FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Griner, PF Blumenthal, D AF Griner, PF Blumenthal, D TI Reforming the structure and management of academic medical centers: Case studies of ten institutions SO ACADEMIC MEDICINE LA English DT Article ID CARE; FUTURE AB The authors describe a variety of strategies that academic medical centers (AMCs) are using to preserve their missions in the face of changing demands and declining resources. The report is based on comparative studies of ten centers conducted by the authors in 1997 and 1998. (AMCs are defined as medical schools and their owned or closely affiliated clinical facilities.) The studies show that the kinds of reforms that AMCs are making in the conduct of their missions and the results they are aiming for are often characteristic of successful organizations described by experts in organizational change and management. The major reforms found included balancing planning and opportunism; developing new approaches for faculty participation in governance; experimenting with the organization of core functions; listening to the customer; aligning incentives; creating a sense of urgency for change; and reducing the emphasis on paper credentials when recruiting far management positions. While these findings are encouraging, it seems clear that AMCs will need to change and adapt at an ever-increasing rate. Competitive pressures will require them to continuously improve the ways they achieve all their missions. New technologies such as informatics will threaten AMCs' near-monopoly in teaching and research. The new environment will require rapid decision making. the setting aside of traditional professional or departmental structures when they inhibit efficiency or quality, and more effective communication with external publics. How well AMCs can maintain their commitment to core values while adopting new methods in pursuit of those values will determine their futures. C1 Assoc Amer Med Coll, Washington, DC 20037 USA. Ctr Assessment & Management Change Acad Med, Washington, DC USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Hlth Policy Res & Dev Unit, Boston, MA USA. RP Griner, PF (reprint author), Assoc Amer Med Coll, 2450 N St NW, Washington, DC 20037 USA. EM pfgriner@aamc.org NR 22 TC 13 Z9 13 U1 0 U2 2 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD JUL PY 1998 VL 73 IS 7 BP 818 EP 825 DI 10.1097/00001888-199807000-00025 PG 8 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 101MW UT WOS:000074873600027 PM 9679475 ER PT J AU Kampman, KM Volpicelli, JR McGinnis, DE Alterman, AI Weinrieb, RM D'Angelo, L Epperson, LE AF Kampman, KM Volpicelli, JR McGinnis, DE Alterman, AI Weinrieb, RM D'Angelo, L Epperson, LE TI Reliability and validity of the Cocaine Selective Severity Assessment SO ADDICTIVE BEHAVIORS LA English DT Article ID ABUSE TREATMENT; WITHDRAWAL; ABSTINENCE; INPATIENT; SLEEP; MOOD AB This article assesses the reliability and validity of the Cocaine Selective Severity Assessment (CSSA), a measure of cocaine abstinence signs and symptoms. Interrater reliability and scale internal consistency were high. Initial CSSA scores were significantly higher in cocaine-dependent subjects than in alcohol-dependent subjects. Initial CSSA scores were highly correlated with recent cocaine use and with severity measures from the Addiction Severity Index (ASI) including the interviewer severity rating and composite score in the drug section. Among cocaine-dependent subjects, initial CSSA scores were higher for those who failed to achieve abstinence or who subsequently dropped out of treatment. Further, CSSA scores showed consistent and marked declines over time for subjects who continued in treatment and remained abstinent. The CSSA appears to be a reliable and valid measure of cocaine abstinence symptoms and a useful predictor of negative outcomes in cocaine dependence treatment. (C) 1998 Elsevier Science Ltd. C1 Univ Penn, Treatment Res Ctr, Sch Med, Philadelphia, PA 19104 USA. Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Kampman, KM (reprint author), Univ Penn, Treatment Res Ctr, Sch Med, 3900 Chestnut St, Philadelphia, PA 19104 USA. EM kampman@research.trc.upenn.edu FU NIDA NIH HHS [DA00172, R18-DA06107] NR 24 TC 134 Z9 135 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4603 J9 ADDICT BEHAV JI Addict. Behav. PD JUL-AUG PY 1998 VL 23 IS 4 BP 449 EP 461 DI 10.1016/S0306-4603(98)00011-2 PG 13 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA ZX356 UT WOS:000074507300003 PM 9698974 ER PT J AU Lew, EA Barbuti, RC Kovacs, TOG Sytnic, B Humphries, TJ Walsh, JH AF Lew, EA Barbuti, RC Kovacs, TOG Sytnic, B Humphries, TJ Walsh, JH TI An ascending single-dose safety and tolerance study of an oral formulation of rabeprazole (E3810) SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID PROTON PUMP INHIBITOR; ACID-SECRETION; OMEPRAZOLE; PANTOPRAZOLE; PHARMACOKINETICS AB Background: Proton pump inhibitors such as omeprazole produce a long-lasting inhibition of gastric acid secretion associated with significant increases in plasma gastrin, Rabeprazole (E3810) is a new substituted benzimidazole H+,K+ ATPase inhibitor. It acts as an irreversible, non-competitive inhibitor of the H+,K+ ATPase and preliminary studies demonstrate that rabeprazole produces a potent and long-lasting inhibition of gastric acid secretion and a low level of hypergastrinaemia. Aim: This randomized, double-blind, placebo-controlled study was performed to further examine the effects of different single doses of rabeprazole on gastric acid secretion and serum gastrin. Methods: In this study, four groups of 10 healthy, nonsmoking Helicobacter pylori-negative men (mean age 22.5 +/- 3.9 years) received single oral doses of 10, 20, 30 and 40 mg of rabeprazole. Two of the 10 volunteers in each group received placebo as part of the double-blind study design. All volunteers who entered into the study had a normal gastric acid secretory capacity as evaluated by pentagastrin challenge. Prior to administration of the first dose of test drug, volunteers underwent an inpatient 24-h measurement of baseline intragastric pH. One week later, volunteers received the test drug and again underwent an inpatient 24-h measurement of intragastric pH, During both periods, plasma samples were collected at specified intervals over 48 h and were sent for analysis of rabeprazole and gastrin levels. Results: Administration of rabeprazole resulted in a dose-dependent increase in the duration and extent of intragastric pH elevation. The response among all volunteers receiving drug was significantly different from placebo, with greater acid inhibition occurring in the 30 and 40 mg groups. In addition, there was also a dose-related increase in plasma gastrin. The pharmacokinetics of rabeprazole were similar to those of other proton pump inhibitors with a t(1/2) of between 0.7 and 1.0 h. There were no clinically significant effects on patient laboratory tests or serious adverse events. Conclusions: The results of this study suggest that rabeprazole is as potent as omeprazole and lansoprazole in inhibiting gastric acid secretion. C1 Univ Calif Los Angeles, W Los Angeles Vet Adm Med Ctr, CURE, Dept Med,Div Digest Dis,Digest Dis Res Ctr, Los Angeles, CA 90073 USA. Eisai & Co Ltd, London, England. RP Walsh, JH (reprint author), Univ Calif Los Angeles, W Los Angeles Vet Adm Med Ctr, CURE, Dept Med,Div Digest Dis,Digest Dis Res Ctr, Bldg 115,Room 115,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jwalsh@ucla.edu RI Barbuti, Ricardo /H-6277-2015 NR 22 TC 20 Z9 20 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0269-2813 J9 ALIMENT PHARM THERAP JI Aliment. Pharmacol. Ther. PD JUL PY 1998 VL 12 IS 7 BP 667 EP 672 PG 6 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 106JT UT WOS:000075126700010 PM 9701531 ER PT J AU Philbin, EF DiSalvo, TG AF Philbin, EF DiSalvo, TG TI Influence of race and gender on care process, resource use, and hospital-based outcomes in congestive heart failure SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CARDIOVASCULAR-DISEASE; SEX-DIFFERENCES; UNITED-STATES; WOMEN; MEN; VALIDATION; QUALITY; IMPACT; HEALTH; BLACK AB Race and gender are important determinants of certain clinical outcomes in cardiovascular disease. To examine the influence of race and gender on care process, resource use, and hospital-based case outcomes for patients with congestive heart failure (CHF), we obtained administrative records on all 1995 New York State hospital discharges assigned ICD-9-CM codes indicative of this diagnosis. The following were compared among black and white women and men: demographics, comorbid illness, care processes, length of stay (LOS), hospital charges, mortality rate, and CHF readmission rate. We identified 45,894 patients (black women, 4,750; black men, 3,370; white women, 21,165; white men, 16,609). Blacks underwent noninvasive cardiac procedures more often than whites; procedure and specialty use rates were lower among women than among men. After adjusting for other patient characteristics and hospital type and location, we found race to be an important determinant of LOS (black, 10.4 days; white, 9.3 days; p = 0.0001), hospital charges (black, $13,711; white, $11,074; p = 0.0001), mortality (black-to-white odds ratio = 0.832; p = 0.003), and readmission (black-to-white odds ratio = 1.301; p 0.0001). Gender was an important determinant of LOS (women, 9.8 days; men, 9.2 days; p = 0.0001), hospital charges (women, $11,690; men, $11,348; p = 0.02), and mortality (women-to-men odds ratio = 0.878; p 0.0008). We conclude that race and gender influence care process and hospital-based case outcomes for patients with CHF. (C) 1998 by Excerpta Medica, Inc. C1 Henry Ford Hosp, Div Cardiovasc Med, Heart Failure & Heart Transplantat Program, Detroit, MI 48202 USA. Massachusetts Gen Hosp, Cardiac Unit, Heart Failure & Transplantat Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Philbin, EF (reprint author), Henry Ford Hosp, Div Cardiovasc Med, Heart Failure & Heart Transplantat Program, 2799 W Grand Blvd, Detroit, MI 48202 USA. NR 28 TC 114 Z9 116 U1 1 U2 2 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JUL 1 PY 1998 VL 82 IS 1 BP 76 EP 81 DI 10.1016/S0002-9149(98)00233-1 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA ZZ194 UT WOS:000074705000016 PM 9671013 ER PT J AU Roberts, WC Braunwald, E AF Roberts, WC Braunwald, E TI Eugene Braunwald, MD: A conversation with the editor SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Editorial Material ID ACUTE MYOCARDIAL-INFARCTION; TISSUE-PLASMINOGEN-ACTIVATOR; LEFT-VENTRICULAR DYSFUNCTION; EXPERIMENTAL CORONARY-OCCLUSION; UNSTABLE ANGINA; ISCHEMIC-INJURY; CONSERVATIVE STRATEGIES; THROMBOLYTIC THERAPY; STUNNED MYOCARDIUM; INTERNAL-MEDICINE C1 Baylor Univ, Med Ctr, Baylor Cardiovasc Inst, Dallas, TX 75246 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. Partners HealthCare Syst, Boston, MA 02115 USA. RP Roberts, WC (reprint author), Baylor Univ, Med Ctr, Baylor Cardiovasc Inst, Dallas, TX 75246 USA. NR 128 TC 2 Z9 2 U1 1 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JUL 1 PY 1998 VL 82 IS 1 BP 93 EP 108 PG 16 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA ZZ194 UT WOS:000074705000019 ER PT J AU Macario, E Sorensen, G AF Macario, E Sorensen, G TI Spousal similarities in fruit and vegetable consumption SO AMERICAN JOURNAL OF HEALTH PROMOTION LA English DT Article DE fruits; vegetables; spouse pairs; similarities ID CANCER PREVENTION; SOCIAL SUPPORT; UNITED-STATES; DIET; RISK; CONCORDANCE; VALIDITY; SMOKING AB Purpose. To explore similar patterns of fruit and vegetable consumption between health center employees and their spouses. Design. Cross-sectional mailed survey assessing frequency of fruit and vegetable consumption, as well as demographics and knowledge, attitudes, access, and social support related to fruit and vegetable consumption. Setting. Six Massachusetts health centers. Subjects. Two hundred eleven health center employee/spouse lairs (422 individuals). Measures. The kappa statistic measured agreement in fruit and vegetable consumption between employees and spouses. The Spearman rho coefficient measured correlations for individual responses. Multiple Linear Regression Models examined variables that explained fruit and vegetable consumption level differences. Results. Response rate was 59%. Mean fruit and vegetable daily intake was 4.68 and 4.30 servings for employees and spouses, respectively. Over 75% of employee and spouse estimates measuring fruit and vegetable consumption-related information, on average, were within one survey response category of each other Knowledge, attitudes, and access indices were significantly correlated with fruit and vegetable consumption for both employees and spouses. The social support index was significantly correlated with fruit and vegetable consumption only for the spouses. Differences in knowledge, attitudes, and access indices between employees and spouses helped to explain different fruit and vegetable consumption levels. Nonresponse, selection, recall, and seasonal reporting biases may limit the findings generalizability. Conclusions. The effectiveness of worksite nutrition interventions may be improved by involving family/household members. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Ctr Community Based Res, Boston, MA 02115 USA. RP Macario, E (reprint author), Dana Farber Canc Inst, L-2,44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [5RO1CA59728-O3S1A1] NR 41 TC 10 Z9 10 U1 0 U2 3 PU AMER J HEALTH PROMOTION INC PI KEEGO HARBOR PA 1660 CASS LAKE RD, STE 104, KEEGO HARBOR, MI 48320 USA SN 0890-1171 J9 AM J HEALTH PROMOT JI Am. J. Health Promot. PD JUL-AUG PY 1998 VL 12 IS 6 BP 369 EP 377 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 102TY UT WOS:000074942400003 PM 10182088 ER PT J AU Revankar, SG Kirkpatrick, WR McAtee, RK Fothergill, AW Redding, SW Rinaldi, MG Hilsenbeck, SG Patterson, TF AF Revankar, SG Kirkpatrick, WR McAtee, RK Fothergill, AW Redding, SW Rinaldi, MG Hilsenbeck, SG Patterson, TF TI A randomized trial of continuous or intermittent therapy with fluconazole for oropharyngeal candidiasis in HIV-infected patients: Clinical outcomes and development of fluconazole resistance SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; RECURRENT ORAL CANDIDIASIS; CLOTRIMAZOLE TROCHES; POSITIVE PATIENTS; DOUBLE-BLIND; ALBICANS; EMERGENCE; AIDS; PROPHYLAXIS; CANDIDOSIS AB PURPOSE: The effects of continuous or intermittent therapy with fluconazole on the recurrence of and the development of fluconazole resistance are not known. PATIENTS AND METHODS: We studied human immunodeficiency virus (HIV)-positive patients with CD, cell count <350 x 10(6)/L and oropharyngeal candidiasis in a prospective, randomized study. After initial treatment, 20 patients (16 of whom completed 3 months of follow-up) received continuous fluconazole at 200 mg/day, and 48 patients (28 of whom completed follow-up) received intermittent therapy at the time of symptomatic relapses. Oral samples were obtained weekly during episodes of infection and quarterly as surveillance cultures. Development of resistance was defined as a fourfold rise in minimum inhibitory concentration (MIC) to at least 16 mu g/mL from the initial culture in the same species, the emergence of new, resistant (MIC greater than or equal to 16 mu g/mL) species, or a significant increase in the proportion of resistant isolates. RESULTS: During a mean follow-up of 11 months, median annual relapse rates were lower in patients on continuous therapy (0 episodes/year) than in patients on intermittent therapy (4.1 episodes/year; P <0.001). Sterile cultures were seen in 6 of 16 (38%) patients on continuous therapy compared with 3 of 28 (11%) on intermittent therapy (P = 0.04). Microbiological resistance developed in 9 of 16 (56%) patients on continuous treatment, compared with 13 of 28 (46%) on intermittent treatment (P = 0.75). However, despite isolates with increased MICs, 42 of 44 patients responded to fluconazole in doses up to 800 mg/day. CONCLUSIONS: In patients with frequent recurrences, continuous suppressive therapy significantly reduced relapses and colonization. Resistance occurred with both continuous and intermittent therapy; however, therapeutic responses were excellent. (C) 1998 by Excerpta Medica, Inc. C1 Univ Texas, Hlth Sci Ctr, Dept Med Infect Dis, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. Audie Murphy Div, San Antonio, TX USA. RP Revankar, SG (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med Infect Dis, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. FU NCRR NIH HHS [M01-RR-01346]; NIDCR NIH HHS [1R01 DE11381-01] NR 25 TC 39 Z9 40 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD JUL PY 1998 VL 105 IS 1 BP 7 EP 11 DI 10.1016/S0002-9343(98)00137-5 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 102HX UT WOS:000074919500002 PM 9688014 ER PT J AU Vonderheide, RH Thadhani, R Kuter, DJ AF Vonderheide, RH Thadhani, R Kuter, DJ TI Association of thrombocytopenia with the use of intra-aortic balloon pumps SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID HEPARIN-INDUCED THROMBOCYTOPENIA; VASCULAR COMPLICATIONS; COUNTERPULSATION; INSERTION AB PURPOSE: The intra-aortic balloon pump has become an important tool in the management of patients with severe coronary artery disease. Although pump-induced thrombocytopenia was described more than 20 years ago, there has been no prospective study of this condition. PATIENTS AND METHODS: In a prospective study of consecutive adult intensive care patients admitted with acute coronary syndromes, we compared serial platelet counts in 58 patients treated with an intra-aortic balloon pump with 51 patients who were not. All patients received intravenous heparin. RESULTS: Clinical characteristics of the two groups were similar, except that unstable angina was more frequent among balloon pump patients. On each of 6 consecutive days, the mean platelet counts of patients treated with a balloon pump were significantly lower than those of non-pump patients. Platelet counts (mean +/- SD) of balloon pump patients decreased to a nadir of 63% +/- 4% of the initial count on day 4, but subsequently stabilized. There was only a slight, transient decrease in the platelet counts of non-pump patients. Overall, 47% of balloon pump patients developed thrombocytopenia (platelet count < 150,000/mm(3)) compared with 12% of non-pump patients (P <0.01). Platelet counts dropped by at least half of initial counts in 26% of balloon pump patients compared with 4% of nog-pump patients (P <0.01). Multivariate analysis demonstrated that the use of an intra-aortic balloon pump was independently associated with a substantial (greater than or equal to 50%) decline in platelet count (odds ratio 7.2, 95% confidence interval 1.4 to 40, P = 0.03). Removal of the balloon pump was associated with a rapid increase in platelet count. CONCLUSIONS: The use of an intra-aortic balloon pump led to a steady and predictable decrease in platelet count, which recovered rapidly if the balloon pump was removed or slowly if the device remained in place. (C) 1998 by:Excerpta Medica, Inc. C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Vonderheide, RH (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL54838] NR 23 TC 35 Z9 38 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD JUL PY 1998 VL 105 IS 1 BP 27 EP 32 DI 10.1016/S0002-9343(98)00128-4 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 102HX UT WOS:000074919500006 PM 9688018 ER PT J AU Tritos, NA Mantzoros, CS AF Tritos, NA Mantzoros, CS TI Recombinant human growth hormone: Old and novel uses SO AMERICAN JOURNAL OF MEDICINE LA English DT Review ID PLACEBO-CONTROLLED TRIAL; CLINICAL RESEARCH-CENTER; NATIONAL COOPERATIVE GROWTH; BONE-MINERAL CONTENT; IMMUNODEFICIENCY-VIRUS INFECTION; CARDIOVASCULAR RISK-FACTORS; CREUTZFELDT-JAKOB-DISEASE; CHRONIC-RENAL-FAILURE; LONG-TERM THERAPY; 60 YEARS OLD AB Recent studies of the growth hormone insulinlike growth factor I (IGF I) axis suggest that these hormones are involved in several physiologic processes, in addition to growth. Thus, several lines of evidence indicate an increasingly important role for recombinant human growth hormone as a part of the modern therapeutic armamentarium. In addition to the treatment of children with,growth hormone deficiency, administration of growth hormone appears to be of considerable benefit to girls with Turner syndrome, children with chronic renal failure, and adults with growth hormone deficiency or human immunodeficiency virus (HIV) wasting syndrome. Moreover, its therapeutic use is being investigated in other conditions, such as children with idiopathic short stature, the healthy elderly, and the critically ill. However, long-term surveillance among growth hormone recipients is needed to fully evaluate its risk-benefit profile. (C) 1998 by Excerpta Medica, Inc. C1 Beth Israel Deaconess Med Ctr, Div Endocrinol, Boston, MA 02215 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. RP Mantzoros, CS (reprint author), Beth Israel Deaconess Med Ctr, Div Endocrinol, RN 325,99 Brookline Ave, Boston, MA 02215 USA. RI Andrade, Hugo/M-6631-2013 OI Andrade, Hugo/0000-0001-6781-6125 NR 203 TC 42 Z9 46 U1 1 U2 2 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD JUL PY 1998 VL 105 IS 1 BP 44 EP 57 DI 10.1016/S0002-9343(98)00135-1 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA 102HX UT WOS:000074919500009 PM 9688021 ER PT J AU To, K Adamian, M Jakobiec, FA Berson, EL AF To, K Adamian, M Jakobiec, FA Berson, EL TI Histopathologic and immunohistochemical study of dominant cone degeneration SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article AB PURPOSE: To report the histopathologic and immunohistochemical findings in autosomal dominant cone degeneration. METHODS: The autopsy eyes of a 75-year-old man with autosomal dominant cone degeneration were studied with both light and electron microscopy, In addition, immunofluorescent studies using antibodies to cone opsins and cone alpha transducin were performed, RESULTS: Histopathologic examination of the fovea disclosed loss of photoreceptors and attenuated retinal pigment: epithelium, Reducecd numbers of cones could be seen in the parafovea, and only occasional cones were visible in the periphery; pods were preserved in the periphery. CONCLUSION: The histopathologic and immunohistochemical findings in this case of dominantly inherited cone degeneration correlate well with the loss of cone function and preservation of normal or nearly normal rod function upon clinical examination. This condition affects red, green, and blue cones. (C) 1998 by Elsevier Science Inc. All rights reserved. C1 Harvard Univ, Berman Gund Lab Study Retinal Degenerat, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. Harvard Univ, Ophthalm Pathol Serv, Massachusetts Eye & Ear Infirm, Sch Med,Dept Ophthalmol, Boston, MA 02114 USA. RP To, K (reprint author), Harvard Univ, Berman Gund Lab Study Retinal Degenerat, Massachusetts Eye & Ear Infirm, Sch Med, 243 Charles St, Boston, MA 02114 USA. NR 3 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD JUL PY 1998 VL 126 IS 1 BP 140 EP 142 DI 10.1016/S0002-9394(98)00085-3 PG 3 WC Ophthalmology SC Ophthalmology GA ZZ322 UT WOS:000074717800023 PM 9683165 ER PT J AU Kieff, DA Curtin, HD Limb, CJ Nadol, JB AF Kieff, DA Curtin, HD Limb, CJ Nadol, JB TI A hairy polyp presenting as a middle ear mass in a pediatric patient SO AMERICAN JOURNAL OF OTOLARYNGOLOGY LA English DT Article ID CHOLESTEATOMA; HEAD; NECK C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol, Boston, MA USA. RP Kieff, DA (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 11 TC 7 Z9 7 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0196-0709 J9 AM J OTOLARYNG JI Am. J. Otolaryngol. PD JUL-AUG PY 1998 VL 19 IS 4 BP 228 EP 231 DI 10.1016/S0196-0709(98)90122-3 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA 101DL UT WOS:000074854300002 PM 9692629 ER PT J AU Kieff, DA Curtin, HD Healy, GB Poe, DS AF Kieff, DA Curtin, HD Healy, GB Poe, DS TI A duplicated tympanic facial nerve and congenital stapes fixation: An intraoperative and radiographic correlation SO AMERICAN JOURNAL OF OTOLARYNGOLOGY LA English DT Article C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. RP Kieff, DA (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 14 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 USA SN 0196-0709 J9 AM J OTOLARYNG JI Am. J. Otolaryngol. PD JUL-AUG PY 1998 VL 19 IS 4 BP 283 EP 286 DI 10.1016/S0196-0709(98)90133-8 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA 101DL UT WOS:000074854300013 PM 9692640 ER PT J AU Xia, MQ Qin, SX Wu, LJ Mackay, CR Hyman, BT AF Xia, MQ Qin, SX Wu, LJ Mackay, CR Hyman, BT TI Immunohistochemical study of the beta-chemokine receptors CCR3 and CCR5 and their ligands in normal and Alzheimer's disease brains SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID EXPRESSION; INFECTION; VIRUS; HIV-1; PROTEIN-1 AB Chemokines belong to an expanding family of cytokines the primary function of which is recruitment of leukocytes to inflammatory sites. Recent evidence has shown their presence in the central nervous system. Because inflammatory responses have been implicated in the pathogenesis of Alzheimer's disease (AD), we studied the expression of CCR3, CCR5, and their ligands in normal and AD brains by immunohistochemistry. CCR3 and CCR5 are present on microglia of both control and AD brains, with increased expression on some reactive microglia in AD. Immunohistochemistry for MIP-1 beta, MIP-1 alpha, RANTES, eotaxin, and MCP-3 (ligands for CCR5 and/or CCR3) revealed the presence of MIP-1 beta predominantly in a subpopulation of reactive astrocytes, which were more widespread in AD than control brains, and MIP-1 alpha predominantly in neurons and weakly in some microglia in both AD and controls. Many of the CCR3(+) or CCR5(+) reactive microglia and MIP-1 beta(+) reactive astrocytes were found associated with amyloid deposits. Immunoreactivity for eotaxin, RANTES, and MCP-S were not detected. Detection of these beta-chemokine receptors on microglia and some of their ligands in reactive astrocytes and neurons as well as microglia suggests a role for this system in glial-glial and glial-neuronal interactions, potentially influencing the progression of AD. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Alzheimers Res Unit, Charlestown, MA USA. Leukosite Inc, Cambridge, MA USA. RP Hyman, BT (reprint author), Massachusetts Gen Hosp E, Alzheimers Res Unit, 149 13th St CNY 6405, Charlestown, MA 02129 USA. EM B_hyman@helix.mgh.harvard.edu RI Mackay, Charles/A-9673-2008 OI Mackay, Charles/0000-0002-6338-7340 FU NIA NIH HHS [AG05134, AG08487, P50 AG005134, R01 AG008487] NR 36 TC 146 Z9 154 U1 0 U2 4 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JUL PY 1998 VL 153 IS 1 BP 31 EP 37 DI 10.1016/S0002-9440(10)65542-3 PG 7 WC Pathology SC Pathology GA ZX920 UT WOS:000074568700006 PM 9665462 ER PT J AU Nielsen, GP Burns, KL Rosenberg, AE Louis, DN AF Nielsen, GP Burns, KL Rosenberg, AE Louis, DN TI CDKN2A gene deletions and loss of p16 expression occur in osteosarcomas that lack RB alterations SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID RETINOBLASTOMA SUSCEPTIBILITY GENE; OSTEO-SARCOMA; MUTATION; HETEROZYGOSITY; P16(INK4) AB Osteosarcomas often suffer mutations of the RB (retinoblastoma) gene, with resultant inactivation of the pRb protein. pRb is one component in a cell-cycle control pathway that includes the p16 (encoded by the CDKN2A gene) and cyclin-dependent kinase 4 (cdk4, encoded by the CDK4 gene) proteins. We therefore sought to determine whether the CDKN2A and CDK4 genes were altered in those osteosarcomas that lacked RE inactivation Twenty-one osteosarcomas (2 low-grade and 19 high-grade) were evaluated for homozygous deletion of the CDKN2A gene, CDK4 amplification, and allelic loss of the RE gene, as well as for expression of p16 and pRb proteins. Five high-grade osteosarcomas showed loss of p16 expression; four of these had homozygous CDKN2A deletions, and the fifth had a probable deletion obscured by numerous nonneoplastic, p16-immunopositive multinucleated giant cells. Thus, p16 immunohistochemistry may provide a sensitive means for assessing CDKN2A status. Twelve tumors (including the two low-grade osteosarcomas) were immunopositive for pRb, and nine tumors were immunonegative for pRb. Of the five cases with CDKN2A/p16 alterations, none had allelic loss of the RE gene and all expressed pRb, suggesting that each of these tumors had an intact RB gene. None of the tumors showed CDK4 amplification. No alterations were detected in the two low-grade osteosarcomas, This study suggests that CDKN2A is a tumor suppressor inactivated in osteosarcomas that lack RB mutations and that the p16-pRb cell-cycle control pathway is deregulated in a large number of high-grade osteosarcomas. C1 Massachusetts Gen Hosp, Dept Pathol, Mol Neurooncol Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, James Homer Wright Pathol Labs, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Ottawa, Dept Pathol, Ottawa, ON K1N 6N5, Canada. RP Nielsen, GP (reprint author), Massachusetts Gen Hosp, Dept Pathol, Mol Neurooncol Lab, Fruit St, Boston, MA 02114 USA. EM gnielsen@partners.org NR 30 TC 60 Z9 65 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JUL PY 1998 VL 153 IS 1 BP 159 EP 163 DI 10.1016/S0002-9440(10)65556-3 PG 5 WC Pathology SC Pathology GA ZX920 UT WOS:000074568700020 PM 9665476 ER PT J AU Dorfman, DM Shahsafaei, A Nadler, LM Freeman, GJ AF Dorfman, DM Shahsafaei, A Nadler, LM Freeman, GJ TI The leukocyte semaphorin CD100 is expressed in most T-cell, but few B-cell, non-Hodgkin's lymphomas SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID DIFFERENTIATION ANTIGEN EXPRESSION; CENTROCYTIC LYMPHOMAS; SOMATIC MUTATIONS; GENES; ACTIVATION; PATTERNS; SURFACE; MEMORY; REGION AB The 150-kd transmembrane protein CD100 is the first semaphorin protein shown to be expressed in lymphoid tissue. CD100 is present in the interfollicular T cell zones and is also expressed by B cells in the germinal centers of secondary lymphoid follicles, but not in the mantle zones. The CD100 molecule was recently cloned, and CD100 transfectants were shown to induce homotypic aggregation of human B cells and improve their viability in vitro, suggesting that CD100 may play a role in lymphocyte aggregation and germinal center formation. We studied the expression of CD100 in 138 clinical cases representing a range of lymphoproliferative disorders, to determine whether this molecule is expressed in these neoplastic processes. In general, we found CD100 expression to be common in peripheral T-cell non-Hodgkin's lymphomas but rare in B-cell non-Hodgkin's lymphomas. CD100 expression was not detectable in low-grade B-cell non-Hodgkin's lymphomas, including cases of small lymphocytic lymphoma (18 cases), marginal zone lymphoma (10 cases), and mantle cell lymphoma (10 cases), as might be expected for these neoplasms that are not of follicular center cell origin. Surprisingly, we found that the vast majority of follicular lymphomas (37 of 40 cases) as well as diffuse large-cell lymphomas of B-cell type (35 cases) did not express CD100. The neoplastic cells in 3 of 11 cases of predominantly large-cell-type follicular lymphoma did express CD100. In contrast, all five cases of high-grade, small non-cleaved (Burkitt-like) E-cell lymphoma were immunoreactive for CD100 expression, as were 18 of 20 cases (90%) of malignant T cell neoplasms. Northern blot analysis of CD100 expression correlated with immunohistochemical findings. Absence of expression of CD100 by neoplastic follicular center B cells is a common feature in follicular lymphomas, but expression of CD100 by T cells is maintained in T-cell lymphoproliferative disorders. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Dana Farber Canc Inst,Dept Adult Oncol, Boston, MA USA. RP Dorfman, DM (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM dmdorfman@bics.bwh.harvard.edu FU NCI NIH HHS [CA40216-11]; NIAID NIH HHS [AI35225-03] NR 36 TC 21 Z9 23 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JUL PY 1998 VL 153 IS 1 BP 255 EP 262 DI 10.1016/S0002-9440(10)65566-6 PG 8 WC Pathology SC Pathology GA ZX920 UT WOS:000074568700030 PM 9665486 ER PT J AU Nelson, RD Stricklett, P Gustafson, C Stevens, A Ausiello, D Brown, D Kohan, DE AF Nelson, RD Stricklett, P Gustafson, C Stevens, A Ausiello, D Brown, D Kohan, DE TI Expression of an AQP2 Cre recombinase transgene in kidney and male reproductive system of transgenic mice SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE water-electrolyte balance; kidney collecting tubule; ion channel physiology; gene expression regulation; promoter region; aquaporin ID WATER CHANNEL; COLLECTING DUCT; GENE-EXPRESSION; RAT-KIDNEY; HUMAN AQUAPORIN; VASOPRESSIN; MOUSE; VARIEGATION; RECEPTOR; EXTRACT AB A transgenic mouse approach was used to examine the mechanism of principal cell-specific expression of aquaporin-2 (AQP2) within the renal collecting duct. RT-PCR and immunocytochemistry revealed that murine AQP2 was expressed in principal cells in the renal collecting duct, epithelial cells of the vas deferens, and seminiferous tubules within testis. The vas deferens expression was confirmed in rats. RT-PCR and immunocytochemistry showed that 14 kb of the human 5'-flanking region confers specific expression of a nucleus-targeted and epitope-tagged Cre recombinase in the principal cells within the renal collecting duct, in the epithelial cells of the vas deferens, and within the testis of transgenic mice. These results suggest that cell-specific expression of AQP2 is mediated at the transcriptional level and that 14 kb of the human AQP2 5'-flanking region contain cis elements that are sufficient for cell-specific expression of AQP2. Finally, renal principal cell expression of Cre recombinase is the first step in achieving cell-specific gene knockouts, thereby allowing focused examination of gene function in this cell type. C1 Vet Affairs Med Ctr, Med Care Ctr 111, Salt Lake City, UT 84148 USA. Univ Utah, Sch Med, Salt Lake City, UT 84132 USA. Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Harvard Med Sch, Charlestown, MA 02129 USA. RP Kohan, DE (reprint author), Vet Affairs Med Ctr, Med Care Ctr 111, 500 Foothill Dr, Salt Lake City, UT 84148 USA. RI Messier, Claude/A-2322-2008 OI Messier, Claude/0000-0002-4791-1763 FU NHLBI NIH HHS [R01-HL-256857]; NIDDK NIH HHS [K08-DK-02132-06, R01-DK-52043] NR 45 TC 83 Z9 83 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD JUL PY 1998 VL 275 IS 1 BP C216 EP C226 PG 11 WC Cell Biology; Physiology SC Cell Biology; Physiology GA ZX377 UT WOS:000074509500024 PM 9688853 ER PT J AU Nishimura, A Fujimoto, M Oguchi, S Fusunyan, RD MacDermott, RP Sanderson, IR AF Nishimura, A Fujimoto, M Oguchi, S Fusunyan, RD MacDermott, RP Sanderson, IR TI Short-chain fatty acids regulate IGF-binding protein secretion by intestinal epithelial cells SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE Caco-2 cells; acetate; butyrate; propionate; polarity; histone; acetylation ID GROWTH FACTOR-I; ENTEROCYTE-LIKE DIFFERENTIATION; SODIUM-BUTYRATE; HUMAN-COLON; GENE-EXPRESSION; TRICHOSTATIN-A; CANCER CELLS; CACO-2 CELLS; LINE CACO-2; SMALL-BOWEL AB Gastrointestinal epithelial cells secrete insulin-like growth factor (IGF)-binding proteins (IGFBPs), which modulate the actions of IGFs on cell proliferation and differentiation. Short-chain fatty acids are bacterial metabolites from unabsorbed carbohydrate (including fiber). We hypothesized that they may alter the pattern of IGFBPs secreted by epithelial cells as part of a wider phenomenon by which luminal molecules regulate gastrointestinal epithelial cell signaling. The intestinal epithelial cell line, Caco-2, predominantly secretes IGFBP-5; however, butyrate increased the secretion of IGFBP-2 in a dose-dependent and reversible manner. Butyrate decreased the secretion of IGFBP-3. Butyrate altered only the synthesis and not the cell sorting of IGFBPs because 1) the secretion of IGFBPs remained polarized despite changes in their rates of production, and 2) IGFBP secretion corresponded to mRNA accumulation. The ability of short-chain fatty acids or the fungicide trichostatin A to stimulate IGFBP-8 correlated with their actions on histone acetylation. In conclusion, intestinal epithelial cells respond to short-chain fatty acids by altering secretion of IGFBPs. C1 Massachusetts Gen Hosp, Harvard Clin Nutr Res Ctr, Dev Gastroenterol Lab, Combined Program Pediat Gastroenterol & Nutr, Charlestown, MA 02129 USA. Lahey Hitchcock Clin, Gastrointestinal Sect, Burlington, MA 01805 USA. RP Sanderson, IR (reprint author), St Bartholomews & Royal London Sch Med & Dent, Dept Paediat Gastroenterol, Dominion House, London EC1A 7BE, England. FU NIDDK NIH HHS [DK-21474, DK-47753, DK-40561] NR 50 TC 28 Z9 29 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD JUL PY 1998 VL 275 IS 1 BP E55 EP E63 PG 9 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA ZZ417 UT WOS:000074727300009 PM 9688874 ER PT J AU Nguyen, TD Okolo, CN Moody, MW AF Nguyen, TD Okolo, CN Moody, MW TI Histamine stimulates ion transport by dog pancreatic duct epithelial cells through H-1 receptors SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE chloride channels; potassium channels; Ussing chamber ID GUINEA-PIG PANCREAS; EXOCRINE SECRETION AB Histamine affects pancreatic secretion, but its direct action on ion transport by pancreatic duct epithelial cells (PDEC) has not been defined. We now characterize the secretory effects of histamine on cultured, well-differentiated, and nontransformed dog PDEC. Histamine stimulated, in a concentration-dependent manner (1-100 mu M), a cellular I-125(-) efflux that was inhibited by 500 mu M 5-nitro-2-(3-phenylpropylamino)benzoic acid, 2.5 mM diphenylamine-2-carboxylate, and 500 mu M DIDS and thus mediated through Ca2+-activated Cl- channels. Histamine-stimulated I-125(-) efflux was 1) inhibited by 100 mu M diphenhydramine, an H-1 receptor antagonist, 2) resistant to 1 mM cimetidine, an H-2 receptor antagonist, 3) not reproduced by 1 mM dimaprit, an H-2 agonist, and 4) inhibited by 50 mu M 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-AM, a Ca2+ chelator, suggesting that it was mediated through H-1 receptors acting via increased cytosolic Ca2+. Histamine also stimulated a Rb-86(+) efflux that was sensitive to 100 nM charybdotoxin and thus mediated through Ca2+-activated K+ channels. When PDEC monolayers were studied in Ussing chambers, a short-circuit current of 21.7 +/- 3.1 mu A/cm(2) was stimulated by 100 mu M histamine. This effect was inhibited by diphenhydramine but not cimetidine, was not reproduced with dimaprit, and was observed only after serosal addition of histamine, suggesting that it was mediated by basolateral H-1 receptors on PDEC. In conclusion, histamine, acting through basolateral H-1 receptors, activates both Ca2+-activated Cl- and K+ channels; in this manner, it may regulate PDEC secretion in normal or inflamed pancreas. C1 Univ Washington, Dept Med, Seattle, WA 98108 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Nguyen, TD (reprint author), Vet Affairs Med Ctr, GI Sect 111 GI, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 24 TC 11 Z9 11 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD JUL PY 1998 VL 275 IS 1 BP G76 EP G84 PG 9 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA ZZ396 UT WOS:000074725200011 PM 9655687 ER PT J AU Nguyen, TD Moody, MW Savard, CE Lee, SP AF Nguyen, TD Moody, MW Savard, CE Lee, SP TI Secretory effects of ATP on nontransformed dog pancreatic duct epithelial cells SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE chloride channels; potassium channels; mucin; short-circuit current; cystic fibrosis; adenosine 5 '-triphosphate ID TRANSMEMBRANE CONDUCTANCE REGULATOR; CYSTIC-FIBROSIS; MUCIN SECRETION; RECEPTOR; ACTIVATION; EXPRESSION; IDENTIFICATION; SELECTIVITY; CHANNELS; CLONING AB Extracellular triphosphate nucleotides, such as ATP, may regulate various cellular functions through specific cell surface receptors. We examine in this report the different secretory effects of ATP and analogs on nontransformed dog pancreatic duct epithelial cells (PDEC). We observed that 1) ATP, UTP, adenosine 5'-O-(3-thiotriphosphate), and, to a lesser extent, beta,gamma-methylene-ATP, but not adenosine, stimulated I-125- efflux from PDEC, suggesting a primary role for P-2Y2 receptors, 2)ATP-stimulated I-125- efflux was inhibited by 5-nitro-2-(3-phenylpropylamino)benzoic acid, diphenylamine-2-carboxylate, and DIDS, suggesting mediation through Ca2+-activated Cl- channels, 3) ATP stimulated an Rb-86(+) efflux sensitive to BaCl2 and charybdotoxin, thus likely occurring through Ca2+-activated K+ channels, 4) serosal or luminal addition of UTP activated apical Cl- conductance and basolateral K+ conductance when nystatin-permeabilized PDEC were studied in an Ussing chamber, suggesting the expression of P-2Y2 receptors on both sides of the cell, 5) ATP stimulated mucin secretion, and 6) ATP increases intracellular Ca2+ concentration ([Ca2+](i)). In conclusion, ATP and UTP interact with P-2Y2 receptors on nontransformed PDEC to increase [Ca2+](i), stimulate mucin secretion, and activate ion conductances; these findings have implications for pancreatic exocrine function in both health and disease, such as cystic fibrosis. C1 Univ Washington, Dept Med, Seattle, WA 98108 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Nguyen, TD (reprint author), Vet Affairs Med Ctr, GI Sect 111 GI, 1660 S Columbian way, Seattle, WA 98108 USA. RI Lee, Sum Ping/C-4333-2009 FU NIDDK NIH HHS [DK-50246] NR 32 TC 34 Z9 34 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD JUL PY 1998 VL 275 IS 1 BP G104 EP G113 PG 10 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA ZZ396 UT WOS:000074725200014 PM 9655690 ER PT J AU Warren, KS Fishman, MC AF Warren, KS Fishman, MC TI "Physiological genomics": mutant screens in zebrafish SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Review DE mutagenesis; embryonic physiology; embryonic cardiovasculature; vertebrate genetic screen ID DEVELOPMENTAL HEMODYNAMIC-CHANGES; CHICK HEART-CELLS; CARDIOVASCULAR DEVELOPMENT; BLOOD-PRESSURE; MURINE HEART; GENE; EMBRYOS; DROSOPHILA; CONDUCTION; SPECIFICATION AB Large-scale mutagenesis screens have proved essential in the search for genes that are important to development in the fly, worm, and yeast. Here we present the power of large-scale screening in a vertebrate, the zebrafish Danio rerio, and propose the use of this genetic system to address fundamental questions of vertebrate developmental physiology. As an example, we focus on zebrafish mutations that reveal single genes essential for normal development of the cardiovascular system. These single gene mutations disrupt specific aspects of rate, rhythm, conduction, or contractility of the developing heart. C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Fishman, MC (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, 149th 13th St, Charlestown, MA 02129 USA. NR 78 TC 49 Z9 53 U1 1 U2 6 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD JUL PY 1998 VL 275 IS 1 BP H1 EP H7 PG 7 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA ZX213 UT WOS:000074490700001 PM 9688889 ER PT J AU Elman, I Adler, CM Malhotra, AK Bir, C Pickar, D Breier, A AF Elman, I Adler, CM Malhotra, AK Bir, C Pickar, D Breier, A TI Effect of acute metabolic stress on pituitary-adrenal axis activation in patients with schizophrenia SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID DEXAMETHASONE SUPPRESSION TEST; PSYCHIATRIC-PATIENTS; VOLUNTEERS; STATE AB Objective: Although several lines of evidence suggest that stress plays a role in the course of schizophrenia, studies that have assessed stress-relevant neurobiological measures have not produced consistent results. The authors examined the effects of acute metabolic stress induced by 2-deoxy-D-glucose (2-DG) on pituitary-adrenal axis activation. Method: Thirteen patients with schizophrenia and 11 healthy comparison subjects were administered pharmacological doses of 2-DG (40 mg/kg). The subjects' arterial plasma was then assayed for levels of adrenocorticotropic hormone (ACTH) and cortisol. Results: 2-DG induced significant increases in the measured hormones in both groups, and ACTH elevations were significantly greater in patients with schizophrenia than in comparison subjects. Conclusions: Patients with schizophrenia have an exaggerated ACTH response to acute metabolic stress exposure. C1 NIMH, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Elman, I (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, W End House,16 Blossom St, Boston, MA 02114 USA. NR 19 TC 55 Z9 56 U1 0 U2 1 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JUL PY 1998 VL 155 IS 7 BP 979 EP 981 PG 3 WC Psychiatry SC Psychiatry GA ZX603 UT WOS:000074534800026 PM 9659871 ER PT J AU Woodin, MA Hauser, R Liu, YC Smith, TJ Siegel, PD Lewis, DM Tollerud, DJ Christiani, DC AF Woodin, MA Hauser, R Liu, YC Smith, TJ Siegel, PD Lewis, DM Tollerud, DJ Christiani, DC TI Molecular markers of acute upper airway inflammation in workers exposed to fuel-oil ash SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID PLASMA-MASS-SPECTROMETRY; NASAL AB Biomarkers in nasal lavage (NL) fluid may be useful in determining the presence and severity of upper airway inflammation. We studied 18 boilermakers overhauling a large, oil-fired boiler and 11 utility workers who served as controls for 6 wk. NL was performed before (NL1), during (NL2), and after (NL3) the overhaul. We measured nasal fluid levels of interleukins 6 (IL-6) and 8 (IL-8), eosinophilic cationic protein (ECP), and myeloperoxidase (MPO) as markers of response to fuel-oil ash exposure. In boilermakers, MPO was elevated during boiler work versus preboiler work (mean = 33.8 versus 22.7 ng/ml, p < 0.05), and at the 2-wk postexposure lavage (NL3) it had declined to 24.2 ng/ml (p = 0.08). Mean IL-8 levels increased in boilermakers between NL1 and NL2 (mean = 83.8 versus 134.8 pg/ml, p < 0.05), then decreased at NL3 (mean = 134.8 versus 89.0 pg/ml, p < 0.05). Nasal fluid vanadium increased in boilermakers between NL1 and NL2 (median < 1.0 versus 4.7 ppb, respectively, p < 0.05), then decreased at NL3 (median, 4.7 versus < 1.0 ppb, respectively, p < 0.05). Levels of IL-6 and ECP did not change significantly during the study. Utility workers showed no significant change in any marker during the study period. Particulate matter < 10 mu m (PM10) levels were higher for boilermakers than for utility workers before boiler work (geometric mean (GM) = 0.40 versus 0.10 mg/m(3), p < 0.05). This difference was more significant during boiler work (GM = 0.47 versus 0.13 mg/m(3), p < 0.001). Ozone levels were low during the study. These data suggest that exposure to fuel-oil ash results in acute upper airway inflammation, potentially mediated by increased IL-8 levels and the recruitment and activation of polymorphonuclear leukocytes. These changes were associated with significantly increased PM10 levels and concentrations of upper airway vanadium. C1 Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Pulm & Crit Care Unit, Boston, MA USA. NIOSH, Div Resp Dis Studies, Morgantown, WV 26505 USA. Allegheny Univ Hlth Sci, Ctr Environm & Occupat Hlth, Philadelphia, PA 19102 USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, 665 Huntington Ave, Boston, MA 02115 USA. FU NIEHS NIH HHS [ES-07069, ES-00002, ES-05947] NR 22 TC 42 Z9 42 U1 0 U2 1 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD JUL PY 1998 VL 158 IS 1 BP 182 EP 187 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA ZZ451 UT WOS:000074730700030 PM 9655727 ER PT J AU Feig, SA D'Orsi, CJ Hendrick, RE Jackson, VP Kopans, DB Monsees, B Sickles, EA Stelling, CB Zinninger, M Wilcox-Buchalla, P AF Feig, SA D'Orsi, CJ Hendrick, RE Jackson, VP Kopans, DB Monsees, B Sickles, EA Stelling, CB Zinninger, M Wilcox-Buchalla, P TI American College of Radiology guidelines for breast cancer screening SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Editorial Material ID AGED 40-49 YEARS; MORTALITY REDUCTION; COST-EFFECTIVENESS; SELF-EXAMINATION; FAMILY HISTORY; RISK-FACTORS; WOMEN; MAMMOGRAPHY; STRATEGIES; BENEFIT C1 Jefferson Univ Hosp, Breast Imaging Ctr, Dept Radiol, Philadelphia, PA 19107 USA. Univ Massachusetts, Med Ctr, Dept Radiol, Worcester, MA 01605 USA. Univ Colorado, Hlth Sci Ctr, Dept Radiol, Denver, CO 80262 USA. Indiana Univ, Sch Med, Dept Radiol, Indianapolis, IN 46202 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Edward Mallinckrodt Inst Radiol, St Louis, MO 63110 USA. Univ Calif San Francisco, Med Ctr, Dept Radiol, San Francisco, CA 94143 USA. Univ Texas, MD Anderson Cancer Ctr, Dept Diagnost Radiol, Houston, TX 77030 USA. Amer Coll Radiol, Reston, VA 22095 USA. RP Feig, SA (reprint author), Jefferson Univ Hosp, Breast Imaging Ctr, Dept Radiol, 1100 Walnut St, Philadelphia, PA 19107 USA. NR 61 TC 107 Z9 111 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JUL PY 1998 VL 171 IS 1 BP 29 EP 33 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZV302 UT WOS:000074291000007 PM 9648758 ER PT J AU Whitman, GJ Kopans, DB McCarthy, KA Stelling, CB Sneige, N Sunku, K Weiss, MK AF Whitman, GJ Kopans, DB McCarthy, KA Stelling, CB Sneige, N Sunku, K Weiss, MK TI Coaxial core needle biopsy under mammographic guidance: Indications and applications SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Roentgen-Ray-Society 98th CY APR 26-MAY 01, 1998 CL SAN FRANCISCO, CALIFORNIA SP Amer Roentgen Ray Soc ID BREAST BIOPSY; ACCURACY C1 Univ Texas, MD Anderson Cancer Ctr, Dept Diagnost Radiol, Houston, TX 77030 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Texas, MD Anderson Cancer Ctr, Div Pathol, Houston, TX 77030 USA. Albany Med Sch, Albany, NY 12208 USA. RP Whitman, GJ (reprint author), Univ Texas, MD Anderson Cancer Ctr, Dept Diagnost Radiol, Box 57,1515 Holcombe Blvd, Houston, TX 77030 USA. NR 9 TC 3 Z9 3 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JUL PY 1998 VL 171 IS 1 BP 67 EP 70 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZV302 UT WOS:000074291000015 PM 9648766 ER PT J AU Kaufman, JA McCarter, D Geller, SC Waltman, AC AF Kaufman, JA McCarter, D Geller, SC Waltman, AC TI Two-dimensional time-of-flight MR angiography of the lower extremities: Artifacts and pitfalls SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID INTENSITY C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. RP Kaufman, JA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 32 Fruit St, Boston, MA 02114 USA. NR 8 TC 30 Z9 30 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JUL PY 1998 VL 171 IS 1 BP 129 EP 135 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZV302 UT WOS:000074291000025 PM 9648776 ER PT J AU Callahan, RJ Bogdanov, A Fischman, AJ Brady, TJ Weissleder, R AF Callahan, RJ Bogdanov, A Fischman, AJ Brady, TJ Weissleder, R TI Preclinical evaluation and phase I clinical trial of a Tc-99m-labeled synthetic polymer used in blood pool imaging SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID HUMAN-SERUM-ALBUMIN; POLYETHYLENE-GLYCOL; COVALENT ATTACHMENT; L-LYSINE; CELLS; INVIVO; TC-99M; CARBOXYMETHYLCELLULOSE; VISUALIZATION; SCINTIGRAPHY AB OBJECTIVE. To obtain initial data on the safety and efficacy of a novel polymeric, synthetic blood pool contrast agent {O-monomethoxypoly(ethylene glycol)-O'-succinyl}poly(N-epsilon-L-lysyl{Tc-99m}diethylenetriamine pentaacetate monoamide, we performed a preclinical evaluation and phase 1 clinical trial under an investigator-sponsored investigational new drug application. MATERIALS AND METHODS. Methoxypoly(ethylene glycol)ethylenetriaminopentaacetic acid was formulated into a kit containing the polymer, stannous chloride, and a buffer. Kits were stored in frozen form for subsequent labeling with technetium-99m. Acute and subacute toxicity studies were carried out in rats and rabbits. Healthy human volunteers (n = 6) were then enrolled in a prospective, open-label phase 1 clinical study. RESULTS. Animal studies showed no signs of acute or subacute toxicity at doses 280 times the proposed dose for humans. In the clinical trial with humans, no significant abnormalities of laboratory values, ECG findings, or hemodynamic parameters were seen. One volunteer experienced facial flushing and palpitations. Four volunteers showed typical blood pool biodistribution, with a blood half-life of 20.6 +/- 2.3 hr.At 24 hr after administration, 22.1% +/- 2.5% of the injected dose had been excreted through the kidneys. Two other volunteers showed a different biodistribution (primarily to liver and spleen), presumably associated with labeling instability. CONCLUSION. Synthetic methoxypoly(ethylene glycol)-grafted polymers can have long circulation times in humans. Pharmaceuticals based on such polymers are expected to have clinical applications in cardiovascular imaging, gastrointestinal bleeding studies, and capillary leak imaging. C1 Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med, Bldg 149,13th St,5403, Charlestown, MA 02129 USA. NR 34 TC 40 Z9 41 U1 0 U2 4 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JUL PY 1998 VL 171 IS 1 BP 137 EP 143 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZV302 UT WOS:000074291000026 PM 9648777 ER PT J AU Pena, CS Chew, FS Keel, SB AF Pena, CS Chew, FS Keel, SB TI Posttransplantation lymphoproliferative disorder of the liver SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Chew, FS (reprint author), Massachusetts Gen Hosp, Dept Radiol, 32 Fruit St, Boston, MA 02114 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JUL PY 1998 VL 171 IS 1 BP 192 EP 192 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZV302 UT WOS:000074291000036 PM 9648787 ER PT J AU Boland, GWL Lee, MJ Gazelle, GS Halpern, EF McNicholas, MMJ Mueller, PR AF Boland, GWL Lee, MJ Gazelle, GS Halpern, EF McNicholas, MMJ Mueller, PR TI Characterization of adrenal masses using unenhanced CT: An analysis of the CT literature SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID CHEMICAL-SHIFT; ATTENUATION VALUE; ADENOMAS; BENIGN; DISTINCTION; TUMORS; DIAGNOSIS; ROC AB OBJECTIVE. Unenhanced CT scanning can reliably characterize incidentally detected adrenal masses when observers use density measurements of the adrenal gland. However, controversy exists as to the optimal density threshold required to differentiate benign from malignant lesions. This study attempts to establish a consensus by performing a pooled analysis of data found in the CT Literature. MATERIALS AND METHODS. Ten CT reports were analyzed, from which individual adrenal lesion density measurements were obtained for 495 adrenal lesions (272 benign lesions and 223 malignant lesions). Threshold analysis generated a range of sensitivities and specificities for lesion characterization at different density thresholds. RESULTS. Sensitivity for characterizing a lesion as benign ranged from 47% at a threshold of 2 H to 88% at a threshold of 20 H. Similarly, specificity varied from 100% at a threshold of 2 H to 84% at a threshold of 20 H. CONCLUSION. The attempt to be absolutely certain that an adrenal lesion is benign may lead to an unacceptably low sensitivity for lesion characterization. The threshold chosen will depend on the patient population and the cost-benefit approach to patient care. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. RP Boland, GWL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. NR 19 TC 313 Z9 334 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JUL PY 1998 VL 171 IS 1 BP 201 EP 204 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZV302 UT WOS:000074291000038 PM 9648789 ER PT J AU Rao, PM Rhea, JT Wittenberg, J Warshaw, AL AF Rao, PM Rhea, JT Wittenberg, J Warshaw, AL TI Misdiagnosis of primary epiploic appendagitis SO AMERICAN JOURNAL OF SURGERY LA English DT Article ID CT FINDINGS; APPENDICITIS; US AB BACKGROUND: The authors determined the radiological misdiagnosis rate of primary epiploic appendagitis (PEA) and its impact on patient management and hospital resource use. METHODS: A total of 660 computed tomography scans performed for clinically suspected diverticulitis (348 cases) or appendicitis (312 cases) were reviewed for cases meeting strict radiological criteria for PEA. Retrospective interpretations were compared with radiological reports. Medical records and hospital cost data were reviewed to estimate impact on patient management and resource use. RESULTS: Eleven scans (2%) met criteria for PEA. Seven scans were initially misdiagnosed as diverticulitis (6 patients) or appendicitis (1 patient). All misdiagnosed patients were hospitalized (mean 4.3 days); 6 received antibiotic therapy. Average cost per patient was $4,117. Four scans were initially correctly diagnosed as PEA. One patient was hospitalized (1 day); none received antibiotic therapy. Average cost per patient was $1,205. CONCLUSIONS: Radiological misdiagnosis of PEA leads to unnecessary hospitalization, medical treatment, and overuse of hospital resources. (C) 1998 by Excerpta Medica, inc. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Rao, PM (reprint author), Massachusetts Gen Hosp, Dept Radiol, 32 Fruit St, Boston, MA 02114 USA. NR 18 TC 49 Z9 52 U1 0 U2 0 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD JUL PY 1998 VL 176 IS 1 BP 81 EP 85 DI 10.1016/S0002-9610(98)00103-2 PG 5 WC Surgery SC Surgery GA 101CM UT WOS:000074852100022 PM 9683140 ER PT J AU Ozdemirli, M Fanburg-Smith, JC Hartmann, DP Shad, AT Lage, JM Magrath, IT Azumi, N Harris, NL Cossman, J Jaffe, ES AF Ozdemirli, M Fanburg-Smith, JC Hartmann, DP Shad, AT Lage, JM Magrath, IT Azumi, N Harris, NL Cossman, J Jaffe, ES TI Precursor B-lymphoblastic lymphoma presenting as a solitary bone tumor and mimicking Ewing's sarcoma - A report of four cases and review of the literature SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE lymphoblastic lymphoma; bone; Ewing's sarcoma; CD79a; CD99 ID POLYMERASE CHAIN-REACTION; NON-HODGKINS LYMPHOMA; ROUND-CELL TUMOR; MALIGNANT-LYMPHOMA; EXPRESSING CYTOKERATIN; NEUROECTODERMAL TUMOR; GENE REARRANGEMENTS; NON-T; DIAGNOSIS; LEUKEMIA AB Precursor B-lymphoblastic lymphoma (B-LBL) may present as a solitary bone tumor. Fewer than 10 cases with a proven precursor B-cell phenotype have been reported in the English literature. In this report, we describe four cases of B-lymphoblastic lymphoma presenting as a localized intraosseous mass, which clinically and histologically mimicked Ewing's sarcoma. Three tumors occurred in the tibia and one in the humerus. In all four cases, the initial diagnosis was either "Ewing's sarcoma" or "consistent with Ewing's sarcoma." All four patients were female. Three were children and one was an adult; mean age was 12.5 years (range, 4 to 31 years). All had extremity pain without significant constitutional symptoms. In three cases, the tumors were osteolytic on radiographic evaluation, and in one case, osteosclerotic. Immunohistochemical stains on paraffin-embedded tissue showed that the neoplastic cells expressed terminal deoxynucleotidyl transferase, CD43, vimentin, and CD99 (MIC2 gene product) in all cases. Three cases were negative for CD45. CD79a was positive in all four cases studied; however, CD20 (L26) was positive in only two of four cases. CD3 was negative in all cases. Two cases showed focal granular cytoplasmic staining for keratin. Two cases analyzed by polymerase chain reaction (PCR) revealed clonal rearrangement of the immunoglobulin heavy chain (IgH) gene. Follow-up revealed that the three pediatric patients, who received a high-dose multiagent chemotherapy regime for LBL, are disease free at follow-up intervals of more than 1, 11, and 12 years, respectively. The adult patient died two years after diagnosis with disseminated disease. Although rare, B-lymphoblastic lymphoma should be considered in the differential diagnosis of small round cell tumors of bone. A diagnosis of Ewing's sarcoma should be made only after complete immunophenotyping and, if necessary, molecular diagnostic tests to exclude lymphoblastic lymphoma. A Limited panel of antibodies can lead to an erroneous diagnosis; B-lymphoblastic lymphoma may be negative for CD45 and CD20 but positive for CD99 and even for keratin, mimicking Ewing's sarcoma. Correct diagnosis is extremely important because LBL usually is curable in the pediatric age group with appropriate therapy. C1 Georgetown Univ, Med Ctr, Dept Pathol, Washington, DC 20007 USA. Georgetown Univ, Med Ctr, Dept Pediat, Washington, DC 20007 USA. Armed Forces Inst Pathol, Washington, DC 20306 USA. Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NCI, Pediat Branch, NIH, Bethesda, MD 20892 USA. RP Azumi, N (reprint author), Georgetown Univ, Med Ctr, Dept Pathol, 3900 Reservoir Rd NW, Washington, DC 20007 USA. NR 49 TC 62 Z9 64 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD JUL PY 1998 VL 22 IS 7 BP 795 EP 804 DI 10.1097/00000478-199807000-00002 PG 10 WC Pathology; Surgery SC Pathology; Surgery GA ZY335 UT WOS:000074610100002 PM 9669342 ER PT J AU Young, RH Hart, WR AF Young, RH Hart, WR TI Metastatic intestinal carcinomas simulating primary ovarian clear cell carcinoma and secretory endometrioid carcinoma - A clinicopathologic and immunohistochemical study of five cases SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE ovary; metastasis; clear cell adenocarcinoma; secretory endometrioid carcinoma; immunohistochemistry; neoplasms ID ALPHA-FETOPROTEIN; CARCINOEMBRYONIC ANTIGEN; DIFFERENTIAL-DIAGNOSIS; MONOCLONAL-ANTIBODIES; MUCINOUS TUMORS; ADENOCARCINOMAS; VARIANT; COLON; CYTOKERATIN-20; KERATIN-7 AB Five cases of ovarian metastases of intestinal adenocarcinomas that suggested the diagnosis of clear cell adenocarcinoma or the secretory variant of endometrioid carcinoma of the ovary are reported. Patient age ranged from 27 to 71 years at the time of diagnosis of the ovarian neoplasms. In four, the ovarian and intestinal tumors were discovered synchronously, and, in the fifth, the ovarian metastasis occurred 1 year after the intestinal primary was diagnosed. The ovarian tumors were unilateral in three patients and bilateral in two. They were up to 18 cm (mean, 12 cm) in maximum dimension and were characterized on microscopic evaluation by glands and cysts lined by cells whose most striking feature was abundant clear cytoplasm. In two cases, striking subnuclear or supranuclear vacuoles were present. An important clue to the diagnosis of metastatic intestinal adenocarcinoma was the presence in all cases of "dirty necrosis." The metastatic nature of the ovarian tumors was supported by the immunohistochemical findings. All tumors stained were strongly positive for carcinoembryonic antigen and cytokeratin 20 and failed to stain for CA125, whereas staining for HAM56 and cytokeratin 7 was absent or only focally positive in one case each. Three intestinal primary tumors involved the small bowel. Microscopic evaluation of the intestinal tumors in three cases and metastases in a fourth, in which the intestinal primary was not resected, showed the features of the uncommon clear cell variant of intestinal adenocarcinoma; the fifth was predominantly a conventional intestinal adenocarcinoma with only a focal clear cell component. Although intestinal adenocarcinomas metastatic in the ovary typically simulate endometrioid adenocarcinoma of the usual type or mucinous adenocarcinoma, they may mimic either primary clear cell adenocarcinoma or the secretory variant of endometrioid adenocarcinoma, particularly when the primary tumor is, even focally, the clear cell variant of intestinal adenocarcinoma. C1 Massachusetts Gen Hosp, Dept Pathol, James Homer Wright Pathol Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Cleveland Clin Fdn, Div Pathol, Dept Anat Pathol, Cleveland, OH 44195 USA. Cleveland Clin Fdn, Lab Med, Cleveland, OH 44195 USA. RP Young, RH (reprint author), Massachusetts Gen Hosp, Dept Pathol, James Homer Wright Pathol Labs, Boston, MA 02114 USA. NR 42 TC 36 Z9 36 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD JUL PY 1998 VL 22 IS 7 BP 805 EP 815 DI 10.1097/00000478-199807000-00003 PG 11 WC Pathology; Surgery SC Pathology; Surgery GA ZY335 UT WOS:000074610100003 PM 9669343 ER PT J AU Weir, MM Bell, DA Young, RH AF Weir, MM Bell, DA Young, RH TI Grade 1 peritoneal serous carcinomas - A report of 14 cases and comparison with 7 peritoneal serous psammocarcinomas and 19 peritoneal serous borderline tumors SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE peritoneum; low-grade serous carcinoma; serous borderline tumor; psammocarcinoma ID SURFACE PAPILLARY CARCINOMA; OVARY; ADENOCARCINOMA; IMPLANTS; OOPHORECTOMY; MALIGNANCY; WOMEN; WOMAN AB Low-grade peritoneal serous carcinomas have been the subject of limited study, and their distinction from peritoneal serous psammocarcinomas and serous borderline tumors is not always easy. The clinicopathologic features of 14 low-grade serous carcinomas, 7 psammocarcinomas, and 19 serous borderline tumors of peritoneal origin were compared. Average ages were 58 years (low-grade serous carcinomas), 48 years (borderline tumors), and 40 years (psammocarcinomas). Typical clinical presentations were abdominal pain, abdominal mass, or both, with the tumors incidental in 37% (borderline tumors), 43% (psammocarcinomas), and 36% (low-grade serous carcinoma). Operative and gross findings varied from nodules to adhesions to a dominant mass. Treatment was surgical debulking in most cases, with biopsy alone for eight borderline tumors. Seven patients with low-grade serous carcinoma were alive when last seen, but follow-up duration is short (average, 1.2 years): five were without disease, one had recurrent disease and one persistent disease. One patient with serous carcinoma died of disease at 3.5 years, and two patients died of other causes. Three patients with psammocarcinoma were alive without disease (average 3.3 years). Fourteen patients with borderline tumors were alive (average 3 years): 10 were without disease, 2 had persistent disease, and serous carcinoma developed in 2. The low-grade serous carcinomas resembled the invasive implants of ovarian serous borderline tumors, lacked high-grade nuclear atypia, showed tissue, lymphovascular space invasion, or both and had appreciable solid epithelial proliferation. Some serous carcinomas showed abundant psammomatous calcification suggesting psammocarcinoma but had too much epithelial proliferation for that diagnosis. The psammocarcinomas showed at least 75% psammoma bodies, no more than moderate cytological atypia, tissue or lymphovascular space invasion, or both, and rare epithelial proliferation less than 15 cells across. Adequate sampling was necessary to identify invasion, with highest yields of invasive foci in omental samples; individual foci in some cases of carcinoma resembled borderline tumor. The serous borderline tumors resembled the noninvasive implants of ovarian serous borderline tumors, lacked invasion, and did not show nuclear atypia of the degree seen in grade 2 or grade 3 serous carcinoma. Low-grade serous carcinoma, psammocarcinoma, and serous borderline tumors of peritoneal origin share some clinicopathologic features and may be underrecognized at surgery and gross examination. Because of overlapping microscopic patterns, adequate sampling is mandatory to identify small foci of invasion that exclude a borderline tumor and identify significant cellularity that excludes a psammocarcinoma. Conservative therapy is merited for younger women with borderline tumors. Maximum debulking is recommended for bulky symptomatic borderline tumors, low-grade serous carcinoma, and psammocarcinoma. Although short-term outcomes for the carcinomas appear favorable, follow-up is too limited to determine long-term outcomes. C1 Massachusetts Gen Hosp, Dept Pathol, James Homer Wright Pathol Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Weir, MM (reprint author), Massachusetts Gen Hosp, Dept Pathol, James Homer Wright Pathol Labs, Fruit St, Boston, MA 02114 USA. NR 38 TC 41 Z9 42 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD JUL PY 1998 VL 22 IS 7 BP 849 EP 862 DI 10.1097/00000478-199807000-00007 PG 14 WC Pathology; Surgery SC Pathology; Surgery GA ZY335 UT WOS:000074610100007 PM 9669347 ER PT J AU Deutsch, JC AF Deutsch, JC TI Spontaneous hydrolysis and dehydration of dehydroascorbic acid in aqueous solution SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID L-ASCORBIC-ACID; VITAMIN-C; DEGRADATION; CHROMATOGRAPHY; PRODUCTS; CATALASE; PLASMA AB The interaction of water with dehydroascorbic acid was examined by incubating dehydroascorbic acid and ascorbic acid in O-18-labeled water for various amounts of time and then oxidizing the products with hydrogen peroxide or reducing the products with mercaptoethanol, with analysis by gas chromatography mass spectrometry. Based on mass changes, dehydroascorbic acid readily exchanged three oxygen atoms with (H2O)-O-18. When mercaptoethanol was used to reduce dehydroascorbic acid (which had been incubated in (H2O)-O-18) to ascorbic acid, the newly formed ascorbic acid also contained three labeled oxygen atoms. However, ascorbic acid incubated in (H2O)-O-18 for the same amount of time under identical conditions exchanged only two labeled oxygen atoms. Electron impact mass spectrometry of derivatized ascorbic acid created a decarboxylation product which had only two labeled oxygen atoms, regardless if 3-oxygen-labeled or 2-oxygen-labeled ascorbic acid was the parent compound, isolating the extra oxygen addition to carbon 1. These data suggest that dehydroascorbic acid spontaneously hydrolyzes and dehydrates in aqueous solution and that the hydrolytic-hydroxyl oxygen is accepted by carbon 1, Ascorbic acid, on the other hand, does not show this same tendency to hydrolyze. (C) 1998 Academic Press. C1 Univ Colorado, Hlth Sci Ctr, Dept Med, Div Gastroenterol, Denver, CO 80262 USA. Denver VAH, Denver, CO 80262 USA. RP Deutsch, JC (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Med, Div Gastroenterol, 4200 E 9th Ave,Campus Box B-170, Denver, CO 80262 USA. NR 25 TC 50 Z9 50 U1 2 U2 12 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD JUL 1 PY 1998 VL 260 IS 2 BP 223 EP 229 DI 10.1006/abio.1998.2700 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA ZZ723 UT WOS:000074760700016 PM 9657882 ER PT J AU Kohane, DS Yieh, J Lu, NT Langer, R Strichartz, GR Berde, CB AF Kohane, DS Yieh, J Lu, NT Langer, R Strichartz, GR Berde, CB TI A re-examination of tetrodotoxin for prolonged duration local anesthesia SO ANESTHESIOLOGY LA English DT Article; Proceedings Paper CT 1997 Annual Meeting of American-Society-of-Anesthesiologists CY OCT 18-23, 1997 CL SAN DIEGO, CALIFORNIA SP Amer Soc Anesthesiologists DE bupivacaine; epinephrine; toxicity ID NERVE BLOOD-FLOW; SODIUM-CHANNELS; SYSTEMIC TOXICITY; CONSCIOUS DOG; BUPIVACAINE; LIDOCAINE; SAXITOXIN; BLOCKADE; RAT; PHARMACOLOGY AB Background: Highly potent toxins such as tetrodotoxin that block sodium channels with great specificity have been studied for many years and can provide prolonged blockade when coadministered with vasoconstrictors or conventional local anesthetics. Their utility has been constrained, however, by systemic toxicity. The authors examined the efficacy of tetrodotoxin with and without epinephrine or bupivacaine for producing prolonged-duration sciatic nerve blockade in the rat, and they assessed the degree of concomitant toxicity, Methods: Rats received percutaneous sciatic nerve blockade using tetrodotoxin with and without epinephrine or bupivacaine. A subset received subcutaneous injections at the nuchal midline, Nociceptive, proprioceptive, and motor blockade were quantified using contralateral leg responses as controls for systemic effects. Results: Tetrodotoxin without epinephrine produced sciatic nerve blockade, but with considerable toxicity at most effective doses. Epinephrine reduced the median effective concentration of tetrodotoxin for nociception from 37.6 to 11.5 mu M and prolonged its duration, such that reversible blocks lasting >13 h were achieved. Epinephrine reduced measures of systemic distribution and increased the median lethal dose of tetrodotoxin from 40 to 53.6 nmole/kg, thus more than quadrupling the therapeutic index. Bupivacaine increased the local anesthetic potency of tetrodotoxin, reduced its systemic toxicity, and, when coinjected subcutaneously, increased the median lethal dose from 43.7 to 47.7 nmole/kg, The addition of epinephrine did not further improve the effectiveness of the bupivacaine-tetrodotoxin combination. Conclusion: Combinations of epinephrine or bupivacaine with tetrodotoxin or with other high-potency toxins active on sodium channels should be examined for the potential to provide clinically useful, prolonged nerve blockade. C1 Childrens Hosp, Dept Anesthesia, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. MIT, Boston, MA USA. RP Berde, CB (reprint author), Childrens Hosp, Dept Anesthesia, 300 Longwood Ave,Farley 306, Boston, MA 02115 USA. FU NIGMS NIH HHS [GM 35647] NR 35 TC 71 Z9 72 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD JUL PY 1998 VL 89 IS 1 BP 119 EP 131 DI 10.1097/00000542-199807000-00019 PG 13 WC Anesthesiology SC Anesthesiology GA ZZ252 UT WOS:000074710800018 PM 9667302 ER PT J AU Li, G Kawamura, K Barrance, P Chao, EYS Kaufman, K AF Li, G Kawamura, K Barrance, P Chao, EYS Kaufman, K TI Prediction of muscle recruitment and its effect on joint reaction forces during knee exercises SO ANNALS OF BIOMEDICAL ENGINEERING LA English DT Article DE knee model; muscle force; joint dynamics; inverse dynamics; optimization ID PHYSIOLOGICAL PREDICTION; ISOKINETIC EXERCISE; EXTENSION; REHABILITATION; MUSCULATURE; FLEXION; MODEL; HIP AB This study examined the hypothesis that muscle recruitment of the tibiofemoral joint and joint reaction forces during isometric and isokinetic exercises depends on the existing degrees of freedom of the knee and the direction and type of external load applied during exercise. When three-dimensional knee joint rotation was considered (three degrees of freedom), antagonistic muscle activities were predicted using an inverse dynamic problem formulation and muscle modeling optimization procedures. The results showed that the antagonistic activities of flexors during knee flexion/extension exercise increased the joint compressive forces and decreased the anterior tibial shear forces. Comparison of different knee joint modeling assumptions indicated that modeling a single degree of freedom in flexion/extension for the knee will underestimate the antagonistic muscle function. (C) 1998 Biomedical Engineering Society. C1 Johns Hopkins Univ, Orthopaed Biomech Lab, Baltimore, MD USA. Univ Pittsburgh, Musculoskeletal Res Ctr, Pittsburgh, PA USA. Mayo Clin & Mayo Fdn, Orthopaed Biomech Lab, Rochester, MN 55905 USA. RP Li, G (reprint author), Harvard Univ, Sch Med, BIDMC, Orthopaed Biomech Lab, 330 Brookline Ave,RN 115, Boston, MA 02215 USA. OI Kaufman, Kenton/0000-0002-7311-3781 FU NCI NIH HHS [CA23751, CA40583] NR 32 TC 22 Z9 23 U1 0 U2 2 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0090-6964 J9 ANN BIOMED ENG JI Ann. Biomed. Eng. PD JUL-AUG PY 1998 VL 26 IS 4 BP 725 EP 733 DI 10.1114/1.104 PG 9 WC Engineering, Biomedical SC Engineering GA ZV306 UT WOS:000074291400021 PM 9662164 ER PT J AU Kwiatkowska, J Jozwiak, S Hall, F Henske, EP Haines, JL McNamara, P Braiser, J Wigowska-Sowinska, J Kasprzyk-Obara, J Short, MP Kwiatkowski, DJ AF Kwiatkowska, J Jozwiak, S Hall, F Henske, EP Haines, JL McNamara, P Braiser, J Wigowska-Sowinska, J Kasprzyk-Obara, J Short, MP Kwiatkowski, DJ TI Comprehensive mutational analysis of the TSC1 gene: observations on frequency of mutation, associated features, and nonpenetrance SO ANNALS OF HUMAN GENETICS LA English DT Article ID TUBEROUS SCLEROSIS COMPLEX; DIAGNOSTIC-CRITERIA; CHROMOSOME 9Q34; HETEROZYGOSITY; HAMARTOMAS; FAMILIES; DISEASE; AUTISM; 16P13 AB We performed a comprehensive analysis for mutations in the TSC1 gene using Southern blot analysis, and SSCP and heteroduplex analysis of amplified exons in 13 families with genetic linkage to the TSC1 region, 22 small families without linkage information, and 126 sporadic patients. 17 unique mutations were identified in 21 patients. Mutations were found in 7/13 (54%) TSC1-linked families, 1/22 (5%) small families without linkage, and 13 of 126 (10%) sporadic cases. The mutations were all chain-terminating with 14 small deletions, 1 small insertion, and 6 nonsense mutations. In families with mutations, all individuals carrying a mutation met formal diagnostic criteria for TSC, apart from a 3-year-old girl who had inherited a deletion mutation, and who had no seizures, normal intelligence, normal abdominal ultrasound, and hypomelanotic macules only on physical exam. We assessed the incidence and severity of mental retardation in the 13 sporadic patients with TSC1 mutations versus the entire sporadic cohort, and found no significant difference. The observations indicate that TSC1 mutations are all inactivating, suggest that TSC1 disease occurs in only 15-20 % of the sporadic TSC population, and demonstrate that presymptomatic TSC does occur. C1 Brigham & Womens Hosp, Div Expt Med & Med Oncol, Boston, MA 02115 USA. Childrens Mem Hosp, Dept Child Neurol, Warsaw, Poland. Vanderbilt Univ, Genet Program, Nashville, TN USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA USA. Univ Med Sci, Dept Dev Neurol, Poznan, Poland. Amer Med Assoc, Chicago, IL 60610 USA. RP Kwiatkowski, DJ (reprint author), Brigham & Womens Hosp, Div Expt Med & Med Oncol, 221 Longwood Ave, Boston, MA 02115 USA. EM kwiatkowski@calvin.harvard.edu RI Haines, Jonathan/C-3374-2012; Jura, Jolanta/F-8889-2015 FU NINDS NIH HHS [NS 24279, NS 31535] NR 29 TC 34 Z9 36 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0003-4800 EI 1469-1809 J9 ANN HUM GENET JI Ann. Hum. Genet. PD JUL PY 1998 VL 62 BP 277 EP 285 DI 10.1046/j.1469-1809.1998.6240277.x PN 4 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 159WE UT WOS:000078197700001 PM 9924605 ER PT J AU Shekelle, PG Courter, I Hurwitz, EL Genovese, B Adams, AH Mior, SA Brook, RH AF Shekelle, PG Courter, I Hurwitz, EL Genovese, B Adams, AH Mior, SA Brook, RH TI Congruence between decisions to initiate chiropractic spinal manipulation for low back pain and appropriateness criteria in North America SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE low back pain; spine; chiropractic; manipulation, orthopedic; quality of health care ID RANDOMIZED CLINICAL-TRIAL; NEW-YORK-STATE; BYPASS GRAFT-SURGERY; CORONARY-ANGIOGRAPHY; NECK COMPLAINTS; MANUAL THERAPY; CAROTID ENDARTERECTOMY; OUTCOME MEASURES; PERSISTENT BACK; FOLLOW-UP AB Background: Recent U.S. practice guidelines recommend spinal manipulation for some patients with low back pain. If followed, these guidelines are likely to increase the number of persons referred for chiropractic care. Concerns have been raised about the appropriate use of chiropractic care, but systematic data are lacking. Objective: To determine the appropriateness of chiropractors' decisions to use spinal manipulation for patients with low back pain. Design: Retrospective review of chiropractic office records against preset criteria for appropriateness that were developed from a systematic review of the literature and a nine-member panel of chiropractic and medical specialists. Appropriateness criteria reflect the expected balance between risk and benefit. Setting: 131 of 185 (71%) chiropractic offices randomly sampled from sites in the United States and Canada. Patients: 10 randomly selected records of patients presenting with low back pain from each office (1310 patients total). Measurements: Sociodemographic data on patients and chiropractors; use of health care services by patients; assessment of the decision to initiate spinal manipulation as appropriate, uncertain, or inappropriate. Results: Of the 1310 patients who sought chiropractic care for low back pain, 1088 (83%) had spinal manipulation. For 859 of these patients (79%), records contained data sufficient to determine whether care was congruent with appropriateness criteria. Care was classified as appropriate in 46% of cases, uncertain in 25% of cases, and inappropriate in 29% of cases. Patients who did not undergo spinal manipulation were less likely to have a presentation judged appropriate and were more likely to have a presentation judged inappropriate than were patients who did undergo spinal manipulation (P = 0.01). Conclusions: The proportion of chiropractic spinal manipulation judged to be congruent with appropriateness criteria is similar to proportions previously described for medical procedures; thus, the findings provide some reassurance about the appropriate application of chiropractic care. However, more than one quarter of patients were treated for indications that were judged inappropriate. The number of inappropriate decisions to use chiropractic spinal manipulation should be decreased. C1 Rand Corp, Santa Monica, CA 90401 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Los Angeles Coll Chiropract, Whittier, CA 90609 USA. Canadian Mem Chiropract Coll, Toronto, ON M4G 3E6, Canada. RP Shekelle, PG (reprint author), Rand Corp, 1700 Main St,POB 2138, Santa Monica, CA 90401 USA. NR 50 TC 25 Z9 25 U1 0 U2 5 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JUL 1 PY 1998 VL 129 IS 1 BP 9 EP + PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA ZX413 UT WOS:000074513300002 PM 9653012 ER PT J AU Grinspoon, S Corcoran, C Askari, H Schoenfeld, D Wolf, L Burrows, B Walsh, M Hayden, D Parlman, K Anderson, E Basgoz, N Klibanski, A AF Grinspoon, S Corcoran, C Askari, H Schoenfeld, D Wolf, L Burrows, B Walsh, M Hayden, D Parlman, K Anderson, E Basgoz, N Klibanski, A TI Effects of androgen administration in men with the AIDS wasting syndrome - A randomized, double-blind, placebo-controlled trial SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE HIV wasting syndrome; acquired immunodeficiency syndrome; hypergonadism; testosterone; body composition ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; MEGESTROL-ACETATE; BODY-COMPOSITION; HYPOGONADAL MEN; MUSCLE MASS; LEAN BODY; TESTOSTERONE; DISORDERS; CACHEXIA; HORMONE AB Background: Development of successful anabolic strategies to reverse the loss of lean body mass is of critical importance to increase survival in men with the AIDS wasting syndrome. Hypogonadism, an acquired endocrine deficiency state characterized by loss of testosterone, occurs in more than half of all men with advanced HIV disease. It is unknown whether testosterone deficiency contributes to the profound catabolic state and loss of lean body mass associated with the AIDS wasting syndrome. Objective: To investigate the effects of physiologic testosterone administration on body composition, exercise functional capacity, and quality of life in androgen-deficient men with the AIDS wasting syndrome. Design: Randomized, double-blind, placebo-controlled study. Setting: University medical center. Patients: 51 HIV-positive men (age 42 +/- 8 years) with wasting (body weight < 90% of ideal body weight or weight loss > 10% of baseline weight) and a free testosterone level less than 42 pmol/L (normal range for men 18 to 49 years of age, 42 to 121 pmol/L [12.0 to 35.0 pg/mL]). Intervention: Patients were randomly assigned to receive testosterone enanthate, 300 mg, or placebo intramuscularly every 3 weeks for 6 months. Measurements: Change in fat-free mass was the primary end point. Secondary clinical end points were weight, lean body mass, muscle mass, exercise functional capacity, and change in perceived quality of life. Virologic variables were assessed by CD4 count and viral load. Results: Compared with patients who received placebo, testosterone-treated patients gained fat-free mass (-0.6 kg and 2.0 kg; P = 0.036), lean body mass (0.0 kg and 1.9 kg; P = 0.041), and muscle mass (-0.8 kg and 2.4 kg; P = 0.005). The changes in weight, fat mass, total-body water content, and exercise functional capacity did not significantly differ between the groups. Patients who received testosterone reported benefit from the treatment (P = 0.036), feeling better (P = 0.033), improved quality of life (P = 0.040), and improved appearance (P = 0.021). Testosterone was well tolerated in all patients. Conclusions: Physiologic testosterone administration increases lean body mass and improves quality of life among androgen-deficient men with the AIDS wasting syndrome. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Boston Vet Affairs Med Ctr, Boston, MA USA. Boston Univ, Med Ctr, Boston, MA USA. Harvard Med Sch, Boston, MA USA. Massachusetts Gen Hosp, Gen Clin Res Ctr, Ctr Biostat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gen Clin Res Ctr, Nutr Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wang Ambulatory Care Ctr 128, Phys Therapy Dept, Boston, MA 02114 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. RP Grinspoon, S (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Bulfinch 457B,55 Fruit St, Boston, MA 02114 USA. FU NCRR NIH HHS [MO1-RR01066]; NIDDK NIH HHS [P32-DK07028, R01-DK49302] NR 39 TC 147 Z9 151 U1 2 U2 6 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JUL 1 PY 1998 VL 129 IS 1 BP 18 EP + PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA ZX413 UT WOS:000074513300003 PM 9652995 ER PT J AU Growdon, JH AF Growdon, JH TI To tap or not to tap: Cerebrospinal fluid biomarkers of Alzheimer's disease SO ANNALS OF NEUROLOGY LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Growdon, JH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. NR 10 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JUL PY 1998 VL 44 IS 1 BP 6 EP 7 DI 10.1002/ana.410440105 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA ZZ257 UT WOS:000074711300003 PM 9667586 ER PT J AU Liedtke, W Cannella, B Mazzaccaro, RJ Clements, JM Miller, KM Wucherpfennig, KW Gearing, AJH Raine, CS AF Liedtke, W Cannella, B Mazzaccaro, RJ Clements, JM Miller, KM Wucherpfennig, KW Gearing, AJH Raine, CS TI Effective treatment of models of multiple sclerosis by matrix metalloproteinase inhibitors SO ANNALS OF NEUROLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; MYELIN BASIC-PROTEIN; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; CENTRAL-NERVOUS-SYSTEM; FACTOR-ALPHA; DEMYELINATING DISEASE; CEREBROSPINAL-FLUID; ADOPTIVE TRANSFER; CLONAL EXPANSION AB The proinflammatory Th1 cytokine, tumor necrosis factor-alpha (TNF alpha), the cell death signaling molecule FasL, and several extracellular matrix degrading metalloproteinases have been implicated in the pathogenesis of multiple sclerosis (MS). The latter enzymes, as web as TNF alpha-converting enzyme and FaL-converting enzyme, can be blocked by matrix metalloproteinase inhibitors (MMPIs). In this study, we show that a potent MMPI was clinically effective in an animal model for MS, experimental autoimmune encephalomyelitis (EAE) in the SJL/J mouse. Efficacy was remarkable, as indicated by blocking and reversal of acute disease and reduced number of relapses and diminished mean cumulative disease score in chronic relapsing animals. Also, demyelination and glial scarring were significantly decreased in MMPI-treated mice with chronic relapsing EAE, as was central nervous system gene expression for TNF alpha. and FaL. It is interesting that expression of the beneficial cytokine interleukin-4 (IL-4) was increased, and IL-4 was expressed on glial cells. The relevance of these compounds for MS was underscored by their ability to specifically inhibit TNF alpha shedding and cytotoxicity of myelin-autoreactive human cytotoxic CD4(+) T-cell clones. This is the first report to show a positive effect by MMPIs on chronic relapsing EAE, its central nervous system cytokine profile, and on TNF alpha shedding by human myelin-autoreactive T cells. C1 Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10467 USA. Albert Einstein Coll Med, Dept Neurol, Bronx, NY 10467 USA. Albert Einstein Coll Med, Dept Neurosci, Bronx, NY 10467 USA. Albert Einstein Coll Med, Dept Microbiol Immunol, Bronx, NY 10467 USA. British Biotechnol Pharmaceut Ltd, Oxford, England. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Liedtke, W (reprint author), Rockefeller Univ, Dept Mol Genet, Howard Hughes Med Inst, 1230 York Ave,Box 305, New York, NY 10021 USA. RI Liedtke, Wolfgang/G-4633-2011 FU NINDS NIH HHS [NS 08952, NS 07098, NS 11920] NR 62 TC 94 Z9 95 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JUL PY 1998 VL 44 IS 1 BP 35 EP 46 DI 10.1002/ana.410440110 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA ZZ257 UT WOS:000074711300008 PM 9667591 ER PT J AU Krings, T Chiappa, KH Cuffin, BN Buchbinder, BR Cosgrove, GR AF Krings, T Chiappa, KH Cuffin, BN Buchbinder, BR Cosgrove, GR TI Accuracy of electroencephalographic dipole localization of epileptiform activities associated with focal brain lesions SO ANNALS OF NEUROLOGY LA English DT Article ID TEMPORAL-LOBE EPILEPSY; IMPLANTED SOURCES; INVERSE SOLUTIONS; QUANTITATIVE MRI; EEG; PROPAGATION; PATTERNS; SURGERY; SPIKES; MEG AB We evaluated the accuracy of an electroencephalographic (EEG) localization technique (dipole inverse solution) in a consecutive series of 12 focal intracerebral lesions of diverse etiologies whose EEGs showed interictal spike activity or rhythmic activity at seizure onset. The calculated equivalent dipole was plotted on three axes in the patients' magnetic resonance image, and the distance between the dipole and the lesion margin was measured assuming that the shell of the lesion constituted an epileptogenic region. In all cases the dipole localized closer than 0.8 cm to the nearest lesion margin. In addition, we compared the postsurgical outcome of 6 patients to the dipole localization and the resection margins. In all 6 patients in whom the dipole, and hence the estimated seizure generator, was removed the surgical outcome was favorable. We conclude that the inverse solution algorithm is a promising method for using the scalp EEG to localize the sources of electrical activity in the human brain in routine clinical electroencephalography and provides three-dimensional data not available from conventional analysis. C1 Massachusetts Gen Hosp, EEG Lab, Neuroradiol Div, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. MIT, Clin Neurophysiol Lab, Serv Neurol, Boston, MA USA. MIT, Francis Bitter Natl Magnet Lab, Boston, MA USA. RP Chiappa, KH (reprint author), Massachusetts Gen Hosp, EEG Lab, Neuroradiol Div, Dept Radiol, Boston, MA 02114 USA. NR 39 TC 39 Z9 42 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JUL PY 1998 VL 44 IS 1 BP 76 EP 86 DI 10.1002/ana.410440114 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA ZZ257 UT WOS:000074711300012 PM 9667595 ER PT J AU Kass, ES Salman, S Montgomery, WW AF Kass, ES Salman, S Montgomery, WW TI Chronic maxillary atelectasis in a child SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article ID SINUS C1 Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Kass, ES (reprint author), NCI, Tumor Immunol & Biol Lab, Bldg 10,Room 8B07,10 Ctr Dr MSC 1750, Bethesda, MD 20892 USA. NR 8 TC 3 Z9 3 U1 0 U2 0 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD JUL PY 1998 VL 107 IS 7 BP 623 EP 625 PG 3 WC Otorhinolaryngology SC Otorhinolaryngology GA 101CW UT WOS:000074852900014 PM 9682860 ER PT J AU Graham, RA Wang, S Catalano, PJ Haller, DG AF Graham, RA Wang, S Catalano, PJ Haller, DG TI Postsurgical surveillance of colon cancer - Preliminary cost analysis of physician examination, carcinoembryonic antigen testing, chest x-ray, and colonoscopy SO ANNALS OF SURGERY LA English DT Article ID POSTOPERATIVE FOLLOW-UP; COLORECTAL-CANCER; CURATIVE RESECTION; HEPATIC RESECTION; RECTUM CANCER; CARCINOMA AB Objective This study is the first to examine the relative and absolute costs of physician examination, carcinoembryonic antigen (CEA) assessment, chest x-ray, and colonoscopy in detecting recurrent disease in patients who have undergone surgical resection for primary colon carcinoma. Methods Of the 1356 Eastern Cooperative Oncology Group patients in Intergroup Protocol 0089 who underwent surgical resection for Dukes' B2 and C colon carcinoma, 421 patients who developed recurrent disease were reviewed. Follow-up testing was performed according to protocol guidelines, with the cost of each test equal to 1995 Medicare reimbursement. Follow-up was defined as the time to recurrence for the 421 patients in whom disease recurred (mean 18.6 months) or up to 5 years for the additional 930 patients in whom disease did not recur (mean 38.6 months). Patients were divided into three categories: nonrecurrent, recurrent but not resectable, and recurrent but resectable with curative intent. The estimated mean cost of each test in detecting group 3 (recurrent but resectable) patients was calculated. Results Of the 421 patients who developed recurrent disease, 96 underwent surgical resection of their disease with curative intent (group 3). For group 3 patients, the first indication of recurrent disease was CEA testing (30), chest x-ray (12), colonoscopy (14), and other (40). Of the 40 "other" patients, 24 presented with symptoms. Routine physician examination, however, failed to identify a single resectable recurrence, and the total cost for physician examination was $418,615. The detection rate for CEA testing was 2.2%, the total cost was $170,880, and the cost per recurrence was $5,696. The detection rate for chest x-ray was 0.9%, the total cost was $120,934, and the cost per recurrence was $10,078. The detection rate of colonoscopy was 1%, the total cost was $641,344, and the cost per recurrence was $45,810. Conclusions CEA measurement was the most cost-effective test in detecting potentially curable recurrent disease. Physician visits were useful only in.the evaluation of symptoms; a routine physician examination had no added benefit. C1 New England Med Ctr, Dept Surg, Boston, MA 02111 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Hosp Univ Penn, Dept Hematol Oncol, Philadelphia, PA 19104 USA. RP Graham, RA (reprint author), 750 Washington St,Box 1043, Boston, MA 02111 USA. FU NCI NIH HHS [CA07190, CA15488, CA23318] NR 23 TC 122 Z9 123 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD JUL PY 1998 VL 228 IS 1 BP 59 EP 63 DI 10.1097/00000658-199807000-00009 PG 5 WC Surgery SC Surgery GA ZZ256 UT WOS:000074711200010 PM 9671067 ER PT J AU Hahn, CW Tam, SKC Vlahakes, GJ Hilgenberg, AD Akins, CW Buckley, MJ AF Hahn, CW Tam, SKC Vlahakes, GJ Hilgenberg, AD Akins, CW Buckley, MJ TI Repeat aortic root replacement SO ANNALS OF THORACIC SURGERY LA English DT Article ID GRAFT REPLACEMENT; COMPOSITE GRAFT; VALVE; HOMOGRAFT; ENDOCARDITIS; EXPERIENCE; OPERATIONS AB Background. Aortic roof replacement in patients who have undergone previous aortic root replacement presents a formidable technical challenge, which may lead to increased surgical mortality. Methods. We reviewed our experience from January 1989 through November 1995, Seven consecutive patients (6 men and 1 woman) underwent eight repeat aortic root replacements. Mean follow-up was 19 months. Previous root replacement had been performed with homograft In 1 patient, with a bioprosthetic valve composite graft in 1 patient, and with a mechanical valve composite graft in 6 patients. The techniques used at the previous procedures were the Cabrol technique (2 patients), Bentall technique (3 patients), and the coronary button technique (3 patients). Reoperation was indicated for pseudoaneurysm formation in 4 patients and for endocarditis in the others. Results. Aortic homografts were implanted in all patients with endocarditis and mechanical valve composite grafts were used in the others. In all reoperations, the coronary button technique was used. No procedures were done emergently. Concomitant procedures were performed in 2 patients, including mitral valve replacement and aortic arch aneurysm repair. One patient had recurrence of his endocarditis 36 months after operation because of continued intravenous drug use requiring a second successful homograft root replacement. There were no early deaths and one late death at 16 months after operation. Conclusions. Repeat aortic root replacement, even in the setting of endocarditis, can be done with low mortality. (Ann Thorac Surg 1998;66:88-91) (C) 1998 by The Society of Thoracic Surgeons. C1 Massachusetts Gen Hosp, Cardiac Surg Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Mt Auburn Hosp, Boston, MA USA. RP Tam, SKC (reprint author), 300 Mt Auburn St,Suite 516, Cambridge, MA 02138 USA. NR 21 TC 25 Z9 25 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD JUL PY 1998 VL 66 IS 1 BP 88 EP 91 DI 10.1016/S0003-4975(98)00352-X PG 4 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 104BH UT WOS:000074992000021 PM 9692444 ER PT J AU Canver, CC Nichols, RD Kroncke, GM AF Canver, CC Nichols, RD Kroncke, GM TI Influence of age-specific lung function on survival after coronary bypass SO ANNALS OF THORACIC SURGERY LA English DT Article ID SURGERY AB Background, Respiratory complications after successful coronary artery bypass grafting influence the immediate recovery of a patient; however, whether they influence the longevity of a patient is largely unknown. The aim of this study was to examine the effects of preoperative pulmonary risk factors in younger patients and older patients on outcome after coronary artery bypass grafting, Methods. A retrospective chart review was performed on 939 patients who underwent primary coronary artery bypass grafting between July 1987 and November 1996. For better comparison, they were arbitrarily divided by age into two groups: group 1, less than 70 years old (n = 710), and group 2, 70 years old or older (n = 229). The variables collected for each patient included history of chronic obstructive pulmonary disease, active smoking, forced expiratory volume, and ventilatory support for more than 48 hours. These variables were compared with postoperative length of stay in the intensive care unit, length of stay in the hospital, and the midterm survival up to 5 years. The data were analyzed by the use of univariate/multivariate log-rank tests and the method of Kaplan-Meier survival estimates. Results. The presence of chronic obstructive pulmonary disease was associated with increased length of stay in the intensive care unit and in the hospital for both groups. Preoperative forced expiratory volume in 1 second, significantly affected length of stay in the hospital only in the patients less than 70 years old (p = 0.0001). Delayed extubation beyond 48 hours of ventilatory support resulted in prolonged length of stay in the intensive care unit and in the hospital for patients less than 70 years old (p = 0.0001, p = 0.0001, respectively) and patients 70 years old or older (p = 0.0001, p = 0.0001, respectively). The 5-year survival after coronary artery bypass grafting for both groups was significantly influenced by the level of preoperative forced expiratory volume in I second (p = 0.0004, p = 0.0282, respectively). Conclusions. Patients with chronic obstructive pulmonary disease, irrespective of age, stay in the intensive care unit and in the hospital longer after coronary artery bypass grafting. In addition, preoperative forced expiratory volume in 1 second is a significant predictor of 5-year survival in the young and aged individuals undergoing coronary artery bypass grafting. (Ann Thorac Surg 1998;66:144-7) (C) 1998 by The Society of Thoracic Surgeons. C1 Univ Wisconsin, Sch Med, William S Middleton Mem Vet Hosp, Sect Cardiothorac Surg, Madison, WI USA. RP Canver, CC (reprint author), Univ Wisconsin, Sch Med, Div Cardiothorac Surg, Ctr Clin Sci, H4-352,600 Highland Ave, Madison, WI 53792 USA. NR 10 TC 25 Z9 26 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD JUL PY 1998 VL 66 IS 1 BP 144 EP 147 DI 10.1016/S0003-4975(98)00322-1 PG 4 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 104BH UT WOS:000074992000032 PM 9692454 ER PT J AU Demmy, TL Krasna, MJ Detterbeck, FC Kline, GG Kohman, LJ DeCamp, MM Wain, JC AF Demmy, TL Krasna, MJ Detterbeck, FC Kline, GG Kohman, LJ DeCamp, MM Wain, JC TI Multicenter VATS experience with mediastinal tumors SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 44th Annual Meeting of the Southern-Thoracic-Surgical-Association CY NOV 06-09, 1997 CL NAPLES, FLORIDA SP So Thorac Surg Assoc ID THORACOSCOPIC RESECTION; IMPLANTATION; CYSTS AB Background. The use of video-assisted thoracic surgery for diagnosis and treatment of mediastinal tumors in a multiinstitution patient population is not well understood. Methods. We studied 48 cases from Cancer and Leukemia Group B thoracic surgeons. Of 21 men and 27 women, aged 41 +/- 16 years, 22 patients were asymptomatic. In the others, 92% of tumor-related symptoms improved or resolved after treatment. Five tumors involved the anterior compartment, 19 the middle, and 24 the posterior compartment. Diagnoses were typical for each compartment but also included uncommon problems such as superior vena cava hemangioma and a histoplasmosis cyst causing hoarseness. Of the lesions, a biopsy of 12 was done without excision and the rest were excised completely. Fifteen were cystic and 10 were malignant (8 biopsy only). Maximal dimensions were 5.2 +/- 3.3 cm. Results. Operations were briefer for 24 posterior (93 +/- 41 min) than 5 anterior (195 +/- 46 min, p < 0.01) or 19 middle mediastinal tumors (170 +/- 78 min, p < 0.01). Although 96% had vital mediastinal relations, only six open conversions were performed because of bleeding (n = 3), large size, impaired exposure, or rib attachments, and no patient had morbidity beyond that expected for the thoracotomy. Postoperative stay was shorter for the nonconversion group (3.2 +/- 2.8 versus 5.5 +/- 2.1 days, p = 0.05), as was chest tube duration (1.7 +/- 1.4 days versus 3.2 +/- 1.9 days, p = 0.03). There were no postoperative deaths or major complications, but 7 patients had minor complications. During a mean of 20 months of surveillance (range, 1 to 52 months), one cyst recurred (asymptomatic) as did one sarcoma that was excised. Conclusions. Video-assisted thoracic surgery is a safe technique for benign mediastinal tumors, typically those in the middle and posterior mediastinum. (Ann Thorac Surg 1998;66:187-92) (C) 1998 by The Society of Thoracic Surgeons. C1 Univ Missouri Hosp & Clin, Div Cardiothorac Surg, Columbia, MO USA. Univ Maryland Hosp, Dept Surg, Baltimore, MD 21201 USA. Univ N Carolina, Dept Surg, Chapel Hill, NC USA. Long Isl Jewish Med Ctr, Dept Surg, Long Isl, NY USA. SUNY Syracuse, Dept Surg, Syracuse, NY USA. Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Demmy, TL (reprint author), Univ Missouri, Div Cardiothorac Surg, 245 Major Hall,Dc119-0, Columbia, MO 65212 USA. NR 15 TC 41 Z9 43 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD JUL PY 1998 VL 66 IS 1 BP 187 EP 192 DI 10.1016/S0003-4975(98)00378-6 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 104BH UT WOS:000074992000042 PM 9692462 ER PT J AU Amado-Cattaneo, R AF Amado-Cattaneo, R TI Combined mitral and aortic homograft valve replacement for acute bacterial endocarditis SO ANNALS OF THORACIC SURGERY LA English DT Article AB Homograft replacement of the aortic valve in cases of acute bacterial endocarditis is considered the ideal choice because of the resistance of the homograft to reinfection. We report a case of aortic and mitral valve bacterial endocarditis, secondary to Streptococcus viridans, with severe aortic and mitral valve regurgitation and hemodynamic instability requiring surgical interventions with the use of aortic and mitral valve homografts. (Ann Thorac Surg 1998;66:267-8). (C) 1998 by The Society of Thoracic Surgeons. C1 Deaconess Med Ctr, Dept Surg, Spokane, WA USA. RP Amado-Cattaneo, R (reprint author), Cardiovasc & Thorac Surg Associates PS, 122 W 7th Ave,Suite440, Spokane, WA 99204 USA. NR 3 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD JUL PY 1998 VL 66 IS 1 BP 267 EP 268 DI 10.1016/S0003-4975(98)00406-8 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 104BH UT WOS:000074992000071 PM 9692485 ER PT J AU Teicher, BA Williams, JI Takeuchi, H Ara, G Herbst, RS Buxton, D AF Teicher, BA Williams, JI Takeuchi, H Ara, G Herbst, RS Buxton, D TI Potential of the aminosterol, squalamine in combination therapy in the rat 13762 mammary carcinoma and the murine Lewis lung carcinoma SO ANTICANCER RESEARCH LA English DT Article DE squalamine; antiangiogenic agents; combination therapy; tumor oxygenation; hypoxia ID PLASMINOGEN-ACTIVATOR ACTIVITY; MEDROXYPROGESTERONE ACETATE; ANGIOSTATIC STEROIDS; TUMOR-GROWTH; HEMOGLOBIN SOLUTION; CORTISONE-ACETATE; HEPARIN FRAGMENT; BREAST-CANCER; ANGIOGENESIS; INHIBITION AB Squalamine, a naturally-occuring aminosterol, has demonstrated antiangiogenic activity in several experimental models Extended treatment with other antiangiogenic agents has been shown to increase tumor oxygenation. Tremor oxygenation was measured using an Eppendorf pO(2) histograph polarographic pO(2) electrode system in the rat 13762 mammary carcinoma after treatment of the tumor-bearing animals with squalamine (40 mglkg) on days 4 through 18 post tumor implantation. Under air breathing conditions, the hypoxic fraction (percent of pO(2) readings <5mmHg) was 53% in controls and was decreased to 38% in the squalamine treated animals. While squalamine administration alone produced only a modest effect on the growth of the 13762 tumor, there were increases in tumor growth delay of 1.9- to 2.5- fold when squalamine was administered along with cyclophosphamide, cisplatin and paclitaxel compared with the tumor growth delays observed with the chemotherapeutic agents alone. To determine the efficacy of squalamine alone and along with cytotoxic therapies against a model of primary and systemic disease, squalamine was administered to animals bearing the Lewis lung carcinoma by daily subcutaneous injection or by continuous infusion on days 4 through 18 post tumor implantation. Squalamine as a single agent had only a modest effect on the growth of the primary Lewis lung tumor but increased the tumor growth delays produced by cyclophosphamide, cisplatin, paclitaxel and 5-fluorouracil by 2.4- to 3.8- fold compared with the anticancer drugs alone. Squalamine administration alone substantially decreased the number of lung metastases found in animals bearing the Lewis lung carcinoma and further decreased the number of lung metastases when administered along with the chemotherapeutic agents. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Joint Ctr Radiat Therapy, Boston, MA 02115 USA. Magainin Pharmaceut Inc, Plymouth Meeting, PA 19462 USA. RP Teicher, BA (reprint author), Lilly Corp Ctr, Lilly Res Labs, DC 0540, Indianapolis, IN 46285 USA. EM TEICHER_BEVERLY_A@LILLY.COM NR 56 TC 42 Z9 42 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 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD JUL-AUG PY 1998 VL 18 IS 4A BP 2567 EP 2573 PG 7 WC Oncology SC Oncology GA 105HY UT WOS:000075068700046 PM 9703911 ER PT J AU Young, AS Sullivan, G Burnam, MA Brook, RH AF Young, AS Sullivan, G Burnam, MA Brook, RH TI Measuring the quality of outpatient treatment for schizophrenia SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article; Proceedings Paper CT National-Institute-of-Mental-Health Conference on Improving the Condition of People with Mental Illness - The Role of Services Research CY SEP 04-05, 1997 CL WASHINGTON, D.C. SP NIMH ID ASSERTIVE COMMUNITY TREATMENT; MENTAL-HEALTH; RATING-SCALE; CARE; OUTCOMES; SURGERY; RELAPSE; POLICY AB Background: Consumers and policy makers are increasingly interested in measuring treatment quality. We developed a standardized approach to measuring the quality of outpatient care for schizophrenia and used it to evaluate routine care. Methods: We randomly sampled 224 patients in treatment for schizophrenia at 2 public mental health clinics. Appropriate medication management was defined according to criteria derived from national treatment recommendations, and focused on recent management of symptoms and side effects. Adequate psychosocial care was defined as the recent provision of case management or family management to patients for whom it is indicated. Care was evaluated using patient interviews and medical records abstractions. Results: Although patients at the 2 clinics had similar illnesses, the treatment they received was quite different. In total, 84 (38%) of patients received poor-quality medication management, and 117 (52%) had inadequate psychosocial care. Clinics differed in the proportion of patients receiving poor-quality medication management not attributable to patient factors (28% vs 16%). The clinic with better-quality medication management provided case management to fewer severely ill patients (48% vs 81%). More than half of the cases of poor care would not have been detected if we had used only medical records data. Conclusions: At these clinics, many schizophrenic patients were receiving poor-quality care and most poor care was likely due to factors that can be modified. One approach to improving care begins by developing systems that monitor quality. These systems may require improved medical records and patient-reported symptoms and side effects. C1 Univ Calif Los Angeles, Inst Neuropsychiat, Dept Psychiat, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Ctr Hlth Serv, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Little Rock Vet Affairs Med Ctr, Little Rock, AR USA. Rand Corp, Hlth Program, Santa Monica, CA USA. RP Young, AS (reprint author), Univ Calif Los Angeles, Inst Neuropsychiat, Dept Psychiat, 760 Westwood Plaza, Los Angeles, CA 90024 USA. RI Young, Alexander/A-1523-2009 OI Young, Alexander/0000-0002-9367-9213 FU NIMH NIH HHS [MH-30911, P50 MH-54623] NR 44 TC 128 Z9 129 U1 2 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD JUL PY 1998 VL 55 IS 7 BP 611 EP 617 DI 10.1001/archpsyc.55.7.611 PG 7 WC Psychiatry SC Psychiatry GA ZZ514 UT WOS:000074737000004 PM 9672051 ER PT J AU Litvan, I MacIntyre, A Goetz, CG Wenning, GK Jellinger, K Verny, M Bartko, JJ Jankovic, J McKee, A Brandel, JP Chaudhuri, KR Lai, EC D'Olhaberriague, L Pearce, RKB Agid, Y AF Litvan, I MacIntyre, A Goetz, CG Wenning, GK Jellinger, K Verny, M Bartko, JJ Jankovic, J McKee, A Brandel, JP Chaudhuri, KR Lai, EC D'Olhaberriague, L Pearce, RKB Agid, Y TI Accuracy of the clinical diagnoses of Lewy body disease, Parkinson disease, and dementia with Lewy bodies SO ARCHIVES OF NEUROLOGY LA English DT Article ID PROGRESSIVE SUPRANUCLEAR PALSY; MULTIPLE SYSTEM ATROPHY; RICHARDSON-OLSZEWSKI-SYNDROME; ALZHEIMERS-DISEASE; SENILE DEMENTIA; INTERNATIONAL WORKSHOP; DIFFERENTIAL-DIAGNOSIS; NATURAL-HISTORY; GAZE PALSY; CRITERIA AB Background: Whether Parkinson disease (PD) and dementia with Lewy bodies (DLB) represent 2 distinct nosologic entities or are diverse phenotypes of Lewy body disease is subject to debate. Objectives: To determine the accuracy of the diagnoses of lewy body disease, PD, and DLB by validating the clinical diagnoses of 6 neurologists with the neuropathologic findings and to identify early predictors of the diagnoses. Methods: Six raters who were unaware of the neuropathologic diagnoses analyzed 105 clinical vignettes corresponding to 29 cases of Lewy body disease (post hoc analysis of 15 patients with PD and 14 with DLB) and 76 patients without PD or DLB whose cases were confirmed through autopsy findings. Main Outcome Measures: Sensitivity and positive predictive value (PPV) were chosen as validity measures and the kappa statistic as a reliability measure, Results: Interrater reliability for the diagnoses of Lewy body disease and PD was moderate for the first visit and substantial for the last, whereas agreement for diagnosis of DLB was fair for the first visit and slight for the last. Median sensitivity for diagnosis of Lewy body disease was 56.9% for the first visit and 67.2% for the last; median PPV was 60.0% and 77.4%, respectively. Median sensitivity for the diagnosis of PD was 73.3% for the first visit and 80.0% for the last; median PPV was 45.9% and 64.1%, respectively. Median sensitivity for the diagnosis of DLB was 17.8% for the first visit and 28.6% for the last; median PPV was 75.0% for the first visit and 55.8% for the last. The raters' results were similar to those of the primary neurologists. Several features differentiated PD from DLB, predicted each disorder, and could be used as clinical pointers. Conclusions: The low PPV with relatively high sensitivity for the diagnosis of PD suggests overdiagnosis. Conversely, the extremely low sensitivity for the diagnosis of DLB suggests underdiagnosis. Although the case mix included in the study may not reflect the frequency of these disorders in practice, limiting the clinical applicability of the validity measures, the raters' results were similar to those of the primary neurologists who were not exposed to such limitations. Overall, our study confirms features suggested to predict these disorders, except for the early presence of postural imbalance, which is not indicative of either disorder. C1 NINDS, Neuroepidemiol Branch, NIH, Bethesda, MD 20892 USA. NIMH, Div Epidemiol & Res Studies, Bethesda, MD 20892 USA. Rush Med Coll, Dept Neurol, Chicago, IL 60612 USA. Lainz Hosp, Ludwig Boltzmann Inst Clin Neurobiol, A-1130 Vienna, Austria. Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. Massachusetts Gen Hosp, Dept Neuropathol, Boston, MA 02114 USA. Inst Neurol, London WC1N 3BG, England. Inst Psychiat, Dept Neurol, London SE5 8AF, England. Parkinsons Dis Soc, Brain Bank, Res Ctr, London, England. Hop La Pitie Salpetriere, Federat Neurol, Paris, France. Hop La Pitie Salpetriere, Raymond Escourolle Neuropathol Lab, Paris, France. RP Litvan, I (reprint author), NINDS, 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 91 TC 205 Z9 206 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD JUL PY 1998 VL 55 IS 7 BP 969 EP 978 DI 10.1001/archneur.55.7.969 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 101CN UT WOS:000074852200010 PM 9678315 ER PT J AU McNamara, MJ Gomez-Isla, T Hyman, BT AF McNamara, MJ Gomez-Isla, T Hyman, BT TI Apolipoprotein E genotype and deposits of A beta 40 and A beta 42 in Alzheimer disease SO ARCHIVES OF NEUROLOGY LA English DT Article ID A-BETA DEPOSITION; MISSENSE MUTATION; PROTEIN; ALLELE; GENE; PRESENILIN-1; RATIO AB Objective: To examine the differential deposition of amyloid beta (A beta) peptide isoforms A beta 40 and A beta 42 in the Alzheimer disease (AD) brain in relation to the apolipoprotein E (APOE) genotype. Background: The APOE epsilon 4 genotype is an inherited risk factor for AD and is associated with increased deposition of A beta protein in the cerebral cortex. Previous data from familial AD duet to mutations in presenilin 1 and presenilin 2 genes and the amyloid precursor protein suggest that the long form of A beta peptide, A beta 42, is selectively increased in these circumstances. herein, we examine whether APOE genotype influenced the species of A beta peptide deposited. Design and Methods: The amount of A beta 40, A beta 42, and total A beta deposited in immunostained temporal lobe tissue of 28 cases of AD of known APOE genotype was determined. Results: Individuals with the APOE epsilon 4 genotype (APOE epsilon 4/4) were associated with both increased A beta 40 (P<.05) and A beta 42 (P<.05) compared with individuals without the APOE epsilon 4/4 genotype. Conclusion: Our results differ from the data from AD due to mutations in presenilin 1 and presenilin 2 genes and the amyloid precursor protein and suggest that the APOE epsilon 4 genotype mediates increased A beta deposition by a mechanism that differs from that found in other genetic causes of AD. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Univ Minnesota, Minneapolis, MN USA. RP Hyman, BT (reprint author), Massachusetts Gen Hosp, Dept Neurol, Alzheimers Unit, 149 13th St,CNY 6405, Charlestown, MA 02129 USA. EM b_hyman@helix.mgh.harvard.edu FU NIA NIH HHS [AG05134, AG12406] NR 27 TC 53 Z9 53 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD JUL PY 1998 VL 55 IS 7 BP 1001 EP 1004 DI 10.1001/archneur.55.7.1001 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 101CN UT WOS:000074852200014 PM 9678319 ER PT J AU Sandberg, MA Pawlyk, BS Dan, J Arnaud, B Dryja, TP Berson, EL AF Sandberg, MA Pawlyk, BS Dan, J Arnaud, B Dryja, TP Berson, EL TI Rod and cone function in the Nougaret form of stationary night blindness SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID HETEROZYGOUS MISSENSE MUTATION; GENE; SUBUNIT AB Background: Recently, a mutation (Gly38Asp) was identified in the alpha subunit of rod transducin in members of the Nougaret pedigree affected with dominantly inherited stationary night blindness. Objective: To evaluate retinal function in patients with the Gly38Asp gene defect. Design: Ocular examinations, including specialized measures of rod and cone function. Setting: A clinical research facility in Boston, Mass. Patients: A father (aged 48 years) and son (aged 25 years) with the Gly38Asp mutation. Main Outcome Measures: Psychophysical thresholds to white and narrowband lights and full-field electroretinographic (ERG) responses. Results: Both patients showed dark-adapted thresholds to white light that were elevated approximately 2 log-units across the retina. Spectral sensitivity testing revealed thresholds that seemed to be governed mostly by rods. Although both patients' dark-adapted ERG responses to a dim blue flash were nondetectable, their dark-adapted ERGs to a white flash showed an a-wave with cone and rod components and a b-wave amplitude larger than what could have been generated by cone function alone. Rod ERGs to bright blue flashes had subnormal, but detectable, amplitudes that seemed to result from a profound reduction in sensitivity. The patients also showed loss of a cone subcomponent in the dark-adapted response to a red flash. The abnormal dark-adapted ERG responses of the patients could be simulated in the ERG responses of normal subjects tested with blue, white, and red flashes presented in the presence of a mesopic background. Conclusions: Although the Nougaret form of stationary night blindness has been cited as a prototype of absent rod function with normal cone function, our findings, based on the genealogically and genotypically documented descendants of Jean Nougaret, show that rod function is present, although subnormal, and that there is slight impairment of cone function. The data also suggest that these abnormalities can be simulated by light-adapting the normal retina, compatible with the proposal that the rod transducin encoded by the mutant gene is constitutively active and that the night blindness results from partial desensitization of rods caused by the constitutive activity. C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Berman Gund Lab Study Retinal Degenerat, Boston, MA 02114 USA. Hop Gui de Chauliac, Montpellier, France. Massachusetts Eye & Ear Infirm, Ocular Mol Genet Inst, Boston, MA 02114 USA. RP Sandberg, MA (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Berman Gund Lab Study Retinal Degenerat, 243 Charles St, Boston, MA 02114 USA. FU NEI NIH HHS [EY08683, EY00169] NR 15 TC 17 Z9 17 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD JUL PY 1998 VL 116 IS 7 BP 867 EP 872 PG 6 WC Ophthalmology SC Ophthalmology GA ZZ720 UT WOS:000074760400004 PM 9682699 ER PT J AU Kuan, NK Passaro, E AF Kuan, NK Passaro, E TI Apoptosis: Programmed cell death SO ARCHIVES OF SURGERY LA English DT Article ID BCL-2 PROTEIN; SURVIVAL; INTERLEUKIN-10; PATHOGENESIS; ADHESION; DISEASE; P53 AB Currently there is much interest and excitement in the understanding of how cells undergo the process of apoptosis or programmed cell death. Understanding how, why, and when cells are instructed to die may provide insight into the aging process, autoimmune syndromes, degenerative diseases, and malignant transformation. This review focuses on the development of apoptosis and describes the process of programmed cell death, some of the factors that incite or prevent its occurrence, and finally some of the diseases in which it may play a role. The hope is that in the not too distant future we may be able to modify or thwart the apoptotic process for therapeutic benefit. C1 W Los Angeles Vet Affairs Med Ctr, Dept Surg, Los Angeles, CA 90073 USA. Univ Cincinnati, Dept Toxicol, Cincinnati, OH USA. RP Passaro, E (reprint author), W Los Angeles Vet Affairs Med Ctr, Dept Surg, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 18 TC 12 Z9 14 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD JUL PY 1998 VL 133 IS 7 BP 773 EP 775 DI 10.1001/archsurg.133.7.773 PG 3 WC Surgery SC Surgery GA ZZ943 UT WOS:000074785000015 PM 9688008 ER PT J AU Penava, SJ Otto, MW Maki, KM Pollack, MH AF Penava, SJ Otto, MW Maki, KM Pollack, MH TI Rate of improvement during cognitive-behavioral group treatment for panic disorder SO BEHAVIOUR RESEARCH AND THERAPY LA English DT Article; Proceedings Paper CT Annual Convention of the Association-for-the-Advancement-of-Behavior-Therapy CY NOV, 1996 CL NEW YORK, NEW YORK SP Assoc Advancement Behav Therapy ID THERAPY; METAANALYSIS; AGORAPHOBIA AB This study examined the rate of symptom improvement in patients receiving cognitive-behavioral group treatment for panic disorder in an outpatient clinic setting. Treatment was a standard program of 12 sessions that emphasized information, interoceptive and situational exposure, and cognitive restructuring, but also included diaphragmatic breathing and relaxation training as elements of treatment. Subjects were 37 patients selected from sequential admissions into an outpatient treatment program; all data were derived from ongoing quality assurance measures that are a standard part of clinical monitoring. Consequently, this study provides data not on the relative efficacy of cognitive-behavioral therapy (CBT), but on rate of improvement and effectiveness of CBT for panic disorder in actual clinical practice. Patients achieved significant treatment gains on all panic disorder dimensions assessed, and the largest reduction in symptoms was during the first third of the treatment program, thereby challenging the notion that CBT delivers its gains slowly over time. Information on rates of symptom improvement is valuable for providing patients with accurate expectations about potential treatment benefits and for helping to maintain motivation during initial treatment sessions. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Penava, SJ (reprint author), Massachusetts Gen Hosp, Dept Psychiat, WACC-815,15 Parkman St, Boston, MA 02114 USA. EM penavas@A1.mgh.harvard.edu NR 20 TC 56 Z9 57 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0005-7967 J9 BEHAV RES THER JI Behav. Res. Ther. PD JUL-AUG PY 1998 VL 36 IS 7-8 BP 665 EP 673 DI 10.1016/S0005-7967(98)00035-7 PG 9 WC Psychology, Clinical SC Psychology GA 100FL UT WOS:000074805100002 PM 9682523 ER PT J AU Ivanov, IB Hadjiiski, A Denkov, ND Gurkov, TD Kralchevsky, PA Koyasu, S AF Ivanov, IB Hadjiiski, A Denkov, ND Gurkov, TD Kralchevsky, PA Koyasu, S TI Energy of adhesion of human T cells to adsorption layers of monoclonal antibodies measured by a film trapping technique SO BIOPHYSICAL JOURNAL LA English DT Article ID MEMBRANE-MEMBRANE ADHESION; MOLECULAR CROSS-BRIDGES; DETAILED MECHANICS; LYMPHOCYTES-T; RECEPTOR; ACTIVATION; SEPARATION; SURFACES; CLONES; MODEL AB A novel method for studying the interaction of biological cells with interfaces (e.g., adsorption monolayers of antibodies) is developed. The method is called the film trapping technique because the cell is trapped within an aqueous film of equilibrium thickness smaller than the cell diameter. A liquid film of uneven thickness is formed around the trapped cell. When observed in reflected monochromatic light, this film exhibits an interference pattern of concentric bright and dark fringes. From the radii of the fringes one can restore the shape of interfaces and the cell. Furthermore, one can calculate the adhesive energy between the cell membrane and the aqueous film surface (which is covered by a layer of adsorbed proteins and/or specific ligands), as well as the disjoining pressure, representing the force of interaction per unit area of the latter film. The method is applied to two human T cell lines: Jurkat and its T cell receptor negative (TCR-) derivative. The interaction of these cells with monolayers of three different monoclonal antibodies adsorbed at a water-air interface is studied. The results show that the adhesive energy is considerable (above 0.5 mJ/m(2)) when the adsorption monolayer contains antibodies acting as specific ligands for the receptors expressed on the cell surface. In contrast, the adhesive energy is close to zero in the absence of such a specific ligand-receptor interaction. In principle, the method can be applied to the study of the interaction of a variety of biological cells (B cells, natural killer cells, red blood cells, etc.) with adsorption monolayers of various biologically active molecules. In particular, film trapping provides a tool for the gentle micromanipulation of cells and for monitoring of processes (say the activation of a T lymphocyte) occurring at the single-cell level. C1 Univ Sofia, Fac Chem, Lab Thermodynam & Physicochem Hydrodynam, BU-1126 Sofia, Bulgaria. Harvard Univ, Sch Med, Dana Farber Canc Inst, Immunobiol Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Keio Univ, Sch Med, Dept Immunol, Tokyo 160, Japan. RP Kralchevsky, PA (reprint author), Univ Sofia, Fac Chem, Lab Thermodynam & Physicochem Hydrodynam, 1 James Bouchier Ave, BU-1126 Sofia, Bulgaria. EM pk@ltph.bol.bg RI Gurkov, Theodor/D-2883-2011; Kralchevsky, Peter/A-1012-2008; Koyasu, Shigeo/J-5583-2015 OI Kralchevsky, Peter/0000-0003-3942-1411; Koyasu, Shigeo/0000-0001-9585-3038 NR 42 TC 12 Z9 12 U1 0 U2 2 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JUL PY 1998 VL 75 IS 1 BP 545 EP 556 PG 12 WC Biophysics SC Biophysics GA 108BM UT WOS:000075246200055 PM 9649417 ER PT J AU Bieganski, RM Fowler, A Morgan, JR Toner, M AF Bieganski, RM Fowler, A Morgan, JR Toner, M TI Stabilization of active recombinant retroviruses in an amorphous dry state with trehalose SO BIOTECHNOLOGY PROGRESS LA English DT Article ID GENE-TRANSFER; STABILITY; TRANSDUCTION; LIPOSOMES; THERAPY AB The disaccharide trehalose is found to be effective for stabilization of active recombinant retroviruses in an amorphous dry state achieved through ambient-temperature vacuum dehydration of retroviral supernatants. Studies revealed that trehalose is a significantly better desiccation protectant than sucrose, glucose, and dextran: dextran has essentially no protective effect on retroviral survival after drying and rehydration. X-ray diffractometry of the retroviral supernatant dried with trehalose demonstrated its amorphous nature. The ability to dehydrate retroviral stocks at ambient temperatures into a stable glassy state will have a profound effect for researchers and commercial biotechnology companies which supply retroviral vectors for human gene therapy and basic research. