUROEPIDEMIOL BRANCH,NIH,FED BLDG,ROOM 714,BETHESDA,MD 20892, USA. OI Litvan, Irene/0000-0002-3485-3445; Ray Chaudhuri, K/0000-0003-2815-0505 NR 65 TC 57 Z9 58 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUL PY 1997 VL 49 IS 1 BP 62 EP 69 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA XK353 UT WOS:A1997XK35300011 PM 9222171 ER PT J AU Cudkowicz, ME Warren, L Francis, JW Lloyd, KJ Friedlander, RM Borges, LF Kassem, N Munsat, TL Brown, RH AF Cudkowicz, ME Warren, L Francis, JW Lloyd, KJ Friedlander, RM Borges, LF Kassem, N Munsat, TL Brown, RH TI Intrathecal administration of recombinant human superoxide dismutase 1 in amyotrophic lateral sclerosis: A preliminary safety and pharmacokinetic study SO NEUROLOGY LA English DT Article ID MOTOR NEURON DISEASE; CEREBROSPINAL-FLUID; PARKINSONS-DISEASE; TRANSGENIC MICE; APOPTOTIC DEATH; ANIMAL-MODEL; CELLS; MUTATIONS; DELIVERY; SYSTEM AB We undertook a safety and pharmacokinetic study of intrathecal (IT) recombinant human superoxide dismutase (rhSOD1). We administered rhSOD1 as an acute bolus in three sheep and 16 human subjects with amyotrophic lateral sclerosis (ALS). Two sheep received chronic IT infusion of rhSOD1 (one at 17.7 mg per day, the second at 38.0 mg per day) for six months. Two of the 16 subjects had familial ALS and mutations in the gene for Cu/Zn SOD1. They both received IT infusion of rhSOD1 (5 to 10 mg per day) for 3 to 6 months. Intrathecal rhSOD1 administration was safe. Bolus IT administration of 0.25 mg rhSOD1 in sheep revealed a mean elimination half-life of 0.4 (SD +/- 0.06) hours, clearance of 12.2 +/- 3.2 ml per hour, and volume of distribution of 7.3 +/- 0.9 ml. After chronic IT infusion, the initial alpha-phase half-life was estimated as 1.2 hours and the extended beta-phase half-life was 15.0 hours. The mean clearance rate was 25.9 ml per hour and the steady-state volume of distribution was 920.6 ml. Bolus IT administration of 20 mu g of rhSOD1 in ALS subjects revealed a mean elimination half-life of 2.2 +/- 0.8 hours, clearance of 1.2 +/- 0.6 ml per hour, and volume of distribution of 3.5 +/- 0.4 ml, With chronic IT infusion of 5 mg per day, cerebrospinal SOD1 levels increased approximately fortyfold. We detected no benefit of this treatment in the two patients with familial ALS. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROL,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROSURG,BOSTON,MA. TUFTS UNIV,SCH MED,NEW ENGLAND MED CTR,DEPT NEUROL,BOSTON,MA 02111. BIOTECHNOL GEN INC,ISELIN,NJ. RP Cudkowicz, ME (reprint author), MASSACHUSETTS GEN HOSP,DEPT NEUROL,DAY NEUROMUSCULAR RES LAB,VBK 811,55 FRUIT ST,BOSTON,MA 02114, USA. RI Friedlander, Robert/A-2845-2016 OI Friedlander, Robert/0000-0003-4423-9219 FU NCRR NIH HHS [M01RR01066]; NIA NIH HHS [1PO1AG12992-01]; NINDS NIH HHS [1PO1NS31248-01] NR 48 TC 20 Z9 20 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUL PY 1997 VL 49 IS 1 BP 213 EP 222 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA XK353 UT WOS:A1997XK35300033 PM 9222193 ER PT J AU Liu, C Weaver, DR Jin, XW Shearman, LP Pieschl, RL Gribkoff, VK Reppert, SM AF Liu, C Weaver, DR Jin, XW Shearman, LP Pieschl, RL Gribkoff, VK Reppert, SM TI Molecular dissection of two distinct actions of melatonin on the suprachiasmatic circadian clock SO NEURON LA English DT Article ID 2-IODOMELATONIN BINDING-SITES; BIOLOGICAL CLOCK; NUCLEUS NEURONS; SYRIAN-HAMSTERS; PHASE ADVANCES; K+ CHANNEL; G-PROTEINS; JET-LAG; RAT; INVITRO AB The pineal hormone melatonin elicits two effects on the suprachiasmatic nuclei (SCN): acute neuronal inhibition and phase-shifting. Melatonin evokes its biological effects through G protein-coupled receptors. Since the Mel(1a) melatonin receptor may transduce the major neurobiological actions of melatonin in mammals, we examined whether it mediates both melatonin effects on SCN function by using mice with targeted disruption of the Mel(1a) receptor. The Mel(1a) receptor accounts for all detectable, high affinity melatonin binding in mouse brain. Functionally, this receptor is necessary for the acute inhibitory action of melatonin on the SCN. Melatonin-induced phase shifts, however, are only modestly altered in the receptor-deficient mice; pertussis toxin still blocks melatonin-induced phase shifts in Mel(1a) receptor-deficient mice. The other melatonin receptor subtype, the Mel(1b) receptor, is expressed in mouse SCN, implicating it in the phase-shifting response. The results provide a molecular basis for two distinct, mechanistically separable effects of melatonin on SCN physiology. C1 MASSACHUSETTS GEN HOSP,SERV PEDIAT,LAB DEV CHRONOBIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. BRISTOL MYERS SQUIBB CO,PHARMACEUT RES INST,CNS ELECTROPHYSIOL,WALLINGFORD,CT 06492. OI Weaver, David/0000-0001-7941-6719 FU NICHD NIH HHS [R37 HD14427]; NIDDK NIH HHS [DK42125] NR 51 TC 443 Z9 462 U1 0 U2 17 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0896-6273 J9 NEURON JI Neuron PD JUL PY 1997 VL 19 IS 1 BP 91 EP 102 DI 10.1016/S0896-6273(00)80350-5 PG 12 WC Neurosciences SC Neurosciences & Neurology GA XN394 UT WOS:A1997XN39400009 PM 9247266 ER PT J AU Elkes, DA Cardozo, DL Madison, J Kaplan, JM AF Elkes, DA Cardozo, DL Madison, J Kaplan, JM TI EGL-36 Shaw channels regulate C-elegans egg-laying muscle activity SO NEURON LA English DT Article ID NEMATODE CAENORHABDITIS-ELEGANS; ACTIVATED POTASSIUM CHANNELS; NERVOUS-SYSTEM; K+ CHANNELS; XENOPUS-OOCYTES; BETA-SUBUNIT; DROSOPHILA; MUTATIONS; SEROTONIN; BEHAVIOR AB The C. elegans egl-36 gene encodes a Shaw-type potassium channel that regulates egg-laying behavior. Gain of function [egl-36(gf)] and dominant negative [egl-36(dn)] mutations in egl-36 cause reciprocal defects in egg laying. An egl-36::gfp reporter is expressed in the egg-laying muscles and in a few other tissues. Expression of an egl-36(gf) cDNA in the egg-laying muscles causes behavioral defects similar to those observed in egl-36(gf) mutants. Gain of function EGL-36 subunits form channels that are active at more negative potentials than wild-type channels. The egl-36(gf) alleles correspond to missense mutations in an amino terminal subunit assembly domain (E138K) and in the S6 transmembrane domain (P435S), neither of which were previously implicated in the voltage dependence of channel activation. Altogether, these results suggest that EGL-36 channels regulate the excitability of the egg-laying muscles. RP Elkes, DA (reprint author), MASSACHUSETTS GEN HOSP,DEPT MOL BIOL,BOSTON,MA 02114, USA. FU NINDS NIH HHS [NS32196] NR 41 TC 24 Z9 26 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0896-6273 J9 NEURON JI Neuron PD JUL PY 1997 VL 19 IS 1 BP 165 EP 174 DI 10.1016/S0896-6273(00)80356-6 PG 10 WC Neurosciences SC Neurosciences & Neurology GA XN394 UT WOS:A1997XN39400015 PM 9247272 ER PT J AU Liu, Y Holmgren, M Jurman, ME Yellen, G AF Liu, Y Holmgren, M Jurman, ME Yellen, G TI Gated access to the pore of a voltage-dependent K+ channel SO NEURON LA English DT Article ID SHAKER POTASSIUM CHANNELS; BINDING-SITE; TETRAETHYLAMMONIUM ION; TEA BLOCKADE; RECEPTOR; MUTATIONS; INACTIVATION; REGION; CONDUCTANCE; ACTIVATION AB Voltage-activated K+ channels are integral membrane proteins that open or close a K+-selective pore in response to changes in transmembrane voltage. Although the S4 region of these channels has been implicated as the voltage sensor, little is known about how opening and closing of the pore is accomplished. We explored the gating process by introducing cysteines at various positions thought to lie in or near the pore of the Shaker K+ channel, and by testing their ability to be chemically modified. We found a series of positions in the S6 transmembrane region that react rapidly with water-soluble thiol reagents in the open state but not the closed state. An open-channel blocker can protect several of these cysteines, showing that they lie in the ion-conducting pore. At two of these sites, Cd2+ ions bind to the cysteines without affecting the energetics of gating; at a third site, Cd2+ binding holds the channel open. The results suggest that these channels open and close by the movement of an intracellular gate, distinct from the selectivity filter, that regulates access to the pore. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP Liu, Y (reprint author), HARVARD UNIV,SCH MED,DEPT NEUROBIOL,BOSTON,MA 02114, USA. OI Yellen, Gary/0000-0003-4228-7866 FU NINDS NIH HHS [R01 NS029693, NS 29693] NR 47 TC 390 Z9 396 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0896-6273 J9 NEURON JI Neuron PD JUL PY 1997 VL 19 IS 1 BP 175 EP 184 DI 10.1016/S0896-6273(00)80357-8 PG 10 WC Neurosciences SC Neurosciences & Neurology GA XN394 UT WOS:A1997XN39400016 PM 9247273 ER PT J AU Lin, FF Varney, M Sacaan, SI Jachec, C Daggett, LP Rao, S Flor, P Kuhn, R Kerner, JA Standaert, D Young, AB Velicelebi, G AF Lin, FF Varney, M Sacaan, SI Jachec, C Daggett, LP Rao, S Flor, P Kuhn, R Kerner, JA Standaert, D Young, AB Velicelebi, G TI Cloning and stable expression of the mGluR1b subtype of human metabotropic receptors and pharmacological comparison with the mGluR5a subtype SO NEUROPHARMACOLOGY LA English DT Article DE cloning; distribution; functional expression; pharmacological profiling ID AMINO-ACID RECEPTORS; CENTRAL-NERVOUS-SYSTEM; GLUTAMATE-RECEPTOR; SIGNAL-TRANSDUCTION; MOLECULAR CHARACTERIZATION; FUNCTIONAL EXPRESSION; MESSENGER-RNA; PHENYLGLYCINE DERIVATIVES; SPLICE VARIANTS; RAT-BRAIN AB We isolated and characterized a cDNA encoding the human metabotropic glutamate receptor subtype 1b (hmGluR1b). In situ hybridization studies in human brain regions revealed a higher distribution of mGluR1 mRNA in the dentate gyrus of the hippocampus, the substantia nigra pars compacta and the Purkinje cell layer of the cerebellum compared to other regions studied. We established stable expression of recombinant hmGluR1b in L(tk(-)) mouse fibroblast and Chinese hamster ovary (CHO-dhfr(-)) cells. In both expression systems, agonist activation of hmGluR1b stimulated inositol phosphate (InsP) formation and elevation of the cytosolic free calcium ([Ca2+](i)), and both responses were blocked by (S)-MCPG. The rank order of potency for agonists was quisqualate > glutamate, (IS,3R)-ACPD in both expression systems. Comparison of the agonist profiles of hmGluR1b and hmGluR5a, both stably expressed in L(tk(-)) cells, indicated the same rank order of potency (quisqualate > glutamate greater than or equal to (RS)-3,5-DHPG greater than or equal to (1S,3R)-ACPD), but each of the four agonists were more potent on hmGluR5a than on hmGluR1b. In antagonist studies, (S)-MCPG inhibited the agonist-induced InsP formation and elevation of [Ca2+](i) in both hmGluR1b- and hmGluR5a-expressing cells. (S)-4CPG and (S)-4C3HPG both inhibited agonist responses only in hmGluR1b-expressing cells. However, in hmGluR5a-expressing cells the antagonist activity of(S)-4CPG and (S)-4C3HPG was dependent on the agonist used in the study, since they inhibited responses to glutamate but not to quisqualate. Stable cell lines expressing specific subtypes of human mGluRs represent valuable tools for the study of the mechanism of action of mGluRs at the molecular and cellular level and as screening targets for identification of subtype-selective agonists or antagonists. (C) 1997 Elsevier Science Ltd. C1 SIBIA NEUROSCI INC,LA JOLLA,CA 92037. NOVARTIS PHARMA INC,CNS RES,CH-4002 BASEL,SWITZERLAND. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. OI Standaert, David/0000-0003-2921-8348 NR 44 TC 44 Z9 47 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD JUL PY 1997 VL 36 IS 7 BP 917 EP 931 DI 10.1016/S0028-3908(97)00078-6 PG 15 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA XM235 UT WOS:A1997XM23500003 PM 9257936 ER PT J AU Mendez, MF Cherrier, MM Cymerman, JS AF Mendez, MF Cherrier, MM Cymerman, JS TI Hemispatial neglect on visual search tasks in Alzheimer's disease SO NEUROPSYCHIATRY NEUROPSYCHOLOGY AND BEHAVIORAL NEUROLOGY LA English DT Article DE Alzheimer's disease; neglect; attention; visuospatial ID UNILATERAL NEGLECT; DIRECTED ATTENTION; RIGHT-HEMISPHERE; LINE BISECTION; ASYMMETRIES; IMPAIRMENT; MOVEMENTS; DEMENTIA; CUES AB Abnormal visual attention may underlie certain visuospatial difficulties in patients with Alzheimer's disease (AD). These patients have hypometabolism and neuropathology in parietal cortex. Given the role of parietal function for visuospatial attention, patients with AD may have relative hemispatial neglect masked by other cognitive disturbances. Fifteen patients with mild-to-moderate AD and 15 healthy elderly controls matched for age, sex, and education were compared on four measures of neglect: the visual search of a complex picture, a letter cancellation task, the Schenkenberg line bisection test, and a computerized line bisection task. Compared with controls, the group with AD was significantly impaired overall in attending to left hemispace on both picture search (F[1,56] = 11.27, p < 0.05) and cancellation tasks (F [1,112] = 12.68, p < 0.01); however, a subgroup of patients with AD had disproportionate difficulty in attending to right hemispace. The performance of the groups did not differ on either of the line bisection tasks regardless of the hand used. In AD, hemispatial neglect on visual search tasks may relate to difficulty in disengaging attention or in visual exploration, as well as to the severity of the disease. Future investigations may implicate neglect in visually related deficits in AD, for example, the prominent difficulty with left turns on driving a car. C1 UNIV CALIF LOS ANGELES,DEPT NEUROL,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,DEPT PSYCHIAT & BIOBEHAV SCI,LOS ANGELES,CA 90024. RP Mendez, MF (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,NEUROBEHAV UNIT 691 116AF,11301 WILSHIRE BLVD,LOS ANGELES,CA 90073, USA. NR 43 TC 33 Z9 33 U1 0 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0894-878X J9 NEUROPSY NEUROPSY BE JI Neuropsychiatr. Neuropsychol. Behav. Neurol. PD JUL PY 1997 VL 10 IS 3 BP 203 EP 208 PG 6 WC Clinical Neurology; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA XU990 UT WOS:A1997XU99000007 PM 9297714 ER PT J AU Pollack, AE Turgeon, SM Fink, JS AF Pollack, AE Turgeon, SM Fink, JS TI Apomorphine priming alters the response of striatal outflow pathways to D-2 agonist stimulation in 6-hydroxydopamine-lesioned rats SO NEUROSCIENCE LA English DT Article DE Fos; striatum; quinpirole; D-2 dopamine; 6-hydroxydopamine; immediate early genes ID C-FOS EXPRESSION; RECEPTOR MESSENGER-RNA; BASAL GANGLIA FUNCTION; PARKINSONS MODEL RATS; D2 DOPAMINE AGONISTS; STRIATOPALLIDAL NEURONS; GENE-EXPRESSION; ACETYLCHOLINE-RELEASE; PHENOTYPICAL CHARACTERIZATION; STRIATONIGRAL NEURONS AB Chronic treatment with dopaminergic agonists is associated with response fluctuations to L-dihydroxyphenylalanine in Parkinson's disease and enhanced motor activity to D-1 and D-2 dopamine agonists in rats with 6-hydroxydopamine lesions of the nigrostriatal pathway. In dopamine-depleted rodents this phenomenon has been referred to as ''priming'' or reverse tolerance. The neurochemical changes that underlie ''priming'' of dopaminergic agonist responses are poorly understood. Some aspects of priming of D-1 agonist-mediated rotation in the 6-hydroxydopamine-lesioned rat have been characterized, but priming of D-2-agonist-dependent motor responses has been less thoroughly studied. In this study, examination of rotational behaviour and induction of Fos-like immunoreactivity were used to investigate changes in the striatal outflow systems in response to treatment with the D-1 agonist quinpirole in 6-hydroxydopamine-lesioned rats that had been primed with apomorphine. Administration of apomorphine (0.5 mg/kg; three injections at three to six day intervals) permitted an otherwise inactive dose of quinpirole (0.25 mg/kg) to produce robust contralateral rotation and to induce the expression of Fos in striatal neurons belonging to the striato-nigro-entopeduncular (''direct'') pathway. The increase in contralateral rotation and ipsilateral striatal Fos expression following administration of quinpirole to apomorphine-primed rats was mediated by a D-2-like receptor and did not appear to be due to a change in sensitivity of D-2 receptors. Apomorphine priming also enhanced the ability of quinpirole to induce Fos expression in the globus pallidus, a target of the striatopallidal (''indirect'') pathway. Western blot analysis confirmed that treatment with quinpirole induced the expression of c-Fos protein with no change in the expression of 35-37,000 mol. wt Fos-related antigens in apomorphine-primed rats treated with water or quinpirole. Induction of Fos expression in the striatum generally results from blockade of D-2 receptors and the striato-nigro-entopeduncular pathway preferentially expresses D-1 receptors. Thus, the quinpirole-dependent induction of striatal Fos in apomorphine-primed 5-hydroxydopamine-lesioned rats represents a qualitative alteration in striatal outflow. These studies demonstrate that pretreatment of 6-hydroxydopamine-lesioned rats with apomorphine increases the activity of the ''direct'' and ''indirect'' striatal outflow pathways in response to D-2 receptor stimulation. These changes have the net result of enhancing thalamocortical activity and likely underlie the enhanced contralateral rotation produced by quinpirole in apomorphine-primed rats. Changes in striatal outflow, particularly in the striato-nigro-entopeduncular pathway, may contribute to alterations in D-2-dependent motor responses observed after chronic dopaminergic stimulation in the dopamine-depleted striatum. (C) 1997. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROL,MOL NEUROBIOL LAB,BOSTON,MA 02114. FU NIDA NIH HHS [DA07496, T32-DA07282]; NINDS NIH HHS [NS31579] NR 77 TC 32 Z9 32 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 JUL PY 1997 VL 79 IS 1 BP 79 EP 93 DI 10.1016/S0306-4522(96)00681-1 PG 15 WC Neurosciences SC Neurosciences & Neurology GA XD400 UT WOS:A1997XD40000005 PM 9178866 ER PT J AU Low, PA Yao, JK Kishi, Y Tritschler, HJ Schmelzer, JD Zollman, PJ Nickander, KK AF Low, PA Yao, JK Kishi, Y Tritschler, HJ Schmelzer, JD Zollman, PJ Nickander, KK TI Peripheral nerve energy metabolism in experimental diabetic neuropathy SO NEUROSCIENCE RESEARCH COMMUNICATIONS LA English DT Article; Proceedings Paper CT 4th International Symposium on Diabetic Neuropathy and Neurodiab VII CY JUL 15-19, 1997 CL NOORDWIJKERHOUT, NETHERLANDS DE diabetic neuropathy; glucose uptake; energy metabolism ID GLUCOSE-TRANSPORTER PROTEINS; ISCHEMIC CONDUCTION FAILURE; BLOOD-FLOW; THIOCTIC ACID; PERINEURIAL CELLS; INSULIN-TREATMENT; SKELETAL-MUSCLE; OXYGEN DELIVERY; MESSENGER-RNA; RAT AB Peripheral nerve has low energy demands at rest and when maximally stimulated. Coupled with the relatively high energy substrates available, it is more resistant to ischemia and anoxia than brain. Diabetic peripheral nerve, by virtue of its enhanced energy stores, and chronic hypoxia, has an increased resistance to ischemic conduction failure, and subsists proportionately more than tissues such as brain on anaerobic metabolism. Since anaerobic metabolism is very inefficient, however, a reduction in energy substrates can increase the risk of fiber degeneration. Glucose uptake into peripheral neural tissues (sciatic; L5 dorsal root ganglion; superior cervical ganglion) are markedly reduced. alpha-lipoic acid dose- dependently improves glucose uptake. This increase in glucose uptake increases energy stores without a reduction in nerve myoinositol. C1 VA PITTSBURGH HLTH CARE SYST,PATHOL & LAB MED SERV 113A,PITTSBURGH,PA. ASTA MED,FRANKFURT,GERMANY. RP Low, PA (reprint author), MAYO CLIN & MAYO FDN,DEPT NEUROL,200 1ST ST SW,ROCHESTER,MN 55905, USA. NR 60 TC 16 Z9 16 U1 0 U2 3 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0893-6609 J9 NEUROSCI RES COMMUN JI Neurosci. Res. Commun. PD JUL-AUG PY 1997 VL 21 IS 1 BP 49 EP 56 PG 8 WC Neurosciences SC Neurosciences & Neurology GA XL978 UT WOS:A1997XL97800007 ER PT J AU Lin, DA Finklestein, SP AF Lin, DA Finklestein, SP TI Basic fibroblast growth factor: A treatment for stroke? SO NEUROSCIENTIST LA English DT Review DE basic fibroblast growth factor; cerebral ischemia; stroke ID FOCAL CEREBRAL-ISCHEMIA; REDUCES INFARCT SIZE; HIPPOCAMPAL-NEURONS; RAT; DAMAGE; BRAIN AB Basic fibroblast growth factor (bFGF) is a polypeptide with potent trophic effects on brain cells. In particular, bFGF promotes the survival and outgrowth of brain neurons, and protects neurons against toxic processes that are important contributors to cell death after cerebral ischemia (stroke). Recent studies in animal models have suggested two potential uses of exogenously administered bFGF for the treatment of stroke: 1) intravenous bFGF to reduce infarct size in acute stroke, and 2) intracisternal bFGF to enhance neurological recovery in chronic stroke. Human clinical trials of the first of these applications are currently in progress. C1 MASSACHUSETTS GEN HOSP, DEPT NEUROL, CNS GROWTH FACTOR RES LAB, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA USA. NR 31 TC 10 Z9 10 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1073-8584 EI 1089-4098 J9 NEUROSCIENTIST JI Neuroscientist PD JUL PY 1997 VL 3 IS 4 BP 247 EP 250 DI 10.1177/107385849700300412 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA XQ598 UT WOS:A1997XQ59800012 ER PT J AU Rizzo, JF Wyatt, J AF Rizzo, JF Wyatt, J TI Prospects for a visual prosthesis SO NEUROSCIENTIST LA English DT Review DE vision; prosthesis; retina; visual cortex; blindness; electrical stimulation ID RETINAL GANGLION-CELLS; ELECTRICAL-STIMULATION; RETINITIS-PIGMENTOSA; REPRESENTATION; CORTEX; ARRAY AB Diseases of the retina and optic nerve are common causes of irreversible blindness, Given the lack of effective treatments, several laboratories are utilizing microelectronic technology to develop either a cortical or retinal prosthesis, Each strategy offers certain advantages, but both face numerous and formidable challenges, Consequently, a clinically useful device of either type is still conceptual. The technological means to build prostheses are available, but the ultimate obstacle is the integration of the technology with the brain, This article reviews achievements of the ongoing efforts and focuses on our project to develop a retinal prosthesis. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,KECK NEURAL PROSTHESIS CTR,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,BOSTON,MA 02114. MIT,DEPT ELECT ENGN & COMP SCI,ELECT RES LAB,CAMBRIDGE,MA 02139. NR 31 TC 96 Z9 102 U1 0 U2 7 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1073-8584 J9 NEUROSCIENTIST JI Neuroscientist PD JUL PY 1997 VL 3 IS 4 BP 251 EP 262 DI 10.1177/107385849700300413 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA XQ598 UT WOS:A1997XQ59800013 ER PT J AU Brisman, JL Feldstein, NA Tarbell, NJ Cohen, D Cargan, AL Haddad, J Bruce, JN AF Brisman, JL Feldstein, NA Tarbell, NJ Cohen, D Cargan, AL Haddad, J Bruce, JN TI Eosinophilic granuloma of the clivus: Case report, follow-up of two previously reported cases, and review of the literature on cranial base eosinophilic granuloma SO NEUROSURGERY LA English DT Review DE clivus; cranial base; eosinophilic granuloma; management; review; stereotactic radiotherapy ID LANGERHANS CELL HISTIOCYTOSIS; TEMPORAL BONE; PEDIATRIC-PATIENT; PETROUS APEX; SKULL; HEAD; NECK; MANIFESTATIONS; MANAGEMENT; CHILDREN AB OBJECTIVE AND IMPORTANCE: To our knowledge, this is the first reported case of the use of stereotactic radiotherapy for an eosinophilic granuloma (EC) of the clivus. We report follow-up information on two previously reported cases and suggest a management plan for this rare lesion. CLINICAL PRESENTATION: We report the case of a 4.5-year-old boy who presented with a complete abducens palsy on the right with an associated head turn. A computed tomographic scan of his head revealed a lytic lesion on that side, and magnetic resonance imaging showed the mass to be of low intensity on T1-weighted images and of high intensity on T2-weighted images with heterogeneous enhancement. INTERVENTION: A transnasal stereotactic biopsy was performed, revealing an EG. The patient was treated with stereotactic radiotherapy, and he became symptom-free with radiographic resolution of his lesion. Reviewing the literature, we found 13 series with 87 cases of EG in the petrous portion of the temporal bone. EG in the cranial base occurring outside of the temporal bone or in the temporal bone and extending intracranially is, however, quite rare, with only nine other cases reported, two of them clival. CONCLUSION: These findings suggest a classification schema in which cranial base EG lesions be grouped with either the more common extracranial petrous temporal bone lesions or the very rare intracranial lesions. Although there are few cases in the literature, treatment results indicate that clival EC, and perhaps all intracranial cranial base EGs, be treated by a biopsy alone, followed by surgery or stereotactic radiotherapy if there is an incomplete resolution of the symptoms or if there is a recurrence. C1 COLUMBIA PRESBYTERIAN MED CTR,INST NEUROL,DEPT NEUROL & NEUROL SURG,NEW YORK,NY 10032. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,NEUROL SERV,BOSTON,MA 02115. COLUMBIA UNIV,DIV PEDIAT OTOLARYNGOL,NEW YORK,NY. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,HARVARD JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. HARVARD UNIV,CHILDRENS HOSP,SCH MED,HARVARD JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. NR 43 TC 22 Z9 22 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 JUL PY 1997 VL 41 IS 1 BP 273 EP 278 DI 10.1097/00006123-199707000-00048 PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA XH585 UT WOS:A1997XH58500133 PM 9218318 ER PT J AU Ojemann, JG Buckner, RL Corbetta, M Raichle, ME AF Ojemann, JG Buckner, RL Corbetta, M Raichle, ME TI Imaging studies of memory and attention SO NEUROSURGERY CLINICS OF NORTH AMERICA LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; WORKING-MEMORY; EPISODIC MEMORY; HUMAN BRAIN; SELECTIVE ATTENTION; FUNCTIONAL-ANATOMY; PREFRONTAL CORTEX; VERBAL MEMORY; BLOOD-FLOW; PET AB Functional brain imaging studies of memory and attention with positron emission tomography and functional magnetic resonance imaging demonstrate involvement of specific regions of the normal human brain. Possible anatomical substrates for different types of memory have been identified. Different aspects of attention mechanisms, such as modulation of early visual areas, shifts of attention, and selection of response, also appear to involve specific anatomic regions revealed by imaging. Many of these studies show activation in regions clinically considered to be ''silent'' regions. C1 WASHINGTON UNIV,SCH MED,DEPT NEUROL SURG,ST LOUIS,MO 63110. MALLINCKRODT INST RADIOL,MCDONNELL CTR HIGHER BRAIN FUNCT,DEPT RADIOL,ST LOUIS,MO. HARVARD UNIV,MASSACHUSETTS GEN HOSP,MED CTR,BOSTON,MA. RP Ojemann, JG (reprint author), WASHINGTON UNIV,SCH MED,DEPT NEUROSURG,BOX 8057,660 S EUCLID AVE,ST LOUIS,MO 63110, USA. OI Ojemann, Jeffrey/0000-0001-7580-8934 FU NINDS NIH HHS [NS 06833] NR 74 TC 14 Z9 14 U1 3 U2 5 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 1042-3680 J9 NEUROSURG CLIN N AM JI Neurosurg. Clin. N. Am. PD JUL PY 1997 VL 8 IS 3 BP 307 EP & PG 22 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA XM589 UT WOS:A1997XM58900005 PM 9188540 ER PT J AU Wittenkeller, JL Storer, B Bittner, G Schiller, JH AF Wittenkeller, JL Storer, B Bittner, G Schiller, JH TI Comparison of spontaneous and induced mutation rates in an immortalized human bronchial epithelial cell line and its tumorigenic derivative SO ONCOLOGY LA English DT Article DE transformation; mutation; fluctuation analysis; hypoxanthine phosphoribosyltransferase; bronchial epithelial cells, human ID METASTATIC VARIANTS; MUTAGENESIS; INSTABILITY; FIBROBLASTS; TUMOR AB To determine the relationship between neoplastic transformation and increased genetic instability, spontaneous and induced mutation rates were compared in a nontumorigenic, immortalized human bronchial epithelial cell line (NL20) and a tumorigenic cell line (NL20T) spontaneously derived from the NL20 line. Using the hypoxanthine phosphoribosyltransferase (HPRT) locus as a marker for determining mutation rate, fluctuation analysis was utilized to evaluate the spontaneous mutation rate. Induced mutation rates were determined for each cell line after N-methyl-N'-nitro-N-nitrosoguanidine exposure. Both the spontaneous and induced mutation rates were noted to be significantly higher in the nontumorigenic NL20 cell line. These findings suggest that increasing genetic instability, as measured by spontaneous or induced mutation rate in the HPRT locus, does not correlate with tumorigenicity in these cells. C1 UNIV WISCONSIN,CTR COMPREHENS CANC,CLIN SCI CTR K4 666,MADISON,WI 53792. WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI. NR 21 TC 10 Z9 10 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0030-2414 J9 ONCOLOGY JI Oncology PD JUL-AUG PY 1997 VL 54 IS 4 BP 335 EP 341 PG 7 WC Oncology SC Oncology GA XH064 UT WOS:A1997XH06400013 PM 9216860 ER PT J AU Haimovici, R Gragoudas, ES Gregor, Z Pesavento, RD Mieler, WF Duker, JS AF Haimovici, R Gragoudas, ES Gregor, Z Pesavento, RD Mieler, WF Duker, JS TI Choroidal metastases from renal cell carcinoma SO OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Academy-of-Ophthalmology CY OCT 30-NOV 03, 1994 CL SAN FRANCISCO, CA SP Amer Acad Ophthalmol ID ENDOTHELIAL GROWTH-FACTOR; TUMOR ANGIOGENESIS FACTOR; DIAGNOSIS; KIDNEY; ADENOCARCINOMA; CHEMOTHERAPY; EXPRESSION; LYMPHOMA; SARCOMA; BLADDER AB Background: Choroidal metastases from renal cell carcinoma are uncommon. The authors investigated the clinical characteristics of patients with renal cell carcinoma in whom choroidal metastases developed. Methods: The clinical records of five patients with histopathologically confirmed renal cell carcinoma and choroidal metastases were reviewed retrospectively. Results: In four patients, choroidal metastases were either the sole initial manifestation of disease or were the initial manifestation of metastatic disease, The interval from nephrectomy to the onset of ocular signs ranged from 6 to 18 years, A reddish-orange appearance of the tumor was present in two patients, but no pathognomonic features distinguishing these tumors from other choroidal metastases were identified, Conclusions: Ocular metastases may precede the diagnosis of renal cell carcinoma or may follow it by years or decades, This interval between its ocular and systemic presentation may be so prolonged as to obscure the relation between the choroidal metastases and the primary tumor. In patients with amelanotic or reddish choroidal lesions without known metastatic disease, evaluation of the kidney may be warranted as part of a metastatic workup to exclude metastatic renal cell carcinoma. C1 BOSTON UNIV,SCH MED,DEPT OPHTHALMOL,BOSTON,MA 02118. MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,BOSTON,MA 02114. MOORFIELDS EYE HOSP,DEPT CLIN OPHTHALMOL,LONDON EC1V 2PD,ENGLAND. OPHTHALM CONSULTANTS BOSTON,BOSTON,MA. MED COLL WISCONSIN,DEPT OPHTHALMOL,MILWAUKEE,WI 53226. NEW ENGLAND EYE CTR,BOSTON,MA. NR 59 TC 9 Z9 11 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD JUL PY 1997 VL 104 IS 7 BP 1152 EP 1158 PG 7 WC Ophthalmology SC Ophthalmology GA XK363 UT WOS:A1997XK36300023 PM 9224469 ER PT J AU Gliklich, RE Metson, R AF Gliklich, RE Metson, R TI Effect of sinus surgery on quality of life SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article; Proceedings Paper CT 99th Annual Meeting of the American-Academy-of-Otolaryngology-Head-and-Neck-Surgery CY SEP 16-20, 1995 CL NEW ORLEANS, LA SP Amer Acad Otolaryngol Head & Neck Surg ID OUTCOMES RESEARCH; ETHMOIDECTOMY AB Although sinus surgery may reduce the incidence of recurrent infection in patients with chronic sinusitis, little is known about the effect of such surgery on a patient's quality of life, One hundred eight patients undergoing ethmoid sinus surgery were prospectively evaluated with statistically validated measures of sinusitis-specific and general health-related quality of life. Twelve months after surgery significant improvements were found in sinus-specific health status, including a reduction in symptoms (p < 0.001) and medication usage (p < 0.001), An overall improvement was found in 82% of patients, whereas 11% were worse, and 7% remained unchanged, Measures of general health status demonstrated preoperative decrements in five of eight subscales as compared with the normal population. Six months after surgery significant improvements were noted in six categories (p < 0.05), and most attained near-normative levels, Individuals with asthma demonstrated greater overall improvement in general health status than did other cohorts (p < 0.05), We conclude that patients with chronic sinusitis achieve large improvements in sinusitis-specific quality-of-life measures 12 months after sinus surgery, as well as improvements in general health status. 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 20 TC 146 Z9 148 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD JUL PY 1997 VL 117 IS 1 BP 12 EP 17 DI 10.1016/S0194-5998(97)70199-2 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA XK508 UT WOS:A1997XK50800003 PM 9230316 ER PT J AU Cohen, J Reddington, C Jacobs, D Meade, R Picard, D Singleton, K Smith, D Caldwell, B DeMaria, A Hsu, HW Stechenberg, B McIntosh, K Pelton, S Tobin, S Pasternack, M Meissner, C Sullivan, J AF Cohen, J Reddington, C Jacobs, D Meade, R Picard, D Singleton, K Smith, D Caldwell, B DeMaria, A Hsu, HW Stechenberg, B McIntosh, K Pelton, S Tobin, S Pasternack, M Meissner, C Sullivan, J TI School-related issues among HIV-infected children SO PEDIATRICS LA English DT Article DE HIV; AIDS; school issues; confidentiality ID HUMAN-IMMUNODEFICIENCY-VIRUS; AGE-CHILDREN; AIDS AB Objective. Many children with human immunodeficiency virus (HIV) infection are surviving long enough to reach school age. This study describes issues related to school attendance and disclosure of HIV infection in a population of HIV-infected children. Methods. A statewide pediatric HIV surveillance system was used to collect data on school-age (5 years old) HIV-infected children. In addition, HIV clinic nurses familiar with the child's history participated in a cross-sectional survey that collected information on school-related issues during the 1993-1994 school year. Results. Of the 92 school-age children, only 3 were too ill to attend school. Another 5 children were home-schooled. Of the 84 who attended school outside the home, 25% had severe symptoms of HIV infection (Centers for Disease Control and Prevention [CDC] clinical category C). Absence from school ranged from less than 2 weeks during the year for half of the children (51%) to more than 8 weeks for 9 children (12%). Twenty-nine percent of the children received medication in school, usually administered by the school nurse. Over two thirds of the 50 children ages 5 to 10 years had not been told that they had HIV infection. Only 1 of the 20 children more than 10 years of age was not aware of her HIV infection. For 53% of the children attending school, no school personnel had been informed of the child's HIV infection. Administration of HIV medications at school, age of child, and treatment at one particular HIV clinic were associated with the parents' decision to inform school personnel. In the 47% of cases where the school had been informed, school nurses were most frequently notified, followed by principals and teachers. Conclusion. Only 3% of school-age children were too ill to attend school, and almost all were enrolled in public schools. The number of HIV-infected children reaching school age will continue to grow, and public schools will bear the responsibility for educating these children. Health care providers will increasingly be called upon for guidance by both educators and families to assure that HIV-infected children receive the best education possible. C1 CHILDRENS HOSP, BOSTON, MA 02115 USA. BOSTON CITY HOSP, BOSTON, MA 02118 USA. GREATER LAWRENCE FAMILY HLTH CTR, LAWRENCE, MA USA. BAYSTATE MED CTR, SPRINGFIELD, MA USA. UNIV MASSACHUSETTS, MED CTR, WORCESTER, MA USA. CTR DIS CONTROL & PREVENT, DIV HIV AIDS PREVENT, ATLANTA, GA USA. MASSACHUSETTS GEN HOSP, BOSTON, MA 02114 USA. TUFTS UNIV NEW ENGLAND MED CTR, BOSTON, MA 02111 USA. RP Cohen, J (reprint author), MASSACHUSETTS DEPT PUBL HLTH, STATE LAB INST, 305 SOUTH ST, 5TH FLOOR, JAMAICA PLAIN, MA 02130 USA. NR 22 TC 25 Z9 25 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JUL PY 1997 VL 100 IS 1 BP art. no. EP e8 DI 10.1542/peds.100.1.e8 PG 5 WC Pediatrics SC Pediatrics GA XJ181 UT WOS:A1997XJ18100025 PM 9200382 ER PT J AU Song, W Koh, S Czako, M Marton, L Drenkard, E Becker, JM Stacey, G AF Song, W Koh, S Czako, M Marton, L Drenkard, E Becker, JM Stacey, G TI Antisense expression of the peptide transport gene AtPTR2-B delays flowering and arrests seed development in transgenic Arabidopsis plants SO PLANT PHYSIOLOGY LA English DT Article ID ESCHERICHIA-COLI; SALMONELLA-TYPHIMURIUM; TOXIN PRODUCTION; THALIANA; DNA; TRANSFORMATION; PHASEOLOTOXIN; SPORULATION; PERMEASE; MUTANTS AB Previously, we identified a peptide transport gene, AtPTR2-B, from Arabidopsis thaliana that was constitutively expressed in all plant organs, suggesting an important physiological role in plant growth and development. To evaluate the function of this transporter, transgenic Arabidopsis plants were constructed expressing antisense or sense AtPTR2-B. Genomic Southern analysis indicated that four independent antisense and three independent sense AtPTR2-B transgenic lines were obtained, which was confirmed by analysis of the segregation of the kanamycin resistance gene carried on the T-DNA. RNA blot data showed that the endogenous AtPTR2-B mRNA levels were significantly reduced in transgenic leaves and Glowers, but not in transgenic roots. Consistent with this reduction in endogenous AtPTR2-B mRNA levels, all four antisense lines and one sense line exhibited significant phenotypic changes, including late flowering and arrested seed development. These phenotypic changes could be explained by a defect in nitrogen nutrition due to the reduced peptide transport activity conferred by AtPTR2-B. These results suggest that AtPTR2-B may play a general role in plant nutrition. The AtPTR2-B gene was mapped to chromosome 2, which is closely linked to the restriction fragment length polymorphism marker m246. C1 UNIV TENNESSEE,CTR LEGUME RES,KNOXVILLE,TN 37996. UNIV TENNESSEE,DEPT MICROBIOL,KNOXVILLE,TN 37996. UNIV S CAROLINA,DEPT BIOL SCI,COLUMBIA,SC 29208. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MOL BIOL,BOSTON,MA 02114. NR 51 TC 49 Z9 50 U1 1 U2 9 PU AMER SOC PLANT PHYSIOLOGISTS PI ROCKVILLE PA 15501 MONONA DRIVE, ROCKVILLE, MD 20855 SN 0032-0889 J9 PLANT PHYSIOL JI Plant Physiol. PD JUL PY 1997 VL 114 IS 3 BP 927 EP 935 DI 10.1104/pp.114.3.927 PG 9 WC Plant Sciences SC Plant Sciences GA XK774 UT WOS:A1997XK77400021 PM 9232875 ER PT J AU Saijo, Y Hata, S Sheen, J Izui, K AF Saijo, Y Hata, S Sheen, J Izui, K TI Molecular cloning and functional expression of maize and rice cDNAs encoding calcium-dependent protein kinases (CDPKs). SO PLANT PHYSIOLOGY LA English DT Meeting Abstract C1 KYOTO UNIV,GRAD SCH AGR,DIV APPL BIOSCI,SAKYO KU,KYOTO 60601,JAPAN. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MOL BIOL,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC PLANT PHYSIOLOGISTS PI ROCKVILLE PA 15501 MONONA DRIVE, ROCKVILLE, MD 20855 SN 0032-0889 J9 PLANT PHYSIOL JI Plant Physiol. PD JUL PY 1997 VL 114 IS 3 SU S BP 1418 EP 1418 PG 1 WC Plant Sciences SC Plant Sciences GA XL119 UT WOS:A1997XL11901447 ER PT J AU Muramoto, T Yokota, A Hwang, I Goodman, HM Kohchi, T AF Muramoto, T Yokota, A Hwang, I Goodman, HM Kohchi, T TI The photomorphogenic mutant hy1 has deficiency in a gene encoding heme oxygenase for phytochrome chromophore biosynthesis in Arabidopsis thaliana. SO PLANT PHYSIOLOGY LA English DT Meeting Abstract C1 NARA INST SCI & TECHNOL,GRAD SCH BIOL SCI,NARA 63001,JAPAN. HARVARD UNIV,SCH MED,DEPT GENET,CAMBRIDGE,MA 02138. MASSACHUSETTS GEN HOSP,DEPT MOL BIOL,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC PLANT PHYSIOLOGISTS PI ROCKVILLE PA 15501 MONONA DRIVE, ROCKVILLE, MD 20855 SN 0032-0889 J9 PLANT PHYSIOL JI Plant Physiol. PD JUL PY 1997 VL 114 IS 3 SU S BP 1468 EP 1468 PG 1 WC Plant Sciences SC Plant Sciences GA XL119 UT WOS:A1997XL11901495 ER PT J AU Schwartz, MW Seeley, RJ Woods, SC AF Schwartz, MW Seeley, RJ Woods, SC TI Wasting illness as a disorder of body weight regulation SO PROCEEDINGS OF THE NUTRITION SOCIETY LA English DT Article; Proceedings Paper CT Symposium on New Perspectives in the Anorexia-Cachexia Syndrome CY DEC 03-05, 1996 CL BLACKPOOL, ENGLAND SP Nutr Soc, Clin Nutr & Metab Grp, British Assoc Parenteral & Enteral Nutr ID CORTICOTROPIN-RELEASING FACTOR; CENTRAL-NERVOUS-SYSTEM; NEUROPEPTIDE-Y; OBESE GENE; ENERGY-BALANCE; EXPRESSION; INSULIN; PROTEIN; RATS; HYPERPHAGIA C1 UNIV WASHINGTON,HARBORVIEW MED CTR,DEPT PSYCHOL,SEATTLE,WA 98108. VA PUGET SOUND HLTH CARE SYST,SEATTLE,WA 98108. RP Schwartz, MW (reprint author), UNIV WASHINGTON,HARBORVIEW MED CTR,DEPT MED,SEATTLE,WA 98108, USA. RI Schwartz, Michael/H-9950-2012 FU NIDDK NIH HHS [DK-12829]; NINDS NIH HHS [NS32273] NR 45 TC 8 Z9 8 U1 0 U2 1 PU C A B INTERNATIONAL PI WALLINGFORD PA C/O PUBLISHING DIVISION, WALLINGFORD, OXON, ENGLAND OX10 8DE SN 0029-6651 J9 P NUTR SOC JI Proc. Nutr. Soc. PD JUL PY 1997 VL 56 IS 2 BP 785 EP 791 DI 10.1079/PNS19970079 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA XR144 UT WOS:A1997XR14400025 PM 9264129 ER PT J AU Tyan, ML AF Tyan, ML TI Modulation of the antibody response to sheep red blood cells in normal and immunodeficient XID mice by myo-inositol SO PROCEEDINGS OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Article ID X-LINKED AGAMMAGLOBULINEMIA; PROTEIN-TYROSINE KINASES; CBA-N MICE; VITAMIN-A; IMMUNE DEFECT; B-CELLS; TRISPHOSPHATE AB Over the dose ranges tested, dietary vitamin A and myo-inositol induce similar changes in murine fetal growth and development. Because vitamin A is also known to affect the immune response, studies were conducted to determine if dietary myo-inositol might have an effect on antibody production. It was found that in vivo in inbred mice myo-inositol (4 mg/g of diet) accelerated the rate of appearance of plaque-forming cells (PFC) in a primary response to sheep red blood cells (SRBC), In vitro, myo-inositol accelerated the rate of appearance of colonies of anti-SRBC PFC (foci) and significantly increased the number of PFC per colony, but did not affect the number of foci per culture noted at the end of the culture period. myo-inositol had no effect on the PFC IgM:IgG ratio following a single exposure to the agent, but exposure to myo-inositol in vivo and In vitro resulted in a decrease in the number of IgM PFC per focus in a primary response and IgM and IgG PFC per focus in a secondary response, Based on studies suggesting that myo-inositol or a phosphorylated metabolite might act downstream from Bruton's tyrosine kinase (Btk) in a signal transduction pathway in B cells, immunodeficient CBA/CaHN-XID/J mice were fed a standard diet or the same diet supplemented with 0.4% myo-inositol. Mice given the supplemented diet produced significantly more IgM anti-SRBC antibody than did XID mice given the control diet (4.3 +/- 2.5 vs 1.7 +/- 2.8, 1/log(2)), and produced approximately the same amount as immunocompetent controls (2.9 +/- 0.9). When rechallenged with SRBC, XID mice given supplemental inositol produced significantly more IgM antibody than did the XID and immunocompetent controls (3.6 +/- 0.5 vs 1.8 +/- 1.1 and 1.5 +/- 0.7, respectively). Added dietary inositol did not have a significant effect on primary or secondary IgG responses to SRBC, which remained impaired. These results suggest that dietary myo-inositol or a derivative may be able to modulate B-cell IgM responses by interacting within the inositol second messenger system downstream from Bruton's tyrosine kinase. RP Tyan, ML (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,11301 WILSHIRE BLVD,LOS ANGELES,CA 90073, USA. NR 21 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0037-9727 J9 P SOC EXP BIOL MED JI Proc. Soc. Exp. Biol. Med. PD JUL PY 1997 VL 215 IS 3 BP 258 EP 263 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA XF600 UT WOS:A1997XF60000007 PM 9207861 ER PT J AU Deyo, SN Lytton, WW AF Deyo, SN Lytton, WW TI Inhibition can disrupt hypersynchrony in model neuronal networks SO PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY LA English DT Review DE computer models; epilepsy; inhibition; oscillations ID THALAMIC NEURONS; HIPPOCAMPUS; SYNCHRONIZATION; INTERNEURONS; CONDUCTANCES; MODULATION AB 1. Model neuronal network simulations were performed using a reduced Traub neuronal network model. In the absence of inhibition the network produced synchronous population bursting. 2. Bursting of individual neurons was dependent on 1 or more of the following: build-up of charge in the dendritic compartment, prolonged current flow through simulated NMDA associated channels, current flow through T channels. Interburst interval duration and consequent burst frequency was dependent on the density of slow afterhyperpolarizing potassium channels. 3. Addition of an inhibitory interneuron population projecting to GABA(A) receptors resulted in rapid desynchronization of the population, generally after only 1-2 cycles. This effect was found to be due to reduced participation in the individual population burst and to the need for multi-synaptic activation of the individual neuron in the presence of inhibition. 4. This desynchronizing effect could be offset by increasing the strength of interburst hyperpolarization either through increased density of I-AHP, Or through the addition of a separate inhibitory interneuron pool projected to GABA(B) receptors. 5. These data suggest that the synchronizing effects of inhibition may vary depending on circumstances - with desynchronization being dominant in cases characterized by large population bursts such as those seen in epilepsy. C1 UNIV WISCONSIN,WILLIAM S MIDDLETON MEM VET HOSP,DEPT NEUROL,MADISON,WI 53706. NR 28 TC 2 Z9 2 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0278-5846 J9 PROG NEURO-PSYCHOPH JI Prog. Neuro-Psychopharmacol. Biol. Psychiatry PD JUL PY 1997 VL 21 IS 5 BP 735 EP 750 DI 10.1016/S0278-5846(97)00076-6 PG 16 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA XP391 UT WOS:A1997XP39100001 PM 9278947 ER PT J AU VanCott, EM Muszbek, L Laposata, M AF VanCott, EM Muszbek, L Laposata, M TI Fatty acid acylation of platelet proteins SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS LA English DT Article ID GLYCOSYL-PHOSPHATIDYLINOSITOL; COVALENT MODIFICATION; PALMITIC ACID; EUKARYOTIC PROTEINS; LIPID MODIFICATIONS; THIOESTER LINKAGES; MEMBRANE-PROTEINS; ATTACHMENT SITE; ALPHA-SUBUNITS; MYRISTOYL-COA AB A variety of fatty acids can become covalently attached to platelet proteins by thioester linkage, These fatty acids include palmitate, myristate, stearate, arachidonate, and eicosapentaenoate. More than 20 platelet proteins can be acylated by fatty acids. Several of the acylated platelet proteins have been identified, including glycoprotein Ib beta, glycoprotein IX, P-selectin, G-protein a subunits, and CD9. This report reviews the fatty acid acylation of platelet proteins. C1 DEBRECEN UNIV MED,SCH MED,DEPT CLIN CHEM,H-40123 DEBRECEN,HUNGARY. MASSACHUSETTS GEN HOSP,CLIN LABS,DIV CLIN LABS,DEPT PATHOL,BOSTON,MA 02114. NR 37 TC 8 Z9 8 U1 1 U2 3 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0952-3278 J9 PROSTAG LEUKOTR ESS JI Prostaglandins Leukot. Essent. Fatty Acids PD JUL PY 1997 VL 57 IS 1 BP 33 EP 37 DI 10.1016/S0952-3278(97)90490-7 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism GA XM424 UT WOS:A1997XM42400007 PM 9250606 ER EF