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Surg Serv, Boston, MA 02114 USA. Shriners Burn Inst, Boston, MA 02114 USA. Univ Massachusetts, Dept Mech Engn, N Dartmouth, MA 02747 USA. RP Toner, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, 55 Fruit St,GRB 1401, Boston, MA 02114 USA. OI Morgan, Jeffrey/0000-0002-7546-3443 FU NICHD NIH HHS [HD28528] NR 28 TC 43 Z9 44 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 8756-7938 J9 BIOTECHNOL PROGR JI Biotechnol. Prog. PD JUL-AUG PY 1998 VL 14 IS 4 BP 615 EP 620 DI 10.1021/bp980057d PG 6 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 110NE UT WOS:000075386600012 PM 9694684 ER PT J AU Xu, FH Sharma, S Gardner, A Tu, YP Raitano, A Sawyers, C Lichtenstein, A AF Xu, FH Sharma, S Gardner, A Tu, YP Raitano, A Sawyers, C Lichtenstein, A TI Interleukin-6-induced inhibition of multiple myeloma cell apoptosis: Support for the hypothesis that protection is mediated via inhibition of the JNK/SAPK pathway SO BLOOD LA English DT Article ID ACTIVATED PROTEIN-KINASES; MALIGNANT PLASMA-CELLS; GROWTH-FACTOR-BETA; C-JUN; GENE-EXPRESSION; JNK ACTIVATION; DEATH; DEXAMETHASONE; LINE; AP-1 AB The mechanism by which interleukin-6 (IL-6) protects multiple myeloma (MM) plasma cells from apoptosis induced by anti-fas antibodies and dexamethasone was studied. Anti-apoptotic concentrations of IL-6 had no effect on cell-cycle distribution or activation of RAF-1 or ERK in dexamethasone or anti-fas-treated 8226 and UCLA #1 MM cell lines. However, IL-6-dependent protection of viability correlated with an inhibition of dexamethasone- and anti-fas-induced activation of jun kinase (JNK) and AP-1 transactivation. To test the hypothesis that cytokine-induced protection was mediated through inhibition of JNK/c-jun, we also inhibited c-jun function in 8226 cells via introduction of a mutant dominant negative c-jun construct. Mutant c-jun-containing MM cells were also resistant to anti-fas-induced apoptosis but were significantly more sensitive to dexamethasone-induced apoptosis, These results support the notion that IL-6 protects MM cells against anti-fas through its inhibitory effects on JNK/c-jun but indicate protection against dexamethasone occurs through separate, yet unknown pathways. (C) 1998 by The American Society of Hematology. C1 Univ Calif Los Angeles, Med Ctr, Dept Med, Los Angeles, CA USA. W Los Angeles Vet Affairs Med Ctr, Dept Med, Los Angeles, CA USA. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. RP Lichtenstein, A (reprint author), VA W LA Hosp, 601 W111H,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. RI Sawyers, Charles/G-5327-2016 NR 54 TC 80 Z9 83 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD JUL 1 PY 1998 VL 92 IS 1 BP 241 EP 251 PG 11 WC Hematology SC Hematology GA ZW916 UT WOS:000074461200033 PM 9639523 ER PT J AU Weinreb, S Delgado, JC Clavijo, OP Yunis, EJ Bayer-Zwirello, L Polanski, L Deluhery, L Cohn, G Yao, JT Stec, TC Higby, D Andrzejewski, C AF Weinreb, S Delgado, JC Clavijo, OP Yunis, EJ Bayer-Zwirello, L Polanski, L Deluhery, L Cohn, G Yao, JT Stec, TC Higby, D Andrzejewski, C TI Transplantation of unrelated cord blood cells SO BONE MARROW TRANSPLANTATION LA English DT Article DE placental blood; unmatched; multiple donors; CML ID BONE-MARROW RECONSTITUTION; ALLELES AB A 43-year-old woman with Philadelphia chromosome (Ph) positive chronic myelogenous leukemia in acute phase received high-dose chemotherapy followed by transfusion of 12 randomly selected units of umbilical cord blood. HLA analysis showed cells of one donor from day +10 to day +43 post-transfusion. This unit was HLA class II identical with that of the patient. C1 Baystate Med Ctr, Dept Pathol, Transfus Med Serv, Springfield, MA 01199 USA. Baystate Med Ctr, Dept Med, Springfield, MA 01199 USA. Baystate Med Ctr, Dept OB GYN, Springfield, MA 01199 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Andrzejewski, C (reprint author), Baystate Med Ctr, Dept Pathol, Transfus Med Serv, 759 Chestnut St, Springfield, MA 01199 USA. NR 15 TC 40 Z9 41 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD JUL PY 1998 VL 22 IS 2 BP 193 EP 196 DI 10.1038/sj.bmt.1701309 PG 4 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 102VT UT WOS:000074947100013 PM 9707029 ER PT J AU Anderson, KC AF Anderson, KC TI Regulation of multiple myeloma (MM) cell growth and apoptosis SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JUL PY 1998 VL 102 IS 1 SU S BP 142 EP 142 PG 1 WC Hematology SC Hematology GA 104TK UT WOS:000075031300562 ER PT J AU Berenson, JR AF Berenson, JR TI Oncogenesis in multiple myeloma SO BRITISH JOURNAL OF HAEMATOLOGY 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 BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JUL PY 1998 VL 102 IS 1 SU S BP 142 EP 142 PG 1 WC Hematology SC Hematology GA 104TK UT WOS:000075031300563 ER PT J AU Neel, BG Gu, H Chen, B Timms, J Kamatkar, S Griffin, JD AF Neel, BG Gu, H Chen, B Timms, J Kamatkar, S Griffin, JD TI Role of SHP-2 in hematopoietic cell signaling SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Meeting Abstract C1 Beth Israel Deaconess Med Ctr, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RI Gu, Haihua/G-6364-2011; Timms, John/A-1556-2010 OI Timms, John/0000-0002-4507-835X NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JUL PY 1998 VL 102 IS 1 SU S BP 274 EP 274 PG 1 WC Hematology SC Hematology GA 104TK UT WOS:000075031301097 ER PT J AU Futaki, M Yamashita, T Yabe, M Kato, S D'Andrea, AD Asano, S Nakahata, T AF Futaki, M Yamashita, T Yabe, M Kato, S D'Andrea, AD Asano, S Nakahata, T TI Analyses of Fanconi anemia genes in Japanese patients SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Tokai Med Sch, Yokohama, Kanagawa, Japan. Univ Tokyo, Inst Med Sci, Tokyo, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JUL PY 1998 VL 102 IS 1 SU S BP 295 EP 295 PG 1 WC Hematology SC Hematology GA 104TK UT WOS:000075031301179 ER PT J AU Glaspy, J Demetri, GD AF Glaspy, J Demetri, GD TI Hematological and quality of life (QOL) outcomes in anaemic cancer patients treated, with Epoetin alfa SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Los Angeles, CA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JUL PY 1998 VL 102 IS 1 SU S BP 336 EP 336 PG 1 WC Hematology SC Hematology GA 104TK UT WOS:000075031301336 ER PT J AU Delabesse, E Bernard, M Meyer, V Smit, L Pulford, K Cayuela, JM Ritz, J Bourquelot, P Strominger, JL Valensi, F Macintyre, EA AF Delabesse, E Bernard, M Meyer, V Smit, L Pulford, K Cayuela, JM Ritz, J Bourquelot, P Strominger, JL Valensi, F Macintyre, EA TI TAL1 expression does not occur in the majority of T-ALL blasts SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE TAL1; T-ALL; GATA1; SIL ID ACUTE LYMPHOBLASTIC-LEUKEMIA; PEDIATRIC-ONCOLOGY-GROUP; SITE-SPECIFIC DELETIONS; LOOP-HELIX PROTEIN; CELL LEUKEMIA; FUSION TRANSCRIPT; MESSENGER-RNA; SCL LOCUS; GENE; TRANSLOCATION AB The TALI gene is disrupted by translocation or deletion (tal(d)) in up to 30% of T-cell acute lymphoblastic leukaemia (T-ALL), leading to aberrant transcriptional activation, as a SIL-TAL1 fused transcript in tald, It has been suggested that TAL1 transcription occurs in approximately 50% of a T-ALLs without apparent rearrangement. SIL-TAL1 was positive in 15/60 (25%) of T-ALL, whereas wild-type TALI transcripts were detected in all 13 SIL-TAL1 and in 19/43 (44%) T-ALL without SIL-TAL1. To investigate the cellular origin of TALI we exploited the fact that GATA1 and TALI are co-ordinately expressed in non-lymphoid haemopoietic cells, whereas only the latter is found in TALL. GATA1 was detected in 10/23 (43%) TALI-negative ALLs but in 17/19 (89%) 'unexplained' TAL1-positive cases, suggesting a common non-lymphoid cellular origin. Immunocytochemical analysis with a TAL1-specific monoclonal antibody showed nuclear expression in the blasts of 10/34(29%) cases, including 8/10 SIL-TAL1(+) and two RT-PCR TAL1(+), SIL-TAL1(-) cases. In the remaining cases TAL1 expression was restricted to a minor population (< 5%) of larger, strongly TAL1-positive cells which comprised erythroid cells, CD34(+)CD3(-) precursors and an unidentified TAL1(+)CD45(-) population which morphologically resembled monocytes/macrophages. We therefore suggest that appropriate diagnostic evaluation of T-ALL should include molecular detection of SIL-TAL1 transcripts and in situ immunocytochemical detection of TAL1 protein expression by leukaemic blasts. This approach will enable accurate analysis of the prognostic significance of TAL1 deregulation in T-ALL. C1 CHU Necker Enfants Malad, Dept Haematol, Paris, France. Univ Paris 05, Paris, France. Leukaemia Res Fund, Immunodiagnost Unit, Oxford, England. Hop St Louis, Inst Hematol, Mol Haematol Lab, Paris, France. Hop St Louis, Inst Hematol, INSERM U462, Paris, France. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Macintyre, EA (reprint author), Hop Necker Enfants Malad, Hematol Lab, Tour Pasteur,149 Rue Sevres, F-75743 Paris 15, France. RI Pulford, Karen/B-3609-2009; Ritz, Jerome/C-7929-2009; OI Pulford, Karen/0000-0002-2989-789X; Ritz, Jerome/0000-0001-5526-4669; DELABESSE, Eric/0000-0002-0928-0753 NR 40 TC 16 Z9 16 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JUL PY 1998 VL 102 IS 2 BP 449 EP 457 DI 10.1046/j.1365-2141.1998.00807.x PG 9 WC Hematology SC Hematology GA 105FV UT WOS:000075062800005 PM 9695959 ER PT J AU Grossbard, ML Fidias, P Kinsella, J O'Toole, J Lambert, JM Blattler, WA Esseltine, D Braman, G Nadler, LM Anderson, KC AF Grossbard, ML Fidias, P Kinsella, J O'Toole, J Lambert, JM Blattler, WA Esseltine, D Braman, G Nadler, LM Anderson, KC TI Anti-B4-blocked ricin: a phase II trial of 7 day continuous infusion in patients with multiple myeloma SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE immunotoxins; immunotherapy; monoclonal antibodies; multiple myeloma; clinical trials ID BONE-MARROW TRANSPLANTATION; B-CELL NEOPLASMS; MONOCLONAL-ANTIBODY; PERIPHERAL-BLOOD; GROWTH-INVIVO; LIGHT-CHAIN; PLASMA-CELL; IMMUNOTOXIN; THERAPY; DIFFERENTIATION AB This phase II trial was undertaken to determine the toxicities, response rate, pharmacokinetics and frequency of human anti-mouse antibody (HAMA) and anti-ricin antibody (HARA) when the B-cell restricted immunotoxin anti-B4-bR was administered to patients with previously treated multiple myeloma (MM). Five patients with MM were scheduled to receive a 7d continuous infusion of anti-B4-bR. The initial four patients received therapy at 40 mu g/kg lean body weight (LBW)/d. Two patients received a 7 d infusion, one patient received 6 d, and another patient 5 d of therapy The fifth patient was treated for 7 d at a lower dose of 30 mu g/kg LBW/d because of the side-effects observed in the initial patients. Pharmacokinetic studies demonstrated a peak serum level >2 .6 nM in three of the patients, Side-effects of therapy included hepatic transaminase elevations, myalgias, thrombocytopenia, nausea, vomiting, decrease in performance status, and capillary leak syndrome, One patient developed HAMA and two patients HARA. One patient developed neurologic toxicity with akinetic mutism, and died following therapy. No patient demonstrated a significant decline in M-component during therapy. We concluded that anti-B4-bR call be administered by continuous infusion to patients with multiple myeloma, although immunotoxin levels >3 nM were associated with increased incidence of toxicity and required dose adjustment. Future trials using anti-B4-bR in MM will be needed to determine the optimal dose and administration schedule in this patient population, and to determine whether there is evidence of biologic activity. C1 Massachusetts Gen Hosp, Hematol Oncol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. ImmunoGen Inc, Cambridge, MA USA. RP Grossbard, ML (reprint author), Massachusetts Gen Hosp, Hematol Oncol Unit, Cox 228,100 Blossom St, Boston, MA 02114 USA. FU NCI NIH HHS [CA55207, CA34183] NR 26 TC 42 Z9 42 U1 1 U2 3 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JUL PY 1998 VL 102 IS 2 BP 509 EP 515 DI 10.1046/j.1365-2141.1998.00799.x PG 7 WC Hematology SC Hematology GA 105FV UT WOS:000075062800012 PM 9695966 ER PT J AU Garcia-Olmo, D Ontanon, J Garcia-Olmo, DC Vallejo, M Cifuentes, J AF Garcia-Olmo, D Ontanon, J Garcia-Olmo, DC Vallejo, M Cifuentes, J TI Lack of genetically detected circulating tumour cells renders the 'no-touch isolation technique' unnecessary in colorectal cancer SO BRITISH JOURNAL OF SURGERY LA English DT Meeting Abstract C1 Albacete Gen Hosp, Expt Res Unit, Albacete, Spain. Albacete Gen Hosp, Dept Gen Surg, Albacete, Spain. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Reprod Endocrine Unit, Boston, MA USA. RI Garcia-Olmo, Dolores C./L-5733-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0007-1323 J9 BRIT J SURG JI Br. J. Surg. PD JUL PY 1998 VL 85 SU 2 BP 14 EP 14 PG 1 WC Surgery SC Surgery GA ZZ631 UT WOS:000074749500044 ER PT J AU Nabradi, Z von Jako, R Wain, J Boni, J AF Nabradi, Z von Jako, R Wain, J Boni, J TI Minimal and direct access in thoracic diagnosis and surgery SO BRITISH JOURNAL OF SURGERY LA English DT Meeting Abstract C1 Univ Med Sch Debrecen, Dept Surg 2, Debrecen, Hungary. Harvard Med Sch, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0007-1323 J9 BRIT J SURG JI Br. J. Surg. PD JUL PY 1998 VL 85 SU 2 BP 209 EP 209 PG 1 WC Surgery SC Surgery GA ZZ631 UT WOS:000074749500705 ER PT J AU Liu, SC Sauter, ER Clapper, ML Feldman, RS Levin, L Chen, SY Yen, TJ Ross, E Engstrom, PF Klein-Szanto, AJP AF Liu, SC Sauter, ER Clapper, ML Feldman, RS Levin, L Chen, SY Yen, TJ Ross, E Engstrom, PF Klein-Szanto, AJP TI Markers of cell proliferation in normal epithelia and dysplastic leukoplakias of the oral cavity SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID UPPER AERODIGESTIVE TRACT; D1 GENE AMPLIFICATION; CYCLIN EXPRESSION; CARCINOMAS; HEAD; NECK; MUCOSA; OVEREXPRESSION; KI-67; P53 AB The expression of several markers of epithelial cell proliferation was analyzed to establish baseline data for future chemoprevention studies of oral premalignant lesions. Punch biopsies (n = 60) from three different sites of oral mucosa (bucca, lateral tongue, and the floor of the mouth) were obtained from 20 normal donors of both sexes, After formaldehyde fixation and paraffin embedding, immunohistochemistry was used to detect the proliferation markers Mib-1, cyclin D1, and centromere-associated protein CENP-F, Analysis of sections stained for the three markers showed similar patterns, i,e,, a low labeling index (LI) in the basal layer and a high LI in the parabasal layer at all three intraoral sites, No proliferative activity was seers above the parabasal layer (superficial layer). All sites showed similar Mib-1 LI values for the proliferative markers. The tongue epithelium exhibited higher parabasal LIs of cyclin D1 and CENP-F than did the other two sites. No significant differences were detected between smokers and nonsmokers. The data from normal mucosa were compared with those from low (n = 30)- and high (n = 17)-grade dysplastic leukoplakias. The Mib-1 LI showed a very significant change, with a 9-fold increase in the basal layer LI in dysplastic leukoplakias, Cyclin D1 and CENP-F showed similar trends with increments of up to 7-fold in the basal layer of high-grade dysplasia, Although the proliferative activity of the parabasal layer was similar in normal and leukoplakic epithelia, the superficial layer showed a significant increment in proliferative activity mainly in high-grade leukoplakia, These studies suggest that proliferation markers in the basal and superficial cells of premalignant lesions may serve as surrogate end point biomarkers for chemoprevention trials. C1 Fox Chase Canc Ctr, Dept Pathol, Div Populat Sci, Philadelphia, PA 19111 USA. Fox Chase Canc Ctr, Div Basic Sci, Philadelphia, PA 19111 USA. Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Univ Penn, Sch Dent Med, Philadelphia, PA 19104 USA. Temple Univ, Sch Med, Dept Pathol, Philadelphia, PA 19140 USA. RP Klein-Szanto, AJP (reprint author), Fox Chase Canc Ctr, Dept Pathol, Div Populat Sci, Philadelphia, PA 19111 USA. EM AJ_Klein-Szanto@fccc.edu RI Klein-Szanto, Andres/E-6218-2010; OI Yen, Tim/0000-0003-2159-0997 FU NCI NIH HHS [CA-06927, CA-71539, MAO-NO1-CN 25436-02] NR 42 TC 33 Z9 40 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUL PY 1998 VL 7 IS 7 BP 597 EP 603 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA ZZ309 UT WOS:000074716500007 PM 9681528 ER PT J AU Wadler, S Atkins, M Karp, D Neuberg, D Haynes, H Dutcher, JP AF Wadler, S Atkins, M Karp, D Neuberg, D Haynes, H Dutcher, JP TI Clinical trial of weekly intensive therapy with 5-fluorouracil on two different schedules combined with interferon alpha-2a and filgrastim in patients with advanced solid tumors: Eastern cooperative oncology group study P-Z991 SO CANCER JOURNAL FROM SCIENTIFIC AMERICAN LA English DT Article DE interferon; filgrastim; fluorouracil; hematopoietic growth factors; phase I ID COLONY-STIMULATING FACTOR; ADVANCED COLORECTAL-CARCINOMA; METASTATIC BREAST-CANCER; THYMIDYLATE SYNTHASE; PHASE-II; CHEMOTHERAPY; NEUTROPENIA; FLUOROURACIL; CSF; RESISTANCE AB PURPOSE The hematopoietic growth factor filgrastim has been shown to reduce both chemotherapy-induced myelosuppression and mucosal toxicities. The aim of this study was to conduct four separate pilot trials to determine the maximum-tolerated doses at which interferon alpha (IFN alpha) followed by 5-fluorouracil (5-FU) could be administered in combination with filgrastim support. PATIENTS AND METHODS Patients were required to have a histologically documented solid tumor with either measurable or evaluable lesions. All patients were fully ambulatory; had adequate bone marrow, renal, and hepatic function; had recovered from surgery; and gave informed consent. Trials were conducted sequentially. In parts A and B, patients received 5-FU as a continuous intravenous infusion daily for 5 days, followed by weekly bolus therapy at the same dose. In parts C and D, patients received 5-FU as a weekly high-dose, 24-hour infusion. Interferon was administered immediately before the 5-FU three times a week Filgrastim was administered at 5 mu g/kg subcutaneously either four (parts A, B) or five (parts C, D) times a week In part A, the starting doses were as follows: 5-FU, 750 mg/m(2), and IFN alpha, 3 MU subcutaneously, and the IFN alpha was escalated between patient cohorts to a maximum of 9 MU. Part B used the dose of IFN alpha established from part A, and the 5-FU was escalated to the maximum-tolerated dose between patient cohorts. In part C, the starting dose of IFN alpha was 3 MU subcutaneously, and that of 5-FU, 2.6 g/m(2), and the dose of IFN alpha was escalated to a maximum of 9 MU. In part D, the dose of IFN alpha was determined from part C, and the dose of 5-FU was escalated. The maximum tolerated dose was the highest dose at which three of three or five of six patients were able to tolerate therapy. RESULTS There were 71 patients entered into the four parts of this trial. In part A (12 patients), the dose of IFN alpha, was escalated to 9 MU subcutaneously three times a week with only one patient experiencing dose-limiting toxicity. In part B (13 patients), the dose of 5-FU could not be escalated beyond 750 mg/m(2) because of sepsis (one patient) and gastrointestinal hemorrhage (one patient). The predominant toxicities were diarrhea (46%), vomiting (23%), and mucositis (31%). In part C (24 patients), two patients experienced dose-limiting toxicities (staphylococcal sepsis [one patient] and neuropsychiatric [one patient]). The dose of IFN alpha was escalated to 9 MU. In part D (21 patients), the dose of 5-FU was escalated to 3.4 g/m(2) administered weekly. No patients at this dose level experienced serious toxicities. At the next highest dose level, 3.6 g/m(2), one patient each experienced gastrointestinal hemorrhage and diarrhea. There were no additive constitutional symptoms resulting from the combination of IFN alpha and filgrastim. In parts C and D, filgrastim could be administered 6 hours after the end of the 5-FU infusion without excessive myelosuppression. CONCLUSIONS The addition of filgrastim allowed escalation of the dose of 5-FU on the meekly, high-dose schedule, but not on the weekly bolus schedule. IFN alpha and filgrastim can be administered without additive toxicities. Filgrastim can be safely administered < 24 hours after completion of the weekly, high dose 5-FU infusion. C1 Montefiore Med Ctr, Albert Einstein Canc Ctr, Dept Oncol, Bronx, NY 10467 USA. Beth Israel Deaconess Med Ctr, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Wadler, S (reprint author), Montefiore Med Ctr, Albert Einstein Canc Ctr, Dept Oncol, Hofheimer 1,111 E 210th St, Bronx, NY 10467 USA. FU NCI NIH HHS [CA21115, CA14958, CA23318] NR 38 TC 1 Z9 1 U1 0 U2 0 PU SCI AMERICAN INC PI NEW YORK PA 415 MADISON AVE, NEW YORK, NY 10017 USA SN 1081-4442 J9 CANCER J SCI AM JI Cancer J. Sci. Am. PD JUL-AUG PY 1998 VL 4 IS 4 BP 261 EP 268 PG 8 WC Oncology SC Oncology GA 104WD UT WOS:000075038300009 PM 9689985 ER PT J AU Gribben, JG AF Gribben, JG TI Molecular basis for stem cell transplantation in indolent lymphomas SO CANCER JOURNAL FROM SCIENTIFIC AMERICAN LA English DT Article DE follicular lymphoma; chronic lymphocytic leukemia; bone marrow transplantation; polymerase chain reaction ID BONE-MARROW TRANSPLANTATION; POLYMERASE CHAIN-REACTION; NON-HODGKINS-LYMPHOMA; CHRONIC LYMPHOCYTIC-LEUKEMIA; HIGH-DOSE THERAPY; IMMUNOGLOBULIN-GENE REARRANGEMENTS; HUMAN FOLLICULAR LYMPHOMAS; BREAKPOINT-CLUSTER REGION; PERIPHERAL-BLOOD; RESIDUAL CELLS AB PURPOSE To assess the role of bone marrow transplantation in indolent lymphomas. PATIENTS AND METHODS Autologous and allogeneic stem cell. transplantations (SCTs) are performed routinely for a number of hematologic malignancies; however, few patients with indolent lymphoma have been treated with SCT, The high incidence of bone marrow infiltration in the indolent lymphomas has made it difficult to perform autologous SCT. In addition, although indolent lymphomas are initially responsive to chemotherapy, many patients have been heavily pretreated, have become chemotherapy resistant, and have a decreased marrow reserve by the time they are considered for high-dose myeloablative therapy. An advantage of studying the indolent lymphomas is that they are characterized by nonrandom chromosomal translocations and/or clonal rearrangements of the immunoglobulin heavy-chain locus. These translocations and unique immunoglobulin rearrangements provide clonal markers of disease that can be amplified with the polymerase chain reaction (PCR), allowing detection and assessment of the clinical significance of minimal residual disease (MRD) after SCT. RESULTS Studies demonstrate that SCT can be performed safely in patients with indolent lymphomas, Although standard-dose therapy rarely eradicates MRD, high-dose therapy and SCT result in eradication of PCR-detectable MRD in a significant number of patients. Furthermore, eradication of MRD is associated with greatly prolonged disease-free survival. CONCLUSION These results suggest that our therapeutic goal should be attainment of a "molecular complete remission" for cure in these malignancies. C1 Harvard Univ, Sch Med, Dept Med, Dana Farber Canc Inst,Div Adult Oncol, Boston, MA 02115 USA. RP Gribben, JG (reprint author), Harvard Univ, Sch Med, Dept Med, Dana Farber Canc Inst,Div Adult Oncol, Boston, MA 02115 USA. NR 58 TC 3 Z9 3 U1 0 U2 0 PU SCI AMERICAN INC PI NEW YORK PA 415 MADISON AVE, NEW YORK, NY 10017 USA SN 1081-4442 J9 CANCER J SCI AM JI Cancer J. Sci. Am. PD JUL PY 1998 VL 4 SU 2 BP S37 EP S45 PG 9 WC Oncology SC Oncology GA 104TG UT WOS:000075031000006 PM 9672773 ER PT J AU Lee, K Belinsky, MG Bell, DW Testa, JR Kruh, GD AF Lee, K Belinsky, MG Bell, DW Testa, JR Kruh, GD TI Isolation of MOAT-B, a widely expressed multidrug resistance-associated protein canalicular multispecific organic anion transporter-related transporter SO CANCER RESEARCH LA English DT Article ID CONJUGATE EXPORT PUMP; HUMAN TUMOR-CELLS; CROSS-RESISTANCE; LEUKEMIA-CELLS; CDNA CLONING; DRUG-EFFLUX; X PUMP; GENE; MRP; CISPLATIN AB Multidrug resistance-associated protein (MRP) and canalicular multispecific organic anion transporter (cMOAT) are closely related mammalian ATP-binding cassette transporters that export organic anions from cells. Transfection studies have established that MRP confers resistance to natural product cytotoxic agents, and recent evidence suggests the possibility that cMOAT may contribute to cytotoxic drug resistance as well. Based upon the potential importance of these transporters in clinical drug resistance and their important physiological roles in the export of the amphiphilic products of phase I and phase ZI metabolism, we sought to identify other MRP-related transporters, Using a degenerate PCR approach, we isolated a cDNA that encodes a novel ATP-binding cassette transporter, which we designated MOAT-B. The MOAT-B gene was mapped using fluorescence in situ hybridization to chromosome band 13q32. Comparison of the MOAT-B predicted protein with other transporters revealed that it is most closely related to MRP, cMOAT, and the yeast organic anion transporter YCF1, Although MOAT-B is closely related to these transporters, it is distinguished by the absence of a similar to 200 amino acid NH2-terminal hydrophobic extension that is present in MRP and cMOAT and which is predicted to encode several transmembrane spanning segments. In addition, the MOAT-B tissue distribution is distinct from MRP and cMOAT, In contrast to MRP, which is widely expressed in tissues, including liver, and cMOAT, the expression of which is largely restricted to liver, the MOAT-B transcript is widely expressed, with particularly high levels in prostate, but is barely detectable in liver, These data indicate that MOAT-B is a ubiquitously expressed transporter that is closely related to MRP and cMOAT and raise the possibility that it may be an organic anion pump relevant to cellular detoxification. C1 Fox Chase Canc Ctr, Div Med Sci, Philadelphia, PA 19111 USA. Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. RP Kruh, GD (reprint author), Fox Chase Canc Ctr, Div Med Sci, 7701 Burholme Ave, Philadelphia, PA 19111 USA. FU NCI NIH HHS [CA06927, CA63173] NR 38 TC 114 Z9 118 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 1 PY 1998 VL 58 IS 13 BP 2741 EP 2747 PG 7 WC Oncology SC Oncology GA ZX317 UT WOS:000074503400013 PM 9661885 ER PT J AU Oyama, T Kashiwabara, K Yoshimoto, K Arnold, A Koerner, F AF Oyama, T Kashiwabara, K Yoshimoto, K Arnold, A Koerner, F TI Frequent overexpression of the cyclin D1 oncogene in invasive lobular carcinoma of the breast SO CANCER RESEARCH LA English DT Article ID PRAD1 PROTEIN EXPRESSION; MANTLE CELL LYMPHOMA; RETINOBLASTOMA-PROTEIN; MAMMARY CARCINOMAS; GENE AMPLIFICATION; ADHESION MOLECULES; DEPENDENT KINASES; CANCER CELLS; BCL-1; CHROMOSOME-11Q13 AB Invasive lobular carcinoma comprises approximately 10% of human mammary cancers, yet little is known about the molecular basis of this carcinoma, Because cyclin D1 plays a role in the pathogenesis of breast carcinomas of the ductal type, we hypothesized that this confirmed oncogene might also participate in the development of lobular carcinomas. We sought to determine the frequency of cyclin D1 protein overexpression in invasive lobular carcinoma, to investigate the cause of the protein accumulation, and to identify the effects of high levels of the protein on the regulation of the cell cycle. The study group comprises 27 indisputable cases of invasive lobular carcinoma showing varying degrees of cytological atypia, Immunohistochemical staining using well-characterized monoclonal and polyclonal antibodies disclosed cyclin D1 protein in the majority of the invasive lobular carcinoma cells in 80% of the tumors. In marked contrast, only rare cells of the noninvasive component (lobular carcinoma in situ) in the same tissue sections showed positive staining. Southern blotting of nine cases did not reveal evidence of cyclin D1 gene amplification. Immunohistochemical staining for Ki-67, a protein present in all dividing cells, showed that most cells positive for cyclin D1 did not stain for Ki-67, We conclude that the vast majority of invasive lobular carcinomas show overexpression of cyclin D1 protein. The absence of cyclin D1 protein expression in the noninvasive cells suggests that the molecule plays a role in the progression to the invasive form of lobular carcinoma. In contrast to the ductal types of breast cancer, cyclin D1 gene amplification does not seem to cause the cyclin D1 protein overexpression in lobular cancers. The lack of correlation between cyclin D1 and Ki-67 expression suggests that the cyclin D1 oncogene acts through mechanisms other than simple acceleration of the cell cycle clock in this subtype of human breast carcinoma. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Lab Endocrine Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Gunma Univ, Sch Med, Dept Pathol, Maebashi, Gumma 371, Japan. Univ Connecticut, Sch Med, Ctr Mol Med, Farmington, CT 06030 USA. RP Koerner, F (reprint author), Massachusetts Gen Hosp, Dept Pathol, Fruit St, Boston, MA 02114 USA. EM Koerner@helix.mgh.harvard.edu FU NCI NIH HHS [CA55909] NR 53 TC 90 Z9 92 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 1 PY 1998 VL 58 IS 13 BP 2876 EP 2880 PG 5 WC Oncology SC Oncology GA ZX317 UT WOS:000074503400033 PM 9661905 ER PT J AU De Sanctis, JT Goldberg, SN Mueller, PR AF De Sanctis, JT Goldberg, SN Mueller, PR TI Percutaneous treatment of hepatic neoplasms: A review of current techniques SO CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Review ID ETHANOL INJECTION THERAPY; SMALL HEPATOCELLULAR-CARCINOMA; INTENSITY FOCUSED ULTRASOUND; INTERSTITIAL LASER HYPERTHERMIA; MICROWAVE COAGULATION THERAPY; COLORECTAL LIVER METASTASES; ND-YAG LASER; CIRRHOTIC-PATIENTS; ALCOHOL INJECTION; ABLATION THERAPY C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Mueller, PR (reprint author), Massachusetts Gen Hosp, Dept Radiol, Fruit St, Boston, MA 02114 USA. NR 138 TC 53 Z9 54 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0174-1551 J9 CARDIOVASC INTER RAD JI Cardiovasc. Interv. Radiol. PD JUL-AUG PY 1998 VL 21 IS 4 BP 273 EP 296 PG 24 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 107HE UT WOS:000075201300001 PM 9688795 ER PT J AU Dempsey, EC Das, M Frid, MG Xu, YJ Stenmark, KR AF Dempsey, EC Das, M Frid, MG Xu, YJ Stenmark, KR TI Hypoxic growth of bovine pulmonary artery smooth muscle cells - Dependence on synergy, heterogeneity, and injury-induced phenotypic change SO CHEST LA English DT Article; Proceedings Paper CT Thomas L Petty 40th Annual Aspen Lung Conference on Biology and Pathobiology of the Lung Circulation CY JUN 04-07, 1997 CL ASPEN, COLORADO C1 Univ Colorado, Ctr Hlth Sci, Cardiovasc Pulm & Dev Biol Res Labs, Boulder, CO 80309 USA. Denver VA Med Ctr, Denver, CO USA. RP Dempsey, EC (reprint author), Univ Colorado, Ctr Hlth Sci, Cardiovasc Pulm & Dev Biol Res Labs, Boulder, CO 80309 USA. FU NHLBI NIH HHS [HL14985, HL07171, HL46481] NR 12 TC 9 Z9 13 U1 0 U2 1 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD JUL PY 1998 VL 114 IS 1 SU S BP 29S EP 30S DI 10.1378/chest.114.1_Supplement.29S PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 102CR UT WOS:000074906100015 PM 9676612 ER PT J AU Das, M Stenmark, KR Ruff, LJ Dempsey, EC AF Das, M Stenmark, KR Ruff, LJ Dempsey, EC TI The Ca2+-dependent isozymes of protein kinase C are uniquely important in the enhanced growth of immature adventitial fibroblasts isolated from the bovine pulmonary arterial wall at a time of heightened susceptibility to vascular injury SO CHEST LA English DT Article; Proceedings Paper CT Thomas L Petty 40th Annual Aspen Lung Conference on Biology and Pathobiology of the Lung Circulation CY JUN 04-07, 1997 CL ASPEN, COLORADO C1 Univ Colorado, Hlth Sci Ctr, CVP & Dev Lung Biol Res Labs, Denver, CO 80262 USA. Denver VA Med Ctr, Denver, CO USA. RP Das, M (reprint author), Univ Colorado, Hlth Sci Ctr, CVP & Dev Lung Biol Res Labs, 4200 E 9th Ave, Denver, CO 80262 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD JUL PY 1998 VL 114 IS 1 SU S BP 68S EP 69S DI 10.1378/chest.114.1_Supplement.68S-a PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 102CR UT WOS:000074906100042 PM 9676640 ER PT J AU Parker, TA Galan, HL Kinsella, JP Richter, G Horan, MP Abman, SH AF Parker, TA Galan, HL Kinsella, JP Richter, G Horan, MP Abman, SH TI Chronic estradiol treatment causes a marked and sustained increase in pulmonary blood flow in the late gestation ovine fetus SO CHEST LA English DT Article; Proceedings Paper CT Thomas L Petty 40th Annual Aspen Lung Conference on Biology and Pathobiology of the Lung Circulation CY JUN 04-07, 1997 CL ASPEN, COLORADO C1 Massachusetts Gen Hosp, Pulm Crit Care Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Parker, TA (reprint author), Massachusetts Gen Hosp, Pulm Crit Care Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD JUL PY 1998 VL 114 IS 1 SU S BP 69S EP 70S DI 10.1378/chest.114.1_Supplement.69S PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 102CR UT WOS:000074906100044 PM 9676641 ER PT J AU Zulian, F Schumacher, HR Calore, A Goldsmith, DP Athreya, BH AF Zulian, F Schumacher, HR Calore, A Goldsmith, DP Athreya, BH TI Juvenile arthritis in Turner's syndrome: A multicenter study SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY LA English DT Article DE Turner's syndrome; juvenile arthritis; autoimmunity; synovium ID SEX-HORMONES; RHEUMATOID-ARTHRITIS; GONADAL-DYSGENESIS; ABNORMALITIES; RESPONSES; DISEASES; INVITRO; MICE AB Objective Turner's syndrome (TS) is a disorder associated with characteristic defects in the X chromosome. Autoimmune conditions such as thyroiditis, inflammatory bowel diseases and diabetes have been described in association with TS. Methods We have studied the association between TS and juvenile arthritis (JA) by using a survey in which 28 pediatric rheumatology centers (15 in the USA, 10 in Europe, and 3 in Canada) participated. Results Eighteen cases of TS in a population of approximately 15,000 JRA patients have been found. Two different patterns of arthritis were present: polyarticular (7) and oligoarticular (11). Children with polyarticular disease had early onset, seronegative, progressively deforming arthritis and growth retardation. Those with oligoarticular arthritis had a benign course and were ANA+ (8/11). The oligoarticular children had varying karyotypes whereas almost all of the polyarthritic patients shared the same 45X0 karyotype (6/7). The light and electron microscopic studies of synovium performed in two patients showed chronic inflammation and hyperplasia of the synovial lining cells, vascular proliferation and infiltration with lymphocytes, plasma cells and mononuclear phagocytes. Conclusion Juvenile arthritis is a new autoimmune condition associated with Turner's syndrome. The prevalence seems to be at least six times greater than would be expected if the two conditions were only randomly associated. This is the first description of the synovium in Turner's syndrome; no differences from other forms of juvenile rheumatoid arthritis were found. C1 Univ Padua, Dipartimento Pediat, I-35128 Padua, Italy. Univ Penn, Childrens Seashore House, Philadelphia, PA 19104 USA. Univ Penn, Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Temple Univ, St Christophers Hosp Children, Sch Med, Philadelphia, PA USA. RP Zulian, F (reprint author), Univ Padua, Dipartimento Pediat, Via Giustiniani 3, I-35128 Padua, Italy. NR 37 TC 27 Z9 30 U1 0 U2 0 PU CLINICAL & EXPER RHEUMATOLOGY PI PISA PA VIA SANTA MARIA 31, 56126 PISA, ITALY SN 0392-856X J9 CLIN EXP RHEUMATOL JI Clin. Exp. Rheumatol. PD JUL-AUG PY 1998 VL 16 IS 4 BP 489 EP 494 PG 6 WC Rheumatology SC Rheumatology GA 106PC UT WOS:000075137200019 PM 9706435 ER PT J AU Cheli, CD Marcus, M Levine, J Zhou, ZQ Anderson, PH Bankson, DD Bock, J Bodin, S Eisen, C Senior, M Schwartz, MK Yeung, KK Allard, WJ AF Cheli, CD Marcus, M Levine, J Zhou, ZQ Anderson, PH Bankson, DD Bock, J Bodin, S Eisen, C Senior, M Schwartz, MK Yeung, KK Allard, WJ TI Variation in the quantitation of prostate-specific antigen in reference material: Differences in commercial immunoassays SO CLINICAL CHEMISTRY LA English DT Article ID SERUM; ALPHA-1-ANTICHYMOTRYPSIN; ASSAY; PSA; COMPLEX; CANCER; FORMS C1 Bayer Corp, Business Grp Diagnost, Tarrytown, NY 10591 USA. Providence St Vincent Med Ctr, Portland, OR 97225 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. SUNY Stony Brook, Stony Brook, NY 11794 USA. Huntsville Hosp, Huntsville, AL 35801 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Hosp Univ Penn, Philadelphia, PA 19104 USA. RP Allard, WJ (reprint author), Bayer Corp, Business Grp Diagnost, Tarrytown, NY 10591 USA. EM jeffrey.allard.b@bayer.com NR 19 TC 10 Z9 11 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUL PY 1998 VL 44 IS 7 BP 1551 EP 1553 PG 3 WC Medical Laboratory Technology SC Medical Laboratory Technology GA ZX975 UT WOS:000074574200028 PM 9665437 ER PT J AU Borges, MF Abelin, NMA Menezes, FOM Dahia, PLM Toledo, SPA AF Borges, MF Abelin, NMA Menezes, FOM Dahia, PLM Toledo, SPA TI Calcitonin deficiency in early stages of chronic autoimmune thyroiditis SO CLINICAL ENDOCRINOLOGY LA English DT Article ID C-CELL HYPERPLASIA; PENTAGASTRIN STIMULATION TEST; MEDULLARY CARCINOMA; CIRCULATING LEVELS; SERUM; DIAGNOSIS; ASSAY; ANTIBODIES; CALCIUM; RADIOIMMUNOASSAY AB OBJECTIVES Although calcitonin (Ct) deficiency has been described in chronic autoimmune thyroiditis (CAT) it is unclear at what stage in the disease it develops. We have analysed the Ct secretory responses of patients in two different evolutionary stages of CAT, namely the goitrous and atrophic phases. DESIGN We studied the Ct response to combined calcium (2 mg/kg) and pentagastrin (0.5 mu g/kg) intravenous infusion in 27 patients with CAT and 30 normal adult controls. The cases were divided into two groups. The first comprised eleven women with CAT and goitrous subclinical hypothyroidism (GH), aged 28.6 +/- 10.1 years-at diagnosis they had increased thyroid autoantibody titres and cytological features compatible with stages 1 and 2 of Hashimoto's thyroiditis. The second comprised 16 females with CAT and an atrophic thyroid confirmed by ultrasound scan, aged 38.0-+9 2 years--these patients were severely hypothyroid at diagnosis and were termed AH (atrophic hypothyroidism). Both groups (GH and AH) received replacement doses of thyroxine sufficient to restore euthyroidism for at least six months before the stimulation tests. Control group (C) consisted of 20 healthy women (A), aged 30 0 +/- 9 6 years, and 10 healthy men (B), aged 34.7 +/- 8 0 years. Serum Ct was measured by IRMA. The Ct secretory response was related to thyroid size and cytological data, when available. RESULTS Basal Ct concentrations in groups GH (0.08ng/l, median) and AH (0.07ng/l, median) were significantly lower than those of female controls (0.58ng/l, median). Stimulated Ct peak values in groups GH (0 08ng/l, median) and AH (0.19ng/l, median) were significantly lower than those of female controls (13.61 ng/l, median). Also, both basal (2.72 ng/l, median) and stimulated Ct levels (35.73 ng/l, median) in male controls were significantly higher than in female controls given already. A positive correlation between the Ct secretory reserve and thyroid dimensions, evaluated by ultrasound scan, was found only in patients with thyroid atrophy (AH; rs = 0 61, P< 0.05). CONCLUSIONS We have found low basal and stimulated calcitonin values in patients with chronic autoimmune thyroiditis and thyroid enlargement, which represents an early phase of chronic autoimmune thyroiditis. Our data have also confirmed previous findings of deficient calcitonin secretion in advanced stages of chronic autoimmune thyroditis in which thyroid atrophy is usually found. These findings may be associated with C-cell destruction following progressive, nonspecific follicular cell damage caused by lymphocytic infiltration and fibrosis of the gland. C1 Fed Sch Med Triangulo Mineiro, Dept Med, Uberaba, Brazil. Univ Sao Paulo, Sch Med, Sao Paulo, Brazil. RP Dahia, PLM (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 29 TC 9 Z9 12 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0300-0664 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD JUL PY 1998 VL 49 IS 1 BP 69 EP 75 DI 10.1046/j.1365-2265.1998.00478.x PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 102JU UT WOS:000074921700011 PM 9797849 ER PT J AU Svensson, PJ Molander, ML Eng, C Anvret, M Nordenskjold, A AF Svensson, PJ Molander, ML Eng, C Anvret, M Nordenskjold, A TI Low frequency of RET mutations in Hirschsprung disease in Sweden SO CLINICAL GENETICS LA English DT Article ID MEDULLARY-THYROID CARCINOMA; ENDOCRINE NEOPLASIA TYPE-2; TYROSINE KINASE DOMAIN; GERMLINE MUTATIONS; PROTOONCOGENE MUTATIONS; LONG ARM; CHROMOSOME-10; DELETION; GDNF; GENE AB Hirschsprung disease is a congenital malformation, where absence of intramural ganglia in the hindgut results in a defect in the coordination of peristaltic movement. This leads to ileus in the newborn or, more often, constipation in children and adults. The disease affects one in 5000 live births. Siblings of affected cases are at an increased risk (4%) of developing the disease. Among cases, males are affected more often than females. The first major susceptibility gene for Hirschsprung disease is the RET proto-oncogene on 10q11.2. Germline RET mutations in Hirschsprung disease are mainly inactivating, and have been reported to account for up to 20 and 50% of sporadic and familial cases, respectively. We have screened Swedish population-based samples from 62 sporadic cases and seven familial cases of Hirschsprung disease with single strand conformation polymorphism (SSCP), and found five mutations. (C) Munksgaard, 1998. C1 Karolinska Hosp, Dept Mol Med, Clin Genet Unit, S-17176 Stockholm, Sweden. Karolinska Hosp, Dept Clin Neurosci, S-17176 Stockholm, Sweden. Karolinska St Goran Hosp, Dept Pediat Surg, Stockholm, Sweden. Harvard Univ, Sch Med, Human Canc Genet Unit,Dana Farber Canc Inst, Translat Res Lab,Dept Adult Oncol,Dept Med, Boston, MA USA. RP Svensson, PJ (reprint author), Karolinska Hosp, Dept Mol Med, Clin Genet Unit, CMM L8 02 60, S-17176 Stockholm, Sweden. NR 33 TC 34 Z9 34 U1 1 U2 2 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0009-9163 J9 CLIN GENET JI Clin. Genet. PD JUL PY 1998 VL 54 IS 1 BP 39 EP 44 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 108TU UT WOS:000075282200008 PM 9727738 ER PT J AU Andes, DR Craig, WA AF Andes, DR Craig, WA TI Pharmacodynamics of fluoroquinolones in experimental models of endocarditis SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Symposium on Pharmacodynamics of Antimicrobials CY JUL 21-23, 1995 CL QUEBEC CITY, CANADA SP Internatl Soc Antiinfect Pharm ID STAPHYLOCOCCUS-AUREUS ENDOCARDITIS; METHICILLIN-RESISTANT STRAINS; AORTIC-VALVE ENDOCARDITIS; PSEUDOMONAS-AERUGINOSA; CIPROFLOXACIN; THERAPY; EFFICACY; VANCOMYCIN; TEMAFLOXACIN; COMBINATION AB We calculated the magnitude of various serum pharmacodynamic parameters for fluoroquinolones in models of experimental endocarditis (EE) described in the literature, Nineteen publications contained data that allowed calculation of these parameters. Data were available for eight fluoroquinolones against methicillin-susceptible Staphylococcus aureus, methicillin-resistant S. aureus, methicillin-resistant Staphylococcus epidermidis, viridans streptococci, Enterobacter aerogenes, and Pseudomonas aeruginosa in rabbit or rat models. Enterococci were excluded because of poor bactericidal activity, A 24-hour area under the concentration curve (AUC)/minimal inhibitory concentration (MIC) ratio greater than or equal to 100, a peak level/MIC ratio > 8, and continuous levels above the time were associated with a significantly lower number of cfu per vegetation after 3-6 days of therapy, The 24-hour AUC/MIC exhibited the best linear correlation with cfu per vegetation after 3-6 days of therapy (r(2) = 45%). The pharmacodynamic parameters predictive of efficacy for fluoroquinolones in the treatment of experimental endocarditis are similar to those for other infectious models. C1 Univ Wisconsin, Dept Med, Madison, WI 53792 USA. William S Middleton Mem Vet Adm Hosp, Madison, WI USA. RP Andes, DR (reprint author), Univ Wisconsin, Dept Med, 600 Highland Ave,Room H4-570, Madison, WI 53792 USA. NR 21 TC 37 Z9 39 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUL PY 1998 VL 27 IS 1 BP 47 EP 50 DI 10.1086/514624 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA ZZ690 UT WOS:000074756900008 PM 9675448 ER PT J AU Miller, KK Daly, PA Sentochnik, D Doweiko, J Samore, M Basgoz, NO Grinspoon, SK AF Miller, KK Daly, PA Sentochnik, D Doweiko, J Samore, M Basgoz, NO Grinspoon, SK TI Pseudo-Cushing's syndrome in human immunodeficiency virus-infected patients SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID CORTICOTROPIN-RELEASING HORMONE; PITUITARY-ADRENAL FUNCTION; HIV-INFECTION; AIDS PATIENTS; FATTY-ACIDS; CORTISOL; DISEASE; ILLNESS; PLASMA; SERUM AB To our knowledge, an association between human immunodeficiency virus infection and pseudo-Cushing's syndrome has not previously been described. We describe four HIV-infected patients with pseudo-Cushing's syndrome, characterized by striking dorsocervical and submandibular fat accumulation and central obesity. In each case, cortisol levels were either normal or suppressed adequately with administration of dexamethasone, excluding the diagnosis of true Cushing's syndrome. Immune function and weight improved significantly preceding the development of pseudo-Cushing's syndrome. Three of the four patients were taking a common protease inhibitor at the onset of symptoms, and the fourth reported the exacerbation of his symptoms with the addition of a protease inhibitor. The observed characteristic pattern of fat deposition may be attributable to a specific effect of new antiretroviral therapies or may relate to recovery independent of medication usage. Distinguishing between pseudo-Cushing's syndrome and true Cushing's syndrome is critical for preventing the unnecessary and potentially harmful treatment of such patients. Further research into the mechanisms of this novel phenomenon is needed. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Infect Dis Unit, Boston, MA USA. Beth Israel Deaconess Med Ctr, Endocrinol & Metab Unit, Boston, MA USA. Lahey Clin Fdn, Infect Dis Unit, Burlington, MA USA. Lahey Clin Fdn, Internal Med Unit, Burlington, MA USA. RP Grinspoon, SK (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Bulfinch 457B, Boston, MA 02114 USA. FU NIDDK NIH HHS [R01 DK49302] NR 30 TC 92 Z9 96 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUL PY 1998 VL 27 IS 1 BP 68 EP 72 DI 10.1086/514638 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA ZZ690 UT WOS:000074756900014 PM 9675454 ER PT J AU Hirsch, MS Klibanski, A AF Hirsch, MS Klibanski, A TI What price progress? Pseudo-Cushing's syndrome associated with antiretroviral therapy in patients with human immunodeficiency virus infection - Response SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material C1 Massachusetts Gen Hosp, Infect Dis Unit, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Hirsch, MS (reprint author), Massachusetts Gen Hosp, Infect Dis Unit, Dept Med, Gray 5,Fruit St, Boston, MA 02114 USA. NR 30 TC 20 Z9 20 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUL PY 1998 VL 27 IS 1 BP 73 EP 75 DI 10.1086/514637 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA ZZ690 UT WOS:000074756900015 PM 9675455 ER PT J AU Harris, A Lally, M Albrecht, M AF Harris, A Lally, M Albrecht, M TI Legionella bozemanii pneumonia in three patients with AIDS SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID LEGIONNAIRES-DISEASE; RISK; INFECTION AB Legionella bozemanii is known to cause pneumonia often in immunocompromised hosts. To our knowledge, we describe the first three cases of L. bozemanii pneumonia in patients with AIDS. At the time of presentation, these patients had varied histories, physical findings, and radiological findings. All three patients had a uniformly excellent response to treatment despite receiving different antibiotic regimens. The cases illustrate the need for thorough diagnostic workups and prompt institution of antibiotic therapy when clinical suspicion for L. bozemanii infection is high. C1 Dept Med, Infect Dis Serv, Boston, MA 02215 USA. RP Harris, A (reprint author), Dept Med, Infect Dis Serv, Beth Israel Deaconess Med Ctr W Campus,Kennedy Bl, Boston, MA 02215 USA. RI Lally, Michelle/I-4865-2016 OI Lally, Michelle/0000-0003-0716-4668 NR 14 TC 22 Z9 22 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUL PY 1998 VL 27 IS 1 BP 97 EP 99 DI 10.1086/514618 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA ZZ690 UT WOS:000074756900021 PM 9675461 ER PT J AU Johnson, M Krosnick, A Carson, P McDade, AM Laraway, K AF Johnson, M Krosnick, A Carson, P McDade, AM Laraway, K TI A retrospective chart review of uncontrolled use of metformin as an add-on therapy in type 2 diabetes SO CLINICAL THERAPEUTICS LA English DT Article DE metformin; type 2 diabetes; combination therapy; obesity ID INSULIN THERAPY; MELLITUS; IMPROVEMENT; OBESE AB The hyperglycemia, hyperinsulinemia, insulin resistance, and obesity syndrome associated with type 2 diabetes can have debilitating consequences. The biguanide metformin has a mechanism of action that is complementary to those of insulin and the sulfonylureas, suggesting that combination therapy that includes metformin may result in improved glycemic control. The purpose of this retrospective chart review was to determine the effects of adding metformin in an uncontrolled fashion to existing therapy in obese patients with type 2 diabetes who had suboptimal glycemic control and insulin resistance. For the review, the records of 124 patients were divided into two groups: group 1 included 71 patients who were taking insulin with or without a sulfonylurea, and group 2 consisted of 53 patients who were taking a sulfonylurea alone. Metformin was added to patients' existing therapy in conjunction with downward titration of the sulfonylurea and insulin doses. A retrospective chart review was conducted at the end of 6 months for group 1 and at the end of 12 months for group 2 to determine the change from baseline in measures of diabetes control tie, insulin and sulfonylurea dose, glycated hemoglobin [Hb A(1c)] value, body mass index [BMI], and Lipid profiles). In group 1, the mean insulin dose decreased from 46.4 U/d at baseline to 6.1 U/d at the end of followup. Eighty-three percent of the patients were able to discontinue insulin therapy completely Similarly, group 2 had statistically significant reductions in mean sulfonylurea dose. Both groups also achieved statistically significant reductions in Hb A(1c), BMI, and total cholesterol level. The addition of metformin to treatment with insulin or sulfonylureas, either alone or in combination, significantly improved glycemic control and cholesterol levels and promoted weight loss in obese type 2 diabetic patients with insulin resistance. Less than 5% of patients reported mild, transient gastrointestinal side effects, none of which required cessation of metformin therapy. Five patients discontinued metformin due to lack of efficacy. C1 Joslin Diabet Ctr, St barnabas Hlth Care Syst, Princeton, NJ 08540 USA. RP Johnson, M (reprint author), Joslin Diabet Ctr, St barnabas Hlth Care Syst, Carnegie Profess Bldg,100 Canal Pointe Blvd,Suite, Princeton, NJ 08540 USA. NR 14 TC 17 Z9 17 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0149-2918 J9 CLIN THER JI Clin. Ther. PD JUL-AUG PY 1998 VL 20 IS 4 BP 691 EP 698 DI 10.1016/S0149-2918(98)80132-X PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 114VG UT WOS:000075629400007 PM 9737829 ER PT J AU Blais, MA Matthews, J Schouten, R O'Keefe, SM Summergrad, P AF Blais, MA Matthews, J Schouten, R O'Keefe, SM Summergrad, P TI Stability and predictive value of self-report personality traits pre- and post-electroconvulsive therapy: A preliminary study SO COMPREHENSIVE PSYCHIATRY LA English DT Article ID MAJOR DEPRESSION; AXIS-II; DISORDERS; STATE; COMORBIDITY; INVENTORY; RECOVERY; MCMI AB The accuracy and value of personality assessment for depressed patients receiving electroconvulsive therapy (ECT) is an underexplored and controversial area. However, there are data suggesting that personality traits and personality disorders affect the ultimate outcome of depressed patients receiving a variety of somatic treatments including ECT. Despite these data, controversy continues regarding the advisability of evaluating personality functioning in patients with severe depression. This study sought to explore the stability and predictive value of self-reported personality traits in depressed patients undergoing ECT Sixteen subjects completed a self-report test of personality functioning and the Beck Depression Inventory (BDI) before and after ECT treatment. The results showed that the majority of self-report personality traits were stable pre- and post-ECT treatment. However, major depressive disorder did significantly affect the report of avoidant, histrionic, aggressive-sadistic, and schizotypal personality traits. Treatment did not change the overall personality profile of these subjects. Furthermore, regression analysis controlling for pretreatment depression showed pretreatment borderline personality traits to be significantly related to the posttreatment depression scores (response to treatment). These findings suggest that routine administration of a standard self-report measure of personality may aid in the evaluation of and treatment planning for patients receiving ECT. Copyright (C) 1998 by W.B. Sanders Company. C1 Massachusetts Gen Hosp, Inpatient Psychiat Serv, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Blais, MA (reprint author), Massachusetts Gen Hosp, Inpatient Psychiat Serv, Dept Psychiat, Blake 11,55 Fruit St, Boston, MA 02114 USA. NR 29 TC 10 Z9 10 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0010-440X J9 COMPR PSYCHIAT JI Compr. Psychiat. PD JUL-AUG PY 1998 VL 39 IS 4 BP 231 EP 235 DI 10.1016/S0010-440X(98)90066-9 PG 5 WC Psychiatry SC Psychiatry GA 100AE UT WOS:000074791100010 PM 9675509 ER PT J AU Podolsky, D AF Podolsky, D TI Inflammatory bowel disease: still looking for definitions SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Gastrointestinal Unit, Boston, MA 02114 USA. RP Podolsky, D (reprint author), Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Gastrointestinal Unit, 55 Fruit St,GRJ-719, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0267-1379 J9 CURR OPIN GASTROEN JI Curr. Opin. Gastroenterol. PD JUL PY 1998 VL 14 IS 4 BP 281 EP 282 DI 10.1097/00001574-199807000-00001 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZZ329 UT WOS:000074718500001 ER PT J AU Sands, BE AF Sands, BE TI Clinical features of inflammatory bowel disease SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Article AB Attentive clinical observation continues to provide fresh insight into the diagnosis and pathogenesis of inflammatory bower disease (IBD). While investigations of the genetic basis of IBD have relied on the ability to distinguish Crohn's disease and ulcerative colitis among distinct phenotypes, recent publications have disputed some of the anatomic and histologic criteria that are the basis of these distinctions. Observational cohorts have provided an increased appreciation of the systemic nature of IBD, and recognition of specific complications both intrinsic and extrinsic to the gastrointestinal tract. Careful interpretation of these data may lead to improved management, as well as hypotheses to be examined at the benchtop. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Sands, BE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 55 Fruit St GRJ-825A, Boston, MA 02114 USA. NR 32 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0267-1379 J9 CURR OPIN GASTROEN JI Curr. Opin. Gastroenterol. PD JUL PY 1998 VL 14 IS 4 BP 300 EP 305 DI 10.1097/00001574-199807000-00005 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZZ329 UT WOS:000074718500005 ER PT J AU Bonventre, JV Force, T AF Bonventre, JV Force, T TI Mitogen-activated protein kinases and transcriptional responses in renal injury and repair SO CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION LA English DT Review ID CYTOSOLIC PHOSPHOLIPASE A(2); SMOOTH-MUSCLE CELLS; P38 MAP KINASE; SIGNAL-TRANSDUCTION; NUCLEAR TRANSLOCATION; TERMINAL KINASES; ARACHIDONIC-ACID; TYROSINE KINASES; 14-3-3 PROTEIN; S6 KINASE AB Mammalian cells respond to external stimuli by activation of a variety of signal transduction pathways which culminate in stereotypical responses important in renal disease, such as proliferation, growth arrest, hypertrophy, differentiation, or apoptosis. A set of intracellular signalling events occurs ultimately leading to the transcription of genes whose encoded proteins mediate the response. In vertebrates many of the stimuli which result in these important cellular responses initiate intracellular signalling events which converge on a set of cellular kinase cascades which are collectively called the mitogen-activated protein (MAP) kinase cascades. There are three families of MAP kinases that have been identified in mammalian cells. These kinase pathways as well as other cellular signalling pathways are critically important for the regulation of transcriptional events. In this review, we will discuss recently published information on how MAP kinases and transcription factors regulated by these kinases may be implicated in renal injury and repair. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Med Serv, Boston, MA USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Bonventre, JV (reprint author), Massachusetts Gen Hosp E, Suite 4002,149-13th St, Charlestown, MA 02129 USA. OI Force, Thomas/0000-0002-0450-8659 NR 89 TC 24 Z9 24 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1062-4821 J9 CURR OPIN NEPHROL HY JI Curr. Opin. Nephrol. Hypertens. PD JUL PY 1998 VL 7 IS 4 BP 425 EP 433 DI 10.1097/00041552-199807000-00013 PG 9 WC Urology & Nephrology; Peripheral Vascular Disease SC Urology & Nephrology; Cardiovascular System & Cardiology GA 102XW UT WOS:000074952400013 PM 9690043 ER PT J AU Mead, PE Kelley, CM Hahn, PS Piedad, O Zon, LI AF Mead, PE Kelley, CM Hahn, PS Piedad, O Zon, LI TI SCL specifies hematopoietic mesoderm in Xenopus embryos SO DEVELOPMENT LA English DT Article DE Xenopus; SCL; hematopoiesis mesoderm; cell fate ID T-CELL LEUKEMIA; BONE MORPHOGENETIC PROTEIN-4; TRANSCRIPTION FACTOR GATA-1; LOOP-HELIX GENES; HOMEOBOX GENE; VENTRAL MESODERM; TAL-1 GENE; ERYTHROID-DIFFERENTIATION; CHROMOSOME-TRANSLOCATION; MICE LACKING AB Targeted gene disruption experiments in the mouse have demonstrated an absolute requirement for several transcription factors for the development of hematopoietic progenitors during embryogenesis. Disruption of the basic helix-loop-helix gene SCL (stem cell leukemia) causes a block early in the hematopoietic program with defects in all hematopoietic lineages. To understand how SCL participates in the organogenesis of blood, we have isolated cDNAs encoding Xenopus SCL and characterized the function of SCI, during embryogenesis. We demonstrate that SCL is expressed in ventral mesoderm early in embryogenesis, SCL expression is induced by BMP-4, and a dominant negative BMP-4 receptor inhibits SCL expression in the ventral region of the embryo. Expression of SCL in either bFGF-treated animal pole explants or dorsal marginal zone explants leads to the expression of globin protein. Furthermore, over-expression of SCL does not alter normal dorsal-ventral patterning in the embryo, indicating that SCL acts to specify mesoderm to a hematopoietic fate after inductive and patterning events have occurred. We propose that SCL is both necessary and sufficient to specify hematopoietic mesoderm, and that it has a similar role in specifying hematopoietic cell fate as MyoD has in specifying muscle cell fate. C1 Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Pediat,Dana Farber Canc Inst, Boston, MA USA. RP Zon, LI (reprint author), Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. RI Kelley, Clair/O-2688-2015 NR 80 TC 96 Z9 97 U1 0 U2 0 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0950-1991 J9 DEVELOPMENT JI Development PD JUL PY 1998 VL 125 IS 14 BP 2611 EP 2620 PG 10 WC Developmental Biology SC Developmental Biology GA 110DN UT WOS:000075365000008 PM 9636076 ER PT J AU Moss, JB Xavier-Neto, J Shapiro, MD Nayeem, SM McCaffery, P Drager, UC Rosenthal, N AF Moss, JB Xavier-Neto, J Shapiro, MD Nayeem, SM McCaffery, P Drager, UC Rosenthal, N TI Dynamic patterns of retinoic acid synthesis and response in the developing mammalian heart SO DEVELOPMENTAL BIOLOGY LA English DT Article ID QUAIL EMBRYO; ANTEROPOSTERIOR POLARITY; MOUSE EMBRYOGENESIS; GENE-EXPRESSION; RXR GENES; MORPHOGENESIS; MICE; DEHYDROGENASE; TRANSCRIPTION; RECEPTORS AB Retinoic acid (RA) has been implicated in cardiac morphogenesis by its teratogenic effects on the heart, although its role in normal cardiogenesis remains unknown. To define the parameters of RA action in cardiac morphogenesis, we analyzed the patterns of ligand synthesis, response, and inactivation in the developing mouse heart. Activation of a lacZ transgene controlled by an RA response element (RARE) was compared to the localization of the retinaldehydeoxidizing dehydrogenase RALDH2, the earliest RA synthetic enzyme in the mouse embryo, and to the expression of a gene encoding an RA-degrading enzyme (P450RA). We observed that RALDH2 localization and RA response were virtually superimposable throughout heart development. Initially, both RALDH2 and RARE-LacZ activity were restricted to the sinus venosa in unlooped hearts, but were high in the dorsal mesocardium, while P450RA expression was restricted to the endocardium. Later stages were characterized by a sequential, noncontiguous progression of RALDH2 accumulation and RA response, from the sinus venosa to atria, dorsal-medial conotruncus, aortic arches, and the epicardium. This dynamic pattern of RA response was a direct result of localized RALDH2 since hearts of cultured embryos were uniformly competent to respond to an exogenous RA challenge. These observations support a model in which the influence of endogenous RA on heart development depends upon localized presentation of the ligand, with only limited diffusion from the source of its synthesis. (C) 1998 Academic Press. C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Univ Sao Paulo, Fac Med, Inst Coracao InCor, Mol Biol Lab, Sao Paulo, Brazil. Harvard Univ, Museum Comparat Zool, Cambridge, MA 02138 USA. Harvard Univ, Dept Organism & Evolutionary Biol, Cambridge, MA 02138 USA. Eunice Kennedy Shriver Ctr Mental Retardat Inc, Div Dev Neurosci, Waltham, MA 02154 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Rosenthal, N (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. OI Drager, Ursula C/0000-0003-1815-190X FU NIA NIH HHS [AG12316]; NIAMS NIH HHS [AR41926]; NICHD NIH HHS [5F32HD07926-03] NR 44 TC 137 Z9 138 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 1 PY 1998 VL 199 IS 1 BP 55 EP 71 DI 10.1006/dbio.1998.8911 PG 17 WC Developmental Biology SC Developmental Biology GA ZZ809 UT WOS:000074769300005 PM 9676192 ER PT J AU Taborsky, GJ Ahren, B Havel, PJ AF Taborsky, GJ Ahren, B Havel, PJ TI Autonomic mediation of glucagon secretion during hypoglycemia - Implications for impaired alpha-cell responses in type 1 diabetes SO DIABETES LA English DT Review ID INSULIN-INDUCED HYPOGLYCEMIA; DEFECTIVE GLUCOSE COUNTERREGULATION; SUBCUTANEOUS INSULIN; PANCREAS TRANSPLANTATION; NERVOUS-SYSTEM; BETA-CELLS; DEFICIENT COUNTERREGULATION; SUBSEQUENT HYPOGLYCEMIA; ANTECEDENT HYPOGLYCEMIA; EPINEPHRINE SECRETION AB This article examines the role of the autonomic nervous system in mediating the increase of glucagon secretion observed during insulin-induced hypoglycemia (IIH). In the first section, we briefly review the importance of the or-cell response in recovery from hypoglycemia under both physiologic conditions and pathophysiologic conditions, such as type 1 diabetes. We outline three possible mechanisms that may contribute to increased glucagon secretion during hypoglycemia but emphasize autonomic mediation. In the second section, we review the critical experimental data in animals, nonhuman primates, and humans suggesting that, in the absence of diabetes, the majority of the glucagon response to IIH is mediated by redundant autonomic stimulation of the islet alpha-cell. Because the glucagon response to hypoglycemia is often impaired in patients with type 1 diabetes, in the third section, we examine the possibility that autonomic impairment contributes to the impairment of the glucagon response in these patients. We review two different types of autonomic impairment. The first is a slow-onset and progressive neuropathy that worsens with duration of diabetes, and the second is a rapid-onset, but reversible, autonomic dysfunction that is acutely induced by antecedent hypoglycemia. We propose that both types of autonomic dysfunction can contribute to the impaired glucagon responses in patients with type 1 diabetes. In the fourth section, rye relate restoration of these glucagon responses to restoration of the autonomic responses to hypoglycemia. Finally, in the fifth section, we summarize the concepts underlying the autonomic hypothesis, the evidence for it, and the implications of the autonomic hypothesis for the treatment of type 1 diabetes. C1 Vet Affairs Puget Sound Hlth Care Syst, Div Endocrinol & Metab 151, Seattle, WA 98108 USA. Univ Washington, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. Lund Univ, Malmo Univ Hosp, Dept Med, Malmo, Sweden. Univ Calif Davis, Dept Nutr, Davis, CA USA. RP Taborsky, GJ (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Div Endocrinol & Metab 151, 1660 S Columbian Way, Seattle, WA 98108 USA. EM taborsky@u.washington.edu FU NIDDK NIH HHS [DK-50154, DK-12829, DK-17047] NR 114 TC 139 Z9 140 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD JUL PY 1998 VL 47 IS 7 BP 995 EP 1005 DI 10.2337/diabetes.47.7.995 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZW656 UT WOS:000074433500001 PM 9648820 ER PT J AU Leech, CA Habener, JF AF Leech, CA Habener, JF TI A role for Ca2+-sensitive nonselective cation channels in regulating the membrane potential of pancreatic beta-cells SO DIABETES LA English DT Article ID INSULIN-SECRETING CELLS; CYCLASE-ACTIVATING POLYPEPTIDE; K-ATP CHANNEL; SULFONYLUREA BINDING; B-CELLS; CALCIUM; CURRENTS; PALYTOXIN; LINE; PERMEABILITY AB The incretin hormones, glucagon-like peptide 1 and pituitary adenylyl cyclase-activating polypeptide, are proposed to activate a maitotoxin (MTX)-sensitive, Ca2+-dependent nonselective cation current in pancreatic beta-cells and insulinoma cells. This MTX-sensitive current is present in human beta-cells as men as in mouse and rat beta-cells, and is accompanied by a rise in cytosolic Ca2+ in voltage-clamped cells in which the activation of voltage-dependent Ca2+ channels is prevented. Activation of the nonselective cation current is inhibited by reduction of disulfide bonds with intracellular, but not extracellular, dithiothreitol, and is also abolished by intracellular dialysis with trypsin. The nonselective cation channels that carry this current have a conductance of about 30 pS, with Na+ as the major extracellular cation. We estimate that these cation channels are expressed on beta-cells at a density similar to that of ATP-sensitive potassium channels (K-ATP channels) and exhibit spontaneous activity at basal glucose concentrations. We propose that this spontaneous cation channel activity constitutes at least part of the depolarizing background conductance that permits changes in the activity of K-ATP channels to regulate the resting potential of beta-cells. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst,Lab Mol Endocrinol, Boston, MA 02114 USA. RP Leech, CA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst,Lab Mol Endocrinol, 55 Fruit St,WEL 320, Boston, MA 02114 USA. EM leech@helix.mgh.harvard.edu NR 39 TC 45 Z9 46 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUL PY 1998 VL 47 IS 7 BP 1066 EP 1073 DI 10.2337/diabetes.47.7.1066 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZW656 UT WOS:000074433500011 PM 9648830 ER PT J AU Schuppin, GT Pons, S Hugl, S Aiello, LP King, GL White, M Rhodes, CJ AF Schuppin, GT Pons, S Hugl, S Aiello, LP King, GL White, M Rhodes, CJ TI A specific increased expression of insulin receptor substrate 2 in pancreatic beta-cell lines is involved in mediating serum-stimulated beta-cell growth SO DIABETES LA English DT Article ID FACTOR-I; SIGNAL-TRANSDUCTION; MESSENGER-RNA; TYROSINE PHOSPHORYLATION; DIFFERENTIAL DISPLAY; HORMONE RECEPTOR; RAT; GLUCOSE; ISLETS; MICE AB Certain nutrients and growth factors can stimulate pancreatic beta-cell growth. However, the appropriate mitogenic signaling pathways in beta-cells have been relatively undefined. In this study, differential gene expression in NEDH rat insulinoma was compared with NEDH rat primary islet beta-cells. Differential mRNA display analysis revealed an elevated expression in insulinoma of VL30 transposons, S24 ribosomal protein, and cytochrome-C oxidase VIIc that is typical for cells undergoing mitosis. A gene candidate approach revealed that mRNA levels of the oncogenes c-fos and c-jun were equivalently expressed in insulinoma and islet cells, as was the mRNA for the mitogenic signal transduction molecule insulin receptor substrate (IRS)-1. However, in contrast to that of IRS-1, IRS-2 gene expression was 60- to 70-fold higher in the insulinoma tissue compared with islets, which was reflected at the protein as well as the mRNA level. The specific elevated IRS-2 expression was a consistent observation across all rodent pancreatic beta-cell lines. To investigate whether IRS-2 was functional, serum-stimulated beta-cell proliferation was examined in isolated insulinoma. cells. After a 48-h period of serum withdrawal, 24 h of serum refeeding rendered an 8- to 10-fold increase in [H-3]thymidine incorporation into insulinoma cells. This serum-stimulated DNA synthesis was prevented by inhibitors of tyrosine protein kinase and phosphatidylinositol (PI) 3-kinase activities, as well as the activation of mitogen-activated protein (MAP) kinase and p70(S6K). Examination of IRS-mediated signal transduction pathways indicated that after 10-15 min of serum refeeding, there was increased tyrosine phosphorylation of IRS-2 and pp60, and PI 3-kinase recruitment to IRS-2. Serum also increased the association of growth factor-bound protein 2/ murine sons of sevenless 1 protein to a PI 3-kinase/IRS-2 protein complex. Moreover, serum also activated MAP-kinase (erk-1 and erk-2 isoforms) and 70 kD S6 kinase. Thus IRS-mediated signal transduction pathways are functional in pancreatic beta-cells. It is conceivable that IRS-2 expression in beta-cells contributes to maintaining the islet beta-cell population, complementary to observations in the IRS-2 knockout mouse in which beta-cell mass is markedly reduced. C1 Univ Texas, SW Med Ctr, Dept Internal Med, Gifford Labs Diabet Res, Dallas, TX 75235 USA. Univ Texas, SW Med Ctr, Dept Pharmacol, Gifford Labs Diabet Res, Dallas, TX 75235 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA USA. RP Rhodes, CJ (reprint author), Univ Texas, SW Med Ctr, Dept Internal Med, Gifford Labs Diabet Res, 5323 Harry Hines Blvd, Dallas, TX 75235 USA. EM rhodes02@utsw.swmed.edu RI Pons , Sebastian/K-7794-2014 OI Pons , Sebastian/0000-0003-1027-0621 FU NEI NIH HHS [EY-10827]; NIDDK NIH HHS [DK-50610, DK-43808] NR 55 TC 44 Z9 44 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUL PY 1998 VL 47 IS 7 BP 1074 EP 1085 DI 10.2337/diabetes.47.7.1074 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZW656 UT WOS:000074433500012 PM 9648831 ER PT J AU Moczulski, DK Rogus, JJ Antonellis, A Warram, JH Krolewski, AS AF Moczulski, DK Rogus, JJ Antonellis, A Warram, JH Krolewski, AS TI Major susceptibility locus for nephropathy in type 1 diabetes on chromosome 3q - Results of novel discordant sib-pair analysis SO DIABETES LA English DT Article ID STAGE RENAL-DISEASE; FAMILIAL PREDISPOSITION; LINKAGE DISEQUILIBRIUM; PIMA-INDIANS; GENE; MELLITUS; POLYMORPHISM; IDDM; AMERICANS; TRAITS AB Diabetic nephropathy (DN) clusters in families with type 1 diabetes and the degree of clustering suggests that a major gene having a common disease allele may be responsible. To investigate the chromosomal regions containing genes for the renin-angiotensin system, we performed a linkage study using pairs of siblings with type 1 diabetes who were discordant for DN. Theoretical considerations supported by simulation studies indicated that such discordant pairs, rather than the usual concordant pairs, mould be more effective in detecting a major susceptibility gene for DN. me applied this novel strategy to test for linkage between DN and chromosomal regions containing genes for the ACE, angiotensinogen (AGT), and angiotensin II type 1 receptor (AT1). Two polymorphic markers mere genotyped in the vicinity of each of the three loci in 66 discordant sib pairs and were analyzed with multipoint methods. The regions containing ACE and AGT loci were not linked with DN, while the region containing the AT1 locus showed linkage with DN. As a result of these positive findings, eight additional polymorphic markers spanning a 63-cM region around AT1 locus mere genotyped. Linkage was demonstrated between DN and a 20-cM region that includes AT1 (P = 7.7 x 10(-5)), an obvious candidate gene for DN. To investigate whether AT1 could account for the observed Linkage, we sequenced all exons, splicing junctions, and the promoter region and examined the identified polymorphisms/mutations for association with DN using the transmission disequilibrium test. Four nem polymorphisms in the gene mere found, but neither these nor previously described polymorphisms were associated with DN. Thus, while our study does not implicate AT1 itself in the etiology of DN, it provides very strong evidence that a 20-cM region around AT1 contains a major locus for susceptibility to DN. C1 Joslin Diabet Ctr, Div Res, Sect Genet & Epidemiol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Program Populat Genet, Boston, MA 02115 USA. RP Krolewski, AS (reprint author), Joslin Diabet Ctr, Div Res, Sect Genet & Epidemiol, 1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK53534] NR 35 TC 131 Z9 135 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUL PY 1998 VL 47 IS 7 BP 1164 EP 1169 DI 10.2337/diabetes.47.7.1164 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZW656 UT WOS:000074433500026 PM 9648845 ER PT J AU Meier, M Brand, J Standl, E Schnell, O AF Meier, M Brand, J Standl, E Schnell, O TI Successful treatment with insulin analog lispro in IDDM with delayed absorption of subcutaneously applied human regular insulin and complicated intraperitoneal insulin infusion - A case report SO DIABETES CARE LA English DT Article ID RESISTANCE AB OBJECTIVE-To subcutaneously administer the insulin analog lispro in a patient with delayed absorption of subcutaneously applied human regular insulin whose continuous intraperitoneal insulin infusion (CIPII) with a percutaneous access device had required multiple surgical interventions because of complications. RESEARCH DESIGN AND METHODS-In a 35-year-old woman with long-term IDDM and delayed absorption of subcutaneously applied human regular insulin, a 3-year CIPII with human regular insulin via a percutaneous access device was complicated by three catheter obstructions and one subcutaneous abscess. Each complication required the implantation of a new percutaneous access device. During a 2-day trial with continuous subcutaneous insulin infusion (CSII) of the insulin analog lispro at basal infusion rates of 0.5-1.1 U/h, stable metabolic control was achieved. A 5-h intermediate attempt with human regular insulin in CSII, however, increased blood glucose concentrations from 6.0 to 28.8 mmol/l, despite identical basal rates and additional injection of 16 U of human regular insulin. Restarting with CSII of the insulin analog lispro reinforced stable metabolic control. CONCLUSIONS-It is suggested that the insulin analog lispro is a promising approach in the treatment of IDDM with delayed absorption of subcutaneously applied human regular insulin and a suitable alternative therapy for patients with complications attributed to percutaneous access devices for CIPII. C1 Schwabing Hosp, Diabet Res Inst, Munich, Germany. Schwabing Hosp, Dept Med 3, Munich, Germany. RP Meier, M (reprint author), Joslin Diabet Ctr, Sect Vasc Cell Biol, 1 Joslin Pl, Boston, MA 02215 USA. NR 14 TC 3 Z9 3 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JUL PY 1998 VL 21 IS 7 BP 1044 EP 1045 DI 10.2337/diacare.21.7.1044 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZW496 UT WOS:000074416800003 PM 9653592 ER PT J AU Pluen, A Tinland, B Sturm, J Weill, G AF Pluen, A Tinland, B Sturm, J Weill, G TI Migration of single-stranded DNA in polyacrylamide gels during electrophoresis SO ELECTROPHORESIS LA English DT Article DE single-stranded DNA; reptation theory; pore diameter; pulsed field gel electrophoresis; fluorescence recovery after photobleaching; electric birefringence; dynamics of orientation of DNA ID ELECTRIC BIREFRINGENCE; REPTATION THEORY; AGAROSE GELS; PORE-SIZE; FIELD; ORIENTATION; MOBILITY; SEPARATION; DIFFUSION; MECHANISM AB By using fluorescence recovery after photobleaching (FRAP) and electric birefringence, the migration of single-stranded DNA in polyacrylamide gels and orientation as a response to an electric pulse were investigated. Electrophoretic mobility is in good agreement with the model of biased reptation including fluctuations. The determination of the electrophoretic mobility in solution, Cc,, allows an estimation of the gel pore diameter seen by the molecule. As previously observed for double-stranded DNA, the electric birefringence results from two processes: the alignment of the molecule along the electric field and the elongation of the primitive path in the gel, for long single-stranded DNA (> 2000 bases). The combination of results obtained with the two techniques allows us to propose experimental conditions to improve the separation of single-stranded DNA with pulsed field techniques. C1 Univ Strasbourg, Strasbourg, France. Inst Charles Sadron, CNRS, F-67083 Strasbourg, France. RP Harvard Univ, Massachusetts Gen Hosp, Sch Med, EL Steele Labs Tumor Biol, 100 Blossom St,Cox 7, Boston, MA 02114 USA. EM aiain-pluen@worldnet.att.net RI Pluen, Alain/F-5300-2015 OI Pluen, Alain/0000-0002-5953-8011 NR 36 TC 23 Z9 23 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0173-0835 EI 1522-2683 J9 ELECTROPHORESIS JI Electrophoresis PD JUL PY 1998 VL 19 IS 10 BP 1548 EP 1559 DI 10.1002/elps.1150191005 PG 12 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 108XD UT WOS:000075290300004 PM 9719524 ER PT J AU Pinzone, JJ Katznelson, L Klibanski, A AF Pinzone, JJ Katznelson, L Klibanski, A TI Acromegalic heart disease SO ENDOCRINOLOGIST LA English DT Review ID GROWTH-HORMONE HYPERSECRETION; SOMATOSTATIN ANALOG OCTREOTIDE; LEFT-VENTRICULAR HYPERTROPHY; I GENE-EXPRESSION; MUSCLE; RATS; PERFORMANCE; SUPPRESSION; MORPHOLOGY; INDUCTION AB Acromegaly is a syndrome of autonomous overproduction of growth hormone (GH), most commonly caused by a pituitary adenoma, Hypersecretion of GH and insulin-like growth factor-I (IGF-I) leads to somatic enlargement, hypertension, and diabetes mellitus. There is increasing awareness that clinically elevated GH and ICE-I levels lead to a cardiomyopathy that is independent of the presence of coexisting risk factors for heart disease. This article will review the clinicopathologic effects of GH and TGF I on the cardio vascular system as investigated in patients with acromegaly and experimental animal models of GH excess. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Dept Med, Neuroendocrine Clin Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Klibanski, A (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Dept Med, Neuroendocrine Clin Ctr, Bulfinch 457B,32 Fruit St, Boston, MA 02114 USA. NR 36 TC 0 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1051-2144 J9 ENDOCRINOLOGIST JI Endocrinologist PD JUL-AUG PY 1998 VL 8 IS 4 BP 273 EP 278 DI 10.1097/00019616-199807000-00007 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 108BP UT WOS:000075246400007 ER PT J AU Ziegler, TR Mantell, MP Chow, JC Rombeau, JL Smith, RJ AF Ziegler, TR Mantell, MP Chow, JC Rombeau, JL Smith, RJ TI Intestinal adaptation after extensive small bowel resection: Differential changes in growth and insulin-like growth factor system messenger ribonucleic acids in jejunum and ileum SO ENDOCRINOLOGY LA English DT Article ID IGF-I; JEJUNOILEAL RESECTION; BINDING PROTEIN-3; HUMAN-FETUS; RAT; RNA; LOCALIZATION; INHIBITION; EXPRESSION; EXTRACTION AB The distal small bowel exhibits greater adaptive growth than proximal segments after partial small intestine resection. To explore this process, we evaluated adaptive cellularity, intestinal insulin-like growth factor (IGF) system messenger RNA (mRNA) transcripts, and effects of recombinant IGF-I treatment in jejunum and ileum of adult rats. Gastrostomy-fed animals underwent 80% jejuno-ileal resection or intestinal transection and reanastomosis without resection, followed by infusion of human recombinant IGF-I (2.4 mg/kg day) or vehicle. After 7 days, resected rats demonstrated modest adaptive growth in jejunum and marked cell proliferation in ileum. Resection increased IGF-I mRNA in both jejunum (183%) and ileum (249%) and up-regulated IGFBP-4 mRNA levels in both tissues. IGFBP-3 mRNA fell significantly in ileum after resection. IGF-I infusion modestly increased ileal cellularity after resection, but had no effect in jejunum. IGF-I markedly increased IGFBP-3 mRNA levels in jejunum after both transection and resection. These data confirm that bowel resection induces greater adaptive growth in ileum than jejunum. IGF-I administration modestly increases ileal, but not jejunal, growth after resection. Increased levels of intestinal IGF-I and IGFBP-4 mRNA suggest roles for IGF-I and IGFBP-4 in mediating small bowel adaptation. Higher levels of jejunal IGFBP-3 mRNA may be related to limited jejunal us, ileal growth after extensive jejuno-ileal resection. C1 Emory Univ, Sch Med, Dept Med, Div Endocrinol & Metab, Atlanta, GA 30322 USA. Hosp Univ Penn, Dept Surg, Philadelphia, PA 19104 USA. Harvard Univ, Sch Med, Joslin Res Lab, Boston, MA 02215 USA. RP Smith, RJ (reprint author), Joslin Diabet Ctr, Metab Sect, 1 Joslin Pl, Boston, MA 02215 USA. EM smithr@joslab.harvard.edu FU NCRR NIH HHS [3-MO1-RR-00039-35S1]; NIDDK NIH HHS [DK-48503, DK-43038] NR 35 TC 41 Z9 42 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 1998 VL 139 IS 7 BP 3119 EP 3126 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZV802 UT WOS:000074342700013 PM 9645684 ER PT J AU Krahl, SE Clark, KB Smith, DC Browning, RA AF Krahl, SE Clark, KB Smith, DC Browning, RA TI Locus coeruleus lesions suppress the seizure-attenuating effects of vagus nerve stimulation SO EPILEPSIA LA English DT Article DE vagus nerve; locus coeruleus; norepinephrine; anticonvulsant; epilepsy ID CERVICAL VAGAL AFFERENTS; NOREPINEPHRINE DEPLETION; ELECTRICAL-STIMULATION; CENTRAL RELAYS; RATS; BRAIN; 6-HYDROXYDOPAMINE; FACILITATION; MODULATION AB Purpose: Although vagus nerve stimulation (VNS) is now marketed throughout most of the world as a treatment for drug-resistant epilepsy, the therapeutic mechanism of action of VNS-induced seizure suppression has not yet been established. Elucidation of this mechanism is an important first step in the development of strategies to improve VNS efficacy. Because the locus coeruleus (LC) has been implicated in the antinociceptive effects of VNS, we chemically lesioned the LC in the present study to determine if it is a critical structure involved in the anticonvulsant mechanisms of VNS. Methods: Rats were chronically depleted of norepinephrine (NE) by a bilateral infusion of 6-hydroxydopamine (6-OHDA) into the LC. Two weeks later, they were tested with maximal electroshock (MES) to assess VNS-induced seizure suppression. In another experiment, the LC was acutely inactivated with lidocaine, and seizure suppression was tested in a similar fashion. Results: VNS significantly reduced seizure severities of control rats. However, in animals with chronic or acute LC lesions, VNS-induced seizure suppression was attenuated. Conclusions: Our data indicate that the LC is involved in the circuitry necessary for the anticonvulsant effects of VNS. Seizure suppression by VNS may therefore depend on the release of NE, a neuromodulator that has anticonvulsant effects. These data suggest that noradrenergic agonists might enhance VNS-induced seizure suppression. C1 W Los Angeles Vet Affairs Med Ctr, Serv Neurol, Los Angeles, CA 90073 USA. So Illinois Univ, Dept Psychol, Carbondale, IL 62901 USA. So Illinois Univ, Dept Physiol, Carbondale, IL 62901 USA. RP Krahl, SE (reprint author), W Los Angeles Vet Affairs Med Ctr, Serv Neurol, Bldg 114,Rm 217,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 32 TC 257 Z9 264 U1 4 U2 24 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD JUL PY 1998 VL 39 IS 7 BP 709 EP 714 DI 10.1111/j.1528-1157.1998.tb01155.x PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA ZY909 UT WOS:000074674700005 PM 9670898 ER PT J AU Bennett, G Provenzale, JM AF Bennett, G Provenzale, JM TI Schistosomal myelitis: findings at MR imaging SO EUROPEAN JOURNAL OF RADIOLOGY LA English DT Article DE schistosomal; myelitis; spinal cord; MR imaging ID SPINAL-CORD SCHISTOSOMIASIS; INVOLVEMENT; MANSONI AB Schistosomal spinal cord involvement is a rare complication of infection by Schistosoma mansoni. This work reports the MR imaging findings in a patient with schistosomal myelitis involving the lower spinal cord and conus medullaris. MR imaging showed a focal mass with a slightly nodular surface and which had peripheral enhancement after contrast administration. The MR appearance of this complication of schistosomal infection is important to recognize so that early medical therapy can be started in an attempt to maximize neurologic recovery. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Provenzale, JM (reprint author), Duke Univ, Med Ctr, Dept Radiol, Durham, NC 27710 USA. NR 12 TC 21 Z9 23 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0720-048X J9 EUR J RADIOL JI Eur. J. Radiol. PD JUL PY 1998 VL 27 IS 3 BP 268 EP 270 DI 10.1016/S0720-048X(98)00006-0 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 110KY UT WOS:000075380900013 PM 9717645 ER PT J AU Velier, J Kim, M Schwarz, C Kim, TW Sapp, E Chase, K Aronin, N DiFiglia, M AF Velier, J Kim, M Schwarz, C Kim, TW Sapp, E Chase, K Aronin, N DiFiglia, M TI Wild-type and mutant huntingtins function in vesicle trafficking in the secretory and endocytic pathways SO EXPERIMENTAL NEUROLOGY LA English DT Article ID SUBSTANCE-P; DISEASE; RECEPTOR; PROTEIN; BRAIN; INTERNALIZATION; CLATHRIN; EXPRESSION; NEURONS; LOCALIZATION AB Huntingtin is a cytoplasmic protein that is found in neurons and somatic cells. In patients with Huntington's disease (HD), the NH2-terminal region of huntingtin has an expanded polyglutamine tract. An abnormal protein interaction by mutant huntingtin has been proposed as a mechanism for HD pathogenesis. Huntingtin associates with vesicle membranes and interacts with proteins involved in vesicle trafficking. It is unclear where along vesicle transport pathways wildtype and mutant huntingtins are found and whether polyglutamine expansion affects this localization. To distinguish wild-type and mutant huntingtin, fibroblasts from normals and HD patients with two mutant alleles (homozygotes) mere examined. Immunofluorescence confocal microscopy showed that mutant huntingtin localized with clathrin in membranes of the trans Golgi network and in clathrin;coated and noncoated endosomal vesicles in the cytoplasm and along plasma membranes. Separation of organelles in Nycodenz gradients showed that in normal and HD homozygote patient cells, huntingtin was present in membrane fractions enriched in clathrin. Similar results were obtained in fibroblasts from heterozyote juvenile HD patients who had a highly expanded polyglutamine tract in the HD allele. Western blot analysis of membrane fractions from rat brain showed that mild-type huntingtin was present in fractions that contained purified clathrin-coated membranes or a mixture of clathrin-coated and noncoated membranes. Electron microscopy of huntingtin immunoreactivity in rat brain revealed labeling along dendritic plasma membranes in association with clathrin-coated pits and clusters of noncoated endosomal vesicles 40-60 nm in diameter. These data suggest that wild-type and mutant huntingtin can influence vesicle transport in the secretory and endocytic pathways through associations with clathrin-coated vesicles. (C) 1998 Academic Press. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Univ Massachusetts, Med Ctr, Worcester, MA 01655 USA. RP Velier, J (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RI Kim, Manho/J-2738-2012 FU NINDS NIH HHS [NS 16367, NS31579] NR 38 TC 183 Z9 185 U1 0 U2 7 PU ACADEMIC PRESS INC 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 JUL PY 1998 VL 152 IS 1 BP 34 EP 40 DI 10.1006/exnr.1998.6832 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 106KC UT WOS:000075127600004 PM 9682010 ER PT J AU Klivenyi, P Matthews, RT Wermer, M Yang, LC MacGarvey, U Becker, DA Natero, R Beal, MF AF Klivenyi, P Matthews, RT Wermer, M Yang, LC MacGarvey, U Becker, DA Natero, R Beal, MF TI Azulenyl nitrone spin traps protect against MPTP neurotoxicity SO EXPERIMENTAL NEUROLOGY LA English DT Article DE MPTP; Parkinson's disease; free radicals; oxidative damage; spin traps; antioxidants ID TERT-BUTYL-NITRONE; TRAPPING AGENTS; FREE-RADICALS; LIPID-PEROXIDATION; DELAYED TREATMENT; OXIDATIVE DAMAGE; PBN; ISCHEMIA; BRAIN; RATS AB Azulenyl nitrones are a unique class of free radical spin-trapping compounds. We administered both a water-soluble and a lipid-soluble azulenyl nitrone to mice prior to administration of MPTP. Both compounds produced significant neuroprotection against depletions of dopamine and its metabolites measured 1 week. after MPTP administration. There were no effects on MPP+ levels. These findings provide further evidence that free radical scavengers can produce significant neuroprotection against MPTP neurotoxicity (C) 1998 Academic Press. C1 Massachusetts Gen Hosp, Neurol Serv, Neurochem Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Florida Int Univ, Dept Chem, Miami, FL 33199 USA. RP Klivenyi, P (reprint author), Massachusetts Gen Hosp, Neurol Serv, Neurochem Lab, Boston, MA 02114 USA. FU NINDS NIH HHS [NS31579] NR 36 TC 17 Z9 17 U1 0 U2 2 PU ACADEMIC PRESS INC 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 JUL PY 1998 VL 152 IS 1 BP 163 EP 166 DI 10.1006/exnr.1998.6824 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 106KC UT WOS:000075127600017 PM 9682023 ER PT J AU Herrmann, JM Brezinski, ME Bouma, BE Boppart, SA Pitris, C Southern, JF Fujimoto, JG AF Herrmann, JM Brezinski, ME Bouma, BE Boppart, SA Pitris, C Southern, JF Fujimoto, JG TI Two- and three-dimensional high-resolution imaging of the human oviduct with optical coherence tomography SO FERTILITY AND STERILITY LA English DT Article DE optical coherence tomography; infrared; imaging; fallopian tube; infertility; endometriosis; salpingoscopy; spectroscopy AB Objective: To evaluate the feasibility of optical coherence tomography, a new method of micron-scale imaging, for high-resolution assessment of the oviduct Optical coherence tomography is analogous to ultrasound except that it measures the backreflection of infrared light rather than acoustical waves. Design: The ampulla of a human fallopian tube was imaged in vitro using optical coherence tomography. Images were generated in 2 and 3 dimensions. Setting: University. Patient(s): Samples were obtained from women who had undergone hysterectomy for leiomyomatosis. Intervention(s): None Main Outcome Measure(s): The ability to perform imaging on a micron scale, which is a level of resolution higher than that of any currently available clinical technology. Result(s): Two- and three-dimensional data sets of the reflectance of a human fallopian tube were acquired. A volume of 5 x 5 x 2.5 mm (length x width x depth) was scanned. The axial resolution was 11 mu m, and the lateral resolution at the focus was 20 mu m. The data sets shelved detailed structures of the fallopian tube. Conclusion(s): Our ability to obtain micron-scale two- and three-dimensional images of an in vitro oviduct suggests that it may be possible to identify and surgically treat tubal causes of infertility. (Fertil Steril(R) 1998;70:155-8. (C) 1998 by American Society for Reproductive Medicine.). C1 MIT, Elect Res Lab, Cambridge, MA 02139 USA. MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA USA. Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Brezinski, ME (reprint author), MIT, Elect Res Lab, Bldg 36-357,77 Massachusetts Ave, Cambridge, MA 02139 USA. RI Boppart, Stephen/C-7338-2009; OI Pitris, Costas/0000-0002-5559-1050 FU NCI NIH HHS [NIH-9-RO1-CA75289]; NEI NIH HHS [NIH-9-RO1-EY11289-10]; NHLBI NIH HHS [NIH-1-R29-HL55686] NR 4 TC 27 Z9 27 U1 0 U2 2 PU AMER SOC REPRODUCTIVE MEDICINE PI BIRMINGHAM PA 1209 MONTGOMERY HIGHWAY, BIRMINGHAM, AL 35216-2809 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD JUL PY 1998 VL 70 IS 1 BP 155 EP 158 DI 10.1016/S0015-0282(98)00097-1 PG 4 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA ZX102 UT WOS:000074479600028 PM 9660439 ER PT J AU Mertz, H Kovacs, T Thronson, M Weinstein, W AF Mertz, H Kovacs, T Thronson, M Weinstein, W TI Gastric metaplasia of the duodenum: identification by an endoscopic selective mucosal staining technique SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID HELICOBACTER-PYLORI; CAMPYLOBACTER-PYLORI; ULCER; ACID; PATHOGENESIS; BULB AB Background: To understand the pathophysiology of duodenal ulcer disease, it is important to identify and quantitate gastric metaplasia of the duodenum, Methylene blue dye is absorbed well by intestinal mucosa, but not by gastric mucosa. Our aim was to validate a methylene blue staining technique for measurement of gastric metaplasia in the duodenum. Methods: Eight subjects with chronic duodenal ulcer disease and seven subjects with other upper intestinal disorders underwent duodenal methylene blue staining after application of a mucolytic agent. Biopsy specimens were obtained from blue-stained and pale unstained areas and assessed for gastric metaplasia histologically. Results: Pink or pale unstained duodenal areas had more gastric surface cell metaplasia than blue-stained areas. Unstained duodenum was also more likely to have extensive (more than 25% of the biopsy specimens) gastric metaplasia (60%) than blue-stained areas (9%). Subjects with duodenal ulcer disease had more unstained mucosa than controls. Conclusion: Methylene blue staining of the duodenum is useful to identify and quantitate gastric metaplasia. C1 Vanderbilt Univ, Div Gastroenterol, Dept Med, CURE Gastroent Biol Ctr, Nashville, TN 37232 USA. Univ Calif Los Angeles, Los Angeles, CA USA. W Los Angeles Vet Adm Med Ctr, Los Angeles, CA USA. RP Mertz, H (reprint author), Vanderbilt Univ, Div Gastroenterol, Dept Med, CURE Gastroent Biol Ctr, 1414 TVC, Nashville, TN 37232 USA. NR 12 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 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD JUL PY 1998 VL 48 IS 1 BP 32 EP 38 DI 10.1016/S0016-5107(98)70125-7 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 100CE UT WOS:000074795700005 PM 9684661 ER PT J AU Nishioka, NS Mycek, MA AF Nishioka, NS Mycek, MA TI Initial experience with a real-time video processor for enhancing endoscopic image contrast SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID ENHANCEMENT; DIAGNOSIS AB Background: An initial experience using a digital video processor to enhance contrast in endoscopic images in real-time is described. Methods: Endoscopic images were examined with a system using locally adaptive processing to balance variations in illumination and sharpen fine features in real-time. For comparison, indigo carmine dye, a popular exogenous contrast agent, was applied to one patient. Results: In general, contrast-enhanced images appeared to contain more mucosal detail, with reduced glare and features in shadowed areas revealed. When used in conjunction with indigo carmine, the enlarged crypt openings in an aberrant crypt focus were visible, the first such detection in vivo without the use of magnifying endoscopy. Conclusions: Real-time video contrast enhancement during endoscopic procedures appears to provide excellent mucosal detail and improve contrast in a clinically useful manner. C1 Massachusetts Gen Hosp, Med Serv, Gastrointestinal Unit, Boston, MA 02114 USA. MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA USA. RP Nishioka, NS (reprint author), Massachusetts Gen Hosp, Med Serv, Gastrointestinal Unit, Bartlett Hall 708,55 Fruit St, Boston, MA 02114 USA. NR 9 TC 9 Z9 9 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD JUL PY 1998 VL 48 IS 1 BP 62 EP 66 DI 10.1016/S0016-5107(98)70132-4 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 100CE UT WOS:000074795700012 PM 9684668 ER PT J AU Lawrence, SP Shimek, CM Deutsch, JC AF Lawrence, SP Shimek, CM Deutsch, JC TI Prostate cancer masquerading as a large rectal cancer: diagnosis by endoscopic ultrasound SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID TRANSRECTAL ULTRASOUND C1 Denver VA Med Ctr, Med Serv 111E, Denver, CO 80220 USA. Univ Colorado, Hlth Sci Ctr, Div Gastroenterol & Hepatol, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Dept Pathol, Denver, CO 80262 USA. RP Lawrence, SP (reprint author), Denver VA Med Ctr, Med Serv 111E, 1055 Clermont St, Denver, CO 80220 USA. NR 5 TC 4 Z9 4 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD JUL PY 1998 VL 48 IS 1 BP 88 EP 89 DI 10.1016/S0016-5107(98)70140-3 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 100CE UT WOS:000074795700020 PM 9684676 ER PT J AU Ronco, LV Karpova, AY Vidal, M Howley, PM AF Ronco, LV Karpova, AY Vidal, M Howley, PM TI Human papillomavirus 16 E6 oncoprotein binds to interferon regulatory factor-3 and inhibits its transcriptional activity SO GENES & DEVELOPMENT LA English DT Article DE IRF-3; HPV16; transcription; protein-protein interactions; oncoprotein ID CARCINOMA CELL-LINES; FULL-LENGTH E6; HUMAN KERATINOCYTES; FACTOR FAMILY; IFN-BETA; EPITHELIAL-CELLS; GENE-EXPRESSION; DNA-DAMAGE; HPV-16 E6; PROTEIN AB Interferon regulatory factor-3 (IRF-3) was found to specifically interact with HPV16 E6 in a yeast two-hybrid screen. IRF-3 is activated by the presence of double-stranded RNA or by virus infection to form a stable complex with other transcriptional regulators that bind to the regulatory elements of the IFN beta promoter. We show that IRF-3 is a potent transcriptional activator and demonstrate that HPV16 E6 can inhibit its transactivation function. The expression of HPV16 E6 in primary human keratinocytes inhibits the induction of IFN beta mRNA following Sendai virus infection. The binding of HPV16 E6 to IRF-3 does not result in its ubiquitination or degradation. We propose that the interaction of E6 with IRF-3 and the inhibition of IRF-3's transcriptional activity may provide the virus a means to circumvent the normal antiviral response of an HPV16-infected cell. C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. RP Howley, PM (reprint author), Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. FU NCI NIH HHS [P01 CA050661, P01-CA-50661-09]; NIAID NIH HHS [F32 AI009167, 5 F32 AI09167-02, P01 AI042257, P01AI42257-01] NR 69 TC 371 Z9 388 U1 1 U2 6 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD JUL 1 PY 1998 VL 12 IS 13 BP 2061 EP 2072 DI 10.1101/gad.12.13.2061 PG 12 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA ZZ144 UT WOS:000074700100013 PM 9649509 ER PT J AU Black, JA Dib-Hajj, S Cohen, S Hinson, AW Waxman, SG AF Black, JA Dib-Hajj, S Cohen, S Hinson, AW Waxman, SG TI Glial cells have heart: rH1 Na+ channel mRNA and protein in spinal cord astrocytes SO GLIA LA English DT Article DE astrocytes; cardiac Na channel; glial cells; immunocytochemistry; in situ hybridization; ion channels; RT-PCR; tetrodotoxin (TTX) ID ROOT GANGLION NEURONS; VOLTAGE-GATED SODIUM; MESSENGER-RNA EXPRESSION; ION CHANNELS; RAT-BRAIN; SKELETAL-MUSCLE; MOLECULAR-CLONING; ALPHA-SUBUNIT; GROWTH CONE; TETRODOTOXIN AB Astrocytes in vitro express several distinct voltage-sensitive sodium currents, including tetrodotoxin (TTX)-resistant in non-stellate astrocytes and TTX-sensitive currents in stellate astrocytes. However, the molecular identity of the underlying channels, and the mechanisms that regulate their expression, have yet to be identified. Since spinal cord astrocytes in vitro express sodium currents that are nearly ten-fold greater that those of astrocytes derived from other regions, we used reverse transcription polymerase chain reaction (RT-PCR), in situ hybridization, and immunocytochemistry to search for a sodium channel mRNA and protein corresponding to a TTX-resistant channel in these cells. RT-PCR did not detect transcripts for SNS, which is known to encode a TTX-resistant current in dorsal root ganglion neurons. However, RT-PCR demonstrated the presence of rH1 mRNA in cultured spinal cord astrocytes derived from postnatal day 0 (P0) Sprague Dawley rats at 7 days in vitro and in also intact spinal cords of P0 and P7 rats. Hybridization signal for rH1 mRNA was detected by in situ hybridization cytochemistry in most non-stellate and, at varying levels, in stellate astrocytes in these cultures. Immunocytochemical studies, utilizing a polyclonal antibody (R-12) generated against a conserved polypeptide sequence of sodium channels, demonstrated sodium channel immunoreactivity in non-stellate and stellate astrocytes in these cultures. Spinal cord cultures reacted with a rH1-specific polyclonal antibody also showed rH1 immunostaining in non-stellate and stellate astrocytes, although the intensity of the rH1 immunoreactivity in both astrocyte morphologies was attenuated compared to that observed with the R-12 generic sodium channel antibody. The presence of rH1 mRNA and protein in non-stellate astrocytes in vitro provides a possible correlate for the TTX-resistant current that has been recorded in these cells. Since TTX-resistant current is not present in stellate astrocytes, the presence of rH1 mRNA and protein in these cells suggests, in addition, that post-translational mechanisms participate in the control of sodium channel expression in these cells. (C) 1998 Wiley-Liss, Inc. C1 Vet Adm Med Ctr, Neurosci Res Ctr 127A, EPVA, PVA, W Haven, CT 06516 USA. Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06510 USA. Univ Penn, Dept Med, Div Cardiol, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Cardiol Sect, Philadelphia, PA USA. RP Black, JA (reprint author), Vet Adm Med Ctr, Neurosci Res Ctr 127A, EPVA, PVA, 950 Campbell Ave, W Haven, CT 06516 USA. EM black@biomed.med.yale.edu NR 62 TC 26 Z9 26 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0894-1491 J9 GLIA JI Glia PD JUL PY 1998 VL 23 IS 3 BP 200 EP 208 DI 10.1002/(SICI)1098-1136(199807)23:3<200::AID-GLIA3>3.0.CO;2-8 PG 9 WC Neurosciences SC Neurosciences & Neurology GA ZQ895 UT WOS:000073913800003 PM 9633805 ER PT J AU Karaivanova, VK Luan, P Spiro, RG AF Karaivanova, VK Luan, P Spiro, RG TI Processing of viral envelope glycoprotein by the endomannosidase pathway: evaluation of host cell specificity SO GLYCOBIOLOGY LA English DT Article DE endomannosidase; glycoprotein processing; vesicular stomatitis virus G protein; influenza virus hemagglutinin; glucosidase inhibition-linked oligosaccharides ID N-LINKED OLIGOSACCHARIDES; ALPHA-D-MANNOSIDASE; GLUCOSIDASE-II-DEFICIENT; ENDOPLASMIC-RETICULUM; RAT-LIVER; INFLUENZA-VIRUS; HEMAGGLUTININ; GLYCOSYLATION; KIFUNENSINE; INHIBITORS AB Endo-alpha-D-mannosidase is an enzyme involved in N-linked oligosaccharide processing which through its capacity to cleave the internal linkage between the glucose-substituted mannose and the remainder of the polymannose carbohydrate unit can provide an alternate pathway for achieving deglucosylation and thereby make possible the continued formation of complex oligosaccharides during a glucosidase blockade. In view of the important role which has been attributed to glucose on nascent glycoproteins as a regulator of a number of biological events, we chose to further define the in vivo action of endomannosidase by focusing on the well characterized VSV envelope glycoprotein (G protein) which can be formed by the large array of cell lines susceptible to infection by this pathogen, Through an assessment of the extent to which the G protein was converted to an endo-beta-N-acetylglucosaminidase (endo H)-resistant form during a castanospermine imposed glucosidase blockade, we found that utilization of the endomannosidase-mediated deglucosylation route was clearly host cell specific, ranging from greater than 90% in HepG2 and PtK1 cells to complete absence in CHO, MDCK, and MDBK cells, with intermediate values in BHK, BW5147,3, LLC-PK1, BRL, and NRK cell lines. In some of the latter group the electrophoretic pattern after endo H treatment suggested that only one of the two N-linked oligosaccharides of the G protein was processed by endomannosidase, In the presence of the specific endomannosidase inhibitor, Glc alpha 1 --> 3(1-deoxy)mannojirimycin, the conversion of the G protein into an endo H-resistant form was completely arrested. While the lack of G protein processing by CHO cells was consistent with the absence of in vitro measured endomannosidase activity in this cell line, the failure of MDBK and MDCK cells to convert the G protein into an endo H-resistant form was surprising since these cell lines have substantial levels of the enzyme. Similarly, we observed that influenza virus hemagglutinin was not processed in castanospermine-treated MDCK cells. Our findings suggest that studies which rely on glucosidase inhibition to explore the function of glucose in controlling such critical biological phenomena as intracellular movement or quality control should be carried out in cell lines in which the glycoprotein under study is not a substrate for endomannosidase action. C1 Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Biol Chem, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. RP Spiro, RG (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK17477, DK17325] NR 29 TC 32 Z9 32 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD JUL PY 1998 VL 8 IS 7 BP 725 EP 730 DI 10.1093/glycob/8.7.725 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZW659 UT WOS:000074433800009 PM 9621113 ER PT J AU Goff, DC Evins, AE AF Goff, DC Evins, AE TI Negative symptoms in schizophrenia: Neurobiological models and treatment response SO HARVARD REVIEW OF PSYCHIATRY LA English DT Review ID CEREBRAL BLOOD-FLOW; POSITRON EMISSION TOMOGRAPHY; PLASMA HOMOVANILLIC-ACID; PLACEBO-CONTROLLED TRIAL; TREATMENT-RESISTANT SCHIZOPHRENIA; DORSOLATERAL PREFRONTAL CORTEX; DOUBLE-BLIND TRIAL; RECENT COCAINE USE; NEUROLEPTIC TREATMENT; CLOZAPINE TREATMENT AB Evidence from lesioning studies and neuroimaging has linked negative symptoms to dysfunction of the prefrontal cortex, the limbic system, and the basal ganglia. Although such symptoms have been most strongly associated with dopaminergic hypoactivity in the prefrontal cortex, other neurotransmitters including norepinephrine, serotonin, and the excitatory amino acids may also play a role. In some patients moderate doses of conventional neuroleptics clearly improve negative symptoms; the response of such symptoms is relatively greater with clozapine and probably with certain serotonin-dopamine antagonists. Recent studies demonstrating improvement of negative symptoms when conventional neuroleptics are augmented with selective serotonin-reuptake inhibitors or with agents active at the glycine-modulatory site of the glutamatergic N-methyl-D-aspartate receptor complex suggest that further amelioration of primary negative symptoms may be possible through pharmacological strategies involving multiple neurotransmitter systems. C1 Harvard Univ, Sch Med, Consolidated Dept Psychiat, Boston, MA USA. Massachusetts Gen Hosp, Psychot Disorders Program, Boston, MA 02114 USA. RP Goff, DC (reprint author), Freedom Trail Clin, 25 Staniford St, Boston, MA 02114 USA. FU NIMH NIH HHS [R01 MH542245] NR 208 TC 40 Z9 42 U1 10 U2 12 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD JUL-AUG PY 1998 VL 6 IS 2 BP 59 EP 77 DI 10.3109/10673229809000313 PG 19 WC Psychiatry SC Psychiatry GA 106ZT UT WOS:000075181900001 PM 10370450 ER PT J AU Grush, LR Cohen, LS AF Grush, LR Cohen, LS TI Treatment of depression during pregnancy: Balancing the risks SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article ID PRENATAL EXPOSURE; MATERNAL CLOMIPRAMINE; IMIPRAMINE; FLUOXETINE; RATS; ANTIDEPRESSANTS; POSTPARTUM; THERAPY; WITHDRAWAL; PREVALENCE C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Grush, LR (reprint author), Massachusetts Gen Hosp, Dept Psychiat, ACC 815,15 Parkman St, Boston, MA 02114 USA. NR 50 TC 6 Z9 6 U1 1 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD JUL-AUG PY 1998 VL 6 IS 2 BP 105 EP 109 DI 10.3109/10673229809000317 PG 5 WC Psychiatry SC Psychiatry GA 106ZT UT WOS:000075181900005 PM 10370454 ER PT J AU Kuhlthau, K Walker, DK Perrin, JM Bauman, L Gortmaker, SL Newacheck, PW Stein, REK AF Kuhlthau, K Walker, DK Perrin, JM Bauman, L Gortmaker, SL Newacheck, PW Stein, REK TI Assessing managed care for children with chronic conditions SO HEALTH AFFAIRS LA English DT Article ID HEALTH AB This paper reviews opportunities to monitor managed care for children and adolescents with chronic conditions and considers how well the Health Plan Employer Data and Information Set, version 3.0 (HEDIS 3.0), assesses care for these children. We propose four steps to strengthen the applicability of HEDIS to children with chronic conditions: (1) develop methods of identifying and monitoring groups of children with chronic conditions; (2) report HEDIS indicators for these children separately from those for other children; (3) develop and implement consumer and provider surveys that elicit information specific to these populations; and (4) develop specific structure, process, and outcomes indicators for children with chronic conditions. C1 Massachusetts Gen Hosp, Gen Pediat Res Unit, Boston, MA 02114 USA. Massachusetts Dept Publ Hlth, Bur Family & Community Hlth, Boston, MA 02111 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Div Gen Pediat, Boston, MA 02114 USA. Albert Einstein Coll Med, New York, NY USA. Harvard Univ, Sch Publ Hlth, Dept Hlth & Social Behav, Cambridge, MA 02138 USA. Univ Calif San Francisco, Sch Med, Inst Hlth Policy Studies, San Francisco, CA 94143 USA. Univ Calif San Francisco, Sch Med, Dept Pediat, San Francisco, CA 94143 USA. RP Kuhlthau, K (reprint author), Massachusetts Gen Hosp, Gen Pediat Res Unit, Boston, MA 02114 USA. FU PHS HHS [MCJ-25R026] NR 29 TC 22 Z9 22 U1 0 U2 2 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD JUL-AUG PY 1998 VL 17 IS 4 BP 42 EP 52 DI 10.1377/hlthaff.17.4.42 PG 11 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 102PM UT WOS:000074933100009 PM 9691549 ER PT J AU Geissler, M Schirmbeck, R Reimann, J Blum, HE Wands, JR AF Geissler, M Schirmbeck, R Reimann, J Blum, HE Wands, JR TI Cytokine and hepatitis B virus DNA co-immunizations enhance cellular and humoral immune responses to the middle but not to the large hepatitis B virus surface antigen in mice SO HEPATOLOGY LA English DT Article ID CYTOTOXIC T-LYMPHOCYTES; ACUTE VIRAL-HEPATITIS; TRANSGENIC MICE; GENE-EXPRESSION; NUCLEOCAPSID ANTIGEN; INFECTION; CELLS; INTERLEUKIN-2; VACCINATION; SEROCONVERSION AB Genetic immunization is a potentially useful strategy to prevent or treat hepatitis B virus (I-IBV) infection, We have previously shown that HBV envelope proteins are highly immunogenic using this technique. The large envelope protein (LHBs), however, induced significantly weaker humoral and cellular immune responses when compared with the middle envelope protein (MHBs), We studied the effect of co-immunizations with cytokine: DNA expression constructs encoding for interleukin (IL)-2 and (GM-CSF) on the immunogenicity of LHBs at the B-and T-cell level, Go-immunizations of mice with plasmids encoding for MHBs and IL-2 or GM-CSF increased anti-HBs responses, helper T-cell proliferative activity, and cytotoxic T lymphocyte (CTL) killing, In contrast, co-immunizations of plasmids encoding for LHBs and IL-2 or GM-CSF had no effect on humoral and cellular immune responses, LHBs did not inhibit the production or secretion of IL-2 and GM-CSE In addition, IL-2, tumor necrosis factor alfa (TNF-alpha), and interferon gamma (IFN-gamma) had no suppressive effect on HBV envelope protein expression in vitro, Based on these data, MMBs, but not LHBs, genetic immunization can be augmented by IL-2 or GM-CSF cytokines. C1 Massachusetts Gen Hosp, Ctr Canc, Mol Hepatol Lab, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. Univ Freiburg, Dept Med 2, D-7800 Freiburg, Germany. Univ Ulm, Inst Med Microbiol, D-89069 Ulm, Germany. RP Geissler, M (reprint author), Univ Freiburg, Med Klin, Innere Med Abt 2, Hugstetter Str 55, D-79106 Freiburg, Germany. FU NCI NIH HHS [CA-35711]; NIAAA NIH HHS [AA-02169] NR 55 TC 35 Z9 37 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JUL PY 1998 VL 28 IS 1 BP 202 EP 210 DI 10.1002/hep.510280126 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZW975 UT WOS:000074467800026 PM 9657113 ER PT J AU Manome, Y Kunieda, T Wen, PY Koga, T Kufe, DW Ohno, T AF Manome, Y Kunieda, T Wen, PY Koga, T Kufe, DW Ohno, T TI Transgene expression in malignant glioma using a replication-defective adenoviral vector containing the Egr-1 promoter: Activation by ionizing radiation or uptake of radioactive iododeoxyuridine SO HUMAN GENE THERAPY LA English DT Article ID THYMIDINE KINASE GENE; INTERNUCLEOSOMAL DNA FRAGMENTATION; BRAIN-TUMORS; IN-VIVO; RECOMBINANT ADENOVIRUS; CANCER CELLS; THERAPY; GROWTH; TRANSDUCTION; SENSITIVITY AB One approach to improving the specificity of gene therapy involves using radiosensitive promoters to activate gene expression selectively in the radiation field. In this study, we evaluated the ability of irradiation to regulate the transcription of a recombinant replication-defective adenovirus vector, Ad.Egr-1/lacZ, containing the radiation-inducible Egr-1 promoter driving the beta-galactosidase reporter gene in glioma cells. Transcripts of the Egr-1 gene in human and rat glioma cells were induced following irradiation with as little as 2 Gy. This dose was 10-fold less than previously reported, and comparable to doses of irradiation used clinically in standard fractionated radiotherapy for brain tumors, When 9L rat gliosarcoma cells were infected with Ad.Egr-1/lacZ in vitro and exposed to 2 Gy of external beam irradiation, there was a threefold increase in beta-galactosidase expression. Irradiation of intracerebral 9L tumors infected with the Ad.Egr-1/lacZ virus, using either external beam radiotherapy (2 Gy) or the thymidine analog 5-iodo-2'-deoxyuridine radiolabeled with the Auger electron emitter iodine-125 ([I-125]IdUrd), also resulted in increased beta-galactosidase activity of the tumor cells. These results indicate that the use of viral vectors containing radiation-inducible promoters represents a novel therapeutic approach that enables gene therapy to be spatially and temporally regulated by ionizing radiation. These findings also support a potential role for radiation-inducible promoters in the treatment of malignant brain tumors. C1 Jikei Univ, Sch Med, Dept Microbiol, Minato Ku, Tokyo 1058461, Japan. Jikei Univ, Sch Med, Dept Neurosurg, Tokyo 1058461, Japan. Jikei Univ, Sch Med, Dept Med 2, Tokyo 1058461, Japan. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Neurol, Boston, MA 02115 USA. Chiba Social Insurance Hosp, Div Clin Lab, Chiba 2600801, Japan. Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Canc Pharmacol, Boston, MA 02115 USA. Jikei Univ, Sch Med, Inst DNA Med, Tokyo 1058461, Japan. RP Manome, Y (reprint author), Jikei Univ, Sch Med, Dept Microbiol, Minato Ku, 3-25-8 Nishi Shinbashi, Tokyo 1058461, Japan. NR 39 TC 72 Z9 88 U1 0 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD JUL 1 PY 1998 VL 9 IS 10 BP 1409 EP 1417 DI 10.1089/hum.1998.9.10-1409 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA ZZ212 UT WOS:000074706800004 PM 9681412 ER PT J AU Klein, C Brin, MF de Leon, D Limborska, SA Ivanova-Smolenskaya, IA Bressman, SB Friedman, A Markova, ED Risch, NJ Breakefield, XO Ozelius, LJ AF Klein, C Brin, MF de Leon, D Limborska, SA Ivanova-Smolenskaya, IA Bressman, SB Friedman, A Markova, ED Risch, NJ Breakefield, XO Ozelius, LJ TI De novo mutations (GAG deletion) in the DYT1 gene in two non-Jewish patients with early-onset dystonia SO HUMAN MOLECULAR GENETICS LA English DT Article ID IDIOPATHIC TORSION DYSTONIA; AUTOSOMAL DOMINANT INHERITANCE; ASHKENAZI JEWS; 9Q34 AB The DYT1 gene recently has been cloned and shown to contain a three nucleotide (GAG) deletion responsible for most cases of autosomal dominant early-onset torsion dystonia. This deletion results in the loss of one of a pair of glutamic acids in a conserved region of a novel ATP-binding protein (torsinA). Previous haplotype analysis revealed that this same deletion had arisen at least two different times in history, suggesting independent mutational events. This deletion is the only sequence change found thus far to be associated uniquely with the disease status, regardless of ethnic origin. Here we describe two patients with typical early-onset torsion dystonia of Swiss-Mennonite and nonJewish Russian origin, respectively, that both carry this same mutation as a de novo GAG deletion. This finding proves that this 3 bp deletion in the DYT1 gene is indeed a mutation that causes early-onset torsion dystonia. The DYT1 mutation is one of the rare examples of the same recurrent mutation causing a dominantly inherited condition. The sequence surrounding the GAG deletion contains an imperfect 24 bp tandem repeat, suggesting a possible mechanism for the high frequency of this mutation. C1 Massachusetts Gen Hosp, Neurol Serv, Mol Neurogenet Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Neurol & Genet, Boston, MA USA. Mt Sinai Hosp, Dept Neurol, Movement Disorders Ctr, New York, NY 10029 USA. Columbia Presbyterian Med Ctr, Dept Neurol, Dystoria Clin Res Ctr, New York, NY 10032 USA. Russian Acad Sci, Inst Mol Genet, Moscow 123182, Russia. Inst Neurol, Moscow, Russia. Stanford Univ, Dept Genet, Stanford, CA 94305 USA. Med Acad Warsaw, Dept Neurol, Warsaw, Poland. RP Ozelius, LJ (reprint author), Massachusetts Gen Hosp, Neurol Serv, Mol Neurogenet Unit, Boston, MA 02114 USA. EM ozelius@helix.mgh.harvard.edu RI Ivanova-Smolenskaya, Irina/C-9041-2012 FU FIC NIH HHS [R03-TW0071-91]; NHGRI NIH HHS [HG00348]; NINDS NIH HHS [R01NS28384-07] NR 22 TC 45 Z9 47 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JUL PY 1998 VL 7 IS 7 BP 1133 EP 1136 DI 10.1093/hmg/7.7.1133 PG 4 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA ZX952 UT WOS:000074571900010 PM 9618171 ER PT J AU Pal, L Leykin, L Schifren, JL Isaacson, KB Chang, YC Nikruil, N Chen, ZY Toth, TL AF Pal, L Leykin, L Schifren, JL Isaacson, KB Chang, YC Nikruil, N Chen, ZY Toth, TL TI Malignancy may adversely influence the quality and behaviour of oocytes SO HUMAN REPRODUCTION LA English DT Article DE fertilization; IVF; malignancy; oocyte; quality ID HODGKINS-DISEASE; CANCER; CRYOPRESERVATION; MEN AB A case series of eight cycles of in-vitro fertilization (IVF) in five women diagnosed with malignant disorders is presented. These patients chose to defer definitive treatment for a chance for preservation of potential fertility. The response of these patients to ovarian stimulation, and the outcome, was compared,vith 17 IVF cycles in 12 age-matched patients with isolated tubal infertility. An apparent adverse influence of malignant disease on the quality and behaviour of oocytes was observed. Despite a comparable total number of oocytes per cycle in the two groups, a significantly reduced percentage of mature oocytes was retrieved per cycle from patients with malignant diseases. The oocytes from patients with malignant disorders were of a poorer quality and exhibited a significantly impaired fertilization rate compared to the controls. We propose that neoplastic processes, irrespective of the site or cell of origin, may have a detrimental impact on the biology of oocytes, an effect akin to that seen on spermatozoa in men with certain malignancies. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Reprod Endocrinol & Infertil, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Gynecol Oncol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Med Practices Evaluat Ctr, Boston, MA USA. RP Pal, L (reprint author), Yale New Haven Hosp, Dept Obstet & Gynecol, 333 Cedar St,POB 208063, New Haven, CT 06520 USA. NR 16 TC 36 Z9 36 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD JUL PY 1998 VL 13 IS 7 BP 1837 EP 1840 DI 10.1093/humrep/13.7.1837 PG 4 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 109LN UT WOS:000075324200025 PM 9740435 ER PT J AU Venkataramanan, L Walsh, JL Kuc, R Sigworth, FJ AF Venkataramanan, L Walsh, JL Kuc, R Sigworth, FJ TI Identification of hidden Markov models for ion channel currents - Part I: Colored background noise SO IEEE TRANSACTIONS ON SIGNAL PROCESSING LA English DT Article DE colored noise; hidden Markov model; ion channel ID DETERMINISTIC INTERFERENCES; PROBABILISTIC FUNCTIONS; RECORDINGS AB Signal processing based on hidden Markov models (HMM's) has been applied recently to the characterization of single ion channel currents as recorded with the patch clamp technique from living cells. The estimation of HMM parameters using the traditional forward-backward and Baum-Welch algorithms can be performed at signal-to-noise ratios (SNR's) that are too low for conventional analysis; however, the application of these algorithms relies on the assumption that the background noise is white. In this paper, the observed single channel current is modeled as a vector hidden Markov process. An extension of the forward-backward and Baum-Welch algorithms is described to model ion channel kinetics under conditions of colored noise like that seen in patch clamp recordings. Using simulated data, we demonstrate that the traditional algorithms result in biased estimates and that the vector HMM approach provides unbiased estimates of the parameters of the underlying hidden Markov scheme. C1 Yale Univ, Dept Elect Engn, New Haven, CT 06520 USA. Massachusetts Gen Hosp, Dept Anesthesiol, Boston, MA 02114 USA. Yale Univ, Sch Med, Dept Cellular & Mol Physiol, New Haven, CT 06520 USA. RP Venkataramanan, L (reprint author), Yale Univ, Dept Elect Engn, New Haven, CT 06520 USA. NR 29 TC 43 Z9 48 U1 0 U2 2 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 USA SN 1053-587X J9 IEEE T SIGNAL PROCES JI IEEE Trans. Signal Process. PD JUL PY 1998 VL 46 IS 7 BP 1901 EP 1915 DI 10.1109/78.700963 PG 15 WC Engineering, Electrical & Electronic SC Engineering GA ZV830 UT WOS:000074345600011 ER PT J AU Snapper, SB Rosen, FS Mizoguchi, E Cohen, P Khan, W Liu, CH Hagemann, TL Kwan, SP Ferrini, R Davidson, L Bhan, AK Alt, FW AF Snapper, SB Rosen, FS Mizoguchi, E Cohen, P Khan, W Liu, CH Hagemann, TL Kwan, SP Ferrini, R Davidson, L Bhan, AK Alt, FW TI Wiskott-Aldrich syndrome protein-deficient mice reveal a role for WASP in T but not B cell activation SO IMMUNITY LA English DT Article ID SRC HOMOLOGY-3 DOMAINS; ANTIGEN-RECEPTOR; ACTIN POLYMERIZATION; TYROSINE KINASES; GENE; MUTATIONS; IDENTIFICATION; LYMPHOCYTES; VAV; THROMBOCYTOPENIA AB The Wiskott-Aldrich syndrome (WAS) is a human X-linked immunodeficiency resulting from mutations in a gene (WASP) encoding a cytoplasmic protein implicated in regulating the actin cytoskeleton. To elucidate WASP function, we disrupted the WASP gene in mice by gene-targeted mutation. WASP-deficient mice showed apparently normal lymphocyte development, normal serum immunoglobulin levels, and the capacity to respond to both T-dependent and T-indepedent type II antigens. However, these mice did have decreased peripheral blood lymphocyte and platelet numbers and developed chronic colitis. Moreover, purified WASP-deficient T cells showed markedly impaired proliferation and antigen receptor cap formation in response to anti-CD3 epsilon stimulation. Yet, purified WASP-deficient B cells showed normal responses to anti-Ig stimulation. We discuss the implications of our findings regarding WASP function in-receptor signaling and cytoskeletal reorganization in T and B cells and compare the effects of WASP deficiency in mice and humans. C1 Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. Ctr Blood Res, Boston, MA 02115 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Med Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Immunopathol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Rush Univ, Rush Presbyterian St Lukes Med Ctr, Dept Immunol Microbiol, Chicago, IL 60612 USA. RP Alt, FW (reprint author), Childrens Hosp, Howard Hughes Med Inst, 300 Longwood Ave, Boston, MA 02115 USA. EM alt@rascal.med.harvard.edu FU NHLBI NIH HHS [HL03749, HL59561]; NIAID NIH HHS [AI20047] NR 63 TC 349 Z9 357 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD JUL PY 1998 VL 9 IS 1 BP 81 EP 91 DI 10.1016/S1074-7613(00)80590-7 PG 11 WC Immunology SC Immunology GA 105HL UT WOS:000075066600008 PM 9697838 ER PT J AU Gans, JS Alonso, A AF Gans, JS Alonso, A TI Difficult patients: Their construction in group therapy SO INTERNATIONAL JOURNAL OF GROUP PSYCHOTHERAPY LA English DT Article ID GROUP-PSYCHOTHERAPY AB Written from the perspective of intersubjective theory, this article addresses how the leader and group members co-construct the difficult patient. Too often therapists and patients have tended to attribute difficulties in therapy groups to "the difficult patient" without appreciating how they themselves contribute to the construction, the needs tills construction serves, and the potential value of such patients to the group. Mistakes in group leadership vicissitudes of intersubjectivity, disturbing intrapsychic defenses, and whole-group dynamics interact to produce the difficult patient. Also discussed is the group member who is difficult but who no longer meets the criteria for patienthood. By exploring the factors involved in the co-construction of the difficult patient, the authors hope to guide clinicians ill the deconstruction of such impediments, thus allowing the difficult patient to become "just another group patient.". C1 Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Ctr Psychoanalyt Studies, Boston, MA 02114 USA. RP Gans, JS (reprint author), 55 Cleveland Rd, Wellesley, MA 02181 USA. NR 17 TC 20 Z9 20 U1 0 U2 0 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0020-7284 J9 INT J GROUP PSYCHOTH JI Int. J. Group Psychother. PD JUL PY 1998 VL 48 IS 3 BP 311 EP 326 PG 16 WC Psychology, Clinical SC Psychology GA ZY670 UT WOS:000074647400002 PM 9661312 ER PT J AU Clement, PB Zubovits, JT Young, RH Scully, RE AF Clement, PB Zubovits, JT Young, RH Scully, RE TI Malignant mullerian mixed tumors of the uterine cervix: A report of nine cases of a neoplasm with morphology often different from its counterpart in the corpus SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Article DE cervix; malignant mullerian mixed tumor; carcinosarcoma ID ADENOID CYSTIC CARCINOMA; FEMALE GENITAL-TRACT; PROGNOSTIC FACTORS; MESODERMAL TUMORS; CELL CARCINOMA; UTERUS; CARCINOSARCOMA; ADENOSARCOMA; EXPERIENCE; STROMA AB Malignant mullerian mixed tumors (MMMTs) of the uterine cervix are rare; less than 30 cases have been reported in the literature and only 14 have been described in detail, As a result, the clinical and pathologic features of these tumors are not well characterized. The clinicopathologic features of nine cervical MMMTs (all cases referred because of problems in differential diagnosis) are reported here and the literature on the previously described cases is reviewed. The patients ranged in age from 23 to 87 (mean 65) years. The initial manifestations were mainly vaginal bleeding or spotting or, less commonly, an abnormal Pap smear. All of the patients had a cervical mass on examination. Of the eight patients for whom staging information was available, seven were stage Ib and one was stage II. Treatment in six patients was hysterectomy with lymphadenectomy in five; postoperative radiation therapy, chemotherapy, or both were given to two of these patients. The remaining three patients were treated by local excision (with lymphadenectomy in one) followed by radiation therapy, chemotherapy, or both in two. Follow-up, available for seven patients, revealed recurrent pelvic tumor in two patients at 1.6 and 3.0 years, respectively; the former patient died from tumor at 3.5 years whereas the latter was alive with tumor at 4.5 years. Another patient was well for 11 years but died 13 years postoperatively from colonic adenocarcinoma, Four other patients were alive with no evidence of tumor at postoperative intervals of less than 2 years. Gross examination revealed polypoid or pedunculated masses 1.1 to 10.0 cm in maximal dimension that invaded the cervical wall in 50% of the hysterectomy specimens. On microscopic examination, three tumors contained a predominant or exclusive epithelial component of basaloid carcinoma, two contained squamous cell carcinoma, and four contained adenocarcinoma (endometrioid in three and nonspecific in one). In seven tumors, the sarcomatous component was homologous, usually resembling fibrosarcoma or endometrial stromal sarcoma; in four of these tumors, myxoid change was prominent. Two tumors contained heterologous sarcomatous elements. In three patients, a pure carcinoma abutted the MMMT: an adenoid basal carcinoma in two (with a minor component of in situ and invasive squamous cell carcinoma in each) and an endometrioid endocervical adenocarcinoma in one. These findings, combined with analysis of the previously reported cases, indicate that cervical MMMTs, compared to their counterparts in the corpus, are more commonly confined to the uterus at presentation, may have a better prognosis, and frequently have a nonglandular epithelial component. C1 Vancouver Hosp & Hlth Sci Ctr, Dept Pathol, Vancouver, BC V5Z 4E3, Canada. Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Clement, PB (reprint author), Vancouver Hosp & Hlth Sci Ctr, Dept Pathol, 910 W 10th Ave,Room 1302, Vancouver, BC V5Z 4E3, Canada. NR 49 TC 54 Z9 59 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0277-1691 J9 INT J GYNECOL PATHOL JI Int. J. Gynecol. Pathol. PD JUL PY 1998 VL 17 IS 3 BP 211 EP 222 DI 10.1097/00004347-199807000-00004 PG 12 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA ZW677 UT WOS:000074435600004 PM 9656116 ER PT J AU Keel, SB Clement, PB Prat, J Young, RH AF Keel, SB Clement, PB Prat, J Young, RH TI Malignant schwannoma of the uterine cervix: A study of three cases SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Article DE uterine cervix; sarcoma; schwannoma; peripheral nerve sheath tumor ID SOFT-PART SARCOMA; CELLULAR SCHWANNOMA; NEUROFIBROMATOSIS; RHABDOMYOSARCOMA; BOTRYOIDES; TUMORS; TRACT AB Pure sarcomas of the uterine cervix are rare; most of those reported have been leiomyosarcomas or rhabdomyosarcomas. Minimal data exists on malignant nerve sheath tumors in this site; only one typical example and one melanocytic example have been reported. We report three additional examples here in three patients 25, 65, and 73 years of age. The two older patients had vaginal bleeding and underwent hysterectomy as initial treatment. The youngest patient initially underwent only polypectomy. The tumors were 1.3, 4.4, and 5.0 cm in greatest dimension. The tumors were red-grey to white; two were polypoid and the third was ulcerated. The dominant microscopic appearance was that of cellular fascicles of spindle cells with hyperchromatic nuclei and eosinophilic cytoplasm. However, hypocellular areas were striking in each case; the hypocellular areas were fibromatous in two tumors and two had areas with a myxoid stroma (prominent in one). One tumor focally had cellular aggregates with a swirling pattern within a hypocellular background. Epithelioid foci in which tumor cells were rounded with conspicuous eosinophilic cytoplasm were focally prominent in one case. Mitoses were readily identified in each case. All three tumors were positive for S-100 protein and vimentin and negative for cytokeratin, HMB-45, and desmin. One case is recent and one patient had multiple metastases in the abdomen 2 years after hysterectomy. The patient treated initially by polypectomy underwent repeat local excision, followed by cone biopsy with positive margins, and then hysterectomy. She is clinically free of disease 15 months after diagnosis. Although the diagnosis of malignant schwannoma was suggested by the histologic features of the tumors, other diagnoses were entertained and immunohistochemistry was crucial in confirming the diagnosis. These tumors should be distinguished from other malignant spindle cell tumors of the cervix, such as leiomyosarcoma, endocervical "stromal sarcoma," and spindle cell melanoma, so their features, behavior, and optimal therapy can be further delineated. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,James Homer Wright Pathol Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02114 USA. Vancouver Gen Hosp, Dept Pathol, Vancouver, BC V5Z 1M9, Canada. Hosp St Crue & St Pau, Dept Pathol, Barcelona, Spain. RP Keel, SB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,James Homer Wright Pathol Labs, 32 Fruit St, Boston, MA 02114 USA. RI Prat, Jaime/G-4679-2011 NR 26 TC 20 Z9 20 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0277-1691 J9 INT J GYNECOL PATHOL JI Int. J. Gynecol. Pathol. PD JUL PY 1998 VL 17 IS 3 BP 223 EP 230 DI 10.1097/00004347-199807000-00005 PG 8 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA ZW677 UT WOS:000074435600005 PM 9656117 ER PT J AU Paster, BJ Dewhirst, FE Coleman, BC Lau, CN Ericson, RL AF Paster, BJ Dewhirst, FE Coleman, BC Lau, CN Ericson, RL TI Phylogenetic analysis of cultivable oral treponemes from the Smibert collection SO INTERNATIONAL JOURNAL OF SYSTEMATIC BACTERIOLOGY LA English DT Article DE phylogeny; 16S rDNA; oral spirochaete; Treponema ID NECROTIZING ULCERATIVE GINGIVITIS; SP-NOV; PERIODONTAL-DISEASE; JUVENILE PERIODONTITIS; DENTAL PLAQUE; FATTY-ACIDS; SPIROCHETE; HUMANS; BACTERIOLOGY; MICROFLORA AB Dr Robert Smibert from the Virginia Polytechnic Institute, USA, isolated and collected over 200 strains of oral treponemes over a 20-year period. Dr Smibert Dr W. E. C. Moore and Dr L. V. Moore separated these isolates and reference strains into different groups on the basis of cellular fatty acid analysis. in this study, the 16S rRNA genes were sequenced for 47 strains that were representative of these groups. Five distinct species were identified on the basis of 16S rRNA sequence comparisons; two of these species are newly named and three have not yet been characterized. The first species, designated Treponema Smibert-1, was represented by the single strain D4B-1 and was later identified as the newly described Treponema maltophilum. However, strain D4B-1 possessed a different flagellar arrangement to that of T. maltophilum. The second species, Treponema Smibert-1 was represented by nine isolates that possessed identical 16S rRNA gene sequences. The closest relatives of this species were Treponema Smibert-3 and Treponema Smibert-4 at approximately 90% sequence similarity. Within Treponema Smibert-2, there was no correlation between phylogenetic analysis and cellular fatty acid analysis since six different cellular fatty acid groups represented the nine strains. Treponema Smibert-3 (strain D36ER-1) and Treponema Smibert-4 (D62CR-12) were each represented by only a single strain and were closely related to each other at 98% sequence similarity. Strain D36ER-1 of Treponema Smibert-3 was identified as belonging to the not-yet-cultivated phylotype 20 [Choi, B. K., Paster, B. J., Dewhirst, F. E. & Gobel, U. B. (1994). Infect Immun 62,1889-1895]. Strain D62CR-I2 of Treponema Smibert-4 was nearly identical in sequence to the newly described Treponema amylovorum. The fifth species, Treponema Smibert-5, was represented by a single strain, D120CR-1, and was closely related at about 98% sequence similarity to the three subspecies of Treponema socranskii. The phylogenetic analyses of strains of Treponema vincentii and of subspecies of T. socranskii are also reported. The closest oral relatives of T. vincentii were Treponema medium at 98.7% sequence similarity and Treponema denticola at 91.5% sequence similarity. T. socranskii subspp. socranskii, buccale and paredis formed three separate phylogenetic branches with sequence similarities of about 98% to each other. The closest relative of the subspecies of T. socranskii and of Smibert-5 was Smibert-2 at about 86% sequence similarity. Historic reference strains Fuji, 'Treponema ambigua', Fm, Ichelson-2, N-39, TD2, TRRD, MRB, IPP, Jethro and T32A, as well as an unknown strain designated only as Treponema oralis, were identified as strains of T. denticola. Reference strains Fuji, Jethro, T32A and IPP plus three isolates of the Smibert collection were also contaminated with a mycoplasma as determined by 16S rRNA comparative analysis. Consequently, spirochaetal cultures should be screened for mycoplasmas. There are presently at least ten species of cultivable oral species of Treponema with the cut-off for separate species designation at about 98% sequence similarity. However, DNA-DNA reassociation experiments are necessary to differentiate species when 16S rDNA sequence similarities are at about this level. C1 Forsyth Dent Ctr, Dept Mol Genet, Boston, MA 02115 USA. RP Paster, BJ (reprint author), Forsyth Dent Ctr, Dept Mol Genet, 140 Fenway, Boston, MA 02115 USA. FU NIDCR NIH HHS [DE-10374, DE-11443] NR 49 TC 25 Z9 26 U1 0 U2 1 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING, BERKS, ENGLAND RG7 1AE SN 0020-7713 J9 INT J SYST BACTERIOL JI Int. J. Syst. Bacteriol. PD JUL PY 1998 VL 48 BP 713 EP 722 PN 3 PG 10 WC Microbiology SC Microbiology GA 114CA UT WOS:000075590500010 PM 9734025 ER PT J AU Walker, BD Basgoz, N AF Walker, BD Basgoz, N TI Treat HIV-1 infection like other infections - Treat it SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID T-LYMPHOCYTES; IN-VIVO C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Div Infect Dis, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Walker, BD (reprint author), Massachusetts Gen Hosp, Partners AIDS Res Ctr, 149 13th St, Charlestown, MA 02129 USA. NR 21 TC 21 Z9 21 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 1 PY 1998 VL 280 IS 1 BP 91 EP 93 DI 10.1001/jama.280.1.91 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA ZW145 UT WOS:000074379400031 PM 9660371 ER PT J AU van de Rijn, M Mehlhop, PD Judkins, A Rothenberg, ME Luster, AD Oettgen, HC AF van de Rijn, M Mehlhop, PD Judkins, A Rothenberg, ME Luster, AD Oettgen, HC TI A murine model of allergic rhinitis: Studies on the role of IgE in pathogenesis and analysis of the eosinophil influx elicited by allergen and eotaxin SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE allergic rhinitis; IgE; IL-5; eotaxin; mouse; model ID ASPERGILLUS-FUMIGATUS ANTIGENS; VASCULAR ENDOTHELIAL-CELLS; NASAL-MUCOSA; IN-VIVO; AIRWAY HYPERRESPONSIVENESS; CHEMOATTRACTANT CYTOKINE; INFLAMMATORY CELLS; ANTIBODY-RESPONSE; DEFICIENT MICE; LYMPHOCYTES-T AB Background: Allergic rhinitis is a prevalent disease with significant morbidity, Studies of its pathophysiology in human subjects have been limited. Nasal biopsy specimens are difficult to obtain, and nasal secretions incompletely reflect the cellular and molecular events in the mucosa, IgE-mediated mast cell activation and the elaboration of factors promoting eosinophil development and chemotaxis are likely to participate in pathogenesis. Objectives: We sought to develop a murine model of allergic rhinitis, to use it to assess the role of IgE in pathogenesis, and to study the effects of IL-5 and eotasin in the nasal mucosa, Methods: A protein extract of Aspergillus fumigatus (Af) was instilled intranasally in mice. Histologic changes were examined in wild-type and IgE-deficient (IgE(-/-)) animals. The effect of eotasin administration was assessed in wild-type and IL-5 transgenic mice. Results: Af-treated mice developed a nasal mucosal eosinophil influx comparable to that described for humans, This histology was distinct from that observed in a murine model Af-induced asthma, The pathology appeared over a time course similar to that reported for human subjects. There was no difference in the intensity of the mucosal inflammatory infiltrate of rif-treated IgE(-/-) mice compared with wild-type mice. Eotaxin mas able to recruit eosinophils to the mucosa but only in IL-5 transgenic animals, Conclusion: We describe a murine model for allergic rhinitis with an eosinophilic infiltrate comparable to that found in human disease and have demonstrated that rhinitis can arise in the absence of IgE, We have shown that the eosinophil influx can be induced by eotaxin in the presence of IL-5. C1 Harvard Univ, Childrens Hosp, Sch Med, Div Immunol, Boston, MA 02115 USA. Univ Penn, Med Syst, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. Childrens Hosp, Med Ctr, Div Pulm Med Allergy & Clin Immunol, Cincinnati, OH 45229 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Infect Dis Unit, Boston, MA USA. RP Oettgen, HC (reprint author), Harvard Univ, Childrens Hosp, Sch Med, Div Immunol, Enders 8,300 Longwood Ave, Boston, MA 02115 USA. FU NIAID NIH HHS [AI 40618]; NICHD NIH HHS [2P30HD28827-06] NR 64 TC 58 Z9 60 U1 0 U2 6 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JUL PY 1998 VL 102 IS 1 BP 65 EP 74 DI 10.1016/S0091-6749(98)70056-9 PG 10 WC Allergy; Immunology SC Allergy; Immunology GA 102DX UT WOS:000074909500011 PM 9679849 ER PT J AU Bush, RK Wood, RA Eggleston, PA AF Bush, RK Wood, RA Eggleston, PA TI Laboratory animal allergy SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article ID FEL-D-I; MOUSE ALLERGENS; AIRBORNE CONCENTRATIONS; SIZE DISTRIBUTION; CASCADE IMPACTOR; RAT ALLERGENS; CAT ALLERGEN; RISK-FACTORS; DOG; ASTHMA AB Approximately one third of laboratory animal workers have occupational allergy to animal danders, and a third of these have symptomatic asthma. Sensitization generally occurs with the first 3 years of employment, and risk factors include atopic background, as well as job description as it relates to the intensity of exposure. A symptomatic worker can reduce allergen exposure with personal protective devices. A laboratory can further reduce exposure with generally available equipment. such as laminar flow caging, and procedures, such as frequent wet washing of vivaria and careful maintenance of ventilation systems. It is advisable to institute periodic medical screening of all laboratory animal workers with questionnaires and allergy skin testing in addition to providing them with training programs to reduce personal exposure. C1 William S Middleton Mem Vet Hosp, Madison, WI 53705 USA. Univ Wisconsin, Dept Med, Madison, WI USA. Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA. RP Bush, RK (reprint author), William S Middleton Mem Vet Hosp, 2500 Overlook Terrace, Madison, WI 53705 USA. NR 79 TC 102 Z9 105 U1 0 U2 2 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JUL PY 1998 VL 102 IS 1 BP 99 EP 112 DI 10.1016/S0091-6749(98)70060-0 PG 14 WC Allergy; Immunology SC Allergy; Immunology GA 102DX UT WOS:000074909500015 PM 9679853 ER PT J AU Gill, TJ Sledge, JB Muller, ME AF Gill, TJ Sledge, JB Muller, ME TI Total hip arthroplasty with use of an acetabular reinforcement ring in patients who have congenital dysplasia of the hip - Results at five to fifteen years SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID FOLLOW-UP; DISLOCATION; REPLACEMENT; RECONSTRUCTION; COMPONENT AB The purpose of our study was to examine the clinical and technical problems associated,vith reconstruction of the hip in patients who had congenital dysplasia and to offer recommendations for their solution. We reviewed the records on 123 consecutive total hip arthroplasties that had been performed by one of us (M. E. M.), between 1981 and 1986, for the treatment of coxarthrosis due to congenital dysplasia of the hip. A minimum of five years of follow-up was required for inclusion in the study, The study group consisted of seventy patients who had had a total of eighty-seven reconstructions. According to the classification of Crowe et al,, eleven hips had type-IV acetabular dysplasia; sixty-five, type-m; and eleven, type-II. Acetabular reconstruction was performed with use of the Muller acetabular roof-reinforcement ring and a polyethylene cup, which was inserted with cement. Autologous graft from the femoral head was used in forty-two hips. Femoral reconstruction was performed with use of the Muller straight-stem component for congenital dysplasia of the hip in eighty hips and with use of a standard Muller straight-stem component in seven hips, At an average of 9.4 years (range, five to fifteen years) postoperatively, the result was described as excellent for sixty hips (69 per cent), as good for twenty-three (26 per cent), as fair for two (2 per cent), and as poor for two. Nine (10 per cent) of the hips had been revised. One revision had been performed because of aseptic loosening of the acetabular component; one, because of aseptic loosening of the femoral component; one, because of aseptic loosening of both components; and six, because of infection. Of the unrevised hips, three had had superior migration of the acetabular component of less than five millimeters, and mild protrusio had developed in one. Two hips had a continuous radiolucent line around the acetabular construct. Two hips had had subsidence of the femoral stem of less than three millimeters; one had a complete, non-progressive radiolucent line at the bone-cement interface; and four had a radiolucent line at the proximal part of the bone-cement interface. Six hips had evidence of endosteal osteolysis. Six hips had grade-III or IV heterotopic ossification according to the system of Brooker et al, These results compare favorably with others in the literature. We recommend restoration of the anatomical hip center with the use of an acetabular roof-reinforcement ring and a polyethylene cup inserted with cement for the reconstruction of a deficient acetabulum, The acetabular reinforcement ring prevents resorption of bone graft and migration of the cup, which are major causes of failure of the cup in patients who have had a reconstruction of a deficient acetabulum, Bone graft should be used medially and superiorly as needed to augment bone stock notably. Cement should not be used to fill acetabular defects as we believe that it contributes to aseptic loosening. C1 Maurice E Muller Inst, Bern, Switzerland. RP Massachusetts Gen Hosp, Dept Orthopaed Surg, 32 Fruit St, Boston, MA 02114 USA. NR 41 TC 48 Z9 53 U1 0 U2 0 PU JOURNAL BONE JOINT SURGERY PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02492 USA SN 0021-9355 EI 1535-1386 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD JUL PY 1998 VL 80A IS 7 BP 969 EP 979 PG 11 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 105ZM UT WOS:000075105300005 PM 9698001 ER PT J AU Chen, W Li, YP AF Chen, W Li, YP TI Generation of mouse osteoclastogenic cell lines immortalized with SV40 large T antigen SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID BONE-MARROW CULTURES; MOLECULAR-CLONING; MULTINUCLEATED CELLS; SIMIAN VIRUS-40; IN-VITRO; MULTIPLE COMPONENTS; MURINE RETROVIRUS; PRECURSOR CELLS; SPLEEN-CELLS; RESORPTION AB Progress in the field of osteoclast gene regulation has been hampered significantly by the lack of such cell lines. In this study, mouse osteoclast precursor cells were elicited in an osteoclast-inductive coculture system and immortalized using SV40 large T antigen. One of the osteoclast precursor cell lines (MOCP-5) forms 95% tartrate-resistant acid phosphatase positive (TRAP(+)) multinuclear osteoclast-like cells (OCLs) in the coculture system. The yield of TRAP(+) OCLs was 4.5-7 x 10(4) cells per 10 cm(2) dish. Expression of SV40 large T antigen was visualized in the nucleus of MOCP-5 cells and OCLs by immunohistochemistry. MOCP-5 cells were positive for MoMa-2 antigen and nonspecific esterase but negative for F4/80 antigen. OCLs derived from MOCP-5 cells were able to form extensive resorption bone pits on bone slices. The resorbing activity of the OCLs was comparable to that of authentic mouse osteoclasts. Pit formation was inhibited by salmon calcitonin (CT). Acid production by OCLs was demonstrated by vital staining with acridine orange. The OCLs expressed cathepsin K and CT receptors, MOCP-5 tells could be transfected by a construct that carries the beta-galactosidase gene. Transfected MOCP-5 cells expressing beta-galactosidase retain the ability to differentiate into OCLs, indicating a useful model for osteoclast gene regulation. To date, the MOCP-5 cell line has been maintained in continuous culture for 23 months and has maintained the capacity to differentiate into osteoclasts throughout this time. In summary, these data show that a stable immortalized osteoclast precursor cell line has beers established and that the immortalization with SV40 large T oncogene does not prevent osteoclast precursor cell differentiation. C1 Forsyth Dent Ctr, Dept Cytokine Biol, Boston, MA 02115 USA. RP Li, YP (reprint author), Forsyth Dent Ctr, Dept Cytokine Biol, 140 Fenway, Boston, MA 02115 USA. FU NIDCR NIH HHS [DE-10887] NR 58 TC 27 Z9 32 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD JUL PY 1998 VL 13 IS 7 BP 1112 EP 1123 DI 10.1359/jbmr.1998.13.7.1112 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZX361 UT WOS:000074507800007 PM 9661075 ER PT J AU Compton, CC Warland, G Kratz, G AF Compton, CC Warland, G Kratz, G TI Melanocytes in cultured epithelial grafts are depleted with serial subcultivation and cryopreservation: Implications for clinical outcome SO JOURNAL OF BURN CARE & REHABILITATION LA English DT Article ID GROWTH-FACTOR; BURN WOUNDS; PERMANENT COVERAGE; LENTIGO-MALIGNA; INVITRO; PROLIFERATION; EPIDERMIS; KERATINOCYTES; CRYOTHERAPY; MULTICENTER AB Patchy hypopigmentation often occurs unpredictably in the skin regenerated from cultured epidermal autografts, especially when that skin is grown from frozen cells, serially passaged, or both. The impact of serial subcultivation and cryopreservation on melanocyte viability in the cultured epidermal autograft culture system was investigated. Serial subcultivation of human keratinocytes through as many as eight passages was performed, and melanocyte densities in confluent cultures at each passage were determined after specific labeling of melanocytes. The experimental cells were frozen before cultivation and between passages to determine the effect of standard cryopreservation on melanocyte survival. freshly passaged cells that had not been frozen served as controls. Melanocytes were gradually depleted during fresh passage of epidermal cells but persisted through as many as seven passages. Freezing before or after the first passage or between subsequent passages resulted in a complete loss of melanocytes by the third or fourth passage. The findings suggest that cryopreservation should be avoided during cultured epidermal autograft production to optimize melanocyte survival and minimize pigmentation abnormalities that may occur after grafting. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Shriners Hosp Crippled Children, Boston Burns Inst, Boston, MA USA. Karolinska Hosp, Dept Plast & Reconstruct Surg, S-10401 Stockholm, Sweden. RP Compton, CC (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren 2,35 Fruit St, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK43351] NR 32 TC 12 Z9 13 U1 0 U2 2 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0273-8481 J9 J BURN CARE REHABIL JI J. Burn Care Rehabil. PD JUL-AUG PY 1998 VL 19 IS 4 BP 330 EP 336 DI 10.1097/00004630-199807000-00011 PG 7 WC Emergency Medicine; Rehabilitation; Surgery SC Emergency Medicine; Rehabilitation; Surgery GA 115VA UT WOS:000075685500010 PM 9710732 ER PT J AU McDonald-Smith, GP AF McDonald-Smith, GP TI BurnWare (c) National TRACS (R) ABA computer use in the burn center SO JOURNAL OF BURN CARE & REHABILITATION LA English DT Editorial Material C1 Massachusetts Gen Hosp, Trauma & Burn Serv, Boston, MA 02114 USA. RP McDonald-Smith, GP (reprint author), 1 Wyoming St,Ste 7000 CHE, Dayton, OH 45409 USA. NR 0 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 USA SN 0273-8481 J9 J BURN CARE REHABIL JI J. Burn Care Rehabil. PD JUL-AUG PY 1998 VL 19 IS 4 BP 354 EP 354 PG 1 WC Emergency Medicine; Rehabilitation; Surgery SC Emergency Medicine; Rehabilitation; Surgery GA 115VA UT WOS:000075685500015 PM 9710737 ER PT J AU McDonald-Smith, GP AF McDonald-Smith, GP TI Progress report: 1998 NATIONAL TRACS (R) ABA Burn Registry and related activities SO JOURNAL OF BURN CARE & REHABILITATION LA English DT Article C1 Massachusetts Gen Hosp, Trauma & Burn Serv, Dept Burn & Trauma Serv, Boston, MA 02114 USA. RP McDonald-Smith, GP (reprint author), Massachusetts Gen Hosp, Trauma & Burn Serv, Dept Burn & Trauma Serv, GRB 1302, Boston, MA 02114 USA. NR 0 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 USA SN 0273-8481 J9 J BURN CARE REHABIL JI J. Burn Care Rehabil. PD JUL-AUG PY 1998 VL 19 IS 4 BP 354 EP 358 PG 5 WC Emergency Medicine; Rehabilitation; Surgery SC Emergency Medicine; Rehabilitation; Surgery GA 115VA UT WOS:000075685500016 PM 9710737 ER PT J AU Farah, SG Azar, DT Gurdal, C Wong, J AF Farah, SG Azar, DT Gurdal, C Wong, J TI Laser in situ keratomileusis: Literature review of a developing technique SO JOURNAL OF CATARACT AND REFRACTIVE SURGERY LA English DT Article; Proceedings Paper CT Meeting of the Refractive-Special-Interest-Group at the American-Academy-of-Ophthalmology Meeting CY OCT, 1997 CL SAN FRANCISCO, CALIFORNIA SP Amer Acad Ophthalmol, Refract Special Interest Grp ID PHOTOREFRACTIVE KERATECTOMY; MYOPIC KERATOMILEUSIS; INSITU KERATOMILEUSIS; CORNEAL FLAP; DIOPTERS AB We reviewed papers published in peer-reviewed journals describing techniques and results of laser in situ keratomileusis (LASIK) and summarized the instruments used, nomograms, preoperative and postoperative refractions, predictability, outcome, safety, and complications. We performed a similar review of abstracts published in the abstract books of the 1996 meeting of the international Society of Refractive Surgery, the 1997 meeting of the Association for Research in Vision and Ophthalmology, and the 1997 meeting of the American Society of Cataract and Refractive Surgery. The number of LASIK and photorefractive keratectomy (PRK) patients described in the abstracts were sorted by city. Mean weighted latitudes were calculated and compared for each procedure. The mean preoperative refraction in the papers was -12.59 diopters (D), which was statistically higher than that in the abstracts, -8.71 D (P < .001), and the mean postoperative refraction, -1.10 and +0.93 D, respectively. The mean percentage of cases within +/-1.00 D was 67.0% in the papers and 82.5% tn the abstracts. Uncorrected visual acuity (UCVA) of 20/40 or better was achieved in 49.2% of eyes in the papers and 83.2% of those in the abstracts; a UCVA of 20/20 or better was achieved in 22.0 and 56.6%, respectively The proportion of eyes that lost two or more lines of best corrected visual acuity was 8.0% in the papers and 0.9% in the abstracts. Complications in the papers included irregular flap (4.0%), incomplete cut (2.5%), free cap (4.9%), perforated lenticule (2,6%), short flap (3.0%), sliding flap (1.4%), interface debris (6.8%), central island (5.3%), decentration (4.7%),epithelial RI ingrowth (4.3%), induced astigmatism (5.1%),wrinkles (5.9%), haze (8.7%), night vision problems (14.0%), and reoperation (8.2%). Mean latitude for LASIK cases (27.00 degrees +/- 13.73 [SD]) was significantly lower than that for PRK cases (42.85 +/- 11.7 degrees). Visual outcomes of LASIK surgery show significant improvements When recent abstracts are compared with published papers. This may reflect continued improvement in the surgical techniques, surgeons' skills, and visual outcomes. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Corneal Surg Serv, Boston, MA 02114 USA. RP Azar, DT (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Corneal Surg Serv, 243 Charles St, Boston, MA 02114 USA. NR 44 TC 190 Z9 213 U1 0 U2 5 PU AMER SOC CATARACT REFRACTIVE SURGERY PI FAIRFAX PA 4000 LEGATO RD, SUITE 850, FAIRFAX, VA 22030 USA SN 0886-3350 J9 J CATARACT REFR SURG JI J. Cataract. Refract. Surg. PD JUL PY 1998 VL 24 IS 7 BP 989 EP 1006 PG 18 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 103GE UT WOS:000075148900026 PM 9682123 ER PT J AU Collins, CL Wasa, M Souba, WW Abcouwer, SF AF Collins, CL Wasa, M Souba, WW Abcouwer, SF TI Determinants of glutamine dependence and utilization by normal and tumor-derived breast cell lines SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID AMINO-ACID-TRANSPORT; MAJOR ENERGY-SOURCE; HUMAN-FIBROBLASTS; END PRODUCTS; METABOLISM; BIOSYNTHESIS; RAT; GLUTATHIONE; OXIDATION; PATHWAYS AB A continual supply of the amino acid glutamine (GLN) may be necessary for cancerous cell growth. GLN plays a central role in multiple metabolic pathways and has long been considered an essential component of tissue culture media. However, the GLN requirements of tumor cell lines and the factors that determine a cell's need for GLN have not been comprehensively studied. Also, it remains unclear how various metabolic pathways contribute to GLN consumption. In the present study, possible determinants of GLN metabolism were examined in seven breast cell lines, two derived from immortalized normal tissue and five of tumor origin. These cells exhibited different dependencies on media GLN concentration for growth and a wide range of GLN utilization rates. GLN uptake was facilitated by a single, common transporter functionally defined as System ASC. However, the affinities for GLN exhibited by this transporter differed appreciably between cell lines. Furthermore, the concentration at which media GLN became a limiting factor for cellular proliferation correlated with transporter affinity. The origin of the cell lines was not a determinant of GLN metabolism because immortalized cells of nontumor origin exhibited GLN dependence and utilization rates comparable to those of tumor-derived cells. The rates of CO2 production from GLN were similar for each cell lines. Rates of GLN disappearance and glutamate appearance in media were strongly correlated, with 32-80% of media GLN converted to glutamate. Both rates were directly affected by media cystine concentration, suggesting that a large portion of glutamate efflux was coupled with cystine import through the amino acid transport system x(c)(-). These results demonstrated that cell growth is a function of GLN influx and suggest that GLN is used to supply glutamate and cystine, perhaps for glutathione synthesis. (C) 1998 Wiley-Liss, Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. RP Abcouwer, SF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Cox Bldg,Room 626,100 Blossom St, Boston, MA 02114 USA. OI Abcouwer, Steven F/0000-0003-2580-1288 FU NIDDK NIH HHS [P30-DK40561] NR 41 TC 67 Z9 67 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD JUL PY 1998 VL 176 IS 1 BP 166 EP 178 DI 10.1002/(SICI)1097-4652(199807)176:1<166::AID-JCP18>3.0.CO;2-5 PG 13 WC Cell Biology; Physiology SC Cell Biology; Physiology GA ZP476 UT WOS:000073757300018 PM 9618156 ER PT J AU Gollub, RL Breiter, HC Kantor, H Kennedy, G Gastfriend, D Mathew, RT Makris, N Guimaraes, A Riordan, J Campbell, T Foley, M Hyman, SE Rosen, B Weisskoff, R AF Gollub, RL Breiter, HC Kantor, H Kennedy, G Gastfriend, D Mathew, RT Makris, N Guimaraes, A Riordan, J Campbell, T Foley, M Hyman, SE Rosen, B Weisskoff, R TI Cocaine decreases cortical cerebral blood flow but does not obscure regional activation in functional magnetic resonance imaging in human subjects SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE cerebral blood flow (CBF); functional magnetic resonance imaging (fMRI); neuroimaging; psychostimulants ID POSITRON EMISSION TOMOGRAPHY; HUMAN BRAIN; SENSORY STIMULATION; ACUTE TOLERANCE; METABOLISM; AREAS AB The authors used functional magnetic resonance imaging (fMRI) to determine whether acute intravenous (IV) cocaine use would change global cerebral blood flow (CBF) or visual stimulation-induced functional activation. They used flow-sensitive alternating inversion recovery (FAIR) scan sequences to measure CBF and blood oxygen level-dependent (BOLD) sensitive T-2* scan sequences during visual stimulation to measure neuronal activation before and after cocaine and saline infusions. Cocaine (0.6 mg/kg IV over 30 seconds) increased heart rate and mean blood pressure and decreased end tidal carbon dioxide (CO2). All measures returned to baseline by 2 hours, the interinfusion interval, and were unchanged by saline. Flow-sensitive alternating inversion recovery imaging demonstrated that cortical gray matter CBF was unchanged after saline infusion (-2.4 +/- 6.5%) but decreased (-14.1 +/- 8.5%) after cocaine infusion (n = 8, P < 0.01). No decreases were detected in white matter, nor were changes found comparing BOLD signal intensity in cortical gray matter immediately before cocaine infusion with that measured 10 minutes after infusion. Visual stimulation resulted in comparable BOLD signal increases in visual cortex in all conditions (before and after cocaine and saline infusion). Despite a small (14%) but significant decrease in global cortical gray matter CBF after acute cocaine infusion, specific regional increases in BOLD imaging, mediated by neurons, can be measured reliably. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Nucl Magnet Resonance Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Ctr Morphometr Anal, Boston, MA 02114 USA. RP Gollub, RL (reprint author), Massachusetts Gen Hosp, CNY 9109,149 13th St, Charlestown, MA 02129 USA. OI Gollub, Randy L./0000-0002-9434-4044 FU NIDA NIH HHS [DA09467-02, DA00265-01, DA00275-01] NR 42 TC 81 Z9 82 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JUL PY 1998 VL 18 IS 7 BP 724 EP 734 PG 11 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA ZX867 UT WOS:000074563400003 PM 9663502 ER PT J AU Palmert, MR Radovick, S Boepple, PA AF Palmert, MR Radovick, S Boepple, PA TI Leptin levels in children with central precocious puberty SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID NORMAL FEMALE MICE; BODY-MASS INDEX; SERUM LEPTIN; PLASMA LEPTIN; OBESE GENE; CIRCULATING LEPTIN; NOCTURNAL RISE; EARLY-ONSET; WEIGHT; GENDER AB Several studies have suggested that sufficient serum leptin levels may be involved in the initiation of puberty. To assess further the relationship between leptin and the onset of puberty in humans, we measured the serum leptin concentration in children with central precocious puberty (CPP). We studied 65 children with either idiopathic (IPP; n = 50 girls and 3 boys) or neurogenic central precocious puberty (NPP; n = 5 girls and 7 boys). The serum leptin levels in these patients were compared with normative data from healthy children and adolescents using so scores that adjust for body mass index (BMI) and Tanner stage. The mean SD scores of IPP and NPP girls were +0.4 +/- 0.1 and +1.0 +/- 0.5, respectively, compared with that of age-matched prepubertal girls and +0.7 +/- 0.2 and +1.6 +/- 0.6 compared with that of girls matched for pubertal stage. The CPP girls with lower BMIs contributed larger so scores, such that the leptin SD score was negatively correlated with BMI. A similar, modest increase in leptin levels in the CPP girls was evident when additional normative data were considered. The mean leptin so scores of IPP and NPP boys were -0.9 +/- 0.5 and +0.7 +/- 0.3, respectively, compared with that, of normal boys at Tanner stage 3-4. Serum leptin levels in the boys with CPP were not different from those in healthy boys in any of the normative studies. These data should be interpreted cautiously, but they suggest that girls with CPP have modestly elevated serum leptin concentrations compared with those in healthy children and adolescents. In addition, the negative correlation between the leptin so score and BMI suggests that sufficient leptin levels may be associated with initiation of puberty in girls. C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Pediat Unit, Boston, MA 02114 USA. Childrens Hosp, Dept Med, Div Endocrinol, Boston, MA 02115 USA. Harvard Univ, MIT,Div Hlth Sci & Technol, Beth Israel Deaconess Med Ctr, Clin Investigator Training Program,Pfizer Inc, Boston, MA 02115 USA. RP Boepple, PA (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, Bartlett Hall Extens 5,Fruit St, Boston, MA 02114 USA. FU NCRR NIH HHS [RR-01066, RR-02172]; NICHD NIH HHS [HD-18169] NR 51 TC 38 Z9 40 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL PY 1998 VL 83 IS 7 BP 2260 EP 2265 DI 10.1210/jc.83.7.2260 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZX855 UT WOS:000074562200006 PM 9661592 ER PT J AU Miller, KK Parulekar, MS Schoenfeld, E Anderson, E Hubbard, J Klibanski, A Grinspoon, SK AF Miller, KK Parulekar, MS Schoenfeld, E Anderson, E Hubbard, J Klibanski, A Grinspoon, SK TI Decreased leptin levels in normal weight women with hypothalamic amenorrhea: The effects of body composition and nutritional intake SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID SERUM LEPTIN; PLASMA LEPTIN; OBESE GENE; HUMANS; HORMONE; EXERCISE; INSULIN; RESPONSES; FOOD AB Leptin is a protein encoded by the ob gene and expressed in adipocytes. A sensitive marker of nutritional status, leptin is known to correlate with fat mass and to respond to changes in caloric intake. Leptin may also be an important mediator of reproductive function, as suggested by the effects of leptin infusions to restore ovulatory function in an animal model of starvation. We hypothesized that leptin levels are decreased in women with hypothalamic amenorrhea and that leptin may be a sensitive marker of overall nutritional status in this population. We, therefore, measured leptin levels and caloric intake in 21 women with hypothalamic amenorrhea (HA) and 30 age-, weight-, and body fat-matched eumenorrheic controls. Age (24 +/- 5 vs. 24 +/- 3 yr), body mass index (20.6 +/- 1.3 vs. 21.1 +/- 1.5 kg/m(2)), percent ideal body weight (94.9 +/- 5% vs. 96.3 +/- 6.3%), and fat mass (14.2 +/- 3.6 vs. 15.5 +/- 2.9 kg, determined by dual energy x-ray absortiometry) did not differ between the groups. Leptin levels were significantly lower in the HA subjects compared with those in the controls (7.1 +/- 3.0 vs. 10.6 +/- 4.9 mu g/L; P = 0.005). Total caloric intake (1768 +/- 335 us. 2215 +/- 571 cal/day; P = 0.003), fat intake (333 +/- 144 vs. 639 +/- 261 cal/day; P < 0.0001), and insulin levels (5.6 +/- 1.2 vs. 7.4 +/- 3.2 mu U/mL; P = 0.015) were lower in the women with HA than in the eumenorrheic controls. The difference in leptin levels remained significant after controlling for insulin (P = 0.023). These data are the first to demonstrate hypoleptinemia, independent of fat mass, in women with HA. The hypoleptinemia may reflect inadequate calorie intake, fat intake, and/or other subclinical nutritional disturbances in women with HA. The mechanism and reproductive consequences of low leptin in this large population of women remain unknown. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gen Clin Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Grinspoon, SK (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Bulfinch 457B, Boston, MA 02114 USA. EM grinspoons@a1.mgh.harvard.edu FU NCRR NIH HHS [M01-RR-0166]; NIDDK NIH HHS [5-T32-DK-07028-23, R01-DK-52625-01] NR 31 TC 94 Z9 97 U1 0 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL PY 1998 VL 83 IS 7 BP 2309 EP 2312 DI 10.1210/jc.83.7.2309 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZX855 UT WOS:000074562200014 PM 9661600 ER PT J AU Rosen, HN Moses, AC Garber, J Ross, DS Lee, SL Ferguson, L Chen, V Lee, K Greenspan, SL AF Rosen, HN Moses, AC Garber, J Ross, DS Lee, SL Ferguson, L Chen, V Lee, K Greenspan, SL TI Randomized trial of pamidronate in patients with thyroid cancer: Bone density is not reduced by suppressive doses of thyroxine, but is increased by cyclic intravenous pamidronate SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID TERM L-THYROXINE; PYRIDINIUM CROSS-LINKS; POSTMENOPAUSAL WOMEN; MINERAL DENSITY; PAGETS-DISEASE; PREMENOPAUSAL WOMEN; SUBCLINICAL HYPERTHYROIDISM; THYROIDECTOMIZED PATIENTS; PHOTON-ABSORPTIOMETRY; REPLACEMENT THERAPY AB Patients taking suppressive doses of T-4 are thought to have accelerated bone loss and increased risk of osteoporosis. We therefore randomize 55 patients taking suppressive doses of T-4 to treatment with pamidronate (APD) 30 mg iv every 3 months for 2 yr (APD/T-4), or placebo (placebo/T-4). Patients had measurements of bone mineral density (BMD) of the spine, hip, radius, and total body every 6 months for 2 yr. There was no significant bone loss at any site in the placebo/T-4 group. Ninety five percent confidence intervals excluded a rate of bone loss >0.89%/yr for the spine and >0.31%/yr at the total hip. When men were excluded from the analysis, there still was no significant bone loss for the placebo/T-4 group, and confidence intervals did not change. The APD/T-4 group showed increases in spine (4.3%, P = 0.0001), total hip (1.4%, P < 0.05), and trochanteric (3.0%, P = 0.0001) BMDs. In conclusion, premenopausal women and men on suppressive therapy with T-4 do not lose bone rapidly, and are not at increased risk of developing osteoporosis. A regimen of 30 mg APD given every 3 months for 2 yr causes significant suppression of bone resorption and increases in BMD, and maybe an acceptable alternative treatment for osteoporosis in patients who cannot tolerate oral bisphosphonates. C1 Beth Israel Deaconess Med Ctr, Div Bone & Mineral Metab, Dept Med, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Charles A Dana Res Inst, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Harvard Thorndike Lab, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Med, Div Gerontol, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Med, Div Endocrinol, Boston, MA 02215 USA. Harvard Pilgrim HealthCare, Endocrinol Sect, Hlth Ctr Div, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Med, Thyroid Unit, Boston, MA 02114 USA. Tufts Univ New England Med Ctr, Endocrinol Diabet Metab & Mol Med Div, Dept Med, Boston, MA 02111 USA. RP Rosen, HN (reprint author), Beth Israel Deaconess Med Ctr, Div Bone & Mineral Metab, Dept Med, RA414,330 Brookline Ave, Boston, MA 02215 USA. FU NCRR NIH HHS [M01RR01032] NR 61 TC 44 Z9 46 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 JUL PY 1998 VL 83 IS 7 BP 2324 EP 2330 DI 10.1210/jc.83.7.2324 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZX855 UT WOS:000074562200017 PM 9661603 ER PT J AU Hayes, FJ Taylor, AE Martin, KA Hall, JE AF Hayes, FJ Taylor, AE Martin, KA Hall, JE TI Use of a gonadotropin-releasing hormone antagonist as a physiologic probe in polycystic ovary syndrome: Assessment of neuroendocrine and androgen dynamics SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID FOLLICLE-STIMULATING-HORMONE; ALPHA-SUBUNIT SECRETION; LUTEINIZING-HORMONE; SECONDARY AMENORRHEA; STEROID-SECRETION; MENSTRUAL-CYCLE; DISEASE; WOMEN; PATHOGENESIS; AGONIST AB The majority of patients with polycystic ovary syndrome (PCOS) exhibit an increase in both the frequency and amplitude of LH secretion, which is thought to contribute to the hyperandrogenism associated with this disorder. The increase in LH pulse amplitude may reflect either enhanced pituitary sensitivity to GnRH and/or an increase in hypothalamic GnRH secretion. To determine whether endogenous GnRH secretion is increased in PCOS and to document the degree and time course of androgen suppression after acute LH inhibition, the Nal-Glu GnRH antagonist was administered sc at 4 doses (5, 15, 50, and 150 mu g/kg) to 11 women with PCOS. The response to GnRH receptor blockade was compared with data from regularly cycling women (n = 50) studied in the early and late follicular, and early luteal phases. The response to more prolonged GnRH receptor blockade was determined in a subset of patients, in whom 150 mu g/kg of the GnRH antagonist was administered sc every 24 h for 3 days (n = 7) and continued for 7 days in 3 subjects. LH levels decreased in a dose-dependent fashion after administration of the GnRH antagonist (P < 0.0001), with a maximum percent inhibition of 83 +/- 2%. At all except the 5 mu g/kg dose, mean LH levels remained significantly lower than baseline for up to 20 h post antagonist (P < 0.002). At all antagonist doses, both the degree and duration of LH suppression were similar in PCOS and normal women. The maximum percent inhibition of FSH was 39 +/- 2%, which was significantly less than that of LH (P < 0.001). Testosterone (T) levels fell significantly within 4 h of antagonist administration, with maximum percent inhibition of 39 +/- 3% occurring at 8 h. In the patients in whom 150 mu g/kg of the antagonist was given for 3-7 days, no further suppression of either gonadotropins or T was noted. Our conclusions were: 1) The equivalent susceptibility of LH to submaximal GnRH receptor blockade in normal and PCOS women suggests that the elevated LH levels in PCOS are not the result of an increase in the quantity of GnRH secreted. These data imply that it is the frequency of GnRH stimulation per se and/or enhanced pituitary sensitivity to endogenous GnRH that underlie the gonadotropin abnormalities in PCOS; and 2) The rapid suppression of T with increasing GnRH antagonist dose is consistent with acute regulation of T secretion by LH. C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Natl Ctr Infertil Res, Boston, MA 02114 USA. RP Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. FU NCRR NIH HHS [GCRC-M01-RR-01066]; NICHD NIH HHS [R01-HD-15080, P30-HD-28138] NR 43 TC 38 Z9 41 U1 0 U2 2 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL PY 1998 VL 83 IS 7 BP 2343 EP 2349 DI 10.1210/jc.83.7.2343 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZX855 UT WOS:000074562200020 PM 9661606 ER PT J AU Ryan, AS Egan, JM Habener, JF Elahi, D AF Ryan, AS Egan, JM Habener, JF Elahi, D TI Insulinotropic hormone glucagon-like peptide-1-(7-37) appears not to augment insulin-mediated glucose uptake in young men during euglycemia SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID RAT SKELETAL-MUSCLE; PEPTIDE-I; DIABETES-MELLITUS; HEALTHY-SUBJECTS; TURNOVER RATES; GLP-1; AMIDE; GLP-1(7-36)AMIDE; POLYPEPTIDE; DEGRADATION AB Glucagon-like peptide-1 (GLP-1) is an intestinal insulinotropic hormone that augments insulin secretion in response to meals and lowers blood glucose levels in both type 1 and type 2 diabetic subjects. It has been proposed that a substantial component of the glucose-lowering effects of GLP-1 occurs via insulin-independent mechanisms. However, the interpretations of the studies have been controversial. This study was conducted to examine whether glucagon-like peptide (GLP-1) has an insulin-like effect during euglycemia. Nine young lean men (age, 25 +/- 1.4 yr; body mass index, 24.0 +/- 0.7 kg/m(2)) volunteered to participate in two euglycemic clamp studies (n = 18 clamps) for 120 min. The initial clamp was performed with a primed continuous infusion of GLP-1 at a final rate of 1.5 pmol/kg.min from 0-60 min. At 60 min, the GLP-1 infusion was terminated, and euglycemia was maintained from 60-120 min. After the GLP-1 study, each individual's plasma insulin level was measured. A second study was performed that was identical to the first, with the infusion of regular insulin in place of GLP-1. Insulin infusion rates were designed in each individual to simulate plasma insulin levels produced during the GLP-1 infusion. The rate of disappearance of glucose was calculated for each subject. Basal plasma insulin levels were similar between studies and averaged 49 +/- 5 pmol/L. Basal GLP-1 levels were also similar (6.0 +/- 1.0 pmol/L). In response to the GLP-1 infusion, although basal plasma glucose levels were clamped, significant increases in insulin occurred in all subjects (P < 0.001). With the nearly identical plasma insulin levels during the two studies (30-60 min levels: GLP-1 study, 151 +/- 48; insulin study, 146 +/- 31 pmol/L), the rate of disappearance of glucose progressively increased in response to both GLP-1 and insulin infusions, but was not significantly different between the studies. The design of the study necessitated conducting the GLP-1 study first, which may have been accompanied by a greater stress than the second study. We, therefore, measured cortisol levels. Basal cortisol land ACTH) levels were not different. However, cortisol levels significantly increased during the GLP-1 infusions, and this was preceded by an increase in ACTH levels. Somatostatin levels were not different either basally or during the clamps. We conclude that in the euglycemic state, an acute infusion of GLP-1 does not have insulinlike effects in lean nondiabetic men. Intravenous administration of GLP-1 activates hypothalamic neuroendocrine neurons. C1 Harvard Univ, Geriatr Res Lab GRJ1215, Massachusetts Gen Hosp, Sch Med,Dept Med, Boston, MA 02114 USA. NIA, NIH, Lab Clin Physiol, Gerontol Res Ctr, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Med, Div Gerontol, Baltimore, MD 21201 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Mol Endocrinol Lab, Boston, MA 02114 USA. RP Elahi, D (reprint author), Harvard Univ, Geriatr Res Lab GRJ1215, Massachusetts Gen Hosp, Sch Med,Dept Med, 55 Fruit St, Boston, MA 02114 USA. FU NCRR NIH HHS [M01-RR-02719]; NIA NIH HHS [AG-00599, T32-AG00219] NR 40 TC 68 Z9 68 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 JUL PY 1998 VL 83 IS 7 BP 2399 EP 2404 DI 10.1210/jc.83.7.2399 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZX855 UT WOS:000074562200032 PM 9661618 ER PT J AU Fishman, MC Kirby, ML AF Fishman, MC Kirby, ML TI Fallen arches, or how the vertebrate got its head SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID NEURAL CREST; EXPRESSION; CELLS C1 Massachusetts Gen Hosp, Div Cardiol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Cambridge, MA 02138 USA. Med Coll Georgia, Dev Biol Program, Inst Mol Med & Genet, Augusta, GA 30912 USA. RP Fishman, MC (reprint author), Massachusetts Gen Hosp, Div Cardiol, Cambridge, MA 02138 USA. NR 16 TC 7 Z9 7 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL 1 PY 1998 VL 102 IS 1 BP 1 EP 3 DI 10.1172/JCI4143 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 103GA UT WOS:000075148500001 PM 9649549 ER PT J AU Takeishi, Y Chu, GX Kirkpatrick, DM Li, ZL Wakasaki, H Kranias, EG King, GL Walsh, RA AF Takeishi, Y Chu, GX Kirkpatrick, DM Li, ZL Wakasaki, H Kranias, EG King, GL Walsh, RA TI In vivo phosphorylation of cardiac troponin I by protein kinase C beta 2 decreases cardiomyocyte calcium responsiveness and contractility in transgenic mouse hearts SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE hypertrophy; signal transduction; transgenic animal; heart failure; protein kinase ID GUINEA-PIG HEARTS; SARCOPLASMIC-RETICULUM; DIABETIC RATS; SENSITIVITY; PHOSPHOLAMBAN; INTACT; HYPERTROPHY; MECHANICS; MUSCLES; FAILURE AB Recently, it has been reported that the protein kinase C (PKC) beta isoform plays a critical role in the development of hypertrophy and heart failure. The purpose of the present study was to clarify the mechanism by which activation of PKC beta led to depressed cardiac function, Thus, we used a PKC beta 2 overexpressing mouse, an animal model of heart failure, to examine mechanical properties and Ca2+ signals of isolated left ventricular cardiomyocytes. The percentage of shortening, rate of shortening, and rate of relengthening of cardiomyocytes were markedly reduced in PKC beta 2 overexpression mice compared to wild-type control mice, although the baseline level and amplitude of Ca2+ signals were similar. These findings suggested a decreased myofilament responsiveness to Ca2+ in transgenic hearts.Therefore, the incorporation of [P-32] inorganic phosphate into cardiac myofibrillar proteins was studied in Langendorff-perfused hearts. There was a significant increase in the degree of phosphorylation of troponin I in PKC beta 2-overexpressing transgenic mice. The depressed cardiomyocyte function improved after the superfusion of a PKC beta selective inhibitor. These findings indicate that in vivo PKC beta 2-mediated phosphorylation of troponin I may decrease myofilament Ca2+ responsiveness, and thus causes cardiomyocyte dysfunction, Since chronic and excess activation of PKC beta 2 plays a direct and contributory role in the progression of cardiac dysfunction, the PKC beta selective inhibitor may provide a new therapeutic modality in the setting of heart failure. C1 Univ Cincinnati, Coll Med, Div Cardiol, Cincinnati, OH 45267 USA. Univ Cincinnati, Coll Med, Dept Internal Med, Cincinnati, OH 45267 USA. Univ Cincinnati, Coll Med, Dept Pharmacol & Cell Biophys, Cincinnati, OH 45267 USA. Brigham & Womens Hosp, Dept Med, Joslin Diabet Ctr, Div Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Walsh, RA (reprint author), Univ Cincinnati, Coll Med, Div Cardiol, 231 Bethesda Ave,Rm 3354, Cincinnati, OH 45267 USA. FU NEI NIH HHS [EY5110]; NHLBI NIH HHS [HL-52318] NR 32 TC 147 Z9 154 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL 1 PY 1998 VL 102 IS 1 BP 72 EP 78 DI 10.1172/JCI2709 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 103GA UT WOS:000075148500011 PM 9649559 ER PT J AU Hill, GR Cooke, KR Teshima, T Crawford, JM Keith, JC Brinson, YS Bungard, D Ferrara, JLM AF Hill, GR Cooke, KR Teshima, T Crawford, JM Keith, JC Brinson, YS Bungard, D Ferrara, JLM TI Interleukin-11 promotes T cell polarization and prevents acute graft-versus-host disease after allogeneic bone marrow transplantation SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE total body irradiation; gastrointestinal tract; endotoxin; inflammatory cytokines; T cells ID COLONY-STIMULATING FACTOR; IFN-GAMMA; CYTOKINE PRODUCTION; BARRIER FUNCTION; HEPATIC GRAFT; RECOVERY; MICE; SURVIVAL; IL-11; RADIATION AB Administration of IL-11 prevented lethal graft-versus-host disease (GVHD) in a murine bone marrow transplant (BMT) model (B6 --> B6D2F1) across MHC and minor I-I antigen barriers (survival at day 50: 90 vs 20%, P < 0.001), Surpisingly, IL-11 administration polarized the donor T cell cytokine responses to host antigen after BMT with a 50% reduction in IFN gamma and IL-2 secretion and a 10-fold increase in IL-4. This polarization of T cell responses was associated with reduced IFN gamma serum levels and decreased IL-12 production in mixed lymphocyte cultures (MLC), In addition, IL-11 prevented small bowel damage and reduced serum endotoxin levels by 80%. Treatment with IL-11 also reduced TNF alpha serum levels and suppressed TNF alpha secretion by macrophages to LPS stimulation in vitro. IL-11 thus decreased GVHD morbidity and mortality by three mechanisms: (a) polarization of donor T cells; (b) protection of the small bowel; and (c) suppression of inflammatory cytokines such as TNF alpha. We conclude that brief treatment with IL-11 may represent a novel strategy to prevent T cell-mediated inflammatory processes such as GVHD. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06520 USA. Genet Inst Inc, Dept Preclin Res & Dev, Andover, MA 01810 USA. RP Ferrara, JLM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. RI teshima, takanori/G-1671-2012; Hill, Geoffrey/O-2630-2016 OI Hill, Geoffrey/0000-0003-2994-0429 NR 62 TC 188 Z9 202 U1 0 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL 1 PY 1998 VL 102 IS 1 BP 115 EP 123 DI 10.1172/JCI3132 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 103GA UT WOS:000075148500016 PM 9649564 ER PT J AU Dong, ZM Chapman, SM Brown, AA Frenette, PS Hynes, RO Wagner, DD AF Dong, ZM Chapman, SM Brown, AA Frenette, PS Hynes, RO Wagner, DD TI Combined role of P- and E-selectins in atherosclerosis SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE leukocyte adhesion; animal model for atherosclerosis; macrophage; smooth muscle cells; lipofuscin ID LEUKOCYTE ADHESION MOLECULE; RECEPTOR KNOCKOUT MICE; DEFICIENT MICE; APOLIPOPROTEIN-E; INTEGRIN VLA-4; IN-VIVO; ENDOTHELIUM; LESIONS; VCAM-1; SUSCEPTIBILITY AB P- and E-selectins are adhesion molecules mediating the first step in leukocyte extravasation. Because their function in leukocyte adhesion is overlapping, we hypothesized that there might be a combined effect of these selectins on the development of atherosclerotic lesions. We bred P- and E-selectin-double-deficient mice onto the low-density lipoprotein receptor (LDLR)-deficient background (LDLR-/- P/E-/-) and compared lesion development in these mice to that in mice wild type for both selectins (LDLR-/- P/E+/+), After 8 wk on atherogenic diet, the LDLR-/- P/E-/- mice developed fatty streaks in the aortic sinus that were five times smaller than those in LDLR-/- P/E+/+ mice. The density of macrophages in the fatty streaks was comparable between LDLR-/- P/E+/+ and LDLR-/- P/E-/- mice. After 22 wk on the diet, the lesions spread throughout the aorta but this process was delayed in LDLR-/- P/E-/- mice. At 37 wk on diet, the lesions progressed to the fibrous plaque stage in both genotypes, However, the lesions in the aortic sinus in LDLR-/- P/E-/- mice were 40% smaller and less calcified than those of LDLR-/- P/E +/+ mice. Our results suggest that P- and E-selectins together play an important role in both early and advanced stages of atherosclerotic lesion development. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. MIT, Howard Hughes Med Inst, Ctr Canc Res, Dept Biol, Cambridge, MA 02139 USA. RP Wagner, DD (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. RI Frenette, Paul/J-8272-2012 FU NHLBI NIH HHS [HL-53756, HL09869, P01-HL-41484] NR 35 TC 279 Z9 285 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL 1 PY 1998 VL 102 IS 1 BP 145 EP 152 DI 10.1172/JCI3001 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 103GA UT WOS:000075148500020 PM 9649568 ER PT J AU Stoffers, DA Stanojevic, V Habener, JF AF Stoffers, DA Stanojevic, V Habener, JF TI Insulin promoter factor-1 gene mutation linked to early-onset type 2 diabetes mellitus directs expression of a dominant negative isoprotein SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE mutated allele; internal translation; gene transactivation ID PANCREATIC-ISLET CELLS; HOMEOBOX FACTOR; SOMATOSTATIN GENE; HOMEODOMAIN; ACTIVATION; REPRESSOR; HORMONE; BINDING; MODEL; IDX-1 AB The homeodomain transcription factor insulin promoter factor-1 (IPF-1) is required for development of the pancreas and also mediates glucose-responsive stimulation of insulin gene transcription. Earlier we described a human subject with pancreatic agenesis attributable to homozygosity for a cytosine deletion in codon 63 of the IPF-1 gene (Pro63fsdelC). Pro63fsdelC resulted in the premature truncation of an IPF-1 protein which lacked the homeodomain required for DNA binding and nuclear localization, Subsequently, we linked the heterozygous state of this mutation with type 2 diabetes mellitus in the extended family of the pancreatic agenesis proband. In the course of expressing the mutant IPF-1 protein in eukaryotic cells, we detected a second IPF-1 isoform, recognized by COOH- but not NH2-terminal-specific antisera. This isoform localizes to the nucleus and retains DNA-binding functions, We provide evidence that internal translation initiating at an out-of-frame AUG accounts for the appearance of this protein. The reading frame crosses over to the wild-type IPF-1 reading frame at the site of the point deletion just carboxy proximal to the transactivation domain. Thus, the single mutated allele results in the translation of two IPF-1 isoproteins, one of which consists of the NH2-terminal transactivation domain and is sequestered in the cytoplasm and the second of which contains the COOH-terminal DNA-binding domain, but lacks the transactivation domain. Further, the COOH-terminal mutant IPF-1 isoform does not activate transcription and inhibits the transactivation functions of wild-type IPF-1. This circumstance suggests that the mechanism of diabetes in these individuals may be due not only to reduced gene dosage, but also to a dominant negative inhibition of transcription of the insulin gene and other beta cell-specific genes regulated by the mutant IPF-1. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol Endocrinol Lab, Boston, MA 02114 USA. Howard Hughes Med Inst, Boston, MA 02114 USA. RP Habener, JF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol Endocrinol Lab, Wellman 320,50 Blossom St, Boston, MA 02114 USA. RI Stoffers, Doris/H-6157-2012 FU NIDDK NIH HHS [DK-30457] NR 34 TC 125 Z9 126 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL 1 PY 1998 VL 102 IS 1 BP 232 EP 241 DI 10.1172/JCI2242 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 103GA UT WOS:000075148500029 PM 9649577 ER PT J AU Souvenir, D Anderson, DE Palpant, S Mroch, H Askin, S Anderson, J Claridge, J Eiland, J Malone, C Garrison, MW Watson, P Campbell, DM AF Souvenir, D Anderson, DE Palpant, S Mroch, H Askin, S Anderson, J Claridge, J Eiland, J Malone, C Garrison, MW Watson, P Campbell, DM TI Blood cultures positive for coagulase-negative staphylococci: Antisepsis, pseudobacteremia, and therapy of patients SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID CLINICAL-SIGNIFICANCE; RAPID CLASSIFICATION; BACTEREMIA; IDENTIFICATION; EPIDERMIDIS; VALIDATION; MODEL AB A blood culture cohort study investigating issues related to isolation of coagulase-negative staphylococci (CoNS) and other skin microflora is reported, Data were collected over 12 weeks to determine the incidence of significant CoNS bacteremia versus that of pseudobacteremia (contaminants) and to evaluate drug therapy in patients with cultures positive for CoNS, In addition, the effectiveness of 0.2% chlorine peroxide as a bactericidal disinfectant was compared to that of 10% providone iodine. A total of 3,276 cultures of blood from 1,433 patients were evaluated in the study. Eighty-nine cultures were positive for skin flora, with 81 of 89 (91%) involving CoNS, The incidence of significant CoNS bacteremia was 20 of 81 (24.7%), that of indeterminate bacteremia was 10 of 81 (12.3%), and that of contamination was 59 of 81 (72.8%), The incidence of significant bacteremia involving CoNS was double the 10 to 12% rate based on previous estimations at our institutions, In tests with the two bactericidal disinfectants, 22 of 1,639 cultures (1.3%) in the chlorine peroxide group versus 37 of 1,637 (2.3%) in the providone iodine group were considered contaminated (P = 0.065). Rates of contamination for venipuncture versus catheter collection were not significantly different (P = 0.46), The overall contamination rate was 59 of 3,276 (1.8%), which is consistent with the lower end of published quality assurance benchmark standards, The low rate was believed to be due to the professional phlebotomy staff in our institutions. There was excellent agreement between retrospective analysis by reviewers, when formal criteria were used, and the attending physicians' intuitive clinical impressions in the classification of significant bloodstream infections (100% agreement) or contamination (95% agreement), However, physicians still used antimicrobial agents to treat nearly one-half of the patients with contaminated blood cultures, with vancomycin being misused in 34% of patients. In addition, 10% of patients with significant bacteremia were treated with inappropriate agents, There were no significant adverse events or prolonged hospital stays due to the unnecessary use of vancomycin; however, the additional costs of treating patients whose cultures contained CoNS contaminants was estimated to be $1,000 per patient, Measures to limit the unnecessary use of vancomycin land other agents) are important. C1 Deaconess Med Ctr, Spokane, WA USA. Internal Med Spokane, Spokane, WA USA. Washington State Univ, Coll Pharm, Spokane, WA USA. RP Anderson, DE (reprint author), Sacred Heart Med Ctr, 101 W 8th Ave,POB 2555, Spokane, WA 99220 USA. NR 30 TC 136 Z9 151 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JUL PY 1998 VL 36 IS 7 BP 1923 EP 1926 PG 4 WC Microbiology SC Microbiology GA ZU042 UT WOS:000074155400018 PM 9650937 ER PT J AU Shin, JH Lee, SK Suh, SP Ryang, SW Kim, NH Rinaldi, MG Sutton, DA AF Shin, JH Lee, SK Suh, SP Ryang, SW Kim, NH Rinaldi, MG Sutton, DA TI Fatal Hormonema dematioides peritonitis in a patient on continuous ambulatory peritoneal dialysis: Criteria for organism identification and review of other known fungal etiologic agents SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID ASPERGILLUS-FUMIGATUS PERITONITIS; CRYPTOCOCCAL PERITONITIS; CANDIDA-PERITONITIS; CURVULARIA-LUNATA; AUREOBASIDIUM-PULLULANS; HISTOPLASMA-CAPSULATUM; CATHETER COLONIZATION; EXOPHIALA-JEANSELMEI; ORAL FLUCONAZOLE; CAPD PERITONITIS AB We report a fatal case a fungal peritonitis caused by the yeast-like dematiaceous mould Hormonema dematioides in a 45-year-old woman. The woman had a 13-year history of insulin-dependent diabetes mellitus and had been on continuous ambulatory peritoneal dialysis for chronic renal failure. H. dematioides was repeatedly isolated from the dialysate culture specimens collected on days 3, 9, 16, and 20 of her hospital stay. preliminary culture reports on day 7 of the growth of a yeast-like fungus, a probable Candida species, prompted the administration of fluconazole (FLU). Intraperitoneal and intravenous FLU failed to eliminate the mould, and the patient expired on day 21 of her hospital stay. We use this case to present what appears to be the first report of fungal peritonitis due to H. dematioides, to provide laboratorians with criteria for differentiating this organism from the similar mould Aureobasidium pullulans and from various yeast genera, and to provide a review of known fungal tars inciting peritonitis. C1 Univ Texas, Hlth Sci Ctr, Dept Pathol, Fungus Testing Lab, San Antonio, TX 78284 USA. Chonnam Univ, Sch Med, Dept Clin Pathol, Kwangju 501190, South Korea. Chonnam Univ, Sch Med, Dept Internal Med, Kwangju 501190, South Korea. S TExas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX 78284 USA. RP Sutton, DA (reprint author), Univ Texas, Hlth Sci Ctr, Dept Pathol, Fungus Testing Lab, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. EM suttond@uthscsa.edu NR 82 TC 13 Z9 15 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JUL PY 1998 VL 36 IS 7 BP 2157 EP 2163 PG 7 WC Microbiology SC Microbiology GA ZU042 UT WOS:000074155400072 PM 9650991 ER PT J AU Cole, BF Solal-Celigny, P Gelber, RD Lepage, E Gisselbrecht, C Reyes, F Sebban, C Sugano, D Tendler, C Goldhirsch, A AF Cole, BF Solal-Celigny, P Gelber, RD Lepage, E Gisselbrecht, C Reyes, F Sebban, C Sugano, D Tendler, C Goldhirsch, A TI Quality-of-life-adjusted survival analysis of interferon alfa-2b treatment for advanced follicular lymphoma: An aid to clinical decision making SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID OPERABLE BREAST-CANCER; ADJUVANT CHEMOTHERAPY; THERAPY; METAANALYSIS; INFECTION AB Purpose: To evaluate the trade-off of toxicity versus improved clinical outcome with interferon alfa-2b (IFN) administered concomitantly with a doxorubicin-containing regimen for the treatment of advanced follicular lymphoma. Patients and Methods: A quality-of-life-adjusted survival analysis (Quality-Adjusted Time Without Symptoms or Toxicity [Q-TWiST]) was applied to the Groups d'Etude des Lymphomes Folliculaires (GELF) trial 86, which compared a regimen of cyclophosphamide, doxorubicin, teniposide, and prednisone (CHVP) versus CHVP plus IFN in 242 patients with confirmed follicular lymphoma. CHVP was administered monthly for 6 months then every other month for 12 months. The IFN dosage was 5 x 10(6) U three times weekly far 18 months. Results: After a median follow-up duration of 72 months, the IFN group gained a mean of 12.3 months of progression-free survival (PFS) and 7.4 months of overall survival (OS), but also experienced additional time with grade 3 or worse toxicity compared with the CHVP group. Sensitivity analysis demonstrated that CHVP plus IFN provided ct greater amount of quality-adjusted survival regardless of the relative quality-of-life valuations placed on time with toxicity due to CVHP alone, time with toxicity due to CHVP plus IFN, and time following disease progression. this gain was significant (P < .05) in all cases except far patients who consider time with toxicity to have a low relative value and time following disease progression to have a high relative value. Conclusion: In patients with advanced follicular lymphoma, the clinical benefits of concomitant IFN can significantly offset the associated grade 3 or worse toxic effects. The magnitude of this clinical benefit depends on an individual patient's relative quality-of-life valuations for time with toxicity and time fallowing disease progression. (C) 1998 by American Society of Clinical Oncology. C1 Dartmouth Med Sch, Epidemiol & Biostat Sect, Lebanon, NH 03756 USA. Grp Etude Lymphomes Folliculaires, Caen, France. Grp Etude Lymphomes Folliculaires, Creteil, France. Grp Etude Lymphomes Folliculaires, Lyon, France. Grp Etude Lymphomes Folliculaires, Marseille, France. Grp Etude Lymphomes Folliculaires, Nantes, France. Grp Etude Lymphomes Folliculaires, Paris, France. Grp Etude Lymphomes Folliculaires, Reims, France. Grp Etude Lymphomes Folliculaires, Rouen, France. Grp Etude Lymphomes Folliculaires, Toulouse, France. Grp Etude Lymphomes Folliculaires, Valence, France. Grp Etude Lymphomes Folliculaires, Namur, Belgium. Dana Farber Canc Inst, Boston, MA 02115 USA. Schering Plough Res Inst, Kenilworth, NJ USA. Osped Civico, Lugano, Switzerland. European Inst Oncol, Milan, Italy. RP Dartmouth Med Sch, Epidemiol & Biostat Sect, 7929 Rubin Bldg, Lebanon, NH 03756 USA. EM bernard.f.cole@dartmouth.edu NR 16 TC 32 Z9 32 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL PY 1998 VL 16 IS 7 BP 2339 EP 2344 PG 6 WC Oncology SC Oncology GA ZY199 UT WOS:000074596200008 PM 9667248 ER PT J AU Fetting, JH Gray, R Fairclough, DL Smith, TJ Margolin, KA Citron, ML Grove-Conrad, M Cella, D Pandya, K Robert, N Henderson, IC Osborne, CK Abeloff, MD AF Fetting, JH Gray, R Fairclough, DL Smith, TJ Margolin, KA Citron, ML Grove-Conrad, M Cella, D Pandya, K Robert, N Henderson, IC Osborne, CK Abeloff, MD TI Sixteen-week multidrug regimen versus cyclophosphamide, doxorubicin, and fluorouracil as adjuvant therapy for node-positive, receptor-negative breast cancer: An intergroup study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID COLORECTAL-CANCER; CLINICAL-TRIALS; DOSE INTENSITY; SEQUENTIAL METHOTREXATE; STAGE-II; CHEMOTHERAPY; 5-FLUOROURACIL; QUALITY; LIFE AB purpose: The Intergroup conducted this breast cancer adjuvant trial to compare an investigational 16-week regimen with cyclophosphamide, doxorubicin, and fluorouracil (5-FU; CAF). The 16-week regimen features greater doxorubicin and 5-FU dose-intensity than CAF and improved scheduling of antimetabolites with sequential methotrexate and 5-FU, as well as infusion 5-FU. patients and Methods: A total of 646 node-positive, receptor-negative patients were randomly assigned to receive either the 16-week regimen or six cycles of CAF. Breast cancer outcomes included recurrence as well as disease-free and overall survival. Toxicity was evaluated by the Common Toxicity Criteria (CTC). Treatment-related quality of life was assessed by the Breast Chemotherapy Questionnaire (BCQ) before, during, and 4 months after treatment in 163 patients. The trial was designed to use one-sided tests of significance for power calculations, but is now reported with both one-sided and the traditional two-sided tests of significance. Results: At a median follow-up of 3.9 years, the estimated 4-year recurrence-free survival rate was 67.5% with the 16-week regimen versus 62.7% with CAF (P = .19, two-sided; P = .095, one-sided). The estimated 4-year survival rate wets 78.1% with the 16-week regimen versus 71.4% with CAF (P = .10, two-sided; P = .05, one-sided). CAF produced significantly higher grades of leukopenia, granulocytopenia, and thrombocytopenia, as well as liver and cardiac toxicity, whereas the 16-week regimen produced significantly higher grades of anemia, nausea, stomatitis, and weight loss, as well as skin and neurotoxicity. There were three treatment-related deaths with CAF but none with the 16-week regimen. During treatment, quality of life declined significantly more with the 16-week regimen than CAF, but by 4 months posttreatment, there was no difference. Conclusion: The 16-week regimen produced marginally better breast cancer outcomes than CAF with similar toxicity but a greater reduction in during-treatment quality of life. The 16-week regimen should not be used instead of a standard-dose regimen without careful consideration of the 16-week regimen's pros and cans, which include its complicated schedule. It should probably not be tested further, but its antimetabolite schedules and frequent drug administration (ie, dose density) should be considered in the development of new regimens. (C) 1998 by American Society of Clinical Oncology. C1 Johns Hopkins Oncol Ctr, Baltimore, MD 21287 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Amer Med Ctr, Canc Res Ctr, Denver, CO USA. Morristown Mem Hosp, Morristown, NJ USA. City Hope Natl Med Ctr, Duarte, CA 91010 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Long Isl Jewish Med Ctr, New Hyde Park, NY 11042 USA. St Marys Hosp, Rochester, NY USA. Univ S Alabama, Mobile, AL 36688 USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. Fairfax Hosp, Falls Church, VA 22046 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. RP Fetting, JH (reprint author), Johns Hopkins Oncol Ctr, Room 135,600 N Wolfe St, Baltimore, MD 21287 USA. EM jfetting@welchlink.welch.jhu.edu FU NCI NIH HHS [CA16116, CA23318, CA46368] NR 34 TC 25 Z9 25 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL PY 1998 VL 16 IS 7 BP 2382 EP 2391 PG 10 WC Oncology SC Oncology GA ZY199 UT WOS:000074596200015 PM 9667255 ER PT J AU Frank, TS Manley, SA Olopade, OI Cummings, S Garber, JE Bernhardt, B Antman, K Russo, D Wood, ME Mullineau, L Isaacs, C Peshkin, B Buys, S Venne, V Rowley, PT Loader, S Offit, K Robson, M Hampel, H Brener, D Winer, EP Clark, S Weber, B Strong, LC Rieger, P McClure, M Ward, BE Shattuck-Eidens, D Oliphant, A Skolnick, MH Thomas, A AF Frank, TS Manley, SA Olopade, OI Cummings, S Garber, JE Bernhardt, B Antman, K Russo, D Wood, ME Mullineau, L Isaacs, C Peshkin, B Buys, S Venne, V Rowley, PT Loader, S Offit, K Robson, M Hampel, H Brener, D Winer, EP Clark, S Weber, B Strong, LC Rieger, P McClure, M Ward, BE Shattuck-Eidens, D Oliphant, A Skolnick, MH Thomas, A TI Sequence analysis of BRCA1 and BRCA2: Correlation of mutations with family history and ovarian cancer risk SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID GERMLINE MUTATIONS; BREAST; GENE; CARRIERS AB Purpose: Previous studies of mutations in BRCA1 or BRCA2 have used detection methods that may underestimate the actual frequency of mutations and have analyzed women using heterogeneous criteria for risk of hereditary cancer. Patients and Methods: A total of 238 women with breast cancer before age 50 or ovarian cancer at any age and at least one first- or second-degree relative with either diagnosis underwent sequence analysis of BRCA1 followed by analysis of BRCA2 (except for 27 women who declined analysis of BRCA2 after a deleterious mutation was discovered in BRCA1). Results were correlated with personal and family history of malignancy. Results: Deleterious mutations were identified in 94 (39%) women, including 59 of 117 (50%) from families with ovarian cancer and 35 of 121 (29%) from families without ovarian cancer. Mutations were identified in 14 of 70 (20%) women with just one other relative who developed breast cancer before age 50. In women with breast cancer, mutations in BRCA1 and BRCA2 were associated with a 10-fold increased risk of subsequent ovarian carcinoma (P = .005). Conclusion: Because mutations in BRCA1 and BRCA2 in women with breast cancer are associated with an increased risk of ovarian cancer, analysis of these genes should be considered for women diagnosed with breast cancer who have a high probability of carrying a mutation according to the statistical model developed with these data. (C) 1998 by American Society of Clinical Oncology. C1 Myriad Genet Labs, Salt Lake City, UT 84108 USA. Univ Utah, Salt Lake City, UT USA. Univ Chicago, Med Ctr, Chicago, IL 60637 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Johns Hopkins Univ, Baltimore, MD 21205 USA. Univ Colorado, Ctr Canc, Denver, CO 80262 USA. Georgetown Univ, Med Ctr, Washington, DC USA. Univ Rochester, Med Ctr, Rochester, NY 14627 USA. Columbia Presbyterian Med Ctr, New York, NY 10032 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Duke Univ, Med Ctr, Durham, NC USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Univ Texas, Md Anderson Canc Ctr, Houston, TX USA. RP Frank, TS (reprint author), Myriad Genet Labs, 320 Wakara Way, Salt Lake City, UT 84108 USA. EM tfrank@myriad.com OI Thomas, Alun/0000-0001-5650-7044 NR 35 TC 304 Z9 312 U1 3 U2 12 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL PY 1998 VL 16 IS 7 BP 2417 EP 2425 PG 9 WC Oncology SC Oncology GA ZY199 UT WOS:000074596200019 PM 9667259 ER PT J AU Kwiatkowski, DJ Harpole, DH Godleski, J Herndon, JE Shieh, DB Richards, W Blanco, R Xu, HJ Strauss, GM Sugarbaker, DJ AF Kwiatkowski, DJ Harpole, DH Godleski, J Herndon, JE Shieh, DB Richards, W Blanco, R Xu, HJ Strauss, GM Sugarbaker, DJ TI Molecular pathologic substaging in 244 stage I non-small-cell lung cancer patients: Clinical implications SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID RAS ONCOGENE PRODUCT; PROGNOSTIC-SIGNIFICANCE; GENE-MUTATIONS; PROTEIN EXPRESSION; SHORTENED SURVIVAL; CARCINOMA; ADENOCARCINOMA; RECURRENCE; MARKERS; ANTIGEN AB Purpose: To retrospectively construct a comprehensive multivariate model of cancer recurrence and to design a molecular pathologic substaging system in stage I non-small-cell lung cancer (NSCLC). Methods: All patients with stage I NSCLC resected at Brigham and Women's Hospital (Boston, MA) between 1984 and 1992 with adequate clinical follow-vp were studied. The importance of three demographic characteristics, surgical extent, 11 pathologic features, and seven molecular factors on cancer-free survival was examined. Results: Two hundred forty-four patients were studied, with 25 noncancer deaths and 80 patients with recurrent disease. Significant univariate predictors (P < .05) of cancer recurrence were age older than 60 years, male sex, wedge resection, World Health Organization (WHO) adenocarcinoma subtype solid tumor with mucin, lymphatic invasion, and p53 expression. Multivariate analysis identified nine independent predictors of recurrence: solid tumor with mucin, a wedge resection,;tumor diameter of 4 cm or greater, lymphatic invasion, age older than 60 years, male sex, p53 expression, K-ras codon 12 mutation, and absence of H-ras p21 expression. Multivariate cancer-free survival (CFS) analysis in the 180 patients who underwent lobectomy or pneumonectomy led to the elimination of sex and age, which left six independent factors. Conclusion: Lobectomy or pneumonectomy should be performed in stage I NSCLC. Using the six independent factors for recurrent disease, we propose a pathologic molecular substaging system. Patients with two factors or less are graded la, with a 5-year CFS rate of 87%; those with three factors are graded Ib, with a 5-year CFS rate of 58%; and those with four factors or more are graded Ic, with a 5-year CFS rate of 21%. (C) 1998 by American Society of Clinical Oncology. C1 Brigham & Womens Hosp, Div Expt Med, Dept Pathol, Boston, MA 02115 USA. Harvard Med Sch, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA USA. Duke Univ, Med Ctr, Div Biometry, Durham, NC USA. Univ Texas, Md Anderson Canc Ctr, Dept Mol Oncol, Div Med, Houston, TX USA. RP Kwiatkowski, DJ (reprint author), Brigham & Womens Hosp, Div Expt Med, Dept Pathol, 221 Longwood Ave, Boston, MA 02115 USA. EM kwiatkowski@calvin.bwh.harvard.edu FU NCI NIH HHS [R29CA73980, R01CA60572] NR 34 TC 141 Z9 151 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL PY 1998 VL 16 IS 7 BP 2468 EP 2477 PG 10 WC Oncology SC Oncology GA ZY199 UT WOS:000074596200026 PM 9667266 ER PT J AU Langevin, AM Casto, DT Thomas, PJ Weitman, SD Kretschmar, C Grier, H Pratt, C Dubowy, R Bernstein, M Blaney, S Vietti, T AF Langevin, AM Casto, DT Thomas, PJ Weitman, SD Kretschmar, C Grier, H Pratt, C Dubowy, R Bernstein, M Blaney, S Vietti, T TI Phase I trial of 9-aminocamptothecin in children with refractory solid tumors: A pediatric oncology group study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID DNA TOPOISOMERASE-I; TOPOTECAN; INFUSION; CANCER AB Purpose: A phase I trial of 9-aminocamptothecin (9-AC) was performed in children with solid tumors to establish the dose-limiting toxicity (DLT), maximum-tolerated dose (MTD), and the pharmacokinetic profile in children and to document any evidence of activity. Patients and Methods: A 72-hour infusion of 9-AC dimethylacetamide formulation was administered every 21 days to 23 patients younger than 21 years of age with malignant tumors refractory to conventional therapy. Doses ranged from 36 to 62 mu g/m(2) per hour. pharmacokinetics were to be performed in at least three patients per dose level, The first course was used to determine the DLT and MTD. Results: Nineteen patients on four dose levels were assessable for toxicities. At 62 mu g/m(2) per hour, three patients experienced dose-limiting neutropenia and one patient experienced dose-limiting thrombocytopenia. pharmacokinetics were performed on 15 patients (nine patients had complete sets of plasma sampling performed). The pharmacokinetics of hath lactone and total 9-AC were highly variable. The percentage of 9-AC lactone at steady-state was 10.8% +/- 3.6%. Total 9-AC and its lactone form had a terminal half-life of 8.1 +/- 3.8 and 7.1 +/- 3.9 hours, respectively, and a volume of distribution at steady-state (Vdss) of 21.2 +/- 13.3 L/m(2) and 135.3 +/- 52.5 L/m(2), respectively. Hepatic metabolism and biliary transport had an important role in 9-AC disposition. Conclusion: The recommended phase II dose of 9 AC administered as a 72-hour infusion every 21 days to children with solid tumors is 52 mu g/m(2) per hour, Neutropenia and thrombocytopenia were dose limiting. (C) 1998 by American Society of Clinical Oncology. C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Baylor Coll Med, Houston, TX 77030 USA. Boston Floating Hosp, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. SUNY Syracuse, Syracuse, NY USA. Washington Univ, Sch Med, St Louis, MO 63130 USA. McGill Univ, Montreal, PQ, Canada. RP Langevin, AM (reprint author), Pediat Oncol Grp, MD 9372,645 N Michigan Ave,Suite 910, Chicago, IL 60611 USA. FU NCI NIH HHS [CA-33587, CA-31566, CA-41573] NR 18 TC 14 Z9 15 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL PY 1998 VL 16 IS 7 BP 2494 EP 2499 PG 6 WC Oncology SC Oncology GA ZY199 UT WOS:000074596200029 PM 9667269 ER PT J AU Minsky, BD Coia, L Haller, DG Hoffman, J John, M Landry, J Pisansky, TM Willett, C Mahon, I Owen, J Berkey, B Katz, A Hanks, G AF Minsky, BD Coia, L Haller, DG Hoffman, J John, M Landry, J Pisansky, TM Willett, C Mahon, I Owen, J Berkey, B Katz, A Hanks, G TI Radiation therapy for rectosigmoid and rectal cancer: Results of the 1992-1994 patterns of care process survey SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 18-23, 1997 CL ORLANDO, FLORIDA SP Amer Soc Therapeut Radiol & Oncol AB Purpose: To determine the US national practice standards for patients with adenocarcinoma of the rectum treated in radiation oncology facilities. Materials and Methods: A national survey of 57 institutions identified 507 eligible patients who received radiation therapy as a component of their treatment for rectal cancer, A stratified two-stage cluster sampling with simple random sampling at each stage for each stratum was used and on-site surveys were performed, Results: Of the 507 patients, 378 (75%) received postoperative therapy, 110 (22%) received preoperative therapy, 17 (2%) received both preoperative and postoperative therapy, and less than 0.5% received intraoperative radiation alone. To more accurately assess the utilization of modern radiation techniques as well as recommendations of the National Cancer Institute (NCI)-sponsored, randomized, postoperative, adjuvant combined modality therapy rectal cancer trials into current practice, the analysis was limited to the 243 (48%) patients with tumor, node, and metastasis staging system classification T3 and/or N1-2MO disease who underwent conventional surgery with negative margins. Although only 7% were treated on a clinical trial, 90% received chemotherapy for a median of 21 weeks. Most were treated with modern radiation treatment techniques. In contrast, techniques to identify and help exclude the small bowel from the radiation field were riot routinely used, Conclusion: Despite the fact that only 7% of patients with T3 and/or N1-2M0 disease were treated on a clinical trial, such trials appear to have resulted in a positive influence on the standard of practice within the oncology community. Although there are still some deficiencies, the majority of these patients received combined modality therapy and were treated with modern radiation therapy techniques. (C) 1998 by American Society of Clinical Oncology. C1 Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY 10021 USA. Community Med Ctr, Dept Radiat Oncol, Toms River, NJ USA. Univ Penn, Med Ctr, Dept Radiat Oncol, Philadelphia, PA 19104 USA. Fox Chase Canc Ctr, Dept Surg Oncol, Philadelphia, PA 19111 USA. Fox Chase Canc Ctr, Dept Radiat Oncol, Philadelphia, PA 19111 USA. Amer Coll Radiol, Patterns Care Study, Philadelphia, PA USA. Canc Ctr St Agnes, Dept Radiat Oncol, Fresno, CA USA. Emory Univ Hosp, Dept Radiat Oncol, Atlanta, GA 30322 USA. Mayo Clin & Mayo Fdn, Dept Radiat Oncol, Rochester, MN 55905 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Minsky, BD (reprint author), Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, 1275 York Ave, New York, NY 10021 USA. EM minskyb@mskcc.org NR 13 TC 19 Z9 19 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL PY 1998 VL 16 IS 7 BP 2542 EP 2547 PG 6 WC Oncology SC Oncology GA ZY199 UT WOS:000074596200036 PM 9667276 ER PT J AU Dranoff, G AF Dranoff, G TI Cancer gene therapy: Connecting basic research with clinical inquiry SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID AUTOLOGOUS BONE-MARROW; TRANSFER IN-VIVO; THYMIDINE KINASE GENE; TUMOR-CELLS; T-LYMPHOCYTES; ADENOVIRUS VECTORS; ANTITUMOR IMMUNITY; DENDRITIC CELLS; BRAIN-TUMORS; HIGH-TITER AB Molecular genetics has spawned an impressive outpouring of insights into the biology of neoplastic transformation and the host-tumor relationship. This deeper understanding of cancer pathogenesis presents a rich opportunity ta develop novel therapeutic agents with improved selectivity for cancer cells. One promising approach involves gene therapy, which is the introduction of genetic material into a patient's tissues with the intent to achieve therapeutic benefit. A number of gene transfer systems have been designed that enable the generic modification of relevant target cells, albeit with varying strengths and limitations. Several strategies to exploit gene transfer as a tool to target specific molecular defects intrinsic to cancer cells, enhance tumor chemosensitivity, and augment tumor immunogenicity are under intensive investigation. A number of these approaches have entered initial clinical testing and already provide intriguing new information about the biology of cancer in patients. In this review, I will highlight the critical issues and controversies that underscore preclinical experiments in cancer gene therapy, discuss some of the preliminary findings from the first wave of clinical trials, and speculate about the prospects that cancer gene therapy will change the way that cancer medicine is practiced. (C) 1998 by American Society of Clinical Oncology. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Dranoff, G (reprint author), Dana Farber Canc Inst, Dana 510E,44 Binney St, Boston, MA 02115 USA. EM glenn_dranoff@dfci.harvard.edu FU NCI NIH HHS [R01 CA74886] NR 85 TC 50 Z9 51 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL PY 1998 VL 16 IS 7 BP 2548 EP 2556 PG 9 WC Oncology SC Oncology GA ZY199 UT WOS:000074596200037 PM 9667277 ER PT J AU Colombo, AP Sakellari, D Haffajee, AD Tanner, A Cugini, MA Socransky, SS AF Colombo, AP Sakellari, D Haffajee, AD Tanner, A Cugini, MA Socransky, SS TI Serum antibodies reacting with subgingival species in refractory periodontitis subjects SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE periodontal diseases; periodontitis; refractory; microorganisms; IgG; antibody; serum ID ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; BACTEROIDES-GINGIVALIS; IMMUNE-RESPONSES; HUMORAL ANTIBODY; YOUNG-ADULTS; DISEASE; BACTERIA; ASSOCIATION; CLINDAMYCIN; PATTERNS AB The purpose of this investigation was to compare the levels of serum IgG antibody to 85 subgingival species in 32 refractory periodontitis, 56 successfully treated, and 33 periodontally healthy subjects. Refractory subjects showed mean full mouth attachment loss and/or >3 sites showing attachment loss >2.5 mm within 1 year after 2 treatment modalities, scaling and root planing and surgery plus systemically administered tetracycline. Successfully-treated subjects showed mean attachment level gain and no sites with attachment loss >2.5 mm, I year post-therapy. Periodontally healthy subjects exhibited no pecker or attachment level >3 mm, and no evidence of progressing attachment loss during I year of monitoring. Baseline serum was obtained from each subject and rested against 85 subgingival species, including reference strains and strains isolated from refractory subjects, using checkerboard immunoblotting. Significance of differences in levels of serum antibody among groups were sought using the Kruskal-Wallis test. Refractory subjects constituted a heterogeneous group based on their serum antibody response to subgingival species. Some individuals had antibody reactions to many subgingival species, while other subjects showed fewer or low numbers of responses. On average, refractory subjects exhibited higher numbers and levels of serum antibody reactions to a wide range of subgingival species than successfully treated or periodontally healthy subjects. Differences in serum antibody among clinical groups were more striking at higher threshold levels of antibody (>50 mu g/ml and >100 mu g/ml). The data showed that a subject was 10.1x more likely to be refractory if the subject exhibited antibody reactions with >9 subgingival species at >50 mu g/ml (p<0.001, after adjusting for multiple comparisons). Serum antibody to a subset of the test species differed among the clinical groups. Porphypromonas gingivalis, Bacteroides forsythus, and some strains isolated from refractory subjects (a novel Neisseria sp., Enterococcus faecalis, Prevotella loescheii and Prevotella oulora) elicited high serum antibody in the successfully treated and refractory subjects. High levels of serum antibody to a Microbacterium lacticum-like organism, Streptococcus oralis, Streptococcus constellatus, Actinobacillus actinomycetemcomitans serotype c and Haemophilus aphrophilus significantly increased the likelihood of a subject being refractory to conventional periodontal therapy. C1 Forsyth Dent Ctr, Dept Periodontol, Boston, MA 02115 USA. Forsyth Dent Ctr, Dept Bioadhes, Boston, MA 02115 USA. Univ Thessaloniki, Sch Dent, Dept Periodontol, Salonika, Greece. RP Haffajee, AD (reprint author), Forsyth Dent Ctr, Dept Periodontol, 140 Fenway, Boston, MA 02115 USA. RI SAKELLARI, DIMITRA/F-3299-2011 FU NIDCR NIH HHS [DE-04881, DE-09543, DE-10977] NR 50 TC 22 Z9 23 U1 0 U2 2 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0303-6979 J9 J CLIN PERIODONTOL JI J. Clin. Periodontol. PD JUL PY 1998 VL 25 IS 7 BP 596 EP 604 DI 10.1111/j.1600-051X.1998.tb02493.x PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA ZX346 UT WOS:000074506300011 PM 9696261 ER PT J AU Osgood-Hynes, DJ Greist, JH Marks, IM Baer, L Heneman, SW Wenzel, KW Manzo, PA Parkin, JR Spierings, CJ Dottl, SL Vitse, HM AF Osgood-Hynes, DJ Greist, JH Marks, IM Baer, L Heneman, SW Wenzel, KW Manzo, PA Parkin, JR Spierings, CJ Dottl, SL Vitse, HM TI Self-administered psychotherapy for depression using a telephone-accessed computer system plus booklets: An open US-UK study SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID MENTAL-HEALTH-TREATMENT; COGNITIVE THERAPY; DISORDER; AMITRIPTYLINE; PHARMACOTHERAPY; EDUCATION; COMMUNITY; SYMPTOMS; PROGRAM AB Objective: To evaluate the efficacy and acceptability of a self-help program for mild-to-moderate depression that combined treatment booklets and telephone calls to a computer-aided Interactive Voice Response (IVR) system. Method: In an open trial, 41 patients from Boston, Massachusetts; Madison, Wisconsin; and London, England, used COPE, a 12-week self-help system for depression. COPE consisted of an introductory videotape and 9 booklets accompanied by 11 telephone calls to an IVR system that made self-help recommendations to patients based on information they entered. Results: All 41 patients successfully completed the self-assessment in the booklets and telephone calls; 28 (68%) also completed the 12-week self-help program. Hamilton Rating Scale for Depression (HAM-D) and Work and Social Adjustment scores improved significantly (41% and 42% mean reduction in the intent-to-treat sample, respectively, p < .001). Eighteen (64%) of the 28 completers were considered responders on the basis of greater than or equal to 50% reduction in their HAM-D scores. There was a higher percentage of completers in the pooled U.S. sites (82% vs. 43%), and U.S, completers improved more than those in the United Kingdom (73% vs. 43% were responders). Most (68%) of the calls were made outside usual office hours, Monday-Friday, 9:00 a.m. to 5:00 p.m. Expectation of effectiveness and time spent making COPE calls (more treatment modules) correlated positively with improvement over 12 weeks. Mean call length for completers was 14 minutes. Conclusion: A self-help system comprised of a computer-aided telephone system and a series of booklets was used successfully by people with mild-to-moderate depression. These preliminary results are encouraging for people who cannot otherwise access ongoing, in-person therapy. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Healthcare Technol Syst LLC, Madison, WI USA. Dean Fdn Hlth Res & Educ Inc, Middleton, WI USA. Bethlem Royal & Maudsley Hosp, Inst Psychiat, London, England. RP Osgood-Hynes, DJ (reprint author), Massachusetts Gen Hosp, Charlestown Navy Yard,13th St,Bldg 149,9th Floor, Charlestown, MA 02129 USA. NR 42 TC 81 Z9 82 U1 3 U2 8 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD JUL PY 1998 VL 59 IS 7 BP 358 EP 365 DI 10.4088/JCP.v59n0704 PG 10 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 107FW UT WOS:000075197500004 PM 9714264 ER PT J AU Hurton, T Morrill, H Mascola, M York, C Bromley, B AF Hurton, T Morrill, H Mascola, M York, C Bromley, B TI Cervical varices: An unusual etiology for third-trimester bleeding SO JOURNAL OF CLINICAL ULTRASOUND LA English DT Article DE cervix; varices; prenatal diagnosis; ultrasonography; pregnancy AB We report an unusual etiology for third-trimester bleeding. A pregnant patient underwent sonographic evaluation after presenting in the third trimester with uterine contractions and bleeding per the vagina. Massive cervical varices were identified on prenatal sonography as the cause of the bleeding and resulted in cesarean delivery and gravid hysterectomy. Cervical varices may result in significant maternal morbidity despite prenatal diagnosis. (C) 1998 John Wiley & Sons, Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Mem Hosp,Dept Obstet & Gynecol, Boston, MA 02114 USA. RP Hurton, T (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Mem Hosp,Dept Obstet & Gynecol, 32 Fruit St,Blake 10, Boston, MA 02114 USA. NR 4 TC 17 Z9 17 U1 0 U2 1 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0091-2751 J9 J CLIN ULTRASOUND JI J. Clin. Ultrasound PD JUL-AUG PY 1998 VL 26 IS 6 BP 317 EP 319 DI 10.1002/(SICI)1097-0096(199807/08)26:6<317::AID-JCU7>3.0.CO;2-L PG 3 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA ZT516 UT WOS:000074095700007 PM 9641393 ER PT J AU Caplan, D Alpert, N Waters, G AF Caplan, D Alpert, N Waters, G TI Effects of syntactic structure and propositional number on patterns of regional cerebral blood flow SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Article ID WORKING-MEMORY; SENTENCE COMPREHENSION; INDIVIDUAL-DIFFERENCES; BRAIN POTENTIALS; CAPACITY; APHASIA; LOCALIZATION; SPEECH; BROCA AB Positron emission tomography (PET) was used to determine regional cerebral blood flow (rCBF) as a function of the syntactic form and propositional density of sentences. rCBF increased in the left pars opercularis, part of Broca's area, when subjects processed syntactically more complex sentences. There were no differences in rCBF in the perisylvian association cortex traditionally associated with language processing when subjects made plausibility judgments about sentences with two propositions as compared to sentences with one proposition, but rCBF increased in infero-posterior brain regions. These results suggest that there is a specialization of neural tissue in Broca's area for constructing aspects of the syntactic form of sentences to determine sentence meaning. They also suggest that this specialization is separate from the brain systems that are involved in utilizing the meaning of a sentence that has been understood to accomplish a task. C1 Massachusetts Gen Hosp, Neuropsychol Lab, Boston, MA 02114 USA. Boston Univ, Boston, MA 02215 USA. RP Caplan, D (reprint author), Massachusetts Gen Hosp, Neuropsychol Lab, Vincent Burnham 827,Fruit St, Boston, MA 02114 USA. EM Caplan@helix.mgh.harvard.edu FU NIDCD NIH HHS [DC02146] NR 45 TC 231 Z9 235 U1 1 U2 8 PU MIT PRESS PI CAMBRIDGE PA 55 HAYWARD STREET, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PD JUL PY 1998 VL 10 IS 4 BP 541 EP 552 DI 10.1162/089892998562843 PG 12 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 122DD UT WOS:000076055900011 PM 9712683 ER PT J AU Eskey, CJ Lev, MH Tatter, SB Gonzalez, RG AF Eskey, CJ Lev, MH Tatter, SB Gonzalez, RG TI Cerebral CT venography in surgical planning for a tentorial meningioma SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article ID SAGITTAL SINUS-THROMBOSIS C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neuroradiol, Boston, MA 02114 USA. RP Lev, MH (reprint author), Massachusetts Gen Hosp, Dept Radiol, GRB285,POB 9657, Boston, MA 02114 USA. NR 5 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD JUL-AUG PY 1998 VL 22 IS 4 BP 530 EP 532 DI 10.1097/00004728-199807000-00006 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 100JE UT WOS:000074812400006 PM 9676441 ER PT J AU Orup, HI Keith, DA Holmes, LB AF Orup, HI Keith, DA Holmes, LB TI Prenatal anticonvulsant drug exposure: Teratogenic effect on the dentition SO JOURNAL OF CRANIOFACIAL GENETICS AND DEVELOPMENTAL BIOLOGY LA English DT Article DE anticonvulsants; antiepileptic drugs; tooth crown size; dental anomalies; dental maturity ID GENE-EXPRESSION; TOOTH AGENESIS; INFANTS; ACID; AGE AB Prenatal exposure to anticonvulsant medication has been shown to cause craniofacial dysmorphology, prenatal growth retardation, hypoplastic nails and phalanges, and visceral abnormalities. In this study we examined maxillary and mandibular stone dental casts (45) and panoramic radiographs (39) from 45 individuals with ages 4.5 to 22.0 years for changes in mesiodistal crown size of deciduous and permanent teeth, and the presence of dental anomalies. These individuals had been exposed prenatally to antiepileptic drugs (AEDs). Mesiodistal crown diameters were measured from the dental casts and converted into standard scores (Z), using published normative data from the University of Michigan Longitudinal Craniofacial Growth Series. A significant increase in mesiodistal crown dimensions of the posterior maxillary teeth was observed, specifically in primary molars and their permanent premolar successors, as well as permanent molars. Changes in tooth size were more common in females than in males. Dental maturity, assessed using the panoramic radiographs, was equal to chronologic age. An increased frequency of hypodontia was the only notable dental anomaly. C1 Massachusetts Gen Hosp, Serv Pediat, Genet & Teratol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pediat, Cambridge, MA 02138 USA. Harvard Univ, Sch Dent Med, Cambridge, MA 02138 USA. RP Holmes, LB (reprint author), Massachusetts Gen Hosp, Serv Pediat, Genet & Teratol Unit, Warren Bldg 801,55 Fruit St, Boston, MA 02114 USA. NR 33 TC 10 Z9 10 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0270-4145 J9 J CRAN GENET DEV BIO JI J. Craniofac. Genet. Dev. Biol. PD JUL-SEP PY 1998 VL 18 IS 3 BP 129 EP 137 PG 9 WC Anatomy & Morphology; Developmental Biology; Genetics & Heredity SC Anatomy & Morphology; Developmental Biology; Genetics & Heredity GA 120AK UT WOS:000075931500001 PM 9785217 ER PT J AU Lane, AH Donahoe, PK AF Lane, AH Donahoe, PK TI New insights into Mullerian inhibiting substance and its mechanism of action SO JOURNAL OF ENDOCRINOLOGY LA English DT Review ID RECEPTOR STEROIDOGENIC FACTOR-1; RIBONUCLEIC-ACID EXPRESSION; TGF-BETA FAMILY; II RECEPTOR; SEXUAL-DIFFERENTIATION; NUCLEAR RECEPTOR; DUCT SYNDROME; DEVELOPMENTAL EXPRESSION; GONADAL DEVELOPMENT; ESTROUS-CYCLE C1 Massachusetts Gen Hosp, Pediat Surg Res Labs, Boston, MA 02114 USA. RP Lane, AH (reprint author), Massachusetts Gen Hosp, Pediat Surg Res Labs, Warren 10,50 Blossom St, Boston, MA 02114 USA. NR 60 TC 37 Z9 41 U1 0 U2 0 PU J ENDOCRINOLOGY LTD PI BRISTOL PA 17/18 THE COURTYARD, WOODLANDS, ALMONDSBURY, BRISTOL BS12 4NQ, ENGLAND SN 0022-0795 J9 J ENDOCRINOL JI J. Endocrinol. PD JUL PY 1998 VL 158 IS 1 BP 1 EP 6 DI 10.1677/joe.0.1580001 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 102RM UT WOS:000074938100001 PM 9713320 ER PT J AU Kis, AM Carnes, M AF Kis, AM Carnes, M TI Detecting iron deficiency in anemic patients with concomitant medical problems SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE iron deficiency; anemia; ferritin; total iron-binding capacity; transferrin saturation ID BONE-MARROW IRON; CHRONIC-RENAL-FAILURE; SERUM FERRITIN ASSAY; RHEUMATOID-ARTHRITIS; CHRONIC DISEASE; HOSPITALIZED-PATIENTS; PERITONEAL-DIALYSIS; STORES; HEMODIALYSIS; ERYTHROCYTE AB OBJECTIVE: To determine the sensitivity and specificity of mean corpuscular volume, transferrin saturation, total iron-binding capacity, and ferritin level in determining iron deficiency in a population of anemic veterans with a wide variety of general medical diagnoses. DESIGN: Retrospective chart review. SETTING: Hospitals of the Department of Veterans Affairs in Madison and Milwaukee, Wisconsin. PARTICIPANTS: One hundred one anemic veterans with any medical condition who underwent bone marrow aspiration and serum iron studies. MEASUREMENTS AND MAIN RESULTS: Using the presence or absence of bone marrow hemosiderin as the reference standard, the sensitivity and specificity of the following serum iron indicators were calculated: mean corpuscular volume, transferrin saturation, total iron-binding capacity, and ferritin level. Of these patients, 41 (40.6%) were categorized as iron deficient, with no stainable bone marrow hemosiderin. A serum ferritin level less than or equal to 100 mu g/L provided the best sensitivity (64.9%) and specificity (96.1%) for evaluating iron stores in this patient population. When performed within 24 hours of bone marrow examination, a serum ferritin level less than or equal to 100 mu g/L was 100% accurate in separating iron-deficient from iron-sufficient patients. None of the other serum iron indicators alone or in combination performed better than ferritin level alone. CONCLUSIONS: In a population of anemic veterans with a wide variety of concomitant medical problems, a serum ferritin level less than or equal to 100 mu g/L was optimal for determining iron deficiency. This is higher than the ferritin level of less than or equal to 50 mu g/L cited in standard textbooks as evidence of iron deficiency in patients with inflammation, infection, or malignancy. C1 Univ Wisconsin, Dept Med, Sect Geriatr & Gerontol, Madison, WI 53706 USA. RP Carnes, M (reprint author), William S Middleton Mem Vet Hosp, GRECC 11G, 2500 Overlook Terrace, Madison, WI 53705 USA. NR 37 TC 24 Z9 24 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 1998 VL 13 IS 7 BP 455 EP 461 DI 10.1046/j.1525-1497.1998.00134.x PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 102DU UT WOS:000074909200004 PM 9686711 ER PT J AU Beresford, PJ Jaju, M Friedman, RS Yoon, MJ Lieberman, J AF Beresford, PJ Jaju, M Friedman, RS Yoon, MJ Lieberman, J TI A role for heat shock protein 27 in CTL-mediated cell death SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TOXIC LYMPHOCYTES-T; REQUIRE GRANZYME-B; CYTOLYTIC LYMPHOCYTES; NATURAL-KILLER; PHOSPHATASE 2A; MYELOID LEUKEMOGENESIS; ACTIN POLYMERIZATION; PUTATIVE ONCOGENE; SERINE PROTEASES; RAPID INDUCTION AB CTL exocytosis of granules containing perforin and granzyme proteases induces apoptotic cell death. Either granzyme A or B can act with perforin to trigger apoptosis, Granzyme B activates a ubiquitous apoptotic cascade induced by caspase cleavage, but the granzyme A pathway is largely unknown, Using affinity chromatography with recombinant mutant inactive granzyme A, we previously isolated two granzyme A-binding proteins, PHAP (putative HLA-associated protein) I and II. PHAP II, a substrate of granzyme A, is degraded within minutes of CTL attack, Two additional cytoplasmic proteins of 27 and 53 kDa bind strongly to the mutant granzyme A column, requiring 6 M urea to elute. Sequencing identified these as the monomer and dimer of hsp27, a small heat shock protein up-regulated by stress and cellular activation. Hsp27 coprecipitates with granzyme A from cytoplasmic lysates and is not a substrate of the enzyme. Hsp27 translocates to the detergent-insoluble fraction of target cells and relocalizes from diffuse cytoplasmic staining to long filamentous fibers, especially concentrated in a perinuclear region, within minutes of CTL attack. Hsp27 may participate in morphologic changes during granule-mediated lysis, Low or absent levels of hsp27 expression in T lymphocytes, even after heat shock, may play a role in CTL resistance to granule-mediated lysis. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RP Lieberman, J (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. RI Lieberman, Judy/A-2717-2015 NR 50 TC 40 Z9 41 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 1 PY 1998 VL 161 IS 1 BP 161 EP 167 PG 7 WC Immunology SC Immunology GA ZV419 UT WOS:000074302700022 PM 9647220 ER PT J AU Henderson, SC Berezovskaya, A English, A Palliser, D Rock, KL Bamezai, A AF Henderson, SC Berezovskaya, A English, A Palliser, D Rock, KL Bamezai, A TI CD4(+) T cells mature in the absence of MHC class I and class II expression in Ly-6A.2 transgenic mice SO JOURNAL OF IMMUNOLOGY LA English DT Article ID POSITIVE SELECTION; THYMOCYTE DEVELOPMENT; DEFICIENT MICE; LYMPHOCYTES-T; B-CELLS; RECEPTOR; ANTIGEN; COMPLEX; STIMULATION; MOLECULES AB The TCRs expressed on T lymphocytes recognize foreign peptides bound to MHC molecules, This reactivity is the basis of specific immune response to the foreign Ag, How such specificities are generated in the thymus is still being debated. Signals generated through TCR upon interaction with self MHC-peptide complexes are critical for maturation of the CD4(+) helper and CD8(+) cytotoxic subsets. We have observed maturation of CD4(+) but not CD8(+) T cells in Ly-6A.2 transgenic MHC null mice. Since there can be no interactions with MHC molecules in these mice, these CD4(+) cells must express the T cell repertoire that exists before positive and negative selection, Interestingly, despite an absence of selection by MHC molecules, the CD4+ cells that mature recognize MHC molecules at a frequency as high as in CD4(+) cells in normal mice, These results demonstrate that: 1) the germline sequences encoding TCRs are biased toward reactivity to MHC molecules; and 2) CD4(+) cells as opposed to CD8(+) cells have distinct lineage commitment signals. These results also suggest that signals originating from Ly-6 can promote or substitute for signals generated from TCR that are required for positive selection. Moreover, this animal model offers a system to study T cell development in the thymus that can provide insights into mechanisms of lineage commitment in developing T cells. C1 Univ Georgia, Dept Cellular Biol, Athens, GA 30602 USA. Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. Univ Massachusetts, Med Ctr, Dept Pathol, Worcester, MA 01655 USA. RP Bamezai, A (reprint author), Univ Georgia, Dept Cellular Biol, 615 Biol Sci Bldg, Athens, GA 30602 USA. EM abamezai@cellmate.cb.uga.edu FU NIGMS NIH HHS [GM 38515] NR 43 TC 13 Z9 13 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 1 PY 1998 VL 161 IS 1 BP 175 EP 182 PG 8 WC Immunology SC Immunology GA ZV419 UT WOS:000074302700024 PM 9647222 ER PT J AU Irie, HY Mong, MS Itano, A Crooks, MEC Littman, DR Burakoff, SJ Robey, E AF Irie, HY Mong, MS Itano, A Crooks, MEC Littman, DR Burakoff, SJ Robey, E TI The cytoplasmic domain of CD8 beta regulates Lck kinase activation and CD8 T cell development SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PROTEIN-TYROSINE KINASE; BETA-CHAIN; THYMIC SELECTION; THYMOCYTE DEVELOPMENT; SURFACE EXPRESSION; NEGATIVE SELECTION; POSITIVE SELECTION; GENE-TRANSFER; MICE LACKING; P56LCK AB Previous studies have shown that CD8 beta plays a role in both enhancing CD8 alpha-associated Lck kinase activity and promoting the development of CDS-lineage T cells. To examine the role of this enhancement in the maturation of CD8-lineage cells, we assessed CD8 alpha-associated Lck kinase activity in both T cell hybridomas and thymocytes of mice expressing CD8 beta mutations known to impair CD8 T cell development. Lack of CD8 beta expression or expression of a cytoplasmic domain-deleted CD8 beta resulted in a severalfold reduction in CD8 alpha-associated Lck kinase activity compared with that observed with cells expressing wild-type CD8 beta chain. This analysis indicated a critical role for the cytoplasmic domain of CD8 beta in the regulation of CD8 alpha-associated Lck activity, Decreased CD8 alpha-associated Lck activity observed with the various CD8 beta mutations also correlated with diminished in vivo cellular tyrosine phosphorylation. In addition, analysis of CD8 beta mutant mice (CD8 beta(-/-) or cytoplasmic domain-deleted CD8 beta transgenic) indicated that the degree of reduction in CD8 alpha-associated Lck activity associated with each mutation correlated with the severity of developmental impairment. These results support the importance of CD8 beta-mediated enhancement of CD8 beta-associated Lck kinase activity in the differentiation of CD8 single-positive thymocytes. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA. NYU, Med Ctr, Skirball Inst Biomol Med, Howard Hughes Med Inst, New York, NY 10016 USA. RP Burakoff, SJ (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, DANA 1640,44 Binney St, Boston, MA 02115 USA. FU NIAID NIH HHS [R01AI32985, AI17258]; NIGMS NIH HHS [GMO7753-16, T32 GM007753] NR 35 TC 34 Z9 35 U1 1 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 1 PY 1998 VL 161 IS 1 BP 183 EP 191 PG 9 WC Immunology SC Immunology GA ZV419 UT WOS:000074302700025 PM 9647223 ER PT J AU Detmar, M Brown, LF Schon, MP Elicker, BM Velasco, P Richard, L Fukumura, D Monsky, W Claffey, KP Jain, RK AF Detmar, M Brown, LF Schon, MP Elicker, BM Velasco, P Richard, L Fukumura, D Monsky, W Claffey, KP Jain, RK TI Increased microvascular density and enhanced leukocyte rolling and adhesion in the skin of VEGF transgenic mice SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE angiogenesis; endothelium; VPF; mast cells ID ENDOTHELIAL GROWTH-FACTOR; VASCULAR-PERMEABILITY FACTOR; STEM-CELL FACTOR; TYROSINE KINASE; C-KIT; FACTOR VPF/VEGF; MAST-CELLS; OVEREXPRESSION; EXPRESSION; PSORIASIS AB Vascular endothelial growth factor (VEGF) has been implicated in the pathologic angiogenesis observed in psoriasis and other chronic inflammatory skin diseases that are characterized by enhanced expression of VEGF by epidermal keratinocytes and of VEGF receptors by tortuous microvessels in the upper dermis, To investigate the functional importance of chronic VEGF overexpression in vivo, we used a keratin 14 promoter expression cassette containing the gene for murine VEGF(164) to selectively target VEGF expression to basal epidermal keratinocytes in transgenic mice. These mice demonstrated an increased density of tortuous cutaneous blood capillaries with elevated expression levels of the high affinity VEGF receptors, VEGFR-1 and VEGFR-2, most prominently during the neonatal period. In contrast, no abnormalities of lymphatic vessels were detected. In addition, the number of mast cells in the upper dermis was significantly increased in transgenic skin. Intravital fluorescence microscopy revealed highly increased leukocyte rolling and adhesion in postcapillary skin venules that were both inhibited after injection of blocking antibodies against E- and P-selectin. Combined blocking antibodies against intercellular adhesion molecule-1 and lymphocyte function-associated antigen-1 were without effect, whereas an antivascular cell adhesion molecule-1/VLA-4 antibody combination almost completely normalized the enhanced leukocyte adhesion in transgenic mice. This study reveals VEGF as a growth factor specific for blood vessels, but not lymphatic vessels, and demonstrates that chronic orthotopic overexpression of VEGF in the epidermis is sufficient to induce cardinal features of chronic skin inflammation, providing a molecular link between angiogenesis, mast cell accumulation, and leukocyte recruitment to sites of inflammation. C1 Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA USA. Beth Israel Deaconess Med Ctr, Dept Dermatol, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Div Rheumatol & Immunol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Detmar, M (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA69184] NR 45 TC 366 Z9 378 U1 0 U2 6 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 1998 VL 111 IS 1 BP 1 EP 6 DI 10.1046/j.1523-1747.1998.00262.x PG 6 WC Dermatology SC Dermatology GA ZW467 UT WOS:000074413900001 PM 9665379 ER PT J AU Lin, TYD Manuskiatti, W Dierickx, CC Farinelli, WA Fisher, ME Flotte, T Baden, HP Anderson, RR AF Lin, TYD Manuskiatti, W Dierickx, CC Farinelli, WA Fisher, ME Flotte, T Baden, HP Anderson, RR TI Hair growth cycle affects hair follicle destruction by ruby laser pulses SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE C57BL6; hair removal; selective thermolysis ID SKIN; EXPRESSION; MICE AB It has been shown that normal mode ruby laser pulses (694 nm) are effective in selectively destroying brown or black pigmented hair follicles in adult Caucasians. This study investigated how the various stages of the hair follicle growth cycle influence follicle destruction by ruby laser treatment, using a model of predictable synchronous hair growth cycles in the infantile and adolescent mice. A range of ruby laser pulse fluences was delivered during different stages of the hair growth cycle, followed by histologic and gross observations of the injury and regrowth of hair. Actively growing and pigmented anagen stage hair follicles were sensitive to hair removal by normal mode ruby laser exposure, whereas catagen and telogen stage hair follicles were resistant to laser irradiation. Selective thermal injury to follicles was observed histologically, and hair regrowth was fluence dependent. In animals exposed during anagen, intermediate fluences induced nonscarring alopecia, whereas high fluences induced scarring alopecia. The findings of this study suggest treatment strategies for optimal laser hair removal. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Wellman Labs Photomed, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Biol Res Ctr, Boston, MA 02114 USA. Univ Ottawa, Sch Med, Ottawa, ON K1N 6N5, Canada. RP Anderson, RR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Wellman Labs Photomed, Boston, MA 02114 USA. NR 28 TC 56 Z9 62 U1 0 U2 4 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 1998 VL 111 IS 1 BP 107 EP 113 DI 10.1046/j.1523-1747.1998.00227.x PG 7 WC Dermatology SC Dermatology GA ZW467 UT WOS:000074413900017 PM 9665395 ER PT J AU Lee, R Neya, K Vlahakes, GJ AF Lee, R Neya, K Vlahakes, GJ TI Effect of cardiopulmonary bypass and calcium administration on the splanchnic circulation SO JOURNAL OF INVESTIGATIVE SURGERY LA English DT Article DE calcium; cardiac surgery; cardiopulmonary bypass; pancreatitis; splanchnic ID REGIONAL BLOOD-FLOW; GASTROINTESTINAL COMPLICATIONS; ABDOMINAL COMPLICATIONS; CARDIAC-SURGERY AB Gastrointestinal complications following cardiopulmonary bypass (CPB) are associated with high mortality rates. The identification of prolonged CPB time and calcium administration as independent predictors of gastrointestinal complications suggests decreased splanchnic perfusion as a possible mechanism. To test this hypothesis, we evaluated splanchnic organ perfusion during CPB and after calcium chloride administration. Mongrel dogs were studied under anesthesia and were cannulated for bypass. CPB was begun at 37 degrees C, and the heart was fibrillated and vented. After 30 min, CPB temperature was reduced to 25 degrees C for 1 h with the heart arrested through cold crystalloid cardioplegia. After rewarming to 37 degrees C for 30 min, the heart was cardioverted, and CPB was weaned off. Calcium chloride (10 mg/kg) or saline was administered. Organ blood flow was determined with radiolabeled microspheres at baseline, during CPB, End after weaning from CPB. Splanchnic organ blood flow did not decrease during any phase of CPB. Calcium chloride administration after CPB had no effect on splanchnic organ blood flow. While gastrointestinal injury may result from CPB, this study suggests that the mechanism of injury is not decreased by splanchnic organ perfusion during bypass. While calcium chloride can cause pancreatic injury, the responsible mechanism is not calcium-induced hypoperfusion. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Vlahakes, GJ (reprint author), Massachusetts Gen Hosp, Dept Surg, 55 Fruit St,EDR105, Boston, MA 02114 USA. EM vlahakes.gus@mgh.harvard.edu NR 17 TC 5 Z9 5 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0894-1939 J9 J INVEST SURG JI J. Invest. Surg. PD JUL-AUG PY 1998 VL 11 IS 4 BP 251 EP 258 DI 10.3109/08941939809032199 PG 8 WC Surgery SC Surgery GA 125TZ UT WOS:000076254300004 PM 9788666 ER PT J AU Raveh, D Kruskal, BA Farland, J Ezekowitz, RAB AF Raveh, D Kruskal, BA Farland, J Ezekowitz, RAB TI T(h)1 and T(h)2 cytokines cooperate to stimulate mannose-receptor-mediated phagocytosis SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE endocytosis; interleukin-1; interferon-gamma ID INTERFERON-GAMMA; DOWN-REGULATION; MOUSE MACROPHAGES; ENDOCYTOSIS; BINDING; MACROPINOCYTOSIS; CELLS; INTERLEUKIN-13; EXPRESSION; ACTIVATION AB The mannose receptor is a macrophage surface receptor that mediates both endocytosis and phagocytosis. Previous work has demonstrated that the prototypical T(h)2 cytokine, interleukin-4 (IL-4), increases both cell-surface receptor expression and mannose receptor-mediated endocytosis, whereas the prototypical T(h)1 cytokine, interferon-gamma (IFN-gamma), decreases both surface expression and endocytosis, In many aspects of the immune response, T(h)1 and T(h)2 cytokines oppose each others' actions, We demonstrate that IL-4 and IFN-gamma alone and together enhance mannose receptor-mediated phagocytosis, despite opposing effects on cell-surface mannose receptor expression and endocytosis, Thus these usually antagonistic cytokines cooperate in increasing mannose receptor phagocytic function. The cooperative effect of these cytokines is not observed for Fc receptor-mediated phagocytosis, The T(h)2 cytokine IL-13 exerts similar effects to IL-4. Our results suggest that T(h)1 and T(h)2 cytokines may act in concert at sites of inflammation to enhance mannose receptor-mediated phagocytosis of microorganisms. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat,Lab Dev Immunol, Boston, MA 02114 USA. RP Ezekowitz, RAB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat,Lab Dev Immunol, 15 Parkman St, Boston, MA 02114 USA. NR 28 TC 47 Z9 47 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD JUL PY 1998 VL 64 IS 1 BP 108 EP 113 PG 6 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA ZY385 UT WOS:000074616000019 PM 9665284 ER PT J AU Curhan, GC AF Curhan, GC TI Interstitial cystitis SO JOURNAL OF NEPHROLOGY LA English DT Editorial Material ID BLADDER; PENTOSANPOLYSULFATE C1 Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. RP Curhan, GC (reprint author), Massachusetts Gen Hosp, Renal Unit, 100 Charles River Plaza, Boston, MA 02114 USA. NR 15 TC 1 Z9 1 U1 0 U2 0 PU WICHTIG EDITORE PI MILAN PA 72/74 VIA FRIULI, 20135 MILAN, ITALY SN 1121-8428 J9 J NEPHROL JI J. Nephrol. PD JUL-AUG PY 1998 VL 11 IS 4 BP 169 EP 170 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 104KU UT WOS:000075014200002 PM 9702866 ER PT J AU Khan, M Pahan, K Singh, AK Singh, I AF Khan, M Pahan, K Singh, AK Singh, I TI Cytokine-induced accumulation of very long-chain fatty acids in rat C6 glial cells: Implication for X-adrenoleukodystrophy SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE adrenoleukodystrophy; cytokines; very long-chain fatty acids; glia; nitric oxide ID NITRIC-OXIDE SYNTHASE; LINKED ADRENOLEUKODYSTROPHY; MEMBRANE MICROVISCOSITY; LIGNOCERIC ACID; ALPHA; BRAIN; GENE; ADRENOMYELONEUROPATHY; OLIGODENDROCYTES; CYTOTOXICITY AB X-Adrenoleukodystrophy (X-ALD) is an inherited metabolic disorder of very long-chain fatty acids (VLCFA) with subsequent manifestation of neuroinflammatory disease. To investigate the possible role of proinflammatory cytokines in the X-ALD disease process, we examined the effect of cytokines on the metabolism of VLCFA in C6 glial cells expressing oligodendrocyte-like properties. C6 glial cells under serum-free conditions were treated with different combinations of cytokines (tumor necrosis factor-alpha, interleukin-1 beta, interferon-gamma) or cytokine with bacterial lipopolysaccharide (LPS). Cytokine-treated C6 cells had higher concentrations of VLCFA, measured as percent weight and also as C-26:0/C-22:0 ratio, which were 300-400% as compared with the controls. We also found increased levels of C-26:1 in cytokine-treated cells. The accumulation of VLCFA paralleled the decrease (35-55%) in peroxisomal beta-oxidation activity and a 12- to 14-fold increase in the production of nitric oxide (NO). Individual cytokines were unable either to produce NO or to increase the levels of VLCFA in C6 cells. Inhibition of cytokine-induced NO production by L-N-methylarginine, an inhibitor of NO synthase (NOS), and N-acetylcysteine, an inhibitor of cytokine-mediated induction of inducible NOS, normalized the peroxisomal beta-oxidation activity and the levels of VLCFA, suggesting a role for the proinflammatory cytokines and NO toxicity in the neuropathological changes associated with abnormal VLCFA metabolism (e.g., X-ALD). X-ALD is a peroxisomal disease having deficient oxidation of VLCFA, resulting in the excessive accumulation of VLCFA in all tissues but especially in brain. We observed greater increase in levels of VLCFA in the inflammatory region of ALD brain (in the demyelinating plaque and the area around the plaque) than in the normal-looking area away from the plaque; this also indicates that cytokines in the proinflammatory region may augment the VLCFA defect caused by the inherited abnormality in X-ALD brain. Although C6 glial cultured cells do not reflect the X-ALD model precisely, the observed relationship between the cytokine-induced inhibition of the oxidation of VLCFA, excessive accumulation of VLCFA, and excessive production of NO and their normalization by inhibitors of NOS in C6 glial cells suggests that NO-mediated toxicity may play a role in VLCFA-associated neuroinflammatory diseases (e.g., X-ALD). C1 Med Univ S Carolina, Dept Pediat, Div Dev Neurogenet, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Dept Pathol & Lab Med, Charleston, SC USA. RP Singh, I (reprint author), Med Univ S Carolina, Dept Pediat, Div Dev Neurogenet, 171 Ashley Ave, Charleston, SC 29425 USA. FU NINDS NIH HHS [NS-22576, NS-37766] NR 36 TC 38 Z9 38 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUL PY 1998 VL 71 IS 1 BP 78 EP 87 PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA ZV232 UT WOS:000074283600008 PM 9648853 ER PT J AU Browne, SE Bowling, AC Baik, MJ Gurney, M Brown, RH Beal, MF AF Browne, SE Bowling, AC Baik, MJ Gurney, M Brown, RH Beal, MF TI Metabolic dysfunction in familial, but not sporadic, amyotrophic lateral sclerosis SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE amyotrophic lateral sclerosis; neurodegeneration; free radicals; oxidative damage; superoxide dismutase ID MOTOR-NEURON DISEASE; ANTERIOR HORN NEURONS; SUPEROXIDE-DISMUTASE ACTIVITY; ENERGY-METABOLISM; OXIDASE ACTIVITY; PROXIMAL AXONS; SOD1 MUTATION; GENE; DEGENERATION; CALCIUM AB Autosomal dominant familial amyotrophic lateral sclerosis (FALS) is associated with mutations in the gene encoding Cu/Zn superoxide dismutase (SOD1). Previous studies have implicated the involvement of metabolic dysfunction in ALS pathogenesis. To further investigate the biochemical features of FALS and sporadic ALS (SALS), we examined SOD activity and mitochondrial oxidative phosphorylation enzyme activities in motor cortex (Brodmann area 4), parietal cortex (Brodmann area 40), and cerebellum from control subjects, FALS patients with and without known SOD mutations, SALS patients, and disease controls (Pick's disease, progressive supranuclear palsy, diffuse Lewy body disease). Cytosolic SOD activity, predominantly Cu/Zn SOD, was decreased similar to 50% in all regions in FALS patients with SOD mutations but was not significantly altered in other patient groups. Marked increases in complex I and II-III activities were seen in FALS patients with SOD mutations but not in SALS patients. We also measured electron transport chain enzyme activities in a transgenic mouse model of FALS, Complex I activity was significantly increased in the forebrain of 60-day-old G93A transgenic mice overexpressing human mutant SOD1, relative to levels in transgenic wild-type animals, supporting the hypothesis that the motor neuron disorder associated with SOD1 mutations involves a defect in mitochondrial energy metabolism. C1 Massachusetts Gen Hosp, Serv Neurol, Neurochem Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Serv Neurol, Day Neuromusc Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Pharmacia & Upjohn Inc, Cent Nervous Syst Res Unit, Kalamazoo, MI 49001 USA. RP Beal, MF (reprint author), Massachusetts Gen Hosp, Serv Neurol, Neurochem Lab, Warren 408,32 Fruit St, Boston, MA 02114 USA. FU NIA NIH HHS [P01 AG 11337, P01 AG 12992] NR 44 TC 97 Z9 98 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUL PY 1998 VL 71 IS 1 BP 281 EP 287 PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA ZV232 UT WOS:000074283600031 PM 9648876 ER PT J AU Marchena, JM Padwa, BL Kaban, LB AF Marchena, JM Padwa, BL Kaban, LB TI Sensory abnormalities associated with mandibular fractures: Incidence and natural history SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article; Proceedings Paper CT 78 Annual AAOMS Meeting CY SEP, 1996 CL MIAMI BEACH, FLORIDA ID RIGID INTERNAL-FIXATION; OSTEOSYNTHESIS; DISTURBANCES; PLATES AB Purpose: The aims of this study were to determine the incidence of inferior alveolar nerve (IAN) abnormalities in patients with mandibular fractures and to document the natural history and spontaneous recovery rate in patients with a sensory disturbance. Patients and Methods: This was a retrospective evaluation of patients (n = 150) with mandibular fractures at risk for IAN injury admitted to the Oral and Maxillofacial Surgery Service between 1985 and 1995. The inclusion criteria were: 1) fractures between the mandibular and mental foramina, 2) availability of the results of a post-injury, preoperative sensory examination, and 3) at least 1 year follow-up. Fracture characteristics, physical examination findings, hospital course, operative treatment, and follow-up were documented. Patient interviews were conducted to determine the incidence of long-term sensory disturbance and associated morbidity. The results were evaluated with chi-square analysis. Results: Fifty-six percent of patients (84 of 150) had a post-injury/pretreatment IAN abnormality. Patients with sensory disturbance had a significantly higher frequency of displaced fractures than those without sensory disturbance (P <.001). Sixteen of 24 patients (66.7%) with an abnormal post-injury/pretreatment sensory examination reported a permanent sensory deficit (mean follow-up, 74.3 months); 55% of these patients complained of impairment. Conclusions: The incidence of postinjury IAN deficits in patients with mandibular fractures was greater than 50% and was related to fracture displacement. One third of these patients regained normal sensation; the remaining two thirds reported a persistent sensory deficit. A significant number of these patients complained of discomfort and impairment after a mean follow-up of greater than 6 years. C1 Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. RP Kaban, LB (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Warren 1201, Boston, MA 02114 USA. NR 17 TC 29 Z9 30 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD JUL PY 1998 VL 56 IS 7 BP 822 EP 825 DI 10.1016/S0278-2391(98)90003-9 PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA ZX684 UT WOS:000074543600004 PM 9663571 ER PT J AU Krebs, DE Robbins, CE Lavine, L Mann, RW AF Krebs, DE Robbins, CE Lavine, L Mann, RW TI Hip biomechanics during gait SO JOURNAL OF ORTHOPAEDIC & SPORTS PHYSICAL THERAPY LA English DT Article DE acetabular contact pressures; hip; gait cycle ID ACETABULAR CONTACT PRESSURES; ELECTROMYOGRAPHIC ANALYSIS; JOINT; MUSCLE; REHABILITATION; WALKING; TORQUES; PHASE; KNEE; LOAD AB The literature is devoid of complete descriptions of hip biomechanics during gait. We present for the first time simultaneously acquired in vivo acetabular contact pressures, ground reaction forces, kinematics, hip torques, and electromyographic (EMG) activity during gait with and without a cane from an 85-year-old male with a left instrumented femoral head prosthesis. Highest acetabular contact pressures occurred in all gait trials at the posterosuperior acetabulum, just prior to peak EMG, adductor torque, and ground reaction force during late stance phase. Contralateral cane use reduced both peak acetabular contact pressure and gluteus medius EMG but not adductor torque or ground reaction force. These data identify a small area of high acetabular and femoral head stress that could occur during each of human's millions of gait cycles annually and indicate that muscle activity, rather than solely body weight, drives hip loading. Clinicians who desire to limit hip loads should reduce both hip muscle contraction and weight bearing in late stance. C1 Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA. Massachusetts Gen Hosp, Biomot Lab, Boston, MA 02114 USA. Spaulding Rehabil Hosp, Boston, MA USA. MIT, Newman Lab Biomech & Rehabil, Cambridge, MA 02139 USA. RP Krebs, DE (reprint author), Massachusetts Gen Hosp, Inst Hlth Profess, 100 Merrimac St, Boston, MA 02114 USA. FU NHLBI NIH HHS [HI33E80024]; NIAMS NIH HHS [R01-AR40036]; NICHD NIH HHS [R01-HD30063] NR 35 TC 38 Z9 39 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0190-6011 J9 J ORTHOP SPORT PHYS JI J. Orthop. Sports Phys. Ther. PD JUL PY 1998 VL 28 IS 1 BP 51 EP 59 PG 9 WC Orthopedics; Rehabilitation; Sport Sciences SC Orthopedics; Rehabilitation; Sport Sciences GA ZW517 UT WOS:000074418900007 PM 9653690 ER PT J AU Sheridan, RL Yu, YM Prelack, K Young, VR Burke, JF Tompkins, RG AF Sheridan, RL Yu, YM Prelack, K Young, VR Burke, JF Tompkins, RG TI Maximal parenteral glucose oxidation in hypermetabolic young children: A stable isotope study SO JOURNAL OF PARENTERAL AND ENTERAL NUTRITION LA English DT Article ID SEVERELY BURNED PATIENTS; TRIGLYCERIDE SECRETION; INDIRECT CALORIMETRY; NUTRITION; INJURY; KINETICS; INFUSION; INSULIN; INFANTS; METABOLISM AB Background: During periods in which nutrition support of critically ill young children must be parenteral, glucose infusions are administered at up to 10 or more mg.kg(-1).min(-1) to meet predicted energy needs. However. data in adults suggest that such high glucose loads exceed the ability to oxidize glucose in the hormonal milieu that, characterizes critical illness. The purpose of this study was to determine if these high glucose loads are oxidized by critically ill young children. Methods: Ten young children ri; serious bums were enrolled in a stable isotope study of glucose metabolism. These five boys and five girls were an average age of 5.2 years (range, 1 to 11 years), weight of 18.4 kg (range, 10 to 31 kg) and burn size of 51.6% of the body surface (range, 35% to 86%). During clinically required episodes of parenteral nutrition support, we used the [C-13(6)]glucose tracer to assess the efficacy of glucose oxidation at both 6 and 8 mg . kg(-1) . min(-1). Serum glucose was recorded and indirect calorimetry was performed. Results: The fraction of exogenous glucose oxidation fell from 59% +/- 6% to 47% + 5% (p < .06). Although there was a significantly increased level of total glucose oxidation (3.2 to 3.8 mg . kg(-1) . min(-1)), this increment (29% +/- 9%) was accompanied by a significant decrease in the efficiency of energy production, because the bulk of the additional glucose above 5 mg . kg(-1) . min(-1) was not being oxidized. Plasma glucose concentration did not change (145 +/- 4 vs 137 +/- 4 mg/dL, p <.01) and whole-body expired gas respiratory quotients remained consistent with a mixed fuel oxidation, implying that there exists an increased rate of exogenous glucose uptake by tissues in nonoxidative pathways. Conclusions: Maximum glucose oxidation in severely burned children occurs at intakes approximating 5 mg . kg(-1) . min(-1). Exogenous glucose in excess of this amount enters nonoxidative pathways and is unlikely to improve energy balance. Clinical markers such as serum glucose levels or expired respiratory quotient may not detect inefficient glucose utilization. C1 Shriners Hosp Children, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. MIT, Dept Nutr Biochem, Boston, MA USA. RP Sheridan, RL (reprint author), Shriners Hosp Children, 51 Blossom St, Boston, MA 02114 USA. NR 39 TC 29 Z9 29 U1 0 U2 1 PU AMER SOC PARENTERAL & ENTERAL NUTRITION PI SILVER SPRING PA 8630 FENTON STREET SUITE 412, SILVER SPRING, MD 20910 USA SN 0148-6071 J9 JPEN-PARENTER ENTER JI J. Parenter. Enter. Nutr. PD JUL-AUG PY 1998 VL 22 IS 4 BP 212 EP 216 DI 10.1177/0148607198022004212 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA ZX875 UT WOS:000074564200005 PM 9661121 ER PT J AU Choi, RS Riegler, M Pothoulakis, C Kim, BS Mooney, D Vacanti, M Vacanti, JP AF Choi, RS Riegler, M Pothoulakis, C Kim, BS Mooney, D Vacanti, M Vacanti, JP TI Studies of brush border enzymes, basement membrane components, and electrophysiology of tissue-engineered neointestine SO JOURNAL OF PEDIATRIC SURGERY LA English DT Article; Proceedings Paper CT 1997 Annual Meeting of the Section on Surgery of the American-Academy-of-Pediatrics CY OCT 31-NOV 02, 1997 CL NEW ORLEANS, LOUISIANA SP Amer Acad Pediat, Sect Surg DE intestinal cell transplantation; tissue engineering; electrophysiology ID TRANSPLANTATION; MUCOSA; SURVIVAL; CELLS; RAT AB Background/Purpose: Previous studies have shown that intestinal crypt cell transplantation using biodegradable scaffolds can generate stratified epithelium reminiscent of embryonic gut. The authors propose to tissue engineer small intestine on biodegradable scaffolds by transplanting intestinal epithelial organoid units, which maintain the epithelial mesenchymal cell-cell interaction necessary for epithelial survival, proliferation, and differentiation. Methods: Intestinal epithelial organoid units were isolated from neonatal Lewis rats by enzyme digestion and differential sedimentation. Organoid units were seeded on to tubular scaffolds made of nonwoven polyglycolic acid (PGA) sprayed with 5% polylactic acid (PLA). Polymers either were coated (28 constructs) or noncoated (33 constructs) with collagen type I. A total of 61 organoid unit polymer constructs were implanted into 61 animals. Animals were killed and constructs harvested at 2, 6, 7, 8, 9, 10, 12, and 14 weeks. Results: Histological analysis showed formation of neomucosa characterized by columnar epithelium with goblet, and paneth cells were evident in 47 of the 61 constructs. The outer walls were composed of fibrovascular tissue, degradable polymer, extracellular matrix, and smooth muscle-like cells. Immunofluorescent microscopy showed apical staining of brush border enzymes, sucrase and lactase, and basolateral staining for laminin, indicating the establishment of cell polarity. Electrophysiology of Ussing-chambered neomucosa and adult ileal mucosa exhibited similar transepithelial resistance. Conclusion: These results suggest that intestinal crypt cells heterotopically transplanted as epithelial organoid units on PGA-PLA tubular scaffolds can survive, reorganize, and regenerate complex composite tissue resembling small intestine demonstrating organ morphogenesis, cytodifferentiation, and phenotypic maturation. J Pediatr Surg 33:991-997 Copyright (C) 1998 by W.B. Saunders Company. C1 Childrens Hosp, Dept Surg, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Gastroenterol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. Univ Michigan, Dept Chem Engn, Ann Arbor, MI 48109 USA. RP Vacanti, JP (reprint author), Childrens Hosp, Dept Surg, 300 Longwood Ave, Boston, MA 02115 USA. RI Kim, Byung-Soo/O-2352-2013 NR 19 TC 59 Z9 61 U1 1 U2 8 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0022-3468 J9 J PEDIATR SURG JI J. Pediatr. Surg. PD JUL PY 1998 VL 33 IS 7 BP 991 EP 996 DI 10.1016/S0022-3468(98)90520-6 PG 6 WC Pediatrics; Surgery SC Pediatrics; Surgery GA 100XU UT WOS:000074841300012 PM 9694083 ER PT J AU Nobuhara, KK DiFiore, JW Ibla, JC Siddiqui, AM Ferretti, ML Fauza, DO Schnitzer, JJ Wilson, JM AF Nobuhara, KK DiFiore, JW Ibla, JC Siddiqui, AM Ferretti, ML Fauza, DO Schnitzer, JJ Wilson, JM TI Insulin-like growth factor-I gene expression in three models of accelerated lung growth SO JOURNAL OF PEDIATRIC SURGERY LA English DT Article; Proceedings Paper CT 1997 Annual Meeting of the Section on Surgery of the American-Academy-of-Pediatrics CY OCT 31-NOV 02, 1997 CL NEW ORLEANS, LOUISIANA SP Amer Acad Pediat, Sect Surg DE lung growth; insulin like growth factor-I; perfluorocarbon; congenital diaphragmatic hernia; pneumonectomy ID CONGENITAL DIAPHRAGMATIC-HERNIA; MESSENGER-RNA; HUMAN-FETUS; PNEUMONECTOMY; IGF-1 AB Background/Purpose: We have learned previously that in utero tracheal ligation reverses the structural and physiological effects of surgically created congenital diaphragmatic hernia. In addition, we have discovered that postnatal lung growth similarly can be accelerated using liquid-based airway distension with perfluorocarbon. Another model of accelerated lung growth is that of compensatory growth seen after neonatal pneumonectomy. In all of these models, growth has occurred because of an increase in alveolar number rather than enlargement of preexisting alveoli. However, the molecular mechanisms underlying these processes remain unknown. The purpose of th is study was to determine if gene expression could be altered by changes in physical forces in the prenatal and postnatal lung. Methods: The three models of accelerated lung growth studied we re the following: (1) The prenatal group, consisted of fetal lambs (n = 12) that underwent the surgical creation of a left diaphragmatic hernia at 90 days' gestation. Six of these animals also underwent simultaneous tracheal ligation. (2) The PFC group consisted of five neonatal animals that underwent isolation of the superior segment of the right upper lobe, with intrabronchial distension with perfluorocarbon to 7 to 10 mm Hg pressure for a 3-week period. (3) The postpneumonectomy group consisted of four neonatal animals that underwent left pneumonectomy. In the fetal study, lungs were retrieved at term (130 days), and in the postnatal study, lungs were retrieved 3 weeks after initial intervention. In all cases, RNA was extracted from snap-frozen lung samples and Northern blot analysis performed. Results: Insulinlike growth factor-I, insulinlike growth factor-II, and vascular endothelial growth factor gene expression were analyzed by densitometry. Insulinlike growth factor-I gene expression was found to be decreased in association with experimental diaphragmatic hernia (P = .005), but restored to normal with tracheal ligation. Insulinlike growth factor-I gene expression was significantly increased in both postnatal models of accelerated lung growth (P = .022, P = .016). No significant differences were found in insulinlike growth factor-II or vascular endothelial growth factor gene expression. Conclusions: The authors conclude from these preliminary data that (1) insulin like growth factor-I gene expression is reduced in experimental fetal diaphragmatic hernia and restored to normal by tracheal ligation, and (2) insulinlike growth factor-I gene expression is increased in both the liquid-based airway distension and postpneumonectomy models of accelerated postnatal lung growth. The authors speculate that all of these manipulations exploit a natural pathway essential for normal lung growth. J Pediatr Surg 33:1057-1061. Copyright (C) 1998 by W.B. Saunders Company. C1 Childrens Hosp, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Pediat Surg, Boston, MA 02114 USA. RP Wilson, JM (reprint author), Childrens Hosp, Dept Surg, Fegan 3,300 Longwood Ave, Boston, MA 02115 USA. NR 22 TC 26 Z9 28 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0022-3468 J9 J PEDIATR SURG JI J. Pediatr. Surg. PD JUL PY 1998 VL 33 IS 7 BP 1057 EP 1060 DI 10.1016/S0022-3468(98)90531-0 PG 4 WC Pediatrics; Surgery SC Pediatrics; Surgery GA 100XU UT WOS:000074841300034 PM 9694094 ER PT J AU Schorge, JO Granter, SR Lerner, LH Feldman, S AF Schorge, JO Granter, SR Lerner, LH Feldman, S TI Postpartum and vulvar necrotizing fasciitis - Early clinical diagnosis and histopathologic correlation SO JOURNAL OF REPRODUCTIVE MEDICINE LA English DT Article DE fasciitis, necrotizing; debridement; vulvar diseases ID PUERPERIUM; EPISIOTOMY AB OBJECTIVE: To review the clinical course and correlate histopathologic findings of obstetrics and gynecology patients with necrotizing fasciitis. STUDY DESIGN: Seventeen patients with postpartum or vulvar necrotizing fasciitis were identified from 1981 to 1996. Medical records were retrospectively reviewed. Information was available for all patients until death or discharge from the hospital. Histopathologic material on 15 patients was available for review. RESULTS: Five postpartum patients were diagnosed and surgically debrided one to nine days after cesarean delivery, with no mortality. Twelve patients with vulvar necrotizing fasciitis were diagnosed and surgically debrided <1-10 days after presentation to a physician, with three deaths (25%). On histopathologic review, all crises had prominent lobular and septal panniculitis. Thirteen cases had histologic evidence of fasciitis. CONCLUSION: Early diagnosis and aggressive surgical debridement in patients with postpartum and vulvar necrotizing fasciitis may improve the outcome. Histopathologic findings are remarkably consistent and may help to confirm the diagnosis. C1 Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Div Gynecol Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. RP Schorge, JO (reprint author), Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Div Gynecol Oncol, 75 Francis St, Boston, MA 02115 USA. NR 15 TC 3 Z9 3 U1 0 U2 1 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA P.O. DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA SN 0024-7758 J9 J REPROD MED JI J. Reprod. Med. PD JUL PY 1998 VL 43 IS 7 BP 586 EP 590 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 103JE UT WOS:000075153300006 PM 9693409 ER PT J AU Warner, JJP Bowen, MK Deng, XH Hannafin, JA Arnoczky, SP Warren, RF AF Warner, JJP Bowen, MK Deng, XH Hannafin, JA Arnoczky, SP Warren, RF TI Articular contact patterns of the normal glenohumeral joint SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Article ID KNEE; MENISCECTOMY; QUANTITATION; AREAS AB The purpose of this study was to determine the articular contact patterns of the normal glenohumeral joint, and to correlate these findings with cartilage and subchondral bone architecture. We studied 10 normal shoulders of cadavers. We removed all soft tissues except the joint capsule and rotator cuff and then placed the shoulders on a testing apparatus that allowed freedom of translation in three planes. After the humerus was placed in a neutral position of rotation, articular contact patterns were measured with specially prepared prescale Fuji film so that it could be inserted between the joint surfaces. Articular contact was analyzed with 222 and 444 N of joint compressive load, and the humerus was positioned in scapular plane abduction of 0 degrees 45 degrees and 90 degrees. The contact patterns were then digitized to determine percentage contact of the humeral head on the glenoid. We studied 12 additional cadaver shoulders with fine microradiographs and histologic techniques after we sectioned the glenoids in the anterior-posterior and superior-inferior planes. We then analyzed articular and subchondral architecture. We found that when the shoulder was adducted the contact area of the humeral head on the glenoid was limited to the anatomic region of the central glenoid known as the "bare area." This was histologically and radiographically an area of cartilage thinning and increased subchondral bone density. As the shoulder was abducted the articular congruity and percentage contact area increased. We concluded that there was a slight articular mismatch with the shoulder adducted in the normal shoulder. Histologic and radiographic studies suggested that the central bare area region of the glenoid was a region of increased compressive loading. As the shoulder was abducted the joint became more congruent and thus the contact area of the humeral head on the glenoid increased. C1 Univ Pittsburgh, Dept Orthopaed Surg, Ctr Sports Med, Shoulder Serv, Pittsburgh, PA 15260 USA. Hosp Special Surg, Sports Med & Shoulder Serv, New York, NY 10021 USA. Hosp Special Surg, Lab Comparat Orthopaed Res, New York, NY 10021 USA. RP Warner, JJP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Shoulder Serv, Dept Orthopaed Surg, GRB-624,55 Fruit St, Boston, MA 02114 USA. NR 29 TC 51 Z9 54 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1058-2746 J9 J SHOULDER ELB SURG JI J. Shoulder Elbow Surg. PD JUL-AUG PY 1998 VL 7 IS 4 BP 381 EP 388 DI 10.1016/S1058-2746(98)90027-1 PG 8 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA 115MQ UT WOS:000075669300007 PM 9752648 ER PT J AU O'Donnell, D Biederman, J Jones, J Wilens, TE Milberger, S Mick, E Faraone, SV AF O'Donnell, D Biederman, J Jones, J Wilens, TE Milberger, S Mick, E Faraone, SV TI Informativeness of child and parent reports on substance use disorders in a sample of ADHD probands, control probands, and their siblings SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE psychoactive substance use disorder; attention-deficit hyperactivity disorder; rater agreement ID ATTENTION-DEFICIT HYPERACTIVITY; ANTISOCIAL PERSONALITY-DISORDER; PSYCHIATRIC-DISORDERS; DRUG-ABUSE; FOLLOW-UP; ALCOHOL; COMORBIDITY; ADOLESCENTS; DEPENDENCE; RELATIVES AB Objective: To evaluate parent-child agreement on psychoactive substance use disorder (PSUD) reporting among children with attention-deficit hyperactivity disorder (ADHD) and to test whether agreement level could be predicted from measures of parent and child psychopathology and substance use severity. Method: The authors examined 348 pairs of child and parent assessments in a sample of 108 ADHD and 68 normal control probands and their 172 siblings aged 12 and older. Results: PSUD rates were higher when the child was the reporter than when the parent was. Agreement between parent and child reports was strongest for cigarette smoking, alcohol dependence, and any PSUD. Although parental reports were frequently endorsed by the child's report, the reverse was rarely true. Predictors of parental awareness of the child's PSUD included impaired social functioning, younger age of the child, presence of multiple substance use disorders in the child, and comorbid bipolar disorder. Conclusions: PSUD rates vary by informant and are higher when the child is the reporter. Because severity of PSUD and multiple substance use were the strangest predictors of parental awareness, more efforts are needed to identify the more covert and milder cases of PSUD that may not reach clinical attention. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit ACC 725, Psychiat Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA USA. Harvard Univ, Sch Med, Harvard Inst Psychiat Epidemiol & Genet, Dept Psychiat, Boston, MA USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit ACC 725, Psychiat Serv, 15 Parkman St, Boston, MA 02114 USA. OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [R01 MH41314-07] NR 30 TC 23 Z9 23 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JUL PY 1998 VL 37 IS 7 BP 752 EP 758 DI 10.1097/00004583-199807000-00015 PG 7 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA ZW690 UT WOS:000074437300016 PM 9666631 ER PT J AU Mathier, MA Rose, GA Fifer, MA Miyamoto, MI Dinsmore, RE Castano, HH Dec, GW Palacios, IF Semigran, MJ AF Mathier, MA Rose, GA Fifer, MA Miyamoto, MI Dinsmore, RE Castano, HH Dec, GW Palacios, IF Semigran, MJ TI Coronary endothelial dysfunction in patients with acute-onset idiopathic dilated cardiomyopathy SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID CONGESTIVE-HEART-FAILURE; BLOOD-FLOW VELOCITY; SUBSELECTIVE MEASUREMENT; MEDIATED VASODILATION; RESISTANCE VESSELS; TRYPANOSOMA-CRUZI; SYRIAN-HAMSTER; RISK-FACTORS; ACETYLCHOLINE; ARTERIES AB Objectives. This study sought to determine whether coronary endothelial dysfunction exists in patients with acute onset idiopathic dilated cardiomyopathy (DCM) and to explore its relation to recovery of left ventricular systolic function in this patient population, Background. Coronary endothelial dysfunction exists in chronic DCM, but its importance in the development and progression of ventricular dysfunction is not known. To address this issue me studied coronary endothelial function in patients with idiopathic DCM <6 months in duration and explored the relation between coronary endothelial function and subsequent changes in left ventricular ejection fraction (LVEF). Methods. Ten patients,vith acute onset idiopathic DCM (duration of heart failure symptoms 2.0 +/- 0.4 months [mean +/- SEM]) and 11 control patients with normal left ventricular function underwent assessment of coronary endothelial function during intracoronary administration of the endothelium-dependent vasodilator acetylcholine and the endothelium-independent vasodilator adenosine. Coronary cross-sectional area (CSA) was determined by quantitative coronary angiography and coronary blood flow (CBF) by the product of coronary CSA and CBF velocity measured by an intracoronary Doppler catheter. Patients with DCM underwent assessment of left ventricular function before and several months after the study. Results. Acetylcholine infusion produced no change in coronary CSA in control patients but significant epicardial constriction in patients,vith DCM (-36 +/- 11%, p < 0.01). These changes were associated with increases in CBF in control patients (+118 +/- 49%, p < 0.01) but no change in patients with DCM. Infusion of adenosine produced increases in coronary caliber and blood flow in both groups. Follow-up assessment of left ventricular function was obtained in nine patients with DCM 7.0 +/- 1.7 months after initial study, at which time LVEF had improved by greater than or equal to 0.10 in four patients. Multiple linear regression revealed a positive correlation between both the coronary CSA (r(2) = 0.57, p < 0.05) and CBF (r(2) = 0.68, p < 0.01) response to acetylcholine and the subsequent improvement in LVEF. Conclusions. Coronary endothelial dysfunction exists at both the microvascular and the epicardial level in patients with acute-onset idiopathic DCM. The preservation of coronary endothelial function in this population is associated with subsequent improvement in left ventricular function. (C) 1998 by the American College of Cardiology. C1 Massachusetts Gen Hosp, Heart Failure Transplant Off, Dept Med, Cardiac Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Semigran, MJ (reprint author), Massachusetts Gen Hosp, Heart Failure Transplant Off, Dept Med, Cardiac Unit, Gray 645,Fruit St, Boston, MA 02114 USA. EM semigran.marc@mgh.harvard.edu NR 49 TC 61 Z9 63 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JUL PY 1998 VL 32 IS 1 BP 216 EP 224 DI 10.1016/S0735-1097(98)00209-5 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA ZZ105 UT WOS:000074696200033 PM 9669273 ER PT J AU Grayburn, PA Weiss, JL Hack, TC Klodas, E Raichlen, JS Vannan, MA Klein, AL Kitzman, DW Chrysant, SG Cohen, JL Abrahamson, D Foster, E Perez, JE Aurigemma, GP Panza, JA Picard, MH Byrd, BF Segar, DS Jacobson, SA Sahn, DJ DeMaria, AN AF Grayburn, PA Weiss, JL Hack, TC Klodas, E Raichlen, JS Vannan, MA Klein, AL Kitzman, DW Chrysant, SG Cohen, JL Abrahamson, D Foster, E Perez, JE Aurigemma, GP Panza, JA Picard, MH Byrd, BF Segar, DS Jacobson, SA Sahn, DJ DeMaria, AN TI Phase III multicenter trial comparing the efficacy of 2% dodecafluoropentane emulsion (EchoGen) and sonicated 5% human albumin (Albunex) as ultrasound contrast agents in patients with suboptimal echocardiograms SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID MYOCARDIAL CONTRAST; MICROBUBBLES AB Objectives. This study was performed to compare the safety and efficacy of intravenous 2% dadecafluoropentane (DDFP) emulsion (EchoGen) with that of active control (sonicated human albumin [Albunex]) for left ventricular (LV) cavity opacification in adult patients with a suboptimal echocardiogram. Background. The development of new fluorocarbon-based echocardiographic contrast agents such as DDFP has allowed opacification of the left ventricle after peripheral venous injection. We hypothesized that DDFP was clinically superior to the Food and Drug Administration-approved active control. Methods. This was a Phase III, multicenter, single blind, active controlled trial. Sequential intravenous injections of active control and DDFP were given 30 min apart to 254 patients with a suboptimal echocardiogram, defined as one in which the endocardial borders mere not visible in at least two segments in either the apical two- or four-chamber views. Studies were interpreted in blinded manner by two readers and the investigators. Results. Full or intermediate LV cavity opacification was more frequently observed after DDFP than after active control (78% vs. 31% for reader A; 69% vs. 34% for reader B; 83% vs. 55% for the investigators, p < 0.0001). LV cavity opacification scores were higher with DDFP (2.0 to 2.5 vs. 1.1 to 1.5, p < 0.0001). Endocardial border delineation was improved by DDFP in 88% of patients versus 45% with active control (p < 0.001). Similar improvement was seen for duration of contrast effect, salvage of suboptimal echocardiograms, diagnostic confidence and potential to affect patient management. There was no difference between agents in the number of patients with adverse events attributed to the test agent (9% for DDFP vs. 6% for active control, p = 0.92). Conclusions. This Phase ill multicenter trial demonstrates that DDFP is superior to sonicated human albumin for LV cavity opacification, endocardial border definition, duration of effect, salvage of suboptimal echocardiograms, diagnostic confidence and potential to influence patient management. The two agents had similar safety profiles. C1 Univ Texas, SW Med Ctr, Echocardiog Labs, Div Cardiol, Dallas, TX 75216 USA. Johns Hopkins Univ, Med Ctr, Baltimore, MD 21218 USA. Deaconess Nashoba Hosp, Ayer, MA USA. Thomas Jefferson Univ, Philadelphia, PA 19107 USA. Tufts Univ New England Med Ctr, Boston, MA 02111 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Bowman Gray Med Ctr, Winston Salem, NC USA. Oklahoma Cardiovasc & Hypotens Ctr, Oklahoma City, OK USA. Vet Affairs Med Ctr, E Orange, NJ USA. Orange Cty Heart Inst & Res Ctr, Orange, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Washington Univ, Med Ctr, St Louis, MO USA. Univ Massachusetts, Med Ctr, Worcester, MA USA. NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Vanderbilt Univ, Nashville, TN USA. Indiana Univ, Indianapolis, IN 46204 USA. Res Hlth Inc, Houston, TX USA. Univ Oregon, Hlth Sci Ctr, Portland, OR USA. Univ Calif San Diego, San Diego, CA 92103 USA. RP Grayburn, PA (reprint author), Univ Texas, SW Med Ctr, Echocardiog Labs, Div Cardiol, 5323 Harry Hines Blvd, Dallas, TX 75216 USA. EM grayburn@ryburn.swmed.edu OI Picard, Michael/0000-0002-9264-3243 NR 26 TC 76 Z9 77 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JUL PY 1998 VL 32 IS 1 BP 230 EP 236 DI 10.1016/S0735-1097(98)00219-8 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA ZZ105 UT WOS:000074696200035 PM 9669275 ER PT J AU Yaffe, K Grady, D Pressman, A Cummings, S AF Yaffe, K Grady, D Pressman, A Cummings, S TI Serum estrogen levels, cognitive performance, and risk of cognitive decline in older community women SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID DEMENTIA-ALZHEIMERS TYPE; POST-MENOPAUSAL WOMEN; POSTMENOPAUSAL WOMEN; REPLACEMENT THERAPY; MEMORY; AGE; LIPOPROTEIN; ESTRADIOL; EDUCATION; DISEASE AB OBJECTIVE: To determine the association between serum estrogen levels, cognitive performance, and risk of cognitive decline in older women. DESIGN: Prospective cohort study with an average follow-up of 5 years. SETTING: Clinical centers in Baltimore, MD, Minneapolis, MN, Portland, OR, and the Monongahela Valley in Pennsylvania. PARTICIPANTS: 532 women aged 65 years or older who were the controls from two nested case-control studies in the ongoing Study of Osteoporotic Fractures. OUTCOME MEASURES:Three cognitive tests - a modified Mini-Mental Status Exam, Digit Symbol, and Trails B - were administered at study initiation and were then repeated approximately 5 years later. Estrone and estradiol levels were determined by radioimmunoassay at two laboratories from baseline stored serum. RESULTS: The characteristics of the women in the four serum estrogen quartiles did not differ except that body weight and change in weight since age 50 increased directly with higher quartile of serum estrogen (P < .001, for both estrone and estradiol). Initial cognitive performance on all three tests did not differ consistently by quartile of estradiol or by the estradiol to estrone ratio. Women in the higher estrone quartiles had 15% lower (worse) scores on Digit Symbol compared with the lower quartiles (P = .004) but there was no difference by quartile on the modified MMSE or on Trails B. Cognitive function test scores declined over the 5 years of follow-up. There was no difference in amount of change by quartile of estradiol, but women in the higher estrone quartiles had greater reduction of scores on Trails B compared with those in the lower quartiles (P = .012), even after adjusting for age, education, depression, stroke history, weight, and change in weight since age 50. The age-adjusted odds of cognitive decline (defined as tenth percentile of women with the largest decline in cognitive performance) did not vary across quartile of estrone or estradiol. CONCLUSIONS: Endogenous estrogens are not associated consistently with cognitive performance or risk of cognitive decline on a selected battery of cognitive tests in older community-dwelling women. Worse performance on two cognitive tests among women with higher estrone levels was surprising and warrants further investigation. C1 Univ Calif San Francisco, Vet Adm Med Ctr, Dept Psychiat, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94121 USA. San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. Kaiser Permanente Med Care Program, Oakland, CA USA. RP Yaffe, K (reprint author), Univ Calif San Francisco, Vet Adm Med Ctr, Dept Psychiat, Box 111G,4150 Clement St, San Francisco, CA 94121 USA. FU NIA NIH HHS [AG05394, AG05407]; NIAMS NIH HHS [AR35582] NR 41 TC 107 Z9 112 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JUL PY 1998 VL 46 IS 7 BP 816 EP 821 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA ZZ397 UT WOS:000074725300002 PM 9670866 ER PT J AU Ohno-Machado, L Gennari, JH Murphy, SN Jain, NL Tu, SW Oliver, DE Pattison-Gordon, E Greenes, RA Shortliffe, EH Barnett, GO AF Ohno-Machado, L Gennari, JH Murphy, SN Jain, NL Tu, SW Oliver, DE Pattison-Gordon, E Greenes, RA Shortliffe, EH Barnett, GO TI The guideline interchange format: A model for representing guidelines SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article ID DECISION-SUPPORT; ARDEN-SYNTAX; SYSTEM; EXAMPLE; LOGIC AB Objective: To allow exchange of clinical practice guidelines among institutions and computer-based applications. Design: The Guideline Interchange Format (GLIF) specification consists of the GLIF model and the GLIF syntax. The GLIF model is an object-oriented representation that consists of a set of classes for guideline entities, attributes for those classes, and data types for the attribute values. The GLIF syntax specifies the format of the test file that contains the encoding. Methods: Researchers from the InterMed Collaboratory at Columbia University, Harvard University (Brigham and Women's Hospital and Massachusetts General Hospital), and Stanford University analyzed four existing guideline systems to derive a set of requirements for guideline representation. The GLIF specification is a consensus representation developed through a brainstorming process. Four clinical guidelines were encoded in GLIF to assess its expressivity and to study the variability that occurs when two people from different sites encode the same guideline. Results: The encoders reported that GLIF was adequately expressive. A comparison of the encodings revealed substantial variability. Conclusion: GLIF was sufficient to model the guidelines for the four conditions that were examined. GLIF needs improvement in standard representation of medical concepts, criterion logic, temporal information, and uncertainty. C1 Brigham & Womens Hosp, Decis Syst Grp, Boston, MA 02115 USA. Stanford Univ, Stanford, CA 94305 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Columbia Univ, New York, NY USA. RP Ohno-Machado, L (reprint author), Brigham & Womens Hosp, Decis Syst Grp, 75 Francis St, Boston, MA 02115 USA. EM machado@dsg.harvard.edu OI Gennari, John/0000-0001-8254-4957; Ohno-Machado, Lucila/0000-0002-8005-7327 FU NLM NIH HHS [LM-43512, LM-43513, LM-43514, R13 LM006929] NR 50 TC 224 Z9 225 U1 0 U2 8 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD JUL-AUG PY 1998 VL 5 IS 4 BP 357 EP 372 PG 16 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA ZY220 UT WOS:000074598300007 PM 9670133 ER PT J AU Nickeleit, V Vamvakas, EC Pascual, M Poletti, BJ Colvin, RB AF Nickeleit, V Vamvakas, EC Pascual, M Poletti, BJ Colvin, RB TI The prognostic significance of specific arterial lesions in acute renal allograft rejection SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID VASCULAR REJECTION; BIOPSY; EOSINOPHIL; PATHOLOGY AB Diagnosis of allograft dysfunction relies on the assessment of arterial lesions. This study was designed to evaluate the prognostic significance of common specific vascular lesions in acute allograft rejection. Renal allograft biopsies (n = 111) with acute cellular rejection were scored for endarteritis, mononuclear cell adherence to endothelial cells, endothelial activation, fibrinoid necrosis, foam cells, and intimal fibrosis. These vascular lesions and other classic histologic features were correlated with outcome. Rejection with endarteritis (found in 54% of biopsies) was less responsive to steroid treatment than rejection without endarteritis, as judged by recovery of creatinine in 3 wk (P = 0.03). Larger numbers of sampled arteries improved the predictive accuracy. Sticking of mononuclear cells to endothelial cells also correlated with steroid resistance (P < 0.05). Rejection with or without endarteritis responded to OKT3/antithymocyte globulin treatment equally well (61% versus 65%, respectively). Rejection with fibrinoid arterial necrosis (4% of biopsies) did not respond to either steroids or antibodies (0%). One-year graft failure was 21% without endarteritis, 28% with endarteritis, and 100% with fibrinoid necrosis. Activated endothelial cells and interstitial hemorrhage were associated with endarteritis and graft failure tall P < 0.05). None of the other scored features had any statistically significant correlation with outcome. Thus, specific arterial lesions (endarteritis, fibrinoid necrosis, activated endothelial cells, mononuclear cell margination) and interstitial hemorrhage, but not the extent of the interstitial infiltrate or tubulitis, are correlated with response to antirejection therapy and/or 1-yr clinical outcome. Grading systems for therapeutic trials and clinical management should emphasize scoring of specific vascular lesions. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Transplantat Unit, Gen Surg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. St Vincents Med Ctr, Dept Pathol, Los Angeles, CA USA. Univ Basel, Kantonsspital, Inst Pathol, CH-4031 Basel, Switzerland. RP Colvin, RB (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren 225, Boston, MA 02114 USA. FU NHLBI NIH HHS [P01-HL-18646] NR 21 TC 81 Z9 82 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD JUL PY 1998 VL 9 IS 7 BP 1301 EP 1308 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA ZV266 UT WOS:000074287400019 PM 9644642 ER PT J AU Goldstein, G Allen, DN Seaton, BE AF Goldstein, G Allen, DN Seaton, BE TI A comparison of clustering solutions for cognitive heterogeneity in schizophrenia SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY LA English DT Article DE schizophrenia; cognitive function; cognitive heterogeneity ID NEUROPSYCHOLOGICAL DEFICITS AB A cluster analytic solution based upon a battery of tests consisting of the Halstead Category and Tactual Performance Tests, the Trail Making Test, and the Wisconsin Card Sorting Test was compared with a solution based on the subtests of the Wechsler intelligence scales, utilizing a sample of 221 schizophrenic patients. Both analyses permitted four-cluster solutions, and we found a weak but significant degree of association between solutions. Examination of external validity of the two solutions revealed stronger associations with clinical variables for the Wechsler-scale-based solution. The major conclusions were that the existence of cognitive heterogeneity in schizophrenia exists across a broad range of abilities, and appears to reflect a combination of continuity of ability level and existence of possible subtypes requiring further neuropsychological and neurobiological verification. C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Univ S Dakota, Vermillion, SD 57069 USA. RP Goldstein, G (reprint author), VA Pittsburgh Healthcare Syst, 151R,7180 Highland Dr, Pittsburgh, PA 15206 USA. NR 22 TC 35 Z9 35 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 1355-6177 J9 J INT NEUROPSYCH SOC JI J. Int. Neuropsychol. Soc. PD JUL PY 1998 VL 4 IS 4 BP 353 EP 362 PG 10 WC Clinical Neurology; Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 104ZF UT WOS:000075046600006 PM 9656609 ER PT J AU Bromley, B Miller, WA Mansour, R Benacerraf, BR AF Bromley, B Miller, WA Mansour, R Benacerraf, BR TI Prenatal findings of branchio-oculo-facial syndrome SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article ID BRANCHIOOCULOFACIAL SYNDROME; SPECTRUM C1 Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Bromley, B (reprint author), Diagnost Ultrasound Associates, 333 Longwood Ave, Boston, MA 02115 USA. NR 8 TC 1 Z9 1 U1 0 U2 0 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD JUL PY 1998 VL 17 IS 7 BP 475 EP 477 PG 3 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA ZX106 UT WOS:000074480000013 PM 9669308 ER PT J AU Jordan, R Pepe, J Schaffer, PA AF Jordan, R Pepe, J Schaffer, PA TI Characterization of a nerve growth factor-inducible cellular activity that enhances herpes simplex virus type 1 gene expression and replication of an ICP0 null mutant in cells of neural lineage SO JOURNAL OF VIROLOGY LA English DT Article ID IMMEDIATE-EARLY GENE-1; PROTEIN-KINASE-C; LATENCY-ASSOCIATED TRANSCRIPTS; UBIQUITIN-PROTEASOME PATHWAY; PC12 CELLS; NEURONAL DIFFERENTIATION; REGULATORY PROTEIN; CALPHOSTIN-C; MACROMOLECULAR-SYNTHESIS; PHEOCHROMOCYTOMA CELLS AB Herpes simplex virus type 1 (HSV-1) ICPO is required for efficient viral gene expression during lytic infection, especially at low multiplicities. A series of cellular activities that can substitute for ICPO has been identified, suggesting that when the activity of ICPO is limiting, these activities can substitute for ICPO to activate viral gene expression, The cellular activities may be especially important during reactivation of HSV from neuronal latency when viral gene expression is initiated in the absence of prior viral protein synthesis. Consistent with this hypothesis, we have identified an inducible activity in cells of neural lineage (PC12) that can complement the low-multiplicity growth phenotype of an ICPO null mutant, n212. Pretreatment of PC12 cells,vith nerve growth factor (NGF) or fibroblast growth factor (FGF) prior to infection produced a 10- to 20-fold increase in the 24-h yield of n212 but only a 2- to ii-fold increase in the yield of wild-type virus relative to mock treatment. Slot blot analysis of nuclear DNA isolated from infected cells treated or mock treated with NGF indicated that NGF treatment does not significantly affect viral entry. The NGF-induced activity in PC12 cells was expressed transiently, with peak complementing activity observed when cells were treated with NGF 12 h prior to infection, Addition of NGF 3 h after infection had little effect on virus yield. The NGF-induced cellular activity was inhibited by pretreatment of PC12 cells with kinase inhibitors that have high specificity for kinases involved in NGF/FGF-dependent signal transduction. RNase protection assays demonstrated that the NGF-inducible PC12 cell activity, like that of ICPO, functions to increase the level of viral mRNA during low-multiplicity infection. These results suggest that activation of viral transcription by ICPO and transcriptional activation of cellular genes by NGF and FGF utilize common signal transduction pathways in PC12 cells. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Mol Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. RP Schaffer, PA (reprint author), Univ Penn, Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA. EM pschfr@mail.med.upenn.edu FU NCI NIH HHS [R37CA20260, R01 CA020260]; NIAID NIH HHS [F32 AI009127, F32 AI09127]; NINDS NIH HHS [P0INS35138] NR 86 TC 14 Z9 14 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 1998 VL 72 IS 7 BP 5373 EP 5382 PG 10 WC Virology SC Virology GA ZU089 UT WOS:000074160500007 PM 9620991 ER PT J AU Kobinger, GP Borsetti, A Nie, ZL Mercier, J Daniel, N Gottlinger, HG Cohen, EA AF Kobinger, GP Borsetti, A Nie, ZL Mercier, J Daniel, N Gottlinger, HG Cohen, EA TI Virion-targeted viral inactivation of human immunodeficiency virus type 1 by using Vpr fusion proteins SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN T-CELLS; GENE-THERAPY; PARTICLES; REPLICATION; P6(GAG); HIV-1; CYCLE; RETROVIRUSES; INHIBITION; ACTIVATION AB Inactivation of progeny virions with chimeric virion-associated proteins represents a novel therapeutic approach against human immunodeficiency virus (HIV) replication. The HIV type 1 (HIV-1) Vpr gene product, which is packaged into virions, is an attractive candidate for such a strategy. In this study, we developed Vpr-based fusion proteins that could be specifically targeted into mature HIV-1 virions to affect their structural organization and/or functional integrity. Two Vpr fusion proteins were constructed by fusing to the first 88 amino acids of HIV-1 Vpr the chloramphenicol acetyltransferase enzyme (VprCAT) or the last 18 C-terminal amino acids of the HIV-1 Vpu protein (VprIE), These Vpr fusion proteins were initially designed to quantify their efficiency of incorporation into HIV-1 virions when produced in cis from the provirus, Subsequently, CD4(+) Jurkat T-cell lines constitutively expressing the VprCAT or the VprIE fusion protein were generated with retroviral vectors. Expression of the VprCAT or the VprIE fusion protein in CD4(+) Jurkat T cells did not interfere,vith cellular viability or growth but conferred substantial resistance to HIV replication. The resistance to HIV replication was more pronounced in Jurkat-VprIE cells than in Jurkat-VprCAT cells. Moreover, the antiviral effect mediated by VprIE was dependent on an intact p6(gag) domain, indicating that the impairment of HIV-1 replication required the specific incorporation of Vpr fusion protein into virions. Gene expression, assembly, or release was not affected upon expression of these Vpr fusion proteins. Indeed, the VprIE and VprCAT fusion proteins were shown to affect the infectivity of progeny virus, since HIV virions containing the VprCAT or the VprIE fusion proteins were, respectively, 2 to 3 times and 10 to 30 times less infectious than the wild-type virus. Overall, this study demonstrated the successful transfer of resistance to HIV replication in tissue cultures by use of Vpr-based antiviral genes. C1 Univ Montreal, Fac Med, Dept Microbiol & Immunol, Lab Retrovirol Humaine, Montreal, PQ H3C 3J7, Canada. Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Human Retrovirol, Boston, MA 02115 USA. RP Cohen, EA (reprint author), Univ Montreal, Fac Med, Dept Microbiol & Immunol, Lab Retrovirol Humaine, CP 6128,Succursale Ctr Ville, Montreal, PQ H3C 3J7, Canada. RI borsetti, alessandra/K-4103-2016 NR 41 TC 28 Z9 34 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 1998 VL 72 IS 7 BP 5441 EP 5448 PG 8 WC Virology SC Virology GA ZU089 UT WOS:000074160500015 PM 9620999 ER PT J AU Yasui, K Wakita, T Tsukiyama-Kohara, K Funahashi, S Ichikawa, M Kajita, T Moradpour, D Wands, JR Kohara, M AF Yasui, K Wakita, T Tsukiyama-Kohara, K Funahashi, S Ichikawa, M Kajita, T Moradpour, D Wands, JR Kohara, M TI The native form and maturation process of hepatitis C virus core protein SO JOURNAL OF VIROLOGY LA English DT Article ID NON-B-HEPATITIS; NON-A; IN-VITRO; HEPATOCELLULAR-CARCINOMA; SUBCELLULAR-LOCALIZATION; ENZYME-IMMUNOASSAY; MAMMALIAN-CELLS; EXPRESSION; GENOME; INFECTION AB The maturation and subcellular localization of hepatitis C virus (HCV) core protein were investigated with both a vaccinia virus expression system and CHO cell lines stably transformed with HCV cDNA. Two HCV core proteins, with molecular sizes of 21 kDa (p21) and 23 kDa (p23), were identified. The C-terminal end of p23 is amino acid 191 of the HCV polyprotein, and p21 is produced as a result of processing between amino acids 174 and 191. The subcellular localization of the HCV core protein,vas examined by confocal laser scanning microscopy. Although HCV core protein resided predominantly in the cytoplasm, it was also found in the nucleus and had the same molecular size as p21 in both locations, as determined by subcellular fractionation. The HCV core proteins had different immunoreactivities to a panel of monoclonal antibodies. Antibody 5E3 stained core protein in both the cytoplasm and the nucleus, C7-50 stained core protein only in the cytoplasm, and 499S stained core protein only in the nucleus. These results clearly indicate that the p23 form of HCV core protein is processed to p21 in the cytoplasm and that the core protein in the nucleus has a higher-order structure different from that of p21 in the cytoplasm. HCV core protein in sera of patients with HCV infection was analyzed in order to determine the molecular size of genuinely processed HCV core protein. HCV core protein in sera was found to have exactly the same molecular weight as the p21 protein. These results suggest that p21 core protein is a component of native viral particles. C1 Tokyo Metropolitan Inst Med Sci, Dept Microbiol, Bunkyo Ku, Tokyo 113, Japan. Tokyo Metropolitan Inst Neurosci, Tokyo, Japan. Kyoto Prefectural Univ Med, Dept Internal Med 3, Kyoto 602, Japan. Chugai Res Inst Mol Med Inc, Ibaraki, Osaka, Japan. Int Reagents Co, Ctr Res & Dev, Nishi Ku, Kobe, Hyogo, Japan. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Hepatol Lab, Boston, MA USA. Univ Hosp Freiburg, Dept Med, Freiburg, Germany. RP Kohara, M (reprint author), Tokyo Metropolitan Inst Med Sci, Dept Microbiol, Bunkyo Ku, 3-18-2 2 Honkomagome, Tokyo 113, Japan. NR 47 TC 188 Z9 196 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 1998 VL 72 IS 7 BP 6048 EP 6055 PG 8 WC Virology SC Virology GA ZU089 UT WOS:000074160500084 PM 9621068 ER PT J AU Choe, H Farzan, M Konkel, M Martin, K Sun, Y Marcon, L Cayabyab, M Berman, M Dorf, ME Gerard, N Gerard, C Sodroski, J AF Choe, H Farzan, M Konkel, M Martin, K Sun, Y Marcon, L Cayabyab, M Berman, M Dorf, ME Gerard, N Gerard, C Sodroski, J TI The orphan seven-transmembrane receptor Apj supports the entry of primary T-cell-line-tropic and dualtropic human immunodeficiency virus type 1 SO JOURNAL OF VIROLOGY LA English DT Article ID HIV-1 ENTRY; AIDS; 7-TRANSMEMBRANE; GLYCOPROTEIN; RETROVIRUS; COFACTOR; CLONING; BRAIN; GENE AB Human immunodeficiency virus type 1 (HIV-1) enters target cells by sequential binding to CD? and specific seven-transmembrane-segment (7TMS) coreceptors. Viruses use the chemokine receptor CCR5 as a coreceptor in the early, asymptomatic stages of HIV-1 infection but can adapt to the use of other receptors such as CXCR4 and CCR3 as the infection proceeds. Here we identify one such coreceptor, Apj, which supported the efficient entry of several primary T-cell-line tropic (T-tropic) and dualtropic HIV-1 isolates and the simian immunodeficiency virus SIVmac316. Another 7TMS protein, CCR9, supported the less efficient entry of one primary T-tropic isolate. mRNAs for both receptors were present in phytohemagglutinin-and interleukin-2-activated peripheral blood mononuclear cells. Apj and CCR9 share with other coreceptors for HIV-1 and SIV an N-terminal region rich in aromatic and acidic residues. These results highlight properties common to 7TMS proteins that can function as HIV-1 coreceptors, and they may contribute to an understanding of viral evolution in infected individuals. C1 Dana Farber Canc Inst, Div Human Retrovirol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Childrens Hosp, Perlmutter Lab, Boston, MA 02115 USA. Harvard Univ, Dept Med, Beth Israel Hosp, Sch Med, Boston, MA 02215 USA. Harvard Univ, Dept Pediat, Beth Israel Hosp, Sch Med, Boston, MA 02215 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Sodroski, J (reprint author), Dana Farber Canc Inst, Div Human Retrovirol, JFB 824,44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [P30 CA006516, T32 CA009141]; NHLBI NIH HHS [R01 HL051366]; NIAID NIH HHS [AI 24755, AI 41851, P30 AI028691, R01 AI041851, R37 AI024755, AI 28691] NR 30 TC 165 Z9 168 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 1998 VL 72 IS 7 BP 6113 EP 6118 PG 6 WC Virology SC Virology GA ZU089 UT WOS:000074160500091 PM 9621075 ER PT J AU Casasnovas, JM Bickford, JK Springer, TA AF Casasnovas, JM Bickford, JK Springer, TA TI The domain structure of ICAM-1 and the kinetics of binding to rhinovirus SO JOURNAL OF VIROLOGY LA English DT Article ID INTERCELLULAR-ADHESION MOLECULE-1; RECEPTOR; NEUTRALIZATION; IMMUNOGLOBULIN; DISRUPTION; DISTINCT; RESIDUES; SYSTEM; LFA-1; SITE AB Fragments of intercellular adhesion molecule 1 (ICAM-1) containing only the two most N terminal of its five immunoglobulin SF domains bind to rhinovirus 3 with the same affinity and kinetics as a fragment with the entire extracellular domain. The fully active two-domain fragments contain 5 or 14 more residues than a previously described fragment that is only partially active. Comparison of X-ray crystal structures show differences at the bottom of domain 2. Four different glycoforms of ICAM-1 bind with identical kinetics. C1 Harvard Univ, Sch Med, Ctr Blood Res, Dept Pathol, Boston, MA 02115 USA. RP Springer, TA (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, Dept Pathol, 200 Longwood Ave, Boston, MA 02115 USA. RI Casasnovas, Jose/L-6299-2014 OI Casasnovas, Jose/0000-0002-2873-6410 FU NIAID NIH HHS [AI31921] NR 26 TC 19 Z9 21 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 1998 VL 72 IS 7 BP 6244 EP 6246 PG 3 WC Virology SC Virology GA ZU089 UT WOS:000074160500114 PM 9621098 ER PT J AU Wobbe, KK Akgoz, M Dempsey, DA Klessig, DF AF Wobbe, KK Akgoz, M Dempsey, DA Klessig, DF TI A single amino acid change in turnip crinkle virus movement protein p8 affects RNA binding and virulence on Arabidopsis thaliana SO JOURNAL OF VIROLOGY LA English DT Article ID CELL-TO-CELL; SATELLITE RNA; MOSAIC-VIRUS; SYMPTOM INTENSIFICATION; IDENTIFICATION; RESISTANCE; PLANTS AB Comparison of the symptoms caused by turnip crinkle virus strain M (TCV-M) and TCV-B infection of a resistant Arabidopsis thaliana line termed Di-17 demonstrates that TCV-B has a greater ability to spread in planta. This ability is due to a single amino acid change in the viral movement protein p8 and inversely correlates with p8 RNA binding affinity. C1 Rutgers State Univ, Waksman Inst, Piscataway, NJ 08854 USA. Rutgers State Univ, Dept Mol Biol & Biochem, Piscataway, NJ 08854 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Worcester Polytech Inst, Dept Chem & Biochem, Worcester, MA 01609 USA. RP Klessig, DF (reprint author), Rutgers State Univ, Waksman Inst, 190 Frelinghuysen Rd, Piscataway, NJ 08854 USA. RI Akgoz, Muslum/A-6234-2015 OI Akgoz, Muslum/0000-0001-5065-8087 NR 28 TC 22 Z9 24 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 1998 VL 72 IS 7 BP 6247 EP 6250 PG 4 WC Virology SC Virology GA ZU089 UT WOS:000074160500115 PM 9621099 ER PT J AU Mahoney, JE Sager, MA Jalaluddin, M AF Mahoney, JE Sager, MA Jalaluddin, M TI New walking dependence associated with hospitalization for acute medical illness: Incidence and significance SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID OLDER PATIENTS; RISK-FACTORS; FALLS; OUTCOMES; ADULTS; TRIAL; CARE; AGE AB Background. The ability to walk independently may become jeopardized during hospitalization. It is unknown which patients are at risk for decline in walking, or to what extent patients will recover. The purpose of this study was to determine the incidence of, risk factors for, and outcomes associated with new walking dependence after hospitalization. Methods. Baseline characteristics and functional outcomes at hospital discharge and 3 months after discharge were measured for 1,181 community-dwelling adults aged 70 and over who were hospitalized for medical illness and who walked independently prior to hospitalization. Results. At discharge, 16.8% of patients were newly dependent in walking. Risk factors included age > 85 (odds ratio [OR] 2.7 vs age <75, 95% confidence interval [CI] 1.5-4.9), functional impairment before hospitalization (OR 1.4 for each impairment, CI 1.1-1.7), Caucasian race (OR 1.9, CI 1.1-3.3), and use of a walker (OR 1.8, CI 1.04-3.2) or wheelchair (OR 3.2, CI 1.3-7.6) before admission. A cancer diagnosis (OR 2.3, CI 1.2-4.6) and more than four comorbid conditions (OR 1.9, CI 1.2-3.0) were also predictive. New walking dependence was associated with discharge to a nursing home (p =.0001) and higher postdischarge mortality (p <.001). Twenty-seven percent of patients who developed new walking dependence and survived 3 months continued to be dependent in walking. Conclusions. New walking dependence occurs frequently with hospitalization, may be predicted by specific risk factors, and portends a poor prognosis. Strategies are needed to help at-risk patients maintain walking independence during and after hospitalization. C1 William S Middleton Mem Vet Hosp, GRECC Serv, Madison, WI 53705 USA. Univ Wisconsin, Sch Med, Dept Med, Madison, WI 53706 USA. Univ Wisconsin, Sch Med, Dept Prevent Med, Madison, WI 53706 USA. Univ Wisconsin, Sch Med, Dept Biostat, Madison, WI 53706 USA. RP Mahoney, JE (reprint author), William S Middleton Mem Vet Hosp, GRECC Serv, 2500 Overlook Terrace, Madison, WI 53705 USA. FU NIA NIH HHS [1 K08 AG00623-01] NR 25 TC 38 Z9 39 U1 1 U2 3 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JUL PY 1998 VL 53 IS 4 BP M307 EP M312 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 101QR UT WOS:000074880100021 PM 18314571 ER PT J AU Dutcher, JP Lee, S Paietta, E Bennett, JM Stewart, JA Wiernik, PH AF Dutcher, JP Lee, S Paietta, E Bennett, JM Stewart, JA Wiernik, PH TI Phase II study of carboplatin in blast crisis of chronic myeloid leukemia: Eastern Cooperative Oncology Group Study E1992 SO LEUKEMIA LA English DT Article DE chronic myeloid leukemia; blast crisis; carboplatin ID CHRONIC MYELOGENOUS LEUKEMIA; TRIAL; MITOXANTRONE AB This study was a phase II evaluation of the activity of carboplatin in patients with Philadelphia chromosome positive accelerated or blastic phase of CML. Carboplatin, 250 mg/m(2)/day as an intravenous continuous infusion was given for 5 days, for a total dose of 1250 mg/m(2) per course. If necessary, a second induction course could be given, and patients achieving complete remission were to receive an additional consolidation cycle at the same dose. Thirty-six patients were eligible and evaluable. There were five complete and three partial remissions for an overall response rate of 22% (95% CI 10.1-39.1%). The complete remission rate was 13.9% (95% CI 4.7-29.9%). The median remission duration was 3 months (range 1.4-8.94 months) and the median survival on study for all patients was 3.5 months (95% CI, 2.4-11.4 months). The median survival of responders was 12.8 months (95% CI, 3.6-17.2 months). Three eligible patients survived 2.0, 2.5 and 3.5 years following carboplatin therapy. Carboplatin has activity in blast crisis of CML, but responses are brief. Response did allow one patient to proceed to bone marrow transplantation and two other patients to continue therapy for chronic phase disease before returning to blast crisis. Activity in combination regimens should be explored. C1 Albert Einstein Canc Ctr, Bronx, NY USA. Dana Farber Canc Ctr, Boston, MA USA. Univ Rochester, Rochester, NY USA. Univ Wisconsin, Madison, WI USA. RP Dutcher, JP (reprint author), Montefiore Med Ctr, Dept Oncol, 111 E 210Th St, Bronx, NY 10467 USA. FU NCI NIH HHS [CA14958, CA23318, CA11083] NR 13 TC 17 Z9 17 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD JUL PY 1998 VL 12 IS 7 BP 1037 EP 1040 DI 10.1038/sj.leu.2401056 PG 4 WC Oncology; Hematology SC Oncology; Hematology GA ZY049 UT WOS:000074581500005 PM 9665187 ER PT J AU Ko, CW Kowdley, KV Haigh, WG Lee, SP AF Ko, CW Kowdley, KV Haigh, WG Lee, SP TI Biliary lipid composition after liver transplantation: Effect of allograft function and cyclosporine SO LIVER TRANSPLANTATION AND SURGERY LA English DT Article ID LIGHT-SCATTERING DETECTION; BILE-ACIDS; P-GLYCOPROTEIN; RAT-LIVER; SECRETION; TRANSPORT; INHIBITION; SALT; HYPERBILIRUBINEMIA; QUANTITATION AB Biliary lipid composition and bile flow are altered after orthotopic liver transplantation. Cyclosporine may have additional effects on biliary lipid composition and secretion. We studied the effects of liver transplantation, allograft function, and cyclosporine on biliary lipids in humans, Changes in lipid composition and secretion were correlated with serum cyclosporine levels, clinical events, and allograft function, Bile samples were withdrawn via a T-tube at interval time points in 17 patients during the first 3 months posttransplantation. Total and individual bile acid, cholesterol, and phospholipid were determined using high-performance liquid chromatography. Biliary lipid profiles were then correlated with clinical events, serum cyclosporine levels, and other clinical laboratory values. Biliary lipid concentrations decreased in 3 patients during periods of graft dysfunction (acute cellular rejection, drug-induced hepatitis, and inferior vena caval thrombosis) and increased with resolution of the graft injury, Serum cyclosporine levels were positively correlated with total bile acid, cholesterol, and phospholipid concentrations in bile. There was no relationship between the composition of secreted bile acids and serum cyclosporine levels, Bile acid, cholesterol, and phospholipid secretion were not uncoupled in the presence of cyclosporine. We concluded that (1) a decrease in biliary lipid concentrations may be an indicator of worsened graft function in some allografts; (2) biliary lipid concentrations are correlated with increasing cyclosporine levels; and (3) bile acid composition is unchanged, and uncoupling of secretion of of her biliary lipids is not observed in the presence of cyclosporine, Copyright (C) 1998 by the American Association for the Study of Liver Diseases. C1 VA Puget Sound Hlth Care Syst, Dept Med 111GI, Seattle, WA 98108 USA. Univ Washington, Dept Med, Seattle, WA USA. RP Lee, SP (reprint author), VA Puget Sound Hlth Care Syst, Dept Med 111GI, 1660 S Columbian Way, Seattle, WA 98108 USA. FU NIDDK NIH HHS [DK 41678, DK 46890] NR 36 TC 3 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 USA SN 1074-3022 J9 LIVER TRANSPLANT SUR JI Liver Transplant. Surg. PD JUL PY 1998 VL 4 IS 4 BP 258 EP 264 DI 10.1002/lt.500040405 PG 7 WC Gastroenterology & Hepatology; Surgery; Transplantation SC Gastroenterology & Hepatology; Surgery; Transplantation GA 142DE UT WOS:000077184000002 PM 9649637 ER PT J AU Roth, JA Atkinson, EN Fossella, F Komaki, R Ryan, MB Putnam, JB Lee, JS Dhingra, H De Caro, L Chasen, M Hong, WK AF Roth, JA Atkinson, EN Fossella, F Komaki, R Ryan, MB Putnam, JB Lee, JS Dhingra, H De Caro, L Chasen, M Hong, WK TI Long-term follow-up of patients enrolled in a randomized trial comparing perioperative chemotherapy and surgery with surgery alone in resectable stage IIIA non-small-cell lung cancer SO LUNG CANCER LA English DT Article DE lung cancer; induction chemotherapy; randomized trial; cisplatin ID PREOPERATIVE CHEMOTHERAPY; PHASE-II; NEOADJUVANT CHEMOTHERAPY; RADIATION-THERAPY; CISPLATIN; IRRADIATION; VINDESINE; CARCINOMA AB Our previously reported randomized study of patients with untreated, potentially resectable clinical stage IIIA non-small-cell lung cancer found that patients treated with perioperative chemotherapy and surgery had a significant increase in median survival compared to patients treated with surgery alone. We have now re-analyzed the results of the study with a median time from random allocation to analysis for all patients of 82 months. The increase in survival conferred by perioperative chemotherapy was maintained during the period of extended observation. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Texas, MD Anderson Canc Ctr, Dept Thorac & Cardiovasc Surg, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Tumor Biol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Biomath, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Radiotherapy, Houston, TX 77030 USA. Bassett Hlth Care, Dept Surg, Cooperstown, NY 13326 USA. VA Med Ctr, Dept Hematol Oncol, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. Clin De Genolier, CH-1272 Genolier, Switzerland. Univ Texas, MD Anderson Canc Ctr, Dept Diagnost Radiol, Houston, TX 77030 USA. RP Roth, JA (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Thorac & Cardiovasc Surg, 1515 Holcombe Blvd,Box 109, Houston, TX 77030 USA. FU NCI NIH HHS [CA16672, P50-CA70907] NR 17 TC 288 Z9 303 U1 0 U2 5 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD JUL PY 1998 VL 21 IS 1 BP 1 EP 6 DI 10.1016/S0169-5002(98)00046-4 PG 6 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 127FF UT WOS:000076339400001 PM 9792048 ER PT J AU Brown, DM Matise, TC Koike, G Simon, JS Winer, ES Zangen, S McLaughlin, MG Shiozawa, M Atkinson, OS Hudson, JR Chakravarti, A Lander, ES Jacob, HJ AF Brown, DM Matise, TC Koike, G Simon, JS Winer, ES Zangen, S McLaughlin, MG Shiozawa, M Atkinson, OS Hudson, JR Chakravarti, A Lander, ES Jacob, HJ TI An integrated genetic linkage map of the laboratory rat SO MAMMALIAN GENOME LA English DT Article ID GENOME AB The laboratory rat, Rattus novegicus, is a major model system for physiological and pathophysiological studies, and since 1966 more than 422,000 publications describe biological studies on the rat (NCBI/Medline). The rat is becoming an increasingly important genetic model for the study of specific diseases, as well as retaining its role as a major preclinical model system for pharmaceutical development. The initial genetic Linkage map of the rat contained 432 genetic markers (Jacob et al. 1995) out of 1171 developed due to the relatively low polymorphism rate of the mapping cross used (SHR x BN) when compared to the interspecific crosses in the mouse. While the rat genome project continues to localize additional markers on the linkage map, and as of 11/97 more than 3,200 loci have been mapped. Current map construction is using two different crosses (SHRSP x BN and FHH x ACI) rather than the initial mapping cross. Consequently there is a need to provide integration among the different maps. We set out to develop an integrated map, as well as increase the number of markers on the rat genetic map. The crosses available for this analysis included the original mapping cross SHR x BN reciprocal F2 intercross (448 markers), a GH x BN intercross (205 markers), a SS/Mcw x BN intercross (235 markers), and a FHH/Eur x ACI/Hsd intercross (276 markers), which is also one of the new mapping crosses. Forty-six animals from each cross were genotyped with markers polymorphic for that cross. The maps appear to cover the vast majority of the rat genome. The availability of these additional markers should facilitate more complete whole genome scans in a greater number of strains and provide additional markers in specific genomic regions of interest. C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Res Genet Inc, Huntsville, AL 35801 USA. Rockefeller Univ, Lab Stat Genet, New York, NY 10021 USA. Case Western Reserve Univ, Dept Genet, Cleveland, OH 44106 USA. MIT, Whitehead Inst Biomed Res, Cambridge, MA 02139 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. RP Jacob, HJ (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. NR 8 TC 65 Z9 65 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD JUL PY 1998 VL 9 IS 7 BP 521 EP 530 PG 10 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA ZX068 UT WOS:000074476200006 PM 9657848 ER PT J AU Yasuda, T Beatty, J Biggs, PJ Gall, K AF Yasuda, T Beatty, J Biggs, PJ Gall, K TI Two-dimensional dose distribution of a miniature x-ray device for stereotactic radiosurgery SO MEDICAL PHYSICS LA English DT Article DE stereotactic radiosurgery; dose isotropy; radiochromic film ID INTERSTITIAL RADIOSURGERY AB The Photon Radiosurgery System is a miniature x-ray device developed for the treatment of small intracranial neoplasms. The x rays are generated at the tip of a 10-cm-long, 3-mm-diam probe with a nearly isotropic distribution. Results from measurements of the two-dimensional dose distribution around the x-ray source are presented using two methods: (1) dose measurement with an ionization chamber and a water phantom system and (2) dose measurement with radiochromic film and a solid water phantom. The shape of the two angular dose distributions in the axial plane agree with each other to within approximately 10% and the dose at 10 mm from the source, orthogonal to the probe axis, was about 20% lower than at the same distance along the axis. The relative dose difference of 20% corresponds to a change in distance from the source of +/- 0.3 mm at 10 mm. It is shown that the anisotropy of radiation distribution in the axial plane can be improved to approximately 10% by adjusting the electron beam with a 12% reduction in the overall radiation output. (C) 1998 American Association of Physicists in Medicine. C1 Northeastern Univ, Dept Phys, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol,Div Radiat Biophys, Boston, MA 02114 USA. RP Yasuda, T (reprint author), Northeastern Univ, Dept Phys, Boston, MA 02115 USA. NR 4 TC 13 Z9 13 U1 0 U2 0 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUL PY 1998 VL 25 IS 7 BP 1212 EP 1216 DI 10.1118/1.598298 PN 1 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 100FU UT WOS:000074805900017 PM 9682208 ER PT J AU Kontoyiannis, DP Ruoff, K Hooper, DC AF Kontoyiannis, DP Ruoff, K Hooper, DC TI Nocardia bacteremia - Report of 4 cases and review of the literature SO MEDICINE LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; BLOOD CULTURE; IMMUNOCOMPROMISED HOST; ASTEROIDES INFECTION; ENDOCARDITIS; PATIENT; DISEASE C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Clin Microbiol Lab, Boston, MA USA. RP Kontoyiannis, DP (reprint author), Univ Texas, MD Anderson Cancer Ctr, Infect Dis Sect, Dept Med Specialties, Box 47,1515 Holcombe Blvd, Houston, TX 77030 USA. NR 52 TC 62 Z9 66 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0025-7974 J9 MEDICINE JI Medicine (Baltimore) PD JUL PY 1998 VL 77 IS 4 BP 255 EP 267 DI 10.1097/00005792-199807000-00004 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 109QA UT WOS:000075333400004 PM 9715730 ER PT J AU Segu, VBG Li, GD Metz, SA AF Segu, VBG Li, GD Metz, SA TI Use of a soluble tetrazolium compound to assay metabolic activation of intact beta cells SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID INDUCED INSULIN RELEASE; ISOLATED PANCREATIC-ISLETS; COLORIMETRIC ASSAY; GLUCOSE-METABOLISM; HIT CELLS; MITOCHONDRIAL; SECRETION; EVENTS; MTT; DEHYDROGENASE AB Although assessments of metabolic activation are central to studies of beta-cell function, available techniques are tedious, insensitive, and/or require cell disruption. We have investigated the use of a new water-soluble tetrazolium salt, MTS (3-[4,5,dimethylthiazol-2-yl]-5-[3-carboxymethoxy-phenyl]-2-[4-sulfophenyl]-2H -tetrazolium, inner salt), in the presence of phenazine methosulfate (PMS), an intermediate electron acceptor that amplifies its signal (fluorescence at 490 nm). During static incubations of glucose-responsive (HIT-T15 or INS-1) dispersed beta cells with increasing glucose concentrations, there was a progressive increase in MTS reduction, with a maximum signal-to-noise (S/N) ratio of 24 with HIT-T15 cells and 10 with INS-1 cells. This was associated with, but not attributable to, parallel increases in insulin secretion. Pure mitochondrial fuels (alpha-ketoisocaproate [KIC], methyl pyruvate [MP], or L-glutamine [GLN] + L-leucine [LEU]) also increased the reduction of MTS in INS-1 cells (6.5-, 4.8-, and 14.4-fold, respectively), but generally less than glucose, suggesting a major role of glycolysis in the signal induced by glucose. Inhibitors of glucose metabolism (mannoheptulose [MH], lodoacetate [IA], or 2-deoxyglucose [2-DG]) markedly reduced the glucose-stimulated MTS signal. in comparison to another tetrazolium compound, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), MTS assay provided a better S/N ratio with glucose or other nutrient secretagogues. Extant theory holds that activation of mitochondrial dehydrogenases by increments in Ca2+ influx couples glycolysis to mitochondrial oxidation of glucose-derived fuels. However, reduction of fuel-induced calcium influx (by Ca2+-free medium or diazoxide [DZX]) or direct stimulation of calcium influx (by 40 mmol/L K+) failed to significantly modulate the signal, arguing against this theory. We conclude that the MTS assay is a facile test that reflects the global metabolic function of insulin-secreting beta cells. Furthermore, since this assay does not require disruption of cells to solubilize the formazan product, and therefore also allows concomitant measurement of insulin secretion, it offers considerable advantages over earlier methods. Copyright (C) 1998 by W.B. Saunders Company. C1 Univ Wisconsin, Ctr Clin Sci, Sch Med, Dept Med, Madison, WI 53792 USA. William S Middleton Mem Vet Adm Hosp, Endocrinol Sect, Madison, WI USA. William S Middleton Mem Vet Adm Hosp, Med Serv, Madison, WI USA. Univ Wisconsin, Sch Med, Endocrinol Sect, Madison, WI 53792 USA. RP Segu, VBG (reprint author), Univ Wisconsin, Ctr Clin Sci, Sch Med, Dept Med, H4-568,600 Highland ave, Madison, WI 53792 USA. FU NIDDK NIH HHS [DK 37312] NR 30 TC 23 Z9 23 U1 1 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD JUL PY 1998 VL 47 IS 7 BP 824 EP 830 DI 10.1016/S0026-0495(98)90120-2 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZY492 UT WOS:000074627200011 PM 9667229 ER PT J AU Patan, S AF Patan, S TI TIE1 and TIE2 receptor tyrosine kinases inversely regulate embryonic angiogenesis by the mechanism of intussusceptive microvascular growth SO MICROVASCULAR RESEARCH LA English DT Article ID CHORIOALLANTOIC MEMBRANE CAM; TUMOR ANGIOGENESIS; ENDOTHELIAL-CELLS; MOLECULAR-CLONING; CAPILLARY GROWTH; EXPRESSION; VASCULOGENESIS; GENES; TEK; LETHALITY AB As shown previously, TIE1 and TIE2 receptor tyrosine kinases are specifically expressed in endothelial cells during embryonic angiogenesis. A detailed analysis of the vascular malformations of homozygous mice for a targeting mutation of both receptors was performed at the histological and cellular level. The data demonstrate that the TIE1 and TIE2 receptor inversely and concomitantly mediate interactions between endothelial cells with their extracellular matrix and with surrounding mesenchymal cells. These interactions are obviously crucial for normal endothelial cell motility and/or attachment and also for recruitment of periendothelial cells. The analysis of the TIE2-deficient embryos demonstrates how these cell/cell- and cell/matrix interactions subsequently influence the formation of normally structured tissue folds that divide the vessel lumen. They are also essential for the formation of vessel loops that compose a new vascular network and for the development of the ventricle in the heart. Fold and loop formation follow the principles of intussusceptive microvascular growth. The localization of the cardiovascular malformations corresponds to the temporal and spatial expression pattern of the TIE2 receptor. Angiopoietin-1, a ligand that activates the TIE2 receptor, is expressed in mesenchymal cells surrounding the endothelium. This local relationship is indicative of a paracrine regulation. (C) 1998 Academic Press. C1 Beth Israel Hosp, Dept Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Patan, S (reprint author), Beth Israel Hosp, Dept Cardiol, Boston, MA 02114 USA. NR 32 TC 131 Z9 135 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0026-2862 J9 MICROVASC RES JI Microvasc. Res. PD JUL PY 1998 VL 56 IS 1 BP 1 EP 21 DI 10.1006/mvre.1998.2081 PG 21 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 110JF UT WOS:000075377100001 PM 9683559 ER PT J AU Kaysen, GA Webster, S Al-Bander, H Jones, H Hutchison, FN AF Kaysen, GA Webster, S Al-Bander, H Jones, H Hutchison, FN TI High-protein diets augment albuminuria in rats with Heymann nephritis by angiotensin II-dependent and -independent mechanisms SO MINERAL AND ELECTROLYTE METABOLISM LA English DT Article DE kinins; nephrotic syndrome; losartan; enalapril; angiotensin receptor binding ID CONVERTING ENZYME-INHIBITION; MESSENGER-RNA; MODULATION; RECEPTOR; RENIN; KIDNEY AB Urinary albumin excretion (UalbV) increases following dietary protein augmentation (DPA) in nephrotic humans and rats, Angiotensin-converting enzyme inhibitors (ACEI) blunt, but do not entirely prevent, increased UalbV at doses that reduce blood pressure and entirely block the presser effect of exogenously administered angiotensin I (Ang-I), suggesting that angiotensin II (Ang-II) might not mediate the effect of DPA on UalbV We determined the effect of losartan (Los), a specific Ang-II receptor antagonist, and compared its effect to that of enalapril(En), an ACEI: on DPA-induced increase in UalbV in rats with passive Heymann nephritis (HN). When Los was administered to HN rats for 48 h prior to DPA from 8.5 to 40% casein, UalbV increased in an identical fashion in treated and untreated rats, even though Los caused hypotension and prevented the presser effect of infused Ang-II, Only on day 6 after DPA did UalbV decrease, We then measured the effect of duration of pretreatment with Los on Ang-II binding to isolated glomeruli, Maximal inhibition of Ang-II binding required treatment with Los for 6 days, We then pretreated HN rats with either En or Los for 6 days prior to DPA. In contrast to administration of Los for 2 days prior to DPA, pretreatment with either Les or En for 6 days entirely prevented any increase in UalbV We then increased dietary NaCl from 0.2% to 2% (HS) to determine whether En or Los would modulate UalbV after DPA when Ang-II activity was suppressed, En reduced the DPA-mediated increase in UalbV regardless of dietary NaCl, while Los was effective only in when dietary NaCl was reduced (0.2%), suggesting that under these conditions ACEI reduces UalbV by a mechanism that is independent of inhibition of Ang-II and that high protein diets augment UalbV by both Ang-II-independent and Ang-II-dependent mechanisms. C1 Univ Calif Davis, Sch Med, Div Nephrol, Dept Med,Renal Biochem Lab, Davis, CA 95616 USA. Dept Vet Affairs No Calif Syst Clin, Pleasant Hill, CA USA. Med Univ S Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA. Ralph H Johnson VAMC, Charleston, SC USA. RP Kaysen, GA (reprint author), Univ Calif Davis, Sch Med, Div Nephrol, Dept Med,Renal Biochem Lab, TB 136, Davis, CA 95616 USA. EM gakaysen@ucdavis.edu FU NIDDK NIH HHS [DK 42297, DK 43186] NR 28 TC 2 Z9 2 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-0392 J9 MINER ELECTROL METAB JI Miner. Electrolyte Metab. PD JUL-AUG PY 1998 VL 24 IS 4 BP 238 EP 245 DI 10.1159/000057376 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZC643 UT WOS:000072602100005 PM 9554562 ER PT J AU Savilo, E Campo, E Mollejo, M Pinyol, M Piris, MA Zukerberg, LR Yang, WI Koelliker, DD Nguyen, PL Harris, NL AF Savilo, E Campo, E Mollejo, M Pinyol, M Piris, MA Zukerberg, LR Yang, WI Koelliker, DD Nguyen, PL Harris, NL TI Absence of cyclin D1 protein expression in splenic marginal zone lymphoma SO MODERN PATHOLOGY LA English DT Article; Proceedings Paper CT 85th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 23-29, 1996 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol DE chronic lymphocytic leukemia; cyclin D1; immunophenotype; mantle cell lymphoma; splenic lymphoma with villous lymphocytes; splenic marginal zone lymphoma ID CIRCULATING VILLOUS LYMPHOCYTES; NON-HODGKINS-LYMPHOMAS; B-CELL LYMPHOMAS; DIFFERENTIAL-DIAGNOSIS; GENE; REARRANGEMENTS; BCL-1 AB Splenic marginal zone lymphoma (SMZL) is a recently recognized primary splenic lymphoma SMZL can be associated with peripheral lymphocytosis, in which some cells have a villous morphology (splenic lymphoma with villous lymphocytes [SLVL]). Several recent studies suggested involvement of the bcl-1 locus and/or the cyclin D1 gene, located on chromosome 11q, in SMZL/SLVL. Translocation t (11;14) is associated with rearrangement of the bcl-1 locus and overexpression of the cyclin D1 gene. Both the translocation and cyclin D1 protein expression are characteristic of mantle cell lymphoma (MCL) and are rare in other lymphoid neoplasms; thus, their detection is useful in the diagnosis of MCL. Because the differential diagnosis of low-grade lymphoma in the spleen can be difficult, it is important to assess the frequency of cyclin D1 expression in SMZL to determine its usefulness in differential diagnosis from MCL, We analyzed the expression of cyclin D1 nuclear protein in paraffin sections using an immunoperoxidase technique in 17 cases diagnosed as SMZL. In eight cases, the presence of cyclin D1 mRNA was also assessed by Northern blot analysis. None of the 17 cases of typical SMZL showed expression of cyclin D1 mRNA or protein. In contrast, four cases used as controls showed either expression of cyclin D1 protein or mRNA or both. We conclude that assessment of cyclin D1 protein expression can be useful in distinguishing SMZL from MCL involving the spleen. C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA. Hosp Clin Barcelona, Barcelona, Spain. Hosp Virgen de la Salud, Toledo, Spain. RP Savilo, E (reprint author), Henderson Gen Hosp, Dept Pathol, 711 Concess St, Hamilton, ON L8V 1C3, Canada. OI Piris, Miguel A/0000-0001-5839-3634; Campo, elias/0000-0001-9850-9793 NR 17 TC 23 Z9 24 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JUL PY 1998 VL 11 IS 7 BP 601 EP 606 PG 6 WC Pathology SC Pathology GA 101DJ UT WOS:000074854100001 PM 9688179 ER PT J AU Kommoss, F Oliva, E Bhan, AK Young, RH Scully, RE AF Kommoss, F Oliva, E Bhan, AK Young, RH Scully, RE TI Inhibin expression in ovarian tumors and tumor-like lesions: An immunohistochemical study SO MODERN PATHOLOGY LA English DT Article DE endocrine function; immunohistochemistry; inhibin; ovarian tumors ID GRANULOSA-CELL TUMORS; POSTMENOPAUSAL WOMEN; FOLLICULAR-FLUID; CARCINOMA; ACTIVINS; RECEPTORS; DIAGNOSIS; PROTEINS; MARKER; TESTIS AB We investigated 203 ovarian tumors and tumor-like lesions for inhibin expression using a monoclonal anti-inhibin alpha antibody. Inhibin was present in the tumor cells in all 14 primary adult granulosa cell tumors (4 luteinized) plus 3 metastatic, all 10 primary juvenile granulosa cell tumors plus 1 metastatic, 10 of 11 thecomas, 3 of 11 fibromas, 4 of 11 sclerosing stromal tumors, 6 of 11 Sertoli cell tumors (1 oxyphilic), 7 of 11 Sertoli-Leydig cell tumors, 1 gynandroblastoma, 10 primary ovarian sex cord tumors with annular tubules plus 2 metastatic, 8 of 9 steroid cell tumors, both pregnancy luteomas, 1 of 2 unclassified sex cord tumors, 2 of 5 gonadoblastomas, 9 of 10 female adnexal tumors of probable wolffian origin, and in the non-neoplastic stroma of many carcinomas and germ cell tumors. The tumor cells were inhibin-negative in 10 fibrosarcomas, 12 small cell carcinomas of hypercalcemic type, 24 germ cell tumors (except for a focus of inhibin-positive syncytiotrophoblast in one case), and 17 ovarian carcinomas. Two of the three inhibin-positive fibromas showed diffuse immunostaining and were associated with evidence of estrogenic activity. Among nine Sertoli-Leydig cell tumors with available clinical data, four that were more than minimally inhibin-positive were accompanied by androgenic manifestations; five inhibin-negative or only minimally positive tumors lacked such evidence. Inhibin immunostaining may be useful in the differential diagnosis of inhibin-positive sex cord tumors versus histologically similar inhibin-negative neoplasms, but inhibin negativity does not preclude a diagnosis of sex cord tumor. The unexpected, common inhibin positivity of female adnexal tumors of probable wolffian origin indicates that inhibin staining cannot be used to differentiate these tumors from Sertoli cell tumors. Inhibin immunostaining is also helpful in identifying potential steroid hormone-secreting cells in the non-neoplastic stromal component of epithelial, germ cell, and other ovarian tumors. C1 Univ Mainz, Dept Pathol, D-55101 Mainz, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, James Homer Wright Pathol Labs, Boston, MA USA. RP Kommoss, F (reprint author), Univ Mainz, Dept Pathol, D-55101 Mainz, Germany. NR 41 TC 109 Z9 116 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JUL PY 1998 VL 11 IS 7 BP 656 EP 664 PG 9 WC Pathology SC Pathology GA 101DJ UT WOS:000074854100009 PM 9688187 ER PT J AU Radomska, HS Huettner, CS Zhang, P Cheng, T Scadden, DT Tenen, DG AF Radomska, HS Huettner, CS Zhang, P Cheng, T Scadden, DT Tenen, DG TI CCAAT enhancer binding protein alpha is a regulatory switch sufficient for induction of granulocytic development from bipotential myeloid progenitors SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID STIMULATING FACTOR-RECEPTOR; TRANSCRIPTION FACTOR EGR-1; HEMATOPOIETIC STEM-CELLS; C/EBP-ALPHA; GENE-EXPRESSION; RETINOIC ACID; MACROPHAGE DIFFERENTIATION; ADIPOCYTE DIFFERENTIATION; TARGETED DISRUPTION; PU.1 SPI-1 AB The transcription factor CCAAT/enhancer binding protein or (C/EBP alpha) regulates a number of myeloid cell-specific genes. To delineate the role of C/EBP alpha in human granulopoiesis,,ve studied its expression and function in human primary cells and bipotential (granulocytic/monocytic) myeloid cell lines. We show that the expression of C/EBP alpha initiates with the commitment of multipotential precursors to the myeloid lineage, is specifically upregulated during granulocytic differentiation, and is rapidly downregulated during the alternative monocytic pathway. Conditional expression of C/EBP alpha alone in stably transfected bipotential cells triggers neutrophilic differentiation, concomitant with upregulation of the granulocyte-specific granulocyte colony-stimulating factor receptor and secondary granule protein genes. Moreover, induced expression of C/EBP alpha in bipotential precursors blocks their monocytic differentiation program. These results indicate that C/EBP alpha serves as a myeloid differentiation switch acting on bipotential precursors and directing them to mature to granulocytes. C1 Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Massachusetts Gen Hosp, AIDS Res Ctr, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Harvard Inst Med, Room 954,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM dtenen@bidmc.harvard.edu FU NCI NIH HHS [CA41456, R01 CA041456]; NHLBI NIH HHS [HL56745, R01 HL044851, R01 HL056745]; NIDDK NIH HHS [DK09721, F32 DK009721, R01 DK050234] NR 87 TC 347 Z9 354 U1 2 U2 5 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 1998 VL 18 IS 7 BP 4301 EP 4314 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA ZW151 UT WOS:000074380100068 PM 9632814 ER PT J AU Kahana, JA Schlenstedt, G Evanchuk, DM Geiser, JR Hoyt, MA Silver, PA AF Kahana, JA Schlenstedt, G Evanchuk, DM Geiser, JR Hoyt, MA Silver, PA TI The yeast dynactin complex is involved in partitioning the mitotic spindle between mother and daughter cells during anaphase B SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID ACTIN-RELATED PROTEIN; VISUAL-SYSTEM DEVELOPMENT; SACCHAROMYCES-CEREVISIAE; CYTOPLASMIC DYNEIN; DROSOPHILA-MELANOGASTER; BUDDING YEAST; MICROTUBULE DEPOLYMERIZATION; MOLECULAR CHARACTERIZATION; P150(GLUED) COMPONENT; CHROMOSOME MOVEMENT AB Although vertebrate cytoplasmic dynein can move to the minus ends of microtubules in vitro, its ability to translocate purified vesicles on microtubules depends on the presence of an accessory complex known as dynactin. We have cloned and characterized a novel gene, NIP100, which encodes the yeast homologue of the vertebrate dynactin complex protein p150(glued). Like strains lacking the cytoplasmic dynein heavy chain Dyn1p or the centractin homologue Act5p, nip100 Delta strains are viable but undergo a significant number of failed mitoses in which the mitotic spindle does not properly partition into the daughter cell. Analysis of spindle dynamics by time-lapse digital microscopy indicates that the precise role of Nip100p during anaphase is to promote the translocation of the partially elongated mitotic spindle through the bud neck. Consistent with the presence of a true dynactin complex in yeast, Nip100p exists in a stable complex with Act5p as well as Jnm1p, another protein required for proper spindle partitioning during anaphase. Moreover, genetic depletion experiments indicate that the binding of Nip100p to Act5p is dependent on the presence of Jnm1p. Finally, we find that a fusion of Nip100p to the green fluorescent protein localizes to the spindle poles throughout the cell cycle. Taken together, these results suggest that the yeast dynactin complex and cytoplasmic dynein together define a physiological pathway that is responsible for spindle translocation late in anaphase. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. RP Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St, Boston, MA 02115 USA. EM pamela_silver@dfci.harvard.edu NR 66 TC 94 Z9 100 U1 0 U2 2 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD JUL PY 1998 VL 9 IS 7 BP 1741 EP 1756 PG 16 WC Cell Biology SC Cell Biology GA 100UV UT WOS:000074834500015 PM 9658168 ER PT J AU Biswas, DK Averboukh, L Sheng, SJ Martin, K Ewaniuk, DS Jawde, TF Wang, FL Pardee, AB AF Biswas, DK Averboukh, L Sheng, SJ Martin, K Ewaniuk, DS Jawde, TF Wang, FL Pardee, AB TI Classification of breast cancer cells on the basis of a functional assay for estrogen receptor SO MOLECULAR MEDICINE LA English DT Article ID RESPONSIVE ELEMENT; TRANSCRIPTIONAL ACTIVITY; PROGESTERONE RECEPTORS; CA2+-BINDING PROTEIN; MESSENGER-RNA; PS2 GENE; HORMONE; ANTIHORMONE; ACTIVATION; MECHANISMS AB Background: The receptor (ER) for estrogen (E2) is routinely assayed as a marker to determine the feasibility of anti-hormone therapy against breast cancer because ER-positive (ER+) tumors are much more likely to respond to anti-hormone therapy than are ER-negative (ER-). However 40% of ER+ breast cancer patients do not respond to anti-hormone therapy. We suggest that this unpredictability of therapeutic responses lies in the current ER assays, which measure only an initial component of the E2-responsive pathway, and that the difference depends upon altered downstream processes. We propose a functional criterion that subclassifies breast cancers on the basis of specific binding of ER to its cognate DNA sequence, the estrogen response element (ERE). Materials and Methods: ER was identified in breast cancer cell lines by immunofluorescence assay, Western blot analysis, identification of ER-specific mRNA, and by interaction of the ER-ERE complex with three different ER-specific antibodies. ER-ERE complex formation was measured by electrophoretic mobility shift assay (EMSA). Transactivation of the E2-responsive gene was studied by transfection of cells with fusion gene construct with the promoter-containing ERE sequence and assay of reporter gene activity in the cell extracts. Results: The growth of ER+ T47D cells was sensitive to tamoxifen, ICI-182,780, and ethynyl estradiol (EE2), whereas another ER+ breast cancer cell line, 21PT, was resistant to these compounds. The estrogen receptor (ER) in the nuclear extracts of MCF-7 and T47D demonstrated hormone-dependent interaction with the response element (ERE) and also downstream transactivation of the E2-responsive PS2 promoter. But in the 21PT cell line that was designated as ER- on the basis of ligand-binding assay and was found to be ER+ by all the other ER assays, ER-ERE interaction and PS2 promoter transactivation were independent of hormone. Conclusions: On the basis of the downstream functional assay of ER interaction with ERE, ER+ breast tumor cells can be subclassified into two categories. The first is E2-dependent (ERd+) and these cells should respond to anti-hormone therapy. The second type of ER interacts with ERE independent of E2 (ERi+) and constitutively transactivates responsive genes. It is predicted that the latter type of breast cancers will not respond to antihormone therapy. C1 Dana Farber Canc Inst, Div Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Biswas, DK (reprint author), Dana Farber Canc Inst, Div Canc Biol, Boston, MA 02115 USA. FU NCI NIH HHS [CA61232] NR 55 TC 20 Z9 20 U1 1 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 1076-1551 J9 MOL MED JI Mol. Med. PD JUL PY 1998 VL 4 IS 7 BP 454 EP 467 PG 14 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 107XG UT WOS:000075235800003 PM 9713824 ER PT J AU Pulsipher, M Kupfer, GM Naf, D Suliman, A Lee, JS Jakobs, P Grompe, M Joenje, H Sieff, C Guinan, E Mulligan, R D'Andrea, AD AF Pulsipher, M Kupfer, GM Naf, D Suliman, A Lee, JS Jakobs, P Grompe, M Joenje, H Sieff, C Guinan, E Mulligan, R D'Andrea, AD TI Subtyping analysis of Fanconi anemia by immunoblotting and retroviral gene transfer SO MOLECULAR MEDICINE LA English DT Article ID BONE-MARROW TRANSPLANTATION; COMPLEMENTATION GROUPS; GROUP-C; CELLS; DIAGNOSIS; FACC; POLYPEPTIDE; EXPRESSION; THERAPY; VECTOR AB Fanconi anemia (FA) is an autosomal recessive cancer susceptibility syndrome with at least eight complementation groups (A-H). Two of the FA genes (FAA and FAG) have been cloned, and mutations in these genes account for approximately 80% of FA patients. subtyping of FA patients is an important first step toward identifying candidates for FA gene therapy. In the current study, we analyzed a reference group of 26 FA patients of known subtype. Most of the patients (18/26) were confirmed as either type A or type C by immunoblot analysis with anti-FAA and anti-FAG antisera. In order to resolve the subtype of the remaining patients, we generated retroviral constructs expressing FAA and FAC for transduction of FA cell lines (pMMP-FAA and pMMP-FAC). The pMMP-FAA construct specifically complemented the abnormal phenotype of cell lines from FA-A patients, while pMMP-FAC complemented FA-C cells. In summary, the combination of immunoblot analysis and retroviral-mediated phenotypic correction of FA cells allows a rapid method of FA subtyping. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Dept Pediat, Boston, MA USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Dept Genet, Boston, MA USA. Oregon Hlth Sci Univ, Dept Pediat, Portland, OR 97201 USA. Free Univ Amsterdam, Dept Human Genet, Amsterdam, Netherlands. RP D'Andrea, AD (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St,Mayer Bldg,Room 640, Boston, MA 02115 USA. EM a_dandrea@farber.harvard.edu FU NHLBI NIH HHS [P01-HL54785, R01-HL52725, KO8-HLO3751-01] NR 35 TC 35 Z9 36 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 1076-1551 J9 MOL MED JI Mol. Med. PD JUL PY 1998 VL 4 IS 7 BP 468 EP 479 PG 12 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 107XG UT WOS:000075235800004 PM 9713825 ER PT J AU Kirchhausen, T AF Kirchhausen, T TI Wiskott-Aldrich syndrome: a gene, a multifunctional protein and the beginnings of an explanation SO MOLECULAR MEDICINE TODAY LA English DT Review ID TYROSINE KINASES; CDC42; MUTATIONS; GTPASES; CELLS; WASP; RAC AB Patients with Wiskott-Aldrich syndrome show various defects in the normal function of platelets and lymphocytes. The recent identification of the gene responsible for this syndrome has led to a surge of studies aimed at solving the puzzle posed by the varied phenotype observed in this disease. It is now known that WASP, the protein product of this gene, can interact with a large number of other proteins known to be involved in the regulation of signal transduction and cytoskeletal organization. Thus, WASP appears to integrate these two basic and fundamental cellular mechanisms. Several groups are now focusing on understanding the function of WASP in detail, and translating this new knowledge into improved therapies. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RP Kirchhausen, T (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 200 Longwood Ave, Boston, MA 02115 USA. EM Kirchhausen@crystal.harvard.edu NR 29 TC 11 Z9 11 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1357-4310 J9 MOL MED TODAY JI Mol. Med. Today PD JUL PY 1998 VL 4 IS 7 BP 300 EP 304 DI 10.1016/S1357-4310(98)01268-4 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 104BQ UT WOS:000074992700007 PM 9743991 ER PT J AU Anand, BS AF Anand, BS TI Drug treatment of portal hypertension SO NATIONAL MEDICAL JOURNAL OF INDIA LA English DT Review ID VASOPRESSIN PLUS NITROGLYCERIN; ESOPHAGEAL VARICEAL HEMORRHAGE; CIRRHOTIC RAT-LIVER; RANDOMIZED TRIAL; NITRIC-OXIDE; ISOSORBIDE MONONITRATE; PRESSURE; PROPRANOLOL; PREVENTION; ISOSORBIDE-5-MONONITRATE AB Despite advances in endoscopic management, variceal bleeding is still associated with a significant mortality. In recent years, several therapeutic agents have been shown to lower the portal pressure and reduce variceal bleeding. In patients presenting with acute variceal bleeding, the drug of choice is somatostatin; it is as effective as endoscopic treatment and is virtually free of side-effects. The second-line drug therapy in acute variceal bleeding is a combination of vasopressin and nitroglycerine. Every patient with a history of variceal bleeding is at an increased risk of rebleeding and should receive some form of preventive therapy. In these patients, non-selective beta-blockers and endoscopic treatment are equally effective and either modality can be used, Since each episode of variceal bleeding carries a 30%-50% risk of death, cirrhotics who have never experienced variceal bleeding but are at high risk to develop this complication (high portal pressure, variceal grade III and IV, and presence of red wale markings over the varices) should be identified and treated. Beta-blockers are the treatment of choice and should be continued for the rest of the patient's life. Isosorbide-5-mononitrate is also useful in lowering the portal pressure and may be combined with beta-blockers in those who do not respond to the use of beta-blockers alone. However, isosorbiXde-5-mononitrate should not be given alone for a long duration because of its adverse haemodynamic effects. Additional measures which are useful in decreasing the risk of variceal breeding are good control of ascites, especially with spironolactone and a low salt diet, and early recognition and treatment of bacterial infections. C1 VA Med Ctr, Digest Dis Sect 3D, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. RP Anand, BS (reprint author), VA Med Ctr, Digest Dis Sect 3D, Dept Med, 2002 Holcombe Blvd, Houston, TX 77030 USA. NR 66 TC 0 Z9 0 U1 0 U2 0 PU ALL INDIA INST MEDICAL SCIENCES PI NEW DELHI PA ANSARI NAGAR, NEW DELHI 110 029, INDIA SN 0970-258X J9 NATL MED J INDIA JI Natl. Med. J. India PD JUL-AUG PY 1998 VL 11 IS 4 BP 173 EP 177 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 134XQ UT WOS:000076769400007 PM 9808974 ER PT J AU Rustgi, AK AF Rustgi, AK TI Cyclooxygenase-2: The future is now SO NATURE MEDICINE LA English DT Editorial Material ID POLYPOSIS C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Rustgi, AK (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. EM rustgi@helix.mgh.harvard.edu NR 10 TC 10 Z9 10 U1 1 U2 1 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD JUL PY 1998 VL 4 IS 7 BP 773 EP 774 DI 10.1038/nm0798-773 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA ZX687 UT WOS:000074543900028 PM 9662366 ER PT J AU Mummidi, S Ahuja, SS Gonzalez, E Anderson, SA Santiago, EN Stephan, KT Craig, FE O'Connell, P Tryon, V Clark, RA Dolan, MJ Ahuja, SK AF Mummidi, S Ahuja, SS Gonzalez, E Anderson, SA Santiago, EN Stephan, KT Craig, FE O'Connell, P Tryon, V Clark, RA Dolan, MJ Ahuja, SK TI Genealogy of the CCR5 locus and chemokine system gene variants associated with altered rates of HIV-1 disease progression SO NATURE MEDICINE LA English DT Article ID INFECTION; RECEPTOR; ENTRY; LESTR/FUSIN; INDIVIDUALS; RESISTANCE; COFACTOR; LIGAND; ALLELE; SDF-1 AB Allelic variants for the HIV-1 co-receptors chemokine receptor 5 (CCR5) and CCR2, as well as the ligand for the co-receptor CXCR4 stromal-derived factor (SDF-1), have been associated with a delay in disease progression. We began this study to test whether polymorphisms in the CCR5 regulatory regions influence the course of HIV-1 disease, as well as to examine the role of the previously identified allelic variants in 1,090 HIV-1 infected individuals. Here we describe the evolutionary relationships between the phenotypically important CCR5 alleles, define precisely the CCR5 regulatory sequences that are linked to the CCR5-Delta 32 and CCR2-64i polymorphisms, and identify genotypes associated with altered rates of HIV-1 disease progression. The disease-retarding effects of the CCR2-641 allele were found in African Americans but not in Caucasians, and the SDF1-3'A/3'A genotype was associated with an accelerated progression to death. In contrast, the CCR5-Delta 32 allele and a CCR5 promoter mutation with which it is tightly linked were associated with limited disease-retarding effects. Collectively, these findings draw attention to a complex array of genetic determinants in the HIV-host interplay. C1 Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX 78284 USA. Wilford Hall USAF Med Ctr, Henry M Jackson Fdn, Lackland AFB, TX 78236 USA. Wilford Hall USAF Med Ctr, Dept Med, Infect Dis Serv, Lackland AFB, TX 78236 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Microbiol, San Antonio, TX 78284 USA. RP Ahuja, SK (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. RI Mummidi, Srinivas/C-1004-2008 OI Mummidi, Srinivas/0000-0002-4068-6380 NR 34 TC 265 Z9 277 U1 1 U2 7 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD JUL PY 1998 VL 4 IS 7 BP 786 EP 793 DI 10.1038/nm0798-786 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA ZX687 UT WOS:000074543900032 PM 9662369 ER PT J AU Boppart, SA Bouma, BE Pitris, C Southern, JF Brezinski, ME Fujimoto, JG AF Boppart, SA Bouma, BE Pitris, C Southern, JF Brezinski, ME Fujimoto, JG TI In vivo cellular optical coherence tomography imaging SO NATURE MEDICINE LA English DT Article ID MICROSCOPY; BIOPSY; SKIN C1 MIT, Elect Res Lab, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Unit, Boston, MA 02114 USA. RP Fujimoto, JG (reprint author), MIT, Elect Res Lab, Dept Elect Engn & Comp Sci, 77 Massachusetts Ave,Room 36-345, Cambridge, MA 02139 USA. RI Boppart, Stephen/C-7338-2009; OI Pitris, Costas/0000-0002-5559-1050 FU NCI NIH HHS [NIH-1-RO1-CA75289-01]; NHLBI NIH HHS [NIH-1-R29-HL55686-01A1]; NIAMS NIH HHS [NIH-RO1-AR44812-01] NR 16 TC 202 Z9 204 U1 0 U2 11 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD JUL PY 1998 VL 4 IS 7 BP 861 EP 865 DI 10.1038/nm0798-861 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA ZX687 UT WOS:000074543900045 PM 9662382 ER PT J AU Hadjikhani, N Liu, AK Dale, AM Cavanagh, P Tootell, RBH AF Hadjikhani, N Liu, AK Dale, AM Cavanagh, P Tootell, RBH TI Retinotopy and color sensitivity in human visual cortical area V8 SO NATURE NEUROSCIENCE LA English DT Article ID STRIATE CORTEX; CEREBRAL-ACHROMATOPSIA; FUNCTIONAL-ANATOMY; SELECTIVE CELLS; RHESUS-MONKEY; MACAQUE; ORGANIZATION; MT; ORIENTATION; PERCEPTION AB Prior studies suggest the presence of a color-selective area in the inferior occipital-temporal region of human visual cortex. It has been proposed that this human area is homologous to macaque area V4, which is arguably color selective, but this has never been tested directly. To test this model, we compared the location of the human color-selective region to the retinotopic area boundaries in the same subjects, using functional magnetic resonance imaging (fMRI), cortical flattening and retinotopic mapping techniques. The human color-selective region did not match the location of area V4 (neither its dorsal nor ventral subdivisions), as extrapolated from macaque maps. Instead this region coincides with a new retinotopic area that we call 'V8', which includes a distinct representation of the fovea and both upper and lower visual fields. We also tested the response to stimuli that produce color afterimages and found that these stimuli, like real colors, caused preferential activation of V8 but not V4. C1 Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Charlestown, MA 02129 USA. RP Hadjikhani, N (reprint author), Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, 149 13th St, Charlestown, MA 02129 USA. EM nouchine@nmr.mgh.harvard.edu RI Hadjikhani, Nouchine/C-2018-2008; Dale, Anders/A-5180-2010 OI Hadjikhani, Nouchine/0000-0003-4075-3106; FU NEI NIH HHS [EY07980, EY09258] NR 50 TC 353 Z9 362 U1 2 U2 32 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD JUL PY 1998 VL 1 IS 3 BP 235 EP 241 DI 10.1038/681 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 127QC UT WOS:000076361200015 PM 10195149 ER PT J AU Frazao, JM Elangovan, L Felsenfeld, AJ Stanley, TM Cohen, AH AF Frazao, JM Elangovan, L Felsenfeld, AJ Stanley, TM Cohen, AH TI Epstein-Barr-virus-induced interstitial nephritis in an HIV-positive patient with progressive renal failure SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Article DE Epstein-Barr virus; interstitial nephritis; HIV; in-situ hybridization; acquired immunodeficiency syndrome ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; IGA NEPHROPATHY; INFECTION; DISEASE C1 W Los Angeles Vet Affairs Med Ctr, Nephrol Sect 111L, Dept Med, Los Angeles, CA 90073 USA. W Los Angeles Vet Affairs Med Ctr, Dept Pathol, Los Angeles, CA 90073 USA. Cedars Sinai Med Ctr, Dept Pathol, Los Angeles, CA 90048 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. RP Frazao, JM (reprint author), W Los Angeles Vet Affairs Med Ctr, Nephrol Sect 111L, Dept Med, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. RI Frazao, Joao/J-9811-2013 OI Frazao, Joao/0000-0002-8081-5474 NR 30 TC 6 Z9 6 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0931-0509 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PD JUL PY 1998 VL 13 IS 7 BP 1849 EP 1852 DI 10.1093/ndt/13.7.1849 PG 4 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA ZZ055 UT WOS:000074691200051 PM 9681746 ER PT J AU Etcheberrigaray, R Hirashima, N Nee, L Prince, J Govoni, S Racchi, M Tanzi, RE Alkon, DL AF Etcheberrigaray, R Hirashima, N Nee, L Prince, J Govoni, S Racchi, M Tanzi, RE Alkon, DL TI Calcium responses in fibroblasts from asymptomatic members of Alzheimer's disease families SO NEUROBIOLOGY OF DISEASE LA English DT Article DE Alzheimer's disease; calcium; fibroblast ID CULTURED FIBROBLASTS; PROTEIN; PATHOPHYSIOLOGY; MANIFESTATIONS; MUTATIONS; MEMORY; DONORS AB We have previously identified alterations of K+ channel function, IP3-mediated calcium release, and Cp20 (a memory-associated GTP binding protein) in fibroblasts from Alzheimer's disease (AD) patients vs controls. Some of these alterations can be integrated into an index that distinguishes AD patients from controls with both high specificity and high sensitivity. We report here that alterations in IP3-mediated calcium responses are present in a large proportion of AD family members (i.e., individuals at high risk) before clinical symptoms of Alzheimer's disease are present. This was not the case if such members later "escaped" AD symptoms. This preclinical calcium signal correlate of later AD does not reflect, however, the presence of the PSI familial AD gene. (C) 1998 Academic Press. C1 Georgetown Univ, Med Ctr, Lab Appl Neurosci, Inst Cognit & Computat Sci, Washington, DC 20007 USA. NINCDS, Lab Adapt Syst, Bethesda, MD 20892 USA. NINCDS, Family Studies Unit, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. Univ Pavia, Inst Pharmacol, I-27100 Pavia, Italy. Sacred Heart FBF Hosp Brescia, Alzheimers Dept, Mol & Cellular Neurobiol Lab, Brescia, Italy. RP Etcheberrigaray, R (reprint author), Georgetown Univ, Med Ctr, Lab Appl Neurosci, Inst Cognit & Computat Sci, Res Bldg,WP14,3970 Reservoir Rd NW, Washington, DC 20007 USA. RI Govoni, Stefano/K-2965-2015; OI Govoni, Stefano/0000-0002-7243-6837; Racchi, Marco/0000-0002-7185-7808 NR 29 TC 82 Z9 83 U1 0 U2 6 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD JUL PY 1998 VL 5 IS 1 BP 37 EP 45 DI 10.1006/nbdi.1998.0176 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 107AM UT WOS:000075183700004 PM 9702786 ER PT J AU Patterson, TA Brot, MD Zavosh, A Schenk, JO Szot, P Figlewicz, DP AF Patterson, TA Brot, MD Zavosh, A Schenk, JO Szot, P Figlewicz, DP TI Food deprivation decreases mRNA and activity of the rat dopamine transporter SO NEUROENDOCRINOLOGY LA English DT Article DE insulin; dopamine transporter; catecholamines; food deprivation; in situ hybridization ID DISK ELECTRODE VOLTAMMETRY; INDUCED DIABETIC RATS; MESSENGER-RNA; PARKINSONS-DISEASE; SUBSTANTIA-NIGRA; SEROTONIN TRANSPORTER; STRIATAL TRANSPORTER; IN-VITRO; COCAINE; BRAIN AB We have hypothesized that the midbrain dopamine (DA) neurons are a target for insulin action in the central nervous system (CNS). In support of this hypothesis, we have previously demon strated that direct intracerebroventricular infusion of insulin results in an increase in mRNA levels for the DA reuptake transporter (DAT). In this study, 24- to 36-hour food deprivation was used as a model of decreased CNS insulin levels, to test whether DAT mRNA levels, DAT protein concentration or DAT functional activity would be decreased. DAT mRNA levels, assessed by in situ hybridization, were significantly decreased in the ventral tegmental area/substantia nigra pars compacta (VTA/SNc) (77 +/- 7% of controls, p < 0.05) of food-deprived (hypoinsulinemic) rats. Binding of a specific high-affinity DAT ligand (I-125-RTI-121) to membranes from brain regions of fasted or free-feeding rats provided an estimate of DAT protein, which was unchanged in both of the major terminal projection fields, the striatum and nucleus accumbens (NAc). In addition, we utilized the rotating disk electrode voltametry technique to assess possible changes in the function of the DAT in fasting (hypoinsulinemic) rats. The V-max of DA uptake was significantly decreased (87 +/- 7% of control, p < 0.05), without a change in the K-m of uptake, in striatum from fasted rats. In vitro incubation with a physiological concentration (1 nM) of insulin resulted in an increase of striatal DA uptake to control levels. We conclude that striatal DAT function can be modulated by fasting and nutritional status, with a contribution transporter by insulin. C1 VA Puget Sound Hlth Care Syst, Dept Psychol, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Dept Psychiat & Behav Sci, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Div Endocrinol & Metab 151, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA 98108 USA. Washington State Univ, Dept Chem, Pullman, WA 99164 USA. RP Figlewicz, DP (reprint author), VA Puget Sound Hlth Care Syst, Dept Psychol, 1660 So Columbian Way, Seattle, WA 98108 USA. EM latte@u.washington.edu FU NIDA NIH HHS [DA073840]; NIDDK NIH HHS [R01 DK40963] NR 54 TC 100 Z9 100 U1 0 U2 5 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 EI 1423-0194 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PD JUL PY 1998 VL 68 IS 1 BP 11 EP 20 DI 10.1159/000054345 PG 10 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 100ZT UT WOS:000074845700002 PM 9695934 ER PT J AU Handforth, A DeGiorgio, CM Schachter, SC Uthman, BM Naritoku, DK Tecoma, ES Henry, TR Collins, SD Vaughn, BV Gilmartin, RC Labar, DR Morris, GL Salinsky, MC Osorio, I Ristanovic, RK Labiner, DM Jones, JC Murphy, JV Ney, GC Wheless, JW AF Handforth, A DeGiorgio, CM Schachter, SC Uthman, BM Naritoku, DK Tecoma, ES Henry, TR Collins, SD Vaughn, BV Gilmartin, RC Labar, DR Morris, GL Salinsky, MC Osorio, I Ristanovic, RK Labiner, DM Jones, JC Murphy, JV Ney, GC Wheless, JW TI Vagus nerve stimulation therapy for partial-onset seizures - A randomized active-control trial SO NEUROLOGY LA English DT Article ID FOCAL EPILEPTIFORM ACTIVITY; LOCUS CERULEUS STIMULATION; INTRACTABLE SEIZURES; RAT; SUPPRESSION; CONNECTIONS; AFFERENT; EPILEPSY; NUCLEUS; SYSTEM AB Objective: The purpose of this multicenter, add-on, double-blind, randomized, active-control study was to compare the efficacy and safety of presumably therapeutic (high) vagus nerve stimulation with less (low) stimulation. Background: Chronic intermittent left vagus nerve stimulation has been shown in animal models and in preliminary clinical trials to suppress the occurrence of seizures, Methods: Patients had at least six partial-onset seizures over 30 days involving complex partial or secondarily generalized seizures. Concurrent antiepileptic drugs were unaltered. After a 3-month baseline, patients were surgically implanted with stimulating leads coiled around the left vagus nerve and connected to an infraclavicular subcutaneous programmable pacemaker-like generator. After randomization, device initiation, and a 2-week ramp-up period, patients were assessed for seizure counts and safety over 3 months. The primary efficacy variable was the percentage change in total seizure frequency compared with baseline. Results: Patients receiving high stimulation (94 patients, ages 13 to 54 years) had an average 28% reduction in total seizure frequency compared with a 15% reduction in the low stimulation group (102 patients, ages 15 to 60 year; p = 0.04). The high-stimulation group also had greater improvements on global evaluation scores, as rated by a blinded interviewer and the patient. High stimulation was associated with more voice alteration and dyspnea. No changes in physiologic indicators of gastric, cardiac, or pulmonary functions occurred. Conclusions: Vagus nerve stimulation is an effective and safe adjunctive treatment for patients with refractory partial-onset seizures. It represents the advent of a new, nonpharmacologic treatment for epilepsy. C1 W Los Angeles Vet Affairs Med Ctr, Neurol Serv W127, Los Angeles, CA 90073 USA. Univ So Calif, Los Angeles, CA USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Florida, Coll Med, DVA Med Ctr, Gainesville, FL USA. So Illinois Univ, Sch Med, Springfield, IL USA. Univ Calif San Diego, La Jolla, CA 92093 USA. Emory Univ, Atlanta, GA 30322 USA. Case Western Reserve Univ, Comprehens Epilepsy Program, Cleveland, OH 44106 USA. Univ N Carolina, Chapel Hill, NC USA. Res Inst Kansas, Wichita, KS USA. Cornell Univ, New York Hosp, New York, NY USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. Univ Arizona, Tucson, AZ USA. Univ Wisconsin Hosp & Clin, Madison, WI 53792 USA. Childrens Mercy Hosp, Kansas City, KS USA. Long Isl Jewish Med Ctr, New Hyde Park, NY 11042 USA. Univ Texas, Houston, TX USA. RP Handforth, A (reprint author), W Los Angeles Vet Affairs Med Ctr, Neurol Serv W127, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. OI Henry, Thomas/0000-0002-5708-903X NR 42 TC 555 Z9 566 U1 4 U2 29 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUL PY 1998 VL 51 IS 1 BP 48 EP 55 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 103HL UT WOS:000075151800014 PM 9674777 ER PT J AU Craft, S Teri, L Edland, SD Kukull, WA Schellenberg, G McCormick, WC Bowen, JD Larson, EB AF Craft, S Teri, L Edland, SD Kukull, WA Schellenberg, G McCormick, WC Bowen, JD Larson, EB TI Accelerated decline in apolipoprotein E-epsilon 4 homozygotes with Alzheimer's disease SO NEUROLOGY LA English DT Article ID E EPSILON-4 ALLELE; E GENOTYPE; NEUROFIBRILLARY TANGLES; COGNITIVE DECLINE; TYPE-4 ALLELE; HEAD-INJURY; BINDING; PROGRESSION; HIPPOCAMPUS; DEPOSITION AB Background: The apolipoprotein E-epsilon 4 (APOE-epsilon 4) allele is a powerful genetic risk factor for the development of Alzheimer's disease (AD). AD patients who are APOE-epsilon 4 homozygotes have an earlier age at onset, increased amyloid burden, and decreased acetylcholine levels-findings that suggest differences in disease severity or rate of progression. Studies of genotype differences in rate of decline, however, have produced negative results that may be due to methodologic biases. The current study examined rate of decline in the largest sample of APOE-genotyped AD patients for whom longitudinal cognitive data have been reported. Methods: Newly diagnosed patients with probable AD (n = 201) comprised four genotype groups: epsilon 2/3 (n = 14), epsilon 3/3 (n = 75), epsilon 3/4 (n = 82), and epsilon 4/4 (n = 30). The Dementia Rating Scale (DRS) was administered at baseline and then annually for 1 to 6 years (mean, 2.5 years). For each subject, a DRS slope was calculated reflecting annual rate of decline. Rate of decline as measured by DRS slope differed according to genotype, with the effect modified by DRS score (p < 0.014). At the mean DRS score observed in our sample (DRS = 105), the epsilon 4/4 group had an increased rate of decline (11.9 points per year) relative to the epsilon 2/3 (5.8 points per year; p < 0.003), epsilon 3/3 (9.3 points per year; p < 0.076), and epsilon 3/4 (9.6 points per year; p < 0.055) groups. At a lower DRS score (DRS = 80), even larger differences were observed among genotypes; the epsilon 4/4 group had a increased rate of decline (22.2 points per year) relative to the epsilon 2/3 (9.7 points per year; p < 0.0006), epsilon 3/4 (15.8 points per year; p < 0.020), and epsilon 3/3 (18.2 points per year; p < 0.173) groups. The epsilon 2/3 group had a significantly slower rate of decline than all other groups at DRS scores of 80 or 105. Conclusions: APOE-epsilon 4 homozygosity is associated with a faster rate of cognitive decline, whereas the epsilon 2 allele slows disease progression. These findings suggest that APOE plays a mechanistic role in the progression of AD, and is not simply related to disease onset. C1 VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr 182B, Seattle, WA 98018 USA. Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Neurol, Seattle, WA 98195 USA. RP Craft, S (reprint author), VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr 182B, 1660 S Columbian Way, Seattle, WA 98018 USA. EM scraft@u.washington.edu FU NIA NIH HHS [R01 AG-05136, R01 AG-10880, U01 AG-06781] NR 34 TC 111 Z9 113 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUL PY 1998 VL 51 IS 1 BP 149 EP 153 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 103HL UT WOS:000075151800031 PM 9674794 ER PT J AU Kaye, JA AF Kaye, JA TI Diagnostic challenges in dementia SO NEUROLOGY LA English DT Article ID LEWY BODY DISEASE; PROGRESSIVE SUBCORTICAL GLIOSIS; IDIOPATHIC PARKINSONS-DISEASE; FRONTAL-LOBE DEGENERATION; ALZHEIMERS-DISEASE; INTERNATIONAL WORKSHOP; COMMUNITY POPULATION; EXTRAPYRAMIDAL SIGNS; CLINICAL-DIAGNOSIS; VASCULAR DEMENTIA AB As the population ages, increasing numbers of patients will present with dementia. Diagnosis may be very straightforward, as in an individual with dementia secondary to an obvious medical illness. However, the differential diagnosis of dementia may be less clear. Diagnostically challenging cases tend to appear in the setting of dementias that present without distinctive neurologic signs or evidence of medical or neurologic disease, such as Alzheimer's disease or the frontotemporal dementias. A similar diagnostic challenge is seen in dementias that present with neurologic signs but without obvious significant medical disorders, such as the parkinsonian dementias or the vascular dementias. In recent years, the presentations of these dementias have become more sharply drawn on the basis of consensus reviews of clinicopathologic correlations. Because each of these disorders has unique treatment and management strategies, the ability of clinicians to differentiate among these syndromes has become critically important. C1 Oregon Hlth Sci Univ, Aging & Alzheimer Dis Ctr, Dept Neurol, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR USA. RP Kaye, JA (reprint author), Oregon Hlth Sci Univ, Aging & Alzheimer Dis Ctr, Dept Neurol, L226,3181 SW Sam Jackson Pk Rd, Portland, OR 97201 USA. FU NIA NIH HHS [AG08017] NR 44 TC 24 Z9 25 U1 2 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUL PY 1998 VL 51 IS 1 SU 1 BP S45 EP S52 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 102GR UT WOS:000074916500006 PM 9674762 ER PT J AU Reppert, SM AF Reppert, SM TI A clockwork explosion! SO NEURON LA English DT Review C1 Massachusetts Gen Hosp, Serv Pediat, Lab Dev Chronobiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Reppert, SM (reprint author), Massachusetts Gen Hosp, Serv Pediat, Lab Dev Chronobiol, Boston, MA 02114 USA. NR 20 TC 108 Z9 108 U1 1 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD JUL PY 1998 VL 21 IS 1 BP 1 EP 4 DI 10.1016/S0896-6273(00)80234-2 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 105FK UT WOS:000075061900001 PM 9697845 ER PT J AU Yamasaki, EN Krupnik, VE Chun, LLY AF Yamasaki, EN Krupnik, VE Chun, LLY TI Developmental study of Muller cells in the rat retina using a new monoclonal antibody, RT10F7 SO NEUROSCIENCE LA English DT Article DE radial glia; astrocytes; tanycytes; retinal development ID INNER PLEXIFORM LAYER; GANGLION-CELLS; S-100 PROTEIN; RABBIT RETINA; GLIAL-CELLS; MICROSCOPICAL IMMUNOCYTOCHEMISTRY; POSTNATAL-DEVELOPMENT; DENDRITIC MATURATION; ALPHA-GANGLION; ION CHANNELS AB We produced the monoclonal antibody RT10F7, characterized its antigenic specificity and expression in the adult and developing retina, in cultured retinal cells and in other parts of the central nervous system. In metabolically-labelled retinal cultures RT10F7 immunoprecipitated a protein of approximately 36,000 mol. wt. In the adult, RT10F7 stained endfeet of Muller cells in the ganglion cell layer, four horizontal bands in the inner plexiform layer, and radial fibres in the outer plexiform layer which terminated at the outer limiting membrane. In the inner nuclear layer, most somata were underlined by Muller processes that wrapped around them, but some cell bodies were immunoreactive for RT10F7 in the cytoplasm. During development, postnatal day 21 was the first age at which the adult pattern of immunoreactivity was present, although a fourth band in the inner plexiform layer was less clear than for the adult. By 14 and eight days after birth, the pattern of RT10F7 immunoreactivity approximated that of the adult; however, only three bands and one band were present, respectively, in the inner plexiform layer. At earlier ages, postnatal days 4, 1 and embryonic ages 19 and 15, the monoclonal antibody stained Muller cell endfeet and radial fibres, from the inner plexiform layer through the neuroblastic layer to the outer limiting membrane. At these ages, the immunoreactivity was more prominent at the level of Muller cell endfeet. The monoclonal antibody stained glia in preparations of dissociated retinal cells maintained in culture but not astrocytes or oligodendrocytes from optic nerve cultures. In brain sections, tanycytes exhibited RT10F7 immunoreactivity. The monoclonal antibody RT10F7 recognized a specific cell type in the retina, the Muller cell. In the adult and developing retina, RT10F7 recognized an antigen that is present primarily in Muller cell processes. This feature allowed us to follow the maturation of the Muller cell and correlate it with developmental events in the retina. RT10F7 is a specific marker for Muller cells in vivo and in vitro and may be useful for studies of function of Muller cells after ablation or after injuries that are known to activate Muller cells. (C) 1998 IBRO. Published by Elsevier Science Ltd. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Retinal Dev & Regenerat Lab,Neurosurg Serv, Boston, MA 02114 USA. Harvard Univ, Program Neurosci, Sch Med, Boston, MA USA. RP Chun, LLY (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Retinal Dev & Regenerat Lab,Neurosurg Serv, Boston, MA 02114 USA. FU NEI NIH HHS [EY08125] NR 74 TC 13 Z9 14 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD JUL PY 1998 VL 85 IS 2 BP 627 EP 636 DI 10.1016/S0306-4522(97)00084-5 PG 10 WC Neurosciences SC Neurosciences & Neurology GA ZN622 UT WOS:000073664400027 PM 9622258 ER PT J AU Timchenko, NA Wilde, M Kosai, KI Heydari, A Bilyeu, TA Finegold, MJ Mohamedali, K Richardson, A Darlington, GJ AF Timchenko, NA Wilde, M Kosai, KI Heydari, A Bilyeu, TA Finegold, MJ Mohamedali, K Richardson, A Darlington, GJ TI Regenerating livers of old rats contain high levels of C/EBP alpha that correlate with altered expression of cell cycle associated proteins SO NUCLEIC ACIDS RESEARCH LA English DT Article ID ENHANCER-BINDING-PROTEIN; DEPENDENT KINASES; ADIPOCYTE DIFFERENTIATION; GENE-EXPRESSION; MESSENGER-RNA; PROLIFERATION; INHIBITION; P21; MICE; P53 AB The nuclear transcription factor, CCAAT/enhancer binding protein alpha (C/EBP alpha) is expressed at high levels in the liver and Inhibits growth in cultured cells. We have tested the correlation between C/EBP alpha levels, cell cycle proteins and hepatocyte proliferation in old and young animals as an in vivo model system in which the proliferative response to partial hepatectomy (PH) has been shown to be reduced and delayed in old animals. Here we present evidence that the expression of C/EBP alpha in old rats (24 months) differs from its expression in young animals (6-10 months) during liver regeneration. Induction of proliferating cell nuclear antigen (PCNA), a marker of DNA synthesis, occurs at 24 h after PH in young rats but is delayed and reduced in old animals. Induction of the mitotic-specific protein, cdc2 p34, is 3-4-fold less in regenerating liver of old rats than in the liver of young animals, confirming the reduced proliferative response in old animals. In young rats,the normal regenerative response involves a reduction of 3-4-fold in the levels of C/EBP alpha protein at 3-24 h. In old animals, C/EBP alpha is not reduced within 24 h after PH, but a decrease of C/EBP alpha protein levels can be detected at 72 h after PH. Induction of C/EBP beta, another member of the C/EBP family, is delayed in old animals. Changes in the expression of C/EBP proteins are accompanied by alteration of the CDK inhibitor, p21, which is also decreased in young rats after PH, but in old animals remains unchanged. High levels of p21 protein in older animals correlate with the lack of cdk2 activation. We suggest that the failure to reduce the amount of C/EBP alpha and p21 is a critical event in the dysregulation of hepatocyte proliferation in old animals following PH. C1 Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. Audie L Murphy Mem Vet Hosp, San Antonio, TX 78248 USA. RP Timchenko, NA (reprint author), Baylor Coll Med, Dept Pathol, 1 Baylor Plaza, Houston, TX 77030 USA. EM nikolait@bcm.tmc.edu FU NIA NIH HHS [AG13663, AG00765-01]; NIDDK NIH HHS [DK45285] NR 30 TC 47 Z9 47 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUL 1 PY 1998 VL 26 IS 13 BP 3293 EP 3299 DI 10.1093/nar/26.13.3293 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZX893 UT WOS:000074566000031 PM 9628932 ER PT J AU Smith, D Shaffer, K Kirn, D Canellos, GP Mauch, PM Shulman, LN AF Smith, D Shaffer, K Kirn, D Canellos, GP Mauch, PM Shulman, LN TI Mediastinal large cell lymphoma: Prognostic significance of CT findings at presentation and after treatment SO ONCOLOGY LA English DT Article DE lymphoma; prognosis; prognostic factors; computed tomography ID NON-HODGKINS LYMPHOMA; DIFFUSE LARGE-CELL; HISTIOCYTIC LYMPHOMA; COMPUTED-TOMOGRAPHY; SCLEROSIS; TUMOR; THERAPY; SUBSET; ADULTS; MASSES AB Objective: Primary mediastinal large cell lymphoma is a distinctive subtype of non-Hodgkin's lymphoma, Computed tomography (CT) has become an integral part of the evaluation of these patients at presentation and after completion of therapy, The purpose of this study is to identify CT features that predict increased risk of relapse, Methods: A retrospective study of patients with primary mediastinal large cell lymphoma who underwent CT scans of the thorax, Results: Tumor volume greater than 100 mi after completion of therapy was a statistically significant predictor of increased risk of relapse (p = 0,02, Fisher exact test), Other measurements (obtained at presentation and after completion of treatment) were not statistically significant in predicting relapse, Conclusion: CT plays an important role in predicting outcome in primary mediastinal large cell lymphoma, Large residual tumor volume after completion of treatment predicts an increased risk of relapse. C1 Brigham & Womens Hosp, Dept Radiol, Boston, MA 02155 USA. Brigham & Womens Hosp, Div Hematol Oncol, Boston, MA 02155 USA. Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Univ Calif San Francisco, Dept Hematol Oncol, San Francisco, CA 94143 USA. Joint Ctr Radiat Therapy, Boston, MA 02115 USA. RP Smith, D (reprint author), Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02155 USA. EM dnsmith@bics.bwh.harvard.edu NR 25 TC 7 Z9 7 U1 1 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0030-2414 J9 ONCOLOGY-BASEL JI Oncology PD JUL-AUG PY 1998 VL 55 IS 4 BP 284 EP 288 DI 10.1159/000011864 PG 5 WC Oncology SC Oncology GA ZW637 UT WOS:000074431600003 PM 9663416 ER PT J AU Houghton, A Coit, D Bloomer, W Buzaid, A Chu, D Eisenberg, B Guitart, J Johnson, T Miller, S Sener, S Tanabe, K Thompson, J Urist, M Walker, M AF Houghton, A Coit, D Bloomer, W Buzaid, A Chu, D Eisenberg, B Guitart, J Johnson, T Miller, S Sener, S Tanabe, K Thompson, J Urist, M Walker, M TI NCCN Melanoma Practice Guidelines SO ONCOLOGY-NEW YORK LA English DT Article ID LYMPH-NODE DISSECTION; MALIGNANT-MELANOMA; CUTANEOUS MELANOMA; 4 MM; RISK; LYMPHADENECTOMY; EFFICACY; EXCISION; MARGINS; THERAPY C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Evanston Hosp, Evanston, IL USA. Univ Texas, MD Anderson Cancer Ctr, Houston, TX 77030 USA. City Hope Natl Med Ctr, Duarte, CA 91010 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Northwestern Univ, Lurie Canc Ctr, Chicago, IL 60611 USA. Univ Michigan, Med Ctr, Ann Arbor, MI USA. Johns Hopkins Outpatient Ctr, Baltimore, MD USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Washington, Seattle, WA 98195 USA. Univ Alabama, Ctr Comprehens Canc, Birmingham, AL 35294 USA. Ohio State Univ, Arthur G James Canc Hosp, Columbus, OH 43210 USA. Ohio State Univ, Res Inst, Columbus, OH 43210 USA. RP Houghton, A (reprint author), Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 25 TC 53 Z9 54 U1 0 U2 0 PU P R R INC PI HUNTINGTON PA 17 PROSPECT ST, HUNTINGTON, NY 11743 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD JUL PY 1998 VL 12 IS 7A SU S BP 153 EP 177 PG 25 WC Oncology SC Oncology GA 103NF UT WOS:000075161900003 PM 9699216 ER PT J AU Demetri, GD Pollock, R Baker, L Balcerzak, S Casper, E Conrad, C Fein, D Hutchinson, R Schupak, K Spiro, I Wagman, L AF Demetri, GD Pollock, R Baker, L Balcerzak, S Casper, E Conrad, C Fein, D Hutchinson, R Schupak, K Spiro, I Wagman, L TI NCCN Sarcoma Practice Guidelines SO ONCOLOGY-NEW YORK LA English DT Article ID SOFT-TISSUE SARCOMAS C1 Dana Farber Canc Inst, Boston, MA 02115 USA. UTMD Anderson, Ctr Canc, Houston, TX USA. Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. Ohio State Univ, Arthur G James Canc Hosp & Res Inst, Columbus, OH 43210 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Washington, Med Ctr, Seattle, WA 98195 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. City Hope Natl Med Ctr, Duarte, CA 91010 USA. RP Demetri, GD (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 7 TC 18 Z9 18 U1 0 U2 0 PU P R R INC PI HUNTINGTON PA 17 PROSPECT ST, HUNTINGTON, NY 11743 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD JUL PY 1998 VL 12 IS 7A SU S BP 183 EP 218 PG 36 WC Oncology SC Oncology GA 103NF UT WOS:000075161900004 PM 9699217 ER PT J AU Scher, H Bahnson, R Cohen, S Eisenberger, M Herr, H Kozlowski, J Lange, P Montie, J Pollack, A Raghaven, D Richie, J Shipley, W AF Scher, H Bahnson, R Cohen, S Eisenberger, M Herr, H Kozlowski, J Lange, P Montie, J Pollack, A Raghaven, D Richie, J Shipley, W TI NCCN Urothelial Cancer Practice Guidelines SO ONCOLOGY-NEW YORK LA English DT Article ID INVASIVE BLADDER-CANCER; TRANSITIONAL-CELL-CARCINOMA; NEOADJUVANT CHEMOTHERAPY; RADICAL RADIOTHERAPY; RADIATION-THERAPY; FOLLOW-UP; ADJUVANT CHEMOTHERAPY; ONCOLOGY-GROUP; CYSTECTOMY; CISPLATIN C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Ohio State Univ, Med Ctr, Columbus, OH 43210 USA. Univ Nebraska, Med Ctr, Omaha, NE USA. Johns Hopkins Oncol Ctr, Baltimore, MD USA. Northwestern Univ, Chicago, IL 60611 USA. Univ Washington, Sch Med, Seattle, WA USA. Univ Michigan, Med Ctr, Ann Arbor, MI USA. Univ Texas, MD Anderson Cancer Ctr, Houston, TX 77030 USA. Roswell Pk Canc Inst, Buffalo, NY 14236 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Scher, H (reprint author), Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 49 TC 36 Z9 36 U1 0 U2 0 PU P R R INC PI HUNTINGTON PA 17 PROSPECT ST, HUNTINGTON, NY 11743 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD JUL PY 1998 VL 12 IS 7A SU S BP 225 EP 271 PG 47 WC Oncology SC Oncology GA 103NF UT WOS:000075161900005 PM 9699218 ER PT J AU Scadden, DT AF Scadden, DT TI Epidemiology and pathogenesis of AIDS-related lymphomas - The Aboulafia article reviewed SO ONCOLOGY-NEW YORK LA English DT Editorial Material C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Scadden, DT (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU P R R INC PI HUNTINGTON PA 17 PROSPECT ST, HUNTINGTON, NY 11743 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD JUL PY 1998 VL 12 IS 7 BP 1086 EP 1087 PG 2 WC Oncology SC Oncology GA 102BZ UT WOS:000074904500023 ER PT J AU Schaumberg, DA Dana, MR Christen, WG Glynn, RJ AF Schaumberg, DA Dana, MR Christen, WG Glynn, RJ TI A systematic overview of the incidence of posterior capsule opacification SO OPHTHALMOLOGY LA English DT Article ID EXTRACAPSULAR CATARACT-EXTRACTION; YAG LASER CAPSULOTOMY; INTRAOCULAR-LENS IMPLANTATION; CYSTOID MACULAR EDEMA; RETINAL-DETACHMENT; CHAMBER LENS; LONG-TERM; MORPHOLOGICAL-CHANGES; CLINICAL-TRIALS; RISK-FACTORS AB Objective: Reported rates of posterior capsule opacification (PCO) vary widely and are based on various definitions of PCO, varying lengths and intervals of follow-up, and the use of different surgical techniques, intraocular lens (IOL) designs, and methods of IOL implantation. This study was designed to obtain a more precise overall estimate of the incidence of PCO and to explore factors that might influence the rate of PCO development. Design: A meta-analysis. Methods: Published articles were selected for study based on a computerized MEDLINE search of the literature and a manual search of the bibliographies of relevant articles, Articles meeting selected inclusion criteria were reviewed systematically, and the reported data were abstracted and synthesized using the statistical techniques of meta-analysis. Main Outcome Measure: Pooled estimates of the proportion of eyes developing PCO at three postoperative timepoints-1 year, 3 years, and 5 years-were measured. Results: There is significant heterogeneity among published rates of PCO. The overall pooled estimates (95% confidence limits) of the incidence of PCO were 11.8% (9.3%-14.3%) at 1 year, 20.7% (16.6%-24.9%) at 3 years, and 28.4% (18.4%-38.4%) at 5 years after surgery. There is no evidence of a significant decline in PCO incidence during the study period. Conclusions: Visually significant PCO develops in more than 25% of patients undergoing standard extracapsular cataract extraction or phacoemulsification with posterior chamber intraocular lens implantation over the first 5 years after surgery. Patient characteristics, surgical techniques, and differences in research design and reporting may account for some of the variability in reported rates. However, no specific factors were identified in the authors' analysis. More precise estimates of incidence and identification of risk factors for PCO will depend on the development of a standardized measurement of PCO and wider adoption of more rigorous study methodology. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Ophthalmol, Boston, MA USA. Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Schaumberg, DA (reprint author), Div Prevent Med, 900 Commonweslth Ave E, Boston, MA 02215 USA. FU NEI NIH HHS [EY06633, EY00365] NR 72 TC 261 Z9 283 U1 1 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD JUL PY 1998 VL 105 IS 7 BP 1213 EP 1221 DI 10.1016/S0161-6420(98)97023-3 PG 9 WC Ophthalmology SC Ophthalmology GA ZY929 UT WOS:000074677100024 PM 9663224 ER PT J AU Merchant, A Zhao, TZ Foster, CS AF Merchant, A Zhao, TZ Foster, CS TI Chronic keratoconjunctivitis associated with congenital dyskeratosis and erythrokeratodermia variablis - Two rare genodermatoses SO OPHTHALMOLOGY LA English DT Article ID DIAGNOSIS; FAMILY AB Objective: The purpose of the study was to report the ocular manifestations and immunohistopathologic description of two rare forms of genodermatosis: congenital dyskeratosis (CD) and erythrokeratodermia variabilis (EKV), Design: Case reports, Participants: Two patients with CD and EKV presenting with chronic keratoconjunctivitis were studied. Intervention: Clinical photography to show ocular manifestations and dermatologic findings was performed. Conjunctival biopsy was performed to determine the histopathology and immunohistopathology. Results: In the patient with EKV, the eyelid skin was dry, erythematous, and thickened. The lid margins showed plugging of some of the Meibomian glands, madarosis, and occasional trichiasis, The epibulbar conjunctiva was injected and had a moderate papillary reaction. Both corneas had pronounced vascularization and stromal scarring. Conjunctival biopsy results disclosed a striking number of degranulating mast cells and moderate numbers of plasma cells. Immunohistopathology showed pronounced immunoglobulin G (IgG)-positive cells in the stroma and immunoglobulin A (IgA) positivity in the epithelium. There was scattered immunoglobulin M (IgM) and moderate C3 and C4 positivity in the stroma, In CD, the patient had keratinized lid margins, entropion formation, trichiasis, cicatrizing conjunctivitis, and symblephra formation. The corneal surface was keratinized, with deep and superficial vascularization. Conjunctival biopsy specimens showed pronounced epithelial keratinization and squamous metaplasia. Degranulating mast cells and eosinophils were prominent in the stroma. Immunohistopathology showed C4 and immunoglobulin D positivity on the keratinized epithelial surface with rare foci of immunoglobulin E-positive cells. Basal epithelial cells were positive for IgA and IgG, and a large number of IgA and IgG plasma cells were present in the substantia propria. Conclusion: To the authors' knowledge, these case reports represent the first clinical description of the ocular manifestation of EKV and the first immunohistopathologic description of the affected conjunctiva in EKV and CD, both of which should be considered in the differential diagnosis of genodermatosis associated with chronic keratoconjunctivitis. C1 Harvard Univ, Serv Immunol, Dept Ophthalmol, Massachusetts Eye & Ear Infirm,Sch Med, Boston, MA 02114 USA. RP Foster, CS (reprint author), Harvard Univ, Serv Immunol, Dept Ophthalmol, Massachusetts Eye & Ear Infirm,Sch Med, 243 Charles St, Boston, MA 02114 USA. NR 17 TC 7 Z9 8 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD JUL PY 1998 VL 105 IS 7 BP 1286 EP 1291 DI 10.1016/S0161-6420(98)97035-X PG 6 WC Ophthalmology SC Ophthalmology GA ZY929 UT WOS:000074677100036 PM 9663235 ER PT J AU Ma, QP Allchorne, AJ Woolf, CJ AF Ma, QP Allchorne, AJ Woolf, CJ TI Morphine, the NMDA receptor antagonist MK801 and the tachykinin NK1 receptor antagonist RP67580 attenuate the development of inflammation-induced progressive tactile hypersensitivity SO PAIN LA English DT Article DE allodynia; hyperalgesia; pain; opiate; NK1; N-methyl-D-aspartate ID DORSAL HORN NEURONS; RAT SPINAL-CORD; NERVE GROWTH-FACTOR; CUTANEOUS MECHANORECEPTIVE FIELDS; PRIMARY SENSORY NEURONS; PROTEIN-KINASE-C; SUBSTANCE-P; MECHANICAL HYPERALGESIA; SECONDARY HYPERALGESIA; PAIN HYPERSENSITIVITY AB Normally-innocuous low-intensity tactile stimuli applied to inflamed tissue induce a progressive decrease in the mechanical flexion withdrawal threshold, the phenomenon of progressive tactile hypersensitivity (PTH). The effects of the mu opioid receptor agonist morphine, the non-competitive NMDA receptor antagonist MK801 and the tachykinin NK1 receptor antagonist RP67580 on the development and maintenance of PTH has now been investigated behaviourally in rats inflamed 48 h earlier by intraplantar complete Freund's adjuvant injection. A standard protocol of eight light tactile stimuli applied to the dorsum of the inflamed paw every 4 s at 5 min intervals resulted, over 60 min, in a 70% fall in mechanical threshold from the pre-conditioning baseline value. Morphine administered before the tactile stimuli at 0.05 mg/kg i.p. had no effect on either baseline thresholds or PTH. At 0.5 mg/kg, morphine prevented the establishment of PTH without changing baseline thresholds. At 5 mg/kg morphine produced analgesia, increasing thresholds above the baseline. MK801 pre treatment at 0.01 and 0.001 mg/kg i.p, significantly attenuated the development of progressive tactile hyperalgesia without an effect on basal thresholds. RP67580 pre-treatment at 0.1 mg/kg i.p. had no effect, but at both 1 and 10 mg/kg, attenuated progressive tactile hypersensitivity without changing baseline values. To test the effect of the drugs on established PTH, they were administered 90 min after the commencement of intermittent tactile stimulation to the inflamed hindpaw, when thresholds had reached a plateau. Morphine (0.5 mg/kg) and MK801 (0.01 mg/kg) produced only a small reduction in sensitivity acid RP67580 (1 mg/kg) had no effect. These results suggest that the induction of inflammatory progressive tactile hypersensitivity is sensitive to morphine, and to a lesser extent NMDA and NK1 receptor antagonists, but these compounds at a dose that do not alter baseline values, do not normalise established tactile hypersensitivity. (C) 1998 International Association for the Study of Pain. Published by Elsevier Science B.V. C1 Massachusetts Gen Hosp, Neuronal Plast Res Grp, Dept Anesthesia & Crit Care, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. UCL, Dept Anat & Dev Biol, London WC1E 6BT, England. RP Woolf, CJ (reprint author), Massachusetts Gen Hosp, Dept Anesthesia, Neuronal Plast Res Grp, MGH E,4th Floor,Bldg 149,13th St, Charlestown, MA 02129 USA. EM woolf@etherdome.mgh.harvard.edu FU Wellcome Trust NR 74 TC 26 Z9 26 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD JUL PY 1998 VL 77 IS 1 BP 49 EP 57 DI 10.1016/S0304-3959(98)00081-5 PG 9 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 115TZ UT WOS:000075682700006 PM 9755018 ER PT J AU Steinberg, WM Barkin, J Bradley, EL DiMagno, E Layer, P Reber, HA Warshaw, AL AF Steinberg, WM Barkin, J Bradley, EL DiMagno, E Layer, P Reber, HA Warshaw, AL TI Controversies in clinical pancreatology - Workup of a patient with a mass in the head of the pancreas SO PANCREAS LA English DT Editorial Material ID CANCER C1 George Washington Univ, Med Ctr, Div Gastroenterol & Nutr, Washington, DC 20037 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. RP Steinberg, WM (reprint author), George Washington Univ, Med Ctr, Div Gastroenterol & Nutr, Washington, DC 20037 USA. NR 13 TC 12 Z9 12 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0885-3177 J9 PANCREAS JI Pancreas PD JUL PY 1998 VL 17 IS 1 BP 24 EP 30 DI 10.1097/00006676-199807000-00002 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZW557 UT WOS:000074422900002 PM 9667516 ER PT J AU Zerbini, MCN Sredni, ST Grier, H Cristofani, LM Latorre, MRDO Hollister, KA Alves, VAF Weinberg, DS Perez-Atayde, AR AF Zerbini, MCN Sredni, ST Grier, H Cristofani, LM Latorre, MRDO Hollister, KA Alves, VAF Weinberg, DS Perez-Atayde, AR TI Primary malignant epithelial tumors of the liver in children: A study of DNA content and oncogene expression SO PEDIATRIC AND DEVELOPMENTAL PATHOLOGY LA English DT Article DE hepatoblastoma; hepatocellular carcinoma; children; image analysis; p53; c-erb-B2; immunohistochemistry; survival analysis; multivariate analysis ID HEPATOCELLULAR-CARCINOMA; HEPATITIS-B; P53 GENE; HEPATOBLASTOMA; CHILDHOOD; ADOLESCENTS; FLOW; RHABDOMYOSARCOMA; CYTOMETRY; ANTIGEN AB Primary malignant epithelial tumors of the liver (PMETL) are rare in the pediatric age group, and very little is known about their biology as compared with adult tumors. The prognostic value of the DNA contents measured by image analysis and expression of oncogene c-erb2 and tumor suppressor gene p53 were studied in 30 cases of PMETL in children, including 24 with hepatoblastomas (HB) and 6 with hepatocellular carcinomas (HCC). p53 overexpression was detected in 12 out of 26 cases (46.0%), or in 3 of 5 HCC and 9 of 21 HB cases. A relatively high concordance of staining was observed with the two antibodies used (clone DO7, Dako and clone DO1, Santa Cruz Biotechnology). c-erb-B2 did not yield the characteristic membrane staining in any of the 27 cases in which reliable staining was obtained. However, 1 out of 1 patients with HCC and 1 of 23 with HB revealed strong granular cytoplasmic staining in several neoplastic cells. Interestingly, these were two of the three aneuploid multiploid cases. DNA histograms of 13 out of 29 cases (54.8%) were classified as DNA aneuploid (5/6 HCC and 8/23 HB): nine were hyperdiploid, one was hypodiploid (1HB), and three were multiploid (2HB and 1HCC). In the HB group, DNA aneuploidy was strongly associated with embryonal histological areas, suggesting that a disturbance in the process of cell differentiation is associated with marked genetic aberrations. Only the group of HB was submitted to univariate analysis of survival by the Kaplan-Meier method for age (<24 months vs. greater than or equal to 24 months), sex, preoperative chemotherapy (yes vs. no), residual disease (metastasis, and/or unresectable tumor), p53 expression by immunohistochemistry (positive vs. negative), and DNA ploidy (diploid vs. aneuploid). Only residual disease at the time of diagnosis (P < 0.017) and preoperative chemotherapy (0.030) were found to be negatively correlated with biological behavior estimated as overall survival. DNA aneuploidy tumors (P < 0.125) and male patients (P = 0.123) showed a trend toward a more aggressive clinical behavior, although the difference was not statistically significant. Combining DNA ploidy and residual disease, patients were categorized into three groups: group I, patients with no adverse prognostic factors, i.e., diploid tumors without residual disease; group II, patients with only one adverse prognostic factor, i.e., aneuploid tumor or residual disease; and group III, patients with both adverse factors, aneuploid tumors and residual disease at time of diagnosis. A log-rank test comparing the three survival curves showed a statistically significant difference between them (P < 0.003). Although the series of cases is small, the results of this study highlight the importance of including DNA ploidy in the protocols designed for HB in children by international cooperative groups. C1 Childrens Hosp, Boston, MA 02115 USA. Univ Sao Paulo, Sch Med, BR-01246 Sao Paulo, Brazil. Univ Sao Paulo, Sch Med, Dept Pathol, BR-01246903 Sao Paulo, Brazil. Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Inst, BR-05403900 Sao Paulo, Brazil. Univ Sao Paulo, Sch Publ Hlth, BR-01246904 Sao Paulo, Brazil. Adolf Lutz Inst, BR-01246901 Sao Paulo, Brazil. RP Perez-Atayde, AR (reprint author), Childrens Hosp, 300 Longwood Ave, Boston, MA 02115 USA. RI Latorre, Maria/J-5780-2014; Zerbini, Maria Claudia/D-1586-2012 OI Latorre, Maria/0000-0002-5189-3457; Zerbini, Maria Claudia/0000-0002-7408-9816 NR 42 TC 7 Z9 8 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 1093-5266 J9 PEDIATR DEVEL PATHOL JI Pediatr. Dev. Pathol. PD JUL-AUG PY 1998 VL 1 IS 4 BP 270 EP 280 DI 10.1007/s100249900039 PG 11 WC Pathology; Pediatrics SC Pathology; Pediatrics GA 142JT UT WOS:000077197700003 PM 10463288 ER PT J AU Newacheck, PW Strickland, B Shonkoff, JP Perrin, JM McPherson, M McManus, M Lauver, C Fox, H Arango, P AF Newacheck, PW Strickland, B Shonkoff, JP Perrin, JM McPherson, M McManus, M Lauver, C Fox, H Arango, P TI An epidemiologic profile of children with special health care needs SO PEDIATRICS LA English DT Article DE children with special health care needs; chronic illness; children; National Health Interview Survey ID CHRONIC ILLNESS; WELL AB Objective. To present an epidemiologic profile of children with special health care needs using a new definition of the population developed by the federal Maternal and Child Health Bureau. Methods. We operationalized the new definition using the recently released 1994 National Health Interview Survey on Disability. Estimates are based on 30 032 completed interviews for children <18 years old. The overall response rate was 87%. Results. Eighteen percent of US children <18 years old in 1994, or 12.6 million children nationally, had a chronic physical, developmental, behavioral, or emotional condition and required health and related services of a type or amount beyond that required by children generally. This estimate includes children with existing special health care needs but excludes the at-risk population. Prevalence was higher for older children, boys, African-Americans, and children from low-income and single-parent households. Children with existing special health care needs had three times as many bed days and school absence days as other children. An estimated 11% of children with existing special health care needs were uninsured, 6% were without a usual source of health care, 18% were reported as dissatisfied with one or more aspects of care received at their usual source of care, and 13% had one or more unmet health needs in the past year. Conclusions. A substantial minority of US children were identified as having an existing special health care need using national survey data. Children with existing special health care needs are disproportionately poor and socially disadvantaged. Moreover, many of these children face significant barriers to health care. C1 Univ Calif San Francisco, Inst Hlth Policy Studies, San Francisco, CA 94109 USA. Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94109 USA. Brandeis Univ, Florence Heller Grad Sch, Waltham, MA 02254 USA. Massachusetts Gen Hosp, Ambulatory Care Programs, Boston, MA 02114 USA. Kansas State Bur Children Youth & Families, Topeka, KS USA. RP Newacheck, PW (reprint author), Univ Calif San Francisco, Inst Hlth Policy Studies, 1388 Sutter St,Suite 1100, San Francisco, CA 94109 USA. NR 24 TC 313 Z9 320 U1 0 U2 9 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JUL PY 1998 VL 102 IS 1 BP 117 EP 123 DI 10.1542/peds.102.1.117 PG 7 WC Pediatrics SC Pediatrics GA 100CF UT WOS:000074795800020 PM 9651423 ER PT J AU McPherson, M Arango, P Fox, H Lauver, C McManus, M Newacheck, PW Perrin, JM Shonkoff, JP Strickland, B AF McPherson, M Arango, P Fox, H Lauver, C McManus, M Newacheck, PW Perrin, JM Shonkoff, JP Strickland, B TI A new definition of children with special health care needs SO PEDIATRICS LA English DT Editorial Material ID CHRONIC ILLNESS C1 Maternal & Child Hlth Bur, Div Serv Children Special Hlth Care Needs, Integrated Serv Branch, Rockville, MD 20857 USA. State Kansas, Bur Children Youth & Families, Topeka, KS USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Ambulatory Care Programs, Boston, MA 02114 USA. Brandeis Univ, Florence Heller Grad Sch, Waltham, MA 02254 USA. RP McPherson, M (reprint author), Maternal & Child Hlth Bur, Div Serv Children Special Hlth Care Needs, Integrated Serv Branch, Room 18A27,Parklawn Bldg,5600 Fishers Ln, Rockville, MD 20857 USA. RI Vollrath, Margarete/G-1297-2011 NR 17 TC 526 Z9 538 U1 0 U2 23 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JUL PY 1998 VL 102 IS 1 BP 137 EP 140 DI 10.1542/peds.102.1.137 PG 4 WC Pediatrics SC Pediatrics GA 100CF UT WOS:000074795800037 PM 9714637 ER PT J AU Nathan, DG AF Nathan, DG TI Prospective on Thalassemia SO PEDIATRICS LA English DT Article; Proceedings Paper CT Special Symposium on Pioneers and Modern Ideas, at the 1996 Annual Meeting of the American-Academy-of-Pediatrics CY OCT 26-30, 1996 CL BOSTON, MASSACHUSETTS SP Amer Acad Pediat C1 Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Nathan, DG (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 10 TC 2 Z9 2 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JUL PY 1998 VL 102 IS 1 SU 2 BP 281 EP 283 PG 3 WC Pediatrics SC Pediatrics GA 100CH UT WOS:000074796000006 PM 9719796 ER PT J AU Lin, AE Lippe, B Rosenfeld, RG AF Lin, AE Lippe, B Rosenfeld, RG TI Further delineation of aortic dilation, dissection, and rupture in patients with Turner syndrome SO PEDIATRICS LA English DT Article DE Turner syndrome; cardiovascular malformation; dysmorphic syndrome; aortic dilation; aortic dissection ID ANEURYSMS; CHILDREN AB Objective. Although cardiovascular malformations (CVMs) are well-recognized congenital anomalies in Turner syndrome, aortic dilation and dissection are less common and less familiar. Most of the relevant literature is limited to single cases reports or small series. We sought to increase the information available about the frequency and characteristics of aortic dilation in patients with Turner syndrome. Design. A 1-page survey of cardiac abnormalities, including aortic dilation, was mailed to similar to 1000 (1040 verified) members of the Turner Syndrome Society as an enclosure in the June 1997 newsletter. We also conducted a literature review. Participants. A total of 245 patients or families of patient members of the Turner Syndrome Society responded to the survey (similar to 24% response rate). Results. A CVM was reported in 120 of 232 (52%) respondents to this questionnaire. Obstructive lesions of the left side of the heart predominated and included bicuspid aortic valve (38%) and coarctation (41%). Aortic dilation was reported in at least 15 of 237 respondents (6.3%; 95% confidence interval: 3.6%-10.3%); 2 of 15 (13%) had dissection. Twelve of 15 (80%) patients had an associated risk factor for aortic dilation such as a CVM or hypertension. The 3 (20%) patients who did not have a CVM or hypertension were all younger than 21 years, In the entire group with aortic dilation, 10 of 15 (67%) patients were younger than 21 years. All patients with aortic dilation had involvement of the ascending aorta, and 2 had additional involvement of the descending aorta distal to a repaired coarctation. An update of the literature revealed 68 patients with aortic dilation, dissection, or rupture. An associated CVM or hypertension was reported in 53 of 59 (90%) informative patients. At least 6 (10%) had no predisposing risk factor (information was inadequate for 9 of 68 patients). The following patterns of aortic involvement were identified: ascending +/- descending aorta with coarctation (14); ascending +/- descending aorta without coarctation (39); descending aorta with coarctation (3); descending thoracic or abdominal aorta without coarctation (4); and unspecified (8). Dissection or rupture was reported in 42/68 (62%). Two reported patients died suddenly from aortic dissection in the third trimester of assisted pregnancy. At least 20 (29%) patients were younger than 21 years. One of the 6 (17%) patients with isolated aortic dilation was in this younger group. Conclusions. More information is needed about the frequency and natural history of aortic dilation in Turner syndrome. This work contributes new patient data and increases the literature review. Despite the well-recognized limitations of self-reporting, this survey detected aortic dilation with or without dissection in similar to 6% of patients with Turner syndrome. Although rare, this is a potentially catastrophic occurrence, warranting greater awareness among health professionals. In this study and the literature, the vast majority of patients with aortic dilation have an associated risk factor such as a CVM, typically bicuspid aortic valve or coarctation, or systemic hypertension These patients represent a higher risk group that should be followed appropriately, usually under the direction of a cardiologist. Patients undergoing assisted pregnancy also should be evaluated closely. It is generally accepted that at the time of diagnosis of Turner syndrome, all patients should have a complete cardiology evaluation including echocardiography. The small number of patients with aortic dilation without a CVM, who would not be under the long-term care of a cardiologist, makes it prudent to screen all patients with Turner syndrome for this potentially lethal abnormality. The specific timing for this screening is controversial. Our recommendations for prospective imaging do not represent a rigid standard of care. C1 Massachusetts Gen Hosp, Genet & Teratol Unit, Boston, MA 02114 USA. Univ Calif Los Angeles, Sch Med, Dept Pediat, Los Angeles, CA 90024 USA. Pharmacia & Upjohn Inc, Peptide Hormones Grp, Los Angeles, CA USA. Oregon Hlth Sci Univ, Dept Pediat, Doernbecher Childrens Hosp, Portland, OR 97201 USA. RP Lin, AE (reprint author), Massachusetts Gen Hosp, Genet & Teratol Unit, Warren 801,32 Fruit St, Boston, MA 02114 USA. NR 46 TC 67 Z9 71 U1 0 U2 2 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JUL PY 1998 VL 102 IS 1 AR e12 DI 10.1542/peds.102.1.e12 PG 9 WC Pediatrics SC Pediatrics GA 100CF UT WOS:000074795800065 PM 9651464 ER PT J AU Aveline, BM Sattler, RM Redmond, RW AF Aveline, BM Sattler, RM Redmond, RW TI Environmental effects on cellular photosensitization: Correlation of phototoxicity mechanism with transient absorption spectroscopy measurements SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID PHOTOPHYSICAL PROPERTIES; SINGLET OXYGEN; PHOTODYNAMIC THERAPY; 3,3'-DIALKYLTHIACARBOCYANINE DYES; ZINC(II) PHTHALOCYANINE; UNILAMELLAR LIPOSOMES; COLORIMETRIC ASSAY; FLASH-PHOTOLYSIS; ORGANIZED MEDIA; EXCITED-STATES AB Little is directly known about the influence of the local environment experienced by a photosensitizer in a biological system on its photophysics and photochemistry. In this paper, we have addressed this issue by correlating mechanistic studies using laser flash photolysis with cellular phototoxicity data, obtained under the same experimental conditions. In particular, we have focused on the interaction between local concentrations of photosensitizer (deuteroporphyrin) and oxygen in determining the mechanism of phototoxicity in L1210 cells. In cells, as well as in models such as liposomes and red blood cell ghosts, hypochromicity and a reduction in fluorescence and intersystem crossing yields are observed on increasing the photosensitizer concentration between 0.5 and 20 mu M, which illustrates the onset of a self-association. In aerated cellular preparations, the phototoxicity is predominantly type II (singlet oxygen) for all concentrations studied but an oxygen-independent mechanism occurs at the higher concentrations in deaerated samples. These observations are readily explained by consideration of triplet state kinetics as a function of oxygen and photosensitizer concentrations in cells. The rate constant for quenching of the photosensitizer triplet state by oxygen in cells was measured as 6.6 x 10(8) M-1 s(-1) and by photosensitizer ground state as similar to 10(6)M(-1) s(-1) (in terms of local concentration). The latter reaction gave rise to a long-lived species that is presumably responsible for the oxygen-independent phototoxicity observed at the higher photosensitizer concentrations used. This self-quenching of the triplet state is postulated to arise from electron transfer resulting in radical ion formation. Under conditions where no self-quenching contributes, the phototoxicity measured as a function of oxygen concentration correlates well with a model based on the determined kinetic parameters, thus, unambiguously proving the intermediacy of singlet oxygen. These effects should be borne in mind when interpreting phototoxicity mechanisms from in vitro cell studies. The excellent correlation achieved between laser flash photolysis data and measured phototoxicity gives credence to the direct use of photophysical techniques to elucidate photochemical mechanisms in biological media. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Wellman Labs Photomed, Boston, MA 02114 USA. RP Redmond, RW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Wellman Labs Photomed, W-224, Boston, MA 02114 USA. FU NCI NIH HHS [R01 CA68524] NR 62 TC 33 Z9 35 U1 0 U2 7 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD JUL PY 1998 VL 68 IS 1 BP 51 EP 62 DI 10.1111/j.1751-1097.1998.tb03252.x PG 12 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 102PE UT WOS:000074932400009 PM 9679451 ER PT J AU Butler, PEM Lee, WPA Sims, CD Randolph, MA Vacanti, CA Yaremchuk, MJ AF Butler, PEM Lee, WPA Sims, CD Randolph, MA Vacanti, CA Yaremchuk, MJ TI Cell transplantation from limb allografts SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the Plastic-Surgery-Research-Council CY JUN 04-07, 1994 CL ANN ARBOR, MICHIGAN SP Plast Surg Res Council ID VASCULARIZED BONE ALLOGRAFTS; CYCLOSPORIN-A; INDEFINITE SURVIVAL; TISSUE ALLOGRAFTS; RATS; ALLOTRANSPLANTATION; IRRADIATION; MYOBLASTS; CARTILAGE; GROWTH AB A murine model of skeletal tissue transplantation was developed to study the allograft rejection process in mice for limb allograft transplantation. Muscle, bone, and skin have been shown to be strong antigenic stimuli in vascularized allograft models, and cells from these sources were used for transplantation. Using enzimatic digestion, keratinocytes, myocytes, and osteocytes were harvested from B10.A mice tissues, dissociated into single cells, and then grown in culture for 14 to 21 days. Each cell type was marked with an intracellular fluorescent marker before transplantation of the cells into pockets in the rectus abdominis muscle of a syngenic host. All cell types remained viable and were detectable 2 weeks following transplantation when examined histologically and observed under a fluorescent microscope. Transplanted osteocytes were found to produce bone 8 weeks following transplantation. These results demonstrate that individual cells transplanted into muscle pockets survive and have the ability to produce extracellular matrix in this mouse model of skeletal tissue transplantation. Use of this model will allow transplantation of the cellular components comprising limb allografts to study the relative antigenicities and the rejection of the separate cells with the advanced immunologic techniques available for mice. A better understanding of immunologic responses to these individual tissue components may enable specific donor tissue or host immune modification to achieve skeletal tissue transplantation without immunosuppression. These findings are particularly valuable to the field of tissue engineering where allogeneic cells may be used in cell/polymer constructs for reconstructive procedures. C1 Massachusetts Gen Hosp, Ambulatory Care Ctr 453, Div Plast Surg, Boston, MA 02114 USA. Univ Massachusetts, Med Ctr, Dept Anesthesia, Worcester, MA USA. RP Lee, WPA (reprint author), Massachusetts Gen Hosp, Ambulatory Care Ctr 453, Div Plast Surg, Boston, MA 02114 USA. NR 40 TC 9 Z9 11 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD JUL PY 1998 VL 102 IS 1 BP 161 EP 168 DI 10.1097/00006534-199807000-00025 PG 8 WC Surgery SC Surgery GA ZX019 UT WOS:000074472100025 PM 9655421 ER PT J AU Gritz, ER Thompson, B Emmons, K Ockene, JK McLerran, DF Nielsen, IR AF Gritz, ER Thompson, B Emmons, K Ockene, JK McLerran, DF Nielsen, IR CA Working Well Res Grp TI Gender differences among smokers and quitters in the Working Well Trial SO PREVENTIVE MEDICINE LA English DT Article DE smoking cessation; women and smoking; gender differences; blue-collar; worksite smoking cessation ID SMOKING CESSATION; UNITED-STATES; CIGARETTE-SMOKING; PROGRAM; CANCER; TRENDS; WOMEN; INTERVENTION; EXPERIENCE; BEHAVIORS AB Background Gender differences in smoking and smoking cessation among participants in the Working Well Trial are characterized. Methods. A prospective randomized matched-pair evaluation was conducted among 90 predominantly blue-collar worksites. Cross-sectional surveys of employees' tobacco use behaviors were conducted at baseline and after a 2.5-year smoking cessation intervention. Respondents included 5,523 females and 12,313 males at baseline and 4,663 females and 10,919 males at follow-up. The main outcome measures included self-reported continuous smoking abstinence rates for 7 days and for 6 months. Results. Smoking prevalence was significantly higher for women than for men at baseline, but not at follow-up, Variables believed to influence smoking cessation were compared at baseline. Significant gender differences were found for number of cigarettes smoked/day number of previous quit attempts, job strain, stage of change, and behavioral processes of change, At follow-up, no gender differences in quit rates were observed; however, women in the intervention condition were more likely to quit than women in the control condition, whereas no differences were seen among men by treatment condition, Conclusions, Gender is not a strong predictor of smoking cessation in this population; however, women were more likely to quit with an intervention than without one. (C) 1998 American Health Foundation and Academic Press. C1 Univ Texas, Md Anderson Canc Ctr, Dept Behav Sci, Houston, TX 77030 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98101 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Massachusetts, Sch Med, Worcester, MA 01655 USA. RP Gritz, ER (reprint author), Univ Texas, Md Anderson Canc Ctr, Dept Behav Sci, Box 243,1515 Holcombe Blvd, Houston, TX 77030 USA. FU NCI NIH HHS [U01 CA51687, U01 CA51671, U01 CA51686] NR 54 TC 53 Z9 55 U1 2 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD JUL-AUG PY 1998 VL 27 IS 4 BP 553 EP 561 DI 10.1006/pmed.1998.0325 PG 9 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA ZZ249 UT WOS:000074710500008 PM 9672949 ER PT J AU Engler, MM Schambelan, M Engler, MB Ball, DL Goodfriend, TL AF Engler, MM Schambelan, M Engler, MB Ball, DL Goodfriend, TL TI Effects of dietary gamma-linolenic acid on blood pressure and adrenal angiotensin receptors in hypertensive rats SO PROCEEDINGS OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Article ID FATTY-ACIDS; EVENING PRIMROSE; OIL; REACTIVITY; RESPONSES; BORAGE; N-6 AB In a previous study, we showed that dietary gamma linolenic acid (GLA), an omega-6 polyunsaturated fatty acid found in borage oil (BOR), attenuates the development of hypertension in young spontaneously hypertensive rats (SHR). The purpose of this study was to determine the effects of dietary GLA on established hypertension in adult rats, as well as its effects on components of the renin-angiotensin-aldosterone axis. For 5 weeks, male SHR (14-15 weeks old) were fed a basal fat-free diet to which 11% by weight of sesame oil (SES) or BOR was added. Systolic blood pressure (SBP), determined by the tail cuff method, and weight were measured weekly. Plasma renin activity (PRA), aldosterone (PA), and corticosterone (PC) levels were measured at the end of the dietary treatments. The adrenal glands were homogenized, and angiotensin II (ANG II) binding was measured and plotted according to Scatchard, Systolic blood pressure was 12 mmHg lower at Week 5 in SHR fed the BOR diet compared to SES-fed rats (P < 0.005). Weight gains were similar in both dietary groups. Plasma aldosterone was lower, PRA was higher, and the PA/PRA ratio was significantly lower (P < 0.05) in BOR-fed rats. Levels of PC were the same in both groups. The BOR-enriched diet reduced adrenal ANG II receptor density and affinity compared to the SES diet. Results suggest that BOR inhibits adrenal responsiveness to ANG II by an action on adrenal receptors. Our findings demonstrated that dietary GLA lowers SEP in adult SHR, This effect may be mediated, at least in part, by interference with the renin-angiotensin-aldosterone system at the level of adrenal ANG II receptors. C1 Univ Calif San Francisco, Dept Physiol Nursing, Lab Cardiovasc Physiol, San Francisco, CA 94143 USA. Univ Calif San Francisco, San Francisco Gen Hosp, Div Endocrinol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Univ Wisconsin, Dept Med, Madison, WI 53705 USA. Univ Wisconsin, Dept Pharmacol, Madison, WI 53705 USA. William S Middleton Mem Vet Hosp, Madison, WI 53705 USA. RP Engler, MM (reprint author), Univ Calif San Francisco, Dept Physiol Nursing, Lab Cardiovasc Physiol, Room N611Y,Box 0610, San Francisco, CA 94143 USA. FU NHLBI NIH HHS [HL 11046] NR 22 TC 22 Z9 24 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0037-9727 J9 P SOC EXP BIOL MED JI Proc. Soc. Exp. Biol. Med. PD JUL PY 1998 VL 218 IS 3 BP 234 EP 237 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA ZU828 UT WOS:000074239500011 PM 9648942 ER PT J AU Petrie, EC Veith, RC Szot, P AF Petrie, EC Veith, RC Szot, P TI Bupropion and desipramine increase dopamine transporter mRNA expression in the ventral tegmental area substantia nigra of rat brain SO PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY LA English DT Review DE bupropion; desipramine; dopamine; mRNA; substantia nigra; transporter; ventral tegmental area ID MESSENGER-RNA; NUCLEUS-ACCUMBENS; LOCUS-CERULEUS; NOREPINEPHRINE TRANSPORTER; INVIVO MICRODIALYSIS; PREFRONTAL CORTEX; BINDING-SITES; IN-VIVO; ANTIDEPRESSANTS; BLOCKADE AB 1. Regulation of dopamine transporter (DAT) mRNA was studied in rats treated with the DAT blocker bupropion (BUP; 15 or 30 mg/kg tid x 2d), the norepinephrine transporter blocker desipramine (DMI; 10 mg/kg/d x 2d), or saline. 2. mRNA expression was assessed via in situ hybridization histochemistry, 3. BUP and DMI both increased DAT mRNA expression in the ventral tegmental area/substantia nigra. 4. These findings suggest that DAT mRNA expression in the brain may be regulated by both noradrenergic and dopaminergic mechanisms. C1 Vet Affairs Puget Sound Hlth Care Syst, Mental Hlth Serv 116, Seattle, WA 98108 USA. Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Petrie, EC (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Mental Hlth Serv 116, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 36 TC 15 Z9 15 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-5846 J9 PROG NEURO-PSYCHOPH JI Prog. Neuro-Psychopharmacol. Biol. Psychiatry PD JUL PY 1998 VL 22 IS 5 BP 845 EP 856 DI 10.1016/S0278-5846(98)00044-X PG 12 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA ZZ480 UT WOS:000074733600010 PM 9723124 ER PT J AU Becker, AE AF Becker, AE TI Postpartum illness in Fiji: A sociosomatic perspective SO PSYCHOSOMATIC MEDICINE LA English DT Article DE sociosomatic; embodiment; social supports; postpartum illness; Fiji ID DEPRESSION; CULTURE AB Objective: The purpose of this study is to explore the apparent social mediation of a postpartum somatic illness, na tadoka ni vasucu, occurring among ethnic Fijian women. Method: During their first two postpartum days, 85 consecutive newly delivered ethnic Fijian women were recruited for a prospective study on na tadoka ni vasucu at the Sigatoka District Hospital in Nadroga, Fiji. Subjects underwent translated structured interviews and responded to the Kellner Symptom Questionnaire and to visual analog scales to assess social supports and occurrence of mood symptoms or an episode of na tadoka. ni vasucu in the postpartum period. Semistructured ethnographic interviews were also conducted with subjects who reported an episode of na tadoka ni vasucu. Data were collected in the initial postpartum days and again at 2 to 5 months postpartum; 82 women completed the study. Results: Na tadoka ni vasucu is a somatic syndrome occurring in 9% (N = 7) of this sample. Both quantitative and narrative data demonstrate that this syndrome is associated with perceived inferior social supports. Despite its relatively infrequent occurrence and benign clinical course, the disorder is a subject of serious social concern within the Fijian community. Conclusions: Although na tadoka ni vasucu seems to be clinically trivial, because of its cultural salience it is nonetheless able to mobilize intensive social surveillance and care for the postpartum mother. The moral concern generated by this culturally marked disorder, as well as its association with perceived inferior social supports, suggest a dialectical relationship between somatic idiom and its social context. C1 Harvard Univ, Sch Med, Dept Social Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Becker, AE (reprint author), Harvard Univ, Sch Med, Dept Social Med, 641 Huntington Ave, Boston, MA 02115 USA. NR 30 TC 18 Z9 18 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD JUL-AUG PY 1998 VL 60 IS 4 BP 431 EP 438 PG 8 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 105BY UT WOS:000075053500006 PM 9710288 ER PT J AU Falk, WE AF Falk, WE TI Concise guide to geriatric psychiatry, 2nd edition SO PSYCHOSOMATICS LA English DT Book Review C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Falk, WE (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD JUL-AUG PY 1998 VL 39 IS 4 BP 388 EP 388 PG 1 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 104KZ UT WOS:000075014800012 ER PT J AU Bronheim, HE Fulop, G Kunkel, EJ Muskin, PR Schindler, BA Yates, WR Shaw, R Steiner, H Stern, TA Stoudemire, A AF Bronheim, HE Fulop, G Kunkel, EJ Muskin, PR Schindler, BA Yates, WR Shaw, R Steiner, H Stern, TA Stoudemire, A TI The Academy of Psychosomatic Medicine practice guidelines for psychiatric consultation in the general medical setting SO PSYCHOSOMATICS LA English DT Review ID PSYCHOTROPIC-DRUG USE; C-L PSYCHIATRY; LIAISON PSYCHIATRY; CONSTANT OBSERVATION; PSYCHOPHARMACOLOGICAL ISSUES; COMPETENCY EVALUATIONS; MECHANICAL RESTRAINTS; PERSONALITY-DISORDERS; ORGAN-TRANSPLANTATION; SURGICAL PATIENTS AB This practice guideline seeks to provide guidance to psychiatrists who regularly evaluate and manage patients with medical illnesses. The guideline is intended to delineate the knowledge base, professional expertise, and integrated clinical approach necessary was drafted by a work group consisting of psychiatrists with clinical and research expertise in the field, who undertook a comprehensive review of the literature. The guideline was reviewed by the executive council of the Academy of Psychosomatic Medicine and revised prior to final approval. Some of the topics discussed include qualifications of C-L consultants, patient assessment, psychiatric interventions (e.g., psychotherapy, pharmacotherapy), medicolegal issues, and child and adolescent consultations. C1 Mt Sinai Hosp, Div Consultat & Behav Med, Dept Psychiat, New York, NY 10029 USA. Merck Medco Managed Care, LLC, Montvale, NJ USA. Thomas Jefferson Univ, Jefferson Med Coll, Dept Psychiat, Philadelphia, PA 19107 USA. Columbia Presbyterian Med Ctr, Div Consultat Liaison Psychiat, New York, NY 10032 USA. Allegheny Univ Hlth Sci, Med Ctr, Dept Psychiat, Philadelphia, PA 19102 USA. Univ Oklahoma, Hlth Sci Ctr, Dept Psychiat, Tulsa, OK USA. Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. Massachusetts Gen Hosp, Psychiat Consultat Serv, Boston, MA 02114 USA. Emory Cent Clin, Sect Psychiat, Atlanta, GA USA. RP Bronheim, HE (reprint author), 1155 Park Ave, New York, NY 10028 USA. NR 141 TC 39 Z9 40 U1 2 U2 3 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD JUL-AUG PY 1998 VL 39 IS 4 BP S8 EP S30 PG 23 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 104KZ UT WOS:000075014800023 PM 9691717 ER PT J AU Keuthen, NJ O'Sullivan, RL Sprich-Buckminster, S AF Keuthen, NJ O'Sullivan, RL Sprich-Buckminster, S TI Trichotillomania: Current issues in conceptualization and treatment SO PSYCHOTHERAPY AND PSYCHOSOMATICS LA English DT Review DE trichotillomania; hairpulling; obsessive-compulsive disorder; behavioral treatment; pharmacotherapy; review ID OBSESSIVE-COMPULSIVE DISORDER; CEREBRAL GLUCOSE-METABOLISM; SELF-INJURIOUS-BEHAVIOR; MGH HAIRPULLING SCALE; CHILDHOOD TRICHOTILLOMANIA; HABIT-REVERSAL; DOUBLE-BLIND; LONG-TERM; CLINICAL CHARACTERISTICS; THUMB-SUCKING AB Trichotillomania is a little-known disorder with wider prevalence and more significant consequences than previously believed. While sharing similarities with obsessive-compulsive disorder, compelling differences from it have also been noted. This fact, coupled with recognized overlap with other obsessive-compulsive spectrum disorders, has resulted in the ongoing evolution of our conceptualization of this illness. While empirical evidence supports the use of behavioral treatment and pharmacotherapy, considerable research is still needed before we can promise highly effective interventions tailored to the individual hairpuller. This review will summarize the evidence supporting, as well as challenging, a hypothesized link with obsessive-compulsive disorder. Current treatment approaches will be reviewed, as well as evidence for their efficacy. Suggestions will be made for future directions in this field. C1 Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Keuthen, NJ (reprint author), Massachusetts Gen Hosp E, OCD Clin & Res Unit, 9th Floor,13th St, Charlestown, MA 02129 USA. EM Keuthen@psych.mgh.harvard.edu RI Citations, TLC SAB/C-4006-2011 NR 175 TC 30 Z9 31 U1 0 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0033-3190 J9 PSYCHOTHER PSYCHOSOM JI Psychother. Psychosom. PD JUL-OCT PY 1998 VL 67 IS 4-5 BP 202 EP 213 DI 10.1159/000012282 PG 12 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 107TP UT WOS:000075226200003 PM 9693347 ER PT J AU Tedlow, J Fava, M Uebelacker, L Nierenberg, AA Alpert, JE Rosenbaum, J AF Tedlow, J Fava, M Uebelacker, L Nierenberg, AA Alpert, JE Rosenbaum, J TI Outcome definitions and predictors in depression SO PSYCHOTHERAPY AND PSYCHOSOMATICS LA English DT Article DE depression; fluoxetine ID PSYCHOTHERAPY; OUTPATIENTS; MELANCHOLIA; CRITERIA; DISORDER; PLACEBO AB Background: The definition of outcome in antidepressant treatment studies may be a crucial factor influencing the relationship between possible treatment variables and treatment response. We therefore wanted to investigate possible relationships between baseline severity of depression and anxiety, and different definitions of outcome among outpatients with major depressive disorder undergoing antidepressant treatment. Methods: Two hundred and forty-eight patients diagnosed with major depression with the Structured Clinical Interview for DSM-III-R Diagnosis - Patient Edition were treated with fluoxetine 20 mg/day for 8 weeks. Patients were evaluated both pretreatment and posttreatment with the 17-item Hamilton Rating Scale for Depression (Ham-D-17), the Clinical Global Impressions Scales for Severity (CGI-S) and Improvement (CGI-I). We chose four continuous definitions of response using a linear regression method to analyze the relationship to baseline anxiety and depression. We used a logistic regression analysis for the relationship between seven categorical definitions of response and baseline severity of depression and anxiety. Results: Greater endpoint severity was significantly positively related to greater baseline severity of depression and anxiety. Lesser baseline severity of depression or anxiety predicted a greater degree of response on either the endpoint CGI-I score (with lower scores indicating greater improvement) or the percent change in HAM-D-17 score (with higher percent change indicating greater improvement). For all seven categorical definitions of response, lower baseline scores were significantly related to the probability of being a responder. Conclusions: These findings support the impression that how outcome is defined affects the strength and direction of observed relationships with predictive variables. Methodological implications are discussed. C1 Massachusetts Gen Hosp, Clin Psychopharmacol Unit, Depress Res Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Consolidated Dept Psychiat, Boston, MA USA. RP Tedlow, J (reprint author), Massachusetts Gen Hosp, Clin Psychopharmacol Unit, Depress Clin & Res Program, WACC 812,15 Parkman St, Boston, MA 02114 USA. OI Alpert, Jonathan/0000-0002-4332-908X NR 28 TC 62 Z9 64 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0033-3190 J9 PSYCHOTHER PSYCHOSOM JI Psychother. Psychosom. PD JUL-OCT PY 1998 VL 67 IS 4-5 BP 266 EP 270 DI 10.1159/000012290 PG 5 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 107TP UT WOS:000075226200011 PM 9693355 ER PT J AU Coumas, JM Palmer, WE AF Coumas, JM Palmer, WE TI Knee arthrography - Evolution and current status SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID DOUBLE-CONTRAST ARTHROGRAPHY; HYALINE CARTILAGE DEFECTS; FEMORAL JOINT MECHANICS; MR-IMAGING EVALUATION; MENISCAL TEARS; CHONDROMALACIA PATELLAE; ARTICULAR-CARTILAGE; OSTEOCHONDRITIS-DISSECANS; ARTHROSCOPIC REPAIR; DIAGNOSIS AB This article explores arthrography of the knee beginning with a brief historical perspective of conventional knee arthrography and culminating in direct and indirect MR arthrography of the knee. This article discusses the advantages of MR arthrography in the radiologic assessment of the postoperative meniscus, abnormalities of articular cartilage, and synovial-based processes. C1 Carolinas Med Ctr, Dept Radiol, Charlotte, NC 28203 USA. Charlotte Radiol, Charlotte, NC USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Coumas, JM (reprint author), Carolinas Med Ctr, Dept Radiol, 1000 Blythe Blvd, Charlotte, NC 28203 USA. NR 98 TC 18 Z9 18 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0033-8389 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD JUL PY 1998 VL 36 IS 4 BP 703 EP + DI 10.1016/S0033-8389(05)70057-9 PG 27 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZZ444 UT WOS:000074730000008 PM 9673648 ER PT J AU de Marco, G Bogdanov, A Marecos, E Moore, A Simonova, M Weissleder, R AF de Marco, G Bogdanov, A Marecos, E Moore, A Simonova, M Weissleder, R TI MR imaging of gene delivery to the central nervous system with an artificial vector SO RADIOLOGY LA English DT Article DE genes and genetics; magnetic resonance (MR), utilization ID RETROGRADE AXONAL-TRANSPORT; THERAPY; ANTEROGRADE; INVIVO; CELLS AB PURPOSE: To determine whether gene delivery by means of a synthetic nonviral DNA delivery system that is capable of gene transfer can be mapped with magnetic resonance (MR) imaging. MATERIALS AND METHODS: The DNA delivery system consisted of aminated (poly-L-lysine-conjugated) dextran chains anchored together with a central super-paramagnetic core. Three different types of constructs were synthesized that differed in their amino content and, thus, DNA-loading capacity. The model plasmid consisted of complementary DNA encoding for humanized green fluorescent protein. Constructs were tested in cell culture and in vivo in a rat model. RESULTS: All three constructs were capable of transfecting human cells in culture with transfection efficiencies ranging from 0.3% to 4.1%, which is similar to that of diethylaminoethyl-dextran. MR imaging experiments showed that DNA constructs induced signal intensity changes that co-localized with phosphorus-33-labeled plasmid distribution at autoradiography. After injection of the constructs into the corpus callosum of rats, weak green fluorescent protein expression of neuronal and glial cells could be detected at immunohistologic examination. CONCLUSION: Dextran-based nonviral DNA delivery systems are capable of transfecting cells and can be visualized with MR imaging. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Dept Radiol, Charlestown, MA 02129 USA. RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Dept Radiol, Charlestown, MA 02129 USA. FU NINDS NIH HHS [5RO1-NS35258-02] NR 37 TC 27 Z9 28 U1 1 U2 4 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUL PY 1998 VL 208 IS 1 BP 65 EP 71 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZV355 UT WOS:000074296300012 PM 9646794 ER PT J AU Boppart, SA Bouma, BE Pitris, C Southern, JF Brezinski, ME Fujimoto, JG AF Boppart, SA Bouma, BE Pitris, C Southern, JF Brezinski, ME Fujimoto, JG TI Intraoperative assessment of microsurgery with three-dimensional optical coherence tomography SO RADIOLOGY LA English DT Article DE blood vessels, stenosis or obstruction; lasers; nerves, injuries; optical coherence tomography; surgery ID LASER SOURCE; RESOLUTION; BIOPSY AB PURPOSE: To evaluate three-dimensional optical coherence tomography (OCT) for use in the assessment of the microsurgical anastomoses of vessels and nerves. MATERIALS AND METHODS: OCT is an optical analogue of ultrasonography and is capable of imaging nontransparent biologic tissue by detecting backscattered infrared light. Cross-sectional in vitro images of rabbit and human vessels and nerves were obtained in as little as 125 msec at 10-mu m resolution by using a solid-state laser as a light source. A surgical microscope was integrated with OCT to perform simultaneous imaging with en face visualization. Cross-sectional images were assembled to produce three-dimensional reconstructions of microsurgical specimens. RESULTS: Three-dimensional OCT reconstructions depicted the structure within an arterial anastomosis and helped identify sites of luminal obstruction. The longitudinal spatial orientation of individual nerve fascicles was tracked in three dimensions to identify changes in position. In vitro human arteries and nerves embedded in highly scattering tissue and not visible at microscopy were located and imaged with OCT at eight frames per second. CONCLUSION: The three-dimensional, micrometer-scale, diagnostic imaging capabilities of OCT permit rapid feedback for assessment of microsurgical procedures. OCT technology can be readily integrated with surgical microscopes and has potential for intraoperative monitoring to improve patient outcome. C1 MIT, Dept Elect Engn & Comp Sci, Elect Res Lab, Cambridge, MA 02139 USA. Harvard Mit Div Hlth Sci & Technol, Boston, MA USA. Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. Harvard Med Sch, Boston, MA 02115 USA. RP Boppart, SA (reprint author), MIT, Dept Elect Engn & Comp Sci, Elect Res Lab, 77 Massachusetts Ave,Rm 36-345, Cambridge, MA 02139 USA. RI Boppart, Stephen/C-7338-2009; OI Pitris, Costas/0000-0002-5559-1050 FU NCI NIH HHS [1-R01-CA75289-01]; NHLBI NIH HHS [1-R29-HL55686-01A1]; PHS HHS [9-RO1-FY11289-11] NR 20 TC 72 Z9 74 U1 0 U2 4 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUL PY 1998 VL 208 IS 1 BP 81 EP 86 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZV355 UT WOS:000074296300014 PM 9646796 ER PT J AU Wysoki, MG Nassar, CJ Koenigsberg, RA Novelline, RA Faro, SH Faerber, EN AF Wysoki, MG Nassar, CJ Koenigsberg, RA Novelline, RA Faro, SH Faerber, EN TI Head trauma: CT scan interpretation by radiology residents versus staff radiologists SO RADIOLOGY LA English DT Article DE brain, injuries; diagnostic radiology, observer performance; education; head, injuries; image, interpretation ID COMPUTED-TOMOGRAPHY; CHEST RADIOGRAPHS; INJURY; EXPERIENCE; MORTALITY; ACCURACY; ERROR; RISK AB PURPOSE: To determine the rate and clinical outcome of discrepancies in interpretation by radiology residents and staff neuroradiologists of posttraumatic cranial computed tomographic (CT) scans. MATERIALS AND METHODS: Prospective evaluation was performed for 419 consecutive emergency posttraumatic cranial CT studies that has been interpreted by radiology residents on call over a 16-month period. Discrepancies between the interpretations made by residents and those made by staff radiologists were divided into two groups; failure to recognize an abnormally (false-negative finding) and interpretation of normal as abnormal (false-positive finding). Discrepancies were considered major if they could affect patient care in the emergency setting and minor if they could not. RESULTS: Major and minor discrepancies were 1.7% and 2.6%, respectively, among interpretations made by residents and those by staff radiologists. Major discrepancies were four subdural hematomas, one pneumocephalus, one hemorrhagic contusion, and one subarachnoid hemorrhage. Minor discrepancies included six skull and five facial fractures. The discrepancy rate was statistically significantly higher (12.2%) when CT findings were abnormal than when they were normal (1.5%). No change in treatment was attributed to the delay in diagnosis. CONCLUSION: A low discrepancy rate was found between interpretations made by radiology residents and those made by staff neuroradiologists of posttraumatic cranial CT scans. There were no adverse clinical outcome. C1 Allegheny Univ Hosp, Dept Radiol, Philadelphia, PA 19129 USA. St Christophers Hosp Children, Dept Radiol, Philadelphia, PA 19133 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Wysoki, MG (reprint author), Allegheny Univ Hosp, Dept Radiol, 3300 Henry Ave, Philadelphia, PA 19129 USA. NR 19 TC 85 Z9 85 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUL PY 1998 VL 208 IS 1 BP 125 EP 128 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZV355 UT WOS:000074296300020 PM 9646802 ER PT J AU Melo, MFV AF Melo, MFV TI Effect of cardiac output on pulmonary gas exchange: role of diffusion limitation with VA/Q mismatch SO RESPIRATION PHYSIOLOGY LA English DT Article DE gas exchange; pulmonary; heterogeneity; model; pulmonary gas exchange; heterogeneity ID RESPIRATORY-DISTRESS SYNDROME; BLOOD-FLOW; SEA-LEVEL; VENTILATION; PERFUSION; IMPAIRMENT; MODEL; LUNG; EXERCISE; O2 AB We studied the effect of the interaction between diffusion limitation and alveolar ventilation to perfusion ratio ((V) over dot(A)/(Q) over dot) mismatch in the relation between blood gas partial pressures and cardiac output ((Q) over dot). The analysis was based on a mathematical model of gas exchange involving two exchanging compartments and a right to left shunt. A system of equations describing alveolar-arterial mass conservation for O-2, CO2 and N-2 and Bohr integration for O-2 and CO2 was iteractively solved to find sets of alveolar and blood gas partial pressures fitting input data. Simulations used values compatible with patients in respiratory failure and neonate piglets. Association of ((V) over dot(A)/(Q) over dot) mismatch and diffusion impairment limited the increase of Pa-O2 with (Q) over dot. A maximum in the Pa-O2 vs. (Q) over dot curve can be attained, further (Q) over dot increases lead to reductions in Pa-O2. The effect was accentuated by increasing ((V) over dot(A)/(Q) over dot) and diffusion to perfusion heterogeneity. Combination of ((V) over dot(A)/(Q) over dot) mismatch and diffusion limitation was synergistic leading to greater reductions in Pa-O2 than expected from simple addition of their independent influences. The findings are compatible with experimental data. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Melo, MFV (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St, Boston, MA 02114 USA. NR 30 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0034-5687 J9 RESP PHYSIOL JI Respir. Physiol. PD JUL PY 1998 VL 113 IS 1 BP 23 EP 32 PG 10 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 121QC UT WOS:000076024000003 ER PT J AU Mellors, JW AF Mellors, JW TI Viral-load tests provide valuable answers SO SCIENTIFIC AMERICAN LA English DT Article C1 Univ Pittsburgh, Med Ctr, HIV AIDS Programs, Pittsburgh, PA 15260 USA. Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Mellors, JW (reprint author), Univ Pittsburgh, Med Ctr, HIV AIDS Programs, Pittsburgh, PA 15260 USA. NR 0 TC 14 Z9 14 U1 0 U2 1 PU SCI AMERICAN INC PI NEW YORK PA 415 MADISON AVE, NEW YORK, NY 10017 USA SN 0036-8733 J9 SCI AM JI Sci.Am. PD JUL PY 1998 VL 279 IS 1 BP 90 EP 93 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZW260 UT WOS:000074391600035 PM 9648302 ER PT J AU Gerweck, LE AF Gerweck, LE TI Tumor pH: Implications for treatment and novel drug design SO SEMINARS IN RADIATION ONCOLOGY LA English DT Article ID P-31 MR SPECTROSCOPY; MAGNETIC-RESONANCE SPECTROSCOPY; SOFT-TISSUE SARCOMAS; EXTRACELLULAR PH; INTRACELLULAR-PH; BLOOD-FLOW; THERAPY; EXPLOITATION; GRADIENT; CANCER C1 Harvard Univ, Sch Med, Dept Radiat Oncol, Massachusetts Gen Hosp, Boston, MA 02192 USA. RP Gerweck, LE (reprint author), Harvard Univ, Sch Med, Dept Radiat Oncol, Massachusetts Gen Hosp, Boston, MA 02192 USA. FU NCI NIH HHS [CA22860] NR 41 TC 104 Z9 106 U1 1 U2 7 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1053-4296 J9 SEMIN RADIAT ONCOL JI Semin. Radiat. Oncol. PD JUL PY 1998 VL 8 IS 3 BP 176 EP 182 DI 10.1016/S1053-4296(98)80043-X PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA ZZ789 UT WOS:000074767300005 PM 9634494 ER PT J AU Huang, CC Faber, PW Persichetti, F Mittal, V Vonsattel, JP MacDonald, ME Gusella, JF AF Huang, CC Faber, PW Persichetti, F Mittal, V Vonsattel, JP MacDonald, ME Gusella, JF TI Amyloid formation by mutant huntingtin: Threshold, progressivity and recruitment of normal polyglutamine proteins SO SOMATIC CELL AND MOLECULAR GENETICS LA English DT Article ID NEURONAL INTRANUCLEAR INCLUSIONS; DISEASE GENE HOMOLOG; AGGREGATES IN-VITRO; GLUTAMINE REPEATS; NEURODEGENERATIVE DISEASES; TISSUE TRANSGLUTAMINASE; EXPANDED POLYGLUTAMINE; NUCLEAR-LOCALIZATION; EMBRYONIC LETHALITY; CAG REPEATS AB Huntington's disease (HD) is caused by an expanded CAG trinucleotide repeat encoding a tract of consecutive glutamines near the amino terminus of huntingtin, a large protein of unknown function. It has been proposed that the expanded polyglutamine stretch confers a new property on huntingtin and thereby causes cell and region-specific neurodegeneration. Genotype-phenotype correlations predict that this novel property appears above a threshold length (similar to 38 glutamines), becomes progressively more evident with increasing polyglutamine length, is completely dominant over normal huntingtin and is not appreciably worsened by a double genetic dose in ND homozygotes. Recently, an amino terminal fragment of mutant huntingtin has been found to form self-initiated fibrillar aggregates in vitro. We have tested the capacity for aggregation to assess whether this property matches the criteria expected for a fundamental role in ND pathogenesis. We find that that in vitro aggregation displays a threshold and progressivity for polyglutamine length remarkably similar to the HD disease process. Moreover the mutant huntingtin amino terminus is capable of recruiting into aggregates normal glutamine tract proteins, such as the amino terminal segments of both normal huntingtin and of TATA-binding protein (TBP). Our examination of in vivo aggregates from HD post-mortem brains indicates that they contain an amino terminal segment of huntingtin of between 179 and 595 residues. They also contain non-huntingtin protein, as evidenced by immunostaining for TBP Interestingly, like the in vitro aggregates, aggregates from ND brain display Congo red staining with green birefringence characteristic of amyloid. Our data support the view that the expanded polyglutamine segment confers on huntingtin a new property that plays a determining role in HD pathogenesis and could be a target for treatment. Moreover the new property might have its toxic consequences by interaction with one or more normal polyglutamine-containing proteins essential for the survival of target neurons. C1 Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Lab Mol Neuropathol, Charlestown, MA 02129 USA. Cold Spring Harbor Lab, Howard Hughes Med Inst, Cold Spring Harbor, NY 11724 USA. RP Gusella, JF (reprint author), Massachusetts Gen Hosp, Mol Neurogenet Unit, Bldg 149,13th St, Charlestown, MA 02129 USA. FU NIMH NIH HHS [MH/NS31862]; NINDS NIH HHS [NS16367, NS32765] NR 49 TC 185 Z9 191 U1 1 U2 6 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0740-7750 J9 SOMAT CELL MOLEC GEN JI Somat.Cell Mol.Genet. PD JUL PY 1998 VL 24 IS 4 BP 217 EP 233 DI 10.1023/B:SCAM.0000007124.19463.e5 PG 17 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA 213JQ UT WOS:000081269300002 PM 10410676 ER PT J AU Ay, H Buonanno, FS Abraham, SA Kistler, JP Koroshetz, WJ AF Ay, H Buonanno, FS Abraham, SA Kistler, JP Koroshetz, WJ TI An electrocardiographic criterion for diagnosis of patent foramen ovale associated with ischemic stroke SO STROKE LA English DT Article DE cerebral ischemia; cerebral infarction; electrocardiography; foramen ovale, patent ID TRANSESOPHAGEAL ECHOCARDIOGRAPHY; CONTRAST ECHOCARDIOGRAPHY; PARADOXICAL EMBOLISM; CRYPTOGENIC STROKE; PREVENTION; DOPPLER; SHUNTS AB Background and Purpose-An M-shaped bifid notch on the ascending branch, or on the zenith, of the R wave in inferior ECG leads (II, III, aVF), so called "crochetage," is an indicator of ostium secundum atrial septal defects. The pathophysiology underlying this finding remains unknown. A crochetage pattern has not been previously reported in patients with patent foramen ovale (PFO); however, the location of this defect and the secundum atrial septum are similar. The purpose of this study was to determine the prevalence of crochetage in cryptogenic stroke patients with or without PFO. Methods-A conservative selection scheme was used to identify patients likely to have had PFO-associated strokes tie, cryptogenic) and to exclude any structural, functional, or vascular heart disease responsible for ECG changes. All patients had a standard 12-lead EGG. The prevalence of crochetage in each group was determined. Results-Sixty consecutive patients were studied (28 with echo-documented PFO and 32 echo-negative control subjects). The crochetage pattern was present in at least 1 inferior limb lead in 10 of 28 PFO patients (36%) and 3 of 32 control subjects (9%) (P<0.05). The sensitivity and specificity of the crochetage pattern for diagnosis of PFO in cryptogenic stroke cases were 36% and 91%, respectively; positive predictive value was 77%. Conclusions-The finding of an ECG crochetage pattern may help to identify stroke patients with PFO, may help to streamline their diagnostic workup, and may warrant future studies to determine its value in stratifying stroke risk in patients with PFO. C1 Massachusetts Gen Hosp, Dept Neurol, Stroke Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Cardiol, Stroke Serv, Boston, MA 02114 USA. RP Buonanno, FS (reprint author), Massachusetts Gen Hosp, Dept Neurol, Stroke Serv, VBK-802,32 Fruit St, Boston, MA 02114 USA. EM buonanno@helix.mgh.harvard.edu FU NINDS NIH HHS [5 P50 NS108288-22, R01 NS33765, R01-NS28371] NR 33 TC 14 Z9 14 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0039-2499 J9 STROKE JI Stroke PD JUL PY 1998 VL 29 IS 7 BP 1393 EP 1397 PG 5 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA ZX128 UT WOS:000074482200020 PM 9660393 ER PT J AU Finklestein, SP AF Finklestein, SP TI Adenovirus-mediated gene transfer in vivo to cerebral blood vessels and perivascular tissue in mice SO STROKE LA English DT Editorial Material C1 Massachusetts Gen Hosp, CNS Growth Factor Res Lab, Boston, MA 02114 USA. RP Finklestein, SP (reprint author), Massachusetts Gen Hosp, CNS Growth Factor Res Lab, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0039-2499 J9 STROKE JI Stroke PD JUL PY 1998 VL 29 IS 7 BP 1416 EP 1416 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA ZX128 UT WOS:000074482200025 ER PT J AU So, JBY Zeitels, SM Rattner, DW AF So, JBY Zeitels, SM Rattner, DW TI Outcomes of atypical symptoms attributed to gastroesophageal reflux treated by laparoscopic fundoplication SO SURGERY LA English DT Article ID NISSEN FUNDOPLICATION; ANTIREFLUX SURGERY; SURGICAL-TREATMENT; CHEST PAIN; DISEASE; SPECTRUM; REPAIR AB Background. The introduction of laparoscopic fundoplication (LF) has lowered the threshold for operation in patients with symptoms attributed to gastroesophageal reflux. We sought to determine whether the outcomes in patients referred for atypical symptoms (pulmonary, pharyngolaryngeal, and pain syndromes) were as good as those referred for correction of heartburn and regurgitation (typical symptoms). Methods. Thirty-five of 150 consecutive patients undergoing LF with a minimum of 12 months of follow-up were referred primarily for correction of atypical symptoms. A standard preoperative evaluation included endoscopy, manometry, upper gastrointestinal contrast radiography and 24-hour pH probe testing (33 of 35 patients with atypical symptom). Patients completed a symptom questionnaire administered by a study nurse before the operation and 3 and 12 months after the operation. Symptoms were scored from 0 to 10. Results. Heartburn was relieved by LF in 93 % of patients, whereas only 56% of patients had relief of atypical symptoms. Furthermore, the degree of improvement in typical symptoms was greater than that seen for atypical symptoms as measured by the 0 to 10-symptom rating score (improvement in typical symptoms = 6.2 vs improvement in atypical symptoms = 4. 4 [p = 0. 01]). The response rate for laryngeal, pulmonary, and epigastric/chest pain symptoms was 78 %, 58 %, and 48 %, respectively. Analysis of factors associated with relief of atypical symptom revealed that response to a preoperative trial of omeprazole or H-2-blockers was significantly associated with successful surgical outcome (p = 0. 03). Six of seven patients with laryngeal symptoms who had acid reflux above the cricopharyngeal level shown by dual-probe pH testing had relief of the symptoms after LF: Manometric findings (amplitude of esophageal body contractions, propagation of contractions, and lower esophageal sphincter resting pressure) neither predicted nor correlated with relief of atypical symptoms after the operation. Conclusions. Relief of atypical symptoms attributed to gastroesophageal reflux by LF is less satisfactory and more difficult to predict than relief of heartburn and regurgitation. The only useful preoperative predictors of relief of atypical symptoms in this study were the response to pharmacologic acid suppression and dual-probe pH testing (only in patients with laryngeal symptoms). C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol, Boston, MA USA. RP Rattner, DW (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. NR 25 TC 111 Z9 117 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD JUL PY 1998 VL 124 IS 1 BP 28 EP 32 DI 10.1016/S0039-6060(98)70071-6 PG 5 WC Surgery SC Surgery GA ZZ208 UT WOS:000074706400005 PM 9663248 ER PT J AU Schwartz, PJ Coyle, JT AF Schwartz, PJ Coyle, JT TI Effects of overexpression of the cytoplasmic copper-zinc superoxide dismutase on the survival of neurons in vitro SO SYNAPSE LA English DT Article DE superoxide dismutase; excitotoxicity; glutamate; kainic acid; transgenic ID AMYOTROPHIC-LATERAL-SCLEROSIS; CEREBELLAR GRANULE CELLS; NERVE GROWTH-FACTOR; TRANSGENIC MICE; GLUTATHIONE METABOLISM; GLUTAMATE TOXICITY; TRISOMY-16 MOUSE; OXIDATIVE STRESS; CORTICAL-NEURONS; PRIMARY CULTURES AB The cytoplasmic copper-zinc superoxide dismutase (Cu, Zn SOD; SOD-1) is an abundant and well-conserved intracellular antioxidant enzyme which has been implicated in a number of oxidative stress mediated phenomena, especially Down Syndrome, in which SOD-1 activity is increased due to triplication of chromosome 21 containing the gene and, in hereditary amyotrophic lateral sclerosis, in which the gene is mutated. Overexpression of SOD-1 could theoretically, therefore, lead to increased vulnerability to oxidative stress in two distinct manners: increasing steady-state hydrogen peroxide levels or increasing toxic side reactions. We used two mouse neuronal culture systems-one in which the murine chromosome containing SOD-1 is triplicated and one in which human SOD-1 is a transgene-to test the effect of overexpression of this enzyme on antioxidant status in general and specifically on glutamate mediated oxidative stress. We found that SOD-1 overexpression increases antioxidant status at the same time it decreases vulnerability to glutamate. (C) 1998 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Lab Mol & Dev Neurosci, Charlestown, MA USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Coyle, JT (reprint author), Harvard Univ, McLean Hosp, Sch Med, Dept Psychiat, 115 Mill St, Belmont, MA 02178 USA. FU NIMH NIH HHS [MH51920]; NINDS NIH HHS [NS13584] NR 46 TC 14 Z9 14 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0887-4476 J9 SYNAPSE JI Synapse PD JUL PY 1998 VL 29 IS 3 BP 206 EP 212 DI 10.1002/(SICI)1098-2396(199807)29:3<206::AID-SYN2>3.0.CO;2-A PG 7 WC Neurosciences SC Neurosciences & Neurology GA ZQ927 UT WOS:000073917000002 PM 9635890 ER PT J AU Wallace, EL Churchill, WH Surgenor, DM Cho, GS McGurk, S AF Wallace, EL Churchill, WH Surgenor, DM Cho, GS McGurk, S TI Collection and transfusion of blood and blood components in the United States, 1994 SO TRANSFUSION LA English DT Article ID ALLOGENEIC TRANSFUSION; RISK; CONTROVERSIES; FILTRATION; MEDICINE AB BACKGROUND: Collections and transfusions of blood in the United States in 1994 were measured and compared with those in 1992. STUDY DESIGN AND METHODS: Completed survey questionnaires were returned by all 147 regional blood centers, 1340 American Association of Blood Banks (AABB) member hospitals, and 523 non-AABB hospitals. Statistical tests verified the representativeness of the sample. RESULTS: The United States domestic blood supply in 1994 (13,340,000 units) was 3.3 percent less than in 1992. It included allogeneic blood (11,773,000 units), autologous blood (1,013,000 units), and directed donations (334,000 units). Of these, 432,000 units were rejected on testing, 11,107,000 units were transfused to 3,398,000 patients, and 1,801,000 units were discarded or unaccounted for. Platelet transfusions amounted to 7,866,000 units. Compared with the totals for 1992, transfusions of single-donor platelets (714,000 packs or 4,284,000 units) increased by 17.6 percent, while transfusions of platelet concentrates (3,582,000 units) fell by 23.6 percent. Fresh-frozen plasma transfusions (2,621,000 units) increased by 16.2 percent over the number for 1992. CONCLUSIONS: The US blood collection rate in 1994 was 74.6 units per 1000 population of donor age, the lowest recorded level since 1971.The US RBC transfusion rate in 1994 was 42.8 units per 1000 population, about the same as 1979. Transfusions of single-donor platelets, 16.5 units per 1000 popluation, exceeded transfusions of platelet concentrate (13.8/1000) for the first time. Plasma transfusions were 10.1 units per 1000 population.The US blood supply in 1994 was adequate to meet patient demands. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Clin Labs,Div Hematol Incol, Boston, MA 02115 USA. Ctr Management Syst, Snowmass Village, CO USA. SUNY Buffalo, Buffalo, NY 14260 USA. RP Surgenor, DM (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL-33774] NR 24 TC 158 Z9 159 U1 0 U2 2 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JUL PY 1998 VL 38 IS 7 BP 625 EP 636 DI 10.1046/j.1537-2995.1998.38798346630.x PG 12 WC Hematology SC Hematology GA 102ZN UT WOS:000074956300003 PM 9683100 ER PT J AU Shipp, TD Bromley, B Lieberman, E Benacerraf, BR AF Shipp, TD Bromley, B Lieberman, E Benacerraf, BR TI The second-trimester fetal iliac angle as a sign of Down's syndrome SO ULTRASOUND IN OBSTETRICS & GYNECOLOGY LA English DT Article DE iliac angle; Down's syndrome; second-trimester fetus ID TRISOMY-21; RISK AB Objective To determine whether the iliac angle of second-trimester fetuses is a useful sonographic marker for the detection of fetuses with Down's syndrome. Methods We prospectively measured the iliac angle for all fetuses karyotyped over a 17-month period. A transverse view of the upper fetal pelvis was obtained at the rime of amniocentesis and, by means of a protractor the angle between the two iliac bones was measured. The angles of all those fetuses with Down's syndrome and the first 500 fetuses with normal karyotypes were compared, as was gestational age and maternal age. Results Nineteen fetuses with Down's syndrome and 1167 fetuses with no?mal karyotypes underwent genetic amniocentesis over the study period. The mean gestational age of the fetuses with Down's syndrome was 16.6 weeks (+/- 1.9 weeks), and for the controls, 16.1 weeks (+/-4 weeks) (p = 0.3). The mean maternal ages were 34.7 years (+/- 4.8 years) and 35.4 years (+/- 4.1 years) for those pregnancies with Down's syndrome and with normal karyotypes, respectively (p = 0.5). The mean iliac angle was 80.1 degrees (+/- 19.7 degrees) for those fetuses wish Down's syndrome, and 63.1 degrees (+/- 20.3 degrees) for those fetuses with normal karyotypes (p = 0.0004). The iliac angle was at least 90 degrees in 36.8% (seven of 19 fetuses) with Down's syndrome and in 12.8% (64 of 500 fetuses) with normal karyotypes (p = 0.003). Conclusion Fetuses with Down's syndrome have a significantly larger iliac angle than fetuses with normal karyotypes. Use of an iliac angle cut-off point of 90 degrees would identify over one-third of second-trimester fetuses with Down's syndrome. However, because of the high false-positive rate (12.8%), the Iliac angle is not useful in a high-risk population as a screening test when used in isolation. C1 Massachusetts Gen Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA USA. RP Shipp, TD (reprint author), Diagnost Ultrasound Associates, 333 Longwood Ave,Suite 400, Boston, MA 02115 USA. NR 10 TC 19 Z9 19 U1 0 U2 2 PU PARTHENON PUBLISHING GROUP PI CARNFORTH LANCASHIRE PA CASTERTON HALL, CARNFORTH LANCASHIRE LA6 2LA, ENGLAND SN 0960-7692 J9 ULTRASOUND OBST GYN JI Ultrasound Obstet. Gynecol. PD JUL PY 1998 VL 12 IS 1 BP 15 EP 18 DI 10.1046/j.1469-0705.1998.12010015.x PG 4 WC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine & Medical Imaging GA 104GN UT WOS:000075006500004 PM 9697278 ER PT J AU Cardinalli, IA Selig, MK Dickersin, GR AF Cardinalli, IA Selig, MK Dickersin, GR TI Alveolar soft-part sarcoma with unusual mitochondrial findings: A case report SO ULTRASTRUCTURAL PATHOLOGY LA English DT Article DE alveolar soft part sarcoma; electron microscopy; mitochondria ID GIANT MITOCHONDRIA; PROTEIN EXPRESSION; DIFFERENTIATION; HISTOGENESIS; ORIGIN; CELL; PARAGANGLIOMA C1 Massachusetts Gen Hosp, Dept Pathol, Electron Microscopy Unit, James Homer Wright Pathol Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Univ Estadual Campinas, Dept Pathol, BR-13081970 Campinas, SP, Brazil. RP Dickersin, GR (reprint author), Massachusetts Gen Hosp, Dept Pathol, Electron Microscopy Unit, James Homer Wright Pathol Labs, 100 Blossom St,COX 546, Boston, MA 02114 USA. NR 33 TC 3 Z9 3 U1 0 U2 1 PU HEMISPHERE PUBL CORP PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 USA SN 0191-3123 J9 ULTRASTRUCT PATHOL JI Ultrastruct. Pathol. PD JUL-AUG PY 1998 VL 22 IS 4 BP 321 EP 329 PG 9 WC Microscopy; Pathology SC Microscopy; Pathology GA 132HN UT WOS:000076624400005 PM 9805357 ER PT J AU Lein, M Nowak, L Jung, K Koenig, F Schnorr, D Loening, SA AF Lein, M Nowak, L Jung, K Koenig, F Schnorr, D Loening, SA TI Plasma concentrations of metalloproteinases (MMP-1, MMP-3) and their inhibitors in patients with prostate cancer SO UROLOGE-AUSGABE A LA German DT Article DE prostate cancer; matrix metalloproteinases; MMP1; MMP3; TIMP1 ID TISSUE INHIBITOR; COLORECTAL-CANCER; EXPRESSION; SERUM; COLLAGENASE; ADENOCARCINOMA; HYPERPLASIA; BENIGN AB Matrix metalloproteinases (MMP) and their tissue inhibitors (TIMP) are involved in important processes of tumor invasion and metastasis. in the study presented, matrix metalloproteinase 1 (MMP1) and 3 (MMP3), the tissue inhibitor of metalloproteinase 1 (TIMP1) and the complex MMP1/TIMP1 were measured by ELISA tests specific for these proteins in blood plasma. These components have been investigated in prostate cancer patients (PCa) with metastases (n = 18; T2, 3, 4 pN1, 2M1), prostate cancer patients without metastases (n = 29; T2, 3 pN0M0), patients with benign prostate hyperplasia (BPH; n = 29) and in healthy men (n = 35). Mean values of MMP1 and of the complex MMP1/TIMP1 were not different among the four groups. The mean values of MMP3 and especially TIMP1 were significantly higher in prostate cancer patients with metastases compared with controls, BPH patients and prostate cancer patients without metastases. Ten of these 18 patients had TIMP1 levels higher than the upper reference limit. TIMP1 concentrations correlate to the tumor stage but not to the tumor grade. These results indicate, that TIMP1 could be an potential marker for metastases in prostate cancer patients. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs, Boston, MA 02114 USA. Humboldt Univ, Univ Klin Charite, Urol Klin & Poliklin, Berlin, Germany. RP Lein, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs, WEL 224, Boston, MA 02114 USA. NR 21 TC 9 Z9 10 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-2592 J9 UROLOGE A JI Urol.-Ausg. A PD JUL PY 1998 VL 37 IS 4 BP 377 EP 381 DI 10.1007/s001200050194 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 103XH UT WOS:000074982800003 PM 9738289 ER PT J AU Brodersen, R Bijlsma, F Gori, K Jensen, KT Chen, W Dominguez, J Haverson, K Moore, PF Saalmuller, A Sachs, D Slierendrecht, WJ Stokes, C Vainio, O Zuckermann, F Aasted, B AF Brodersen, R Bijlsma, F Gori, K Jensen, KT Chen, W Dominguez, J Haverson, K Moore, PF Saalmuller, A Sachs, D Slierendrecht, WJ Stokes, C Vainio, O Zuckermann, F Aasted, B TI Analysis of the immunological cross reactivities of 213 well characterized monoclonal antibodies with specificities against various leucocyte surface antigens of human and 11 animal species SO VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY LA English DT Article DE cross reaction; monoclonal antibodies; leucocyte antigens; human; horse; cattle; sheep; goat; swine; dog; cat; mink; rabbit; guinea pig; toad; chicken; turtle; trout ID PERIPHERAL-BLOOD; LEUKOCYTE ANTIGENS; CANINE LYMPHOCYTES; LEUKOINTEGRIN; EVOLUTION; MOLECULES; RUMINANTS; MARKERS; TISSUE; CELLS AB 213 Monoclonal antibodies (mAbs) raised against leucocyte surface antigens from human and 11 animal species were analyzed for reactivities against leucocytes from human and 15 different animal species. We found 77 mAbs (36%) to cross-react. Altogether, 217 cross reactions were registered out of 3195 possible combinations (7%). Most of the cross reacting mAbs had integrin or MHC class II specificities. This study defined cross reactions on the following markers: CD1a, 1c, 2, 4, 5, 8, 9, 11a, 11b, 14, 18, 20, 21, 23, 29, 31, 41, 43; 44, 45, 45R, 46, 49, 61, 62L, TCR gamma/delta, BCR, Thy-1, MHC class I and MHC class II, Swine-WC7 and Cattle-WC1. In order to characterize the molecular weight (MW) of the corresponding cross reacting antigens, selected mAbs were used to immunoprecipitate the antigens. The MW's of the analyzed precipitated antigens were in good agreement with the MWs of the homologous antigens. The followed strategy was found to be efficient and economical in defining new leucocyte antigen reactive mAbs. (C) 1998 Elsevier Science B.V. Ah rights reserved. C1 Royal Vet & Agr Univ, Dept Vet Microbiol, Lab Virol & Immunol, DK-1870 Frederiksberg C, Denmark. INIA, CISA, Madrid 28130, Spain. Univ Bristol, Sch Med, Dept Vet Med, Bristol BS18 7DV, Avon, England. Univ Calif Davis, Dept Vet Pathol, Davis, CA 95616 USA. Fed Res Ctr Virus Dis Anim, D-72001 Tubingen, Germany. Massachusetts Gen Hosp East, Transplantat Biol Res Ctr, Boston, MA 02129 USA. Danish Trout Culture Res Stn, Skaerbaek, Denmark. Univ Turku, Dept Med Microbiol, Turku, Finland. Univ Illinois, Dept Vet Pathol, Urbana, IL 61801 USA. RP Aasted, B (reprint author), CSIRO, Div Anim Hlth, Private Bag 1, Parkville, Vic 3052, Australia. RI Dominguez, Javier/I-1210-2015 NR 43 TC 79 Z9 79 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2427 J9 VET IMMUNOL IMMUNOP JI Vet. Immunol. Immunopathol. PD JUN 30 PY 1998 VL 64 IS 1 BP 1 EP 13 DI 10.1016/S0165-2427(98)00117-2 PG 13 WC Immunology; Veterinary Sciences SC Immunology; Veterinary Sciences GA ZW076 UT WOS:000074371500001 PM 9656427 ER PT J AU Thorin, E Huang, PL Fishman, MC Bevan, JA AF Thorin, E Huang, PL Fishman, MC Bevan, JA TI Nitric oxide inhibits alpha(2)-adrenoceptor-mediated endothelium-dependent vasodilation SO CIRCULATION RESEARCH LA English DT Article DE nitric oxide; alpha(2)-adrenoceptor; vasodilation ID CYCLIC GUANOSINE 3'-5'-MONOPHOSPHATE; ALPHA-2-ADRENERGIC RECEPTOR SUBTYPES; VASCULAR SMOOTH-MUSCLE; METHYLENE-BLUE; GLYCERYL TRINITRATE; POTASSIUM CHANNELS; CORONARY-ARTERIES; RELAXING FACTOR; IN-VITRO; RELAXATION AB This study was designed to investigate the interaction between the NO/L-arginine pathway and the alpha(2)-adrenoceptor-mediated endothelium-dependent vasorelaxation, Reactivity of isolated resistance mesenteric arterial segments from mice lacking the gene for constitutive endothelial NO synthase (eNOS(-) mice, n=14) and from their wild-type controls (WT mice, n=46) was studied in isometric conditions in the presence of indomethacin (blocker of cyclooxygenase). Oxymetazoline (OXY, 0.01 to 30 mu mol/L; a selective alpha(2)-adrenoceptor agonist) induced an endothelium-dependent relaxation of eNOS- but not WT arteries preconstricted either with phenylephrine or serotonin, In the presence of N-omega-nitro-L-arginine (1-NNA, 100 mu mol/L), an inhibitor of NOS, OXY induced an endothelium-dependent relaxation of WT mesenteric arteries. 1-NNA had no effect on the relaxation caused by OXY in eNOS(-) arterial rings, Therefore, the relaxation caused by OXY was independent of NO formation. To demonstrate the inhibitory role of NO on the alpha(2)-adrenoceptor-mediated relaxation, subthreshold (0.1 nmol/L) to threshold (1 nmol/L) concentrations of sodium nitroprusside (donor of NO) were added to 1-NNA-treated arteries before OXY challenges: in these conditions, the alpha(2)-adrenoceptor-mediated relaxation of eNOS(-) and WT arteries was inhibited. OXY-induced relaxation was restored on readdition of methylene blue (1 mu mol/L, inhibitor of guanylate cyclase), suggesting that cGMP may be the mechanism of inhibition of the alpha(2)-adrenergic pathway in the presence of NO, Finally, OXY-mediated relaxation was blocked by tetraethylammonium (1 mmol/L) but nor glibenclamide (1 mu mol/L), suggesting the involvement of an endothelium-derived hyperpolarizing factor that activates Ca2+-activated K+ channels. In conclusion, alpha(2)-adrenoceptor activation caused relaxation of isolated murine mesenteric arteries that was functionally blocked by NO through a mechanism that may involve activation of the soluble guanylate cyclase and cGMP formation. The endothelium-dependent alpha(2)-adrenoceptor-mediated relaxation is likely to be due to an endothelium-derived hyperpolarizing factor, whose release and/or production is reduced by concurrent NO formation. C1 Inst Cardiol Montreal, Ctr Rech, Montreal, PQ H1T 1C8, Canada. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Med Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Med Serv, Boston, MA USA. Univ Vermont, Totman Lab Human Cerebrovasc Res, Burlington, VT USA. RP Thorin, E (reprint author), Inst Cardiol Montreal, Ctr Rech, 5000 Rue Belanger, Montreal, PQ H1T 1C8, Canada. NR 47 TC 68 Z9 69 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD JUN 29 PY 1998 VL 82 IS 12 BP 1323 EP 1329 PG 7 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA ZW958 UT WOS:000074466100011 PM 9648729 ER PT J AU O'Grady, P Thai, TC Saito, H AF O'Grady, P Thai, TC Saito, H TI The laminin-nidogen complex is a ligand for a specific splice isoform of the transmembrane protein tyrosine phosphatase LAR SO JOURNAL OF CELL BIOLOGY LA English DT Article ID CELL-ADHESION; RECEPTOR; PHOSPHORYLATION; DOMAINS; CAM; FIBRONECTIN; DROSOPHILA; EXPRESSION; BINDING; KINASE AB Leukocyte antigen-related protein (LAR) is a prototype for a family of transmembrane protein tyrosine phosphatases whose extracellular domain is composed of three Ig and several fibronectin type III (FnIII) domains. Complex alternative splicing of the LAR-FnIII domains 4-8 has been observed, The extracellular matrix laminin-nidogen complex was identified as a ligand for the LAR-FnIII domain 5 (Fn5) using a series of GST-LAR-FnIII domain fusion proteins and testing them in in vitro ligand-binding assays, LAR-laminin-nidogen binding was regulated by alternative splicing of a small exon within the LAR-Fn5 so that in elusion of this exon sequence resulted in disruption of the laminin-nidogen-binding activity. Long cellular processes were observed when HeLa cells were plated on laminin-nidogen, but not when plated on a fibronectin surface. Indirect immunofluorescent antibody staining revealed high expression of LAR in a punctate pattern, throughout the length of these cellular processes observed on laminin-nidogen. Antibody-induced crosslinking of LAR inhibited formation of these cellular processes, and inhibition was correlated with changes in cellular actin cytoskeletal structure. Thus, LAR-laminin-nidogen binding may play a role in regulating cell signaling induced by laminin-nidogen, resulting in cell morphological changes. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Saito, H (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NIGMS NIH HHS [GM53415] NR 43 TC 109 Z9 109 U1 1 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD JUN 29 PY 1998 VL 141 IS 7 BP 1675 EP 1684 DI 10.1083/jcb.141.7.1675 PG 10 WC Cell Biology SC Cell Biology GA ZY290 UT WOS:000074605300017 PM 9647658 ER PT J AU Mulley, AG Barry, MJ AF Mulley, AG Barry, MJ TI Controversy in managing patients with prostate cancer SO BRITISH MEDICAL JOURNAL LA English DT Editorial Material ID RANDOMIZATION; MANAGEMENT C1 Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Mulley, AG (reprint author), Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. NR 11 TC 11 Z9 11 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0959-8138 J9 BRIT MED J JI Br. Med. J. PD JUN 27 PY 1998 VL 316 IS 7149 BP 1919 EP 1920 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA ZY568 UT WOS:000074636700003 PM 9641924 ER PT J AU Crawford, SE Stellmach, V Murphy-Ullrich, JE Ribeiro, SMF Lawler, J Hynes, RO Boivin, GP Bouck, N AF Crawford, SE Stellmach, V Murphy-Ullrich, JE Ribeiro, SMF Lawler, J Hynes, RO Boivin, GP Bouck, N TI Thrombospondin-1 is a major activator of TGF-beta 1 in vivo SO CELL LA English DT Article ID TRANSFORMING GROWTH-FACTOR; HAMSTER OVARY CELLS; FACTOR-BETA; TGF-BETA; ENDOTHELIAL-CELLS; FACTOR-BETA-1-DEFICIENT MICE; EXTRACELLULAR-MATRIX; EPITHELIAL-CELLS; TRANSGENIC MICE; LATENT FORMS AB The activity of TGF-beta 1 is regulated primarily extracellularly where the secreted latent form must be modified to expose the active molecule. Here we show that thrombospondin-1 is responsible for a significant proportion of the activation of TGF-beta 1 in vivo. Histological abnormalities in young TGF-beta 1 null and thrombospondin-1 null mice were strikingly similar in nine organ systems. Lung and pancreas pathologies similar to those observed in TGF-beta 1 null animals could be induced in wild-type pups by systemic treatment with a peptide that blocked the activation of TGF-beta 1 by thrombospondin-1. Although these organs produced little active TGF-beta 1 in thrombospondin null mice, when pups were treated with a peptide derived from thrombospondin-l that could activate TGF-beta 1, active cytokine was detected in situ, and the lung and pancreatic abnormalities reverted toward wild type. C1 Northwestern Univ, Sch Med, Robert H Lurie Canc Ctr, Chicago, IL 60611 USA. Northwestern Univ, Sch Med, Dept Immunol Microbiol, Chicago, IL 60611 USA. Northwestern Univ, Sch Med, Dept Pathol, Chicago, IL 60611 USA. Childrens Mem Hosp, Childrens Mem Inst Educ & Res, Chicago, IL 60614 USA. Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA. Harvard Univ, Sch Med, Beth Israel Deaconness Med Ctr, Dept Pathol, Boston, MA 02215 USA. MIT, Dept Biol, Ctr Canc Res, Howard Hughes Med Inst, Cambridge, MA 02139 USA. Univ Cincinnati, Dept Pathol, Cincinnati, OH 45267 USA. RP Crawford, SE (reprint author), Northwestern Univ, Sch Med, Robert H Lurie Canc Ctr, Chicago, IL 60611 USA. FU NCI NIH HHS [CA52750, CA64239]; NHLBI NIH HHS [HL28749, R01 HL050061] NR 72 TC 749 Z9 780 U1 0 U2 9 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD JUN 26 PY 1998 VL 93 IS 7 BP 1159 EP 1170 DI 10.1016/S0092-8674(00)81460-9 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA ZX217 UT WOS:000074491100011 PM 9657149 ER PT J AU Endres, M Scott, GS Salzman, AL Kun, E Moskowitz, MA Szabo, C AF Endres, M Scott, GS Salzman, AL Kun, E Moskowitz, MA Szabo, C TI Protective effects of 5-iodo-6-amino-1,2-benzopyrone, an inhibitor of poly(ADP-ribose) synthetase against peroxynitrite-induced glial damage and stroke development SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE nitric oxide (NO); superoxide; glia; inflammation; reperfusion ID NITRIC-OXIDE; CELLS; ACTIVATION AB Peroxynitrite triggers DNA single-strand breakage, which activates the nuclear enzyme poly(ADP-ribose) synthetase (PARS). Activation of PARS depletes its substrate, NAD(+), slowing the rate of glycolysis, electron transport, and ATP formation, resulting in cell necrosis. Here, we demonstrate that inhibition of PARS with the novel, potent PARS inhibitor 5-iodo-6-amino-1,2-benzopyrone (INH2BP) protects against peroxynitrite-induced cell death (as measured by measurement of mitochondrial respiration and release of lactate dehydrogenase) in C6 glioma cells in vitro, and in a murine stroke model in vivo. Inhibition of PARS with INH2BP may represent a novel approach for the experimental therapy of stroke. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Childrens Hosp, Med Ctr, Div Crit Care, Cincinnati, OH 45229 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Stroke & Neurovasc Regulat Lab, Charlestown, MA 02129 USA. San Francisco State Univ, Romberg Tiburon Ctr, Octamer Res Fdn, Lab Environm Toxicol & Chem, Tiburon, CA 94920 USA. RP Szabo, C (reprint author), Childrens Hosp, Med Ctr, Div Crit Care, 3333 Burnet Ave, Cincinnati, OH 45229 USA. RI Moskowitz, Michael/D-9916-2011 FU NHLBI NIH HHS [R01HL59266]; NINDS NIH HHS [NS10828] NR 22 TC 42 Z9 42 U1 0 U2 4 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 JUN 26 PY 1998 VL 351 IS 3 SI SI BP 377 EP 382 DI 10.1016/S0014-2999(98)00381-1 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 107KQ UT WOS:000075207300015 PM 9721031 ER PT J AU Nagy, AK Knowles, AF Nagami, GT AF Nagy, AK Knowles, AF Nagami, GT TI Molecular cloning of the chicken oviduct ecto-ATP-diphosphohydrolase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NUCLEOSIDE TRIPHOSPHATE HYDROLASE; TOXOPLASMA-GONDII; PURIFICATION; PROTEIN; CD39; DIPHOSPHATASE; ANTIBODIES; APYRASE; MUSCLE; COMMON AB The chicken oviduct ecto-ATP diphosphohydrolase (ATPDase), a member of the ecto-ATPase family, was purified to homogeneity previously (Strobel, R. S., Nagy, A. K., Knowles, A, F,, Buegel, J., and Rosenberg, M. O. (1996) J. Biol. Chem. 271, 16323-16331), It is an 80-kDa glycoprotein with high specific activity (approximately 1,000 mu mol/min/mg with MgATP as the substrate) and hydrolyzes both nucleoside triphosphates and diphosphates. Using amino acid sequence information obtained from the purified enzyme, two partial cDNA clones were obtained using reverse transcriptase-polymerase chain reaction and library screening. This is the second ecto-ATPase family member and the first ecto-ATPDase to be cloned hom information derived from purified proteins. The deduced primary sequence of the chicken oviduct ecto-ATPDase indicates a protein of 493 amino acid residues with a molecular mass of 54 kDa. The predicted orientation shows it to be anchored to the membrane by two transmembranous segments near the NH2 and COOH termini with very short intracytoplasmic peptides at either end. The bulk of the protein is extracellular and contains 12 potential N-glycosylation sites, several potential phosphorylation sites, and five sequences that are conserved in seven other related membrane proteins, Four of the conserved sequences, designated as apyrase conserved regions, are present in both ecto-ATPases and soluble E-type ATPases, The fifth conserved region, which occurs near the COOH terminus of the eight proteins, is observed only in the membrane-bound ecto-ATPases. Unexpectedly, sequence comparison revealed that the chicken oviduct ecto-ATPDase is equally distant from the two ecto-ATPases, which exhibit low activity toward ADP, and the four putative ecto-ATPDases, which are closely related to CD39. C1 W Los Angeles Vet Affairs Med Ctr, Nephrol Sect 111L, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. San Diego State Univ, Dept Chem, San Diego, CA 92182 USA. RP Nagami, GT (reprint author), W Los Angeles Vet Affairs Med Ctr, Nephrol Sect 111L, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 45 TC 35 Z9 36 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 26 PY 1998 VL 273 IS 26 BP 16043 EP 16049 DI 10.1074/jbc.273.26.16043 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZW685 UT WOS:000074436600026 PM 9632655 ER PT J AU Smine, A Xu, XM Nishiyama, K Katada, T Gambetti, P Yadav, SP Wu, X Shi, YC Yasuhara, S Homburger, V Okamoto, T AF Smine, A Xu, XM Nishiyama, K Katada, T Gambetti, P Yadav, SP Wu, X Shi, YC Yasuhara, S Homburger, V Okamoto, T TI Regulation of brain G-protein G(o) by Alzheimer's disease gene presenilin-1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HETEROTRIMERIC-G-PROTEINS; IN-VIVO; ENDOPLASMIC-RETICULUM; MISSENSE MUTATIONS; GLIOMA-CELLS; PRECURSOR; RECEPTOR; TRANSPORT; TOXIN; LOCALIZATION AB To investigate a possible association between G-proteins and presenilin-1 (PS-1), a series of glutathione S-transferase-fusion proteins containing portions of PS-1 were prepared and used in vitro in binding experiments with tissue and recombinant G-proteins. The results demonstrate that the 39 C-terminal amino acids of PS-1 selectively bind the brain G-protein, G(o). Addition of guanosine 5'-3-O-(thio)triphosphate promoted G(o) dissociation from PS-1, indicating that this domain mimics the function of G-protein-coupling domains found in receptors. The 39-amino acid synthetic polypeptide activated G(o) in a magnesium ion-dependent manner, Physical interaction of full-length PS-1 and G(o) was also demonstrated. Following transfection of G(o alpha) and N-terminally FLAG-tagged PS-1 in COS-7 cells, G(o) was immunoprecipitated by FLAG antibodies. In addition, endogenous PS-1 and G(o alpha) were colocalized immunocytochemically in human glioma cell lines. The results indicate that PS-1 regulates G(o) activities in living cells. C1 Cleveland Clin Fdn, Dept Neurosci, Lerner Res Inst, Cleveland, OH 44195 USA. Cleveland Clin Fdn, Mol Biotechnol Core Facil, Cleveland, OH 44195 USA. Univ Tokyo, Fac Pharmaceut Sci, Tokyo 113, Japan. Case Western Reserve Univ, Dept Pathol, Cleveland, OH 44106 USA. Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA. CNRS, UPR 9023, CCIPE, F-34094 Montpellier 5, France. RP Okamoto, T (reprint author), Cleveland Clin Fdn, Dept Neurosci, Lerner Res Inst, 9500 Euclid Ave, Cleveland, OH 44195 USA. OI xu, xuemin/0000-0002-7426-272X FU NIMH NIH HHS [MH-56036] NR 47 TC 48 Z9 48 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 26 PY 1998 VL 273 IS 26 BP 16281 EP 16288 DI 10.1074/jbc.273.26.16281 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZW685 UT WOS:000074436600059 PM 9632688 ER PT J AU Weng, QP Kozlowski, M Belham, C Zhang, AH Comb, MJ Avruch, J AF Weng, QP Kozlowski, M Belham, C Zhang, AH Comb, MJ Avruch, J TI Regulation of the p70 S6 kinase by phosphorylation in vivo - Analysis using site-specific anti-phosphopeptide antibodies SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-KINASES; RAPAMYCIN; INSULIN; ACTIVATION; P70(S6K); WORTMANNIN; INHIBITION AB The p70 S6 kinase is activated by diverse stimuli through a multisite phosphorylation directed at three separate domains as follows: a cluster of (Ser/Thr) Pro sites in an autoinhibitory segment in the noncatalytic carboxyl-terminal tail; Thr-252 in the activation loop of the catalytic domain; and Ser-394 and Thr-412 in a segment immediately carboxyl-terminal to the catalytic domain. Phosphorylation of Thr-252 in vitro by the enzyme phosphatidylinositol 3-phosphate-dependent kinase-1 or mutation of Thr-412 --> Glu has each been shown previously to engender some activation of the p70 S6 kinase, whereas both modifications together produce 20-30-fold more activity than either alone. We employed phospho-specific anti-peptide antibodies to examine the relative phosphorylation at several of these sites in wild type and various p70 mutants, in serum-deprived cells, and in response to activators and inhibitors of p70 S6 kinase activity. Substantial phosphorylation of p70 Thr-252 and Ser-434 was present in serum-deprived cells, whereas Thr-412 and Thr-444/Ser-447 were essentially devoid of phospho-specific immunoreactivity, Activation of p70 by insulin was accompanied by a coordinate increase in phosphorylation at all sites examined, together with a slowing in mobility on SDS-PAGE of a portion of p70 polypeptides. Upon addition of rapamycin or wortmannin to insulin-treated cells, the decrease in activity of p70 was closely correlated with the disappearance of anti-Thr-412(P) immunoreactivity and the most slowly migrating p70 polypeptides, whereas considerable phosphorylation at Ser-434 and Thr-252 persisted after the disappearance of 40 S kinase activity. The central role of Thr-412 phosphorylation in the regulation of kinase activity was further demonstrated by the close correlation of the effects of various deletions and point mutations on p70 activity and Thr-412 phosphorylation. In conclusion, although p70 activity depends on a disinhibition from the carboxyl-terminal tail and the simultaneous phosphorylation at both Thr-252 and Thr-412, p70 activity in vivo is most closely related to the state of phosphorylation at Thr-412. C1 Massachusetts Gen Hosp, Dept Biol Mol, Diabet Res Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. New England Biolabs Inc, Beverly, MA 01915 USA. RP Avruch, J (reprint author), Massachusetts Gen Hosp, Dept Biol Mol, Diabet Res Lab, 50 Blossom St, Boston, MA 02114 USA. EM avruch@helix.mgh.harvard.edu FU NIDDK NIH HHS [DK17776] NR 24 TC 293 Z9 297 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 26 PY 1998 VL 273 IS 26 BP 16621 EP 16629 DI 10.1074/jbc.273.26.16621 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZW685 UT WOS:000074436600107 PM 9632736 ER PT J AU Tarazi, FI Campbell, A Baldessarini, RJ AF Tarazi, FI Campbell, A Baldessarini, RJ TI Effects of hippocampal lesions on striatolimbic ionotropic glutamatergic receptors SO NEUROSCIENCE LETTERS LA English DT Article DE autoradiography; Caudate-Putamen; ionotropic glutamate receptors; hippocampus; kainic acid; nucleus accumbens ID AMINO-ACID RECEPTORS; SCHIZOPHRENIA; BINDING; RELEASE; BRAIN; RAT AB Changes in ionotropic N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate glutamatergic (Glu) receptor binding in rat caudate putamen (CPu) and nucleus accumbens (NAc) and hippocampal CA(1) and CA(3) regions were examined after unilateral injections of kainic acid (KA) into hippocampus to degenerate local intrinsic neurons and remove the glutamatergic afferents projecting to CPU and NAc. KA injections produced large losses of NMDA, AMPA and kainate receptors in hippocampal CA(1) and CA(3) regions. In addition, NMDA and kainate, but not AMPA, receptors were significantly reduced in NAc and CPu. These results suggest that a large proportion of NMDA, AMPA and kainate receptors in rat hippocampus arise on intrinsic postsynaptic neurons, and that some NMDA and kainate, but not AMPA, receptors also occur on presynaptic terminals of hippocampostriatal afferents innervating the CPu and NAc. (C) 1998 Elsevier Science ireland Ltd. All rights reserved. C1 Massachusetts Gen Hosp, McLean Div, Mailman Res Ctr, Belmont, MA 02178 USA. Harvard Univ, Sch Med, Consolidated Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. RP Tarazi, FI (reprint author), Massachusetts Gen Hosp, McLean Div, Mailman Res Ctr, 115 Mill St, Belmont, MA 02178 USA. FU NIMH NIH HHS [MH-19905, MH-47370, MH-34006] NR 20 TC 14 Z9 14 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD JUN 26 PY 1998 VL 250 IS 1 BP 13 EP 16 DI 10.1016/S0304-3940(98)00433-9 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 103JT UT WOS:000075154300004 PM 9696054 ER PT J AU Blumenthal, D Buntin, MB AF Blumenthal, D Buntin, MB TI Carve outs: Definition, experience, and choice among candidate conditions SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article; Proceedings Paper CT Workshop of the Agency-for-Health-Care-Policy-and-Research CY JAN 28, 1998 CL ROCKVILLE, MARYLAND SP Agcy Hlth Care Policy & Res, US DHHS ID MEDICAL OUTCOMES; ASTHMA; PHYSICIANS; SPECIALTY; PATTERNS; PROGRAM; SYSTEMS; VOLUME AB Despite increasing discussion of carve outs as a device for controlling costs and improving quality of care, little systematic information exists on the effects of carve outs on cost, quality, and access to healthcare services. In the absence of such information, a conceptual framework is useful for deciding which conditions and populations may benefit from carve-out strategies, and how such arrangements should be designed. After carefully defining carve outs, and distinguishing them from other similar arrangements, this paper identifies five characteristics of a healthcare condition that increase the likelihood that a carve out's benefits will outweigh its drawbacks. The paper also examines the advantages and disadvantages of alternative approaches to structuring and administering carve-out arrangements, including how to pay for services, how to integrate them with mainstream care, provisions for consumer choice and provisions for carve-out accountability. The piece concludes that population carve outs, in which all the healthcare problems of a group of patients are managed by the carve-out organization, have inherent advantages, and identifies candidate conditions for population carve outs. C1 Massachusetts Gen Hosp, Res & Dev Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. RP Blumenthal, D (reprint author), Massachusetts Gen Hosp, Res & Dev Unit, 50 Staniford,9th Floor, Boston, MA 02114 USA. NR 37 TC 10 Z9 10 U1 1 U2 1 PU AMER MED PUBLISHING, M W C COMPANY PI OLD BRIDGE PA 1816 ENGLISHTOWN RD, STE 101, OLD BRIDGE, NJ 08857 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD JUN 25 PY 1998 VL 4 SI SI BP SP45 EP SP57 PG 13 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA ZY970 UT WOS:000074681900004 PM 10184946 ER PT J AU Shekelle, PG Kahan, JP Bernstein, SJ Leape, LL Kamberg, CJ Park, RE AF Shekelle, PG Kahan, JP Bernstein, SJ Leape, LL Kamberg, CJ Park, RE TI The reproducibility of a method to identify the overuse and underuse of medical procedures SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID NEW-YORK-STATE; COST-EFFECTIVENESS; CORONARY-ANGIOGRAPHY; MYOCARDIAL-INFARCTION; APPROPRIATENESS; HYSTERECTOMY; VARIABILITY; TRIALS; CARE; AGREEMENT AB Background To assess the overuse and underuse of medical procedures, various methods have been developed, but their reproducibility has not been evaluated. This study estimates the reproducibility of one commonly used method. Methods We performed a parallel, three-way replication of the RAND-University of California at Los Angeles appropriateness method as applied to two medical procedures, coronary revascularization and hysterectomy. Three nine-member multidisciplinary panels of experts were composed for each procedure by stratified random sampling from a list of experts nominated by the relevant specialty societies. Each panel independently rated the same set of clinical scenarios in terms of the appropriateness of the relevant procedure on a risk-benefit scale ranging from 1 to 9. Final ratings were used to classify the procedure in each scenario as necessary or not necessary (to evaluate underuse) and inappropriate or not inappropriate (to evaluate overuse). Reproducibility was measured by overall agreement and by the kappa statistic. The criteria for underuse and overuse derived from these ratings were then applied to real populations of patients who had undergone coronary revascularization or hysterectomy. Results The rates of agreement among the three coronary-revascularization panels were 95, 94, and 96 percent for inappropriate-use scenarios and 93, 92, and 92 percent for necessary-use scenarios. Agreement among the three hysterectomy panels was 88, 70, and 74 percent for inappropriate-use scenarios. Scenarios involving necessary use of hysterectomy were not assessed. The three-way kappa statistic to detect overuse was 0.52 for coronary revascularization and 0.51 for hysterectomy. The three-way kappa statistic to detect underuse of coronary revascularization was 0.83. Application of individual panels' criteria to real populations of patients resulted in a 100 percent variation in the proportion of cases classified as inappropriate and a 20 percent variation in the proportion of cases classified as necessary. Conclusions The appropriateness method is far from perfect. Appropriateness criteria may be useful in comparing levels of appropriate procedures among populations but should not by themselves be used to direct care for individual patients. (N Engl J Med 1998; 338:1888-95.) (C) 1998, Massachusetts Medical Society. C1 Rand Corp, Santa Monica, CA 90407 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Vet Affairs Med Ctr, Ann Arbor, MI USA. Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Hlth Management & policy, Ann Arbor, MI 48109 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Shekelle, PG (reprint author), Rand Corp, 1700 Main St,POB 2138, Santa Monica, CA 90407 USA. FU AHRQ HHS [HSO7185-02] NR 36 TC 235 Z9 236 U1 0 U2 4 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 25 PY 1998 VL 338 IS 26 BP 1888 EP 1895 DI 10.1056/NEJM199806253382607 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA ZV898 UT WOS:000074352800007 PM 9637810 ER PT J AU Hirsch, MS Conway, B D'Aquila, RT Johnson, VA Brun-Vezinet, F Clotet, B Demeter, LM Hammer, SM Jacobsen, DM Kuritzkes, DR Loveday, C Mellors, JW Vella, S Richman, DD AF Hirsch, MS Conway, B D'Aquila, RT Johnson, VA Brun-Vezinet, F Clotet, B Demeter, LM Hammer, SM Jacobsen, DM Kuritzkes, DR Loveday, C Mellors, JW Vella, S Richman, DD CA Int AIDS Society USA Panel TI Antiretroviral drug resistance testing in adults with HIV infection - Implications for clinical management SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; TYPE-1 REVERSE-TRANSCRIPTASE; ZIDOVUDINE RESISTANCE; COMBINATION THERAPY; IN-VIVO; PROTEASE INHIBITORS; CONFERS RESISTANCE; CELL-CULTURE; MUTATIONS; SENSITIVITY AB Objectives.-To review current knowledge of the biology and clinical implications of human immunodeficiency virus (HIV) resistance to antiretroviral drugs, describe assays for measuring resistance, and assess their use in clinical practice. Participants.-The international AIDS Society-USA assembled a panel of 13 physicians with expertise in basic science, clinical research, and patient care relevant to HIV resistance to antiretroviral drugs. Evidence.-We reviewed available data from published reports and presented at national and international research conferences. Basic science research, clinical trial results, and expert opinions were used to form the basis of this report, Data on methods for and characteristics of specific genotypic and phenotypic assays were obtained from manufacturers and service providers. Consensus Process.-The panel met regularly between October 1997 and April 1998, Panel subgroups developed and discussed different sections of the report before discussing them with the entire panel. Conclusions and suggested approaches to the use of resistance testing were determined by group consensus. Conclusions.-Plasma HIV RNA level and CD4(+) cell count are the primary values that should be used to guide the initiation of antiretroviral therapy and subsequent changes in therapy. Possible causes of treatment failure other than development of drug resistance that should be considered are adherence, drug potency, and pharmacokinetic issues, Genotypic and phenotypic testing for HIV resistance to antiretroviral drugs may prove useful for individual patient management. Assays under development need validation, standardization, and a clearer definition of their clinical roles, Possible current roles of resistance testing for choosing an initial regimen or changing antiretroviral therapy, as well as possible implications of the presence or absence of phenotypic resistance and genotypic changes, are discussed. C1 Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Infectious Dis Unit, Boston, MA 02114 USA. St Pauls Hosp, Vancouver, BC V6Z 1Y6, Canada. Univ Alabama, Sch Med, Birmingham, AL USA. Vet Affairs Med Ctr, Birmingham, AL USA. Hop Bichat Claude Bernard, F-75877 Paris, France. Hosp Univ Germans Trias & Pujol, Fdn Irsa Caixa, Barcelona, Spain. Hosp Univ Germans Trias & Pujol, HIV Unit, Barcelona, Spain. Univ Rochester, Rochester, NY 14627 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Royal Free Hosp, Sch Med, London, England. Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15260 USA. Ist Super Sanita, I-00161 Rome, Italy. Univ Calif San Diego, San Diego, CA 92103 USA. Vet Affairs Med Ctr, San Diego, CA 92161 USA. Int AIDS Soc USA, San Francisco, CA 94129 USA. RP Hirsch, MS (reprint author), Int AIDS Soc USA, 1001-B Oreilly Ave,Box 29916, San Francisco, CA 94129 USA. EM hirsch.martin@mgh.harvard.edu RI Vella, Stefano/D-4912-2015 OI Vella, Stefano/0000-0003-2347-5984 NR 90 TC 482 Z9 494 U1 0 U2 11 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 24 PY 1998 VL 279 IS 24 BP 1984 EP 1991 DI 10.1001/jama.279.24.1984 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA ZU945 UT WOS:000074252100036 PM 9643863 ER PT J AU Aikawa, M Rabkin, E Okada, Y Voglic, SJ Clinton, SK Brinckerhoff, CE Sukhova, GK Libby, P AF Aikawa, M Rabkin, E Okada, Y Voglic, SJ Clinton, SK Brinckerhoff, CE Sukhova, GK Libby, P TI Lipid lowering by diet reduces matrix metalloproteinase activity and increases collagen content of rabbit atheroma - A potential mechanism of lesion stabilization SO CIRCULATION LA English DT Article DE metalloproteinases; atherosclerosis; diet; hypercholesterolemia; collagen ID HUMAN ATHEROSCLEROTIC PLAQUES; SMOOTH-MUSCLE CELLS; VASCULAR ENDOTHELIAL-CELLS; ACUTE CORONARY SYNDROMES; GENE-EXPRESSION; CHOLESTEROL LEVELS; REGRESSION DIETS; MACROPHAGE; INHIBITORS; PRAVASTATIN AB Background-Proteolytic enzyme activity in lipid-rich atheroma may promote plaque rupture and precipitate acute coronary syndromes, This study tested the hypothesis that lipid lowering stabilizes plaques by reducing proteolytic activity. Methods and Results-We produced experimental atheroma in 33 rabbits by balloon injury and an atherogenic diet (0.3% cholesterol and 4.7% coconut oil) for 4 months. At that time, 15 rabbits were killed (baseline group). The remaining animals were divided into two groups: a hyperlipemic group continued to consume a cholesterol-enriched diet (0.05% to 0.2%) for 16 more months (n=5) and a lipid-lowering group consumed a purified chow diet with no added cholesterol or fat for 8 (n=3) or 16 months (n=10), Macrophage accumulation and interstitial collagenase (matrix metalloproteinase-1, MMP-1) expression in the lesion were measured by quantitative image analysis of standardized sections of immunostained aortas, Baseline lesions expressed high levels of MMP-1 and contained many macrophages. These features of plaque instability persisted in the hyperlipemic group, However, the lipid-lowering group showed progressive reduction in both macrophage content and MMP-1 immunoreactivity with time. Aortic rings of the baseline and hyperlipemic groups elaborated gelatinolytic, caseinolytic, and elastinolytic activity attributable to MMP-2, MMP-3, or MMP-9, monitored by SDS-PAGE zymography, Proteolytic activity decreased markedly in the lipid-lowering group. Aortic content of interstitial collagen, determined by sirius red staining, increased in the lipid-lowering group compared with the baseline or continued hyperlipemic groups, indicating that lipid lowering reinforced the fibrous skeleton of the atheroma. Conclusions-These results establish a mechanism by which lipid lowering may stabilize vulnerable plaques by reduced expression and activity of enzymes that degrade the arterial extracellular matrix and render atheroma less susceptible to disruption and thrombosis by favoring collagen accumulation in the fibrous cap. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp,Div Cardiovasc, Dept Med,Vasc Med & Atherosclerosis Unit, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Dana Farber Canc Inst, Boston, MA USA. Dartmouth Med Sch, Dept Med, Hanover, NH USA. RP Libby, P (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp,Div Cardiovasc, Dept Med,Vasc Med & Atherosclerosis Unit, 221 Longwood Ave,LMRC 307, Boston, MA 02115 USA. EM plibby@rics.bwh.harvard.edu FU NHLBI NIH HHS [P01 HL-48743] NR 44 TC 412 Z9 426 U1 1 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 23 PY 1998 VL 97 IS 24 BP 2433 EP 2444 PG 12 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA ZV035 UT WOS:000074261800010 PM 9641696 ER PT J AU Shapiro, L Heidenreich, KA MEintzer, MK Dinarello, CA AF Shapiro, L Heidenreich, KA MEintzer, MK Dinarello, CA TI Role of p38 mitogen-activated protein kinase in HIV type 1 production in vitro SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE interleukin 1 ID HUMAN-IMMUNODEFICIENCY-VIRUS; MAP KINASE; IN-VITRO; CELLS; PHOSPHORYLATION; INTERLEUKIN-1; EXPRESSION; CASCADE; STRESS; CYTOKINES AB The proinflammatory cytokines interleukin (LL)-1 and tumor necrosis factor (TNF) promote HIV type 1 viral replication in vitro. In the present studies, HIV production was increased in the macrophagic U1 cell line expressing the HIV genome after exposure to IL-1 beta, osmotic stress, or surface adhesion, suggesting a confluence of signaling pathways for proinflammatory cytokines and cell stressors. The p38 mitogen-activated protein kinase (MAPK) mediates both cytokine and stress responses; thus the role of this kinase in HIV production was investigated. HIV production as measured by p24 antigen correlated with changes in the expression of a specific (non-alpha) isoform of p38 MAPK. In the presence of a specific p38 MAPK inhibitor (p38 inh), IL-1 beta-induced HIV production was suppressed by more than 90% and IL-1 beta-induced IL-8 production was suppressed completely, both with IC50 of 0.01 mu M. p38 inhibition blocked cell-associated p24 antigen and secreted virus to a similar extent. The p38 inh also decreased constitutive HIV production in freshly infected peripheral blood mononuclear cells by up to 50% (P < 0.05:. Interruption of p38 MAPK activity represents a viable target for inhibition of HIV. C1 Univ Colorado, Hlth Sci Ctr, Dept Med, Div Infect Dis, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Denver, CO 80262 USA. RP Dinarello, CA (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Med, Div Infect Dis, Box B168,4200 E 9th Ave, Denver, CO 80262 USA. EM Charles.Dinarello@UCHSC.edu FU NIAID NIH HHS [R01 AI015614, AI 15614, R56 AI015614] NR 28 TC 77 Z9 81 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 23 PY 1998 VL 95 IS 13 BP 7422 EP 7426 DI 10.1073/pnas.95.13.7422 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZW683 UT WOS:000074436400035 PM 9636165 ER PT J AU Taura, T Krebber, H Silver, PA AF Taura, T Krebber, H Silver, PA TI A member of the Ran-binding protein family, Yrb2p, is involved in nuclear protein export SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SACCHAROMYCES-CEREVISIAE; IMPORT RECEPTOR; RAN/TC4 GTPASE; YEAST; RNA; TRANSPORT; IDENTIFICATION; CHROMOSOME; SIGNAL; RCC1 AB Yeast cells mutated in YRB2, which encodes a nuclear protein with similarity to other Ran-binding proteins, fail to export nuclear export signal (NES)-containing proteins including HIV Rev out of the nucleus. Unlike Xpo1p/ Crm1p/exportin, an NES receptor, Yrb2p does not shuttle between the nucleus and the cytoplasm but instead remains inside the nucleus. However, by both biochemical and genetic criteria, Yrb2p interacts with Xpo1p and not with other members of the importin/karyopherin beta superfamily. Moreover, the Yrb2p region containing nucleoporin-like FG repeats is important for NES-mediated protein export. Taken together, these data suggest that Yrb2p acts inside the nucleus to mediate the action of Xpo1p in at least one of several nuclear export pathways. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Silver, PA (reprint author), Dana Farber Canc Inst, Smith Bldg,Room 922,44 Binney St, Boston, MA 02115 USA. NR 49 TC 79 Z9 81 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 23 PY 1998 VL 95 IS 13 BP 7427 EP 7432 DI 10.1073/pnas.95.13.7427 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZW683 UT WOS:000074436400036 PM 9636166 ER PT J AU Robinson, CP Brayer, J Yamachika, S Esch, TR Peck, AB Stewart, CA Peen, E Jonsson, R Humphreys-Beher, MG AF Robinson, CP Brayer, J Yamachika, S Esch, TR Peck, AB Stewart, CA Peen, E Jonsson, R Humphreys-Beher, MG TI Transfer of human serum IgG to nonobese diabetic Ig mu(null) mice reveals a role for autoantibodies in the loss of secretory function of exocrine tissues in Sjogren's syndrome SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID LABIAL SALIVARY-GLANDS; NOD MICE; T-CELLS; RECEPTORS; MOUSE; HYPERTENSION; MECHANISMS; SIGNAL; NERVES; MODEL AB The NOD (nonobese diabetic) mouse has been studied as an animal model for autoimmune insulin-dependent diabetes and Sjogren's syndrome, NOD.Ig mu(null) mice, which lack functional B lymphocytes, develop progressive histopathologic lesions of the submandibular and lachrymal glands similar to NOD mice, but in the absence of autoimmune insulitis and diabetes. Despite the focal appearance of T cells in salivary and lachrymal tissues, NOD.Ig mu(null) mice fail to lose secretory function as determined by stimulation of the muscarinic/cholinergic receptor by the agonist pilocarpine, suggesting a role for B cell autoantibodies in mediating exocrine dryness. Infusion of purified serum IgG or F(ab')(2) fragments from parental NOD mice or human primary Sjogren's syndrome patients, but not serum IgG from healthy controls, alters stimulated saliva production, an observation consistent with antibody binding to neural receptors, Furthermore, human patient Ige fractions competitively inhibited the binding of the muscarinic receptor agonist, [H-3]quinuclidinyl benzilate, to salivary gland membranes. This autoantibody activity is lost after preadsorption with intact salivary cells. These findings indicate that autoantibodies play an important part in the functional impairment of secretory processes seen in connection with the autoimmune exocrinopathy of Sjogren's syndrome. C1 Univ Florida, Dept Oral Biol, Gainesville, FL 32610 USA. Univ Florida, Dept Oral Surg, Gainesville, FL 32610 USA. Univ Florida, Ctr Orphaned Autoimmune Dis, Gainesville, FL 32610 USA. Forsyth Dent Ctr, Boston, MA 02115 USA. Univ Bergen, Dept Internal Med B, N-5021 Bergen, Norway. Univ Bergen, Broegelmann Res Lab, N-5021 Bergen, Norway. Univ Bergen, Dept Med B, Div Rheumatol, N-5021 Bergen, Norway. RP Humphreys-Beher, MG (reprint author), Univ Florida, Dept Oral Biol, POB 100424, Gainesville, FL 32610 USA. FU NIDCR NIH HHS [DE 10515] NR 34 TC 147 Z9 151 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 23 PY 1998 VL 95 IS 13 BP 7538 EP 7543 DI 10.1073/pnas.95.13.7538 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZW683 UT WOS:000074436400055 PM 9636185 ER PT J AU Owen, AM Stern, CE Look, RB Tracey, I Rosen, BR Petrides, M AF Owen, AM Stern, CE Look, RB Tracey, I Rosen, BR Petrides, M TI Functional organization of spatial and nonspatial working memory processing within the human lateral frontal cortex SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PREFRONTAL CORTEX; SENSORY STIMULATION; OBJECT; DISSOCIATION; ACTIVATION; SYSTEMS; TASKS; PET AB The present study used functional magnetic resonance imaging to demonstrate that performance of visual spatial and visual nonspatial working memory tasks involve the same regions of the lateral prefrontal cortex when all factors unrelated to the type of stimulus material are appropriately controlled. These results provide evidence that spatial and nonspatial working memory may not be mediated, respectively, by mid-dorsolateral and mid-ventrolateral regions of the frontal lobe, as widely assumed, and support the alternative notion that specific regions of the lateral prefrontal cortex make identical executive functional contributions to both spatial and nonspatial working memory. C1 MRC, Appl Psychol Unit, Cambridge CB2 2EF, England. Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Charlestown, MA 02129 USA. McGill Univ, Montreal Neurol Inst, Cognit Neurosci Lab, Montreal, PQ H3A 2B4, Canada. RP Owen, AM (reprint author), MRC, Appl Psychol Unit, 15 Chaucer Rd, Cambridge CB2 2EF, England. RI Owen, Adrian/B-4997-2015 NR 23 TC 249 Z9 253 U1 0 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 23 PY 1998 VL 95 IS 13 BP 7721 EP 7726 DI 10.1073/pnas.95.13.7721 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZW683 UT WOS:000074436400087 PM 9636217 ER PT J AU Atlas, SJ Benzer, TI Borowsky, LH Chang, YC Burnham, DC Metlay, JP Halm, EA Singer, DE AF Atlas, SJ Benzer, TI Borowsky, LH Chang, YC Burnham, DC Metlay, JP Halm, EA Singer, DE TI Safely increasing the proportion of patients with community-acquired pneumonia treated as outpatients - An interventional trial SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID MANAGEMENT; DIAGNOSIS; THERAPY; ADULTS; COSTS AB Background: Patients with community-acquired pneumonia who are at low risk for short-term mortality can be identified using a validated prediction rule, the Pneumonia Severity Index. Such patients should be candidates for outpatient treatment, yet many are hospitalized. Objective: To assess a program to safely increase the proportion of low-risk patients with pneumonia treated at home. Methods: The intervention provided physicians with the Pneumonia Severity Index score and corresponding mortality risk for eligible patients and offered enhanced visiting nurse services and the antibiotic clarithromycin. Prospectively enrolled, consecutive low-risk patients with pneumonia presenting to an emergency department during the intervention period (n = 166) were compared with consecutive retrospective controls (n = 147) identified during the prior year. A second group of 208 patients from the study hospital who participated in the Pneumonia Patient Outcomes Research Team cohort study served as controls for patient-reported measures of recovery. Results: There were no significant baseline differences between patients in the intervention and control groups. The percentage initially treated as outpatients increased from 42% in the control period to 57% in the intervention period (36% relative increase; 95% confidence interval, 8%-72%; P =.01). However, more outpatients during the intervention period were subsequently admitted to the study hospital (9% vs 0%). When any admission to the study hospital within 4 weeks of presentation was considered, there was a trend toward more patients receiving all their care as outpatients in the intervention group (42% vs 52%; 25% relative increase; 95% confidence interval -2% to 59%; P =.07). No patient in the intervention group died in the 4-week follow-up period. Symptom resolution and functional status were not diminished. Satisfaction with overall care was similar, but patients treated in the outpatient setting during the intervention were less frequently satisfied with the initial treatment location than comparable control patients (71% vs 90%; P =.04). Conclusions: Use of a risk-based algorithm coupled with enhanced outpatient services effectively identified low-risk patients with community-acquired pneumonia in the emergency department and safely increased the proportion initially treated as outpatients. Outpatients in the intervention group were more likely to be subsequently admitted than were controls, lessening the net impact of the intervention. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gen Med Div,Med Serv, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Med Practices Evaluat Ctr, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA 02114 USA. RP Atlas, SJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gen Med Div,Med Serv, 50 Staniford St, Boston, MA 02114 USA. NR 19 TC 159 Z9 164 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JUN 22 PY 1998 VL 158 IS 12 BP 1350 EP 1356 DI 10.1001/archinte.158.12.1350 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA ZV323 UT WOS:000074293100009 PM 9645830 ER PT J AU McGee, SR Boyko, EJ AF McGee, SR Boyko, EJ TI Physical examination and chronic lower-extremity ischemia - A critical review SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID PERIPHERAL ARTERIAL-DISEASE; CLINICAL-EVALUATION; OCCLUSIVE DISEASE; PULSE PALPATION; DIAGNOSTIC METHODS; PREDICTIVE VALUE; CLAUDICATION; PRESSURE; EXERCISE AB Objective: To determine the clinical utility of physical examination in patients with suspected chronic ischemia of the lower extremities. Data Sources: MEDLINE search (January 1966 to January 1997), personal files, and bibliographies of textbooks on physical diagnosis, surgery, and vascular surgery. Study Selection: Both authors independently graded the studies as level 1, 2, or 3, according to predetermined criteria. Criteria deemed essential for analysis of sensitivity, specificity, and likelihood ratios were (1) clear definition of study population, (2) clear definition of physical examination maneuver, and (3) use of an acceptable criterion standard test for comparison. Results: The following positive findings help clinicians diagnose the presence of peripheral arterial disease: abnormal pedal pulses, a unilaterally cool extremity, a prolonged venous filling time, and a femoral bruit. Other physical signs help determine the extent and distribution of vascular disease, including an abnormal femoral pulse, lower-extremity bruits, warm knees, and the Buerger test. The capillary refill test and the findings of foot discoloration, atrophic skin, and hairless extremities are unhelpful in diagnostic decisions. Mathematical formulas, derived from 2 studies using multivariate analysis, allow clinicians to estimate the probability of peripheral arterial disease in their patients. Conclusion: Certain aspects of the physical examination help clinicians make accurate judgments about the presence of peripheral arterial disease and its distribution. C1 Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Seattle, WA 98108 USA. RP McGee, SR (reprint author), Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Mailstop 111,1660 S Columbian Way, Seattle, WA 98108 USA. NR 52 TC 59 Z9 63 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JUN 22 PY 1998 VL 158 IS 12 BP 1357 EP 1364 DI 10.1001/archinte.158.12.1357 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA ZV323 UT WOS:000074293100010 PM 9645831 ER PT J AU Yao, JK Reddy, R McElhinny, LG van Kammen, DP AF Yao, JK Reddy, R McElhinny, LG van Kammen, DP TI Reduced status of plasma total antioxidant capacity in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE antioxidant defense system; total antioxidant status; haloperidol ID FREE-RADICAL PATHOLOGY; LIPID-PEROXIDATION; INDICATORS; DISMUTASE; PSYCHOSIS; DISULFIDE; VITAMINS; COTININE; DEFENSE; FLUIDS AB To examine whether antioxidant capacity is reduced in patients with schizophrenia, we determined plasma total antioxidant status (TAS) by quenching the absorbance of the radical cation formed by the reaction of 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) with a metmyoglobin and hydrogen peroxide. TAS serves as an index of net antioxidant activity derived from various antioxidants in plasma. Male schizophrenic patients were compared with age- and sex-matched healthy control subjects, using a within-subject, repeated measures, on-off-on haloperidol treatment design. Drug-free patients were free of all psychotropic medications for an average of 32 days. Plasma TAS was significantly lower in patients with schizophrenia than in normal controls. Plasma TAS in patients was significantly and inversely correlated with symptom severity during the drug-free condition. There were no significant differences between on and off haloperidol-treatment conditions. When patients returned to haloperidol treatment after relapse, the plasma TAS remained fairly constant and was not significantly different from the same individuals during haloperidol-stabilization or drug-free periods. These findings are indicative of an impaired antioxidant defense system, not attributable to neuroleptic treatment, and lend further support to the notion that oxidative stress may have a pathophysiological role in schizophrenia. (C) 1998 Elsevier Science B.V. All rights reserved. C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA 15213 USA. RP Yao, JK (reprint author), VA Pittsburgh Healthcare Syst, 7180 Highland Dr, Pittsburgh, PA 15206 USA. NR 32 TC 103 Z9 104 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD JUN 22 PY 1998 VL 32 IS 1 BP 1 EP 8 DI 10.1016/S0920-9964(98)00030-9 PG 8 WC Psychiatry SC Psychiatry GA 103KW UT WOS:000075156100001 PM 9690328 ER PT J AU Serra-Pages, C Medley, QG Tang, M Hart, A Streuli, M AF Serra-Pages, C Medley, QG Tang, M Hart, A Streuli, M TI Liprins, a family of LAR transmembrane protein-tyrosine phosphatase-interacting proteins SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NERVOUS-SYSTEM; AXON GUIDANCE; COILED COILS; ASSOCIATION; DROSOPHILA; EXPRESSION; ISOFORMS; KINASES; DELTA; SUPERFAMILY AB LAR family transmembrane protein-tyrosine phosphatases function in axon guidance and mammary gland development. In cultured cells, LAR binds to the intracellular, coiled coil LAB-interacting protein at discrete ends of focal adhesions, implicating these proteins in the regulation of cell-matrix interactions. We describe seven LAB-interacting protein-like genes in humans and Caenorhabditis elegans that form the liprin gene family, Based on sequence similarities and binding characteristics, liprins are subdivided into alpha-type and beta-type liprins. The C-terminal, non-coiled coil regions of alpha-liprins bind to the membrane-distal phosphatase domains of LAR family members, as well as to the C-terminal, non-coiled coil region of beta-liprins. Both alpha- and beta-liprins homodimerize via their N-terminal, coiled coil regions. Liprins are thus multivalent proteins that potentially form complex structures. Some liprins have broad mRNA tissue distributions, whereas others are predominately expressed in the brain. Go-expression studies indicate that liprin-alpha 2 alters LAR cellular localization and induces LAR clustering. We propose that liprins function to localize LAR family tyrosine phosphatases at specific sites on the plasma membrane, possibly regulating their interaction with the extracellular environment and their association with substrates. C1 Dana Farber Canc Inst, Div Tumor Immunol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. RP Streuli, M (reprint author), Dana Farber Canc Inst, Div Tumor Immunol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA55547] NR 39 TC 166 Z9 182 U1 1 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 19 PY 1998 VL 273 IS 25 BP 15611 EP 15620 DI 10.1074/jbc.273.25.15611 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZV238 UT WOS:000074284200047 PM 9624153 ER PT J AU Maynard, KI Arango, PM Chen, D Ogilvy, CS AF Maynard, KI Arango, PM Chen, D Ogilvy, CS TI Acetylsalicyclate administered during simulated ischemia reduces the recovery of neuronal function in the in vitro rabbit retina SO NEUROSCIENCE LETTERS LA English DT Article DE aspirin; ischemia; lysine acetylsalicylate; retina; stroke ID ASPIRIN AB Aspirin is widely used as an analgesic, in the secondary prevention of stroke, and has recently been suggested to be a putative neuroprotective agent, yet whether it acts directly on the central nervous system (CNS) is not yet clarified. We therefore examined the effect of lysine acetylsalicylate (L-ASA, 4-2000 mu M) on neuronal function under normal conditions and following 1 h of ischemia using the in vitro rabbit retina preparation. L-ASA inhibited the light-evoked compound action potentials, but not the electroretinogram, in a concentration-dependent manner. In addition, L-ASA (2000 mu M, but not 4, 40 or 200 mu M) administered during ischemia, reduced the recovery of neuronal function compared to control (untreated) retinas. L-ASA therefore inhibits CNS neurotransmission, but not phototransduction, in a concentration-dependent manner. In addition, high concentration L-ASA impairs the recovery of neuronal function following an ischemic episode. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Neurosurg Serv, Neurophysiol Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Pontificia Univ Javeriana, Dept Neurosurg, Bogota, Colombia. RP Maynard, KI (reprint author), Massachusetts Gen Hosp, Neurosurg Serv, Neurophysiol Lab, Edwards 414,55 Fruit St, Boston, MA 02114 USA. FU NINDS NIH HHS [NS 01732] NR 19 TC 11 Z9 11 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD JUN 19 PY 1998 VL 249 IS 2-3 BP 159 EP 162 DI 10.1016/S0304-3940(98)00416-9 PG 4 WC Neurosciences SC Neurosciences & Neurology GA ZZ591 UT WOS:000074745500023 PM 9682841 ER PT J AU Wyatt, R Sodroski, J AF Wyatt, R Sodroski, J TI The HIV-1 envelope glycoproteins: Fusogens, antigens, and immunogens SO SCIENCE LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN MONOCLONAL-ANTIBODY; AMINO-ACID-RESIDUES; INTERCELLULAR-ADHESION MOLECULE-1; TYPE-1 GP120 GLYCOPROTEIN; CD4 BINDING-SITE; HUMAN CELL-LINES; NEUTRALIZING ANTIBODIES; RECEPTOR-BINDING; HTLV-III AB The human immunodeficiency virus-type 1 (HIV-1) envelope glycoproteins interact with receptors on the target cell and mediate virus entry by fusing the viral and cell membranes. The structure of the envelope glycoproteins has evolved to fulfill these functions while evading the neutralizing antibody response. An understanding of the viral strategies for immune evasion should guide attempts to improve the immunogenicity of the HIV-1envelope glycoproteins and, ultimately, aid in HIV-1vaccine development. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol AIDS,Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Sodroski, J (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol AIDS,Dept Pathol, Boston, MA 02115 USA. FU NIAID NIH HHS [AI 31783, AI 39420, AI28691] NR 178 TC 1065 Z9 1090 U1 12 U2 98 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JUN 19 PY 1998 VL 280 IS 5371 BP 1884 EP 1888 DI 10.1126/science.280.5371.1884 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZV618 UT WOS:000074323800046 PM 9632381 ER PT J AU Rizzuto, CD Wyatt, R Hernandez-Ramos, N Sun, Y Kwong, PD Hendrickson, WA Sodroski, J AF Rizzuto, CD Wyatt, R Hernandez-Ramos, N Sun, Y Kwong, PD Hendrickson, WA Sodroski, J TI A conserved HIV gp120 glycoprotein structure involved in chemokine receptor binding SO SCIENCE LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; AMINO-ACID CHANGES; ENVELOPE GLYCOPROTEIN; INFLUENZA HEMAGGLUTININ; FUNCTIONAL EXPRESSION; MOLECULAR-CLONING; VARIABLE LOOP; FUSION; INFECTION; PEPTIDE AB The entry of primate immunodeficiency viruses into target cells depends on a sequential interaction of the gp120 envelope glycoprotein with the cellular receptors, CD4 and members of the chemokine receptor family. The gp120 third variable (V3) loop has been implicated in chemokine receptor binding, but the use of the CCR5 chemokine receptor by diverse primate immunodeficiency viruses suggests the involvement of an additional, conserved gp120 element. Through the use of gp120 mutants, a highly conserved gp120 structure was shown to be critical for CCR5 binding. This structure is located adjacent to the V3 loop and contains neutralization epitopes induced by CD4 binding. This conserved element may be a useful target for pharmacologic or prophylactic intervention in human immunodeficiency virus (HIV) infections. C1 Harvard Univ, Sch Med, Dept Pathol, Dana Farber Canc Inst,Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Columbia Univ, Howard Hughes Med Inst, Dept Biochem & Mol Biophys, New York, NY 10032 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Sodroski, J (reprint author), Harvard Univ, Sch Med, Dept Pathol, Dana Farber Canc Inst,Dept Canc Immunol & AIDS, Boston, MA 02115 USA. FU NIAID NIH HHS [AI 40895, AI 41851] NR 49 TC 676 Z9 695 U1 2 U2 36 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JUN 19 PY 1998 VL 280 IS 5371 BP 1949 EP 1953 DI 10.1126/science.280.5371.1949 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZV618 UT WOS:000074323800068 PM 9632396 ER PT J AU Mele, D Pedini, I Alboni, P Levine, RA AF Mele, D Pedini, I Alboni, P Levine, RA TI Anatomic M-mode: A new technique for quantitative assessment of left ventricular size and function SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article; Proceedings Paper CT 9th International Congress on Echocardiography - Clinical Cardiology CY FEB 05-08, 1997 CL ROME, ITALY AB To overcome the limitations of conventional M-mode echocardiography, a new technique refereed to as anatomic M-mode has been recently developed. This technique is based on postprocessing of digitally acquired two-dimensional (2D) cineloops, and allows the operator to position one or multiple independent M-mode cursors freely on the 2D images. Initial clinical data show that anatomic M-mode can increase the reproducibility and accuracy of standard M-mode measurements of the left ventricle. Also, this quantitative technique hers the potential to improve assessment of left ventricular wall motion and thickening, and could be particularly useful in providing objective measures during stress echocardiography. (C) 1998 by Excerpta Medica, Inc. C1 Osped Civile SS Annunziata, Div Cardiol, I-44042 Cento, Fe, Italy. Massachusetts Gen Hosp, Noninvas Cardiac Lab, Boston, MA 02114 USA. RP Mele, D (reprint author), Osped Civile SS Annunziata, Div Cardiol, Via Vicini 2, I-44042 Cento, Fe, Italy. NR 4 TC 20 Z9 22 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JUN 18 PY 1998 VL 81 IS 12A SI SI BP 82G EP 85G DI 10.1016/S0002-9149(98)00060-5 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA ZY513 UT WOS:000074629200017 PM 9662234 ER PT J AU Mele, D Maehle, J Pedini, I Alboni, P Levine, RA AF Mele, D Maehle, J Pedini, I Alboni, P Levine, RA TI Three-dimensional echocardiographic reconstruction: Description and applications of a simplified technique for quantitative assessment of left ventricular size and function SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article; Proceedings Paper CT 9th International Congress on Echocardiography - Clinical Cardiology CY FEB 05-08, 1997 CL ROME, ITALY ID 3-DIMENSIONAL ECHOCARDIOGRAPHY; VOLUME; VALIDATION AB A simplified system for three-dimensional (3D) reconstruction of the left ventricle and quantitation of its size and function is described. This system requires the acquisition of a minimum number of two-dimensional (2D) echocardiographic apical views, which are obtained by rotation of the probe about the initial imaging point. Traced endocardial borders are spatially reconstructed according to the common apex and longitudinal axis of the views and to the measured or assumed angular relation between scanned planes. This technique has been applied in vitro to regular and irregular ventricular phantoms, yielding excellent accuracy for volume calculation. Also, it has been applied clinically for left ventricular volume, stroke volume, and ejection fraction calculation in both normal subjects and patients with various cardiac diseases, providing good results compared with other independent imaging techiques and showing increased accuracy with respect to 2D echocardiographic methods. Because this is obtained without substantial increase in time, effort, or cost, this simplified technique for 3D reconstruction should therefore be of value in daily clinical echocardiographic practice. (C) 1998 by Excerpta Medica, Inc. C1 Osped Civile SS Annunziata, Div Cardiol, I-44042 Cento, Fe, Italy. Univ Trondheim, Dept Biomed Engn, N-7006 Trondheim, Norway. Massachusetts Gen Hosp, Noninvas Cardiac Lab, Boston, MA 02114 USA. RP Mele, D (reprint author), Osped Civile SS Annunziata, Div Cardiol, Via Vicini 2, I-44042 Cento, Fe, Italy. NR 31 TC 19 Z9 19 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JUN 18 PY 1998 VL 81 IS 12A SI SI BP 107G EP 110G DI 10.1016/S0002-9149(98)00065-4 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA ZY513 UT WOS:000074629200022 PM 9662239 ER PT J AU Towle, CA Wright, M Hecht, AC Kuong, SJ Papanicolas, LE Totkovic, R Mankin, HJ Treadwell, BV AF Towle, CA Wright, M Hecht, AC Kuong, SJ Papanicolas, LE Totkovic, R Mankin, HJ Treadwell, BV TI A matrix metalloproteinase proenzyme activator produced by articular cartilage SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID OSTEOARTHRITIC CARTILAGE; CLEAVAGE-SITE; LINK PROTEIN; STROMELYSIN; COLLAGENASE; TISSUE; INTERLEUKIN-1; PURIFICATION; CHONDROCYTES; PLASMINOGEN AB Matrix metalloproteinases (MMPs) are involved in connective tissue turnover under physiological and pathological conditions. MMP activity is regulated by the requirement for zymogen activation. This report describes a proMMP-3 activator produced by articular cartilage. The activator initiates a step-wise processing of proMMP-3 to generate an array of active species. Sequencing of activation intermediates demonstrated cleavage on the NH2-terminal side of certain basic residues in the MMP-3 propeptide. Metal ion chelators inhibited activator-dependent proteolysis, and activity was restored by low levels of ZnCl2. These catalytic properties suggest similarity to members of the insulinase superfamily of metalloendopeptidases with in vitro specificity for single arginine or paired basic processing sites in a variety of prohormones. Dibasic sites also exist in the propeptides of several MMPs including proMMP-3. This is the first report that cartilage produces a potent MMP proenzyme activator, opening the possibility of a novel intrinsic activation pathway for catabolic processes in this avascular tissue. (C) 1998 Academic Press. C1 Massachusetts Gen Hosp, Orthopaed Res Labs GRJ 1124, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Towle, CA (reprint author), Massachusetts Gen Hosp, Orthopaed Res Labs GRJ 1124, 32 Fruit St, Boston, MA 02114 USA. FU NIAMS NIH HHS [R0-1 AR16265, ARO7112] NR 35 TC 4 Z9 4 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 18 PY 1998 VL 247 IS 2 BP 324 EP 331 DI 10.1006/bbrc.1998.8781 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA ZV933 UT WOS:000074356400024 PM 9642125 ER PT J AU Kumar, V Heinemann, FS Ozols, J AF Kumar, V Heinemann, FS Ozols, J TI Interleukin-2 induces N-glycosylation in T-cells: Characterization of human lymphocyte oligosaccharyltransferase SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID AMINO-ACID-SEQUENCE; PROTEIN COMPLEX; ENDOPLASMIC-RETICULUM; TRANSFERASE-ACTIVITY; RIBOSOME BINDING; ROUGH MICROSOMES; 50-KDA SUBUNIT; RIBOPHORINS-I; YEAST WBP1P; MEMBRANE AB We have investigated the enzyme mediating N-glycosylation in "resting" and activated lymphocytes. Normal peripheral blood lymphocytes (PBLs) were found to have low activity for glycosylation of a synthetic glycan acceptor peptide. N-glycosylation activity increased 10-fold after mitogen activation of PBLs. N-glycosylation activity remained elevated during longterm culture and expansion of human lymphocytes when growth was supported by interleukin-a. To our knowledge, this is the first biochemical evidence for induction of endoplasmic reticulum functions during T-cell activation. The enzyme mediating N-glycosylation in lymphocytes was localized predominantly but not entirely to a microsomal organelle by subcellular fractionation. After solubilization and 85-fold purification from salt-washed microsomes, the enzyme preparation contained four predominant proteins. N-terminal sequence analysis identified the proteins as ribophorin I, ribophorin II (doublet), and a 50-kDa homologue of Wbp1, a yeast protein essential for N-glycosylation. (C) 1998 Academic Press. C1 Univ Connecticut, Ctr Hlth, Dept Biochem, Farmington, CT 06030 USA. Hoag Mem Hosp Presbyterian, Dept Pathol, Newport Beach, CA 92663 USA. RP Kumar, V (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. FU NIGMS NIH HHS [R01-GM-26351] NR 29 TC 8 Z9 9 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 18 PY 1998 VL 247 IS 2 BP 524 EP 529 DI 10.1006/bbrc.1998.8780 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA ZV933 UT WOS:000074356400062 PM 9642163 ER PT J AU Kwong, PD Wyatt, R Robinson, J Sweet, RW Sodroski, J Hendrickson, WA AF Kwong, PD Wyatt, R Robinson, J Sweet, RW Sodroski, J Hendrickson, WA TI Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody SO NATURE LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; CRYSTAL-STRUCTURE; TRANSMEMBRANE GLYCOPROTEIN; VARIABLE REGIONS; ATOMIC-STRUCTURE; BINDING; RESOLUTION; FRAGMENT; AIDS; HEMAGGLUTININ AB The entry of human Immunodeficiency virus (HIV) into cells requires the sequential interaction of the viral exterior envelope glycoprotein, gp120, with the CD4 glycoprotein and a chemokine receptor on the cell surface. These interactions initiate a fusion of the viral and cellular membranes. Although gp120 can elicit virus-neutralizing antibodies, HIV eludes the Immune system. We have solved the X-ray crystal structure at 2.5 Angstrom resolution of an HIV-1 gp120 core complexed with a two-domain fragment of human con and an antigen-binding fragment of a neutralizing antibody that blocks chemokine-receptor binding. The structure reveals a cavity-laden CD4-gp120 interface, a conserved binding site for the chemokine receptor, evidence for a conformational change upon CD4 binding, the nature of a CD4-induced antibody epitope, and specific mechanisms for immune evasion. Our results provide a framework for understanding the complex biology of HIV entry into cells and should guide efforts to Intervene. C1 Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA. Columbia Univ, Howard Hughes Med Inst, New York, NY 10032 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. Tulane Univ, Med Ctr, Dept Pediat, New Orleans, LA 70112 USA. SmithKline Beecham Pharmaceut, Dept Immunol, King Of Prussia, PA 19406 USA. RP Hendrickson, WA (reprint author), Columbia Univ, Dept Biochem & Mol Biophys, 630 W 168th St, New York, NY 10032 USA. EM wayne@convex.hhmi.columbia.edu NR 50 TC 1993 Z9 2055 U1 23 U2 213 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD JUN 18 PY 1998 VL 393 IS 6686 BP 648 EP 659 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZV288 UT WOS:000074289600043 PM 9641677 ER PT J AU Boden, WE O'Rourke, RA Crawford, MH Blaustein, AS Deedwania, PC Zoble, RG Wexler, LF Kleiger, RE Pepine, CJ Ferry, DR Chow, BK Lavori, PW AF Boden, WE O'Rourke, RA Crawford, MH Blaustein, AS Deedwania, PC Zoble, RG Wexler, LF Kleiger, RE Pepine, CJ Ferry, DR Chow, BK Lavori, PW CA VANQWISH Trial Investigators TI Outcomes in patients with acute non-Q-wave myocardial infarction randomly assigned to an invasive as compared with a conservative management strategy SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID BYPASS GRAFT-SURGERY; CLINICAL-TRIALS; SHORT-TERM; MORTALITY; PROGNOSIS; REINFARCTION; EXTENSION; EVOLUTION; DILTIAZEM; ISCHEMIA AB Background Non-Q-wave myocardial infarction is usually managed according to an "invasive" strategy (i.e., one of routine coronary angiography followed by myocardial revascularization). Methods We randomly assigned 920 patients to either "invasive" management (462 patients) or "conservative" management, defined as medical therapy and noninvasive testing, with subsequent invasive management if indicated by the development of spontaneous or inducible ischemia (458 patients), within 72 hours of the onset of a non-Q-wave infarction. Death or nonfatal infarction made up the combined primary end point. Results During an average follow-up of 23 months, 152 events (80 deaths and 72 nonfatal infarctions) occurred in 138 patients who had been randomly assigned to the invasive strategy, and 139 events (59 deaths and 80 nonfatal infarctions) in 123 patients assigned to the conservative strategy (P=0.35). Patients assigned to the invasive strategy had worse clinical outcomes during the first year of follow-up. The number of patients with one of the components of the primary end point (death or nonfatal myocardial infarction) and the number who died were significantly higher in the invasive-strategy group at hospital discharge (36 vs. 15 patients, P=0.004, for the primary end point; 21 vs. 6, P=0.007, for death), at one month (48 vs. 26, P=0.072; 23 vs. 9, P=0.021), and at one year (111 vs. 85, P=0.05; 58 vs. 36, P=0.025). Overall mortality during follow-up did not differ significantly between patients assigned to the conservative-strategy group and those assigned to the invasive-strategy group (hazard ratio, 0.72; 95 percent confidence interval, 0.51 to 1.01). Conclusions Most patients with non-Q-wave myocardial infarction do not benefit from routine, early invasive management consisting of coronary angiography and revascularization. A conservative, ischemia-guided initial approach is both safe and effective. (C) 1998, Massachusetts Medical Society. C1 Vet Affairs Healthcare Network Upstate NY, Med Serv, Syracuse, NY 13210 USA. SUNY Hlth Sci Ctr, Syracuse, NY 13210 USA. Vet Affairs Med Ctr, San Antonio, TX USA. Vet Affairs Med Ctr, Albuquerque, NM USA. Vet Affairs Med Ctr, Houston, TX 77030 USA. Vet Affairs Med Ctr, Fresno, CA USA. James A Haley Vet Adm Med Ctr, Tampa, FL 33612 USA. Vet Affairs Med Ctr, Cincinnati, OH 45267 USA. Washington Univ, Jewish Hosp St Louis, Sch Med, St Louis, MO 63110 USA. Vet Affairs Med Ctr, Gainesville, FL 32608 USA. Jerry L Pettis Mem Vet Adm Med Ctr, Loma Linda, CA 92354 USA. Dept Vet Affairs, Cooperat Studies Program Coordinating Ctr, Palo Alto, CA USA. Vet Affairs Med Ctr, Syracuse, NY 13210 USA. RP Boden, WE (reprint author), Vet Affairs Healthcare Network Upstate NY, Med Serv, 800 Irving Ave, Syracuse, NY 13210 USA. NR 45 TC 545 Z9 578 U1 2 U2 3 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 18 PY 1998 VL 338 IS 25 BP 1785 EP 1792 DI 10.1056/NEJM199806183382501 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA ZU443 UT WOS:000074197500001 PM 9632444 ER PT J AU Maulik, N Sato, M Price, BD Das, DK AF Maulik, N Sato, M Price, BD Das, DK TI An essential role of NF kappa B in tyrosine kinase signaling of p38 MAP kinase regulation of myocardial adaptation to ischemia SO FEBS LETTERS LA English DT Article DE nuclear factor kappa B; mitogen associated protein kinase; tyrosine kinase; ischemia; heart; adaptation; oxidative stress; signal transduction ID HUMAN-IMMUNODEFICIENCY-VIRUS; FREE-RADICALS; REPERFUSION ARRHYTHMIAS; TRANSCRIPTION FACTOR; OXIDATIVE STRESS; GENE-EXPRESSION; INFARCT SIZE; RAT HEARTS; ACTIVATION; BINDING AB We hale recently demonstrated that myocardial adaptation to ischemia triggers a tyrosine kinase regulated signaling pathway leading to the translocation and activation of p38 MAP kinase and MAPKAP kinase 2, Since oxidative stress is developed during ischemic adaptation and since free radicals have recently been shown to function as an intracellular signaling agent leading to the activation of nuclear transcription factor, NF kappa B, we examined whether NF kappa B was involved in the ischemic adaptation process. Isolated perfused rat hearts were adapted to ischemic stress by repeated ischemia and reperfusion, Hearts were pretreated with genistein to block tyrosine kinase while SE 203580 was used to inhibit p38 MAP kinases, Ischemic adaptation was associated with the nuclear translocation and activation of NF kappa B which was significantly blocked by both genistein and SE 203580, The ischemically adapted hearts were more resistant to ischemic reperfusion injury as evidenced by better function recovery and less tissue injury during postischemic reperfusion. Ischemic adaptation developed oxidative stress which was reflected by increased malonaldehyde formation. A synthetic peptide containing a cell membrane-permeable motif and nuclear sequence, SN 50, which blocked nuclear translocation of NF kappa B during ischemic adaptation, significantlp inhibited the beneficial effects of adaptation on functional recovery and tissue injury. In concert, SN 50 reduced the oxidative stress developed in the adapted myocardium. These results demonstrate that p38 MAP kinase might be upstream of NF kappa B which plays a role in ischemic preconditioning of heart. (C) 1998 Federation of European Biochemical Societies. C1 Univ Connecticut, Sch Med, Mol Cardiol Lab, Farmington, CT 06030 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Maulik, N (reprint author), Univ Connecticut, Sch Med, Mol Cardiol Lab, Farmington, CT 06030 USA. EM nmulik@neuron.uchc.edu FU NHLBI NIH HHS [HL 34360, HL 22559, HL 33889] NR 32 TC 191 Z9 208 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD JUN 16 PY 1998 VL 429 IS 3 BP 365 EP 369 DI 10.1016/S0014-5793(98)00632-2 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA ZX337 UT WOS:000074505400031 PM 9662450 ER PT J AU Koelling, TM Kirmse, M Di Salvo, TG Dec, GW Zapol, WM Semigran, MJ AF Koelling, TM Kirmse, M Di Salvo, TG Dec, GW Zapol, WM Semigran, MJ TI Inhaled nitric oxide improves exercise capacity in patients with severe heart failure and right ventricular dysfunction SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID THERAPY; MORTALITY; PRESSURE AB Fourteen cardiac transplant candidates were studied with cardiopulmonary exercise testing at baseline and while breathing nitric oxide (40 ppm). Oxygen consumption at the anaerobic threshold was improved by breathing nitric oxide in patients with pulmonary hypertension and in patients with an elevated left ventricular end-diastolic volume index. C1 Massachusetts Gen Hosp, Heart Failure & Cardiac Transplantat Ctr, Cardiac Unit, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Semigran, MJ (reprint author), Massachusetts Gen Hosp, Heart Failure & Cardiac Transplantat Ctr, Cardiac Unit, Dept Med, Bigelow 645,55 Fruit St, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL-42397] NR 10 TC 20 Z9 21 U1 3 U2 3 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JUN 15 PY 1998 VL 81 IS 12 BP 1494 EP + DI 10.1016/S0002-9149(98)00214-8 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA ZU633 UT WOS:000074217600019 PM 9645904 ER PT J AU Platz, EA Giovannucci, E Rimm, EB Curhan, GC Spiegelman, D Colditz, GA Willett, WC AF Platz, EA Giovannucci, E Rimm, EB Curhan, GC Spiegelman, D Colditz, GA Willett, WC TI Retrospective analysis of birth weight and prostate cancer in the health professionals follow-up study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE birth weight; cohort studies; prostatic neoplasms ID RISK AB The authors retrospectively evaluated the relation between birth weight and prostate cancer (1986-1994) among 21,140 men of the Health Professionals Follow-up Study who reported in 1994 their weight at birth. No relation between birth weight and prostate cancer (n = 545) was observed in multivariate logistic models. For high stage/grade tumors (n = 213), compared with birth weights <7.0 Ibs (<3,175 g), the relative risks were 1.20 (95% confidence interval (CI) 0.79-1.83) for 8.5-9.9 Ibs (3,855.6-4,490.6 g) and 1.30 (95% CI 0.80-2.10) for greater than or equal to 10 Ibs (greater than or equal to 4,536 g). These findings do not support an overall association between birth weight and prostate cancer incidence, but the possibility of a modest positive association between birth weight and high stage/grade prostatic cancer cannot be excluded. C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Channing Lab, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Med Serv, Renal Unit, Boston, MA 02114 USA. RP Platz, EA (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA. RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [CA55075, T32 CA 09001-20]; NHLBI NIH HHS [HL35464] NR 14 TC 35 Z9 35 U1 0 U2 1 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 15 PY 1998 VL 147 IS 12 BP 1140 EP 1144 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA ZV942 UT WOS:000074357700006 PM 9645792 ER PT J AU Labbate, LA Grimes, JB Arana, GW AF Labbate, LA Grimes, JB Arana, GW TI Serotonin reuptake antidepressant effects on sexual function in patients with anxiety disorders SO BIOLOGICAL PSYCHIATRY LA English DT Article DE serotonin reuptake inhibitors; antidepressants; orgasm; sex dysfunction; adverse effects ID PREMATURE EJACULATION; DYSFUNCTION AB Background: Serotonin reuptake inhibitor (SRI) antidepressants have been associated with sexual dysfunction, though there have been few prospective reports specifically examining this problem. The purpose of this study was to determine if three SRIs affected sexual function in anxiety disorder patients over a 3-month period. Methods: Thirty-one patients were enrolled in a prospective study of the effect of three SRIs, fluoxetine, sertraline, and paroxetine, on five aspects of sexual function: libido, erection/lubrication, orgasm quality, orgasm delay, and sexual frequency. Measurements were made at baseline and at each month on visual analogue scales. Results: For men and women, orgasm quality was lower and orgasm delay longer at months one, two, and three compared to baseline (p <.01). Erection scores were lower over time, but this change was not statistically significant. Lubrication, libido, and sexual frequency were not appreciably changed over 3 months. A higher rate of anorgasmia was noted in women at months one and two, but this did not achieve significance. Conclusions: Orgasm appears to be a primary sexual function affected by SRIs. Published 1998 Society of Biological Psychiatry. C1 Ralph H Johnson VA Med Ctr, Mental Hlth Serv, Charleston, SC 29401 USA. Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. Walter Reed Army Med Ctr, Dept Psychiat & Neurol, Washington, DC 20307 USA. RP Labbate, LA (reprint author), Ralph H Johnson VA Med Ctr, Mental Hlth Serv, 109 Bee St, Charleston, SC 29401 USA. NR 10 TC 44 Z9 47 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUN 15 PY 1998 VL 43 IS 12 BP 904 EP 907 DI 10.1016/S0006-3223(97)00391-0 PG 4 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZT022 UT WOS:000074039800008 PM 9627745 ER PT J AU Ross, TS Bernard, OA Berger, R Gilliland, DG AF Ross, TS Bernard, OA Berger, R Gilliland, DG TI Fusion of Huntingtin Interacting protein 1 to platelet-derived growth factor beta receptor (PDGF beta R) in chronic myelomonocytic leukemia with t(5;7)(q33;q11.2) SO BLOOD LA English DT Article ID ACUTE MYELOID-LEUKEMIA; MYELODYSPLASTIC-SYNDROMES; GENE; TEL; TRANSLOCATION; KINASE; REGION; PHOSPHOTYROSINE; CHROMOSOME-7; DELETIONS AB We report the fusion of the Huntingtin interactin protein I (HIP1) gene to the platelet-derived growth factor Preceptor (PDGF beta R) gene in a patient with chronic myelomonocytic leukemia (CMML) with a t(5;7)(q33;q11.2) translocation. Southern blot analysis of patient bone marrow cells with a PDGF beta R gene probe demonstrated rearrangement of the PDGF beta R gene. Anchored polymerase chain reaction using PDGF beta R primers identified a chimeric transcript containing the HIP1 gene located at 7q11.2 fused to the PDGF beta R gene on 5q33. HIP1 is a 116-kD protein recently cloned by yeast two-hybrid screening for proteins that interact with Huntingtin, the mutated protein in Huntington's disease. The consequence of t(5;7)(q33;q11.2) is an HIP1/PDGF beta R fusion gene that encodes amino acids 1 to 950 of HIP1 joined in-frame to the transmembrane and tyrosine kinase domains of the PDGF beta R. The reciprocal PDGF beta R/HIP1 transcript is not expressed, HIP1/PDGF beta R is a 180-kD protein when expressed in the murine hematopoietic cell line, Ba/F3, and is constitutively tyrosine phosphorylated. Furthermore, HIP1/PDGF beta R transforms the Ba/F3 cells to interleukin-3-independent growth, These data are consistent with an alternative mechanism for activation of PDGF beta R tyrosine kinase activity by fusion with HIP1, leading to transformation of hematopoietic cells, and may implicate Huntingtin or HIP1 in the pathogenesis of hematopoietic malignancies. (C) 1998 by The American Society of Hematology. C1 Brigham & Womens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Oncol, Boston, MA 02115 USA. INSERM, SD 401 301 CNRS, Inst Genet Mol, Paris, France. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Gilliland, DG (reprint author), Brigham & Womens Hosp, Div Hematol Oncol, 4 Blackfan Circle, Boston, MA 02115 USA. RI Bernard, Olivier/E-5721-2016 FU NCI NIH HHS [P01CA66996-01]; NHLBI NIH HHS [T32 HL07623] NR 32 TC 134 Z9 144 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 15 PY 1998 VL 91 IS 12 BP 4419 EP 4426 PG 8 WC Hematology SC Hematology GA ZT469 UT WOS:000074091000002 PM 9616134 ER PT J AU Mach-Pascual, S Legare, RD Lu, D Kroon, M Neuberg, D Tantravahi, R Stone, RM Freedman, AS Nadler, LM Gribben, JG Gilliland, DG AF Mach-Pascual, S Legare, RD Lu, D Kroon, M Neuberg, D Tantravahi, R Stone, RM Freedman, AS Nadler, LM Gribben, JG Gilliland, DG TI Predictive value of clonality assays in patients with non-Hodgkin's lymphoma undergoing autologous bone marrow transplant: A single institution study SO BLOOD LA English DT Article ID X-CHROMOSOME INACTIVATION; ACUTE MYELOID-LEUKEMIA; ACUTE MYELOGENOUS LEUKEMIA; STEM-CELL TRANSPLANTATION; HIGH-DOSE CHEMOTHERAPY; MYELODYSPLASTIC SYNDROME; MYELOABLATIVE THERAPY; FOLLICULAR LYMPHOMA; LATE COMPLICATION; APLASTIC-ANEMIA AB Recent studies have documented an increased risk of therapy-related myelodysplastic syndrome or acute myelogenous leukemia (t-MDS/AML) after autologous bone marrow transplant (ABMT) for non-Hodgkin's lymphoma (NHL). To develop methods to identify patients at risk for this complication, we have investigated the predictive value of clonal bone marrow (BM) hematopoiesis for the development of t-MDS/AML, as defined by an X-inactivation based clonality assay at the human androgen receptor locus (HUMARA), in a group of patients undergoing ABMT for NHL from a single institution (Dana-Farber Cancer Institute, Boston, MA). One hundred four female patients were analyzed. At the time of ABMT, the prevalence of polyclonal hematopoiesis was 77% (80/104), of skewed X-inactivation pattern (XIP) was 20% (21/104), and of clonal hematopoiesis was 3% (3/104). To determine the predictive value of clonality for the development of t-MDS/AML, a subgroup of 78 patients with at least 18 months follow-up was analyzed. As defined by the HUMARA assay, 53 of 78 patients had persistent polyclonal hematopoiesis, 15 of 78 had skewed XIP, and 10 of 78 (13.5%) either had clonal hematopoiesis at the time of ABMT or developed clonal hematopoiesis after ABMT. t-MDS/AML developed in 2 of 53 patients with polyclonal hematopoiesis and in 4 of 10 with clonal hematopoiesis. We conclude that a significant proportion of patients have clonal hematopoiesis at the time of ABMT and that clonal hematopoiesis, as detected by the HUMARA assay, is predictive of the development of t-MDS/AML (P = .004). (C) 1998 by The American Society of Hematology. C1 Brigham & Womens Hosp, Div Hematol Oncol, Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Gilliland, DG (reprint author), Brigham & Womens Hosp, Div Hematol Oncol, Dept Med, HIM 421,4 Blackfan Circle, Boston, MA 02115 USA. FU NCI NIH HHS [1 PO1 CA 6696-01A1] NR 40 TC 33 Z9 33 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 15 PY 1998 VL 91 IS 12 BP 4496 EP 4503 PG 8 WC Hematology SC Hematology GA ZT469 UT WOS:000074091000012 PM 9616144 ER PT J AU Caplan, D Hanna, JE AF Caplan, D Hanna, JE TI Sentence production by aphasic patients in a constrained task SO BRAIN AND LANGUAGE LA English DT Article ID WORD-ORDER PROBLEM; SYNTACTIC COMPREHENSION; GRAMMATICAL MORPHEMES; AGRAMMATISM; AVAILABILITY; DEFICITS; DISORDERS; CATEGORY; CAPACITY AB Sixty aphasic patients and 55 normal control subjects were tested on a sentence production protocol that required subjects to produce specific sentence types from semantic representations. Normal subjects produced the expected targets with great reliability. Analysis of the patients' performance indicated that patients had difficulty producing both grammatical forms and thematic roles. Patients had mon trouble producing grammatical elements than content words, and showed differential difficulty on sentence types that had more grammatical elements and in which the order of thematic roles was non-canonical. The results provide evidence regarding the processing load imposed by different components of the sentence production process. (C) 1998 Academic Press. C1 Massachusetts Gen Hosp, Dept Neurol, Neuropsychol Lab, Boston, MA 02114 USA. Boston VA Med Ctr, Aphasia Res Ctr, Boston, MA USA. RP Caplan, D (reprint author), Massachusetts Gen Hosp, Dept Neurol, Neuropsychol Lab, Vincent Burnham 827,Fruit St, Boston, MA 02114 USA. FU NIDCD NIH HHS [DC00081] NR 53 TC 42 Z9 42 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0093-934X J9 BRAIN LANG JI Brain Lang. PD JUN 15 PY 1998 VL 63 IS 2 BP 184 EP 218 DI 10.1006/brln.1998.1930 PG 35 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA ZX791 UT WOS:000074555800002 PM 9654431 ER PT J AU Dominitz, JA Samsa, GP Landsman, P Provenzale, D AF Dominitz, JA Samsa, GP Landsman, P Provenzale, D TI Race, treatment, and survival among colorectal carcinoma patients in an equal-access medical system SO CANCER LA English DT Article; Proceedings Paper CT 97th Annual Meeting of the American-Gastroenterological-Association CY MAY 18-23, 1996 CL SAN FRANCISCO, CALIFORNIA SP Amer Gastroenterol Assoc DE colorectal neoplasms; epidemiology; racial stocks; surgery; survival; chemotherapy; adjuvant; radiation oncology; veterans ID OF-VETERANS-AFFAIRS; COLON-CANCER; RACIAL VARIATION; PROSTATE-CANCER; WOMEN; RATES; MAMMOGRAPHY; POPULATION; SURGERY; DISEASE AB BACKGROUND. The aim of this study was to assess the influence of race on the treatment and survival of patients with colorectal carcinoma. METHODS. This retrospective cohort study included all white or black male veterans given a new diagnosis of colorectal carcinoma in 1989 at Veterans Affairs Medical Centers nationwide. After adjusting for patient demographics, comorbidity, distant metastases, and tumor location, the authors determined the likelihood of surgical resection, chemotherapy, radiation therapy, and death in each case. RESULTS. Of the 3176 veterans identified, 569 (17.90%) were black. Bivariate analyses and logistic regression revealed no significant differences in the proportions of patients undergoing surgical resection (70% vs. 73%, odds ratio 0.92, 95% confidence interval 0.74-1.15), chemotherapy (23% vs. 23%, odds ratio 0.99, 95% confidence interval 0.78-1.24), or radiation therapy (17% vs. 16%, odds ratio 1.10, 95% confidence interval 0.85-1.43) for black versus white patients. Five-year relative survival rates were similar for black and white patients (42% vs. 39%, respectively; P = 0.16), though the adjusted mortality risk ratio was modestly increased (risk ratio 1.13, 95% confidence interval 1.01-1.28). CONCLUSIONS. Overall, race was not associated with the use of surgery, chemotherapy, or radiation therapy in the treatment of colorectal carcinoma among veterans seeking health care at Veterans affairs Medical Centers. Although mortality from all causes was higher among black veterans with colorectal carcinoma, this finding may be attributed to underlying racial differences associated with survival. This study suggests that when there is equal access to care, there are no differences with regard to race. (C) 1998 American Cancer Society. C1 VA Puget Sound Hlth Care Syst, Dept Med, Div Gastroenterol, Seattle Div 111GI, Seattle, WA 98108 USA. Vet Affairs Med Ctr, Ctr Hlth Serv Res & Dev, Durham, NC 27705 USA. Duke Univ, Med Ctr, Dept Med, Div Gastroenterol, Durham, NC 27710 USA. Duke Univ, Ctr Clin Hlth Policy Res, Durham, NC USA. RP Dominitz, JA (reprint author), VA Puget Sound Hlth Care Syst, Dept Med, Div Gastroenterol, Seattle Div 111GI, 1660 S Columbian Way, Seattle, WA 98108 USA. OI Dominitz, Jason/0000-0002-8070-7086 NR 38 TC 128 Z9 129 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD JUN 15 PY 1998 VL 82 IS 12 BP 2312 EP 2320 DI 10.1002/(SICI)1097-0142(19980615)82:12<2312::AID-CNCR3>3.0.CO;2-U PG 9 WC Oncology SC Oncology GA ZT941 UT WOS:000074143700003 PM 9635522 ER PT J AU Gutsmann-Conrad, A Heydari, AR You, SH Richardson, A AF Gutsmann-Conrad, A Heydari, AR You, SH Richardson, A TI The expression of heat shock protein 70 decreases with cellular senescence in vitro and in cells derived from young and old human subjects SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID HUMAN-DIPLOID FIBROBLASTS; DNA-BINDING ACTIVITY; TRANSCRIPTION FACTOR; GENE-EXPRESSION; MOLECULAR-CLONING; MESSENGER-RNA; HSP70; ACTIVATION; STRESS; AGE AB Because heat shock proteins have been shown to play a critical role in protecting cells from hyperthermia and other types of stresses, it was of interest to determine what effect cellular senescence in vitro and cells cultured in vitro from young and old human donors have on the ability of cells to regulate the expression of heat shock protein 70 (hsp70), the most prominent and most evolutionary conserved of the heat shock proteins. The ability of early and late passage IMR-90 lung fibroblasts and epidermal melanocytes and skin fibroblasts obtained from young and old human donors to express hsp70 was determined after a brief heat shock. We found that the levels of hsp70 protein and mRNA were lower in late passage cells and cells from old donors than in early passage cells and cells from young donors. The binding activity of the heat shock transcription factor HSF1, as measured by a gel shift assay, was significantly higher in early passage cells and cells from young donors in comparison to late passage cells and cells from old donors. In addition, the levels of HSF1 decreased significantly in late passage cells and cells from old donors in comparison to early passage cells and cells from young donors. Thus, our study demonstrates that the induction of hsp70 by hyperthermia in fibroblasts is significantly lower in late passage fibroblasts and in fibroblasts from old donors. In addition, our study shows that the decline in hsp70 expression during cellular senescence in vitro and in cells derived from old human subjects is paralleled by a decrease in the levels of HSF1. (C) 1998 Academic Press. C1 Univ Texas, Hlth Sci Ctr, Ctr Geriatr Res Educ & Clin, S Texas Vet Hlth Care Syst,Audie L Murphy Div, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Struct & Cellular Biol, San Antonio, TX 78284 USA. RP Richardson, A (reprint author), Audie L Murphy Mem Vet Hosp, GRECC 182, 7400 Merton Minter Blvd, San Antonio, TX 78284 USA. EM richardsona@uthscsa.edu FU NIA NIH HHS [AG01548] NR 44 TC 69 Z9 78 U1 1 U2 4 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD JUN 15 PY 1998 VL 241 IS 2 BP 404 EP 413 DI 10.1006/excr.1998.4069 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA ZW008 UT WOS:000074364300014 PM 9637782 ER PT J AU Zeng, WL Silverman, GA Remold-O'Donnell, E AF Zeng, WL Silverman, GA Remold-O'Donnell, E TI Structure and sequence of human M/NEI (monocyte/neutrophil Elastase Inhibitor), an Ov-serpin family gene SO GENE LA English DT Article DE gene structure; serpins; elastase inhibitor; protease inhibitor ID IN-SITU HYBRIDIZATION; NEUTROPHIL ELASTASE; CHICKEN OVALBUMIN; MOLECULAR-CLONING; BONE-MARROW; CATHEPSIN-G; EXPRESSION; ALPHA-1-ANTITRYPSIN; PROTEINASE-3; SUPERFAMILY AB Human monocyte/neutrophil Elastase Inhibitor (M/NEI) is a proteinase inhibitor that regulates the activity of the neutrophil proteases: elastase, cathepsin G and proteinase-3. Evidence indicates that M/NEI belongs to the Ov-serpin family (ovalbumin-related serpins), functionally diverse proteins with shared structural features. Recombinant lambda phage clones were isolated that encompass the full-length M/NEI gene plus upstream and downstream regions. The gene, 9.5 kb long, consists of 7 exons and 6 introns. The 5' transcription start site identified by primer extension corresponds to a 60 bp exon 1; the translation start site is in exon 2. Southern blots established a gene copy number of one. The 3' untranslated region (UTR) contains three AATAAA/ATTAAA sites; these were shown to function as alternative polyadenylation signals. A 14-nucleotide upstream motif including the atypical TATA box TATAAGAG otherwise occurs only twice in GenBank, in the genes encoding neutrophil elastase and proteinase-3, target proteases inhibited by M/NEI. Comparison of M/NEI and previously characterized related genes strongly suggests that all Ov-serpins, despite a difference in chromosomal localization and exon number, nonetheless, share a common basic gene structure. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Ctr Blood Res, Boston, MA 02115 USA. Childrens Hosp, Joint Program Neonatol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Remold-O'Donnell, E (reprint author), Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA69331]; NHLBI NIH HHS [HL41579] NR 37 TC 14 Z9 15 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD JUN 15 PY 1998 VL 213 IS 1-2 BP 179 EP 187 DI 10.1016/S0378-1119(98)00189-9 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA ZX116 UT WOS:000074481000022 PM 9630619 ER PT J AU Calautti, E Cabodi, S Stein, PL Hatzfeld, M Kedersha, N Dotto, GP AF Calautti, E Cabodi, S Stein, PL Hatzfeld, M Kedersha, N Dotto, GP TI Tyrosine phosphorylation and src family kinases control keratinocyte cell-cell adhesion SO JOURNAL OF CELL BIOLOGY LA English DT Article ID EPIDERMAL GROWTH-FACTOR; BETA-CATENIN; E-CADHERIN; SIGNAL-TRANSDUCTION; CYTOPLASMIC DOMAIN; ALPHA-CATENIN; FACTOR RECEPTOR; MUTANT MICE; PROTEIN; DIFFERENTIATION AB In their progression from the basal to upper differentiated layers of the epidermis, keratinocytes undergo significant structural changes, including establishment of close intercellular contacts. An important but so far unexplored question is how these early structural events are related to the biochemical pathways that trigger differentiation. We show here that beta-catenin, gamma-catenin/plakoglobin, and p120-Cas are all significantly tyrosine phosphorylated in primary mouse keratinocytes induced to differentiate by calcium, with a time course similar to that of cell junction formation. Together with these changes, there is an increased association of alpha-catenin and p120-Cas with E-cadherin, which is prevented by tyrosine kinase inhibition. Treatment of E-cadherin complexes with tyrosine-specific phosphatase reveals that the strength of alpha-catenin association is directly dependent on tyrosine phosphorylation. In parallel with the biochemical effects, tyrosine kinase inhibition suppresses formation of cell adhesive structures, and causes a significant reduction in adhesive strength of differentiating keratinocytes, The Fyn tyrosine kinase colocalizes with E-cadherin at the cell membrane in calcium-treated keratinocytes, Consistent with an involvement of this kinase, fyn-deficient keratinocytes have strongly decreased tyrosine phosphorylation levels of beta- and gamma-catenins and p120-Cas, and structural and functional abnormalities in cell adhesion similar to those caused by tyrosine kinase inhibitors. Whereas skin of fyn -/- mice appears normal, skin of mice with a disruption in both the fyn and sr e genes shows intrinsically reduced tyrosine phosphorylation of beta-catenin, strongly decreased p120-Cas levels, and important structural changes consistent with impaired keratinocyte cell adhesion. Thus, unlike what has been proposed for oncogene-transformed or mitogenically stimulated cells, in differentiating keratinocytes tyrosine phosphorylation plays a positive role in control of cell adhesion, and this regulatory function appears to be important both in vitro and in vivo. C1 Harvard Univ, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Univ Turin, Dipartimento Genet Biol & Chim Med, I-10126 Turin, Italy. Wistar Inst, Philadelphia, PA 19104 USA. Univ Halle, Fac Med, Mol Biol Grp, D-06097 Halle, Germany. Brigham & Womens Hosp, Div Rheumatol & Immunol, Boston, MA 02115 USA. RP Dotto, GP (reprint author), Harvard Univ, Sch Med, Cutaneous Biol Res Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. OI CALAUTTI, Vincenzo/0000-0002-4439-9709; Cabodi, Sara/0000-0003-1248-6549 FU NCI NIH HHS [CA64043, CA73796, R01 CA064043, R01 CA073796]; NIAMS NIH HHS [AR39190, R01 AR039190] NR 62 TC 195 Z9 196 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD JUN 15 PY 1998 VL 141 IS 6 BP 1449 EP 1465 DI 10.1083/jcb.141.6.1449 PG 17 WC Cell Biology SC Cell Biology GA ZV428 UT WOS:000074303600015 PM 9628900 ER PT J AU Rajavashisth, T Qiao, JH Tripathi, S Tripathi, J Mishra, N Hua, M Wang, XP Loussararian, A Clinton, S Libby, P Lusis, A AF Rajavashisth, T Qiao, JH Tripathi, S Tripathi, J Mishra, N Hua, M Wang, XP Loussararian, A Clinton, S Libby, P Lusis, A TI Heterozygous osteopetrotic (op) mutation reduces atherosclerosis in LDL receptor-deficient mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE hypercholesterolemia; atherogenesis; osteopetrosis; monocytes; macrophages ID COLONY-STIMULATING FACTOR; LOW-DENSITY LIPOPROTEINS; FACTOR MESSENGER-RNA; GROWTH-FACTOR; FACTOR GENE; CELL-PROLIFERATION; PLASMA-CHOLESTEROL; FACTOR CSF-1; C-FMS; MACROPHAGE AB Previous studies of osteopetrotic (op) mice lacking macrophage colony-stimulating factor (M-CSF) have revealed an inhibition of atherosclerosis development in the apolipoprotein E (apo E)-deficient model and in a diet-induced model. Using LDH, receptor-deficient mice, we now show that atheroma development depends on M-CSF concentration, as not only did homozygous osteopetrotic (op/op) mice have dramatically reduced lesions (similar to 0.3% of control lesion size) but heterozygous (op/+) mice had lesions <1% of controls. Mice heterozygous for the op mutation (op/+) had plasma levels of M-CSF about half those in controls (+/+), The finding that an similar to 2-fold reduction in M-CSF expression reduced lesion size similar to 100-fold suggests the requirement for a threshold level of M-CSF. The effect of M-CSF on atherosclerosis did not appear to be mediated either by changes in plasma lipoprotein levels or alterations in the number of circulating monocytes, since both op/op and op/+ mice exhibited higher levels of atherogenic lipoprotein particles and (op/+) mice showed a near normal number of circulating monocytes, EDL receptor-null littermates of genotypes from op/op, op/+, to +/+ showed monocyte differentials of similar to 4.5, 8, and 10%, respectively. Taken together, these results suggest that the effects of M-CSF on atherogenesis may not be mediated by expression of M-CSF systemically or by modulation of the number of circulating monocytes. These studies support the conclusion that M-CSF participates critically in fatty streak formation and progression to a complex fibrous lesion. C1 Cedars Sinai Med Ctr, Div Cardiol, Atherosclerosis Res Ctr, Dept Med, Los Angeles, CA 90048 USA. Cedars Sinai Med Ctr, Dept Pathol & Lab Med, Los Angeles, CA 90048 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Microbiol & Mol Genet, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90095 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Vasc Med & Atherosclerosis Unit, Boston, MA 02115 USA. RP Rajavashisth, T (reprint author), Cedars Sinai Med Ctr, Div Cardiol, Atherosclerosis Res Ctr, Dept Med, Davis Res Bldg,Room D-1062,8700 Beverly Blvd, Los Angeles, CA 90048 USA. EM raja@cshs.org FU NHLBI NIH HHS [HL-51980, HL-30568, HL-34636] NR 44 TC 150 Z9 155 U1 0 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUN 15 PY 1998 VL 101 IS 12 BP 2702 EP 2710 DI 10.1172/JCI119891 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA ZY285 UT WOS:000074604800012 PM 9637704 ER PT J AU Choudhury, GG Ghosh-Choudhury, N Abboud, HE AF Choudhury, GG Ghosh-Choudhury, N Abboud, HE TI Association and direct activation of signal transducer and activator of transcription1 alpha by platelet-derived growth factor receptor SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE mesangial cells; PDGFR; STAT1 alpha ID STIMULATES TYROSINE PHOSPHORYLATION; HUMAN MESANGIAL CELLS; FACTOR BETA-RECEPTOR; INTERFERON-GAMMA; SRC FAMILY; PHOSPHATIDYLINOSITOL 3-KINASE; MEDIATED ACTIVATION; CYTOKINE RECEPTORS; KINASES; BINDING AB PDGF stimulates tyrosine phosphorylation of Janus kinase 1 (JAK1) and the signal transducer and activator of transcription 1 (STAT1 alpha), However, it is not known whether JAKs are required for STAT1 alpha phosphorylation or if the PDGF receptor itself can directly tyrosine phosphorylate and activate STAT1 alpha, In vitro immunecomplex kinase assay of PDGF beta receptor (PDGFR) or STAT1 alpha immunoprecipitates from lysates of mesangial cells treated with PDGF showed phosphorylation of a 91- and an 185-kD protein. Incubation of lysates prepared from quiescent mesangial cells with purified PDGFR resulted in STAT1 alpha activation. Immunodepletion of Janus kinases from the cell lysate before incubation with the purified PDGFR showed no effect on STAT1 alpha activation. Moreover, lysates from mesangial cells treated with JAK2 inhibitor, retained significant STAT1 alpha activity. To confirm that STAT1 alpha is a substrate for PDGFR, STAT1 alpha protein was prepared by in vitro transcription and translation. The addition of purified PDGFR to the translated STAT1 alpha resulted in its phosphorylation, This in vitro phosphorylated and activated protein a:lso forms a specific protein-DNA complex. Dimerization of the translated STAT1 alpha protein was also required for its DNA binding. Incubation of pure STAT1 alpha with autophosphorylated PDGFR resulted in physical association of the two proteins. These data indicate that activated PDGFR may be sufficient to tyrosine phosphorylate and thus directly activate STAT1 alpha. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Nephrol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78284 USA. Audie L Murphy Mem Vet Adm Med Ctr, Dept Geriatr, San Antonio, TX 78284 USA. RP Choudhury, GG (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Nephrol, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. EM choudhuryg@uthscsa.edu FU NIDDK NIH HHS [DK43988, DK 50190] NR 43 TC 39 Z9 40 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUN 15 PY 1998 VL 101 IS 12 BP 2751 EP 2760 DI 10.1172/JCI1044 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA ZY285 UT WOS:000074604800017 PM 9637709 ER PT J AU Kovacs, CS Ho-Pao, CL Hunzelman, JL Lanske, B Fox, J Seidman, JG Seidman, CE Kronenberg, HM AF Kovacs, CS Ho-Pao, CL Hunzelman, JL Lanske, B Fox, J Seidman, JG Seidman, CE Kronenberg, HM TI Regulation of murine fetal-placental calcium metabolism by the calcium-sensing receptor SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE placenta; PTH; parathyroid glands; 1,25-dihydroxyvitamin D; calcitonin ID HORMONE-RELATED PROTEIN; FAMILIAL HYPOCALCIURIC HYPERCALCEMIA; NEONATAL SEVERE HYPERPARATHYROIDISM; PARATHYROID-HORMONE; CA2+-SENSING RECEPTOR; TRANSPORT; GENE; CLONING; CELLS; RAT AB The calcium-sensing receptor (CaSR) regulates PTH secretion to control the extracellular calcium concentration in adults, but its role in fetal life is unknown. We used CaSR gene knockout mice to investigate the role of the CaSR In regulating fetal calcium metabolism. The normal calcium concentration in fetal blood is raised above the maternal level, an increase that depends upon PTH-related peptide (PTHrP). Heterozygous (+/-) and homozygous (-/-) disruption of the CaSR caused a further increase in the fetal calcium level. This increase was modestly blunted by concomitant disruption of the PTHrP gene and completely reversed by disruption of the PTH/PTHrP receptor gene. Serum levels of PTH and 1,25-dihydroxyvitamin D were substantially increased above the normal low fetal levels by disruption of the CaSR. The free deoxypyridinoline level was increased in the amniotic fluid (urine) of CaSR-/- fetuses; this result suggests that fetal bone resorption is increased. Placental calcium transfer was reduced, and renal calcium excretion was increased, by disruption of the CaSR. These studies indicate that the CaSR normally suppresses PTH secretion in the presence of the normal raised (and PTHrP-dependent) fetal calcium level. Disruption of the CaSR causes fetal hyperparathyroidism and hypercalcemia, with additional effects on placental calcium transfer. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. NPS Pharmaceut Inc, Salt Lake City, UT 84108 USA. RP Kronenberg, HM (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Wellman 501,50 Blossom St, Boston, MA 02114 USA. OI Kovacs, Christopher/0000-0002-5219-9993 FU NIDDK NIH HHS [DK-46422, DK-47038] NR 33 TC 75 Z9 75 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUN 15 PY 1998 VL 101 IS 12 BP 2812 EP 2820 DI 10.1172/JCI2940 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA ZY285 UT WOS:000074604800023 PM 9637715 ER PT J AU Garcia-Rodriguez, C Rao, A AF Garcia-Rodriguez, C Rao, A TI Nuclear factor of activated T cells (NFAT)-dependent transactivation regulated by the coactivators p300 CREB-binding protein (CBP) SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE transcriptional regulation; histone acetyltransferases; T cells; nuclear factor of activated T cells; cytokine gene expression ID TRANSCRIPTION FACTOR NFATP; HISTONE ACETYLTRANSFERASE; SYSTEM; CALCINEURIN; EXPRESSION; ADAPTER; E1A AB p300 and cAMP response element-binding protein (CREB)-binding protein (CBP) are members of a family of coactivators involved in the regulation of transcription and chromatin. We show that transcription factors of the nuclear factor of activated T cells (NFAT) family bind p300/CBP and recruit histone acetyltransferase activity from T cell nuclear extracts. The NH2-terminal transactivation domain of NFAT1 and the phospho-CREB- and E1A-binding sites of p300/CBP are involved in the interaction. The viral oncoprotein E1A inhibits NFAT-dependent transactivation in a p300-dependent manner. Recruitment of the coactivators p300/CBP by the transactivation domains of NFAT proteins is likely to play a critical role in NFAT-dependent gene expression during the immune response. C1 Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Rao, A (reprint author), Ctr Blood Res, 200 Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA42471, R01 CA042471, R37 CA042471] NR 36 TC 145 Z9 147 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUN 15 PY 1998 VL 187 IS 12 BP 2031 EP 2036 DI 10.1084/jem.187.12.2031 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA ZV462 UT WOS:000074307000010 PM 9625762 ER PT J AU Wekerle, T Sayegh, MH Hill, J Zhao, Y Chandraker, A Swenson, KG Zhao, GL Sykes, M AF Wekerle, T Sayegh, MH Hill, J Zhao, Y Chandraker, A Swenson, KG Zhao, GL Sykes, M TI Extrathymic T cell deletion and allogeneic stem cell engraftment induced with costimulatory blockade is followed by central T cell tolerance SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE tolerance; transplantation; costimulation; chimerism; bone marrow ID BONE-MARROW TRANSPLANTATION; VIVO CD40-GP39 INTERACTIONS; DEPENDENT HUMORAL IMMUNITY; ANTIBODY MAB INJECTIONS; WHOLE-BODY IRRADIATION; CD28 COSTIMULATION; MIXED CHIMERISM; CD40 LIGAND; NEGATIVE SELECTION; THYMIC IRRADIATION AB A reliable, nontoxic method of inducing transplantation tolerance is needed to overcome the problems of chronic organ graft rejection and immunosuppression-related toxicity. Treatment of mice with single injections of an anti-CD40 ligand antibody and CTLA4Ig, a low dose (3 Gy) of whole body irradiation, plus fully major histocompatibility complex-mismatched allogeneic bone marrow transplantation (BMT) reliably induced high levels (>40%) of stable (>8 mo) multilineage donor hematopoiesis. Chimeric mice permanently accepted donor skin grafts (>100 d), and rapidly rejected third party grafts. Progressive deletion of donor-reactive host T cells occurred among peripheral CD4+ lymphocytes, beginning as early as 1 wk after bone marrow transplantation. Early deletion of peripheral donor-reactive host CD4 cells also occurred in thymectomized, similarly treated marrow recipients, demonstrating a role for peripheral clonal deletion of donor-reactive T cells after allogeneic BMT in the presence of costimulatory blockade. Central intrathymic deletion of newly developing T cells ensued after donor stem cell engraftment had occurred. Thus, we have shown that high levels of chimerism and systemic T cell tolerance can be reliably achieved without myeloablation or T cell depletion of the host. Chronic immunosuppression and rejection are avoided with this powerful, nontoxic approach to inducing tolerance. C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect, Boston, MA 02129 USA. Brigham & Womens Hosp, Dept Med, Lab Immunogenet & Transplantat, Boston, MA 02115 USA. RP Sykes, M (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect, MGH E,13th St,Bldg 149-5102, Boston, MA 02129 USA. OI Wekerle, Thomas/0000-0001-5159-2796 FU NHLBI NIH HHS [R01 HL049915, R01 HL-49915] NR 45 TC 256 Z9 260 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUN 15 PY 1998 VL 187 IS 12 BP 2037 EP 2044 DI 10.1084/jem.187.12.2037 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA ZV462 UT WOS:000074307000011 PM 9625763 ER PT J AU Manis, JP Gu, YS Lansford, R Sonoda, E Ferrini, R Davidson, L Rajewsky, K Alt, FW AF Manis, JP Gu, YS Lansford, R Sonoda, E Ferrini, R Davidson, L Rajewsky, K Alt, FW TI Ku70 is required for late B cell development and immunoglobulin heavy chain class switching SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE immunoglobulin class switch recombination; Ku70; recombination activating gene 2; B cell development ID DEPENDENT PROTEIN-KINASE; STRAND BREAK REPAIR; SEVERE COMBINED IMMUNODEFICIENCY; V(D)J RECOMBINATION; SCID MICE; SACCHAROMYCES-CEREVISIAE; CIRCULAR DNA; DIFFERENTIATION; REGION; MOUSE AB Immunoglobulin (Ig) heavy chain (HC) class switch recombination (CSR) is a late B cell process that involves intrachromosomal DNA rearrangement. Ku70 and Ku80 form a DNA end-binding complex required for DNA double strand break repair and V(D)J recombination. Ku70(-/-) (K70T) mice, like recombination activating gene (RAG)-1- or RAG-2-deficient (R1T or R2T) mice, have impaired B and T cell development at an early progenitor stage, which is thought to result at least in part from defective V(D)J recombination (Gu, Y., IC.J. Seidl, G.A. Rathbun, C. Zhu, J.P. Manis, N. van der Steep, L. Davidson, H.L. Cheng, J.M. Sekiguchi, It. Frank, et al. 1997. Immunity. 7:653-665; Ouyang, H., A. Nussenzweig, A. Kurimasa, V.C. Soares, X. Li, C. Cordon-Cardo, W. Li, N. Cheong, M. Nussenzweig, G. Iliakis, et al. 1997.J. Exp.. Mcd. 186:921-929). Therefore, to examine the potential role of Ku70 in CSR, we generated K70T mice that carry a germline Ig HC locus in which the JH region was replaced with a functionally rearranged VH(D)JH and Ig lambda light chain transgene (referred to as K70T/HL mice). Previously, we have shown that B cells from R1T or R2T mice carrying these rearranged Ig genes (R1T/HL or R2T/HL mice) can undergo CSR to IgG isotypes (Lansford, R., J. Manis, E. Sonoda, K. Rajewsky, and F. Alt. 1998. Int. Immunol. 10.325-332). K70T/HL mice had significant numbers of peripheral surface IgM(+) B cells, which generated serum IgM levels similar to those of R2T/HL mice. However, in contrast to R2T/HL mice, K70T/HL mice had no detectable serum IgG isotypes. In vitro culture of K70T/HL B cells with agents that induce CSR in normal or R2T/HL B cells did lead to the induction of germline CH transcripts, indicating that initial signaling pathways for CSR were intact in K70T/HL cells. However, treatment with such agents did not lead to detectable CSII by K70T/HL B cells, and instead, led to cell death within 72 h. We conclude that Ku70 is required for the generation of B cells that have undergone Ig HC class switching. Potential roles for Ku70 in the CSR process are discussed. C1 Howard Hughes Med Inst, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Kyoto Univ, Dept Mol Immunol & Allergy, Kyoto 60601, Japan. Univ Cologne, Inst Genet, D-5000 Cologne 41, Germany. RP Alt, FW (reprint author), Howard Hughes Med Inst, 861,320 Longwood Ave, Boston, MA 02115 USA. RI Lansford, Rusty/C-6956-2014 FU NIAID NIH HHS [AI-31541, AI-01285, AI-240047, P01 AI031541, U19 AI031541] NR 63 TC 220 Z9 223 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUN 15 PY 1998 VL 187 IS 12 BP 2081 EP 2089 DI 10.1084/jem.187.12.2081 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA ZV462 UT WOS:000074307000016 PM 9625768 ER PT J AU Wong, YW Gill, DS Parhami-Seren, B Short, MK Sompuram, SR Margolies, MN AF Wong, YW Gill, DS Parhami-Seren, B Short, MK Sompuram, SR Margolies, MN TI Structural requirements for a specificity switch and for maintenance of affinity using mutational analysis of a phage-displayed anti-arsonate antibody of fab heavy chain first complementarity-determining region SO JOURNAL OF IMMUNOLOGY LA English DT Article ID AZOPHENYLARSONATE-SPECIFIC ANTIBODIES; AMINO-ACID SUBSTITUTION; STRAIN-A MOUSE; VARIABLE REGION; IMMUNE-RESPONSE; HYPERVARIABLE REGIONS; DIRECTED MUTAGENESIS; SOMATIC MUTATION; GENETIC-BASIS; V REGION AB We previously showed that a single mutation at heavy (H) position 35 of Abs specific for p-azophenylarsonate (Ars) resulted in acquisition of binding to the structurally related hapten p-azophenylsulfonate (Sulf), To explore the sequence and structural diversity of the H chain first complementarity-determining region (HCDR1) in modulating affinity and specificity, positions 30-36 in Ab 36-65 were randomly mutated and expressed as Fab in a bacteriophage display vector, Ab 36-65 is germline encoded, lacking somatic mutations. Following affinity selection on Sulf resins, 55 mutant Fab were isolated, revealing seven unique HCDR1 sequences containing different amino acids at position EI:35, All Fab bound Sulf, but not Ars, Site-directed mutagenesis in a variety of HCDR1 sequence contexts indicates that H:35 is critical for hapten specificity, independent of the sequence of the remainder of HCDR1, At H:35, Asn is required for Ars specificity, consistent with the x-ray crystal structure of the somatically mutated anti-Ars Ab 36-71, while Sulf binding occurs with at least seven different H:35 residues. All Sulf-binding clones selected following phage display contained H:Gly33, observed previously for Ars-binding Abs that use the same germline V-H sequence. Site directed mutagenesis at H:33 indicates that Gly plays an essential structural role in HCDR1 for both Sulf- and Ars-specific Abs. C1 Ohio State Univ, Dept Obstet & Gynecol, Columbus, OH 43210 USA. IntreImmune Therapies, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Childrens Hosp, Med Ctr, Dept Hematol Oncol, Cincinnati, OH 45229 USA. Boston Univ, Sch Med, Dept Pathol, Boston, MA 02118 USA. Boston Univ, Sch Med, Hubert Humphrey Canc Ctr, Boston, MA 02118 USA. RP Margolies, MN (reprint author), Massachusetts Gen Hosp E, 149 13th St,Box 31, Charlestown, MA 02129 USA. FU NCI NIH HHS [R01 CA24432]; NIAID NIH HHS [R29 AI33175] NR 38 TC 5 Z9 5 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 15 PY 1998 VL 160 IS 12 BP 5990 EP 5997 PG 8 WC Immunology SC Immunology GA ZU094 UT WOS:000074161000038 PM 9637513 ER PT J AU Allen, TM Sidney, J del Guercio, MF Glickman, RL Lensmeyer, GL Wiebe, DA DeMars, R Pauza, CD Johnson, RP Sette, A Watkins, DI AF Allen, TM Sidney, J del Guercio, MF Glickman, RL Lensmeyer, GL Wiebe, DA DeMars, R Pauza, CD Johnson, RP Sette, A Watkins, DI TI Characterization of the peptide binding motif of a rhesus MHC class I molecule (Mamu-A*01) that binds an immunodominant CTL epitope from simian immunodeficiency virus SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; CYTOTOXIC T-LYMPHOCYTES; SYNTHETIC PEPTIDE; HIV-1 INFECTION; CELL ACTIVITY; SIV ENVELOPE; NEF GENE; HLA-A; MONKEYS; MACAQUES AB The majority of immunogenic CTL epitopes bind to MHC class I molecules with high sanity. However, peptides longer or shorter than the optimal epitope rarely bind with high affinity, Therefore, identification of optimal CTL epitopes from pathogens may ultimately be critical for inducing strong CTL responses and developing epitope-based vaccines. The SIV-infected rhesus macaque is an excellent animal model for HIV infection of humans. Although a number of CTL epitopes have been mapped in SIV-infected rhesus macaques, the optimal epitopes have not been wed defined, and their anchor residues are unknown. We have now defined the optimal SIV gag CTL epitope restricted by the rhesus MHC class I molecule Mamu-A*01 and defined a general peptide binding motif for this molecule that is characterized by a dominant position 3 anchor (proline), We used peptide elution and sequencing, peptide binding assays, and bulk and clonal CTL assays to demonstrate that the optimal Mamu-A*01-restricted SIV gag CTL epitope was CTPYDINQM(181-189). Mamu-A*01 is unique in that it is found at a high frequency in rhesus macaques, and all SIV-infected Mamu-A*01-positive rhesus macaques studied to date develop an immunodominant gag-specific CTL response restricted by this molecule. Identification of the optimal SIV gag CTL epitope, will be critical for a variety of studies designed to induce CD8(+) CTL responses specific for SIV in the rhesus macaque. C1 Univ Wisconsin, Wisconsin Reg Primate Res Ctr, Madison, WI 53715 USA. Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI 53715 USA. Harvard Univ, Sch Med, New England Reg Primate Res Ctr, Div Immunol, Southborough, MA 01772 USA. Eppimune, San Diego, CA 92121 USA. Massachusetts Gen Hosp, Infect Dis Unit, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA 02129 USA. Univ Wisconsin, Genet Lab, Madison, WI 53706 USA. RP Allen, TM (reprint author), Univ Wisconsin, Wisconsin Reg Primate Res Ctr, 1223 Capitol Court, Madison, WI 53715 USA. RI Allen, Todd/F-5473-2011 FU NCRR NIH HHS [RR00167]; NIAID NIH HHS [AI32426, AI41913] NR 79 TC 185 Z9 188 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 15 PY 1998 VL 160 IS 12 BP 6062 EP 6071 PG 10 WC Immunology SC Immunology GA ZU094 UT WOS:000074161000048 PM 9637523 ER PT J AU Liou, GI Fei, YJ Peachey, NS Matragoon, S Wei, SH Blaner, WS Wang, YX Liu, CY Gottesman, ME Ripps, H AF Liou, GI Fei, YJ Peachey, NS Matragoon, S Wei, SH Blaner, WS Wang, YX Liu, CY Gottesman, ME Ripps, H TI Early onset photoreceptor abnormalities induced by targeted disruption of the interphotoreceptor retinoid-binding protein gene SO JOURNAL OF NEUROSCIENCE LA English DT Article DE homologous recombination; interphotoreceptor retinoid-binding protein (IRBP); photoreceptor degeneration; retinal development; vitamin A deficiency; electroretinography (ERG) ID ROD OUTER SEGMENTS; PIGMENT-EPITHELIUM; TRANSGENIC MICE; VITAMIN-A; RHODOPSIN REGENERATION; EARLY EXPRESSION; BOVINE RETINA; STEM-CELLS; IRBP; DEGENERATION AB Vision in all vertebrates is dependent on an exchange of retinoids between the retinal pigment epithelium and the visual photoreceptors. It has been proposed that the interphotoreceptor retinoid-binding protein (IRBP) is essential for this intercellular exchange, and that it serves to prevent the potentially cytotoxic effects of retinoids. Although its precise function in vivo has yet to be defined, the early expression of IRBP suggests that it may also be required for normal photoreceptor development. To further assess the biological role of IRBP, we generated transgenic mice with targeted disruption of the IRBP gene (IRBP -/- mice). Specifically, homologous recombination was used to replace the first exon and promoter region of the IRBP gene with a phosphoglycerate kinase-promoted neomycin-resistant gene, Immunocytochemical and Western blot analyses demonstrated the absence of IRBP expression in the IRBP -/- mice. As early as postnatal day 11, histological examination of the retinas of IRBP -/- mice revealed a loss of photoreceptor nuclei and changes in the structural integrity of the receptor outer segments. At 30 d of age, the photoreceptor abnormalities in IRBP -/- mice were more severe, and electroretinographic recordings revealed a marked loss in photic sensitivity. In contrast, no morphological or electrophysiological changes were detected in age-matched heterozygotes. These observations indicate that normal photoreceptor development and function are highly dependent on the early expression of IRBP, and that in the absence of IRBP there is a slowly progressive degeneration of retinal photoreceptors. C1 Med Coll Georgia, Dept Ophthalmol, Augusta, GA 30912 USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. Loyola Univ, Med Ctr, Dept Neurol, Maywood, IL 60153 USA. Columbia Univ, Inst Human Nutr, New York, NY 10032 USA. Columbia Univ, Canc Res Inst, New York, NY 10032 USA. Univ Illinois, Dept Ophthalmol & Visual Sci, Chicago, IL 60612 USA. RP Liou, GI (reprint author), Med Coll Georgia, Dept Ophthalmol, Augusta, GA 30912 USA. RI Peachey, Neal/G-5533-2010 FU NEI NIH HHS [EY03829, EY06516] NR 54 TC 74 Z9 77 U1 0 U2 3 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUN 15 PY 1998 VL 18 IS 12 BP 4511 EP 4520 PG 10 WC Neurosciences SC Neurosciences & Neurology GA ZT273 UT WOS:000074068000009 PM 9614228 ER PT J AU Siklodi, B Jacobs, R Vandenbark, AA Offner, H AF Siklodi, B Jacobs, R Vandenbark, AA Offner, H TI Neonatal exposure of TCR BV8S2 transgenic mice to recombinant TCR BV8S2 results in reduced T cell proliferation and elevated antibody response to BV8S2, and increased severity of EAE SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE transgenics; EAE; neonatal tolerance ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; IMMUNIZATION; TOLERANCE; DISEASE; THERAPY; T(H)1 AB Transgenic (Tg) mouse models are unique tools for investigating regulatory mechanisms of the immune system, Mice bearing a T cell receptor (TCR) BV8S2 transgene derived from an encephalitogenic T cell clone are highly susceptible to experimental autoimmune encephalomyelitis (EAE), a T cell-mediated neurological disorder. Although the pathogenesis of EAE is not yet fully understood, TCR-specific regulatory T cells seem to play a role in its remission and/or recovery process. In previous studies, we showed that immunization of BV8S2 Tg mice with recombinant BV8S2 protein induced TCR-specific T cells and protection against EAE, clearly indicating the persistence of a functional TCR regulatory network in spite of the highly skewed T cell repertoire, To further investigate the natural regulatory role of TCR-specific T cells, we evaluated the effect on EAE of inducing neonatal tolerance to heterologous (rat) and homologous BV8S2 proteins in Tg mice. Neonatal exposure to rat BV8S2 protein induced "split" tolerance, characterized by decreased T cell proliferation but increased antibody responses to both rat and mouse BV8S2 proteins that are known to be cross-reactive. When challenged as adults with an encephalitogenic emulsion, Tg mice tolerized with rat but not mouse BV8S2 protein developed more severe EAE compared to control mice, These results demonstrate that immunity to BV8S2 determinants in BV8S2 Tg mice is naturally induced and functions to limit the severity of EAE, (C) 1998 Wiley-Liss, Inc. C1 Portland VA Med Ctr, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Neurol, Portland, OR USA. Oregon Hlth Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97201 USA. Biogal Pharmaceut, Debrecen, Hungary. RP Offner, H (reprint author), Portland VA Med Ctr, 3710 SW US Vet Hosp Rd, Portland, OR 97201 USA. FU NINDS NIH HHS [NS23221, NS23444] NR 23 TC 8 Z9 8 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD JUN 15 PY 1998 VL 52 IS 6 BP 750 EP 756 DI 10.1002/(SICI)1097-4547(19980615)52:6<750::AID-JNR14>3.0.CO;2-2 PG 7 WC Neurosciences SC Neurosciences & Neurology GA ZW471 UT WOS:000074414300014 PM 9669324 ER PT J AU Ventura, J Liberman, RP Green, MF Shaner, A Mintz, J AF Ventura, J Liberman, RP Green, MF Shaner, A Mintz, J TI Training and quality assurance with the structured clinical interview for DSM-IV (SCID-I/P) SO PSYCHIATRY RESEARCH LA English DT Article DE interrater reliability; diagnostic accuracy ID INTERRATER RELIABILITY; DIAGNOSTIC CRITERIA; SCHIZOPHRENIA; RATIONALE AB Accuracy in psychiatric diagnosis is critical for evaluating the suitability of the subjects for entry into research protocols and for establishing comparability of findings across study sites. However, training programs in the use of diagnostic instruments for research projects are not well systematized. Furthermore, little information has been published on the maintenance of interrater reliability of diagnostic assessments. At the UCLA Research Center for Major Mental Illnesses, a Training and Quality Assurance Program for SCID interviewers was used to evaluate interrater reliability and diagnostic accuracy. Although clinically experienced interviewers achieved better interrater reliability and overall diagnostic accuracy than neophyte interviewers, both groups were able to achieve and maintain high levels of interrater reliability, diagnostic accuracy, and interviewer skill. At the first quality assurance check after training, there were no significant differences between experienced and neophyte interviewers in interrater reliability or diagnostic accuracy. Standardization of training and quality assurance procedures within and across research projects may make research findings from study sites more comparable. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved. C1 W Los Angeles Vet Affairs Med Ctr, Intervent Res Ctr Major Mental Illness 116AR, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Med Ctr, W Los Angeles, CA USA. RP Ventura, J (reprint author), W Los Angeles Vet Affairs Med Ctr, Intervent Res Ctr Major Mental Illness 116AR, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 38 TC 325 Z9 325 U1 2 U2 14 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD JUN 15 PY 1998 VL 79 IS 2 BP 163 EP 173 DI 10.1016/S0165-1781(98)00038-9 PG 11 WC Psychiatry SC Psychiatry GA ZZ092 UT WOS:000074694900007 PM 9705054 ER PT J AU Glasziou, PP Cole, BF Gelber, RD Hilden, J Simes, RJ AF Glasziou, PP Cole, BF Gelber, RD Hilden, J Simes, RJ TI Quality adjusted survival analysis with repeated quality of life measures SO STATISTICS IN MEDICINE LA English DT Article ID OF-LIFE; BREAST-CANCER; ADJUVANT THERAPY; CHEMOTHERAPY AB One way of examining trade-offs between quantity and quality of life (QOL) is to combine them into a single measure such as quality-adjusted life year (QALY). If censoring occurs, then estimation presents some difficulties. One approach, known as Q-TWiST, is to define a series of health states, use a 'partitioned' survival analysis to calculate the average time in each state, and then weight each state according to its quality of life to calculate QALYs, Such health-state models, however, are unhelpful when the transitions between health states are unclear or if they do not adequately reflect variations in quality of life. We therefore examine an alternative analysis to be used when repeated measures of quality of life are available from individual patients in a clinical trial. The method proceeds by separating quality of life and survival, that is, dQALY/dt = S(t)Q(t), where S(t) is the survival curve, estimated from the standard Kaplan-Meier method, and Q(t) is the quality of life function, derived from individual repeated measures of quality of life. We derive single health-state (QALY) and multiple health-state (Q-TWiST) models and illustrate the approach by comparing different durations of adjuvant chemotherapy for breast cancer. (C) 1998 John Wiley & Sons, Ltd. C1 Univ Queensland, Sch Med, Dept Social & Prevent Med, Herston, Qld 4006, Australia. Brown Univ, Dept Community Hlth, Ctr Stat Sci, Providence, RI 02912 USA. Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Copenhagen, Dept Biostat, DK-2200 Copenhagen N, Denmark. Univ Sydney, NHMRC, Clin Trials Ctr, Sydney, NSW 2006, Australia. RP Glasziou, PP (reprint author), Univ Queensland, Sch Med, Dept Social & Prevent Med, Herston, Qld 4006, Australia. EM p.glasziou@spmed.uq.edu.au RI Simes, Robert/P-1497-2014; Glasziou, Paul/A-7832-2008 OI Glasziou, Paul/0000-0001-7564-073X NR 25 TC 53 Z9 53 U1 0 U2 7 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD JUN 15 PY 1998 VL 17 IS 11 BP 1215 EP 1229 DI 10.1002/(SICI)1097-0258(19980615)17:11<1215::AID-SIM844>3.0.CO;2-Y PG 15 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA ZT158 UT WOS:000074055000003 PM 9670411 ER PT J AU Tan, K Casasnovas, JM Liu, JH Briskin, MJ Springer, TA Wang, JH AF Tan, K Casasnovas, JM Liu, JH Briskin, MJ Springer, TA Wang, JH TI The structure of immunoglobulin superfamily domains 1 and 2 of MAdCAM-1 reveals novel features important for integrin recognition SO STRUCTURE WITH FOLDING & DESIGN LA English DT Article DE IgSF domain; integrin-binding sites; integrin ligand; MAdCAM-1; X-ray crystallography ID MUCOSAL VASCULAR ADDRESSIN; CELL-ADHESION MOLECULE-1; CRYSTAL-STRUCTURE; ANGSTROM RESOLUTION; MUSCLE PROTEIN; L-SELECTIN; LYMPHOCYTE; BINDING; FRAGMENT; VCAM-1 AB Background: Mucosal addressin cell adhesion molecule 1 (MAdCAM-1) is a cell adhesion molecule that is expressed on the endothelium in mucosa, and guides the specific homing of lymphocytes into mucosal tissues. MAdCAM-1 belongs to a subclass of the immunoglobulin superfamily (IgSF), the members of which are ligands for integrins, Human MAdCAM-1 has a unique dual function compared to other members in the same subclass in that it binds both the integrin alpha 4 beta 7, through its two IgSF domains, and a selectin expressed on leukocytes, via carbohydrate sidechains. The structure determination of the two IgSF domains and comparison to the N-terminal two-domain structures of vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecules (ICAM-1 and ICAM-2) allow us to assess the molecular basis of the interactions between integrins and their preferred ligands, Results: The crystal structure of a fragment containing the two IgSF domains of human MAdCAM-1 has been determined to 2.2 Angstrom resolution. The structure of MAdCAM-1 reveals two separate integrin-recognition motifs, The key integrin-binding residue, Asp42, resides in the CD loop of domain 1; a buried arginine residue (Arg70) plays a critical role in maintaining the conformation of this loop. The second binding site is associated with an unusual long D strand in domain 2, The D and E strands extend beyond the main body of the domain, forming a negatively charged beta ribbon unique to MAdCAM-1,This ribbon is located on the same face as the key aspartate residue in domain 1, consistent with evidence that it is involved in integrin binding. Conclusions: The structural comparison of MAdCAM-1 to other members of the same IgSF subclass reveals some interesting features. Firstly, MAdCAM-1, like VCAM-1, has the key integrin-binding residue located on the protruding CD loop of domain 1 and binds to an integrin that lacks an I domain, This is in contrast to ICAM-1 and ICAM-2 where the key residue is located at the end of the C strand on a fiat surface and which bind to integrins that contain I domains. Secondly, architectural differences in the CD loops of MAdCAM-1 and VCAM-1 cause an 8 A shift in position of the critical aspartate residue, and may partly determine their binding preference for different integrins, Finally, the unusual charge distribution of the two-domain fragment of MAdCAM-1 is predicted to orient the molecule optimally for integrin binding on the top of its long mucin-like stalk. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. LeukoSite Inc, Cambridge, MA 02142 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Dana Farber Canc Inst, Immunobiol Lab, Boston, MA 02115 USA. RP Wang, JH (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 200 Longwood Ave, Boston, MA 02115 USA. EM springer@sprsgi.med.harvard.edu; jwang@red.dfci.harvard.edu RI Casasnovas, Jose/L-6299-2014 OI Casasnovas, Jose/0000-0002-2873-6410 NR 49 TC 41 Z9 42 U1 0 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON W1P 6LB, ENGLAND SN 0969-2126 J9 STRUCT FOLD DES JI Struct. Fold. Des. PD JUN 15 PY 1998 VL 6 IS 6 BP 793 EP 801 DI 10.1016/S0969-2126(98)00080-X PG 9 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA ZZ471 UT WOS:000074732700012 PM 9655832 ER PT J AU Arita, S Une, S Ohtsuka, S Atiya, A Kasraie, A Shevlin, L Mullen, Y AF Arita, S Une, S Ohtsuka, S Atiya, A Kasraie, A Shevlin, L Mullen, Y TI Prevention of primary islet isograft nonfunction in mice with pravastatin SO TRANSPLANTATION LA English DT Article ID TUMOR-NECROSIS-FACTOR; MEVALONATE PATHWAY; CYTO-TOXICITY; RAT ISLETS; NICOTINAMIDE; INTERLEUKIN-1; CELLS; HYPERCHOLESTEROLEMIA; 15-DEOXYSPERGUALIN; TRANSPLANTATION AB Background. Nonspecific inflammatory damage in the early stages of transplantation is the major cause of primary islet graft nonfunction, Using murine isografts, we attempted to prevent this islet graft damage by treating recipients with pravastatin (Pravacol), a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor. Nicotinamide was also tested to determine the synergistic effect of both agents. Methods. Unpurified newborn BALB/c islets, ranging in number from 1800 to 2500, were transplanted into the left renal subcapsular space of a syngeneic adult mouse made diabetic with streptozotocin. Recipient mice were divided into the following four groups, based on treatment protocols: treatment with 40 mg/kg pravastatin (group 1), 500 mg/kg nicotinamide (group 2), 40 mg/kg pravastatin and 500 mg/kg nicotinamide (group 3), and vehicle alone (group 4), Pravastatin and nicotinamide were administered orally every day for 14 days, starting on the day of transplantation (day 0). Nonfasting blood glucose levels, urine glucose levels, and the intravenous glucose tolerance test were used to monitor the diabetic state. The reversal of diabetes was defined by normoglycemia and negative urine glucose maintained for more than 7 days. Results. After islet transplantation, levels of blood and urine glucose were significantly lower in groups 1 and 3, compared with those in group 4. K-values of an intravenous glucose tolerance test performed on day 14 were significantly higher in groups 1 and 3 than those of group 4, Reversal of diabetes had occurred in 63% of mice in group 1 and 67% in group 3, levels that were higher than those in group 2 (17%) and group 4 (0%) (P<0.02, groups 1 and 3 vs, group 4), Histological examination of grafts, biopsied on day 21, revealed well preserved islets with little sign of inflammation in groups 1 and 3, whereas grafts in groups 2 and 4 contained broken, smaller islets surrounded by severe fibrosis and mononuclear cell infiltration. Conclusion. Our results in mice have shown the effectiveness of pravastatin for protecting islets from nonspecific inflammatory damage. Nicotinamide did not show a synergistic effect with pravastatin at the dosage used in this study. These results indicate that pravastatin may be a useful agent for clinical islet transplantation. C1 W Los Angeles Vet Affairs Med Ctr, Human Islet Program, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, VA Human Islet Program, Los Angeles, CA 90073 USA. RP Mullen, Y (reprint author), W Los Angeles Vet Affairs Med Ctr, Human Islet Program, Bldg 304,Room E1-206,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 23 TC 20 Z9 21 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD JUN 15 PY 1998 VL 65 IS 11 BP 1429 EP 1433 DI 10.1097/00007890-199806150-00003 PG 5 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA ZV202 UT WOS:000074280600002 PM 9645797 ER PT J AU Saltsman, KA Prentice, HL Kingston, RE AF Saltsman, KA Prentice, HL Kingston, RE TI The C-terminal hydrophobic repeat of Schizosaccharomyces pombe heat shock factor is not required for heat-induced DNA-binding SO YEAST LA English DT Article DE heat shock; protein-DNA interactions; transcriptional regulation ID TRANSCRIPTION FACTOR; COILED-COIL; SACCHAROMYCES-CEREVISIAE; MOLECULAR-CLONING; HUMAN HSP70; CELL-CYCLE; YEAST; GENE; ACTIVATION; PROTEIN AB The C-terminal hydrophobic repeat (CTR) of heat shock transcription factor (HSF) has been proposed to regulate DNA binding by intramolecular interactions with the leucine zipper motifs present in the HSF trimerization domain. Schizosaccharomyces pombe provides a useful model organism for the study of the regulation of HSF DNA binding because, unlike Saccharomyces cerevisiae, S. pombe hsf is highly heat shock inducible for DNA binding and contains a clear homology to the CTR. We examined the role that the CTR plays in the regulation of S. pombe hsf by constructing isogenic strains bearing deletion and point mutations in the chromosomal copy of hsf Surprisingly, we found that point mutation of key hydrophobic amino acids within the CTR, as well as full deletion of it, yielded factors that show normal binding at normal growth temperatures and full levels of heat-induced binding. Deletion of the CTR did, however, slightly lower the temperature required for maximal activation. In contrast, a large deletion of the C-terminus, which removes close to a third of the coding sequence, was deregulated and bound DNA at control temperature. Several of the deletion mutants were significantly reduced in their level of expression, yet they showed wild-type levels of DNA binding activity following heat shock. These experiments demonstrate that appropriate regulation of the DNA binding activity of S. pombe hsf is not solely dependent upon the CTR, and imply that a feedback mechanism exists that establishes proper levels of DNA binding following heat shock despite mutations that significantly alter levels of total hsf. (C) 1998 John Wiley & Sons, Ltd. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. RP Kingston, RE (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Wellman 10, Boston, MA 02114 USA. NR 45 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0749-503X J9 YEAST JI Yeast PD JUN 15 PY 1998 VL 14 IS 8 BP 733 EP 746 DI 10.1002/(SICI)1097-0061(19980615)14:8<733::AID-YEA270>3.0.CO;2-8 PG 14 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology GA ZU680 UT WOS:000074222300004 PM 9675818 ER PT J AU Weimann, J Bauer, H Bigatello, L Bloch, KD Martin, E Zapol, WM AF Weimann, J Bauer, H Bigatello, L Bloch, KD Martin, E Zapol, WM TI ABO blood group and inhaled nitric oxide in acute respiratory distress syndrome SO LANCET LA English DT Article C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA 02114 USA. Univ Heidelberg, Klin Anaesthesiol, Heidelberg, Germany. RP Weimann, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL 55377, HL 42397] NR 5 TC 6 Z9 6 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON WC1B 3SL, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD JUN 13 PY 1998 VL 351 IS 9118 BP 1786 EP 1787 DI 10.1016/S0140-6736(05)78748-1 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA ZU444 UT WOS:000074197600019 PM 9635958 ER PT J AU Lu, CF Oxvig, C Springer, TA AF Lu, CF Oxvig, C Springer, TA TI The structure of the beta-propeller domain and C-terminal region of the integrin alpha M subunit - Dependence on beta subunit association and prediction of domains SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PLATELET GLYCOPROTEIN-IIB; INTRACHAIN DISULFIDE BONDS; I-DOMAIN; LIGAND-BINDING; MONOCLONAL-ANTIBODIES; ELECTRON-MICROSCOPY; DYNAMIC REGULATION; OVERLAP EXTENSION; CRYSTAL-STRUCTURE; MAC-1 CD11B/CD18 AB The alpha M subunit of integrin Mac-1 contains several distinct regions in its extracellular segment. The N-terminal region has been predicted to fold into a beta-propeller domain composed of seven beta-sheets each about 60 amino acid residues long, with the I-domain inserted between beta-sheets 2 and 3. The structure of the C-terminal region is unknown. We have used monoclonal antibodies (mAbs) as probes to study the dependence of the structure of different regions of the alpha M subunit on association with the beta 2 subunit in the alpha M/beta 2 heterodimer. All of the mAbs to the I-domain immunoprecipitated the unassociated alpha M precursor and reacted with the alpha M subunit expressed alone on the surface of COS cells. By contrast, four mAbs to the beta-propeller domain did not react with the unassociated alpha M precursor nor with the uncomplexed alpha M subunit expressed on COS cell surface. The four mAbs were mapped to three subregions in three different beta-sheets, making it unlikely that each recognized an interface between the alpha and beta subunits. These results suggest that folding of different beta-propeller subregions is coordinate and is dependent on association with the beta 2 subunit. The segment C-terminal to the beta-propeller domain, residues 599-1092, was studied with nine mAbs. A subset of four mAbs that reacted with the alpha M/beta 2 complex but not with the unassociated alpha M subunit were mapped to one subregion, residues 718-759, and five other mAbs that recognized both the unassociated and the complexed alpha M subunit were localized to three other subregions, residues 599-679, 820-882, and 943-1047. This suggests that much of the region C-terminal to the beta-propeller domain folds independently of association with the beta 2 subunit. Our data provide new insights irate how different domains in the integrin alpha and beta subunits may interact. C1 Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Springer, TA (reprint author), Ctr Blood Res, 200 Longwood Ave, Boston, MA 02115 USA. EM springer@sprsgi.med.harvard.edu FU NCI NIH HHS [CA31799] NR 51 TC 53 Z9 54 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 12 PY 1998 VL 273 IS 24 BP 15138 EP 15147 DI 10.1074/jbc.273.24.15138 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZU088 UT WOS:000074160400068 PM 9614126 ER PT J AU Goodfriend, TL Ball, DL Oelkers, W Bahr, V AF Goodfriend, TL Ball, DL Oelkers, W Bahr, V TI Torsemide inhibits aldosterone secretion in vitro SO LIFE SCIENCES LA English DT Article DE diuretics; hypokalemia; hypertension; torsemide ID TORASEMIDE; POTASSIUM AB Torsemide inhibited aldosterone secretion by adrenal cells from rats, cows, and guinea pigs stimulated in vitro by potassium, angiotensin, dibutyryl cyclic AMP, ACTH, or corticosterone. Inhibitory concentrations for adrenal cells (micromolar) were comparable with those reported to inhibit ion transport in isolated renal tubules. Inhibition of aldosterone secretion could reduce kaliuresis, and that may explain why torsemide causes less kaliuresis than other diuretics. Published by Elsevier Science Inc. C1 William S Middleton Mem Vet Hosp, Madison, WI 53705 USA. Free Univ Berlin, Klinikum Benjamin Franklin, Med Klin & Poliklin, D-12200 Berlin, Germany. RP Goodfriend, TL (reprint author), William S Middleton Mem Vet Hosp, 2500 Overlook Terrace, Madison, WI 53705 USA. NR 18 TC 16 Z9 28 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0024-3205 J9 LIFE SCI JI Life Sci. PD JUN 12 PY 1998 VL 63 IS 3 BP PL45 EP PL50 DI 10.1016/S0024-3205(98)00265-3 PG 6 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA ZV834 UT WOS:000074346000011 PM 9698054 ER PT J AU Xia, MQ Berezovska, O Kim, TW Xia, WM Liao, A Tanzi, RE Selkoe, D Hyman, BT AF Xia, MQ Berezovska, O Kim, TW Xia, WM Liao, A Tanzi, RE Selkoe, D Hyman, BT TI Lack of specific association of presenilin 1 (PS-1) protein with plaques and tangles in Alzheimer's disease SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article DE presenilins; AD; plaque; tangle; immunohistochemistry; flow cytometry; human brain; immunoprecipitation ID MESSENGER-RNA EXPRESSION; AMYLOID-BETA-PROTEIN; NEURONAL EXPRESSION; BRAIN; GENE; IMMUNOREACTIVITY; IDENTIFICATION; CLONING AB Missense mutations in the presenilin-1 (PS-I) gene are causally related to the majority of familial early-onset Alzheimer's disease (FAD). PS-1 immunohistochemical expression in normal human brain and in brains with Alzheimer's disease (AD) has so far been controversial. Here, we report a study of PS-1 expression in brains, cell lines and peripheral blood mononuclear cells using a panel of well characterized PS-1-specific antibodies. These antibodies were characterized by immunofluorescent staining of PS-1 transfectants followed by flow cytometric analysis. In human brain, widespread neuronal staining was observed. PS-1 immunoreactivity was primarily confined to neuronal cell bodies and proximal dendrites. Weaker staining of microglia was also detected, in accord with the finding of PS-1 immunoreactivity in monocytes. PS-1 expression is not particularly associated with neurons either containing or spared from neurofibrillary tangles, nor with senile plaques. The level of PS-I expression does not differ between normal and AD brains. Immunoprecipitation from AD, FAD and control brains revealed only a 32 kDa N-terminal fragment and an 18-20 kDa C-terminal fragment. Little or no full length PS-1was detected. The enriched presence of PS-1 in neurons implies an important role in neuronal function, however, the lack of apparent association of its expression with AD pathology signifies the need for a better understanding of its pathophysiological role. (C) 1998 Elsevier Science B.V. C1 Massachusetts Gen Hosp E, Dept Neurol, Alzheimers Res Unit, Boston, MA 02129 USA. Massachusetts Gen Hosp, Dept Neurol, Genet & Aging Unit, Boston, MA 02129 USA. Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. RP Hyman, BT (reprint author), Massachusetts Gen Hosp E, Dept Neurol, Alzheimers Res Unit, 149 13th St,CNY 6405, Boston, MA 02129 USA. EM B_hyman@helix.mgh.harvard.edu FU NIA NIH HHS [AG14744, AG08487, AG05134] NR 43 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD JUN 11 PY 1998 VL 158 IS 1 BP 15 EP 23 DI 10.1016/S0022-510X(98)00106-3 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA ZV705 UT WOS:000074332800003 PM 9667772 ER PT J AU Fishman, JA Rubin, RH AF Fishman, JA Rubin, RH TI Infection in organ-transplant recipients SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID CYTOMEGALO-VIRUS INFECTION; ORTHOTOPIC LIVER-TRANSPLANTATION; DEVELOPING CHRONIC REJECTION; RENAL-TRANSPLANTATION; ALLOGRAFT RECIPIENTS; FUNGAL-INFECTIONS; CMV INFECTION; HEART-TRANSPLANTATION; GANCICLOVIR THERAPY; SEROPOSITIVE DONORS C1 Massachusetts Gen Hosp, Program Transplantat Infect Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Med, Div Hlth Sci & Technol, Ctr Expt Pharmacol & Therapeut, Cambridge, MA 02138 USA. MIT, Cambridge, MA 02139 USA. RP Rubin, RH (reprint author), Massachusetts Gen Hosp, Program Transplantat Infect Dis, 55 Fruit St, Boston, MA 02114 USA. NR 80 TC 905 Z9 938 U1 2 U2 44 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 11 PY 1998 VL 338 IS 24 BP 1741 EP 1751 DI 10.1056/NEJM199806113382407 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA ZT654 UT WOS:000074109800007 PM 9624195 ER PT J AU Rosen, FS Bhan, AK Connolly, SA Ezekowitz, ARB Mark, EJ Shannon, DC Robinson, JC AF Rosen, FS Bhan, AK Connolly, SA Ezekowitz, ARB Mark, EJ Shannon, DC Robinson, JC TI A 54-day-old premature girl with respiratory distress and persistent pulmonary infiltrates - Severe combined immunodeficiency due to adenosine deaminase deficiency. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID MUTATIONS; GENE C1 Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Rosen, FS (reprint author), Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. NR 18 TC 1 Z9 1 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 11 PY 1998 VL 338 IS 24 BP 1752 EP 1758 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA ZT654 UT WOS:000074109800008 ER PT J AU Oliveira, MLS Roberts, TM Druker, BJ Armelin, MCS AF Oliveira, MLS Roberts, TM Druker, BJ Armelin, MCS TI Mapping of polyomavirus middle T domain that is responsible for AP-1 activation SO ONCOGENE LA English DT Article DE polyomavirus; middle T antigen; cell transformation; AP-1 activation; phosphatidylinositol-3 kinase ID PHOSPHATIDYLINOSITOL KINASE-ACTIVITY; SIZED TUMOR-ANTIGEN; RECOMBINANT RETROVIRUSES; CELL-TRANSFORMATION; PROTEIN-KINASES; INTACT-CELLS; WILD-TYPE; C-FOS; JUN; EXPRESSION AB Cell transformation by Polyomavirus middle T (MT) oncoprotein involves binding and activation of several cytoplasmic proteins that participate in growth factors-induced mitogenic signal transduction to the nucleus. We have previously reported that the AP-I transcriptional complex is a target for MT during cell transformation. To analyse the interactions between MT and cellular proteins that are required for constitutive AP-1 activation, we compared wild type and transformation-defective MT mutant cell lines. High AP-1 activity, assessed by gel mobility shift assays, displayed by MT-overexpressing cells, is dependent on MT binding to phosphatidylinositol-3 kinase (PI3K). Treatment with wortmannin (a specific PI3K inhibitor) leads to decreased AP-I activity. Supershift and Western blot analysis with specific antisera, indicate that JunB and cJun, but not cFos or FosB are present in the AP-1 complex. The results confirm the AP-1 complex as a downstream MT target and indicate that AP-1 activation may not be sufficient for cell transformation, since two transformation-defective MT mutants (250phe and MT322) display high AP-1 activity. C1 Univ Sao Paulo, Inst Quim, BR-05599970 Sao Paulo, SP, Brazil. Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Cellular & Mol Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Armelin, MCS (reprint author), Univ Sao Paulo, Inst Quim, CP 26077, BR-05599970 Sao Paulo, SP, Brazil. RI Oliveira, Maria Leonor/F-4988-2012 NR 51 TC 5 Z9 5 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUN 11 PY 1998 VL 16 IS 23 BP 2975 EP 2982 DI 10.1038/sj.onc.1201841 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA ZT782 UT WOS:000074125300003 PM 9662329 ER PT J AU Rainov, NG Dobberstein, KU Sena-Esteves, M Herrlinger, U Kramm, CM Philpot, RM Hilton, J Chiocca, EA Breakefield, XO AF Rainov, NG Dobberstein, KU Sena-Esteves, M Herrlinger, U Kramm, CM Philpot, RM Hilton, J Chiocca, EA Breakefield, XO TI New prodrug activation gene therapy for cancer using cytochrome P450 4B1 and 2-aminoanthracene/4-ipomeanol SO HUMAN GENE THERAPY LA English DT Article ID SPECIES-DEPENDENT EXPRESSION; TARGET ORGAN ALKYLATION; THYMIDINE KINASE GENES; METABOLIC-ACTIVATION; BRAIN-TUMORS; LUNG-CANCER; CYTO-TOXIN; 2B1 GENE; 4-IPOMEANOL; RABBIT AB Vector-mediated transfer of prodrug-activating genes provides a promising means of cancer gene therapy. In a search for more selective and more potent bioactivating enzymes for gene therapy of malignant brain tumors, the toxicity-generating capacity of the rabbit cytochrome P450 isozyme CYP4B1 was investigated. Rabbit CYP4B1, but not rat or human isozymes, efficiently converts the inert prodrugs, 2-aminoanthracene (2-AA) and 4-ipomeanol (4-IM), into highly toxic alkylating metabolites. Toxicity of these two prodrugs was evaluated in culture in parental and genetically modified rodent (9L) and human (U87) glioma cell lines stably expressing CYP4B1, and in vivo in a subcutaneous 9L tumor model in nude mice. The most sensitive CYP4B1-expressing glioma clone, 9L4B1-60, displayed an LD50 of 2.5 mu M for 2-AA and 4-IM after 48 h of prodrug incubation, whereas 20 times higher prodrug concentrations did not cause any significant toxicity to control cells. Substantial killing of control tumor cells by 2-AA was achieved by co-culturing these cells with CYP4B1-expressing cells at a ratio of 100:1, and toxic metabolites could be transferred through medium. In both CYP4B1-expressing cells and cocultured control cells, prodrug bioactivation was associated with DNA fragmentation, as assayed by fluorescent TUNEL, assays and by annexin V staining. Alkaline elution of cellular DNA after exposure to 4-IM revealed extensive protein-DNA crosslinking with single-strand breakage. Growth of 9L-4B1 tumors in nude mice was inhibited by intraperitoneal Injection of 4-IM with minimal side effects. Potential advantages of the CYP4B1 gene therapy paradigm include: the low concentrations of prodrug needed to kill sensitized tumor cells; low prodrug conversion by human isozymes, thus reducing toxicity to normal cells; a tumor-killing bystander effect that can occur even without cell-to-cell contact; and the utilization of lipophilic prodrugs that can penetrate the blood-brain barrier. C1 Massachusetts Gen Hosp East, Ctr Neurosci, Serv Neurol, Mol Neurogenet Unit, Boston, MA 02129 USA. Martin Luther Univ, Fac Med, Dept Neurosurg, D-06097 Halle, Germany. Univ Dusseldorf, Pediat Clin, D-40225 Dusseldorf, Germany. NIEHS, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA. Johns Hopkins Univ, Ctr Oncol, Baltimore, MD 21287 USA. Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Mol Neurooncol Lab, Boston, MA 02114 USA. RP Breakefield, XO (reprint author), Massachusetts Gen Hosp East, Ctr Neurosci, Serv Neurol, Mol Neurogenet Unit, 13th St,Bldg 149, Boston, MA 02129 USA. FU NCI NIH HHS [CA69246] NR 44 TC 58 Z9 58 U1 1 U2 3 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD JUN 10 PY 1998 VL 9 IS 9 BP 1261 EP 1273 DI 10.1089/hum.1998.9.9-1261 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA ZU536 UT WOS:000074207900002 PM 9650611 ER PT J AU Basu, S Rosenzweig, KR Youmell, M Price, BD AF Basu, S Rosenzweig, KR Youmell, M Price, BD TI The DNA-dependent protein kinase participates in the activation of NF kappa B following DNA damage SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID TRANSCRIPTION FACTOR; INDUCED APOPTOSIS; ALPHA; PHOSPHORYLATION; BINDING AB The NFkB transcription factor is activated by diverse stimuli, including Ionizing Radiation (IR) and the cytokine TNF alpha. The role of DNA-PK, a protein kinase involved in the response to DNA damage, in the activation of NF kappa B by IR and TNF alpha was examined. In M059K cells, which express DNA-PK, NF kappa B was activated by both TNF alpha and IR. In M059J cells, which do not express DNA-PK, IR did not activate NF kappa B, whereas TNF alpha induction of NF kappa B was still observed. In HeLa cells, wortmannin, an inhibitor of DNA-PK, blocked the induction of NF kappa B by IR but not by TNF alpha. DNA-PK also phosphorylated the NF kappa B inhibitory proteins IkB-alpha and IkB-beta in vitro, and deletion analysis demonstrated that DNA-PK phosphorylates 2 distinct regions of IkB-beta, These results indicate that DNA-PK participates in the activation of NF kappa B by IR but not by TNF alpha. (C) 1998 Academic Press. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Joint Ctr Radiat Therapy, Boston, MA 02115 USA. RP Price, BD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Joint Ctr Radiat Therapy, JF209,44 Binney St, Boston, MA 02115 USA. EM brendan_price@dfci.harvard.edu FU NCI NIH HHS [CA64585] NR 29 TC 90 Z9 92 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 9 PY 1998 VL 247 IS 1 BP 79 EP 83 DI 10.1006/bbrc.1998.8741 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA ZU593 UT WOS:000074213600016 PM 9636658 ER PT J AU Sobel, BE Woodcock-Mitchell, J Schneider, DJ Holt, RE Marutsuka, K Gold, H AF Sobel, BE Woodcock-Mitchell, J Schneider, DJ Holt, RE Marutsuka, K Gold, H TI Increased plasminogen activator inhibitor type 1 in coronary artery atherectomy specimens from type 2 diabetic compared with nondiabetic patients - A potential factor predisposing to thrombosis and its persistence SO CIRCULATION LA English DT Article; Proceedings Paper CT 70th Scientific Session of the American-Heart-Association Meeting CY NOV 09-13, 1997 CL ORLANDO, FLORIDA SP Amer Heart Assoc DE diabetes mellitus; coronary disease; fibrinolysis; insulin; thrombosis ID OBESE SUBJECTS; INSULIN RESISTANCE; VASCULAR-DISEASE; RISK FACTOR; IN-VIVO; HYPERINSULINEMIA; FIBRINOLYSIS; AUGMENTATION; PROINSULIN; INDUCTION AB Background-Inhibition of fibrinolysis attributable to elevated concentrations of plasminogen activator inhibitor type 1 (PAI-1) in blood is associated with insulin resistance, hyperinsulinemia, and type 2 diabetes mellitus. Because we have shown that insulin can stimulate PAI-1 synthesis in vivo and because accelerated vascular disease is common in such patients as well, we hypothesized that increased PAI-1, potentially predisposing to thrombosis, acute occlusion, and accelerating atherosclerosis because of thrombus-associated mitogens, would be present in excess in atheroma from type 2 diabetic subjects. Methods and Results-Samples acquired by directional coronary atherectomy from 25 patients with type 2 diabetes and 18 patients without diabetes were characterized qualitatively histologically for cellularity and by immunohistochemistry visually and qualitatively and by quantitative image analysis for assessment of urokinase-type plasminogen activator (u-PA) and PAI-1, Patients with and without diabetes were similar with respect to demographic features and the distribution and severity of coronary artery disease, Substantially more PAI-1 and substantially less u-PA were present in the atherectomy samples from subjects with diabetes. Conclusions-The disproportionate elevation of PAI-1 compared with u-PA observed in atheromatous material extracted from vessels of diabetic subjects is consistent with increased gene expression of PAI-1 in vessels as well as the known increase of PAI-1 in blood, presumably reflecting increased synthesis. The increased PAI-1 detected in the atheroma may contribute in vivo to accelerated or persistent thrombosis underlying acute occlusion and to vasculopathy exacerbated by clot-associated mitogens in the vessel wall. Because the changes were observed to be associated with insulin resistance and type 2 diabetes mellitus, they may be modifiable by reduction of insulin resistance with insulin sensitizers and stringent control of hyperglycemia. C1 Univ Vermont, Coll Med, Dept Med, Burlington, VT USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Sobel, BE (reprint author), Dept Med, FAHC MCHV Campus,Fletcher 311,111 Colchester Ave, Burlington, VT 05401 USA. EM burton.sobel@vtmednet.org NR 24 TC 192 Z9 195 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 9 PY 1998 VL 97 IS 22 BP 2213 EP 2221 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA ZR875 UT WOS:000074023500006 PM 9631870 ER PT J AU Ganiatsas, S Kwee, L Fujiwara, Y Perkins, A Ikeda, T Labow, MA Zon, LI AF Ganiatsas, S Kwee, L Fujiwara, Y Perkins, A Ikeda, T Labow, MA Zon, LI TI SEK1 deficiency reveals mitogen-activated protein kinase cascade crossregulation and leads to abnormal hepatogenesis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID C-JUN; EMBRYONIC LETHALITY; MESSENGER-RNA; MICE LACKING; CYCLIN D1; LIVER; STRESS; GROWTH; TRANSCRIPTION; EXPRESSION AB SEK1 (MKK4/JNKK) is a mitogen-activated protein kinase activator that has been shown to participate in vitro in two stress-activated cascades terminating with the SAPK and p38 kinases. To define the role of SEK1 in vivo, we studied stress-induced signaling in SEK1(-/-) embryonic stem and fibroblast cells and evaluated the phenotype of SEK1(-/-) mouse embryos during development. Studies of SEK1(-/-) embryonic stem cells demonstrated defects in stimulated SAPK phosphorylation but not in the phosphorylation of p38 kinase. In contrast, SEK1(-/-) fibroblasts exhibited defects in both SAPK and p38 phosphorylation, demonstrating that crosstalk exists between the stress-activated cascades. Tumor necrosis factor LY and interleukin 1 stimulation of both stress-activated cascades are severely affected in the SEK1(-/-) fibroblast cells. SEK1 deficiency leads to embryonic lethality after embryonic day 12.5 and is associated with abnormal liver development, This phenotype is similar to c-jun null mouse embryos and suggests that SEK1 is required for phosphorylation and activation of c-jun during the organo-genesis of the liver. C1 Harvard Univ, Sch Med, Childrens Hosp, Dana Farber Canc Inst,Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Dana Farber Canc Inst,Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Hoffmann La Roche Inc, Nutley, NJ 07110 USA. RP Zon, LI (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Dana Farber Canc Inst,Howard Hughes Med Inst, 300 Longwood Ave, Boston, MA 02115 USA. RI Perkins, Andrew/M-3216-2014 OI Perkins, Andrew/0000-0003-3644-7093 FU NHLBI NIH HHS [2 PO1 HL32262, P01 HL032262] NR 35 TC 161 Z9 166 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 9 PY 1998 VL 95 IS 12 BP 6881 EP 6886 DI 10.1073/pnas.95.12.6881 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZT829 UT WOS:000074131900057 PM 9618507 ER PT J AU Marciniak, RA Lombard, DB Johnson, FB Guarente, L AF Marciniak, RA Lombard, DB Johnson, FB Guarente, L TI Nucleolar localization of the Werner syndrome protein in human cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HYBRIDIZABLE RIBOSOMAL DNA; ESCHERICHIA-COLI RECQ; AGE-DEPENDENT LOSS; MONOCLONAL-ANTIBODIES; SYNDROME GENE; HELICASE; HOMOLOG; IDENTIFICATION; FIBROBLASTS; INTERACTS AB Werner Syndrome (WS) is a human genetic disorder with many features of premature aging. The gene defective in WS (WRN) has been cloned and encodes a protein homologous to several helicases, including Escherichia coli RecQ, the human Bloom syndrome protein (BLM), and Saccharomyces cerevisiae Sgs1p. To better define the function of WRN protein we have determined its subcellular localization. Indirect immunofluorescence using polyclonal anti-human WRN shows a predominant nucleolar localization. Studies of WRN mutant cells lines confirmed the specificity of antibody recognition. No difference was seen in the subcellular localization of the WRN protein in a variety of normal and transformed human cell lines, including both carcinomas and sarcomas, The nucleolar localization of human WRN protein was supported by the finding that upon biochemical subcellular fractionation, WRN protein is present in an increased concentration in a subnuclear fraction enriched for nucleolar proteins. We have also determined the subcellular localization of the mouse WRN homologue (mWRN). In contrast to human WRN protein, mWRN protein is present diffusely throughout the nucleus. Understanding the function of WRN in these organisms of vastly differing lifespan may yield new insights into the mechanisms of lifespan determination. C1 MIT, Dept Biol, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Guarente, L (reprint author), MIT, Dept Biol, 77 Massachusetts Ave, Cambridge, MA 02139 USA. FU NIA NIH HHS [K08AG00775-01, R01AG11119, R01 AG011119, K08AG00790-01] NR 45 TC 151 Z9 155 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 9 PY 1998 VL 95 IS 12 BP 6887 EP 6892 DI 10.1073/pnas.95.12.6887 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZT829 UT WOS:000074131900058 PM 9618508 ER PT J AU Goldsmith, MA Mikami, A You, Y Liu, KD Thomas, L Pharr, P Longmore, GD AF Goldsmith, MA Mikami, A You, Y Liu, KD Thomas, L Pharr, P Longmore, GD TI Absence of cytokine receptor-dependent specificity in red blood cell differentiation in vivo SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID COLONY-STIMULATING FACTOR; MURINE ERYTHROPOIETIN RECEPTOR; SIGNAL-TRANSDUCTION; INTERLEUKIN-2 RECEPTOR; HEMATOPOIETIC-CELLS; ACTIVATED ERYTHROPOIETIN; CYTOPLASMIC DOMAIN; PROGENITOR CELLS; DISTINCT REGIONS; DEFICIENT MICE AB Erythropoietin (EPO) is required for red blood cell development, hut whether EPO-specific signals directly instruct erythroid differentiation is unknown. We used a dominant system in which constitutively active variants of the EPO receptor were introduced into erythroid progenitors in mice. Chimeric receptors were constructed by replacing the cytoplasmic tail of constitutively active variants of the EPO receptor with tails of diverse cytokine receptors. Receptors linked to granulocyte or platelet production supported complete erythroid development in vitro and in vivo, as did the growth hormone receptor, a nonhematopoietic receptor. Therefore, EPOR-specific signals are not required for terminal differentiation of erythrocytes. Furthermore, we found that cellular context can influence cytokine receptor signaling. C1 Univ Calif San Francisco, Sch Med, Gladstone Inst Virol & Immunol, San Francisco, CA 94141 USA. Univ Calif San Francisco, Sch Med, Dept Med, San Francisco, CA 94141 USA. Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Cell Biol, St Louis, MO 63110 USA. Med Univ S Carolina, Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC 29401 USA. Med Univ S Carolina, Dept Med, Charleston, SC 29401 USA. RP Longmore, GD (reprint author), Univ Calif San Francisco, Sch Med, Gladstone Inst Virol & Immunol, San Francisco, CA 94141 USA. FU NCI NIH HHS [CA75315]; NIGMS NIH HHS [R01 GM054351, R01 GM54351] NR 41 TC 35 Z9 36 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 9 PY 1998 VL 95 IS 12 BP 7006 EP 7011 DI 10.1073/pnas.95.12.7006 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZT829 UT WOS:000074131900079 PM 9618529 ER PT J AU Papisov, MI AF Papisov, MI TI Theoretical considerations of RES-avoiding liposomes: Molecular mechanics and chemistry of liposome interactions SO ADVANCED DRUG DELIVERY REVIEWS LA English DT Review DE drug carrier; drug delivery; drug targeting; liposome; macromolecule; modeling; pharmacokinetics; polymer; steric protection ID STERICALLY STABILIZED LIPOSOMES; LPS-BINDING-PROTEIN; IN-VIVO; LIPOPOLYSACCHARIDE LPS; PROLONGED CIRCULATION; FIBRONECTIN STRUCTURE; COMPLEMENT PROTEINS; IMMUNE CLEARANCE; COVALENT BINDING; GLYCOPROTEIN-I AB The development of long-circulating, RES-avoiding liposomes has become a remarkable milestone in the progress of contemporary pharmacology. Drugs incorporated in such liposomes are protected from fast metabolization and clearance, and can be further targeted to a desired tissue site. Ideally, future developments should result in drug carriers which can identify and act upon their targets with even higher efficiency and selectivity, preferably close to or exceeding that of the natural immune cells. Further increasing carrier 'inertness' with regard to the normal biological milieu is the major requirement for future success. The ability of natural blood components to circulate with blood for several days and weeks presents both the motivation and the challenge for further research. Today, even the best available preparations are inferior to natural proteins and cells with regard to their ability to remain in circulation by approximately two orders of magnitude. In view of the above, it seems vitally important to determine the mechanisms responsible for glycolipid- or polymer-modified liposome protection against RES, and whether any potentially useful mechanisms have been underutilized. Furthermore, identification of quantitative dependencies between liposome structure and pharmacokinetics (and mechanisms underlying such dependencies) would benefit future research and reduce the cost of development. This paper discusses the relationships between liposome structure and circulation with respect to the theoretical mechanistic models of mass transfer, liposome interactions with cells and blood proteins, and boundary effects resulting from surface modification. Special attention is paid to the practical application and limitations of the models. (C) 1998 Elsevier Science B.V. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Nucl Med, Boston, MA 02114 USA. RP Papisov, MI (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Nucl Med, Radiol EDR-517, Boston, MA 02114 USA. EM misha@nmr.mgh.harvard.edu NR 87 TC 60 Z9 63 U1 1 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-409X J9 ADV DRUG DELIVER REV JI Adv. Drug Deliv. Rev. PD JUN 8 PY 1998 VL 32 IS 1-2 BP 119 EP 138 DI 10.1016/S0169-409X(97)00135-X PG 20 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZY339 UT WOS:000074610500009 ER PT J AU Pedraza-Alva, G Merida, LB Burakoff, SJ Rosenstein, Y AF Pedraza-Alva, G Merida, LB Burakoff, SJ Rosenstein, Y TI T cell activation through the CD43 molecule leads to Vav tyrosine phosphorylation and mitogen-activated protein kinase pathway activation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID WISKOTT-ALDRICH SYNDROME; C-CBL PROTOONCOGENE; ANTIGEN RECEPTOR; LYMPHOBLASTOID-CELLS; SIGNAL-TRANSDUCTION; POSITIVE SELECTION; SHC PROTEINS; ZETA-CHAIN; GRB2; ASSOCIATION AB CD43, the most abundant membrane protein of T lymphocytes, is able to initiate signals that lead to Ca(2+) mobilization and interleukin-a production yet the molecular events involved in signal transduction pathway of the CD43 molecule are only beginning to be understood. We have shown recently that cross-linking CD43 on the cell surface of human T lymphocytes with the anti-CD43 monoclonal antibody L10 leads to CD43-Fyn kinase interactions and to Fyn phosphorylation on tyrosine residues. This interaction seems to be mediated by the SH3 domain of Fyn and a proline-rich sequence located in the cytoplasmic domain of CD43. Here we show that CD43-specific activation of human T lymphocytes induced tyrosine phosphorylation of the adaptor protein Shc and of the guanine exchange factor Vav, as well as the formation of a macromolecular complex that comprises She, GRB2, and Vav. CD43 Ligation resulted in enhanced formation of Vav-SLP-76 complexes and in the activation and nuclear translocation of ERK2. Crosslinking of the CD43 molecule in 3T3-CD43(+) cells induced luciferase activity from a construct under the control of the Fos serum responsive element, Altogether, these data suggest that the mitogen-activated protein kinase pathway is involved in CD43-dependent interleukin-2 gene expression. C1 Univ Nacl Autonoma Mexico, Inst Biotechnol, Cuernavaca 62250, Morelos, Mexico. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Rosenstein, Y (reprint author), Univ Nacl Autonoma Mexico, Inst Biotechnol, APDO Postal 510-3, Cuernavaca 62250, Morelos, Mexico. EM yvonne@ibt.unam.mx NR 64 TC 49 Z9 49 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 5 PY 1998 VL 273 IS 23 BP 14218 EP 14224 DI 10.1074/jbc.273.23.14218 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZR856 UT WOS:000074021500027 PM 9603925 ER PT J AU Hara, K Yonezawa, K Weng, QP Kozlowski, MT Belham, C Avruch, J AF Hara, K Yonezawa, K Weng, QP Kozlowski, MT Belham, C Avruch, J TI Amino acid sufficiency and mTOR regulate p70 S6 kinase and eIF-4E BP1 through a common effector mechanism SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID POLYPEPTIDE-CHAIN INITIATION; CAP-DEPENDENT TRANSLATION; ACTIVATED PROTEIN-KINASE; RAT SKELETAL-MUSCLE; HAMSTER OVARY CELLS; PHOSPHATIDYLINOSITOL 3-KINASE; HEPATIC PROTEOLYSIS; PLASMA-MEMBRANE; FACTOR 4E; IN-VIVO AB The present study identifies the operation of a signal tranduction pathway in mammalian cells that provides a checkpoint control, linking amino acid sufficiency to the control of peptide chain initiation. Withdrawal of amino acids from the nutrient medium of CHO-IR cells results in a rapid deactivation of p70 SG kinase and dephosphorylation of eIF-4E BP1, which become unresponsive to all agonises. Readdition of the amino acid mixture quickly restores the phosphorylation and responsiveness of p70 and eIF-4E BP1 to insulin. Increasing the ambient amino acids to twice that usually employed increases basal p70 activity to the maximal level otherwise attained in the presence of insulin and abrogates further stimulation by insulin, withdrawal of most individual amino acids also inhibits p70, although with differing potency. Amino acid withdrawal from CHO-IR cells does not significantly alter insulin stimulation of tyrosine phosphorylation, phosphotyrosine-associated phosphatidylinositol 3-kinase activity, c-Akt/protein kinase B activity, or mitogen-activated protein kinase activity. The selective inhibition of p70 and eIF-4E BP1 phosphorylation by amino acid withdrawal resembles the response to rapamycin, which prevents p70 reactivation by amino acids, indicating that mTOR is required for the response to amino acids. A p70 deletion mutant, p70 Delta 2-46/Delta CT104, that is resistant to inhibition by rapamycin (but sensitive to wortmannin) is also resistant to inhibition by amino acid withdrawal, indicating that amino acid sufficiency and mTOR signal to p70 through a common effector, which could be mTOR itself, or an mTOR-controlled downstream element, such as a protein phosphatase. C1 Massachusetts Gen Hosp, Med Serv, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. Kobe Univ, Biosignal Res Ctr, Kobe, Hyogo 657, Japan. Massachusetts Gen Hosp, Dept Mol Biol, Diabet Res Lab, Diabet Unit, Boston, MA 02114 USA. RP Avruch, J (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Diabet Res Lab, Diabet Unit, 50 Blossom St, Boston, MA 02114 USA. EM avruch@helix.mgh.harvard.edu FU NCI NIH HHS [CA73818]; NIDDK NIH HHS [DK17776] NR 62 TC 820 Z9 840 U1 7 U2 31 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 5 PY 1998 VL 273 IS 23 BP 14484 EP 14494 DI 10.1074/jbc.273.23.14484 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZR856 UT WOS:000074021500064 PM 9603962 ER PT J AU Nierenberg, DW Nordgren, RE Chang, MB Siegler, RW Blayney, MB Hochberg, F Toribara, TY Cernichiari, E Clarkson, T AF Nierenberg, DW Nordgren, RE Chang, MB Siegler, RW Blayney, MB Hochberg, F Toribara, TY Cernichiari, E Clarkson, T TI Delayed cerebellar disease and death after accidental exposure to dimethylmercury SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID METHYLMERCURY; MERCURY; IRAQ; ACID C1 Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Med,Sect Clin Pharmacol, Hanover, NH 03756 USA. Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Pharmacol Toxicol,Sect Clin Pharmacol, Hanover, NH 03756 USA. Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Pathol, Hanover, NH 03756 USA. Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Med,Sect Neurol, Hanover, NH 03756 USA. Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Pediat,Sect Neurol, Hanover, NH 03756 USA. Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Off Environ Hlth & Safety, Hanover, NH 03756 USA. Univ Rochester, Sch Med, Dept Environm Med, Rochester, NY USA. Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. RP Nierenberg, DW (reprint author), Dartmouth Hitchcock Med Ctr, Hinman Box 7506, Lebanon, NH 03756 USA. FU NIEHS NIH HHS [ES 01247] NR 30 TC 98 Z9 102 U1 1 U2 6 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 4 PY 1998 VL 338 IS 23 BP 1672 EP 1676 DI 10.1056/NEJM199806043382305 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA ZR451 UT WOS:000073978000005 PM 9614258 ER PT J AU Pesche, S Latil, A Muzeau, F Cussenot, O Fournier, G Longy, M Eng, C Lidereau, R AF Pesche, S Latil, A Muzeau, F Cussenot, O Fournier, G Longy, M Eng, C Lidereau, R TI PTEN/MMAC1/TEP1 involvement in primary prostate cancers SO ONCOGENE LA English DT Article DE prostate cancer; chromosome arm 10q; LOH; PTEN ID ALLELIC LOSS; MICROSATELLITE INSTABILITY; DISTINCT REGIONS; CHROMOSOME-10; HETEROZYGOSITY; DELETION; LOCI; GENE; PROGRESSION; ADENOCARCINOMA AB The PTEN/MMAC1/TEP1 gene, located at 10q23.3, is a tumor suppressor gene responsible for the familial cancer syndromes Cowden disease and Bannayan-Zonana syndrome, and is commonly somatically mutated in several types of cancers. Mutations of the PTEN gene have been found in prostate cancer cell lines and LOH at 10q22-24 in prostate tumors have also been described with a high frequency. To determine the role of this gene in prostate tumorigenesis, we therefore analysed 22 primary tumors for loss of heterozygosity (LOH) within the 10q22-23 region such that tumors hemizygous at those loci may be examined for somatic PTEN mutations. Losses of heterozygosity of at least one locus was found in 12 (55%) of the 22 tumors DNAs. Among these, six tumors exhibited allele loss in the interval between D10S1765 and D10S541 wherein lies the PTEN gene. We searched the entire coding region of PTEN for somatic mutations in these six tumors. One somatic mutation (17%), a 1 bp deletion, was detected in exon 7 of the gene, in ode tumor, indicating that somatic mutations of the PTEN gene may occur in primary prostate tumors. C1 Ctr Rene Huguenin, Lab Oncogenet, F-92211 St Cloud, France. CHU St Louis, Dept Urol, F-75010 Paris, France. Hop Cavale Blanche, Dept Urol, F-29609 Brest, France. Ctr Reg Lutte Canc, Inst Bergonie, F-33076 Bordeaux, France. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Cambridge, CRC, Human Canc Genet Res Grp, Cambridge CB2 2QQ, England. RP Lidereau, R (reprint author), Ctr Rene Huguenin, Lab Oncogenet, 9 Rue Gaston Latouche, F-92211 St Cloud, France. OI Eng, Charis/0000-0002-3693-5145 NR 46 TC 110 Z9 116 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUN 4 PY 1998 VL 16 IS 22 BP 2879 EP 2883 DI 10.1038/sj.onc.1202081 PG 5 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA ZR544 UT WOS:000073988200006 PM 9671408 ER PT J AU Weeks, JC Cook, EF O'Day, SJ Petersen, LM Wenger, N Reding, D Harrell, FE Kussin, P Dawson, NV Connors, AF Lynn, J Phillips, RS AF Weeks, JC Cook, EF O'Day, SJ Petersen, LM Wenger, N Reding, D Harrell, FE Kussin, P Dawson, NV Connors, AF Lynn, J Phillips, RS TI Relationship between cancer patients' predictions of prognosis and their treatment preferences SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ADVANCE DIRECTIVES; CARDIOPULMONARY-RESUSCITATION; BREAST-CANCER; SURVIVAL; LIFE; CARE; DECISIONS; DOCTORS; TRUTH AB Context.-Previous studies have documented that cancer patients tend to overestimate the probability of long-term survival. If patient preferences about the trade-offs between the risks and benefits associated with alternative treatment strategies are based on inaccurate perceptions of prognosis, then treatment choices may not reflect each patient's true values. Objective.-To test the hypothesis that among terminally ill cancer patients an accurate understanding of prognosis is associated with a preference for therapy that focuses on comfort over attempts at life extension. Design.-Prospective cohort study. Setting.-Five teaching hospitals in the United States. Patients.-A total of 917 adults hospitalized with stage III or IV non-small cell lung cancer or colon cancer metastatic to liver in phases 1 and 2 of the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments (SUPPORT), Main Outcome Measures.-Proportion of patients favoring life-extending therapy over therapy focusing on relief of pain and discomfort, patient and physician estimates of the probability of 6-month survival, and actual 6-month survival, Results.-Patients who thought they were going to live for at least 6 months were more likely (odds ratio [OR], 2.6; 95% confidence interval [CI], 1.8-3.7) to favor life-extending therapy over comfort care compared with patients who thought there was at least a 10% chance that they would not live 6 months. This OR was highest (8.5; 95% CI, 3.0-24.0) among patients who estimated their 6-month survival probability at greater than 90% but whose physicians estimated it at 10% or less. Patients overestimated their chances of surviving 6 months, while physicians estimated prognosis quite accurately. Patients who preferred life-extending therapy were more likely to undergo aggressive treatment, but controlling for known prognostic factors, their 6-month survival was no better. Conclusions.-Patients with metastatic colon and lung cancer overestimate their survival probabilities and these estimates may influence their preferences about medical therapies. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Gen Med, Clin Epidemiol Sect, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. Univ Calif Los Angeles, Med Ctr, Dept Med, Los Angeles, CA 90024 USA. Marshfield Clin Fdn Med Res & Educ, Marshfield, WI 54449 USA. Univ Virginia, Sch Med, Dept Hlth Evaluat Sci, Div Biostat & Epidemiol, Charlottesville, VA 22908 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Case Western Reserve Univ, Dept Med, Metrohlth Med Ctr, Cleveland, OH 44106 USA. George Washington Univ, Ctr Improve Care Dying, Washington, DC USA. Beth Israel Hosp, Dept Med, Div Gen Med & Primary Care, Boston, MA 02215 USA. RP Weeks, JC (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. EM jane_weeks@dci.harvard.edu NR 31 TC 559 Z9 561 U1 8 U2 25 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 3 PY 1998 VL 279 IS 21 BP 1709 EP 1714 DI 10.1001/jama.279.21.1709 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA ZQ544 UT WOS:000073878700031 PM 9624023 ER PT J AU Schorge, JO Muto, MG Welch, WR Bandera, CA Rubin, SC Bell, DA Berkowitz, RS Mok, SC AF Schorge, JO Muto, MG Welch, WR Bandera, CA Rubin, SC Bell, DA Berkowitz, RS Mok, SC TI Molecular evidence for multifocal papillary serous carcinoma of the peritoneum in patients with germline BRCA1 mutations SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID X-CHROMOSOME INACTIVATION; FAMILIAL-OVARIAN-CANCER; UNIFOCAL ORIGIN; PROPHYLACTIC OOPHORECTOMY; ADENOCARCINOMA; MANAGEMENT AB Background: Papillary serous carcinoma of the peritoneum (PSCP) diffusely involves peritoneal surfaces, while it spares or only superficially involves the ovaries. PSCP is histologically indistinguishable from serous epithelial ovarian carcinoma, and it may develop years after oophorectomy, The molecular pathogenesis of PSCP remains unresolved, although preliminary data suggest a multifocal origin in some cases. Patients with germline BRCA1 mutations may develop PSCP in addition to breast and ovarian carcinomas. The purpose of this study was to utilize the androgen receptor (AR) gene locus to test the hypothesis that some cases of PSCP have a multifocal origin and to determine if patients with germline BRCA1 mutations develop multifocal PSCP. Methods: Specimens of normal and tumor tissues from 22 women with PSCP were obtained, and DNA was extracted. The AR gene locus was evaluated for patterns of loss of heterozygosity (LOH) and X-chromosome inactivation. The methylation-sensitive Hpa II restriction enzyme was used to differentiate the active and inactive X chromosomes. Germline BRCA1 mutation status of the patients was determined previously, Results: Genetic analysis of tumor specimens indicated that five (23%) of 22 case subjects had patterns of selective LOH at the AR locus, consistent with multifocal, polyclonal disease origin. Two patients with selective LOH also had alternating X-chromosome inactivation patterns. Patients with germline BRCA1 mutations were more likely to have evidence of multifocal disease (two-sided Fisher's exact test, P = .01), Conclusions: Our results show that PSCP has a multifocal origin in at least some cases. Furthermore, patients with germline BRCA1 mutations are more likely to develop multifocal PSCP than are patients without BRCA1 mutations. C1 Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Lab Gynecol Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Div Gynecol Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Womens & Perinatal Pathol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. Univ Penn, Ctr Canc, Div Gynecol Oncol, Philadelphia, PA 19104 USA. RP Schorge, JO (reprint author), Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Lab Gynecol Oncol, 221 Longwood Ave,BLI-447, Boston, MA 02115 USA. EM JOSCHORGE@BICS.BWH.HARVARD.EDU FU NCI NIH HHS [R01CA69291, R01CA63381, R01CA69453] NR 30 TC 78 Z9 80 U1 0 U2 1 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUN 3 PY 1998 VL 90 IS 11 BP 841 EP 845 DI 10.1093/jnci/90.11.841 PG 5 WC Oncology SC Oncology GA ZR701 UT WOS:000074005100012 PM 9625172 ER PT J AU Griner, PF Blumenthal, D AF Griner, PF Blumenthal, D TI New bottles for vintage wines: The changing management of the medical school faculty SO ACADEMIC MEDICINE LA English DT Article AB Medical schools are being challenged to develop innovative mechanisms of faculty governance and manage ment that enlist faculty in meeting the demands of a competitive marketplace. The authors describe some of these mechanisms in this article, which is the result of case studies made in 1997 of ten schools. Measures to increase the accountability of faculty to the strategic directions of the school include having appointment letters that specify explicitly the roles and responsibilities of the faculty member, conducting annual performance reviews based upon more objective criteria, tying salary to performance, lengthening the pre-tenure probation period, instituting post-tenure review, and redefining the salary guarantees of tenured faculty. Equally important is balancing these policies with initiatives to strengthen the accountability of schools to their faculty. Improved methods of communication between administrators and faculty and more efficient processes to enable faculty to participate in decision making are appearing. Formal approaches to mentoring and faculty development are being implemented, Recognition and reward programs are being strengthened. Alternatives to tenure are being developed in recognition of the need for increasingly diverse roles of faculty and to ensure job security. The reengineering of the processes that will lead to shared vision and accountability will require massive cultural change. The realization of these goals is likely to depend on the skill of medical school managers and the ability and willingness of faculty members to work collaboratively and creatively in designing new methods to accomplish old missions, Next month's AAMC Paper will explore changes in the structure and management of medical schools and their owned or closely affiliated facilities to improve the efficiency of achieving their core missions. C1 Assoc Amer Med Coll, Ctr Assessment & Management Change Acad Med, Washington, DC 20037 USA. Harvard Med Sch, Boston, MA USA. Massachusetts Gen Hosp, Hlth Policy Res & Dev Unit, Boston, MA 02114 USA. RP Griner, PF (reprint author), Assoc Amer Med Coll, Ctr Assessment & Management Change Acad Med, 2450 N St NW, Washington, DC 20037 USA. NR 7 TC 11 Z9 11 U1 0 U2 2 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD JUN PY 1998 VL 73 IS 6 BP 720 EP 724 DI 10.1097/00001888-199806000-00022 PG 5 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA ZW182 UT WOS:000074383900034 PM 9653414 ER PT J AU Yager, J Burt, V Mohl, PC AF Yager, J Burt, V Mohl, PC TI Downsizing psychiatric residency programs - A pilot study SO ACADEMIC PSYCHIATRY LA English DT Article ID MEDICINE AB Under the varied pressures of decreasing recruitment of American medical school graduates into psychiatry, the thrust of health care policymakers to decrease the production of specialist physicians, and financial cutbacks for training by hospitals, universities, and governments at all levels, many psychiatric training programs are considering downsizing or have already implemented plans to do so. The authors describe the motivations, early experiences, anticipated concerns, and thoughts regarding downsizing obtained from interviews or questionnaires provided by 17 programs in 1993. On the basis of the authors' experiences, some recommendations are offered for the many programs likely to deal with this issue in the future. C1 Univ New Mexico, Dept Psychiat, Sch Med, Albuquerque, NM 87131 USA. Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Univ Texas, SW Med Ctr, Dept Psychiat, Austin, TX USA. W Los Angeles Vet Affairs Med Ctr, Brentwood Div, Mental Hlth Clin, Los Angeles, CA 90073 USA. RP Yager, J (reprint author), Univ New Mexico, Dept Psychiat, Sch Med, 2400 Tucker NE, Albuquerque, NM 87131 USA. NR 4 TC 5 Z9 5 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA SN 1042-9670 J9 ACAD PSYCHIATR JI Acad. Psych. PD SUM PY 1998 VL 22 IS 2 BP 127 EP 134 PG 8 WC Education & Educational Research; Psychiatry SC Education & Educational Research; Psychiatry GA ZQ798 UT WOS:000073904100006 PM 24442938 ER PT J AU Caskey, NH Wirshing, WC Jarvik, ME Madsen, DC Elins, JL AF Caskey, NH Wirshing, WC Jarvik, ME Madsen, DC Elins, JL TI Smoking influences on symptoms in schizophrenia SO ADDICTION LA English DT Meeting Abstract C1 W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Sch Med, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU CARFAX PUBL CO PI ABINGDON PA PO BOX 25, ABINGDON, OXFORDSHIRE, ENGLAND OX14 3UE SN 0965-2140 J9 ADDICTION JI Addiction PD JUN PY 1998 VL 93 IS 6 BP 913 EP 913 PG 1 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA ZV421 UT WOS:000074302900022 ER PT J AU Ferbas, J AF Ferbas, J TI Perspectives on the role of CD8(+) cell suppressor factors and cytotoxic T lymphocytes during HIV infection SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID TYPE-1 INFECTION; CD8+ LYMPHOCYTES; VIRUS-REPLICATION; LYMPH-NODES; AIDS; DISEASE; SDF-1; CHEMOATTRACTANT; IDENTIFICATION; MIP-1-ALPHA AB It is clear that HIV burden drives CD8(+) cell expansion and activation in vivo, but it has been difficult to determine whether the CD8(+) cell response represents a significant anti-HIV force during the natural history of infection. This issue is illustrated by the fact that CD8(+) cells cannot clear HIV infection, providing less than satisfactory evidence that CD8(+) cells have any substantial effect on viral replication in vivo. The diligent efforts of a number of laboratories, however, are revealing the magnitude of the anti-HIV CD8(+) cell arsenal. It is now well established that CD8(+) cells can suppress viral dissemination and rates of HIV transcription in addition to their ability to destroy virus-infected cells directly. This is achieved through production of a growing family of HIV suppressor factors. These exciting developments are paving the way for new studies to readdress and potentially redefine the role of HIV-specific CD8(+) cell responses during HN infection. As we complete our understanding of how these effector activities work in concert to oppose HIV, the potential that CD8(+) cell responses can be manipulated by vaccination or used in conjunction with HAART holds promise in the ongoing effort to eradicate HN infection in chronically infected individuals. C1 Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90095 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP Ferbas, J (reprint author), Univ Calif Los Angeles, Sch Med, Dept Med, 12-236 Louis Factor Bldg, Los Angeles, CA 90095 USA. FU NIAID NIH HHS [AI37613] NR 84 TC 21 Z9 21 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD JUN PY 1998 VL 14 SU 2 BP S153 EP S160 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA ZX734 UT WOS:000074549300005 PM 9672233 ER PT J AU Rosenberg, ES Walker, BD AF Rosenberg, ES Walker, BD TI HIV type 1-specific helper T cells: A critical host defense SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID ACQUIRED IMMUNODEFICIENCY SYNDROME; LOW VIRAL LOAD; IMMUNE-RESPONSES; INFECTION; VIRUS; LYMPHOCYTES; AIDS; RECOGNITION; INDIVIDUALS; PEPTIDE C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Rosenberg, ES (reprint author), Massachusetts Gen Hosp, Partners AIDS Res Ctr, 55 Fruit St, Boston, MA 02114 USA. NR 32 TC 44 Z9 47 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD JUN PY 1998 VL 14 SU 2 BP S143 EP S147 PG 5 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA ZX734 UT WOS:000074549300003 PM 9672231 ER PT J AU Rodriguez, A Bernardi, V Fernandez, M Mauvecin, C Ayala, F Santaera, O Martinez, J Mele, E Roubin, GS Palacios, I Ambrose, JA AF Rodriguez, A Bernardi, V Fernandez, M Mauvecin, C Ayala, F Santaera, O Martinez, J Mele, E Roubin, GS Palacios, I Ambrose, JA TI In-hospital and late results of coronary stents versus conventional balloon angioplasty in acute myocardial infarction (GRAMI trial) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID THROMBOLYTIC THERAPY; LUMINAL DIAMETER; ARTERY DISEASE; IMMEDIATE ANGIOPLASTY; THREATENED CLOSURE; IMPLANTATION; RESTENOSIS AB One hundred four patients presenting with acute myocardial infarction <24 hours after onset were randomized to 2 groups: group I (n = 52) was treated with balloon angioplasty followed electively with Gianturco Roubin II stents, and group II was treated with conventional balloon angioplasty alone (n = 52). All lesions were suitable for stenting. Baseline clinical, demographic, and angiographic characteristics were similar in the 2 groups. Procedural success was defined as no laboratory death or emergent coronary bypass, Thrombolysis In Myocardial Infarction (TIMI) trial 2 or 3 flow after the procedure in a culprit vessel, and a residual stenosis less than or equal to 30% for coronary angioplasty and <20% for stent. Procedural success was 98% in group I versus 94.2% in group II, p = NS. Thirteen patients in group II (25%) had bailout stenting during the initial procedure. Adverse in-hospital events including either death, non-elective coronary bypass, recurrent ischemia, and reinfarction occurred in 3.8% in group I versus 19.2% in group II, p = 0.03. Repeat angiography performed routinely before hospital discharge revealed TIMI 3 flow in the infarct-related artery in 98% in group I versus 83% in group II, p <0.03. At late follow-vp, event-free survival was significantly better in the stent (83%) than in the coronary angioplasty (65%) group (p = 0.002). The procedural in-hospital and late outcomes of this randomized study demonstrate that balloon angioplasty followed electively by coronary stents can be used as the primary modality for patients undergoing coronary interventions for acute myocardial infarction, increasing TIMI 3 flow, reducing in-hospital adverse events, and improving late outcome compared with balloon angioplasty alone. (C) 1998 by Excerpta Medico, Inc. C1 Anchorena Hosp, Cardiac Unit Otamendi, Buenos Aires, DF, Argentina. Univ Alabama, Cardiac Unit, Birmingham, AL USA. Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. Mt Sinai Hosp, Cardiovasc Inst, New York, NY 10029 USA. RP Rodriguez, A (reprint author), Ayacucho 1547 10 B, RA-1112 Buenos Aires, DF, Argentina. NR 27 TC 121 Z9 126 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JUN 1 PY 1998 VL 81 IS 11 BP 1286 EP 1291 DI 10.1016/S0002-9149(98)00154-4 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA ZR823 UT WOS:000074017900002 PM 9631964 ER PT J AU Bullman, TB Kang, HK AF Bullman, TB Kang, HK TI Mortality among World War II veterans exposed to mustard gas. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 Environm Epidemiol Serv, US Dept Vet Affairs, Washington, DC 20036 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1998 VL 147 IS 11 SU S MA 145 BP S37 EP S37 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA ZR584 UT WOS:000073992800146 ER PT J AU Rabeneck, L Wray, NP Graham, DY AF Rabeneck, L Wray, NP Graham, DY TI Managing dyspepsia: What do we know and what do we need to know? SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID ULCER-LIKE DYSPEPSIA; HELICOBACTER-PYLORI; SCORING SYSTEM; ENDOSCOPIC FINDINGS; GENERAL-POPULATION; COST-EFFECTIVENESS; PREDICTIVE VALUE; WORKING PARTY; UNITED-STATES; PEPTIC-ULCER AB Objective: The conceptual revolution concerning the role of Helicobacter pylori in the pathogenesis of peptic ulcer disease has raised the larger question of how to integrate this new information into the management of patients with dyspepsia. The aim of this research was to critically evaluate current knowledge about dyspepsia and its management. Methods: Relevant articles on dyspepsia were identified from MEDLINE searches and from the bibliographies of identified articles. Studies that contained information on the prevalence of dyspepsia, endoscopic findings, and evaluations of alternative management strategies were reviewed. Results: By coupling H. pylori serological testing with clinical factors such as age and nonsteroidal antiinflammatory drug use, strategies have been developed that identify patients with organic disease. Although the use of these strategies can reduce the volume of endoscopies, their effects on dyspepsia symptoms are unknown. Computerized decision analysis models have been used to evaluate the cost-effectiveness of alternative strategies. The indirect evidence obtained from these models suggests that empiric therapy, guided by H. pylori testing, may be the preferred approach. However, the models have been hampered by the lack of information concerning dyspepsia symptoms, the primary health outcome of the majority of patients seen in primary practice settings. Conclusions: Currently, the knowledge needed to integrate H. pylori tests and antimicrobial therapies into the management of patients with dyspepsia in primary practice settings has not been developed. A pressing need exists for a randomized controlled trial to evaluate alternative management strategies. In conducting such a trial, valid, reliable instruments for measuring dyspepsia will be needed. (C) 1998 by Am. Coll. of Gastroenterology. C1 Dept Vet Affairs Med Ctr, Houston, TX USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, HSR&D Field Program, Houston, TX 77030 USA. RP Rabeneck, L (reprint author), Vet Affairs Med Ctr, 2002 Holcombe Blvd,111D, Houston, TX 77030 USA. NR 51 TC 24 Z9 24 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD JUN PY 1998 VL 93 IS 6 BP 920 EP 924 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZV664 UT WOS:000074328500012 PM 9647019 ER PT J AU Neuhausen, SL Godwin, AK Gershoni-Baruch, R Schubert, E Garber, J Stoppa-Lyonnet, D Olah, E Csokay, B Serova, O Lalloo, F Osorio, A Stratton, M Offit, K Boyd, J Caligo, MA Scott, RJ Schofield, A Teugels, E Schwab, M Cannon-Albright, L Bishop, T Easton, D Benitez, J King, MC Ponder, BAJ Weber, B Devilee, P Borg, A Narod, SA Goldgar, D AF Neuhausen, SL Godwin, AK Gershoni-Baruch, R Schubert, E Garber, J Stoppa-Lyonnet, D Olah, E Csokay, B Serova, O Lalloo, F Osorio, A Stratton, M Offit, K Boyd, J Caligo, MA Scott, RJ Schofield, A Teugels, E Schwab, M Cannon-Albright, L Bishop, T Easton, D Benitez, J King, MC Ponder, BAJ Weber, B Devilee, P Borg, A Narod, SA Goldgar, D TI Haplotype and phenotype analysis of nine recurrent BRCA2 mutations in 111 families: Results of an international study SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID ASHKENAZI-JEWISH INDIVIDUALS; BREAST-CANCER; CARRIER FREQUENCY; GENE; WOMEN; MAP AB Several BRCA2 mutations are found to occur in geographically diverse breast and ovarian cancer families. To investigate both mutation origin and mutation-specific phenotypes due to BRCA2, we constructed a haplotype of 10 polymorphic short tandem-repeat (STR) markers flanking the BRCA2 locus, in a set of 111 breast or breast/ovarian cancer families selected for having one of nine recurrent BRCA2 mutations. Six of the individual mutations are estimated to have arisen 400-2,000 years ago. In particular, the 6174delT mutation, found in similar to 1% of individuals of Ashkenazi Jewish ancestry, was estimated to have arisen 29 generations ago (1-LOD support interval 22-38). This is substantially more recent than the estimated age of the BRCA1 185delAG mutation (46 generations), derived from our analogous study of BRCA1 mutations. In general, there was no evidence of multiple origins of identical BRCA2 mutations. Our study data were consistent with the previous report of a higher incidence of ovarian cancer in families with mutations in a 3.3-kb region of exon 11 (the ovarian cancer cluster region [OCCR]) (P = .10); but that higher incidence was not statistically significant. There was significant evidence that age at diagnosis of breast cancer varied by mutation (P < .001), although only 8% of the variance in age at diagnosis could be explained by the specific mutation, and there was no evidence of family-specific effects. When the age at diagnosis of the breast cancer cases was examined by OCCR, cases associated with mutations in the OCCR had a significantly older mean age at diagnosis than was seen in those outside this region (48 years vs. 42 years; P = .0005). C1 Univ Utah, Sch Med, Dept Med Informat, Div Genet Epidemiol,Genet Epidemiol Grp, Salt Lake City, UT 84108 USA. Univ Penn, Fox Chase Canc Ctr, Dept Med Oncol, Philadelphia, PA 19104 USA. Univ Penn, Dept Hematol Oncol, Philadelphia, PA 19104 USA. Rambam Med Ctr, Dept Human Genet, Haifa, Israel. Univ Washington, Dept Med, Seattle, WA USA. Univ Washington, Dept Genet, Seattle, WA USA. Inst Curie, Unite Genet Oncol, Paris, France. Dana Farber Canc Inst, Boston, MA 02115 USA. Natl Inst Oncol, Budapest, Hungary. Int Agcy Res Canc, F-69372 Lyon, France. Univ Manchester, Dept Med Genet, Manchester, Lancs, England. St Marys Hosp, Reg Genet Serv, Manchester M13 0JH, Lancs, England. Fdn Jimenez Diaz, Dept Genet, E-28040 Madrid, Spain. Inst Canc Res, Sect Mol Carcinogenesis, Sutton, Surrey, England. Mem Sloan Kettering Canc Ctr, Dept Human Genet, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10021 USA. Univ Pisa, Dept Oncol, Pisa, Italy. Kantonsspital Basel, Dept Human Genet, Basel, Switzerland. Univ Aberdeen, Sch Med, Dept Med Genet, Aberdeen AB9 2ZD, Scotland. Free Univ Brussels, Ctr Oncol, Brussels, Belgium. German Canc Res Ctr, D-6900 Heidelberg, Germany. Imperial Canc Res Fund, Genet Epidemiol Lab, Leeds, W Yorkshire, England. Inst Publ Hlth, Genet Epidemiol Unit, CRC, Cambridge, England. Univ Cambridge, Dept Oncol, Human Canc Genet Grp, CRC, Cambridge, England. Leiden Univ, Dept Human Genet, NL-2300 RA Leiden, Netherlands. Univ Lund Hosp, Dept Oncol, S-22185 Lund, Sweden. Univ Toronto, Ctr Res Womens Hlth, Toronto, ON, Canada. RP Neuhausen, SL (reprint author), Univ Utah, Sch Med, Dept Med Informat, Div Genet Epidemiol,Genet Epidemiol Grp, 391 Chipeta Way,Suite D2, Salt Lake City, UT 84108 USA. RI Osorio, Ana/I-4324-2014; OI Osorio, Ana/0000-0001-8124-3984; Bishop, Tim/0000-0002-8752-8785; albright, lisa/0000-0003-2602-3668 FU NCI NIH HHS [N01-CN-6700, R01 CA27632] NR 20 TC 109 Z9 110 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JUN PY 1998 VL 62 IS 6 BP 1381 EP 1388 DI 10.1086/301885 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA ZU224 UT WOS:000074174700014 PM 9585613 ER PT J AU Halpern, MT Palmer, CS Foster, CS Pal, A Battista, C AF Halpern, MT Palmer, CS Foster, CS Pal, A Battista, C TI A pharmacoeconomic analysis of rimexolone for the treatment of ophthalmic inflammatory conditions SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID UVEITIS; SURGERY AB Topical steroids are the standard first-line therapy for treating ophthalmic inflammatory conditions. However, potent ophthalmic steroids can lead to an elevation of intraocular pressure (IOP), which can result in greater medical resource utilization and increased costs. We have developed a decision analysis model from a societal perspective to evaluate the costs and consequences of the treatment of ophthalmic inflammatory conditions with two potent topical steroids: prednisolone and rimexolone. Data for the model are based on information from clinical trials, national databases, published literature, and responses by ophthalmologists to a questionnaire on treatment patterns for elevated IOP. Three steroid-responsive conditions are examined separately with the model: uveitis; postoperative inflammation following cataract surgery; and other ophthalmic inflammatory conditions (blepharitis, episcleritis, postoperative refractive surgery, and corneal transplant). The model evaluates patients with acute conditions versus those with chronic conditions and those with mild to moderate elevation of IOP versus those with severe elevation of IOP. Although the unit cost of rimexolone is higher than that of prednisolone, use of rimexolone leads to cost savings because the incidence of elevated IOP is decreased. If rimexolone is used instead of prednisolone for the treatment of ophthalmic inflammatory conditions, the estimated cost saved (at 1995 AWP prices) is approximately $10 million across the entire US population. The savings across the health maintenance organization population on an annualized basis is approximately $3.9 million. Even if rimexolone were priced higher than current market charges (at 130% to 150% of the AWP of prednisolone), cost savings ranging from $2.9 million to $720,000 would accrue with use of rimexolone compared with prednisolone. However, if rimexolone were priced at 160% of the AWP of prednisolone, its use would incur an additional cost of $300,000. The primary medical resource utilized in treating elevated IOP in ophthalmic inflammatory conditions is physician visits. Medications are responsible for only one-fifth to one-third of the total cost of treating elevated IOP. This analysis indicates that rimexolone is associated with decreased medical resource utilization and cost savings to the entire healthcare system. C1 MEDTAP Int Inc, Bethesda, MD 20814 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA USA. Alcon Labs Inc, Ft Worth, TX 76101 USA. RP Halpern, MT (reprint author), MEDTAP Int Inc, 7101 Wisconsin Ave,Suite 600, Bethesda, MD 20814 USA. NR 11 TC 5 Z9 5 U1 0 U2 0 PU AMER MED PUBLISHING, M W C COMPANY PI OLD BRIDGE PA 1816 ENGLISHTOWN RD, STE 101, OLD BRIDGE, NJ 08857 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD JUN PY 1998 VL 4 IS 6 BP 854 EP 862 PG 9 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA ZX602 UT WOS:000074534700006 PM 10181071 ER PT J AU Meigs, JB Barry, MJ Giovannucci, E Rimm, EB Stampfer, MJ Kawachi, I AF Meigs, JB Barry, MJ Giovannucci, E Rimm, EB Stampfer, MJ Kawachi, I TI High rates of prostate-specific antigen testing in men with evidence of benign prostatic hyperplasia SO AMERICAN JOURNAL OF MEDICINE LA English DT Article; Proceedings Paper CT 19th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 02-04, 1996 CL WASHINGTON, D.C. SP Soc Gen Internal Med ID ASSOCIATION SYMPTOM INDEX; RISK-FACTORS; CANCER; DECISION; MARKER; IMPACT AB PURPOSE: Benign prostatic hyperplasia is common among men who may be candidates for prostate cancer screening using prostate-specific antigen (PSA) testing. Patterns of PSA testing among men with evidence of benign prostatic hyperplasia have not been studied. METHODS: We examined the prevalence and correlates of a self-reported history of PSA testing. In 1994, 33,028 US health professionals without prostate cancer aged 47 to 85 years provided information on prior PSA tearing, lower urinary tract symptoms characteristic of benign prostatic hyperplasia, history of prostatectomy, and prostate cancer risk factors. In 1995, a subset of 7,070 men provided additional information on diagnosis and treatment of benign prostatic hyperplasia. RESULTS: From 39% of men in their 50s to 53% of men in their 80s reported PSA testing in the prior year (P <0.0001 for trend with age). Men were more likely to report PSA resting if they had lower urinary tract symptoms characteristic of benign prostatic hyperplasia (age-adjusted odds ratio for severe symptoms 2.2, 95% confidence interval 1.8 to 2.6), a prior history of prostatectomy (age-adjusted odds ratio 1.1, 95% confidence interval 1.02 to 1.2), or a physician diagnosis of benign prostatic hyperplasia (odds ratio 1.9, 95% confidence interval 1.7 to 2.2; adjusted for age, signs or symptoms of benign prostatic hyperplasia, and prostate cancer risk factors). CONCLUSIONS:These US health professionals reported preferential use of PSA testing among men least likely to benefit from early cancer detection (older men) and among men most likely to have a false-positive PSA result (men with benign prostatic hyperplasia). Physician and patient education are needed to promote more rational and selective use of this screening test. (C) 1998 by Excerpta Medica, Inc. C1 Massachusetts Gen Hosp, Gen Internal Med Unit S509, Div Gen Med, Med Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Channing Lab, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Dept Hlth, Boston, MA USA. Dept Social Behav, Boston, MA USA. RP Meigs, JB (reprint author), Massachusetts Gen Hosp, Gen Internal Med Unit S509, Div Gen Med, Med Serv, Boston, MA 02114 USA. FU NCI NIH HHS [CA55075]; NHLBI NIH HHS [HL35464]; NIDDK NIH HHS [DK45779] NR 36 TC 25 Z9 25 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD JUN PY 1998 VL 104 IS 6 BP 517 EP 525 DI 10.1016/S0002-9343(98)00113-2 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA ZX817 UT WOS:000074558400002 PM 9674713 ER PT J AU Fowler, FJ Bin, L Collins, MM Roberts, RG Oesterling, JE Wasson, JH Barry, MJ AF Fowler, FJ Bin, L Collins, MM Roberts, RG Oesterling, JE Wasson, JH Barry, MJ TI Prostate cancer screening and beliefs about treatment efficacy: A national survey of primary care physicians and urologists SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID MEDICARE PROVIDE REIMBURSEMENT; ANTIGEN; GUIDELINES AB PURPOSE: To describe practice patterns and beliefs of primary care physicians and urologists regarding early detection and treatment of prostate cancer. SUBJECTS AND METHODS: National probability samples of primary care physicians (n = 444) and urologists (n = 394) completed mail survey instruments in 1995. Physicians were asked about their use of prostate-specific antigen (PSA)testing for men of different ages and their beliefs about the value of radical prostatectomy, external-beam radiation therapy, and watchful waiting for men with differing life expectancies. RESULTS: Mosi primary care physicians report doing PSA tests during routine examination of men older than 50 years of age. The majority say they continue to do them on patients over 80 years and to refer men with abnormal values for biopsy. In contrast, only a minority of urologists would recommend PSA tests or biopsy for abnormal values for men over 75 years of age. More than 80% of primary care physicians and urologists doubt the value of radical prostatectomy for men with <10 years of life expectancy; more primary care physicians than urologists see probable survival benefit in radiation therapy for patients with life expectancy <10 years (48% versus 36%) or >10 years (67% versus 53%). Thirteen percent of primary care physicians and only 3% of urologists consider watchful waiting to be as appropriate as aggressive therapy for men with >10 years of life expectancy. CONCLUSIONS: Primary care physicians are more aggressive about PSA testing and referral for biopsy than most urologists recommend. Both groups recommend PSA testing and believe that aggressive treatment is more beneficial than existing evidence indicates. (C) 1998 by Excerpta Medica, Inc. C1 Univ Massachusetts, Survey Res Ctr, Boston, MA 02125 USA. Massachusetts Gen Hosp, Med Practices Evaluat Ctr, Boston, MA 02114 USA. Univ Wisconsin, Sch Med, Dept Family Med, Madison, WI USA. Midwest Prostate Inst, Saginaw, MI USA. Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Ctr Evaluat Clin Sci, Hanover, NH 03756 USA. RP Fowler, FJ (reprint author), Univ Massachusetts, Survey Res Ctr, 100 Morrissey Blvd, Boston, MA 02125 USA. FU AHRQ HHS [HS 08397] NR 17 TC 84 Z9 85 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD JUN PY 1998 VL 104 IS 6 BP 526 EP 532 DI 10.1016/S0002-9343(98)00124-7 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA ZX817 UT WOS:000074558400003 PM 9674714 ER PT J AU Sorensen, AG AF Sorensen, AG TI Investigating multiple sclerosis with spectroscopic imaging: Harbinger of a new paradigm SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Sorensen, AG (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD JUN-JUL PY 1998 VL 19 IS 6 BP 1002 EP 1003 PG 2 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA ZW798 UT WOS:000074449400003 PM 9672000 ER PT J AU Sherman, MD Holland, GN Holsclaw, DS Weisz, JM Omar, OHM Sherman, RA AF Sherman, MD Holland, GN Holsclaw, DS Weisz, JM Omar, OHM Sherman, RA TI Delusions of ocular parasitosis SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID PIMOZIDE; DISEASE AB PURPOSE: To describe four cases of delusions of parasitosis in which self-inflicted ocular trauma occurred. Delusions of parasitosis is a somatic delusional disorder in which patients have the irrational belief that their bodies are infested by parasites or other infectious organisms. Self-inflicted trauma can result from attempts to eliminate the supposed infestation. METHODS: We reviewed the case histories of four patients tone male, three females, 35 to 45 years of age) who presented with complaints of ocular infestation but had no evidence of infectious ocular disease. The characteristics of these cases were compared with the features of delusions of parasitosis. RESULTS: All patients maintained their beliefs regarding infestation, despite extensive clinical and laboratory investigations that found no evidence of infectious diseases, Self-inflicted eye injury, associated with attempts to eliminate the infestation, occurred in each case. CONCLUSIONS: The cases presented in this report are consistent with a diagnosis of delusions of parasitosis. The eye can be a principal focus of attention in this disorder, which may lead to vision loss caused by self-inflicted injury. (C) 1998 by Elsevier Science Inc, All rights reserved.). C1 So Calif Permanente Med Grp, Cornea External Dis Serv, Los Angeles, CA 90027 USA. Univ Calif Los Angeles, Sch Med, Ocular Inflammatory Dis Ctr, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Jules Stein Eye Inst, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Ophthalmol, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Med Ctr, Surg Serv, Ophthalmol Sect, Los Angeles, CA 90073 USA. Univ Calif San Francisco, Sch Med, Dept Ophthalmol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Francis I Proctor Fdn, San Francisco, CA 94143 USA. Univ Calif Irvine, Sch Med, Dept Med, Div Infect Dis, Irvine, CA 92717 USA. RP Sherman, MD (reprint author), Dept Ophthalmol, 411 N Lakeview Ave, Anaheim, CA 92807 USA. OI Sherman, Ronald/0000-0003-3096-0355 NR 23 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 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD JUN PY 1998 VL 125 IS 6 BP 852 EP 856 DI 10.1016/S0002-9394(98)00048-8 PG 5 WC Ophthalmology SC Ophthalmology GA ZU244 UT WOS:000074176800010 PM 9645723 ER PT J AU Emma, F Breton, S Morrison, R Wright, S Strange, K AF Emma, F Breton, S Morrison, R Wright, S Strange, K TI Effect of cell swelling on membrane and cytoplasmic distribution of pI(Cln) SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE anion channels; organic osmolytes; cell volume regulation; osmoregulation ID CHLORIDE CHANNELS; XENOPUS-OOCYTES; EXPRESSION; PROTEIN; CLONING AB pI(Cln) is found ubiquitously in mammalian cells and is postulated to play a critical role in cell volume regulation. Mutagenesis studies led to the proposal that pI(Cln) is a swelling-activated anion channel. However, recent studies in Madin-Darby canine kidney cells and endothelial cells have shown that the protein is localized primarily to the cytoplasm. It has therefore been postulated that activation involves reversible translocation of pI(Cln) from the cytoplasm and insertion into the plasma membrane. We tested this hypothesis using several different approaches. Fractionation of C-6 glioma cells into plasma membrane-and cytoplasm-containing fractions demonstrated that similar to 90% of the recovered pI(Cln), was confined to the cytosol. Swelling had no effect on the relative amount of protein present in the plasma membrane fraction. Immunofluorescence microscopy revealed that pI(Cln) is localized primarily, if not exclusively, to the cytoplasm of swollen and nonswollen cells. Similarly, transfection of cells with a green fluorescent protein-labeled pI(Cln) construct failed to reveal any membrane localization of the protein. These findings do not support the hypothesis that pI(Cln) is a volume regulatory anion channel activated by swelling-induced membrane insertion. C1 Vanderbilt Univ, Med Ctr, Dept Anesthesiol, Lab Cellular & Mol Physiol, Nashville, TN 37232 USA. Childrens Hosp, Div Renal, Boston, MA 02115 USA. Massachusetts Gen Hosp, Renal Unit, Boston, MA 02129 USA. Vanderbilt Univ, Med Ctr, Dept Pharmacol, Lab Cellular & Mol Physiol, Nashville, TN 37232 USA. Univ Arizona, Dept Physiol, Tucson, AZ 85724 USA. RP Strange, K (reprint author), Vanderbilt Univ, Med Ctr, Dept Anesthesiol, Lab Cellular & Mol Physiol, 504 Oxford House,1313 21st Ave S, Nashville, TN 37232 USA. RI Emma, Francesco/H-2116-2012 FU NIDDK NIH HHS [DK-38452, DK-51610]; NINDS NIH HHS [NS-30591] NR 26 TC 25 Z9 25 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD JUN PY 1998 VL 274 IS 6 BP C1545 EP C1551 PG 7 WC Cell Biology; Physiology SC Cell Biology; Physiology GA ZQ772 UT WOS:000073901500013 PM 9696697 ER PT J AU Makhlouf, AA McDermott, PJ AF Makhlouf, AA McDermott, PJ TI Increased expression of eukaryotic initiation factor 4E during growth of neonatal rat cardiocytes in vitro SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE myocyte; hypertrophy; collagen; translation; initiation factors ID MYOSIN HEAVY-CHAIN; ATRIAL-NATRIURETIC-FACTOR; ADULT FELINE CARDIOCYTES; RIBOSOMAL-RNA SYNTHESIS; PROTEIN-SYNTHESIS; TRANSLATION INITIATION; HEART-CELLS; MESSENGER-RNA; FACTOR EIF-4E; ELECTRICAL-STIMULATION AB Eukaryotic initiation factor 4E (eIF-4E) is rate limiting for translational initiation. The purpose of this study was to determine whether eIF-4E levels are increased during cardiocyte growth produced by increased load in the form of electrically stimulated contraction. Neonatal rat cardiocytes were cultured on a matrix of aligned type I collagen. The cardiocytes aligned in parallel to the direction of the collagen fibrils and exhibited an elongated, rod-shaped morphology. Cardiocytes were electrically stimulated to contract at 3 Hz (alternating polarity, 5-ms pulse width). Nonstimulated cardiocytes were quiescent and used as controls. Electrically stimulated contraction produced hypertrophic growth as determined by the following criteria: 1) increased protein content, 2) increased RNA content, 3) accelerated rate of protein synthesis, and 4) threefold increase in promoter activity of the atrial natriuretic factor gene. Cardiocyte growth was associated with an increase in eIF-4E mRNA levels that reached 48 +/- 9% after 2 days of electrically stimulated contraction. eIF-4E protein levels were increased by more than twofold over the same time period. We conclude that an adaptive increase in eIF-4E is an important mechanism for maintaining translational efficiency during cardiocyte growth. C1 Med Univ S Carolina, Dept Med, Charleston, SC 29403 USA. Med Univ S Carolina, Gazes Cardiac Res Inst, Charleston, SC 29403 USA. Vet Affairs Med Ctr, Ralph H Johnson Dept, Charleston, SC 29403 USA. RP McDermott, PJ (reprint author), Gazes Thurmond Biomed Res Bldg,Rm 303,114 Doughty, Charleston, SC 29403 USA. NR 47 TC 13 Z9 13 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD JUN PY 1998 VL 274 IS 6 BP H2133 EP H2142 PG 10 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA ZR475 UT WOS:000073980600034 PM 9841540 ER PT J AU Kaneko, H Mitsuma, T Nagai, H Mori, S Iyo, T Kusugami, K Tache, Y AF Kaneko, H Mitsuma, T Nagai, H Mori, S Iyo, T Kusugami, K Tache, Y TI Central action of adrenomedullin to prevent ethanol-induced gastric injury through vagal pathways in rats SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE calcitonin gene-related peptide antagonist; nitric oxide; prostaglandins; atropine; vagus ID GENE-RELATED PEPTIDE; ENDOGENOUS NITRIC-OXIDE; RECEPTOR; PROJECTIONS; PROTECTION; CLONING; HORMONE; DAMAGE AB Adrenomedullin (AM), belongs to the calcitonin gene-related peptide (CGRP) family and interacts with AM and CGRP(1) receptors. Specific AM receptors and immunoreactivity are present in the rat brain. The effect of intracisternal injection of rat AM on ethanol-induced gastric lesions was studied in conscious Wistar rats. The peptide was injected intracisternally or intravenously under short anesthesia 20 min before intragastric injection of 70% ethanol. Corpus lesions were determined 1 h after ethanol. Intracisternal AM (75, 150, and 300 pmol) dose-dependently inhibited ethanol-induced gastric lesions by 40-72% and rat alpha-CGRP (150 pmol ic) by 76%. Intravenous AM (300 pmol) had no effect. The CGRP(1) receptor antagonist CGRP-(8-37) (9.6-19.2 nmol ic) dose-dependently inhibited the protective effect of intracisternal alpha-CGRP but not that of AM. Subdiaphragmatic vagotomy and peripheral injection of atropine, indomethacin, or N-G-nitro-L-arginine methyl ester (L-NAME) prevented AM protective action. L-Arginine but not D-arginine blocked L-NAME action. These data suggest that both AM and CGRP act in the brain to prevent ethanol-induced gastric lesions through interaction with their specific receptors. AM action may involve vagal cholinergic-dependent modulation of prostaglandins and nitric oxide protective mechanisms. C1 Aichi Med Univ, Dept Internal Med 4, Nagakute, Aichi 4801195, Japan. Nagoya Univ, Sch Med, Dept Internal Med 1, Nagoya, Aichi 4668560, Japan. Univ Calif Los Angeles, Ctr Ulcer Res & Educ,Digest Dis Res Ctr, W Los Angeles Vet Affairs Med Ctr, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90073 USA. RP Kaneko, H (reprint author), Aichi Med Univ, Dept Internal Med 4, 21 Karimata, Nagakute, Aichi 4801195, Japan. FU NIDDK NIH HHS [DK-30110]; NIMH NIH HHS [MH-00663] NR 37 TC 30 Z9 30 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD JUN PY 1998 VL 274 IS 6 BP R1783 EP R1788 PG 6 WC Physiology SC Physiology GA ZQ835 UT WOS:000073907700033 PM 9841551 ER PT J AU Raybould, HE Meyer, JH Tabrizi, Y Liddle, RA Tso, P AF Raybould, HE Meyer, JH Tabrizi, Y Liddle, RA Tso, P TI Inhibition of gastric emptying in response to intestinal lipid is dependent on chylomicron formation SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE cholecystokinin; Pluronic L-81; rat ID SENSITIVE AFFERENT PATHWAYS; PLASMA CHOLECYSTOKININ; ACID SECRETION; MEDIUM-CHAIN; RAT; VAGAL; TRANSPORT; TRIGLYCERIDE; HUMANS; FOOD AB Lipid in the intestine initiates feedback inhibition of proximal gastrointestinal function and food intake. In rats and humans, inhibition of gastric emptying is mediated, at least in part, by cholecystokinin (CCK)-A receptors, and in rats there is evidence for involvement of an intestinal vagal afferent pathway. The mechanism by which luminal lipid acts to release CCK or activate vagal afferent nerve terminals is unclear. The role of chylomicron formation in this sensory transduction pathway has been investigated using the hydrophobic surfactant Pluronic L-81 that inhibits chylomicron formation. Gastric emptying of liquids was measured in awake rats fitted with a Thomas gastric fistula and a duodenal cannula. Intestinal perfusion of lipid induced a dose-dependent inhibition of gastric emptying (6, 12, and 39% inhibition for 25, 50, and 100 mg lipid, respectively). Perfusion of lipid with Pluronic L-81 (2.8% wt/vol) reversed the lipid-induced inhibition of gastric emptying. Pluronic L-63, a chemically similar surfactant that has no effect on chylomicron formation, had no effect on lipid-induced inhibition of gastric emptying. Per fusion of the intestine with lipid (100 mg) increased plasma levels of CCK from 1.9 +/- 0.8 to 6.5 +/- 1 pM. This increase was blocked by Pluronic L-81 but unaffected by L-63. These results provide evidence that chylomicron formation is important in the signaling of lipid in the intestinal lumen to CCK endocrine cells and to producing feedback inhibition of gastric emptying. C1 Univ Calif Los Angeles, Sch Med,Ctr Ulcer Res & Educ, Digest Dis Res Ctr,Dept Physiol, W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med,Ctr Ulcer Res & Educ, Digest Dis Res Ctr,Dept Med, W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Univ Cincinnati, Dept Pathol, Cincinnati, OH 45267 USA. RP Raybould, HE (reprint author), Vet Adm Wadsworth Med Ctr, Ctr Ulcer Res & Educ, Bldg 115,Rm 209,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [DK-41004] NR 31 TC 62 Z9 62 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD JUN PY 1998 VL 274 IS 6 BP R1834 EP R1838 PG 5 WC Physiology SC Physiology GA ZQ835 UT WOS:000073907700040 PM 9841489 ER PT J AU Antes, LM Villar, MM Decker, S Nicosia, RF Kujubu, DA AF Antes, LM Villar, MM Decker, S Nicosia, RF Kujubu, DA TI Serum-free in vitro model of renal microvessel development SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE angiogenesis; vasculogenesis; renal endothelium ID HGF-INDUCED TUBULOGENESIS; ANGIOGENESIS INVITRO; ENDOTHELIAL-CELLS; RAT AORTA; DIFFERENTIATION; CULTURE; KIDNEY; MATRIX; EXPRESSION; GROWTH AB The differentiation and organization of the embryonic renal vasculature is a crucial event in renal development. To study this process, we developed a serum-free in vitro model of renal microvessel development. Mouse embryonic kidney explants, when embedded specifically in type I collagen, demonstrate outgrowth of microvascular structures when stimulated by the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA, 10-50 ng/ml). Other polypeptide growth factors stimulated little, if any, microvessel outgrowth from the explants. Similar outgrowths were not observed when other embryonic tissue explants were used. The number of microvessels observed depended on the gestational age of the explants. We hypothesize that TPA induces the in situ differentiation of metanephric mesenchymal cells into endothelial cell precursors and that specific matrix proteins and cell-matrix interactions are necessary for the organization of these precursors into microvessels. Our model will allow us to examine in detail the responsiveness of metanephric kidney cells to both growth factors and extracellular matrix molecules and to understand how they influence renal endothelial cell differentiation. C1 Vet Affairs Med Ctr, Dept Med, Renal Electrolyte & Hypertens Div, Philadelphia, PA 19104 USA. Univ Penn, Sch Vet Med, Ctr Oral Hlth Res, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Allegheny Univ Hlth Sci, Dept Pathol, Philadelphia, PA 19102 USA. RP Kujubu, DA (reprint author), Vet Affairs Med Ctr, Dept Med, Renal Electrolyte & Hypertens Div, Philadelphia, PA 19104 USA. FU NHLBI NIH HHS [R01-HL-52585]; NIDDK NIH HHS [DK-09575, DK-07006] NR 30 TC 3 Z9 4 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD JUN PY 1998 VL 274 IS 6 BP F1150 EP F1160 PG 11 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA ZT310 UT WOS:000074071600020 PM 9841508 ER PT J AU Gans, JS AF Gans, JS TI Narrative lessons for the psychotherapist - Kafka's The Metamorphosis SO AMERICAN JOURNAL OF PSYCHOTHERAPY LA English DT Article AB Psychotherapists can learn a great deal about their craft from reading literacy fiction. This paper will utilize Frank Kafka's short story, The Metamorphosis, to describe and discuss some of the parallels between the therapist-reader's relationship with a work of fiction and a therapist's psychotherapeutic relationship with his patient. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Gans, JS (reprint author), 55 Cleveland Rd, Wellesley, MA 02181 USA. NR 14 TC 2 Z9 2 U1 1 U2 2 PU ASSN ADVAN PSYCHOTHERAPY PI BRONX PA BELFER EDUC CENTER, ROOM 402 ALBERT EINSTEIN COLL MED 1300 MORRIS PARK AVE, BRONX, NY 10461-1602 USA SN 0002-9564 J9 AM J PSYCHOTHER JI Am. J. Psychother. PD SUM PY 1998 VL 52 IS 3 BP 352 EP 366 PG 15 WC Psychology, Clinical; Psychiatry; Psychology; Psychology, Psychoanalysis SC Psychology; Psychiatry GA 114CG UT WOS:000075591100007 PM 9742316 ER PT J AU Mascola, MA Van Vunakis, H Tager, IB Speizer, FE Hanrahan, JP AF Mascola, MA Van Vunakis, H Tager, IB Speizer, FE Hanrahan, JP TI Exposure of young infants to environmental tobacco smoke: Breast-feeding among smoking mothers SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID COTININE CONCENTRATIONS; PASSIVE SMOKING; MATERNAL SMOKING; DEATH-SYNDROME; URINE; NICOTINE; MILK; ASTHMA; PREGNANCY; SERUM AB Objectives. This study examined the degree to which breastfeeding and cigarette smoking by mothers and smoking by other household members contribute to the exposure of infants to the products of tobacco smoke. Methods. The subjects were 330 mother-infant pairs derived from a cohort of 1000 pairs enrolled in a longitudinal study of the pulmonary effects of prenatal and postnatal smoking. The main outcome measure was corrected urinary cotinine levels. Results. Urinary cotinine levels were 10-fold higher in breast-fed infants of smoking mothers than among bottle-fed infants of smoking mothers. Among infants of nonsmoking mothers, urine cotinine levels were significantly increased in infants living in homes with other smokers: in this group there was no significant difference between bottle-fed and breast-fed infants. Infants whose mothers smoked in the same room as the infant had only non-significant increases in cotinine levels compared with infants whose mothers restricted their smoking to other rooms. Conclusions. Breast-fed infants of smoking mothers have urine cotinine levels 10-fold higher than bottle-fed infants whose mothers smoke, suggesting that breast-feeding, rather than direct inhalation of environmental tobacco smoke, is the primary determinant of cotinine levels in infants whose mothers smoke. C1 Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. Brandeis Univ, Dept Biochem, Waltham, MA 02254 USA. Univ Calif Berkeley, Sch Publ Hlth, Div Publ Hlth Biol & Epidemiol, Berkeley, CA 94720 USA. RP Mascola, MA (reprint author), Massachusetts Gen Hosp, Dept Obstet & Gynecol, Fruit St, Boston, MA 02114 USA. FU NHLBI NIH HHS [R01 HL-36474, HL-07427] NR 18 TC 38 Z9 43 U1 0 U2 2 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JUN PY 1998 VL 88 IS 6 BP 893 EP 896 DI 10.2105/AJPH.88.6.893 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA ZT683 UT WOS:000074114100008 PM 9618615 ER PT J AU Perrin, JM Ettner, SL McLaughlin, TJ Gortmaker, SL Bloom, SR Kuhlthau, K AF Perrin, JM Ettner, SL McLaughlin, TJ Gortmaker, SL Bloom, SR Kuhlthau, K TI State variations in Supplemental Security Income enrollment for children and adolescents SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article AB Objectives. The purpose of this study was to determine the effects of poverty, program generosity, and health on state variations in enrollment of children and adolescents in the Supplemental Security Income (SSI) program during recent program expansions. Methods. The relationship of state SSI rates for 1989 and 1992 to child poverty, health, and program generosity were determined by multi-regression. Results. The mean percentage of children enrolled grew from 0.36% (1989) to 0.75% (1992). Poverty rates accounted for 78% of the variance among states in 1989 and 53% in 1992. Other indicators accounted for little variance. Conclusions. Differences in state poverty levels explained almost all variation in SSI enrollment. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Cambridge, MA 02138 USA. Harvard Pilgrim Hlth Care, Cambridge, MA USA. Harvard Univ, Sch Publ Hlth, Dept Hlth & Soc Behav, Cambridge, MA 02138 USA. RP Perrin, JM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat, Fruit St,WACC 715, Cambridge, MA 02138 USA. FU PHS HHS [MCJ-250634] NR 17 TC 11 Z9 11 U1 1 U2 3 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JUN PY 1998 VL 88 IS 6 BP 928 EP 931 DI 10.2105/AJPH.88.6.928 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA ZT683 UT WOS:000074114100015 PM 9618622 ER PT J AU Silverman, EK Chapman, HA Drazen, JM Weiss, ST Rosner, B Campbell, EJ O'Donnell, WJ Reilly, JJ Ginns, L Mentzer, S Wain, J Speizer, FE AF Silverman, EK Chapman, HA Drazen, JM Weiss, ST Rosner, B Campbell, EJ O'Donnell, WJ Reilly, JJ Ginns, L Mentzer, S Wain, J Speizer, FE TI Genetic epidemiology of severe, early-onset chronic obstructive pulmonary disease - Risk to relatives for airflow obstruction and chronic bronchitis SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID ALPHA-1-ANTITRYPSIN DEFICIENCY; ENVIRONMENTAL DETERMINANTS; CIGARETTE-SMOKING; IDENTICAL-TWINS; COMPLEX TRAITS; NON-SMOKERS; VARIABILITY; CAPACITY; FAMILY; RESEMBLANCE AB Severe alpha-l-antitrypsin deficiency is the only proven genetic risk factor for chronic obstructive pulmonary disease (COPD). We have assembled a cohort of 44 probands with severe, early-onset COPD, who do not have severe alpha-l-antitrypsin deficiency. A surprisingly high prevalence of females (79.6%) was found. Assessment of the risk to relatives of these early-onset COPD probands for airflow obstruction and chronic bronchitis was performed to determine whether significant familial aggregation for COPD, independent of alpha-l-antitrypsin deficiency, could be demonstrated. First-degree relatives of early-onset COPD probands had significantly lower FEV1 and FEV1/FVC values than control subjects (p < 0.01), despite similar pack-years of smoking. Reduced spirometric values in first-degree relatives of early-onset COPD probands were found only in current or ex-cigarette smokers. The mean FEV1 in current or ex-smoking first-degree relatives was 76.1 +/- 20.9% predicted compared to 89.2 +/- 14.4% predicted in current or ex-smoking control subjects (p < 0.01); in lifelong nonsmokers, the mean FEV1 was 93.4% predicted for both control subjects and first-degree relatives of early-onset COPD probands. Generalized estimating equations, adjusting for age and pack-years of smoking, demonstrated increased odds of reduced FEV1 and chronic bronchitis in current or ex-smoking first-degree relatives of early-onset COPD probands. Using a new method to estimate relative risk from relative odds, we estimate that the relative risks for FEV1 below 60%, FEV1 below 80%, and chronic bronchitis are each approximately three in current or ex-smoking first-degree relatives of early-onset COPD probands. The increased risk to relatives of early-onset COPD probands for reduced FEV1 and chronic bronchitis, limited to current or ex-smokers, suggests genetic risk factor(s) for COPD that are expressed in response to cigarette smoking. C1 Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Div Pulm & Crit Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Surg, Div Thorac Surg, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Div Gen Thorac Surg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Utah, Hlth Sci Ctr, Dept Internal Med, Salt Lake City, UT USA. RP Silverman, EK (reprint author), Brigham & Womens Hosp, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. EM ed_silverman@channing.harvard.edu RI Drazen, Jeffrey/E-5841-2012 FU NCRR NIH HHS [MO1 RR02635]; NHLBI NIH HHS [P50 HL56383, HL48621] NR 43 TC 218 Z9 221 U1 1 U2 7 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD JUN PY 1998 VL 157 IS 6 BP 1770 EP 1778 PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA ZV294 UT WOS:000074290200010 PM 9620904 ER PT J AU Koziel, H Phelps, DS Fishman, JA Armstrong, MYK Richards, FF Rose, RM AF Koziel, H Phelps, DS Fishman, JA Armstrong, MYK Richards, FF Rose, RM TI Surfactant protein-A reduces binding and phagocytosis of Pneumocystis carinii by human alveolar macrophages in vitro SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; LINING MATERIAL; RAT; LUNG; INFECTION; PNEUMONIA; GLYCOPROTEIN; ATTACHMENT; COMPLEMENT; RECEPTORS AB Surfactant protein-A (SP-A) levels are increased in Pneumocystis carinii pneumonia. but the role of SP-A in the pathogenesis of P. carinii pneumonia is not completely understood. This study investigated the effect of SP-A on the in vitro binding and phagocytosis of P. carinii by normal human alveolar macrophages (AM). Determination of binding and phagocytosis was done with a fluorescence-based assay, utilizing fluorescein isothiocyanate (FITC)-labeled P. carinii. Binding and phagocytosis of P. carinii to AM correlated inversely with the levels of SP-A present on the surface of the organisms (r = -0.6323, P = 0.0086; and r = -0.9837, P < 0.0001, respectively). The addition of exogenous SP-A to organisms with low surface-associated SP-A reduced P. carinii binding by 30% (P < 0.05) and reduced phagocytosis by 20% (P < 0.05), whereas this effect was reversed with ethylenediamine tetraacetic acid (EDTA) or anti-SP-A antibody. Furthermore, binding and phagocytosis were enhanced after enzymatic removal of P, carinii surface-associated SP-A, and this effect was reversed with the addition of exogenous SP-A. The observed inhibitory effect of SP-A on P. carinii binding and phagocytosis reflected binding of SP-A to the organisms rather than a direct effect of SP-A on the macrophages. These data suggest that increased levels of SP-A may contribute to the pathogenesis of P. carinii pneumonia through binding to the surface of the organism and interfering with AM recognition of this opportunistic pulmonary pathogen. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med,Div Pulm & Crit Care Med, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Penn State Univ, Milton S Hershey Med Ctr, Coll Med, Dept Pediat, Hershey, PA 17033 USA. Yale Univ, Sch Med, MacArthur Ctr Mol Parasitol, New Haven, CT USA. RP Koziel, H (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med,Div Pulm & Crit Care Med, Palmer Bldg,Room 108,W 1 Deaconess Rd, Boston, MA 02215 USA. EM hkoziel@west.bidmc.harvard.edu FU NHLBI NIH HHS [HL48006, HL43510]; NIAID NIH HHS [AI24194] NR 50 TC 45 Z9 47 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD JUN PY 1998 VL 18 IS 6 BP 834 EP 843 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA ZV946 UT WOS:000074358200013 PM 9618388 ER PT J AU Rao, PM Rhea, JT Novelline, RA Dobbins, JM Lawrason, JN Sacknoff, R Stuk, JL AF Rao, PM Rhea, JT Novelline, RA Dobbins, JM Lawrason, JN Sacknoff, R Stuk, JL TI Helical CT with only colonic contrast material for diagnosing diverticulitis: Prospective evaluation of 150 patients SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Roentgen-Ray-Society 98th CY APR 26-MAY 01, 1998 CL SAN FRANCISCO, CALIFORNIA SP Amer Roentgen Ray Soc ID BARIUM ENEMA; SIGMOID DIVERTICULITIS; PERCUTANEOUS DRAINAGE; QUADRANT PERITONITIS; COMPUTED-TOMOGRAPHY; DISEASE AB OBJECTIVE. We prospectively evaluated a helical CT technique in which contrast material is administered only through the colon for the imaging of suspected diverticulitis. SUBJECTS AND METHODS. One hundred fifty consecutive patients who presented to our emergency department with clinically suspected diverticulitis underwent helical abdominal CT after contrast material was administered only through the colon. CT findings of diverticulitis included diverticula, muscular wall hypertrophy, focal colonic wall thickening, and pericolonic fat stranding. CT results were correlated with clinical follow-up (all patients) and with pathologic findings (41 patients). RESULTS. A final clinical diagnosis of diverticulitis was made in 64 patients (43%), of whom 62 (97%) had CT results positive for diverticulitis. Of the 86 patients for whom diverticulitis was clinically excluded, all (100%) had CT results that were negative for diverticulitis CT interpretations had a sensitivity of 97%, a specificity of 100%, a positive predictive value of 100%, a negative predictive value of 98%, and an overall accuracy of 99%. Alternative diagnoses were noted on CT in 50 (58%) of 86 patients who did not have diverticulitis and included 50 (78%) of the 64 patients in whom an alternative condition other than nonspecific abdominal pain was established. CONCLUSION. Helical CT obtained after contrast material administered only through the colon is accurate (99%) for confirming or excluding clinically suspected diverticulitis and for suggesting alternative conditions (78%) when they are present. This CT technique avoids the risks, discomforts, and costs of oral and IV contrast material administration and allows immediate scanning. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Rao, PM (reprint author), Massachusetts Gen Hosp, Dept Radiol, 32 Fruit St, Boston, MA 02114 USA. NR 24 TC 98 Z9 102 U1 0 U2 2 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JUN PY 1998 VL 170 IS 6 BP 1445 EP 1449 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZP598 UT WOS:000073769500007 PM 9609151 ER PT J AU Truong, M Atri, M Bret, PM Reinhold, C Kintzen, G Thibodeau, M Aldis, AE Chang, Y AF Truong, M Atri, M Bret, PM Reinhold, C Kintzen, G Thibodeau, M Aldis, AE Chang, Y TI Sonographic appearance of benign and malignant conditions of the colon SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID INFLAMMATORY BOWEL-DISEASE; CROHNS-DISEASE; PSEUDOMEMBRANOUS COLITIS; ULCERATIVE-COLITIS; DIAGNOSIS; ULTRASOUND; ULTRASONOGRAPHY; DIVERTICULITIS; FEATURES; INVITRO AB OBJECTIVE. The objective of this study was to compare the sonographic appearance of different abnormalities of the colon to evaluate the role of sonography in their differential diagnosis. MATERIALS AND METHODS. We retrospectively reviewed videotaped sonographic examinations of 99 patients with proven diagnoses that included diverticulitis (n = 35), malignancy (n = 20), Crohn's disease (n = 16), pseudomembranous colitis (n = 14), ischemic colitis (n = 9), and ulcerative colitis (n = 5), Data were collected with regard to gut features, including the site of colonic involvement, associated small-bowel involvement, length of diseased segment, stratification, luminal contents, pneumatosis, and diverticula. Perigut features evaluated included abnormal fat, abscess, fistula, and ascites. RESULTS. On sonography, the following features were statistically significant (p < .05). Involvement of the small bowel was more common in patients with Crohn's disease than in the remainder of the study population (44% versus 1%). Left-sided colonic disease (91% versus 38%), diverticula (91% versus 3%), and perigut findings (91% versus 57%), including abnormal fat (83% versus 39%) and abscess (34% versus 8%), were features that indicated diverticulitis. Malignant conditions were more common in patients with a greater wall thickness (mean, 26.2 mm versus 10.2 mm), asymmetric involvement (85% versus 39%), loss of stratification (85% versus 20%), absence of perigut findings (65% versus 22%), and involvement of a short diseased segment (70% versus 16%). Involvement of the entire colon (50% versus 2%), luminal contents (64% versus 28%), and ascites (64% versus 26%) were features suggesting pseudomembranous colitis. CONCLUSION. Although the sonographic appearances of abnormalities of the colon overlap, some sonographic features are helpful in the differential diagnosis of colonic abnormalities. C1 McGill Univ, Montreal Gen Hosp, Dept Radiol, Montreal, PQ H3G 1A4, Canada. Univ Texas, Md Anderson Canc Ctr, Dept Radiol, Houston, TX 77030 USA. Massachusetts Gen Hosp, Med Practices Evaluat Ctr, Boston, MA 02114 USA. RP Atri, M (reprint author), McGill Univ, Montreal Gen Hosp, Dept Radiol, 1650 Cedar Ave, Montreal, PQ H3G 1A4, Canada. NR 20 TC 43 Z9 44 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JUN PY 1998 VL 170 IS 6 BP 1451 EP 1455 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZP598 UT WOS:000073769500008 PM 9609152 ER PT J AU Slanetz, PJ Giardino, AA McCarthy, KA Hall, DA Halpern, EF Moore, RH Kopans, DB AF Slanetz, PJ Giardino, AA McCarthy, KA Hall, DA Halpern, EF Moore, RH Kopans, DB TI Previous breast biopsy for benign disease rarely complicates or alters interpretation on screening mammography SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID CORE AB OBJECTIVE. It has been suggested that breast screening leads to too many biopsies for benign disease that permanently scar the breast and confuse the interpretation of subsequent mammograms. We undertook retrospective and prospective studies to determine how often an excisional biopsy for benign breast disease complicates or alters interpretation of screening mammograms. MATERIALS AND METHODS. Retrospective review of our screening center database yielded 31,025 asymptomatic patients who had routine mammographic screening studies between 1993 and 1996. Of the 58,538 examinations of these patients, 53,510 were of patients who had no history of breast biopsy and 5028 were of patients who had a history of breast biopsy for benign disease. Recall rates were compared between the two groups. In the prospective study, radiologists reviewed the mammograms of 1997 consecutive patients presenting to the screening center, 173 of whom reported a prior breast biopsy for benign disease. The radiologist interpreting the images determined how often evidence of the biopsy site was apparent on the mammogram and how often such changes necessitated additional imaging. RESULTS. Ln the retrospective study, 3296 (6%) of the 53,510 studies done in patients who did not have a biopsy for benign disease and 360 (7%) Of the 5028 studies done in women who had a biopsy for benign disease led to additional imaging. Eight recalls for further imaging (0.16%) among the 5028 studies in women with a prior biopsy for benign disease were related to the biopsy site. Ln the prospective study, 24 (14%) of the 173 women who had a biopsy for benign disease had mammographic evidence of the biopsy sire. Nine (5%) of the 173 women who had previously had a biopsy for benign disease and 86 (5%) of the 1824 patients without a prior biopsy were recalled for additional imaging. No women were recalled because a previous breast biopsy for benign disease led to confusion or diagnostic concern. CONCLUSION. Changes in patients' breasts due to previous excisional biopsies for benign breast disease rarely pose a diagnostic dilemma in the interpretation of routine screening mammograms. C1 Massachusetts Gen Hosp, Dept Radiol ACC 219, Div Breast Imaging & Ambulatory Radiol, Boston, MA 02114 USA. RP Slanetz, PJ (reprint author), Massachusetts Gen Hosp, Dept Radiol ACC 219, Div Breast Imaging & Ambulatory Radiol, 15 Parkman St, Boston, MA 02114 USA. NR 12 TC 12 Z9 12 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JUN PY 1998 VL 170 IS 6 BP 1539 EP 1541 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZP598 UT WOS:000073769500026 PM 9609170 ER PT J AU Chew, FS Ramsdell, MG Keel, SB AF Chew, FS Ramsdell, MG Keel, SB TI Metallosis after total knee replacement SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Chew, FS (reprint author), Massachusetts Gen Hosp, Dept Radiol, 32 Fruit St, Boston, MA 02114 USA. NR 4 TC 10 Z9 10 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JUN PY 1998 VL 170 IS 6 BP 1556 EP 1556 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZP598 UT WOS:000073769500029 PM 9609173 ER PT J AU Young, RH Koelliker, DD Scully, RE AF Young, RH Koelliker, DD Scully, RE TI Sertoli cell tumors of the testis, not other-wise specified - A clinicopathologic analysis of 60 cases SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE testis; neoplasm; Sertoli cell tumor; prognostic factors ID PEUTZ-JEGHERS SYNDROME; SEX-CORD TUMOR; GONADAL STROMAL TUMORS; TESTICULAR-TUMORS; TUBULAR SEMINOMA; ANNULAR TUBULES; LESIONS; LEYDIG AB Sixty Sertoli cell tumors of the testis, excluding large cell calcifying and sclerosing subtypes, are described. Patient age ranged from 15 to 80 years (mean, 45 years). The initial manifestation was usually a testicular mass; in 14 cases it had been enlarging slowly for a period of up to 14 years (mean 3.7 years). Only five patients had testicular pain. Four patients had metastatic disease at the time of presentation. All the tumors were unilateral and ranged from 0.3 cm to 15 cm (mean 3.6 cm). They were typically well circumscribed. Sectioning usually disclosed firm, tan-say, white, or yellow tissue with areas of hemorrhage and a minor cystic component in approximately one third. Microscopic evaluation usually revealed diffuse sheets or large, nodular aggregates of tumor cells, within which solid or hollow, sometimes dilated, tubules and, less often, cords were usually at lease focally identifiable. A relatively acellular, often vascular, fibrous to hyalinized stroma was frequently conspicuous. The tumor cells typically had moderate amounts of pale to lightly eosinophilic cytoplasm, but 10 tumors had cells with abundant eosinophilic cytoplasm. Large cytoplasmic vacuoles were prominent in 26 tumors. Nuclear atypicality was absent or mild in 54 cases, moderate in 4 cases, and marked in 2 cases. Mitotic rate ranged from less than 1 to 21 per 10 high power fields, with 50 tumors having no or only rare mitoses. Vascular space invasion was present in 11 cases and was prominent in 8. Follow-up of more than five years (average 8.4 years), or until evidence of metastasis was seen, was available for 16 patients. Nine were alive and well with no evidence of disease. Four were alive with disease and three died of disease. The pathologic features that best correlated with a clinically malignant course were as follows: a tumor diameter of 5.0 cm or greater, necrosis, moderate to severe nuclear atypia, vascular invasion and a mitotic rate of more than 5 mitoses per IO high power fields. Only one of nine benign tumors for which follow-up data of 5 years or more were available had more than one of these features, whereas five of seven malignant tumors had at least three. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,James Homer Wright Pathol Labs, Boston, MA 02114 USA. RP Young, RH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,James Homer Wright Pathol Labs, 32 Fruit St, Boston, MA 02114 USA. NR 73 TC 89 Z9 93 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD JUN PY 1998 VL 22 IS 6 BP 709 EP 721 DI 10.1097/00000478-199806000-00008 PG 13 WC Pathology; Surgery SC Pathology; Surgery GA ZT312 UT WOS:000074071900008 PM 9630178 ER PT J AU London, MJ Shroyer, AL Coll, JR MaWhinney, S Fullerton, DA Hammermeister, KE Grover, FL AF London, MJ Shroyer, AL Coll, JR MaWhinney, S Fullerton, DA Hammermeister, KE Grover, FL TI Early extubation following cardiac surgery in a veterans population SO ANESTHESIOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Society-of-Anesthesiologists CY OCT 17-25, 1996 CL NEW ORLEANS, LOUISIANA SP Amer Soc Anesthesiologists DE clinical protocols; complications; epidemiology; length of stay; mortality ID FAST-TRACK RECOVERY; PULMONARY-FUNCTION; BYPASS OPERATIONS; OUTCOMES; CARE; RISK; MODELS; COST; DETERMINANTS; REGRESSION AB Background Early tracheal extubation is an important component of the "fast track" cardiac surgery pathway, Factors associated with time to extubation in the Department of Veterans Affairs (DVA) population are unknown. The authors determined associations of preoperative risk and intraoperative clinical process variables with time to extubation in this population. Methods: Three hundred four consecutive patients undergoing coronary artery bypass graft, valve surgery, or both on a fast track clinical pathway between October 1, 1993 and September 30, 1995 at a university-affiliate DVA medical center were studied retrospectively. After univariate screening of a battery of preoperative risk and intraoperative clinical process variables, stepwise logistic regression was used to determine associations with tracheal extubation less than or equal to 10 h (early) or >10 h (late) after surgery. Postoperative lengths of stay, complications, and 30-day and 6-month mortality rates were compared between the two groups. Results: One hundred forty-six patients (48.3%) were extubated early; one patient required emergent reintubation (0.7%). Of the preoperative risk variables considered, only age (odds ratio, 1.80 per 10-yr increment) and preoperative intraaortic balloon pump (odds ratio, 7.88) were multivariately associated with time to extubation (model R) ("late" association is indicated by an odds ratio >1.00; "early" association is indicated by an odds ratio <1.00). Entry of these risk variables into a second regression model, followed by univariately significant intraoperative clinical process variables, yielded the following associations (model R-P): age (odds ratio, 1.86 per 10-yr increment), sufentanil dose (odds ratio, 1.54 per 1-mu g/kg increment), major inotrope use (odds ratio, 5.73), platelet transfusion (odds ratio, 10.03), use of an arterial graft (odds ratio, 0.32), and fentanyl dose (odds ratio, 1.45 per 10-mu g/kg increment). Time of arrival in the intensive care unit after surgery was also significant (odds ratio, 1.42 per 1-h increment), Intraoperative clinical process variables added significantly to model performance (P < 0.001 by the likelihood ratio test). Conclusions: In this population, early tracheal extubation was accomplished in 48% of patients. Intraoperative clinical process variables are important factors to be considered in the timing of postoperative extubation after fast track cardiac surgery. C1 Univ Colorado, Hlth Sci Ctr, Denver Vet Affairs Med Ctr, Denver, CO 80220 USA. RP London, MJ (reprint author), Univ Colorado, Hlth Sci Ctr, Denver Vet Affairs Med Ctr, 1055 Clermont St, Denver, CO 80220 USA. RI Coll, Joseph/C-3165-2012; Shroyer, Annie Laurie/B-8836-2016 OI Shroyer, Annie Laurie/0000-0001-6461-0623 NR 36 TC 47 Z9 50 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD JUN PY 1998 VL 88 IS 6 BP 1447 EP 1458 DI 10.1097/00000542-199806000-00006 PG 12 WC Anesthesiology SC Anesthesiology GA ZU022 UT WOS:000074153400005 PM 9637636 ER PT J AU Forman, SA Raines, DE AF Forman, SA Raines, DE TI Nonanesthetic volatile drugs obey the Meyer-Overton correlation in two molecular protein site models SO ANESTHESIOLOGY LA English DT Article; Proceedings Paper CT 1997 Annual Meeting of American-Society-of-Anesthesiologists CY OCT 18-23, 1997 CL SAN DIEGO, CALIFORNIA SP Amer Soc Anesthesiologists DE kinetic states; mechanisms of anesthesia; mutagenesis ID NICOTINIC ACETYLCHOLINE-RECEPTOR; GENERAL-ANESTHETICS; DESENSITIZATION KINETICS; POTENTIATION; CURRENTS; POTENCY; BINDING; CUTOFF AB Background: Nonanesthetic volatile compounds fail to inhibit movement in response to noxious stimulation at concentrations predicted to induce anesthesia from their oil-water partitioning. Thus they represent tools to determine whether molecular models behave like the targets that mediate in vivo anesthetic actions. The effects of volatile anesthetics and non-anesthetics were examined in two experimental models in which anesthetics interact directly with proteins: the pore of the nicotinic acetylcholine receptor and human serum albumin. Methods: Wild-type mouse muscle nicotinic receptors and receptors containing pore mutations (alpha S252I + beta T263I) were studied electrophysiologically in membrane patches from Xenopus oocytes, Patch currents evoked by brief pulses of acetylcholine were measured in the presence of enflurane and two nonanesthetics, 1,2-dichlorohexafluorocyclobutane and 2,3-dichlorooctafluorobutane. Nonanesthetic interactions with human serum album were assessed by quenching of intrinsic protein fluorescence. Results: Both anesthetic and nonanesthetic volatile com pounds inhibited wild-type and alpha S252I +/- beta T263I mutant nicotinic channels but displayed different selectivity for open versus resting receptor states, Median inhibitory concentrations (IC(50)s) in wild-type nicotinic receptors were 870 +/- 20 mu m for enflurane, 37 +/- 3 mu M for 1,2-dichlorohexafluorocylcobutane, and 11.3 +/- 5.6 mu M for 2,3-dichlorooctafluorobutane. For all three drugs, ratios of mild-type IC(50)s to mutant IC50max ranged from 7-10, and ratios of wild-type IC(50)s to predicted anesthetic median effective concentrations (EC(50)s) ranged from 1.8-2.3, 1,2-Dichlorohexafluorocyclobutane quenched human serum albumin with an apparent dissociation constant (K-d) of 160 +/- 11 mu M. The ratios of dissociation constants to predicted EC(50)s for the nonanesthetics were within a factor of two of the dissociation constant:EC50 ratios calculated for halothane and chloroform from previous published results. Conclusions: In two models in which anesthetics bind to protein sites, both anesthetic and nonanesthetic volatile drugs cause similar steady state effects with potencies that are predicted by hydrophobicity, These protein sites do not sterically discriminate between anesthetic and nonanesthetic drugs. However, differential state-selective actions on ion channel targets may underlie the distinct in vivo effects of anesthetics and nonanesthetics. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Clin 3, Boston, MA 02114 USA. RP Forman, SA (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Clin 3, Boston, MA 02114 USA. EM forman@helix.mgh.harvard.edu FU NIAAA NIH HHS [K21-AA00206]; NIGMS NIH HHS [R29-GM53481] NR 36 TC 24 Z9 24 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD JUN PY 1998 VL 88 IS 6 BP 1535 EP 1548 DI 10.1097/00000542-199806000-00018 PG 14 WC Anesthesiology SC Anesthesiology GA ZU022 UT WOS:000074153400017 PM 9637648 ER PT J AU Zimetbaum, PJ Kim, KY Josephson, ME Goldberger, AL Cohen, DJ AF Zimetbaum, PJ Kim, KY Josephson, ME Goldberger, AL Cohen, DJ TI Diagnostic yield and optimal duration of continuous-loop event monitoring for the diagnosis of palpitations - A cost-effectiveness analysis SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE cost-benefit analysis; electrocardiography, ambulatory; time factors; arrhythmia; palpitations AB Background: Continuous-loop event recorders are widely used for the evaluation of palpitations, but the optimal duration of monitoring is unknown. Objective: To determine the yield, timing, and incremental cost-effectiveness of each week of event monitoring for palpitations. Design: Prospective cohort study. Patients: 105 consecutive outpatients referred for the placement of a continuous-loop event recorder for the evaluation of palpitations. Measurements: Diagnostic yield, incremental cost, and cost-effectiveness for each week of monitoring. Results: The diagnostic yield of continuous-loop event recorders was 1.04 diagnoses per patient in week 1, 0.15 diagnoses per patient in week 2, and 0.01 diagnoses per patient in week 3 and beyond. Over time, the cost effectiveness ratio increased from $98 per new diagnosis in week 1 to $576 per new diagnosis in week 2 and $5832 per new diagnosis in week 3. Conclusions: In patients referred for evaluation of palpitations, the diagnostic yield of continuous-loop event recording decreases rapidly after 2 weeks of monitoring. A 2-week monitoring period is reasonably cost-effective for most patients and should be the standard period for continuous-loop event recording for the evaluation of palpitations. C1 Bath Israel Deaconess Med Ctr, Cardiovasc Div GZ435, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Cohen, DJ (reprint author), Bath Israel Deaconess Med Ctr, Cardiovasc Div GZ435, 330 Brookline Ave, Boston, MA 02115 USA. NR 7 TC 53 Z9 56 U1 0 U2 1 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JUN 1 PY 1998 VL 128 IS 11 BP 890 EP + PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA ZP980 UT WOS:000073808600002 PM 9634426 ER PT J AU Cudkowicz, ME McKenna-Yasek, D Chen, C Hedley-Whyte, ET Brown, RH AF Cudkowicz, ME McKenna-Yasek, D Chen, C Hedley-Whyte, ET Brown, RH TI Limited corticospinal tract involvement in amyotrophic lateral sclerosis subjects with the A4V mutation in the copper/zinc superoxide dismutase gene SO ANNALS OF NEUROLOGY LA English DT Article ID POINT MUTATION; DISEASE; FAMILY; ALS; HETEROGENEITY; MUTANT AB We examined 11 subjects with inherited amyotrophic lateral sclerosis (familial amyotrophic lateral sclerosis, FALS) associated with the most common copper/zinc superoxide dismutase 1 (SOD1) mutation, an alanine for valine substitution in codon 4 (A4V). Autopsies were performed on 5 subjects. The clinical and pathological findings are described and compared with those of 9 sporadic ALS (SALS) subjects. There was no clinical evidence of upper motor neuron (UMN) involvement in 10 FALS A4V subjects. All subjects had lower motor neuron (LMN) signs and electrophysiological evidence of denervation in at least three limbs. All SALS subjects had signs of both UMN and LMN involvement. Pathological studies found severe abnormalities of LMNs in all FALS and SALS subjects. UMN involvement was either absent or mild in the A4V SOD1 FALS subjects and severe in the SALS subjects. Pathological abnormalities in systems other than the motor neurons were more frequent in the FALS A4V subjects. This information suggests that current diagnostic criteria for ALS, requiring clinical evidence for both upper and lower motor neuron involvement, should be modified; ie, the diagnosis should be deemed established when there is evidence of denervation in three or more limbs and a mutation in the gene for SOD1, even without clinical signs of UMN involvement. C1 Harvard Univ, Dept Neurol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Harvard Univ, Dept Neuropathol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA USA. RP Cudkowicz, ME (reprint author), Harvard Univ, Dept Neurol, Massachusetts Gen Hosp, Sch Med, 32 Blossom St,Room ACC 836, Boston, MA 02114 USA. FU NIA NIH HHS [1PO1AG12992-01]; NINDS NIH HHS [1PO1NS31248-01, R1NS34913] NR 42 TC 88 Z9 89 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JUN PY 1998 VL 43 IS 6 BP 703 EP 710 DI 10.1002/ana.410430604 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA ZR877 UT WOS:000074023800003 PM 9629839 ER PT J AU Poorkaj, P Bird, TD Wijsman, E Nemens, E Garruto, RM Anderson, L Andreadis, A Wiederholt, WC Raskind, M Schellenberg, GD AF Poorkaj, P Bird, TD Wijsman, E Nemens, E Garruto, RM Anderson, L Andreadis, A Wiederholt, WC Raskind, M Schellenberg, GD TI Tau is a candidate gene for chromosome 17 frontotemporal dementia SO ANNALS OF NEUROLOGY LA English DT Article ID FAMILIAL PRESENILE-DEMENTIA; FRONTAL-LOBE DEGENERATION; PERIPHERAL NERVOUS-SYSTEM; NON-ALZHEIMER TYPE; HUMAN GENOME; PROTEIN TAU; DISEASE; NEUROPATHOLOGY; LOCALIZATION; PARKINSONISM AB Frontotemporal dementia with parkinsonism, chromosome 17 type (FTDP-17), a recently defined disease entity, is clinically characterized by personality changes sometimes associated with psychosis, hyperorality, and diminished speech output, disturbed executive function and nonfluent aphasia, bradykinesia, and rigidity. Neuropathological changes include frontotemporal atrophy often associated with atrophy of the basal ganglia, substantia nigra, and amygdala. Neurofibrillary tangles (NFTs) are seen in some but not all families. Inheritance is autosomal dominant and the gene has been regionally localized to 17q21-22 in a 2- to 4-centimorgan (cM) region flanked by markers D17S800 and D17S791. The gene for tau, the primary component of NFTs, is located in the same region of chromosome 17. Tau was evaluated as a candidate gene. Physical mapping studies place tau within 2 megabases or less of D17S791, but it is probably outside the D17S800-D17S791 FTDP-17 interval. DNA sequence analysis of tau coding regions in affected subjects from two FTDP-17 families revealed nine DNA sequence variants, eight of which were also identified in controls and are thus polymorphisms. A ninth variant ((Val)279(Met)) was found in one FTDP-17 family but not in the second FTDP-17 family. Three lines of evidence indicate that the (Val)279(Met) change is an FTDP-17 causative mutation. First, the mutation site is highly conserved, and a normal valine is found at this position in all three tau interrepeat sequences and in other microtubule associated protein tau homologues. Second, the mutation co-segregates with the disease in family A. Third, the mutation is not found in normal controls. C1 GRECC 182 B, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Vet Affairs Puget Sound Hlth Care Syst, Dept Psychiat, Seattle, WA 98108 USA. Univ Washington, Div Gerontol & Geriatr Med, Seattle, WA 98195 USA. Univ Washington, Div Med Genet, Seattle, WA 98195 USA. Univ Washington, Dept Neurol, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Univ Washington, Dept Psychiat, Seattle, WA 98195 USA. Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA. SUNY Binghamton, Dept Anthropol, Binghamton, NY USA. EK Shriver Ctr Mental Retardat, Walthem, MA USA. Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA. RP Schellenberg, GD (reprint author), GRECC 182 B, Vet Affairs Puget Sound Hlth Care Syst, 1660 S Columbian Way, Seattle, WA 98108 USA. FU NIA NIH HHS [AG05136, AG1176-03, P01 AG14382] NR 42 TC 923 Z9 942 U1 6 U2 34 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JUN PY 1998 VL 43 IS 6 BP 815 EP 825 DI 10.1002/ana.410430617 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA ZR877 UT WOS:000074023800016 PM 9629852 ER PT J AU Kobler, JB Hillman, RE Zeitels, SM Kuo, J AF Kobler, JB Hillman, RE Zeitels, SM Kuo, J TI Assessment of vocal function using simultaneous aerodynamic and calibrated videostroboscopic measures SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article; Proceedings Paper CT Meeting of the American-Laryngological-Association CY MAY 10-11, 1997 CL SCOTTSDALE, ARIZONA SP Amer Laryngol Assoc DE aerodynamics; endoscopy; larynx; vocal fold; voice ID PRESSURE MEASUREMENTS; FLOW AB Despite many attempts to model how vocal fold movements relate to the aerodynamic forces acting on them during phonation, there have been few simultaneous measurements of glottal area and transglottal air pressures and flows. A novel system is described that combines endoscopic measurement of glottal area with aerodynamic flow and pressure measures made during phonation. Results from bench top model tests and from one human subject are presented. For both tests, an aerodynamic model of airflow through a constriction was used to predict the area of the constriction (glottis), and these predictions were compared with endoscopic measurements. The results showed good correlation between predicted and observed areas; however, for small constrictions (<0.025 cm(2)), whether artificial or glottal, the errors in estimating areas with either optical or aerodynamic methods increase significantly. These results suggest that this measurement system has the potential to enhance the assessment of vocal function. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Harris Peyton Mosher Laryngol Res Lab, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA. MIT, Elect Res Lab, Boston, MA 02139 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Voice & Speech Lab, Boston, MA 02114 USA. RP Kobler, JB (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Harris Peyton Mosher Laryngol Res Lab, 243 Charles St, Boston, MA 02114 USA. FU NIDCD NIH HHS [R01 DC00266] NR 14 TC 10 Z9 10 U1 0 U2 0 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD JUN PY 1998 VL 107 IS 6 BP 477 EP 485 PG 9 WC Otorhinolaryngology SC Otorhinolaryngology GA ZU030 UT WOS:000074154200005 PM 9635457 ER PT J AU Coast-Senior, EA Kroner, BA Kelley, CL Trilli, LE AF Coast-Senior, EA Kroner, BA Kelley, CL Trilli, LE TI Management of patients with type 2 diabetes by pharmacists in primary care clinics SO ANNALS OF PHARMACOTHERAPY LA English DT Article DE type 2 diabetes; primary care; pharmacists ID EXPERIENCE; MODEL AB OBJECTIVE: TO determine the impact of clinical pharmacists involved in direct patient care on the glycemic control of patients with type 2 diabetes mellitus. DESIGN: Eligible patients included those with type 2 diabetes who received insulin or were initiated on insulin therapy by the pharmacists and were willing to perform self-monitoring of blood glucose. The pharmacists provided diabetes education, medication counseling, monitoring, and insulin initiation and/or adjustments, All initial patient interactions with the pharmacists were face-to-face. Thereafter, patient-pharmacist interactions were either face-to-face or telephone contacts. SETTING: Two primary care clinics in a university-affiliated Veterans Affairs Medical Center. PARTICIPANTS: Study subjects were patients with type 2 diabetes who were referred to the pharmacists by their primary care providers for better glycemic control. OUTCOME MEASURES: Primary outcome variables were changes from baseline in glycosylated hemoglobin, fasting blood glucose, and random blood glucose measurements. Secondary outcomes were the number and severity of symptomatic episodes of hypoglycemia, and the number of emergency room visits or hospitalizations related to diabetes. Twenty-three veterans aged 65 - 9.4 years completed the study. Fifteen (65%) patients were initiated on insulin by the pharmacists; 8 (35%) were already using insulin. Patients were followed for a mean - SD of 27 - 10 weeks. Glycosylated hemoglobin, fasting blood glucose concentrations, and random blood glucose concentrations significantly decreased from baseline by 2.2% (p = 0.00004), 65 mg/dL (p < 0.01), and 82 mg/dL (p = 0.00001), respectively. Symptomatic hypoglycemic episodes occurred in 35% of patients, None of these episodes required physician intervention. CONCLUSIONS: This study demonstrates that pharmacists working as members of interdisciplinary primary care teams can positively impact glycemic control in patients with type 2 diabetes requiring insulin. C1 Vet Affairs Pittsburgh Hlth Care Syst, Dept Pharm, Pittsburgh, PA USA. Univ Pittsburgh, Sch Pharm, Pittsburgh, PA USA. RP Coast-Senior, EA (reprint author), Med Ctr, Dept Pharm, 1000 Dutch Ridge Rd, Beaver, PA 15009 USA. NR 24 TC 92 Z9 95 U1 0 U2 4 PU HARVEY WHITNEY BOOKS CO PI CINCINNATI PA PO BOX 42696, CINCINNATI, OH 45242 USA SN 1060-0280 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD JUN PY 1998 VL 32 IS 6 BP 636 EP 641 DI 10.1345/aph.17095 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZU472 UT WOS:000074200900002 PM 9640480 ER PT J AU Akins, CW Buckley, MJ Daggett, WM Hilgenberg, AD Vlahakes, GJ Torchiana, DF Madsen, JC AF Akins, CW Buckley, MJ Daggett, WM Hilgenberg, AD Vlahakes, GJ Torchiana, DF Madsen, JC TI Risk of reoperative valve replacement for failed mitral and aortic bioprostheses SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 34th Annual Meeting of the Society-of-Thoracic-Surgeons CY JAN 26-28, 1998 CL NEW ORLEANS, LOUISIANA SP Soc Thorac Surgeons ID PORCINE BIOPROSTHESIS; DETERMINANTS; PROSTHESES; FAILURE; SURGERY; PATIENT; TISSUE; AGE AB Background. One factor influencing the choice of mechanical versus bioprosthetic valves is reoperation for bioprosthetic valve failure. To define its operative risk, we reviewed our results with valve reoperation for bioprosthetic valve failure. Methods. Records of 400 consecutive patients having reoperative mitral, aortic, or mitral and aortic bioprosthetic valve replacement from January 1985 to March 1997 were reviewed. Results. Reoperations were for failed bioprosthetic mitral valves in 219 patients, failed aortic valves in 153 patients, and failed aortic and mitral valves in 28 patients. Including 26 operations (6%) for acute endocarditis, 153 operations (38%) were nonelective. One hundred nine patients (27%) had other valves repaired or replaced, and 72 (18%) had coronary bypass grafting. The incidence of death in the mitral, aortic, and double-valve groups was respectively, 15 (6.8%), 12 (7.8%), and 4 (14.3%); and the incidence of prolonged postoperative hospital stay (> 14 days) was, respectively, 57 (26.0%), 41 (26.8%), and 8 (28.6%). Only 7 of 147 patients (4.8%) having elective, isolated, first-time valve reoperation died. Multivariable predictors (p < 0.05) of hospital death were age greater than 65 years, male sex, renal insufficiency, and nonelective operation; and predictors of prolonged stay were acute endocarditis, renal insufficiency, any concurrent cardiac operation, and elevated pulmonary artery systolic pressure. Conclusions. Reoperative bioprosthetic valve replacement can be performed with acceptable mortality and hospital stay. The best results are achieved with elective valve replacement, without concurrent cardiac procedures. (C) 1998 by The Society of Thoracic Surgeons. C1 Massachusetts Gen Hosp, Cardiac Surg Unit, Boston, MA 02114 USA. RP Akins, CW (reprint author), Massachusetts Gen Hosp, Cardiac Surg Unit, White 503,32 Fruit St, Boston, MA 02114 USA. NR 14 TC 96 Z9 101 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD JUN PY 1998 VL 65 IS 6 BP 1545 EP 1551 DI 10.1016/S0003-4975(98)00301-4 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA ZV146 UT WOS:000074274100011 PM 9647056 ER PT J AU Canver, CC Patel, AK Kosolcharoen, P Voytovich, MC AF Canver, CC Patel, AK Kosolcharoen, P Voytovich, MC TI Fungal purulent constrictive pericarditis in a heart transplant patient SO ANNALS OF THORACIC SURGERY LA English DT Article ID CANDIDA AB Purulent pericarditis caused by Candida species is rare and is associated with very high mortality. Immunosuppressed transplant patients are particularly susceptible to fungal infections. We report a case of Candida purulent constrictive pericarditis in an immunocompromised heart transplant patient who was treated successfully with antifungal agents, surgical drainage, and pericardiectomy. (C) 1998 by The Society of Thoracic Surgeons. C1 Univ Wisconsin, William S Middleton Mem Vet Hosp, Sch Med, Sect Cardiothorac Surg, Madison, WI USA. Univ Wisconsin, William S Middleton Mem Vet Hosp, Sch Med, Cardiol Sect, Madison, WI USA. Univ Wisconsin, William S Middleton Mem Vet Hosp, Sch Med, Sect Pathol, Madison, WI USA. RP Canver, CC (reprint author), Univ Wisconsin, Sch Med, Div Cardiothorac Surg, Ctr Clin Sci, H4-352,600 Highland Ave, Madison, WI 53792 USA. NR 5 TC 13 Z9 15 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD JUN PY 1998 VL 65 IS 6 BP 1792 EP 1794 DI 10.1016/S0003-4975(98)00277-X PG 3 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA ZV146 UT WOS:000074274100080 PM 9647112 ER PT J AU Fishman, JA AF Fishman, JA TI Treatment of infection due to Pneumocystis carinii SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Review ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; TRIMETHOPRIM-SULFAMETHOXAZOLE; CLINDAMYCIN-PRIMAQUINE; RANDOMIZED TRIAL; DOUBLE-BLIND; IN-VITRO; ORNITHINE DECARBOXYLASE; DAPSONE-TRIMETHOPRIM; VIRUS INFECTION; PNEUMONIA C1 Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. RP Fishman, JA (reprint author), Massachusetts Gen Hosp, Infect Dis Unit, 55 Fruit St, Boston, MA 02114 USA. EM jfishman@helix.mgh.harvard.edu NR 61 TC 57 Z9 60 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JUN PY 1998 VL 42 IS 6 BP 1309 EP 1314 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA ZR221 UT WOS:000073952400001 PM 9624465 ER PT J AU Fujiwara, T Sato, A El-Farrash, M Miki, S Abe, K Isaka, Y Kodama, M Wu, YM Chen, LB Harada, H Sugimoto, H Hatanaka, M Hinuma, Y AF Fujiwara, T Sato, A El-Farrash, M Miki, S Abe, K Isaka, Y Kodama, M Wu, YM Chen, LB Harada, H Sugimoto, H Hatanaka, M Hinuma, Y TI S-1153 inhibits replication of known drug-resistant strains of human immunodeficiency virus type 1 SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID HIV-1 REVERSE-TRANSCRIPTASE; DYNAMICS IN-VIVO; NONNUCLEOSIDE INHIBITORS; PROTEASE INHIBITOR; POTENT; CELLS; THERAPY; RETROVIRUS; MACROPHAGE; GENERATION AB S-1153 is a new imidazole compound that inhibits human immunodeficiency virus (HIV) type 1 (HIV-1) replication by acting as a nonnucleoside reverse transcriptase inhibitor (NNRTI), This compound inhibits replication of HIV-1 strains that are resistant to nucleoside and nonnucleoside reverse transcriptase inhibitors. S-1153 has a 50% effective concentration in the range of 0.3 to 7 ng/ml for strains with single amino acid substitutions that cause NNRTI resistance, including the Y181C mutant, and also has potent activity against clinical isolates. The emergence of S-1153-resistant variants is slower than that for nevirapine, and S-1153-resistant variants contained at least two amino acid substitutions, including F227L or L234I. S-1153-resistant variants are still sensitive to the nucleoside reverse transcriptase inhibitors zidovudine (AZT) and lamivudine. In a mouse and MT-4 (human T-cell line) in vivo HIV replication model, S-1153 and AZT administered orally showed a marked synergy for the inhibition of HIV-1 replication. S-1153 shows a significant accumulation in lymph nodes, where most HIV-1 infection is thought to occur. S-1153 may be an appropriate candidate for two- to three-drug combination therapy for HTS' infection. C1 Shionogi & Co Ltd, Shionogi Res Labs, Fukushima Ku, Osaka 553, Japan. Shionogi BioRes Corp, Lexington, MA 02173 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Fujiwara, T (reprint author), Shionogi & Co Ltd, Shionogi Inst Med Sci, 2-5-1 Mishima, Settsu 5660022, Japan. NR 32 TC 114 Z9 125 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JUN PY 1998 VL 42 IS 6 BP 1340 EP 1345 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA ZR221 UT WOS:000073952400008 PM 9624472 ER PT J AU Schulin, T Wennersten, CB Ferraro, MJ Moellering, RC Eliopoulos, GM AF Schulin, T Wennersten, CB Ferraro, MJ Moellering, RC Eliopoulos, GM TI Susceptibilities of Legionella spp. to newer antimicrobials in vitro SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID EXPERIMENTAL LEGIONNAIRES-DISEASE; GUINEA-PIGS; OXAZOLIDINONES U-100592; PNEUMOPHILA PNEUMONIA; PENICILLIN-RESISTANT; INVITRO ACTIVITY; RP 59500; AGENTS; ERYTHROMYCIN; RIFAMPIN AB The in vitro activities of 13 antimicrobial agents against 30 strains of legionella spp. were determined. Rifapentine, rifampin, and clarithromycin were the most potent agents (MICs at which 90% of isolates are inhibited [MIC(90)s], less than or equal to 0.008 mu g/ml). The ketolide HMR 3647 and the fluoroquinolones levofloxacin and BAY 12-8039 (MIC(90)s, 0.03 to 0.06 mu g/ml) were more active than erythromycin A or roxithromycin. The MIC(90)s of dalfopristin-quinupristin and linezolid were 0.5 and 8 mu g/ml, respectively. Based on class characteristics and in vitro activities, several of these agents may have potential roles in the treatment of Legionella infections. C1 Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Eliopoulos, GM (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, W Campus,1 Deaconess Rd, Boston, MA 02215 USA. EM geliopou@bidmc.harvard.edu NR 36 TC 88 Z9 89 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JUN PY 1998 VL 42 IS 6 BP 1520 EP 1523 PG 4 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA ZR221 UT WOS:000073952400045 PM 9624509 ER PT J AU Lin, CP Kelly, MW AF Lin, CP Kelly, MW TI Cavitation and acoustic emission around laser-heated microparticles SO APPLIED PHYSICS LETTERS LA English DT Article ID COLLOIDAL SUSPENSIONS; PULSES; RADIATION; ABLATION; ABSORPTION; GENERATION; TRANSIENT; SURGERY AB We studied transient cavitation bubble formation and acoustic emission around individual laser-heated microparticles using subnanosecond time-resolved microscopy. Microcavitation babbles were observed as early as 0.5 ns after the particles were heated by a 30 ps laser pulse. The bubbles expanded to a few micrometers in size and collapsed on the time scale of 0.1-1 mu sec. We discuss microcavitation as the origin of anomalously large photoacoustic effects and nonlinear optical responses observed in laser-heated colloidal suspensions, as well as a mechanism for cellular damage in biologic tissue containing pigment particles. (C) 1995 American Institute of Physics. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA 02114 USA. RP Lin, CP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA 02114 USA. NR 28 TC 100 Z9 100 U1 3 U2 14 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 USA SN 0003-6951 J9 APPL PHYS LETT JI Appl. Phys. Lett. PD JUN 1 PY 1998 VL 72 IS 22 BP 2800 EP 2802 DI 10.1063/1.121462 PG 3 WC Physics, Applied SC Physics GA 108PB UT WOS:000075273700008 ER PT J AU Ge, ZF Schomacker, KT Nishioka, NS AF Ge, ZF Schomacker, KT Nishioka, NS TI Identification of colonic dysplasia and neoplasia by diffuse reflectance spectroscopy and pattern recognition techniques SO APPLIED SPECTROSCOPY LA English DT Article DE diffuse reflectance spectroscopy; endoscopy; tissue identification; colon; neoplasm; pattern recognition ID LASER-INDUCED FLUORESCENCE; EX-VIVO; DIAGNOSIS; TISSUE; ADENOMAS AB Diffuse reflectance spectroscopy of colonic tissue was employed to determine whether the spectra can be used to distinguish between neoplastic and non-neoplastic tissue in vivo. A total of 224 spectra were obtained in the wavelength range of 350-800 nm from 107 non-neoplastic tissue samples (84 normal mucosa, 23 hyperplastic polyps) and 53 neoplastic tissue samples (44 adenomatous polyps, 9 adenocarcinomas). Pattern recognition algorithms including multiple linear regression (MLR), linear discriminant analysis (LDA), and backpropagating neural network (BNN) were used to distinguish between the two tissue classes. The spectra were randomly separated into training and prediction sets for data analyses. The mean predictive accuracies of distinguishing neoplastic tissue from non-neoplastic tissue with MLR, LDA, and BNN were 85, 82, and 85%, respectively. In a similar fashion, the more clinically relevant problem of distinguishing adenomatous polyps from hyperplastic polyps was assessed. The mean predictive accuracies of distinguishing adenomatous polyps from hyperplastic polyps with MLR, LDA, and BNN were 85, 81, and 82%, respectively. The major spectral differences between tissues were attributed to changes in blood volume, oxygen saturation of hemoglobin, mean vessel depth within tissue, and tissue scattering. C1 Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Med Serv, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. RP Schomacker, KT (reprint author), Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. NR 27 TC 65 Z9 64 U1 0 U2 2 PU SOC APPLIED SPECTROSCOPY PI FREDERICK PA 201B BROADWAY ST, FREDERICK, MD 21701 USA SN 0003-7028 J9 APPL SPECTROSC JI Appl. Spectrosc. PD JUN PY 1998 VL 52 IS 6 BP 833 EP 839 DI 10.1366/0003702981944571 PG 7 WC Instruments & Instrumentation; Spectroscopy SC Instruments & Instrumentation; Spectroscopy GA ZY337 UT WOS:000074610300009 ER PT J AU Theodossiadis, PG D'Amico, DJ Weissgold, DJ AF Theodossiadis, PG D'Amico, DJ Weissgold, DJ TI Repair of a complex retinal detachment with proliferative vitreoretinopathy in an eye with extreme scleral thinning SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article C1 Massachusetts Eye & Ear Infirm, Retina Serv, Boston, MA 02114 USA. RP D'Amico, DJ (reprint author), Massachusetts Eye & Ear Infirm, Retina Serv, 243 Charles St, Boston, MA 02114 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD JUN PY 1998 VL 116 IS 6 BP 812 EP 814 PG 3 WC Ophthalmology SC Ophthalmology GA ZU461 UT WOS:000074199400019 PM 9639457 ER PT J AU Azar, DT Clamen, LM AF Azar, DT Clamen, LM TI Iris fixation of a decentered silicone plate haptic intraocular lens - Double knot technique SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID CAPSULAR SUPPORT; IMPLANTATION; ABSENCE AB We describe a novel technique for fixating a decentered silicone plate haptic intraocular lens. In the absence of posterior capsular tear or zonular dehiscence, the superior eyelet of the silicone plate haptic intraocular lens is sutured to the iris at the 12-o'clock position using a double knot technique. Two 10-0 nonabsorbable surgical (Prolene) sutures used to preplace an iris loop and a loop around the intraocular lens eyelet are sutured together at the 9-o'clock position. The intraocular lens is repositioned by anchoring the iris sutures at the l2-o'clock position. This technique allows one to avoid an explantation of the lens and implantation of a new intraocular lens. C1 Massachusetts Eye & Ear Infirm, Cornea Serv, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Refract Surg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA USA. RP Azar, DT (reprint author), Massachusetts Eye & Ear Infirm, Cornea Serv, 243 Charles St, Boston, MA 02114 USA. NR 11 TC 2 Z9 2 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD JUN PY 1998 VL 116 IS 6 BP 821 EP 823 PG 3 WC Ophthalmology SC Ophthalmology GA ZU461 UT WOS:000074199400023 PM 9639461 ER PT J AU Wong, RJ Gliklich, RE Rubin, PAD Goodman, M AF Wong, RJ Gliklich, RE Rubin, PAD Goodman, M TI Bilateral nasolacrimal duct obstruction managed with endoscopic techniques SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID LACRIMAL DRAINAGE OBSTRUCTION; ETIOLOGIC CLASSIFICATION-SYSTEM; WEGENERS GRANULOMATOSIS; DACRYOCYSTORHINOSTOMY; SAC AB We present 3 cases of bilateral acquired nasolacrimal duct obstruction secondary to Wegener granulomatosis, sarcoidosis, and chronic lymphocytic leukemia. In all cases significant paranasal sinus and intranasal disease coincided with bilateral nasolacrimal duct obstruction. Surgical treatment of the nasolacrimal duct obstruction with dacryocystorhinostomy was more successful if the paranasal sinus disease was also treated. Nontraumatic bilateral nasolacrimal duct obstruction heralds unusual underlying systemic diseases, and coexisting paranasal sinus disease should be suspected. The simultaneous surgical treatment of both lacrimal and paranasal sinus disease through an endoscopic approach is advocated. C1 Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Gliklich, RE (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 16 TC 18 Z9 18 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD JUN PY 1998 VL 124 IS 6 BP 703 EP 706 PG 4 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA ZU733 UT WOS:000074229000015 PM 9639483 ER PT J AU Scremin, OU Cuevas-Trisan, RL Scremin, AME Brown, CV Mandelkern, MA AF Scremin, OU Cuevas-Trisan, RL Scremin, AME Brown, CV Mandelkern, MA TI Functional electrical stimulation effect on skeletal muscle blood flow measured with (H2O)-O-15 positron emission tomography SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article ID SPINAL-CORD INJURY; INPUT FUNCTION; EXERCISE; INSULIN; RESPONSES; PATIENT; DISEASE; GLUCOSE; INVIVO AB Objective: To test the hypothesis that the limitation in muscle power development with functional electrical stimulation (FES) results from an insufficient increase in muscle blood how (MBF) in response to activity. Subjects and Methods: Five subjects with neurologically complete spinal cord injury (SCI) were tested to measure the MBF response to FES-induced knee extension. The MBF response to voluntary knee extension was measured in five age-matched, able-bodied controls. MBF was measured with positron emission tomography (PET) using (H2O)-O-15 as a tracer. Three scans were performed with muscle at rest (baseline), immediately after 16min of FES-induced or voluntary knee extension (activity), and 20min after the second scan (recovery). Results: In SCI subjects, mean +/-SE MBF (mL/100g/min) values were: baseline = 1.85 +/- .48; post-FES = 31.9 +/- 5.65 (p = .0058 vs baseline); recovery = 6.06 +/- 1.52 (p = .0027 vs baseline). In able-bodied controls, mean +/-SE MBF values were: baseline = 8.52 +/- 3.24, post-voluntary exercise = 12.62 +/- 3.03 (p = .023 vs post-FES in SCI subjects); recovery = 10.7 +/- 6.01. Conclusions: MBF does not appear to be the limiting factor in muscle power generation with FES, The greater increase in MBF observed with FES in SCI subjects when compared with able-bodied subjects performing a similar task (unloaded knee extension against gravity) may relate to abnormal metabolism in FES-stimulated muscle. (C) 1998 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation. C1 W Los Angeles Vet Affairs Med Ctr, Dept Phys Med & Rehabil, Los Angeles, CA 90073 USA. W Los Angeles Vet Affairs Med Ctr, Dept Nucl Med, Los Angeles, CA 90073 USA. W Los Angeles Vet Affairs Med Ctr, Dept Res, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Physiol, Los Angeles, CA 90024 USA. RP Scremin, OU (reprint author), W Los Angeles Vet Affairs Med Ctr, Dept Phys Med & Rehabil, 11301 Wilshire Blvd,Bldg 115, Los Angeles, CA 90073 USA. NR 39 TC 12 Z9 12 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD JUN PY 1998 VL 79 IS 6 BP 641 EP 646 DI 10.1016/S0003-9993(98)90037-5 PG 6 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA ZT554 UT WOS:000074099500007 PM 9630142 ER PT J AU Escary, JL Choy, HA Reue, K Schotz, MC AF Escary, JL Choy, HA Reue, K Schotz, MC TI Hormone-sensitive lipase overexpression increases cholesteryl ester hydrolysis in macrophage foam cells SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE hormone-sensitive lipase; foam cells; cholesteryl ester hydrolysis ID HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA; LOW-DENSITY-LIPOPROTEIN; J774 MACROPHAGES; GENE-EXPRESSION; ADIPOSE-TISSUE; MESSENGER-RNA; METABOLISM; PROTEIN; PHOSPHORYLATION; LOCALIZATION AB Atherosclerosis is a complex physiopathologic process initiated by the formation of cholesterol-rich lesions in the arterial wall. Macrophages play a crucial role in this process because they accumulate large amounts of cholesterol esters (CEs) to form the foam cells that initiate the formation of the lesion and participate actively in the development of the lesion: Therefore, prevention or reversal of CE accumulation in macrophage foam cells could result in protection from multiple pathological effects. In this report, we show that the CE hydrolysis catalyzed by neutral cholesterol ester hydrolase (nCEH) can be modulated by overexpression of hormone-sensitive lipase (HSL) in macrophage foam cells. For these studies, RAW 264.7 cells, a murine macrophage cell line, were found to be a suitable model of foam cell formation. HSL expression and nCEH activity in these cells and in peritoneal macrophages were comparable. In addition, antibody titration showed that essentially all nCEH activity in murine macrophages was accounted for by HSL. To examine the effect of HSL overexpression on foam cell formation, RAW 264.7 cells were stably transfected with a rat HSL cDNA. The resulting HSL overexpression increased hydrolysis of cellular CEs 2- to 3-fold in lipid-laden cells in the presence of an acyl coenzyme A:cholesterol acyltransferase (ACAT) inhibitor. Furthermore, addition of cAMP produced a 5-fold higher rate of CE hydrolysis in cholesterol-laden, HSL-overexpressing cells than in control cells and resulted in nearly complete hydrolysis of cellular CEs in only 9 hours, compared with <50% hydrolysis in control cells. Thus, HSL overexpression stimulated the net hydrolysis of CEs, leading to faster hydrolysis of lipid deposits in model foam cells. These data suggest that HSL overexpression in macrophages, alone or in combination with ACAT inhibitors, may constitute a useful therapeutic approach for impeding CE accumulation in macrophages in vivo. C1 W Los Angeles Vet Affairs Med Ctr, Lipid Res Lab, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. RP Schotz, MC (reprint author), W Los Angeles Vet Affairs Med Ctr, Lipid Res Lab, Bldg 113,Room 312, Los Angeles, CA 90073 USA. NR 41 TC 49 Z9 52 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JUN PY 1998 VL 18 IS 6 BP 991 EP 998 PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA ZU232 UT WOS:000074175500020 PM 9633942 ER PT J AU Bribiescas, RG AF Bribiescas, RG TI Testosterone and dominance: Between-population variance and male energetics SO BEHAVIORAL AND BRAIN SCIENCES LA English DT Editorial Material ID ENDOGENOUS TESTOSTERONE; MEN; SERUM; HORMONES AB The testosterone-dominance model is noteworthy but should incorporate the ecological factors that often underlie variability in basal testosterone. This is evident in the ethnic testosterone differences discussed in the target article (sect. 8). The significance of acute changes in testosterone levels in response to competition is also poorly understood. Significant metabolic effects have been reported, suggesting that other physiological explanations should be explored, independent of potential behavioral or social factors. C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. RP Bribiescas, RG (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. NR 17 TC 1 Z9 1 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0140-525X J9 BEHAV BRAIN SCI JI Behav. Brain Sci. PD JUN PY 1998 VL 21 IS 3 BP 364 EP + DI 10.1017/S0140525X98241227 PG 9 WC Psychology, Biological; Behavioral Sciences; Neurosciences SC Psychology; Behavioral Sciences; Neurosciences & Neurology GA 115TE UT WOS:000075680800022 ER PT J AU Weller, EA Ryan, LM AF Weller, EA Ryan, LM TI Testing for trend with count data SO BIOMETRICS LA English DT Article DE dose-response; efficiency; Jonckheere-Terpstra; Poisson; trend tests AB Among the tests that can be used to detect dose-related trends in count data from toxicological studies are nonparametric tests such as the Jonckheere-Terpstra and likelihood-based tests, for example, based on a Poisson model. This paper was motivated by a data set of tumor counts in which conflicting conclusions were obtained using these two tests. To define situations where one test may be preferable, we compared the small and large sample performance of these two tests as vi ell as a robust and conditional version of the likelihood-based test in the absence and presence of a dose-related trend for both Poisson and overdispersed Poisson data. Based on our results, we suggest using the Poisson test when little overdispersion is present in the data. For more overdispersed data, we recommend using the robust Poisson test for highly discrete data (response rate lower than 2-3) and the robust Poisson test or the Jonckheere-Terpstra test for moderately discrete or continuous data (average responses larger than 2 or 3). We also studied the effects of dose metameter misspecification. A clear effect on efficiency was seen when the 'wrong' dose metameter was used to compute the test statistic. In general, unless there is strong reason to do otherwise, we recommend the use of equally spaced dose levels when applying the Poisson or robust Poisson test for trend. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Weller, EA (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 FU NCI NIH HHS [CA48061]; PHS HHS [5T32OS07142] NR 9 TC 14 Z9 14 U1 0 U2 1 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 808 17TH ST NW SUITE 200, WASHINGTON, DC 20006-3910 USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD JUN PY 1998 VL 54 IS 2 BP 762 EP 773 DI 10.2307/3109782 PG 12 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA ZU099 UT WOS:000074161600032 PM 9629655 ER PT J AU Kaulin, YA Schagina, LV Bezrukov, SM Malev, VV Feigin, AM Takemoto, JY Teeter, JH Brand, JG AF Kaulin, YA Schagina, LV Bezrukov, SM Malev, VV Feigin, AM Takemoto, JY Teeter, JH Brand, JG TI Cluster organization of ion channels formed by the antibiotic syringomycin E in bilayer lipid membranes SO BIOPHYSICAL JOURNAL LA English DT Article ID CONDUCTANCE STATES; PSEUDOMONAS-SYRINGAE; SODIUM-CHANNEL; PHYTOTOXIN; MECHANISM AB The cyclic lipodepsipeptide, syringomycin E, when incorporated into planar lipid bilayer membranes, forms two types of channels (small and large) that are different in conductance by a factor of sixfold. To discriminate between a cluster organization-type channel structure and other possible different structures for the two channel types, their ionic selectivity and pore size were determined. Pore size was assessed using water-soluble polymers, ion selectivity was found to be essentially the same for both the small and large channels. Their reversal (zero current) potentials with the sign corresponding to anionic selectivity did not differ by more than 3 mV at a twofold electrolyte gradient across the bilayer. Reduction in the single-channel conductance induced by poly(ethylene glycol)s of different molecular weights demonstrated that the aqueous pore sizes of the small and large channels did not differ by more than 2% and were close to 1 nm. Based on their virtually identical selectivity and size, we conclude that large syringomycin E channels are clusters of small ones exhibiting synchronous opening and closing. C1 Monell Chem Senses Ctr, Philadelphia, PA 19104 USA. Russian Acad Sci, Inst Cytol, St Petersburg 194064, Russia. NICHD, NIH, Lab Phys & Struct Biol, Bethesda, MD 20892 USA. Russian Acad Sci, Inst Nucl Phys, Gatchina 188350, Russia. Utah State Univ, Logan, UT 84322 USA. Univ Penn, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Brand, JG (reprint author), Monell Chem Senses Ctr, 3500 Market St, Philadelphia, PA 19104 USA. EM brand@monell.org RI Takemoto, Jon/A-5309-2011 OI Takemoto, Jon/0000-0001-9919-9168 FU NIDCD NIH HHS [DC-00356, DC-01838] NR 25 TC 66 Z9 69 U1 1 U2 2 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JUN PY 1998 VL 74 IS 6 BP 2918 EP 2925 PG 8 WC Biophysics SC Biophysics GA ZT214 UT WOS:000074061500020 PM 9635746 ER PT J AU Luo, Y Wu, JL Gergely, J Tao, T AF Luo, Y Wu, JL Gergely, J Tao, T TI Localization of Cys(133) of rabbit skeletal troponin-l with respect to troponin-C by resonance energy transfer SO BIOPHYSICAL JOURNAL LA English DT Article ID CONFORMATIONAL TRANSITION; TRANSFER SPECTROSCOPY; DISTANCE MEASUREMENTS; MYOSIN SUBFRAGMENT-1; MUSCLE-CONTRACTION; PHOTOCROSS-LINKING; PEPTIDE COMPLEX; CROSS-LINKING; FLUORESCENCE; ACTIN AB We have used the technique of resonance energy transfer in conjunction with distance geometry analysis to localize Cys(133) of troponin-l (Tnl) with respect to troponin-C (TnC) in the ternary troponin complex and the binary TnC.Tnl complex in the presence and absence of Ca2+. Cys(133) of Tnl was chosen because our previous work has shown that the region of Tnl containing this residue undergoes Ca2+-dependent movements between actin and TnC, and may play an important role in the regulatory function of troponin. For this purpose, a Tnl mutant with a single Cys at position 133, and TnC mutants, each with a single Cys at positions 5, 12, 21, 41, 49, 89, 98, 133, and 158, were constructed by site-directed mutagenesis. The distances between Tnl Cys(133) and each of the nine residues in TnC were then measured. Using a least-squares minimization procedure, we determined the position of Tnl Cys(133) in the coordinate system of the crystal structure of TnC. Our results show that in the presence of Ca2+, Tnl Cys(133) is located near residue 12 beneath the N-terminal lobe of TnC, and moves away by 12.6 Angstrom upon the removal of Ca2+. Tnl Cys(133) and the region of TnC that undergoes major change in conformation in response to Ca2+ are located roughly on opposite sides of TnC's central helix. This suggests that the region in Tnl that undergoes Ca2+-dependent interaction with TnC is distinct from that interacting with actin. C1 Boston Biomed Res Inst, Muscle Res Grp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Tufts Univ, Sch Med, Dept Biochem, Boston, MA 02111 USA. RP Tao, T (reprint author), Boston Biomed Res Inst, Muscle Res Grp, 20 Staiford St, Boston, MA 02114 USA. EM tao@bbri.harvard.edu FU NHLBI NIH HHS [HL 5949]; NIAMS NIH HHS [AR21673] NR 42 TC 18 Z9 18 U1 1 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JUN PY 1998 VL 74 IS 6 BP 3111 EP 3119 PG 9 WC Biophysics SC Biophysics GA ZT214 UT WOS:000074061500038 PM 9635764 ER PT J AU Martin, KJ Kwan, CP O'Hare, MJ Pardee, AB Sager, R AF Martin, KJ Kwan, CP O'Hare, MJ Pardee, AB Sager, R TI Identification and verification of differential display cDNAs using gene-specific primers and hybridization arrays SO BIOTECHNIQUES LA English DT Article ID MAMMARY EPITHELIAL-CELLS; BREAST-CANCER; MESSENGER-RNA; EXPRESSION; 5'-NUCLEOTIDASE; PRECISION; CARCINOMA; CLONING; GROWTH AB An accurate and streamlined approach to differential display (DD) band identification and verification is described. To minimize false positives, the strategy avoids the use of impure Northern blot probes obtained from PCR-amplified DD bands. To increase throughput, the cloning of DD bands is replaced by a gene-specific primer approach, and hybridization arrays are rued in place of Northern blots. In summary, DD bands obtained with long primers were directly sequenced to allow the design and synthesis of gene-specific primers, which were then used to PCR-amplify homogeneous probes for the verification of expression patterns by hybridization array analysis. Differential expression of 60 of the 63 genes tested was confirmed Thug false positives are not inherent to DD. The results demonstrate the power of DD used with hybridization arrays to rapidly generate information on expression patterns of differentially expressed genes. C1 Dana Farber Canc Inst, Div Canc Genet, Boston, MA 02115 USA. UCL, LICR, Sch Med, London, England. RP Martin, KJ (reprint author), Dana Farber Canc Inst, Div Canc Genet, 44 Binney St, Boston, MA 02115 USA. NR 26 TC 25 Z9 28 U1 1 U2 2 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD JUN PY 1998 VL 24 IS 6 BP 1018 EP + PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZT019 UT WOS:000074039500023 PM 9631197 ER PT J AU Yakushijin, Y Steckel, J Kharbanda, S Hasserjian, R Neuberg, D Jiang, WM Anderson, I Shipp, MA AF Yakushijin, Y Steckel, J Kharbanda, S Hasserjian, R Neuberg, D Jiang, WM Anderson, I Shipp, MA TI A directly spliced exon 10-containing CD44 variant promotes the metastasis and homotypic aggregation of aggressive non-Hodgkin's lymphoma SO BLOOD LA English DT Article ID HOMING RECEPTOR CD44; CELL-SURFACE GLYCOPROTEIN; ACTIVATED B-CELLS; ADHESION MOLECULES; T-CELLS; HYALURONATE; ISOFORMS; BINDING; EXPRESSION; ANTIGEN AB Variants of the CD44 cell-surface adhesion molecule include additional sequences encoded by combinations of exons from the membrane proximal domain (exons 6-14). Preliminary studies suggest that these additional variable membrane proximal sequences may alter the ligand specificity, glycosylation, and biologic function of CD44. In earlier studies, we found that primary extranodal and widely disseminated aggressive non-Hodgkin's lymphomas (NHLs) and normal activated B cells expressed a directly spliced exon 10-containing variant (CD44ex10), whereas normal resting B cells expressed larger exon 10-containing variants (CD44ex10-14 and CD44ex7-14). To obtain additional information regarding the function of exon 10-containing CD44 variants in aggressive NHL, we generated aggressive NHL transfectants that expressed CD44ex10, CD44ex10-14, CD44ex7-14, the standard CD44 isoform (CD44H), or vector alone, and evaluated the local tumorogenicity, aggregation, and metastatic potential of these transfectants. CD44ex10 aggressive NHL transfectants were more likely to cause local tumor formation in nude mice than transfectants expressing the larger exon 10-containing variants, CD44H, or vector alone. In addition, cell suspensions derived from CD44ex10 local tumors exhibited far greater homotypic aggregation than those obtained from other CD44 or vector-only local tumors. In nude mice that received CD44ex10 transfectants, distant metastases were also significantly more likely to develop than in animals that were given either the CD44ex10-14, CD44ex7-14, CD44H, or vector-only transfectants. These data provide the first evidence that the directly spliced exon 10-containing CD44 variant (CD44ex10) has a unique biologic function in aggressive NHL. (C) 1998 by The American Society of Hematology. C1 Dana Farber Canc Inst, Div Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA USA. RP Shipp, MA (reprint author), Dana Farber Canc Inst, Div Hematol Malignancies, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA66996] NR 51 TC 23 Z9 24 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 1 PY 1998 VL 91 IS 11 BP 4282 EP 4291 PG 10 WC Hematology SC Hematology GA ZP871 UT WOS:000073797000034 PM 9596677 ER PT J AU Soiffer, RJ Freedman, AS Neuberg, D Fisher, DC Alyea, EP Gribben, J Schlossman, RL Bartlett-Pandite, L Kuhlman, C Murray, C Freeman, A Mauch, P Anderson, KC Nadler, LM Ritz, J AF Soiffer, RJ Freedman, AS Neuberg, D Fisher, DC Alyea, EP Gribben, J Schlossman, RL Bartlett-Pandite, L Kuhlman, C Murray, C Freeman, A Mauch, P Anderson, KC Nadler, LM Ritz, J TI CD6(+) T cell-depleted allogeneic bone marrow transplantation for non-Hodgkin's lymphoma SO BONE MARROW TRANSPLANTATION LA English DT Article DE lymphoma; allogeneic BMT; T cell depletion ID CHRONIC MYELOGENOUS LEUKEMIA; HOST DISEASE; GRAFT; CHEMOTHERAPY; RELAPSE; INTERLEUKIN-2 AB For patients with non-hodgkin's lymphoma (NHL) undergoing blood or bone marrow transplantation (BMT), the use of autologous grafts has often been preferred to that of allogeneic stem cells because of a significantly lower incidence of non-relapse mortality. If complications associated with allo-BMT could be minimized without compromising efficacy, then it might become a preferred strategy for certain subsets of patients. In this report, we describe the toxicity and long-term efficacy of T cell-depleted allogeneic BMT using anti-CD6 monoclonal antibody and complement alone to reduce the risk of GVHD and its sequelae, Twenty-two patients, aged 18-60 years, with high (n = 10), intermediate (n = 9), or low (n = 3) grade NHL underwent HLA-identical allogeneic BMT from siblings, Patients had either relapsed after at least one remission or never achieved a full remission with chemotherapy, Twenty patients had a history of marrow involvement. Bone marrow was depleted of CD6(+) T cells with T12 monoclonal antibody and complement as the sole form of GVHD prophylaxis. Stable hematopoietic engraftment occurred in all 22 patients. Four patients developed grade 2 and 1 patient grade 3 GVHD (23% grades 2-4 GVHD), Chronic GVHD has occurred in three patients. Treatment-related mortality was very low. Only one patient died while in remission. Thirteen patients are alive and free of disease with a median follow-up of 30 months. Estimated event-free and overall survivals are 54 and 59%, respectively. CD6 allogeneic marrow transplantation is associated with a low risk of transplant-related complications and may offer advantages for certain patients with recurrent NHL felt to be at high risk for relapse after autologous transplantation. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Joint Ctr Radiat Therapy, Boston, MA 02115 USA. RP Soiffer, RJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Malignancies, 44 Binney St, Boston, MA 02115 USA. RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NIAID NIH HHS [AI29530] NR 28 TC 31 Z9 31 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD JUN PY 1998 VL 21 IS 12 BP 1177 EP 1181 DI 10.1038/sj.bmt.1701271 PG 5 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA ZX054 UT WOS:000074475600002 PM 9674848 ER PT J AU Ferrara, JLM AF Ferrara, JLM TI The cytokine modulation of acute graft-versus-host disease SO BONE MARROW TRANSPLANTATION LA English DT Article; Proceedings Paper CT 2nd International Symposium on Allogeneic Peripheral Blood and Cord Blood Transplantation CY OCT 30-NOV 01, 1997 CL GENEVA, SWITZERLAND DE graft-versus-host disease; bone marrow transplantation; cytokines; TNF-alpha; interleukin-1; interferon-gamma ID MINOR HISTOCOMPATIBILITY ANTIGENS; BONE-MARROW TRANSPLANTATION; COLONY-STIMULATING FACTOR; TOTAL-BODY IRRADIATION; NECROSIS-FACTOR-ALPHA; T-CELLS; IONIZING-RADIATION; TH1/TH2 PARADIGM; MURINE MODEL; ACUTE GVHD AB Acute graft-versus-host disease (GVHD), the major complication of allogeneic bone marrow transplantation (BMT), significantly limits the application of this important therapy, Advances in basic immunobiology, and particularly in the dissection of the complex networks of cytokines that affect the function of immune cells, have increased our understanding of the effector mechanisms of acute GVHD, Data from both experimental and clinical studies suggest that inflammatory cytokines are critical components of acute GVHD that can be modulated by a number of proteins, including anti-inflammatory cytokines and cytokine antagonists. C1 Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. RP Ferrara, JLM (reprint author), Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA. NR 37 TC 40 Z9 48 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD JUN PY 1998 VL 21 SU 3 BP S13 EP S15 PG 3 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 105GJ UT WOS:000075064100005 PM 9712485 ER PT J AU Kohn, SE Melvold, J Shipper, V AF Kohn, SE Melvold, J Shipper, V TI The role of feature geometry in accounting for patterns of consonant substitutions in fluent aphasis speech SO BRAIN AND COGNITION LA English DT Article; Proceedings Paper CT TENNET VIII - Theoretical and Experimental Neuropsychology Conference CY JUN 16-18, 1997 CL MONTREAL, CANADA C1 Moss Rehabil Res Inst, Philadelphia, PA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kohn, SE (reprint author), Moss Rehabil Res Inst, Philadelphia, PA USA. NR 3 TC 1 Z9 1 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0278-2626 J9 BRAIN COGNITION JI Brain Cogn. PD JUN PY 1998 VL 37 IS 1 BP 18 EP 21 PG 4 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA ZZ523 UT WOS:000074737900010 ER PT J AU Hetherington, R Dennis, M Kennedy, D Barnes, M Drake, J AF Hetherington, R Dennis, M Kennedy, D Barnes, M Drake, J TI Congenital cerebellar dysmorphology: Motor function and MRI-based morphometric analyses SO BRAIN AND COGNITION LA English DT Article; Proceedings Paper CT TENNET VIII - Theoretical and Experimental Neuropsychology Conference CY JUN 16-18, 1997 CL MONTREAL, CANADA ID DANDY-WALKER SYNDROME; HYDROCEPHALIC CHILDREN; MALFORMATION AB We explored the relation between motor function and congenital cerebellar dysmorphologies in two 14-year-old girls with cerebellar dysmorphology as part of a history of shunted hydrocephalus. MRI-based morphometric analyses demonstrated reduced cerebellar volume in both subjects. The cerebellum of the subject with an Arnold-Chiari II malformation was 19% smaller than that of the subject with the Dandy Walker Syndrome; however, the Dandy Walker subject's medial cerebellum was 26% smaller than that of the Arnold-Chiari II subject. Functional deficits conformed with morphometric findings. The Arnold-Chiari II subject showed signs of bilateral cerebellar dysfunction (e.g., limb dysmetria, dysdiadokokinesia) as well as bimanual and visuomotor impairments, while the Dandy-Walker subject showed only subtle signs of medial cerebellar dysfunction in gait and balance. C1 Univ Toronto, Hosp Sick Children, Toronto, ON, Canada. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cambridge, MA 02138 USA. RP Hetherington, R (reprint author), Univ Toronto, Hosp Sick Children, 100 Coll St, Toronto, ON, Canada. NR 20 TC 1 Z9 1 U1 1 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0278-2626 J9 BRAIN COGNITION JI Brain Cogn. PD JUN PY 1998 VL 37 IS 1 BP 34 EP 40 PG 7 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA ZZ523 UT WOS:000074737900015 ER PT J AU Buckner, RL AF Buckner, RL TI Functional changes associated with long-term memory: Distinct effects of implicit and explicit retrieval. SO BRAIN AND COGNITION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0278-2626 J9 BRAIN COGNITION JI Brain Cogn. PD JUN PY 1998 VL 37 IS 1 BP 142 EP 142 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA ZZ523 UT WOS:000074737900065 ER PT J AU Figlewicz, DP Patterson, TA Johnson, LB Zavosh, A Israel, PA Szot, P AF Figlewicz, DP Patterson, TA Johnson, LB Zavosh, A Israel, PA Szot, P TI Dopamine transporter mRNA is increased in the CNS of Zucker fatty (fa/fa) rats SO BRAIN RESEARCH BULLETIN LA English DT Article DE in situ hybridization; neurotransmitter transporters; Zucker ID BRAIN MONOAMINE METABOLISM; GENETICALLY-OBESE RATS; MESSENGER-RNA; ADIPOSE-TISSUE; INSULIN; NOREPINEPHRINE; MICRODIALYSIS; GENOTYPE; ENZYMES; NEURONS AB The obese Zucker fa/fa rat is characterized by hyperinsulinemia, obesity, and altered monoamine metabolism in the central nervous system (CNS), It has been proposed that the changes in monoamine metabolism may contribute to the metabolic pathophysiology of these animals. Because it has been reported that insulin may regulate the catecholamine reuptake transporters, which terminate monoaminergic synaptic signaling, in the present study we tested whether messenger ribonucleic acid (mRNA) levels for the noradrenergic (NE) or dopaminergic (DA) transporters were altered in obese fa/fa vs. lean Fa/Fa Zucker rats. We found significantly elevated DA transporter levels in both the ventral tegmental area/substantia nigra pars compacta (VTA/SNc) and zona incerta (ZI) of obese Zucker fa/fa rats (164 +/- 24% of control levels, p = .024; and 316 +/- 61% of control levels, p = .019, respectively), Measurement of mRNA for tyrosine hydroxylase (TH), the rate-limiting enzyme for NE and DA synthesis revealed no effect of the fa gene in either NE or DA neurons. These findings suggest that increased DA clearance, and perhaps decreased DA signaling, may occur in the obese Zucker fa/fa rat. Published 1998 Elsevier Science Inc. C1 VA Puget Sound Hlth Care Syst, Div Endocrinol & Metab, Seattle Div, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, GRECC, Seattle, WA 98108 USA. Univ Washington, Dept Psychol, Seattle, WA 98195 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Figlewicz, DP (reprint author), VA Puget Sound Hlth Care Syst, Div Endocrinol & Metab, Seattle Div, 1660 So Columbian Way, Seattle, WA 98108 USA. FU NIDDK NIH HHS [DK40963] NR 29 TC 33 Z9 34 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0361-9230 J9 BRAIN RES BULL JI Brain Res. Bull. PD JUN PY 1998 VL 46 IS 3 BP 199 EP 202 DI 10.1016/S0361-9230(98)00009-4 PG 4 WC Neurosciences SC Neurosciences & Neurology GA ZW451 UT WOS:000074412300003 PM 9667812 ER PT J AU Ortel, B Chen, N Brissette, J Dotto, GP Maytin, E Hasan, T AF Ortel, B Chen, N Brissette, J Dotto, GP Maytin, E Hasan, T TI Differentiation-specific increase in ALA-induced protoporphyrin IX accumulation in primary mouse keratinocytes SO BRITISH JOURNAL OF CANCER LA English DT Article DE photodynamic therapy; 5-aminolaevulinic acid; differentiation; keratinocyte; protoporphyrin IX ID DELTA-AMINOLEVULINIC-ACID; ADRENAL PHEOCHROMOCYTOMA CELLS; HEME PATHWAY ENZYMES; NERVE GROWTH-FACTOR; PHOTODYNAMIC THERAPY; 5-AMINOLEVULINIC ACID; ERYTHROLEUKEMIA-CELLS; ERYTHROID-DIFFERENTIATION; COPROPORPHYRINOGEN OXIDASE; ENDOGENOUS PORPHYRINS AB A treatment regimen that takes advantage of the induction of intracellular porphyrins such as protoporphyrin IX (PPIX) by exposure to exogenous 5-amino-laevulinic acid (ALA) followed by localized exposure to visible light represents a promising new approach to photodynamic therapy (PDT). Acting upon the suggestion that the effectiveness of ALA-dependent PDT may depend upon the state of cellular differentiation, we investigated the effect of terminal differentiation upon ALA-induced synthesis of and the subsequent phototoxicity attributable to PPIX in primary mouse keratinocytes. Induction of keratinocyte differentiation augmented intracellular PPIX accumulation in cells treated with ALA. These elevated PPIX levels resulted in an enhanced lethal photodynamic sensitization of differentiated cells. The differentiation-dependent increase in cellular PPIX levels resulted from several factors including: (a) increased ALA uptake, (b) enhanced PPIX production and (c) decreased PPIX export into the culture media. Simultaneously, steady-state levels of coproporphyrinogen oxidase mRNA increased but aminolaevulinic acid dehydratase mRNA levels remained unchanged. From experiments using 12-o-tetradecanoylphorbol-13-acetate, transforming growth factor beta 1 and calcimycin we demonstrated that the increase in PPIX concentration in terminally differentiating keratinocytes is calcium- and differentiation specific. Stimulation of the haem synthetic capacity is seen in primary keratinocytes, but not in PAM 212 cells that fail to undergo differentiation. Interestingly, increased PPIX formation and elevated coproporphyrinogen oxidase mRNA levels are not limited to differentiating keratinocytes; these were also elevated in the C2C12 myoblast and the PC12 adrenal cell lines upon induction of differentiation. Overall, the therapeutic implications of these results are that the effectiveness of ALA-dependent PDT depends on the differentiation status of the cell and that this may enable selective targeting of several tissue types. C1 Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol,Cutaneous Biol Res Ctr, Boston, MA USA. RP Hasan, T (reprint author), Massachusetts Gen Hosp, Wellman Labs Photomed, 55 Fruit St, Boston, MA 02114 USA. NR 46 TC 74 Z9 76 U1 0 U2 4 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD JUN PY 1998 VL 77 IS 11 BP 1744 EP 1751 DI 10.1038/bjc.1998.292 PG 8 WC Oncology SC Oncology GA 194RP UT WOS:000080207600005 PM 9667642 ER PT J AU Ma, JY Endres, M Moskowitz, MA AF Ma, JY Endres, M Moskowitz, MA TI Synergistic effects of caspase inhibitors and MK-801 in brain injury after transient focal cerebral ischaemia in mice SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE MK-801; NMDA receptor; ICE-family caspases; focal cerebral ischaemia; apoptosis ID METHYL-D-ASPARTATE; DNA FRAGMENTATION; CELL-DEATH; ARTERY OCCLUSION; ANTAGONIST DEXTRORPHAN; INFARCT VOLUME; BLOOD-FLOW; ISCHEMIA; RAT; APOPTOSIS AB 1 Excitotoxic and apoptotic mechanisms have been implicated in the pathophysiology of cerebral ischaemia. Both MK-801, an NMDA receptor antagonist, or peptide inhibitors of the caspase family (z-VAD.FMK and z-DEVD.FMK), protect mouse brain from ischaemic cell damage. In this study, we examined whether these drugs which act via distinct mechanisms, afford even greater neuroprotection when given in combination following 2 h MCA occlusion (filament model) and 18 h reperfusion. 2 Given alone as pretreatment, MK-801 (1, 3 and 5 mg kg(-1), but not 0.3 mg kg(-1), i.p.) decreased infarct size by 34-75%. When injected 1 h after occlusion and before reperfusion, 3 mg kg(-1) reduced injury but not when administered 1 h after reperfusion. 3 Pretreatment with a subthreshold dose of MK-801 (0.3 mg kg(-1)) plus a subthreshold dose of z-VAD.FMK (27 ng) or z-DEVD (80 ng) significantly decreased infarct size by 29 and 309/0, respectively, and enhanced neurological function. 4 Administering a subthreshold dose of z-VAD.FMK (27 ng) or z-DEVD.FMK (80 ng) as pretreatment extended the time window for MK-801 (3 mg kg(-1)) by 2 h from 1 h before reperfusion to at least 1 h after reperfusion. 5 Pretreating with a subthreshold dose of MK-801 (0.3 mg kg(-1)) extended the time window for z-DEVD.FMK (480 ng) from 1 h after reperfusion to at least 3 h after reperfusion. 6 We conclude that caspase inhibitors which putatively block apoptotic cell death and inhibit cytokine production and the NMDA antagonist MK-801 act synergistically and prolong their respective therapeutic windows in cerebral ischaemia. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Neurol Serv, Stroke & Neurovasc Regulat Lab, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med,Neurosurg Serv, Stroke & Neurovasc Regulat Lab, Charlestown, MA 02129 USA. RP Moskowitz, MA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Neurol Serv, Stroke & Neurovasc Regulat Lab, 149 13th St,Room 6403, Charlestown, MA 02129 USA. RI Moskowitz, Michael/D-9916-2011 FU NINDS NIH HHS [NS10828] NR 48 TC 119 Z9 127 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD JUN PY 1998 VL 124 IS 4 BP 756 EP 762 DI 10.1038/sj.bjp.0701871 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZU405 UT WOS:000074193800018 PM 9690868 ER PT J AU Jones, RE Blackburn, WD AF Jones, RE Blackburn, WD TI Joint replacement surgery: Preoperative management SO BULLETIN ON THE RHEUMATIC DISEASES LA English DT Article ID BLOOD-LOSS; RISK C1 Birmingham VA Med Ctr, Birmingham, AL 35233 USA. Univ Alabama, Birmingham, AL USA. RP Jones, RE (reprint author), Birmingham VA Med Ctr, Birmingham, AL 35233 USA. NR 14 TC 1 Z9 1 U1 0 U2 0 PU ARTHRITIS FOUNDATION PI ATLANTA PA 1314 SPRING STREET NW, ATLANTA, GA 30309 USA SN 0007-5248 J9 B RHEUM DIS JI Bull. Rheum. Dis. PD JUN PY 1998 VL 47 IS 4 BP 5 EP COVER4 PG 4 WC Rheumatology SC Rheumatology GA ZV648 UT WOS:000074326900003 PM 9624823 ER PT J AU Wu, Y Ackerman, JL Chesler, DA Li, J Neer, RM Wang, J Glimcher, MJ AF Wu, Y Ackerman, JL Chesler, DA Li, J Neer, RM Wang, J Glimcher, MJ TI Evaluation of bone mineral density using three-dimensional solid state phosphorus-31 NMR projection imaging SO CALCIFIED TISSUE INTERNATIONAL LA English DT Article DE densitometry; bone mineral content; hydroxyapatite; MRI ID NUCLEAR-MAGNETIC-RESONANCE; X-RAY ABSORPTIOMETRY; SYNTHETIC CALCIUM PHOSPHATES; COMPUTED-TOMOGRAPHY; TRABECULAR BONE; IN-VIVO; P-31; SPECTROSCOPY; ACCURACY; INVIVO AB A solid state magnetic resonance imaging technique is used to measure true three-dimensional mineral density of synthetic hydroxyapatite phantoms and specimens of bone ex vivo. The phosphorus-31 free induction decay at 2.0 T magnetic field strength is sampled following application of a short, hard radiofrequency excitation pulse in the presence of a fixed amplitude magnetic field gradient. Multiple gradient directions covering the unit sphere are used in an efficient spherical polar to Cartesian interpolation and Fourier transform projection reconstruction scheme to image the three-dimensional distribution of phosphorus within the specimen. Using 3-6 Gauss/cm magnetic field gradients, a spatial resolution of 0.2 cm over a field of view of 10 cm is achieved in an imaging time of 20-35 minutes. Comparison of solid state magnetic resonance imaging with dual energy X-ray absorptiometry (DXA), gravimetric analysis, and chemical analysis of calcium and phosphorus demonstrates good quantitative accuracy. Direct measurement of bone mineral by solid state magnetic resonance opens up the possibility of imaging variations in mineral composition as well as density. Advantages of the solid state magnetic resonance technique include avoidance of ionizing radiation; direct measurement of a constituent of the mineral without reliance on assumptions about, or models of, tissue composition; the absence of shielding, beam hardening, or multiple scattering artifacts; and its three-dimensional character. Disadvantages include longer measurement times and lower spatial resolution than DXA and computed tomography, and the inability to scan large areas of the body in a single measurement, although spatial resolution is sufficient to resolve cortical from trabecular bone for the purpose of measuring bone mineral density. C1 Massachusetts Gen Hosp, Dept Radiol, Biomat Lab, NMR Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Childrens Hosp, Dept Orthopaed Surg, Lab Study Skeletal Disorders & Rehabil, Boston, MA 02115 USA. Harvard Univ, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Ackerman, JL (reprint author), Massachusetts Gen Hosp, Dept Radiol, Biomat Lab, NMR Ctr, Room 2301,149 13th St, Charlestown, MA 02129 USA. RI Ackerman, Jerome/E-2646-2015 OI Ackerman, Jerome/0000-0001-5176-7496 FU NCRR NIH HHS [RR10099]; NIAMS NIH HHS [AR34081, AR42258] NR 49 TC 41 Z9 42 U1 0 U2 5 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0171-967X J9 CALCIFIED TISSUE INT JI Calcif. Tissue Int. PD JUN PY 1998 VL 62 IS 6 BP 512 EP 518 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZN165 UT WOS:000073616400008 PM 9576979 ER PT J AU Vogelzang, NJ Crawford, ED Zietman, A AF Vogelzang, NJ Crawford, ED Zietman, A CA Consensus Panel TI Current clinical trial design issues in hormone-refractory prostate carcinoma SO CANCER LA English DT Editorial Material ID SOUTHWEST-ONCOLOGY-GROUP; PALLIATIVE END-POINTS; LOW-DOSE PREDNISONE; PHASE-II EVALUATION; FLUTAMIDE WITHDRAWAL; RANDOMIZED TRIAL; BONE METASTASES; CANCER; ESTRAMUSTINE; CHEMOTHERAPY C1 Univ Chicago, Pritzker Sch Med, Dept Med & Surg Urol, Hematol Oncol Sect, Chicago, IL 60637 USA. Univ Chicago, Pritzker Sch Med, Prostate Canc Res Program, Chicago, IL 60637 USA. Univ Chicago, Pritzker Sch Med, Prostate Comm Canc, Chicago, IL 60637 USA. Univ Chicago, Pritzker Sch Med, Leukemia Grp B, Chicago, IL 60637 USA. Univ Colorado, Hlth Sci Ctr, Div Urol, Denver, CO 80262 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Vogelzang, NJ (reprint author), Univ Chicago, Pritzker Sch Med, Dept Med & Surg Urol, Hematol Oncol Sect, 5841 S Maryland Ave,MC 2115, Chicago, IL 60637 USA. NR 83 TC 16 Z9 21 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD JUN 1 PY 1998 VL 82 IS 11 BP 2093 EP 2101 PG 9 WC Oncology SC Oncology GA ZP472 UT WOS:000073756900003 PM 9610688 ER PT J AU Forastiere, AA Shank, D Neuberg, D Taylor, SG DeConti, RC Adams, G AF Forastiere, AA Shank, D Neuberg, D Taylor, SG DeConti, RC Adams, G TI Final report of a phase II evaluation of paclitaxel in patients with advanced squamous cell carcinoma of the head and neck - An Eastern Cooperative Oncology Group Trial (PA390) SO CANCER LA English DT Article DE head and neck carcinoma; paclitaxel; chemotherapy; response ID CISPLATIN; TAXOL; FLUOROURACIL; METHOTREXATE AB BACKGROUND. A number of single agents have been tested in patients with carcinoma of the head and neck receiving palliative treatment. In general, 15-30% of patients achieve a partial response lasting 3-4 months. Treatment has not been shown to alter survival rates. It is clear that new drugs with potentially greater activity need to be identified. For this purpose, the Eastern Cooperative Oncology Group conducted a Phase LI evaluation of paclitaxel. METHODS. Patients with recurrent, metastatic, or locally advanced, incurable squamous cell carcinoma of the head and neck were eligible. The dose and schedule tested was the maximum tolerable dose of 250 mg/m(2) determined from Phase I trials using a 24-hour infusion schedule and granulocyte-colony stimulating factor support. Courses were given at 3-week intervals until progression of disease was documented. Dose modifications were specified for hematologic toxicity and for neurotoxicity. RESULTS. Thirty-four patients were registered on study and 30 were eligible. Severe or life-threatening granulocytopenia was the most frequent toxicity observed, occurring in 91% of patients. Prior to response evaluation, one patient died of sepsis and one died of a myocardial infarct. Response was observed in 40% of eligible patients (4 complete and 8 partial responses). The median duration of response was 4.5 months (range, 2-20 months), with a median survival of 9.2 months and a 1-year survival rate of 33%. CONCLUSIONS. These results indicate that paclitaxel is an active agent for the treatment of squamous cell carcinoma of the head and neck. Studies evaluating alternative infusion schedules and combination regimens currently are underway. (C) 1998 American Cancer Society. C1 Johns Hopkins Oncol Ctr, Baltimore, MD 21287 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. Albany Med Coll, Albany, NY 12208 USA. Univ Minnesota, Minneapolis, MN USA. RP Forastiere, AA (reprint author), Johns Hopkins Oncol Ctr, 600 N Wolfe St,Room 128, Baltimore, MD 21287 USA. FU NCI NIH HHS [CA16116, CA23318, CA25988] NR 9 TC 146 Z9 150 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD JUN 1 PY 1998 VL 82 IS 11 BP 2270 EP 2274 DI 10.1002/(SICI)1097-0142(19980601)82:11<2270::AID-CNCR24>3.0.CO;2-Q PG 5 WC Oncology SC Oncology GA ZP472 UT WOS:000073756900024 PM 9610709 ER PT J AU Ruescher, TJ Sodeifi, A Scrivani, SJ Kaban, LB Sonis, ST AF Ruescher, TJ Sodeifi, A Scrivani, SJ Kaban, LB Sonis, ST TI The impact of mucositis on alpha-hemolytic streptococcal infection in patients undergoing autologous bone marrow transplantation for hematologic malignancies SO CANCER LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Dental-Association CY OCT, 1997 CL WASHINGTON, D.C. SP Amer Dental Assoc DE mucositis; bone marrow transplantation; streptococcal; sepsis; bacteremia; finance ID VIRIDANS STREPTOCOCCI; NEUTROPENIC PATIENTS; RISK-FACTORS; SEPTICEMIA; BACTEREMIA; PREVENTION; CANCER; COMPLICATIONS; LEUKEMIA; EFFICACY AB BACKGROUND, Antibacterial prophylaxis with quinolone antibiotics has resulted in an increase in streptococcal infections among bone marrow transplantation (BMT) recipients with myelosuppression. Oral ulceration (mucositis), which frequently occurs as a consequence of chemotherapy, has been implicated as a significant portal of entry for streptococci. The objectives of this study were to confirm the correlation between mucositis and streptococcal bacteremia, determine the risk associated with this correlation, and evaluate the impact of mucositis and streptococcal bacteremia on hospital course and costs associated with autologous BMT. METHODS. This was a retrospective, case-control study in which the charts of autologous BMT recipients treated for hematologic malignancies between 1990 and 1996 were reviewed. Twenty-four patients were identified who met the criteria of autologous BMT; their blood cultures confirmed (x2) alpha-hemolytic streptococcal sepsis. A control group of 45 without positive cultures was matched by gender, age, diagnosis, and treatment to the study group. RESULTS. The results confirm that ulcerative mucositis is a significant risk factor for alpha-hemolytic streptococcal bacteremia among autologous BMT patients. Of the 24 patients with bacteremia, 15 of 24 (62%) had ulcerative mucositis, compared with 16 of 45 (36%) of patients in the control population (P < 0.05). Patients with ulcerative mucositis were found to be three times as likely to develop alpha-hemolytic streptococcal bacteremia as those without ulcerative mucositis (odds ratio = 3.02). Both independently and as a cofactor associated with bacteremia, mucositis adversely affected the length of hospital stay (LOS). Of all the patients studied, those with oral ulcerations had a LOS of 34 days, compared with 29 days for patients without Oral ulcerations (P < 0.05). Of patients in the study group, those with oral ulcerations stayed in the hospital 6 days longer than patients without oral ulcerations (40 days vs. 34 days, P < 0.05). CONCLUSIONS. Oral ulcerative mucositis is a significant, common, and important risk factor for cu-hemolytic streptococcal bacteremia in BMT recipients with myelosuppression; it results in longer hospital stay and increased costs. (C) 1998 American Cancer Society. C1 Brigham & Womens Hosp, Dept Oral Med, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Dent, Boston, MA 02115 USA. RP Sonis, ST (reprint author), Brigham & Womens Hosp, Dept Oral Med, 75 Francis St, Boston, MA 02115 USA. NR 17 TC 120 Z9 125 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD JUN 1 PY 1998 VL 82 IS 11 BP 2275 EP 2281 DI 10.1002/(SICI)1097-0142(19980601)82:11<2275::AID-CNCR25>3.3.CO;2-8 PG 7 WC Oncology SC Oncology GA ZP472 UT WOS:000073756900025 PM 9610710 ER PT J AU Teicher, BA Wong, JS Takeuchi, H Gravelin, LM Ara, G Buxton, D AF Teicher, BA Wong, JS Takeuchi, H Gravelin, LM Ara, G Buxton, D TI Allosteric effectors of hemoglobin as modulators of chemotherapy and radiation therapy in vitro and in vivo SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE radiosensitization; allosteric effectors; chemosensitization; combined modality therapy ID COENZYME-A REDUCTASE; MOUSE MAMMARY-TUMOR; 3-HYDROXY-3-METHYLGLUTARYL-COENZYME-A REDUCTASE; COMPETITIVE INHIBITOR; OXYGEN-AFFINITY; INVIVO; INVITRO; RATS; RADIOSENSITIVITY; DERIVATIVES AB Introduction: A series of molecules designed to be allosteric effecters of hemoglobin were examined for their potential as radiation sensitizers in vitro and in vivo and for their potential as chemosensitizers in vivo as well as for their antimetastatic effect. Results: At a concentration of 100 mu M for 1 h prior to, during and for 1.5 h after radiation exposure, the allosteric effecters decreased the shoulder of the radiation survival curve of normally oxygenated EMT-6 cells and increased the slope of the radiation survival curves of hypoxic EMT-6 cells resulting in dose-modifying factors of 1.8 to 2.1. In vivo the allosteric effecters had antitumor activity against the Lewis lung carcinoma and produced primarily additive tumor growth delay when administered along with fractionated radiation therapy. When administered on days 4 through 18 after tumor implantation, the allosteric effectors. especially JP-7, RSR-13 and RSR-4, were highly effective antimetastatic agents in animals bearing Lewis lung carcinoma. In cell culture, simultaneous exposure to the allosteric effectors (at 100 mu M) effectively sensitized EMT-6 cells to the effects of 4-hydroperoxycylophosphamide, thiotepa and carboplatin. The allosteric effectors were not very cytotoxic toward EMT-6 tumor cells from tumors treated in vivo with single doses of each molecule nor were these agents very cytotoxic toward bone marrow CFU-GM taken from the same animals. Conclusions: It is likely that the allosteric effectors have a molecular target in addition to hemoglobin. Other possible targets include hydroxymethyl-glutaryl-COA reductase or microsomal cytochrome b(5). C1 Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Joint Ctr Radiat Therapy, Boston, MA 02115 USA. RP Teicher, BA (reprint author), Lilly Corp Ctr, Lilly Res Labs, DC 0540, Indianapolis, IN 46285 USA. EM teicher_beverly_a@lilly.com NR 39 TC 13 Z9 13 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD JUN PY 1998 VL 42 IS 1 BP 24 EP 30 DI 10.1007/s002800050780 PG 7 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA ZR269 UT WOS:000073957200004 PM 9619754 ER PT J AU Lu, KH Bell, DA Welch, WR Berkowitz, BS Mok, SC AF Lu, KH Bell, DA Welch, WR Berkowitz, BS Mok, SC TI Evidence for the multifocal origin of bilateral and advanced human serous borderline ovarian tumors SO CANCER RESEARCH LA English DT Article ID TERM FOLLOW-UP; CLONAL ORIGIN; HISTOLOGIC FEATURES; PERITONEAL IMPLANTS; EPITHELIAL TUMORS; UNIFOCAL ORIGIN; CARCINOMA; MALIGNANCY; PROGNOSIS; BEHAVIOR AB Borderline ovarian turners (BOTs), or ovarian tumors of low malignant potential, represent a distinct category of epithelial ovarian neoplasms that have a clinically more favorable outcome than invasive epithelial ovarian cancer. Histologically, BOTs and invasive ovarian carcinomas both show cellular proliferation and pleomorphism, but unlike invasive ovarian carcinomas, BOTs lack stromal invasion. Although serous BOTS are frequently confined to a single ovary at the time of diagnosis, bilateral or extra-ovarian spread occurs in 30-40% of cases, The purpose of this study is to determine whether bilateral or extraovarian serous borderline lesions are metastatic sites from the original tumor, or represent separate primary tumors, DNA specimens from multiple tumor sites and normal tissue controls were obtained in eight women with bilateral or extra-ovarian serous borderline turners. The pattern of loss of heterozygosity at the androgen receptor locus on the X chromosome was evaluated in the multiple tumor sites. Tn addition, the pattern of X-chromosome inactivation was determined using HpaII restriction endonuclease digestion, followed by PCR amplification of the androgen receptor locus, Multifocality, was determined when alternate patterns of X-chromosome inactivation occurred, In two of the eight patients, the left and right ovarian tumor sites had different androgen receptor alleles inactivated, indicating that the bilateral tumors derived independently. In a third patient, the TF, inactivation pattern in the left ovarian tumor differed from the two peritoneal implants, suggesting that the implants were separate primary tumors, and not metastatic, from the left ovarian tumor, The remaining five patients had the same pattern of loss of heterozygosity and X inactivation in the tumor sites studied, These results suggest that bilateral and advanced stage serous BOTs may be multifocal in origin, This result is in contrast to invasive epithelial ovarian cancer, which has been shown to be unifocal in origin. C1 Harvard Univ, Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Sch Med,Lab Gynecol Oncol,Div Gynecol Oncol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Mok, SC (reprint author), Harvard Univ, Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Sch Med,Lab Gynecol Oncol,Div Gynecol Oncol, 221 Longwood Ave,RF 472, Boston, MA 02115 USA. FU NCI NIH HHS [R01CA69453, R01CA63381, R01CA69291] NR 28 TC 61 Z9 61 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 1998 VL 58 IS 11 BP 2328 EP 2330 PG 3 WC Oncology SC Oncology GA ZR703 UT WOS:000074005300012 PM 9622067 ER PT J AU Jin, SF Inoue, S Weaver, DT AF Jin, SF Inoue, S Weaver, DT TI Differential etoposide sensitivity of cells deficient in the Ku and DNA-PKcs components of the DNA-dependent protein kinase SO CARCINOGENESIS LA English DT Article ID STRAND BREAK REPAIR; SEVERE COMBINED IMMUNODEFICIENCY; COMBINED IMMUNE-DEFICIENCY; V(D)J RECOMBINATION; TOPOISOMERASE-II; SACCHAROMYCES-CEREVISIAE; CATALYTIC SUBUNIT; ADENOCARCINOMA CELLS; IONIZING-RADIATION; MAMMALIAN-CELLS AB Etoposides block cell division by interfering with the action of topoisomerase II, leaving enzyme-DNA double-strand breaks. We found that certain components of the trimeric DNA-dependent protein kinase influence cell survival following etoposide damage. Interestingly, either Ku70- or Ku80-deficient cell lines, but not mutant cell lines of the DNA-PK catalytic sub-unit (DNA-PKcs), were found to be hypersensitive to the effects of etoposide VP16, Ku70- and Ku80-deficient cells can be complemented to an etoposide resistant phenotype by introducing wildtype Ku70 or Ku80 cDNAs, Mutational analysis of introduced Ku70 cDNAs into murine embryonic stem cells deleted for Ku70 (-/-) showed that mutants where heterodimerization and DNA binding functions of Ku were disrupted, also blocked the restoration of etoposide resistance. In contrast with the differential etoposide sensitivity of DNA-PK mutants, both Ku- and DNA-PKcs-deficient cell lines showed G(2) ionizing radiation-induced delays, a cell cycle phase where topoisomerase II function is critical. Thus, the topoisomerase II cleaved complexes may be an example of DNA lesions requiring the Ku heterodimer, but not DNA-PK for DNA repair. C1 Dana Farber Canc Inst, Div Tumor Immunol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Cambridge, MA 02138 USA. RP Weaver, DT (reprint author), Dana Farber Canc Inst, Div Tumor Immunol, 44 Binney St, Boston, MA 02115 USA. NR 67 TC 40 Z9 42 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUN PY 1998 VL 19 IS 6 BP 965 EP 971 DI 10.1093/carcin/19.6.965 PG 7 WC Oncology SC Oncology GA ZV977 UT WOS:000074361300002 PM 9667732 ER PT J AU Rines, RD van Orsouw, NJ Sigalas, I Li, FP Eng, C Vijg, J AF Rines, RD van Orsouw, NJ Sigalas, I Li, FP Eng, C Vijg, J TI Comprehensive mutational scanning of the p53 coding region by two-dimensional gene scanning SO CARCINOGENESIS LA English DT Article ID GRADIENT GEL-ELECTROPHORESIS; STRAND CONFORMATION POLYMORPHISM; POLYMERASE CHAIN-REACTION; SINGLE-BASE CHANGES; BREAST-CANCER; GC-CLAMP; DNA; AMPLIFICATION; PCR AB A comprehensive mutational scanning test for the p53 coding region based on multiplex PCR and two-dimensional DNA electrophoresis was designed and evaluated. In a 2-step multiplex PCR, the p53 coding region (exons 2-11) was amplified as a single 8646-bp fragment by long-distance PCR in step one. This fragment served as a template for the subsequent co-amplification of the individual exons in two multiplex groups in step two. The multiplex products were then separated, first on the basis of size in non-denaturant polyacrylamide gels and then on the basis of sequence by denaturing gradient gel electrophoresis (DGGE), Primers for optimal PCR, melting behavior and 2-D gel distribution were designed using a recently developed computer program. The resulting two-dimensional gene scanning (TDGS) test was evaluated by screening, in a blinded fashion, 29 coded DNA samples from Li-Fraumeni syndrome patients with previously identified germline mutations, All mutations were correctly detected. This assay provides an accurate, cost-effective and nonradioactive method for simultaneous mutational scanning of all p53 coding exons. C1 Harvard Univ, Inst Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Charles A Dana Human Canc Genet Unit, Translat Res Lab, Boston, MA 02115 USA. Dana Farber Canc Inst, Charles A Dana Human Canc Genet Unit, Program Populat Sci, Boston, MA 02115 USA. RP Vijg, J (reprint author), Harvard Univ, Inst Med, Beth Israel Deaconess Med Ctr, 77 Ave Louis Pasteur,Suite 921, Boston, MA 02115 USA. EM jvijg@bidmc.harvard.edu OI Eng, Charis/0000-0002-3693-5145 FU NIA NIH HHS [1P30AG13314-02] NR 24 TC 25 Z9 25 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUN PY 1998 VL 19 IS 6 BP 979 EP 984 DI 10.1093/carcin/19.6.979 PG 6 WC Oncology SC Oncology GA ZV977 UT WOS:000074361300004 PM 9667734 ER PT J AU Peters, A Morrison, JH Rosene, DL Hyman, BT AF Peters, A Morrison, JH Rosene, DL Hyman, BT TI Are neurons lost from the primate cerebral cortex during normal aging? SO CEREBRAL CORTEX LA English DT Article ID PRIMARY VISUAL-CORTEX; NERVE-CELL LOSS; RHESUS-MONKEY; ALZHEIMERS-DISEASE; STEREOLOGICAL METHODS; PATHOLOGICAL RESEARCH; HUMAN HIPPOCAMPUS; STRIATE CORTEX; TOTAL NUMBER; AGE C1 Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA. CUNY, Mt Sinai Med Ctr, Arthur M Fishberg Res Ctr Neurobiol, Neurobiol Aging Labs, New York, NY 10029 USA. Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. Emory Univ, Yerkes Reg Primate Res Ctr, Atlanta, GA 30322 USA. RP Peters, A (reprint author), Boston Univ, Sch Med, Dept Anat & Neurobiol, 80 E Concord St, Boston, MA 02118 USA. RI Morrison, John/F-9229-2012; Rosene, Douglas/G-1973-2015 FU NIA NIH HHS [2PO1-AG00001, AG 06647, AG 08487] NR 61 TC 157 Z9 168 U1 2 U2 9 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD JUN PY 1998 VL 8 IS 4 BP 295 EP 300 DI 10.1093/cercor/8.4.295 PG 6 WC Neurosciences SC Neurosciences & Neurology GA ZQ260 UT WOS:000073839500001 PM 9651126 ER PT J AU Kennedy, DN Lange, N Makris, N Bates, J Meyer, J Caviness, VS AF Kennedy, DN Lange, N Makris, N Bates, J Meyer, J Caviness, VS TI Gyri of the human neocortex: An MRI-based analysis of volume and variance SO CEREBRAL CORTEX LA English DT Article ID HUMAN VISUAL-CORTEX; POSITRON EMISSION TOMOGRAPHY; ADULT SQUIRREL-MONKEYS; HUMAN CEREBRAL-CORTEX; PRIMARY MOTOR CORTEX; MONOZYGOTIC TWINS; HUMAN BRAIN; INDIVIDUAL VARIABILITY; MAGNETIC STIMULATION; CORTICAL SURFACE AB This magnetic resonance imaging (MRI)-based morphometric analysis of cortical topography in the human brain is based upon the segmentation and parcellation of volumetric T1-weighted MRI data for a set of 20 young adult brains including 10 males and 10 females. For the most part, each parcellation unit (PU) of the neocortex corresponds to a single or a portion of a single gyrus. The volumes of each PU were computed for each brain. Subsets of PUs were also grouped so as to represent the neocortex for the frontal, temporal, parietal and occipital lobes. The coefficient of variation of the mean volume of total neocortex and that of the neocortex assigned to individual lobes cluster around 10%. whereas that of neocortex assigned to the individual gyri (PU) is more than twice that value. Approximately 80% of the total variance in gyral volume arises from determinants interactive for individual and specific gyri, while only similar to 10% of the total Variance appears to be a reflection of uniform scaling to total neocortical volume. Sexual dimorphism contributes a pervasive though relatively small component of this variance. These results have implications for the study of structure-function correlation, and the proper statistical methods of handling volumetric data in morphometric studies. In addition, the nature of the covariance structure of the data will lead to future hypotheses regarding the relationships between the various potential genetic and epigenetic gyral influencing factors. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, McLean Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Kennedy, DN (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RI Kennedy, David/H-3627-2012 FU NIDA NIH HHS [DA09467]; NINDS NIH HHS [NS27950, NS34189] NR 88 TC 184 Z9 184 U1 0 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD JUN PY 1998 VL 8 IS 4 BP 372 EP 384 DI 10.1093/cercor/8.4.372 PG 13 WC Neurosciences SC Neurosciences & Neurology GA ZQ260 UT WOS:000073839500007 PM 9651132 ER PT J AU Kirmse, M Hess, D Fujino, Y Kacmarek, RM Hurford, WE AF Kirmse, M Hess, D Fujino, Y Kacmarek, RM Hurford, WE TI Delivery of inhaled nitric oxide using the ohmeda INOvent delivery system SO CHEST LA English DT Article DE critical care; inhaled nitric oxide; mechanical ventilation; nitrogen dioxide ID NITROGEN-DIOXIDE PRODUCTION; VENTILATION AB Objectives: We evaluated the Ohmeda INOvent Nitric Oxide Delivery System, which uses an inspiratory flow sensor to inject a synchronized and proportional nitric oxide (NO) flow into the mechanical ventilator circuit, This system should deliver a constant NO concentration independent of ventilator mode, minute ventilation, fraction of inspired oxygen, or ventilator brand, It should also minimize nitrogen dioxide (NO2) formation. Methods: NO delivery by the INOvent and a premixing NO delivery system were compared using two ventilators (Puritan-Bennett 7200 and Servo 900C). NO concentration was measured within the trachea of an attached lung model using a fast-response chemiluminescence NO analyzer, NO concentration was also measured in the inspiratory limb using the electrochemical analyzer of the INOvent. For three NO concentrations (2, 5, and 20 ppm), the ventilators were set for constant flow volume control ventilation, pressure control ventilation, and spontaneous breathing with pressure support ventilation or synchronized intermittent mandatory ventilation, Different tidal volumes (300, 500, 750, and 1,000 mL) and inspiratory times (1 and 2 s) were evaluated, NO2 formation for both ventilators and delivery systems were evaluated at 20 ppm and 95% O-2. Results: Regardless of ventilatory pattern, both systems delivered a constant NO concentration, The error between the target and the delivered NO dose for the INOvent was -1.3+/-3.6% with the Puritan-Bennett 7200 and -3.9+/-4.3% with the Servo 900C, For the premixing system, the error was -5.5+/-4.8% with the Puritan-Bennett 7200 and -6.7+/-6.2% with the Servo 900C, NO2 concentrations were 0.5+/-0.1 ppm during NO delivery by the INOvent, 5.8+/-1.6 ppm when NO was premixed with air, 0.3+/-0.1 ppm when NO was premixed with N-2. Conclusion: The INOvent provides a constant NO concentration independent of the ventilatory pattern, and NO2 formation is minimal. C1 Massachusetts Gen Hosp, Resp Care Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Hess, D (reprint author), Massachusetts Gen Hosp, Resp Care Lab, Ellison 401, Boston, MA 02114 USA. RI Hurford, William/G-6386-2013 OI Hurford, William/0000-0003-1201-0313 NR 21 TC 23 Z9 24 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD JUN PY 1998 VL 113 IS 6 BP 1650 EP 1657 DI 10.1378/chest.113.6.1650 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA ZT762 UT WOS:000074123100041 PM 9631807 ER PT J AU Elias, AD Wheeler, C Ayash, LJ Schwartz, G Ibrahim, J Mills, L McCauley, M Coleman, N Warren, D Schnipper, L Antman, KH Teicher, BA Frei, E AF Elias, AD Wheeler, C Ayash, LJ Schwartz, G Ibrahim, J Mills, L McCauley, M Coleman, N Warren, D Schnipper, L Antman, KH Teicher, BA Frei, E TI Dose escalation of the hypoxic cell sensitizer etanidazole combined with ifosfamide, carboplatin, etoposide, and autologous hematopoietic stem cell support SO CLINICAL CANCER RESEARCH LA English DT Article ID PHASE-I TRIAL; FLUOSOL-DA CARBOGEN; BONE-MARROW SUPPORT; RADIOSENSITIZER SR-2508; ANTITUMOR-ACTIVITY; RADIATION-THERAPY; SR 2508; MISONIDAZOLE; CANCER; AGENTS AB Multiple mechanisms of drug resistance contribute to treatment failure. Although high-dose therapy attempts to overwhelm these defenses pharmacologically, this approach is only successful in a fraction of treated patients. Many drug resistance mechanisms are shared between malignant and normal cells, but the expression of various drug resistance mechanisms associated with hypoxia is largely confined to tumor tissue. Thus, reversal of this mechanism is likely to provide a therapeutic advantage to the host. This study was designed to define the dose-limiting toxicities and maximum tolerated dose of etanidazole when it is given concurrently with high-dose ifosfamide, carboplatin, and etoposide (ICE), with hematopoietic stem cell support. The maximum tolerated doses of high-dose ICE were administered concurrently with dose escalations of etanidazole, a hypoxic cell sensitizer. All agents were given by 96-h continuous i.v. infusion beginning on day -7, Mesna uroprotection was provided. Autologous marrow and cytokine mobilized peripheral blood progenitor cells were reinfused on day 0, Granulocyte colony-stimulating factor was administered following reinfusion until the granulocytes recovered to >1000/mu l. Fifty-five adults with advanced malignancies were enrolled in cohorts of five to nine patients. Four dose levels of etanidazole between 3 and 5.5 g/m(2)/day (12, 16, 20, and 22 g/m(2) total doses) and two doses of carboplatin (1600 and 1800 mg/m(2) total doses) were evaluated. Seven patients died of organ toxicity (13%); two each from veno-occlusive disease of liver and sepsis; and one each from sudden death, renal failure, and refractory thrombocytopenic hemorrhage, Five deaths occurred at the top dose level. One additional patient suffered a witnessed cardiorespiratory arrest from ventricular fibrillation and was resuscitated, Dose-dependent and largely reversible peripheral neuropathy was observed consisting of two syndromes: severe cramping myalgic/neuralgic pain, predominantly in stocking glove distribution, occurring between day -3 and day 0, and a sensory peripheral neuropathy with similar distribution peaking around day +60, The maximal achievable dose of etanidazole (16 g/m2 dose level) resulted in a mean serum level of 38 mu g/ml (25-55 mu g/ml). Etanidazole significantly enhanced host toxicity of high-dose ICE. Effective modulatory doses of etanidazole could not be given with acceptable toxicity using this schedule. C1 Dana Farber Canc Inst, Div Clin Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Joint Ctr Radiat Therapy, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Dartmouth Hitchcock Med Ctr, Div Hematol Oncol, Lebanon, NH 03756 USA. RP Elias, AD (reprint author), Dana Farber Canc Inst, Div Clin Oncol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA13849] NR 42 TC 6 Z9 6 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN PY 1998 VL 4 IS 6 BP 1443 EP 1449 PG 7 WC Oncology SC Oncology GA ZU654 UT WOS:000074219700011 PM 9626461 ER PT J AU Hammond, LA Eckardt, JR Ganapathi, R Burris, HA Rodriguez, GA Eckhardt, SG Rothenberg, ML Weiss, GR Kuhn, JG Hodges, S Von Hoff, DD Rowinsky, EK AF Hammond, LA Eckardt, JR Ganapathi, R Burris, HA Rodriguez, GA Eckhardt, SG Rothenberg, ML Weiss, GR Kuhn, JG Hodges, S Von Hoff, DD Rowinsky, EK TI A phase I and translational study of sequential administration of the topoisomerase I and II inhibitors topotecan and etoposide SO CLINICAL CANCER RESEARCH LA English DT Article ID DNA UNTWISTING ENZYME; ACTIVE-SITE TYROSINE; ACUTE-LEUKEMIA; CAMPTOTHECIN; MUTANTS; CELLS; EXPRESSION; POISONS; SINGLE; CANCER AB Because topoisomerase (topo) I- and topo II-targeting agents exert their principal effects on the two major classes of enzymes involved in regulating DNA topology in the cell, there has been considerable interest in evaluating combinations of these classes of agents. In preclinical studies of inhibitors of topo I and topo II in combination, drug scheduling and sequencing have been critical determinants of antitumor activity, with a greater magnitude of cytotoxicity generally occurring when treatment with the topo I inhibitor precedes treatment with the topo II-targeting agent. The underlying mechanism that has been proposed to explain this schedule dependency is compensatory up-regulation of topo II, and, therefore, enhanced cytotoxicity of topo II inhibitors in cells treated initially with topo I inhibitors. The feasibility of sequentially administering the topo I inhibitor topotecan (TPT) followed by the topo II inhibitor etoposide to patients with advanced solid malignancies was evaluated in this Phase I and translational laboratory study. Fifty patients with solid neoplasms were treated with TPT doses ranging from 0.17 to 1.05 mg/m(2)/day as a 72-h continuous (i.v.) infusion on days 1-3 followed by etoposide, 75 or 100 mg/m(2)/day as a 2-h i.v. infusion daily on days 8-10, The combined rate of severe neutropenia and thrombocytopenia was unacceptably high above the TPT (mg/m(2)/day)/etoposide (mg/m(2)/day) dose levels of 0.68/100 and 0.68/75 in minimally and heavily pretreated patients, respectively, and these dose levels are recommended for further disease-directed evaluations of TPT/etoposide on this administration schedule. Successive biopsies of accessible tumors were obtained for quantitation of topo I and II levels prior to and immediately after treatment with TPT and prior to and immediately after treatment with etoposide in seven patients. The results of these limited studies in tumors did not fully support the proposed mechanistic rationale favoring the development of this particular sequential TPT/etoposide regimen, because only two of the six patients' tumors in whom topo I was successively measured had either modest or substantial decrements in topo I levels following treatment with TPT, and the principal effect of interest, upregulation of topo II following treatment with TPT, was clearly documented in the tumors of only one of six subjects in whom successive measurements of topo I were performed. Even in view of the notable objective antitumor activity in three subjects, including a complete response in a patient with colorectal carcinoma and partial responses in one patient each with non-small cell lung and gastric carcinomas, the toxicity and ancillary laboratory results do not provide substantial evidence that sequential treatment with TPT and etoposide might be more advantageous than either TPT or etoposide administered as a single agent. C1 Canc Therapy & Res Ctr, Inst Drug Dev, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78229 USA. Audie L Murphy Mem Vet Hosp, San Antonio, TX 78229 USA. Cleveland Clin Fdn, Dept Expt Therapeut Program, Cleveland, OH 44195 USA. Brooke Army Med Ctr, Dept Med, Div Oncol, Ft Sam Houston, TX 78234 USA. RP Hammond, LA (reprint author), Canc Therapy & Res Ctr, Inst Drug Dev, 8122 Datapoint Dr,6th Floor, San Antonio, TX 78229 USA. FU NCI NIH HHS [CM-07035, T32-CA09434]; NCRR NIH HHS [RR01346] NR 51 TC 40 Z9 43 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN PY 1998 VL 4 IS 6 BP 1459 EP 1467 PG 9 WC Oncology SC Oncology GA ZU654 UT WOS:000074219700013 PM 9626463 ER PT J AU Gudrais, P AF Gudrais, P TI Advantages of the automated AIA-PACK CA-125 on the TOSOH AIA Nex IA vs. manual centocor RIA II CA-125. SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 1998 VL 44 SU 6 MA 180 BP A41 EP A41 PN 2 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA ZT249 UT WOS:000074065700183 ER PT J AU Hughes, MP Carlson, TH McLaughlin, MK Bankson, DD AF Hughes, MP Carlson, TH McLaughlin, MK Bankson, DD TI Evaluation of NaF as a preservative in homocysteine measurements. SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 1998 VL 44 SU 6 MA 605 BP A139 EP A139 PN 2 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA ZT249 UT WOS:000074065700608 ER PT J AU Letts, G Lewandrowski, K AF Letts, G Lewandrowski, K TI Evaluation and implementation of the Chiron Diagnostics 860 blood gas analyzer: process improvement and workstation consolidation in an acute care laboratory SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 1998 VL 44 SU 6 MA 481 BP A111 EP A111 PN 2 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA ZT249 UT WOS:000074065700483 ER PT J AU John, MDV Hibberd, PL Karchmer, AW Sleeper, LA Calderwood, SB AF John, MDV Hibberd, PL Karchmer, AW Sleeper, LA Calderwood, SB TI Staphylococcus aureus prosthetic valve endocarditis: Optimal management and risk factors for death SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID INFECTIVE ENDOCARDITIS; COMPLICATIONS; THERAPY; REPLACEMENT; EXPERIENCE; SURVIVAL AB The mortality rate associated with Staphylococcus aureus prosthetic valve endocarditis (PVE) remains high. To identify clinical events; associated with an increased risk of death among patients with S. aureus PVE and to evaluate the role of valve replacement surgery in reducing mortality, we conducted a retrospective cohort study of patients who met strict criteria for definite S. aureus PVE. The primary endpoint for the study was survival at 3 months from the date of diagnosis. S. aureus PVE was diagnosed in 33 patients. Of these, 14 (42%) died within 90 days of the diagnosis. Cardiac complications were detected in 22 (67%), and central nervous system (CNS) complications were detected in 11 (33%). A stepwise logistic regression multivariate model demonstrated that cardiac complications, but not CNS complications, were associated with increased mortality and that performing valve replacement surgery during antibiotic therapy was associated with decreased mortality. These associations were confirmed by using a Cox proportional hazards model with time-dependent covariates to control for survival bias. Performing valve replacement surgery during antimicrobial therapy will reduce the mortality among patients with S. aureus PVE, even those without evidence of cardiac complications. C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Massachusetts Gen Hosp, Med Serv, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA USA. New England Res Inst, Watertown, MA 02172 USA. RP Calderwood, SB (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. NR 25 TC 84 Z9 89 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUN PY 1998 VL 26 IS 6 BP 1302 EP 1309 DI 10.1086/516378 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA ZU252 UT WOS:000074177900019 PM 9636852 ER PT J AU McLoud, TC AF McLoud, TC TI CT and MR in pleural disease SO CLINICS IN CHEST MEDICINE LA English DT Article ID CHEST-WALL INVASION; ASBESTOS-RELATED DISEASES; HIGH-RESOLUTION CT; COMPUTED-TOMOGRAPHY; FIBROUS TUMORS; ROUNDED ATELECTASIS; LUNG ABSCESS; MESOTHELIOMA; EMPYEMA; DIAGNOSIS AB A number of different imaging modalities can be used in the assessment of pleural disease. Although ultrasound has been the more traditional method, CT has found increasing utility for the assessment of the empyema and loculated pleural fluid collections prior to drainage and the evaluation of benign and malignant pleural tumors. MRT has a limited but important role particularly in the evaluation of focal pleural tumors such as lipomas and in determining the extent of malignant mesothelioma prior to therapy. C1 Massachusetts Gen Hosp, Dept Radiol FND 216, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Div Thorac & Cardiac Radiol, Boston, MA 02114 USA. RP McLoud, TC (reprint author), Massachusetts Gen Hosp, Dept Radiol FND 216, 32 Fruit St, Boston, MA 02114 USA. NR 60 TC 27 Z9 31 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-5231 J9 CLIN CHEST MED JI Clin. Chest Med. PD JUN PY 1998 VL 19 IS 2 BP 261 EP + DI 10.1016/S0272-5231(05)70076-9 PG 18 WC Respiratory System SC Respiratory System GA ZX575 UT WOS:000074531900004 PM 9646980 ER PT J AU Heathcote, GM Stodder, ALW Buckley, HR Hanson, DB Douglas, MT Underwood, JH Taisipic, TF Diego, VP AF Heathcote, GM Stodder, ALW Buckley, HR Hanson, DB Douglas, MT Underwood, JH Taisipic, TF Diego, VP TI On treponemal disease in the Western Pacific: Corrections and critique SO CURRENT ANTHROPOLOGY LA English DT Editorial Material ID NEW-WORLD; YAWS; SYPHILIS; MANIFESTATIONS; MICRONESIA; ANTIQUITY; ISLANDS; ORIGIN C1 Univ Guam, Anthropol Resource & Res Ctr, UOG Stn, Mangilao, GU 96923 USA. Field Museum Nat Hist, Chicago, IL 60605 USA. Univ Otago, Dept Anat & Struct Biol, Dunedin, New Zealand. Forsyth Dent Ctr, Boston, MA 02115 USA. Univ Arizona, Dept Anthropol, Tucson, AZ 85721 USA. Univ Guam, Marine Lab, Mangilao, GU 96923 USA. RP Heathcote, GM (reprint author), Univ Guam, Anthropol Resource & Res Ctr, UOG Stn, Mangilao, GU 96923 USA. OI Diego, Vincent/0000-0002-0007-2085 NR 95 TC 14 Z9 17 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0011-3204 J9 CURR ANTHROPOL JI Curr. Anthropol. PD JUN PY 1998 VL 39 IS 3 BP 359 EP 368 DI 10.1086/204745 PG 10 WC Anthropology SC Anthropology GA ZN884 UT WOS:000073693200009 ER PT J AU Park, SS Girard, B Font, RL Hauw, JJ Young, LHY AF Park, SS Girard, B Font, RL Hauw, JJ Young, LHY TI Immunohistochemical localization of ganciclovir in the human retina SO CURRENT EYE RESEARCH LA English DT Article DE AIDS; cytomegalovirus; drug delivery; immunohistochemistry; retinitis; ganciclovir; retinal cellular localization ID SUSTAINED-RELEASE GANCICLOVIR; CYTOMEGALO-VIRUS RETINITIS; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; INTRAVITREAL GANCICLOVIR; THERAPY; GENTAMICIN AB Purpose. To localize ganciclovir in the retina of human eyes treated with intravenous or intravitreal ganciclovir for cytomegalovirus (CMV) retinitis. Methods. Paraffin-embedded five-micron sections of autopsy eyes were obtained from seven patients as follows: two patients with CMV retinitis treated with intravenous ganciclovir; two patients with CMV retinitis treated with an intravitreal sustained-release ganciclovir device; one patient with CMV retinitis treated with intravenous foscarnet; and two patients with AIDS without CMV retinitis who did not receive any anti-CMV therapy. The paraffin was removed from the sections, and indirect immunofluorescent staining was performed, using an antiserum to ganciclovir. Results. Bright fluorescent staining was noted in the retinal pigment epithelium (RPE) and photoreceptor outer segments of eyes treated with intravenous or intravitreal ganciclovir, but not in eyes treated with foscarnet or without CMV retinitis. In addition, patches of bright fluorescent staining of the internal limiting membrane was noted in eyes treated with intravitreal ganciclovir. Conclusions. Ganciclovir is detected in the outer retina of patients with CMV retinitis treated with intravenous or intravitreal therapy. The drug is detected also in the internal limiting membrane in eyes treated with the intravitreal sustained-release ganciclovir device. C1 Univ Texas, SW Med Ctr, Dept Ophthalmol, Dallas, TX 75235 USA. Massachusetts Eye & Ear Infirm, Retina Serv, Boston, MA 02114 USA. Hop Aulnay Bois, Dept Ophthalmol, Aulnay Sous Bois, France. Baylor Coll Med, Dept Ophthalmol, Houston, TX 77030 USA. Hop La Pitie Salpetriere, Dept Neuropathol, Paris, France. RP Park, SS (reprint author), Univ Texas, SW Med Ctr, Dept Ophthalmol, 5323 Harry Hines Blvd, Dallas, TX 75235 USA. EM spark@mednet.swmed.edu NR 21 TC 1 Z9 1 U1 0 U2 0 PU AEOLUS PRESS PI BUREN PA PO BOX 740, 4116 ZJ BUREN, NETHERLANDS SN 0271-3683 J9 CURR EYE RES JI Curr. Eye Res. PD JUN PY 1998 VL 17 IS 6 BP 663 EP 667 PG 5 WC Ophthalmology SC Ophthalmology GA ZT748 UT WOS:000074121200014 PM 9663857 ER PT J AU McClatchey, AI Jacks, T AF McClatchey, AI Jacks, T TI Tumor suppressor mutations in mice: the next generation SO CURRENT OPINION IN GENETICS & DEVELOPMENT LA English DT Article ID MULTIPLE INTESTINAL NEOPLASIA; DROSOPHILA PATCHED GENE; CELL-CYCLE CONTROL; APC GENE; MAJOR MODIFIER; HUMAN HOMOLOG; MOUSE; LOCUS; IDENTIFICATION; PROTEIN AB Mouse strains carrying tumor suppressor mutations genetically mimic familial forms of human cancer. New tumor suppressors have and will be identified and mutated in the mouse; however, it is clear that future investigation will focus on a new generation of experiments aimed at improving existing models, and using them to delineate the molecular pathways to tumorigenesis and to test the value of rationally designed drug therapies. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Pathol, Charlestown, MA 02129 USA. MIT, Howard Hughes Med Inst, Dept Biol, Cambridge, MA 02139 USA. RP McClatchey, AI (reprint author), Massachusetts Gen Hosp, Ctr Canc, Bldg 149,13th St, Charlestown, MA 02129 USA. EM mcclatch@helix.mgh.harvard.edu; tjacks@mit.edu NR 57 TC 13 Z9 14 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON W1P 6LB, ENGLAND SN 0959-437X J9 CURR OPIN GENET DEV JI Curr. Opin. Genet. Dev. PD JUN PY 1998 VL 8 IS 3 BP 304 EP 310 DI 10.1016/S0959-437X(98)80086-5 PG 7 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 100VN UT WOS:000074836200007 PM 9690995 ER PT J AU Agarwal, S Rao, A AF Agarwal, S Rao, A TI Long-range transcriptional regulation of cytokine gene expression SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID INTERFERON-GAMMA GENE; T-CELLS; INTERLEUKIN-2 GENE; IL-2 GENE; CD4 GENE; IN-VIVO; PROMOTER; BINDING; ACTIVATION; ELEMENTS AB Most studies on the control of cytokine gene expression have involved the functional analysis of proximal promoters. Recent work has identified distal elements that mediate long-range cytokine gene regulation and has implicated chromatin reorganization in regulation of cytokine gene loci. These studies have begun to elucidate the basis for cell-specificity and high-level expression of cytokine genes. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RP Agarwal, S (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 200 Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA42471]; NIAID NIH HHS [AI40127] NR 65 TC 65 Z9 66 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON W1P 6LB, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD JUN PY 1998 VL 10 IS 3 BP 345 EP 352 DI 10.1016/S0952-7915(98)80174-X PG 8 WC Immunology SC Immunology GA ZU253 UT WOS:000074178100015 PM 9638372 ER PT J AU Gusella, JF MacDonald, ME AF Gusella, JF MacDonald, ME TI Huntingtin: a single bait hooks many species SO CURRENT OPINION IN NEUROBIOLOGY LA English DT Article ID DISEASE GENE-PRODUCT; SACCHAROMYCES-CEREVISIAE; EMBRYONIC LETHALITY; CYTOPLASMIC DYNEIN; CAG REPEAT; CELL-LINES; PROTEIN; LOCALIZATION; BRAIN; EXPRESSION AB Cloning of the Huntington's disease gene uncovered huntingtin, which is remarkable for its lack of similarity with known proteins despite its large size, similar to 350 kDa. Subsequent experiments established that huntingtin has an as yet unknown function, crucial for embryonic development and neurogenesis. Recent protein trapping to identify huntingtin interactors now reveals that many different prey fall victim to huntingtin bait. C1 Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA 02129 USA. RP Gusella, JF (reprint author), Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA 02129 USA. EM gusella@helix.mgh.harvard.edu; macdonam@helix.mgh.harvard.edu FU NINDS NIH HHS [NS16367] NR 56 TC 56 Z9 57 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON W1P 6LB, ENGLAND SN 0959-4388 J9 CURR OPIN NEUROBIOL JI Curr. Opin. Neurobiol. PD JUN PY 1998 VL 8 IS 3 BP 425 EP 430 DI 10.1016/S0959-4388(98)80071-8 PG 6 WC Neurosciences SC Neurosciences & Neurology GA ZV415 UT WOS:000074302300018 PM 9687360 ER PT J AU Mathisen, D AF Mathisen, D TI Surgery of the trachea SO CURRENT PROBLEMS IN SURGERY LA English DT Review ID SLIDE TRACHEOPLASTY; CRICOID RESECTION; STENOSIS; MANAGEMENT; AIRWAY; ANASTOMOSIS; RECONSTRUCTION; EXPERIENCE; TRAUMA; INTUBATION C1 Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Mathisen, D (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 63 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 USA SN 0011-3840 J9 CURR PROB SURG JI Curr. Probl. Surg. PD JUN PY 1998 VL 35 IS 6 BP 458 EP 542 PG 85 WC Surgery SC Surgery GA ZT598 UT WOS:000074103900002 ER PT J AU Roberts, DJ Smith, D Goff, D Tabin, C AF Roberts, DJ Smith, D Goff, D Tabin, C TI Epithelial/mesenchymal interactions in the development of the Vertebrate hindgut, role of Hoxd13 in large intestinal epithelial differentiation SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 1 PY 1998 VL 198 IS 1 MA 161 BP 186 EP 186 PG 1 WC Developmental Biology SC Developmental Biology GA ZV215 UT WOS:000074281900170 ER PT J AU Sutherland, DJ Raftery, LA AF Sutherland, DJ Raftery, LA TI Multiple requirements for Medea, a Drosophila smad4 homologue, during wing development. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, CBRC, Charlestown, MA USA. RI Raftery, Laurel/H-1406-2012 OI Raftery, Laurel/0000-0003-4797-4163 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 1 PY 1998 VL 198 IS 1 MA 239 BP 199 EP 199 PG 1 WC Developmental Biology SC Developmental Biology GA ZV215 UT WOS:000074281900246 ER PT J AU de Nooij, JC Hariharan, IK AF de Nooij, JC Hariharan, IK TI Dacapo and regulation of cell cycle exit during development SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 1 PY 1998 VL 198 IS 1 MA 313 BP 212 EP 212 PG 1 WC Developmental Biology SC Developmental Biology GA ZV215 UT WOS:000074281900316 ER PT J AU Koya, D King, GL AF Koya, D King, GL TI Protein kinase C activation and the development of diabetic complications SO DIABETES LA English DT Review ID GLOMERULAR MESANGIAL CELLS; GROWTH-FACTOR-BETA; ELEVATED GLUCOSE-LEVELS; RETINAL BLOOD-FLOW; SODIUM-POTASSIUM-ATPASE; SMOOTH-MUSCLE CELLS; EXTRACELLULAR-MATRIX; NITRIC-OXIDE; ALBUMIN PERMEABILITY; DIACYLGLYCEROL MASS AB Recent studies have identified that the activation of protein kinase C (PKC) and increased diacylglycerol (DAG) levels initiated by hyperglycemia are associated with many vascular abnormalities in retinal, renal, and cardiovascular tissues. Among the various PKC isoforms, the beta- and delta-isoforms appear to be activated preferentially in the vasculatures of diabetic animals, although other PKC isoforms are also increased in the renal glomeruli and retina. The glucose-induced activation of PKC has been shown to increase the production of extracellular matrix and cytokines; to enhance contractility, permeability, and vascular cell proliferation; to induce the activation of cytosolic phospholipase A(2); and to inhibit Na+-K+-ATPase. The synthesis and characterization of a specific inhibitor for PKC-beta isoforms have confirmed the role of PKC activation in mediating hyperglycemic effects on vascular cells, as described above, and provide in vivo evidence that PKC activation could be responsible for abnormal retinal and renal hemodynamics in diabetic animals. Transgenic mice overexpressing PKC-beta isoform in the myocardium developed cardiac hypertrophy and failure, further supporting the hypothesis that PKC-beta isoform activation can cause vascular dysfunctions. interestingly, hyperglycemia-induced oxidative stress may also mediate the adverse effects of PKC-beta isoforms by the activation of the DAG-PKC pathway, since treatment with D-alpha-tocopherol was able to prevent many glucose-induced vascular dysfunctions and inhibit DAG-PKC activation. Clinical studies are now in progress to determine whether PKC-beta inhibition can prevent diabetic complications. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02115 USA. RP King, GL (reprint author), 1 Joslin Pl, Boston, MA 02215 USA. EM kingg@joslab.harvard.edu RI Koya, Daisuke /J-3257-2014 FU NEI NIH HHS [EY-05110-11]; NIDDK NIH HHS [DK-36836] NR 110 TC 810 Z9 869 U1 0 U2 37 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUN PY 1998 VL 47 IS 6 BP 859 EP 866 DI 10.2337/diabetes.47.6.859 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZP494 UT WOS:000073759100001 PM 9604860 ER PT J AU Malecki, MT Antonellis, A Casey, P Ji, LN Wantman, R Warram, JH Krolewski, AS AF Malecki, MT Antonellis, A Casey, P Ji, LN Wantman, R Warram, JH Krolewski, AS TI Exclusion of the hepatocyte nuclear factor 4 alpha as a candidate gene for late-onset NIDDM linked with chromosome 20q SO DIABETES LA English DT Article ID DIABETES-MELLITUS; MUTATIONS; GLUCOKINASE; LOCUS C1 Joslin Diabet Ctr, Sect Genet & Epidemiol, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Krolewski, AS (reprint author), Joslin Diabet Ctr, Sect Genet & Epidemiol, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK-47475, DK-36836] NR 18 TC 36 Z9 36 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUN PY 1998 VL 47 IS 6 BP 970 EP 972 DI 10.2337/diabetes.47.6.970 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZP494 UT WOS:000073759100018 PM 9604877 ER PT J AU Bernal, D Almind, K Yenush, L Ayoub, M Zhang, YT Rosshani, L Larsson, C Pedersen, O White, MF AF Bernal, D Almind, K Yenush, L Ayoub, M Zhang, YT Rosshani, L Larsson, C Pedersen, O White, MF TI Insulin receptor substrate-2 amino acid polymorphisms are not associated with random type 2 diabetes among Caucasians SO DIABETES LA English DT Article ID MELLITUS; GENE; MUTATIONS C1 Joslin Diabet Ctr, Howard Hughes Med Inst, Boston, MA 02215 USA. Harvard Univ, Sch Med, Grad Program Biomed & Biol Sci, Boston, MA USA. Steno Diabet Ctr, DK-2820 Gentofte, Denmark. Karolinska Hosp, Dept Mol Med, S-10401 Stockholm, Sweden. RP White, MF (reprint author), Joslin Diabet Ctr, Howard Hughes Med Inst, 1 Joslin Pl, Boston, MA 02215 USA. RI Bernal, Dolores/K-7769-2014; Yenush, Lynne/J-8815-2014 OI Bernal, Dolores/0000-0003-4627-8393; Yenush, Lynne/0000-0001-8589-7002 FU NIDDK NIH HHS [DK-07260, DK-43808] NR 16 TC 60 Z9 65 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUN PY 1998 VL 47 IS 6 BP 976 EP 979 DI 10.2337/diabetes.47.6.976 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZP494 UT WOS:000073759100020 PM 9604879 ER PT J AU Hitchcock, P Marsh, G Larme, AC Correa, A Meyer, J Pugh, JA AF Hitchcock, P Marsh, G Larme, AC Correa, A Meyer, J Pugh, JA TI Patient choice in diabetes education curriculum - Nutritional versus standard content for type 2 diabetes SO DIABETES CARE LA English DT Article ID MEXICAN-AMERICANS; SELF-MANAGEMENT; ADULTS; INTERVENTION; ATTRITION; MELLITUS; IMPACT; TRIALS; NIDDM AB OBJECTIVE - To examine the effects of patient choice between two education curriculums that emphasized either the standard or nutritional management of type 2 diabetes on class attendance and other outcomes among a mostly Hispanic patient population. RESEARCH DESIGN AND METHODS - A total of 596 patients with type 2 diabetes were randomly assigned to either a choice or no choice condition. Patients in the choice condition were allowed to choose their curriculum, while patients in the no choice condition were randomly assigned to one of the two curriculums. Outcomes were assessed at baseline and at a B-month follow-up. RESULTS - When given a choice, patients chose the nutrition curriculum almost four times more frequently than the standard curriculum. Contrary to our hypothesis, however, patients who had a choice did not significantly increase their attendance rates or demonstrate improvements in other diabetes outcomes compared with patients who were randomly assigned to the two curriculums. Patients in the nutrition curriculum had significantly lower serum cholesterol at a 6-month follow-up, whereas patients in the standard curriculum had significant improvements in glycemic control. Of the randomized patients, 30% never attended any classes; the most frequently cited reasons for nonattendance were socioeconomic. Hispanic patients, however were just as likely as non-Hispanic patients to attend classes and participate at the follow-up. Patients who attended all five classes of either curriculum significantly increased their diabetes knowledge, gained less weight, and reported improved physical functioning compared with patients who did not attend any classes. CONCLUSIONS - Although providing patients with a choice in curriculums at the introductory level did not improve outcomes, differential improvements were noted between patients who attended curriculums with different content emphasis. We suggest that diabetes education programs should provide the opportunity for long-term, repetitive contacts to expand on the modest gains achieved at the introductory level, as well as provide more options to match individual needs and interests and to address socioeconomic barriers to participation. C1 Univ Texas, Hlth Sci Ctr, ALMD, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. Univ Hlth Syst, Texas Diabet Inst, San Antonio, TX USA. Mexican Amer Med Treatment Effectiveness Ctr, San Antonio, TX USA. RP Hitchcock, P (reprint author), Univ Texas, Hlth Sci Ctr, ALMD, 7400 Merton Minter Blvd, San Antonio, TX 78284 USA. OI Pugh, Jacqueline/0000-0003-4933-141X NR 24 TC 5 Z9 6 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JUN PY 1998 VL 21 IS 6 BP 896 EP 901 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZN874 UT WOS:000073692200005 ER PT J AU Tearney, GJ Brezinski, ME Southern, JF Bouma, BE Boppart, SA Fujimoto, JG AF Tearney, GJ Brezinski, ME Southern, JF Bouma, BE Boppart, SA Fujimoto, JG TI Optical biopsy in human pancreatobiliary tissue using optical coherence tomography SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE optical coherence tomography; optical biopsy; microscopy; imaging; pancreatobiliary tissue ID INTRADUCTAL ULTRASONOGRAPHY; ENDOSCOPIC ULTRASONOGRAPHY; PANCREATIC-CANCER; DIAGNOSIS; DISEASES AB Optical coherence tomography (OCT) is a new technique for performing high-resolution, cross-sectional tomographic imaging in human tissue. OCT is analogous to ultrasound B mode imaging except that it uses light rather than acoustical waves. As a result, OCT has over 10 times the resolution of currently available clinical high-resolution cross-sectional imaging technologies. In this work, we investigate the capability of OCT to differentiate the architectural morphology of pancreatobiliary tissues. Normal pancreatobiliary tissues, including the gallbladder, common bile duct, pancreatic duct, and pancreas were taken postmortem and imaged using OCT. Images were compared to corresponding histology to confirm tissue identity. Microstructure was delineated in different tissues, including tissue layers, glands, submucosal microvasculature, and pancreatic islets of Langerhans. The ability of OCT to provide high-resolution imaging of pancreatobiliary architectural morphology suggests the feasibility of using OCT as a powerful diagnostic endoscopic imaging technology to image early stages of pancreatobiliary disease. C1 MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. MIT, Elect Res Lab, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. RP Fujimoto, JG (reprint author), MIT, Dept Elect Engn & Comp Sci, 77 Massachusetts Ave,Bldg 36-357, Cambridge, MA 02139 USA. RI Boppart, Stephen/C-7338-2009 FU NCI NIH HHS [1-R01-CA75289-01]; NEI NIH HHS [9-RO1-EY11289]; NHLBI NIH HHS [1-R29-HL55686-01A1] NR 18 TC 45 Z9 45 U1 0 U2 7 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD JUN PY 1998 VL 43 IS 6 BP 1193 EP 1199 DI 10.1023/A:1018891304453 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZU134 UT WOS:000074165700010 PM 9635607 ER PT J AU Brown, SA Weirich, CS Newton, EM Kingston, RE AF Brown, SA Weirich, CS Newton, EM Kingston, RE TI Transcriptional activation domains stimulate initiation and elongation at different times and via different residues SO EMBO JOURNAL LA English DT Article DE heat shock; nucleosomes; transcriptional activation; transcriptional elongation ID RNA-POLYMERASE-II; ESCHERICHIA-COLI; GENE; PROTEINS; PROMOTER; VP16; EXPRESSION; FACTOR-1; INVITRO; HSF1 AB Transcriptional activators can stimulate multiple steps in the transcription process. We have used GAL4 fusion proteins to characterize the ability of different transcriptional activation domains to stimulate transcriptional elongation on the hsp70 gene irt vitro. Stimulation of elongation apparently occurs via a mechanistic pathway different from that of stimulation of initiation: the herpes simplex virus VP16, heat shock factor 1 (HSF1) and amphipathic helix (AH) activation domains all stimulate initiation, but only VP16 and HSF1 stimulate elongation; and mutations in hydrophobic residues of the HSF1 activation domains impair stimulation of elongation but not of initiation, while mutations in adjacent acidic residues impair stimulation of initiation more than of elongation. Experiments in which activators were exchanged between initiation and elongation demonstrate that the elongation function of HSF1 will stimulate RNA polymerase that has initiated and is transcriptionally engaged. Transcriptional activators thus appear to have at least two distinct functions that reside in the same domain, and that act at different times to stimulate initiation and elongation. C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. RP Kingston, RE (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. NR 36 TC 52 Z9 54 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD JUN 1 PY 1998 VL 17 IS 11 BP 3146 EP 3154 DI 10.1093/emboj/17.11.3146 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA ZU084 UT WOS:000074159600017 PM 9606196 ER PT J AU Goldmann, WH Guttenberg, Z Tang, JX Kroy, K Isenberg, G Ezzell, RM AF Goldmann, WH Guttenberg, Z Tang, JX Kroy, K Isenberg, G Ezzell, RM TI Analysis of the F-actin binding fragments of vinculin using stopped-flow and dynamic light-scattering measurements SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article DE vinculin; actin; stopped-flow kinetics; dynamic light scattering ID CYTOSKELETAL PROTEIN VINCULIN; INTRAMOLECULAR ASSOCIATION; ACIDIC PHOSPHOLIPIDS; FOCAL ADHESIONS; ALPHA-ACTININ; TALIN-BINDING; TAIL DOMAINS; SITE; HEAD; PHOSPHORYLATION AB Using amino acids 884-1066 and 884-1012 expressed from chicken vinculin as fusion proteins with schistosomal glutathione S-transferase, we determined the binding kinetics of the protein fragments with F-actin. We established by the stopped-flow method a two-step binding process: an initial rapid reaction followed by a slower process. The latter is attributed to F-actin cross-linking and/or bundling, which was previously detected by viscometry and electron microscopy [Johnson, R. P. & Craig, S. W. (1995) Nature 373, 261-264]. This is also supported by dynamic light-scattering measurements, indicating dramatic changes in the internal actin filament dynamics, i.e. in bending undulations due to thermal noise. The similar size of the binding reaction for both fusion proteins with F-actin indicates that the F-actin binding site(s) on vinculin are located between residues 884-1012. No binding of pure glutathione S-transferase or its fusion protein with vinculin peptide 1012-1066 with F-actin was detected by either method. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Surg Res Labs, Charlestown, MA 02129 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Expt Med, Boston, MA 02115 USA. Tech Univ Munich, Dept Phys, D-8046 Garching, Germany. RP Goldmann, WH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Surg Res Labs, Bldg 149,13th St, Charlestown, MA 02129 USA. EM goldmann@helix.mhg.harvard.edu RI Goldmann, Wolfgang/H-5572-2013 NR 40 TC 15 Z9 15 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD JUN 1 PY 1998 VL 254 IS 2 BP 413 EP 419 DI 10.1046/j.1432-1327.1998.2540413.x PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZU077 UT WOS:000074158900028 PM 9660199 ER PT J AU Bartsch, H Malaveille, C Lowenfels, AB Maisonneuve, P Hautefeuille, A Boyle, P AF Bartsch, H Malaveille, C Lowenfels, AB Maisonneuve, P Hautefeuille, A Boyle, P CA Int Pancreatic Dis Study Grp TI Genetic polymorphism of N-acetyltransferases, glutathione S-transferase M1 and NAD(P)H : quinone oxidoreductase in relation to malignant and benign pancreatic disease risk SO EUROPEAN JOURNAL OF CANCER PREVENTION LA English DT Article DE alcoholic pancreatitis; asymptomatic Caucasian subjects; diet; genetic polymorphism; glutathione S-transferase M1; heterocyclic/aromatic amines; NAD(P)H : quinone oxidoreductase; N-acetyltransferase; pancreatic cancer ID BLADDER-CANCER SUSCEPTIBILITY; 2-AMINO-1-METHYL-6-PHENYLIMIDAZO<4,5-B>PYRIDINE PHIP; HETEROCYCLIC AMINES; METABOLIC-ACTIVATION; COLORECTAL-CANCER; CIGARETTE-SMOKING; DT-DIAPHORASE; ACETYLATION; POPULATION; TOBACCO AB Carcinogens present in cigarette smoke and diet have been associated with pancreatic cancer. We hypothesized that heterocyclic and aromatic amines implicated in these exposures could be involved as causative agents and that therefore genetic variation in enzymes metabolizing these carcinogens could modify the risk of developing malignant and benign pancreatic disease, The effect of the genetic polymorphism of acetyltransferases (NAT1 and NAT2), glutathione S-transferase M1 (GSTM1) and NAD(P)H: quinone oxidoreductase 1 (NQO1) on the risk of pancreatic diseases (cancer, pancreatitis) was examined in a case-control study, PCR-based assays were used for genotype analysis of genomic DNA from whole blood cells, Samples collected from Caucasian patients with diagnosed pancreatic cancer (n = 81), with non-alcoholic (n = 41) and alcoholic pancreatitis (n = 73) and from asymptomatic control subjects (n = 78) were analysed, The prevalence of GSTM1 null genotype and of NAT2 fast and slow acetylator genotypes and the distribution of frequencies for NQO1 genotypes did not differ in subjects with pancreatic diseases vs controls. For NAT1 slow acetylators a non-significant excess (P = 0.18) was found among pancreatic cancer cases vs controls. There was a significant over-representation of the GSTM1 AB or B genotype in all pancreatic disease cases combined (OR = 2.6; P < 0.05). When concurrent controls were pooled with literature controls (n = 1427), OR was 1.4 (P = 0.08), The results of this study, requiring confirmation, suggest that the polymorphism of GSTM1 and NAT1 enzymes may be associated with a modest increase in susceptibility to pancreatic disease. (C) 1998 Lippincott-Raven Publishers. C1 German Canc Res Ctr, Div Toxicol & Canc Risk Factors 0325, D-69120 Heidelberg, Germany. Int Agcy Res Canc, F-69372 Lyon, France. New York Med Coll, Valhalla, NY 10595 USA. Ist Europeo Oncol, Milano, Italy. Harvard Univ, Sch Med, Boston, MA USA. Clin Med Policlin, Verona, Italy. Orebro Med Ctr Hosp, S-70185 Orebro, Sweden. Dept Med & Gastroenterol, Bologna, Italy. Natl Board Hlth, Copenhagen, Denmark. Stadt Krankenhaus, Luneburg, Germany. Our Lady Mercy Hosp, Bronx, NY USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Bartsch, H (reprint author), German Canc Res Ctr, Div Toxicol & Canc Risk Factors 0325, Neuenheimer Feld 280, D-69120 Heidelberg, Germany. RI Boyle, Peter/A-4380-2014; OI Boyle, Peter/0000-0001-6251-0610; Maisonneuve, Patrick/0000-0002-5309-4704 NR 65 TC 58 Z9 61 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0959-8278 J9 EUR J CANCER PREV JI Eur. J. Cancer Prev. PD JUN PY 1998 VL 7 IS 3 BP 215 EP 223 DI 10.1097/00008469-199806000-00006 PG 9 WC Oncology SC Oncology GA 107FV UT WOS:000075197400006 PM 9696930 ER PT J AU Melnik, G Schwesinger, WH Teng, R Dogolo, LC Vincent, J AF Melnik, G Schwesinger, WH Teng, R Dogolo, LC Vincent, J TI Hepatobiliary elimination of trovafloxacin and metabolites following single oral doses in healthy volunteers SO EUROPEAN JOURNAL OF CLINICAL MICROBIOLOGY & INFECTIOUS DISEASES LA English DT Article ID PHARMACOKINETICS; CP-99,219; QUINOLONE AB Trovafloxacin, a fluoronaphthyridone derivative related to fluoroquinolones, has significant activity against gram-negative and gram-positive pathogens, including penicillin-resistant Streptococcus pneumoniae, anaerobes and atypical organisms, good tissue penetration and a long elimination half-life. Following oral administration, less than 10% of the dose is renally eliminated as unchanged drug. Hepatobiliary elimination of trovafloxacin was examined by comparing the time course and bile and serum concentrations of trovafloxacin and its metabolites following oral administration to three patients with in-dwelling nasobiliary catheters or T-tubes. Following a single 200 mg oral dose? the mean maximum plasma trovafloxacin concentration was 2.0 +/- 0.4mg/l, the area under the concentration-time curve 22.0 +/- 5.5 mg.h/l and the elimination half-life 8.5 h. Values in bile for the same subjects were 27.8 +/- 9.6 mg/l, 327.7 +/- 142.9 mg.h/l and 10.7 h. Corresponding values for the N-acetyl metabolite in bile were 3.8 +/- 3.4 mg/l, 35.3 +/- 29.8 mg.h/l and 8.3 h. The mean bile : serum ratio of trovafloxacin was 14:9 and consistent with biliary elimination. Serum concentrations of trovafloxacin in this study were similar to these reported in healthy volunteers. Bile concentrations of trovafloxacin substantially exceeded those of the N-acetyl metabolite, suggesting efficient clearance of the metabolite or that hepatic metabolism of trovafloxacin is not extensive. C1 Pfizer Inc, Div Cent Res, Dept Clin Res, Groton, CT 06340 USA. Univ Texas, Hlth Sci Ctr, Dept Pharmacol, S Texas Vet Hlth Care Syst, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Surg, S Texas Vet Hlth Care Syst, San Antonio, TX 78284 USA. RP Vincent, J (reprint author), Pfizer Inc, Div Cent Res, Dept Clin Res, Eastern Point Rd, Groton, CT 06340 USA. NR 15 TC 9 Z9 9 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0934-9723 J9 EUR J CLIN MICROBIOL JI Eur. J. Clin. Microbiol. Infect. Dis. PD JUN PY 1998 VL 17 IS 6 BP 424 EP 426 DI 10.1007/BF01691576 PG 3 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 116DR UT WOS:000075708800014 PM 9758286 ER PT J AU Sykes, M Szot, GL Swenson, K Pearson, DA Wekerle, T AF Sykes, M Szot, GL Swenson, K Pearson, DA Wekerle, T TI Separate regulation of peripheral hematopoietic and thymic engraftment SO EXPERIMENTAL HEMATOLOGY LA English DT Article DE hematopoiesis; thymopoiesis; T cell development; thymus; hematopoietic stem cell ID BONE-MARROW TRANSPLANTATION; ANTIBODY MAB INJECTIONS; WHOLE-BODY IRRADIATION; ADULT-MOUSE THYMUS; T CELL MABS; STEM-CELLS; MIXED CHIMERISM; MONOCLONAL-ANTIBODIES; CLONAL DELETION; PRECURSOR CELLS AB Long-term multilineage chimerism, indicating pluripotent hematopoietic stem cell engraftment, was achieved in an Ly5-congenic strain combination without irradiation or other host conditioning when a large number of donor marrow cells (1.4-2x10(8)) was administered. However, the initial (2-4 weeks posttransplantation) percentages of T and B lymphocytes of donor origin were markedly lower than those of myeloid lineages. Steady-state levels of donor and host repopulation of all lineages were reached by 7 to 15 weeks posttransplantation and remained relatively constant for at least 41 weeks. B cell chimerism was similar to that seen in myeloid lineages at steady state. In contrast, long-term donor representation in the T cell lineage was much lower than in the B cell or myeloid lineages. Host treatment with depleting anti-T cell monoclonal antibodies increased the donor contribution to early T cell repopulation, but long-term T cell chimerism was still significantly lower in all lymphohematopoietic tissues, including the thymus, than B cell or myeloid cell chimerism. Pretreatment of hosts with 3.5 Gy of local irradiation to the thymic region further increased the donor contribution to initial T cell repopulation, which equaled that of other lineages at 4 to 7 weeks. However, donor representation in the T cell lineage declined by the time steady-state chimerism was attained and was lower than donor representation in the B cell or myeloid lineages. A higher dose of thymic irradiation (7 Gy) led to a reduction in this discrepancy, so that levels of donor thymopoiesis and hematopoiesis in other lineages were similar by 23 to 27 weeks posttransplantation. The differential contribution of adult donor marrow to long-term, steady-state thymopoiesis vs. hematopoiesis in other lineages under certain conditions in this competitive repopulation assay suggests that functionally distinguishable progenitors are responsible for these activities. C1 Harvard Univ, Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect, Massachusetts Gen Hosp,Sch Med,Surg Serv, Boston, MA 02129 USA. RP Sykes, M (reprint author), Harvard Univ, Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect, Massachusetts Gen Hosp,Sch Med,Surg Serv, MGH E,Bldg 149-5102,13th St, Boston, MA 02129 USA. OI Wekerle, Thomas/0000-0001-5159-2796 FU NHLBI NIH HHS [R01 HL49915] NR 42 TC 30 Z9 31 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JUN PY 1998 VL 26 IS 6 BP 457 EP 465 PG 9 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA ZQ411 UT WOS:000073858500002 PM 9620278 ER PT J AU Chung, DC AF Chung, DC TI Molecular prognostic markers and colorectal cancer: The search goes on SO GASTROENTEROLOGY LA English DT Editorial Material ID ALLELIC LOSS; IN-VIVO; SURVIVAL; CARCINOMA; MUTATIONS; PROTEIN; GENE C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Chung, DC (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, GRJ 825,32 Fruit St, Boston, MA 02114 USA. NR 24 TC 28 Z9 29 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JUN PY 1998 VL 114 IS 6 BP 1330 EP 1332 DI 10.1016/S0016-5085(98)70441-X PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZQ211 UT WOS:000073833900029 PM 9618651 ER PT J AU Herrlinger, U Kramm, CM Aboody-Guterman, KS Silver, JS Ikeda, K Johnston, KM Pechan, PA Barth, RF Finkelstein, D Chiocca, EA Louis, DN Breakefield, XO AF Herrlinger, U Kramm, CM Aboody-Guterman, KS Silver, JS Ikeda, K Johnston, KM Pechan, PA Barth, RF Finkelstein, D Chiocca, EA Louis, DN Breakefield, XO TI Pre-existing herpes simplex virus 1 (HSV-1) immunity decreases, but does not abolish, gene transfer to experimental brain tumors by a HSV-1 vector SO GENE THERAPY LA English DT Article DE HSV-1; immunity; gene transfer; glioma ID ADENOVIRUS VECTORS; NERVOUS-SYSTEM; RECOMBINANT ADENOVIRUS; VIRAL-ANTIGENS; RAT-BRAIN; RESPONSES; THERAPY; REPLICATION; TYPE-1; RECOGNIZE AB The influence of pre-existing anti-herpes simplex type 1 (HSV-1) immunity on HSV-1-vector-mediated gene transfer to glioma cells was analyzed in this gene marking study using intracranial D74 gliomas in syngeneic Fischer rats. The HSV-1 mutant virus used, hrR3, is defective in ribonucleotide reductase and bears the marker genes E. coli lacZ and HSV-1 thymidine kinase (HSVtk). Initial marker gene expression in tumors 12 h after direct virus injection was reduced in immunized animals to about 15% of that in non-immunized animals. Marker gene expression in both sets stayed at initial levels for 2 days after intratumoral injection and declined markedly on day 5. Inflammatory infiltrates in the tumor were more prominent in HSV-1-immunized, as compared with nonimmunized animals, at 12 and 24 h, but appeared similar at 2-5 days after injection. By day 10, the immune reaction had subsided in immunized animals and macrophages remained only in nonimmunized animals. In conclusion, gene transfer to brain tumors using a HSV-1 vector was greatly reduced, but not competely abolished, under pre-immunization conditions. Pre-existing antibodies to HSV-1 may also serve a positive role in providing an increased margin of safety in intracranial application of HSV-1 vectors by limiting spread of the virus within the brain and to other tissues. C1 Massachusetts Gen Hosp, MGH Canc Ctr, Mol Neurogenet Unit, Charlestown, MA USA. Massachusetts Gen Hosp, Mol Neurooncol Lab, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. Univ Tubingen, Dept Neurol, D-72074 Tubingen, Germany. Univ Dusseldorf, Childrens Hosp, D-4000 Dusseldorf, Germany. McGill Univ, Montreal Gen Hosp, Dept Neurosurg, Montreal, PQ H3G 1A4, Canada. Ohio State Univ, Dept Pathol, Columbus, OH 43210 USA. RP Breakefield, XO (reprint author), Massachusetts Gen Hosp E, Mol Neurogenet Unit, CNY 6, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA69246] NR 48 TC 66 Z9 68 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD JUN PY 1998 VL 5 IS 6 BP 809 EP 819 DI 10.1038/sj.gt.3300643 PG 11 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA ZU961 UT WOS:000074253900011 PM 9747461 ER PT J AU Volko, SM Boller, T Ausubel, FM AF Volko, SM Boller, T Ausubel, FM TI Isolation of new Arabidopsis mutants with enhanced disease susceptibility to Pseudomonas syringae by direct screening SO GENETICS LA English DT Article ID SYSTEMIC ACQUIRED-RESISTANCE; PATHOGENESIS-RELATED PROTEINS; PLANT DEFENSE RESPONSES; SALICYLIC-ACID; ANTIFUNGAL ACTIVITY; TRANSGENIC TOBACCO; BIOLOGICAL FUNCTION; AVIRULENCE GENE; CHITINASES; THALIANA AB To identify plant defense components that are important in restricting the growth of virulent pathogens, we screened for Arabidopsis mutants in the accession Columbia (carrying the transgene BGL2-GUS) that display enhanced disease susceptibility to the virulent bacterial pathogen Pseudomonas syringae pv. maculicola (Psm) ES4326. Among six (out of a total of 11 isolated) enhanced disease susceptibility (eds) mutants that were studied in detail, we identified one allele of the previously described npr1/nim1/sai1 mutation, which is affected in mounting a systemic acquired resistance response, one allele of the previously identified EDS5 gene, and four EDS genes that have not been previously described. The six eds mutants studied in detail (npr1-4, eds5-2, eds10-1, eds11-1, eds12-1, and eds13-1) displayed different patterns of enhanced susceptibility to a variety of phytopathogenic bacteria and to the obligate biotrophic fungal pathogen Erysiphe orontii, suggesting that particular EDS genes have pathogen-specific roles in conferring resistance. All six eds mutants retained the ability to mount a hypersensitive response and to restrict the growth of the avirulent strain Psm ES4326/avrRpt2. With the exception of npr1-4 the mutants were able to initiate a systemic acquired resistance (SAR) response, although enhanced growth of Psm ES4326 was still detectable in leaves of SAR-induced plants. The data presented here indicate that eds genes define a variety of components involved in limiting pathogen growth, that many additional EDS genes remain to be discovered, and that direct screens for mutants with altered susceptibility to pathogens are helpful in the dissection of complex pathogen response pathways in plants. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Univ Basel, Dept Bot, CH-4056 Basel, Switzerland. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Ausubel, FM (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM ausubel@frodo.mgh.harvard.edu RI Boller, Thomas/G-3500-2012 FU NIGMS NIH HHS [GM-48707] NR 56 TC 52 Z9 53 U1 1 U2 3 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD JUN PY 1998 VL 149 IS 2 BP 537 EP 548 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA ZR912 UT WOS:000074028400008 PM 9611172 ER PT J AU Mertz, H Fullerton, S Naliboff, B Mayer, EA AF Mertz, H Fullerton, S Naliboff, B Mayer, EA TI Symptoms and visceral perception in severe functional and organic dyspepsia SO GUT LA English DT Article DE dyspepsia; hyperalgesia; visceral afferents ID IRRITABLE-BOWEL-SYNDROME; MECHANISMS; OCTREOTIDE; ENDOSCOPY; PAIN AB Background-Hypersensitivity of gastric afferent pathways may play an aetiological role in symptoms of functional dyspepsia. Aims-To determine whether patients with severe organic dyspepsia (associated with tissue irritation/injury) and those with functional dyspepsia (no detectable tissue irritation) differ in their perception of gastric distension and whether this difference is reflected in differences in their gastrointestinal and psychological symptoms. Methods-Perceptual thresholds, referral patterns, and gastraintestinal and psychological symptoms were compared in 23 patients with functional dyspepsia, 10 organic dyspeptics, and 15 healthy controls. Results-Fifteen (65%) functional dyspeptics and no organic dyspeptics had reduced perceptual thresholds far fullness, discomfort, or pain (odds ratio (OR) 19.56, 95% confidence interval (CI) 1.95 to 476.09, p=0.0017). Either reduced perceptual thresholds or altered referral was found in 20 (87%) functional dyspeptics and four (20%) organic dyspeptics (OR 10.0, 95% CI 1.34 to 89.54, p=0.014). During sham distension fullness, discomfort and pain were reported by healthy controls, organic dyspeptics, and functional dyspeptics. A sham response of pain but no other sensation was more frequent among functional dyspeptics (43%) than healthy controls (7%) (OR 10.77, 95% CI 1.10 to 257.35, p=0.026). Gastrointestinal and psychological symptoms and gastric compliance were similar in the functional and organic groups. Conclusions-Alterations in the perception of gastric distension distinguishes California, USA between functional and organic dyspepsia, while symptoms do not. A total of 87% of functional dyspeptics studied had evidence of altered visceral afferent function. In this study population, psychological abnormalities or changes in compliance did not explain the findings. C1 W Los Angeles Vet Affairs Med Ctr, CURE, Neuroenter Dis Program, Digest Dis Res Ctr, Los Angeles, CA 90073 USA. Vanderbilt Univ, Dept Med, Nashville, TN USA. RP Mayer, EA (reprint author), W Los Angeles Vet Affairs Med Ctr, CURE, Neuroenter Dis Program, Digest Dis Res Ctr, 11301 Wilshire Blvd,Bldg 115,Rm 223, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [DK 40919] NR 27 TC 175 Z9 185 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD JUN PY 1998 VL 42 IS 6 BP 814 EP 822 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZU024 UT WOS:000074153600012 PM 9691920 ER PT J AU Perrin, JM Kuhlthau, K Ettner, SL McLaughlin, TJ Gortmaker, SL AF Perrin, JM Kuhlthau, K Ettner, SL McLaughlin, TJ Gortmaker, SL TI Previous Medicaid status of children newly enrolled in supplemental security income SO HEALTH CARE FINANCING REVIEW LA English DT Article ID CARE AB The Supplemental Security Income (SSI) program for children and adolescents has experienced a fourfold enrollment growth since 1989. Most SSI recipients also receive Medicaid, and SSI growth could therefore lead to major new Medicaid expenditures if new SSI recipients were not Previous Medicaid enrollees. Using Medicaid claims for 1989-92, we determined whether SSI expansions included many children new to Medicaid as well as whether children with certain disabilities were more likely to have had Medicaid prior to SSI enrollment. Rates of new SSI enrollees without previous Medicaid coverage decreased from 53 percent in 1989 to 39 percent by 1992. C1 Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. RP Perrin, JM (reprint author), Massachusetts Gen Hosp, WACC 715, Boston, MA 02114 USA. NR 17 TC 4 Z9 4 U1 1 U2 1 PU HEALTH CARE FINANCING REVIEW PI BALTIMORE PA 7500 SECURITY BLVD, C-3-11-07, BALTIMORE, MD 21224-1850 USA SN 0195-8631 J9 HEALTH CARE FINANC R JI Health Care Finan. Rev. PD SUM PY 1998 VL 19 IS 4 BP 117 EP 127 PG 11 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 155VQ UT WOS:000077967400008 ER PT J AU Dubinett, SM Miller, PW Sharma, S Batra, RK AF Dubinett, SM Miller, PW Sharma, S Batra, RK TI Gene therapy for lung cancer SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Review ID COLONY-STIMULATING FACTOR; ENDOTHELIAL GROWTH-FACTOR; WILD-TYPE P53; TUMOR-INFILTRATING LYMPHOCYTES; INTERFERON-GAMMA-PRODUCTION; LASTING ANTITUMOR IMMUNITY; PULSED DENDRITIC CELLS; NECROSIS-FACTOR-ALPHA; IN-VIVO; PERIPHERAL-BLOOD AB Lung cancer is the major cause of cancer-realted mortality, accounting for approximately 30% of all such deaths in the United States every year. Although few patients have been treated, the preliminary results of the phase I lung cancer gene therapy clinical trials are promising. Clinically relevant basic research in the molecular pathogenesis and immunology of lung cancer is progressing. As improved vector technologies are developed, new opportunities will be available to initiate lung cancer gene therapy trials based on a more detailed understanding of lung cancer biology. Although important biological and technical questions remain unanswered, recent research suggests that gene therapy will have a profound impact on lung cancer treatment. C1 Univ Calif Los Angeles, Sch Med, Div Pulm & Crit Care Med, Wadsworth Pulm Immunol Lab, Los Angeles, CA USA. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Sch Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, W Los Angeles Vet Affairs Med Ctr, Sch Med, Los Angeles, CA 90024 USA. RP Dubinett, SM (reprint author), Univ Calif Los Angeles, Sch Med, Ctr Hlth Sci 37-131, Div Pulm & Crit Care Med, 10833 Le Conte Ave, Los Angeles, CA 90095 USA. NR 239 TC 20 Z9 20 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD JUN PY 1998 VL 12 IS 3 BP 569 EP + DI 10.1016/S0889-8588(05)70009-5 PG 28 WC Oncology; Hematology SC Oncology; Hematology GA 105AJ UT WOS:000075049400007 PM 9684099 ER PT J AU Tyler, KL Sokol, RJ Oberhaus, SM Le, MS Karrer, FM Narkewicz, MR Tyson, RW Murphy, JR Low, R Brown, WR AF Tyler, KL Sokol, RJ Oberhaus, SM Le, MS Karrer, FM Narkewicz, MR Tyson, RW Murphy, JR Low, R Brown, WR TI Detection of reovirus RNA in hepatobiliary tissues from patients with extrahepatic biliary atresia and choledochal cysts SO HEPATOLOGY LA English DT Article; Proceedings Paper CT Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY MAY 10-11, 1997 CL WASHINGTON, D.C. SP Amer Assoc Study Liver Dis ID POLYMERASE CHAIN-REACTION; NEONATAL HEPATITIS; TYPE-3 INFECTION; LIVER-TRANSPLANTATION; SEROTYPE-3 INFECTION; POLYSPLENIA SYNDROME; SIGMA-1 PROTEIN; TRACT DISEASE; MICE; INFANTS AB Extrahepatic biliary atresia (EHBA) and choledochal cysts (CDC) are important causes of obstructive jaundice in pediatric patients. Viruses in general, and reoviruses in particular, have long been considered as possible etiologic agents responsible for inciting the inflammatory process that leads to these infantile obstructive cholangiopathies, In an effort to determine whether reovirus infection is associated with these disorders, we used a sensitive and specific reverse-transcriptase polymerase chain reaction (RT-PCR) technique designed to amplify a portion of the reovirus L1 gene segment from extracts of liver and/or biliary tissues. These tissues were obtained at the time of liver biopsy or surgical procedures from 23 patients with EHBA, 9 patients with CDC, and 33 patients with other hepatobiliary diseases. Hepatic and biliary tissues obtained at autopsy from 17 patients who died without known liver or biliary disease were also analyzed. Reovirus RNA was detected in hepatic and/or biliary tissues from 55% of patients with EHBA and 78% of patients with CDC, Reovirus RNA was found also in extracts of hepatic and/or biliary tissue from 21% of patients with other hepatobiliary diseases and in 12% of autopsy cases. The prevalence of reovirus RNA in tissues from patients with EHBA and CDC was significantly greater than that in patients with other hepatobiliary diseases (chi(2) P = .012 EHBA vs. OTHER, P = .001 CDC vs. OTHER), or AUTOPSY cases (chi(2) P = .006 EHBA vs, AUTOPSY, P < .001 CDC vs. AUTOPSY). C1 Univ Colorado, Hlth Sci Ctr, Dept Neurol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Pediat, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Immunol & Microbiol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Surg, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Prevent Med & Biometr, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Pathol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Hepatobiliary Res Ctr, Denver, CO 80262 USA. Denver VA Med Ctr, Serv Neurol, Denver, CO USA. Denver VA Med Ctr, Med Serv, Denver, CO USA. Denver VA Med Ctr, Res Serv, Denver, CO USA. Childrens Hosp, Pediat Liver Ctr, Denver, CO 80218 USA. RP Tyler, KL (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Neurol, Campus Box B-182,4200 E 9th Ave, Denver, CO 80262 USA. OI Tyler, Kenneth/0000-0003-3294-5888 FU NCI NIH HHS [CA 46934]; NCRR NIH HHS [5M01 RR00069]; NIA NIH HHS [R01AG14071] NR 79 TC 121 Z9 130 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JUN PY 1998 VL 27 IS 6 BP 1475 EP 1482 DI 10.1002/hep.510270603 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZQ460 UT WOS:000073864300003 PM 9620316 ER PT J AU Li, MKK Tsui, CP Sung, JJY Scremin, OU Leung, FW AF Li, MKK Tsui, CP Sung, JJY Scremin, OU Leung, FW TI Potassium channels participate in gastric mucosal protection in rats with partial portal vein ligation SO HEPATOLOGY LA English DT Article ID HYDROGEN GAS CLEARANCE; SENSITIVE K+ CHANNELS; HYPERTENSIVE RATS; BLOOD-FLOW; ADRENOCEPTOR ANTAGONISTS; ETHANOL INJURY; SMOOTH-MUSCLE; CROMAKALIM; GLIBENCLAMIDE; INVOLVEMENT AB Glybenclamide, an adenosine triphosphate-dependent potassium (K-ATP(+)) channel blocker, lowered portal pressure and attenuated the hyperdynamic splanchnic circulation in rats with partial portal vein ligation (PPVL). The purpose of this report was to confirm these observations and to test the hypothesis that glybenclamide could reduce acidified ethanol-induced gastric mucosal injury in rats with PPVL, Gastric mucosal blood flow (hydrogen gas clearance), systemic blood pressure, and portal pressure were monitored in rats with PPVL or sham operation (SO). Intravenous glybenclamide (20 mg/kg) or vehicle was administered, followed by intragastric acidified ethanol (0.15 N HCl and 15% ethanol), The area of gastric mucosal lesions was assessed by image analysis. In contrast to published findings, there was no significant elevation of portal pressure after glybenclamide administration in rats with PPVL, Glybenclamide did not alter the gastric mucosal hyperemia in these rats. Glybenclamide significantly increased mucosal injury. The data are consistent with the hypothesis that K-ATP(+) channels play a role in protecting the gastric mucosa in rats with PPVL. C1 Vet Adm Med Ctr, Div Gastroenterol 111G, Sepulveda, CA 91343 USA. Chinese Univ Hong Kong, Dept Med, Hong Kong, Hong Kong. W Los Angeles Vet Affairs Med Ctr, Res Serv, Los Angeles, CA 90073 USA. W Los Angeles Vet Affairs Med Ctr, Med Serv, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Ctr Ulcer Res & Educ, Los Angeles, CA USA. RP Leung, FW (reprint author), Vet Adm Med Ctr, Div Gastroenterol 111G, 16111 Plummer St, Sepulveda, CA 91343 USA. RI Hossain, Sarah /C-7332-2009 OI Hossain, Sarah /0000-0003-1355-0979 NR 47 TC 4 Z9 5 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JUN PY 1998 VL 27 IS 6 BP 1530 EP 1535 DI 10.1002/hep.510270610 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZQ460 UT WOS:000073864300010 PM 9620323 ER PT J AU Allen, MI Deslauriers, M Andrews, CW Tipples, GA Walters, KA Tyrrell, DLJ Brown, N Condreay, LD AF Allen, MI Deslauriers, M Andrews, CW Tipples, GA Walters, KA Tyrrell, DLJ Brown, N Condreay, LD CA Lamivudine Clinical Invest Grp TI Identification and characterization of mutations in hepatitis B virus resistant to lamivudine SO HEPATOLOGY LA English DT Article ID HERPES-SIMPLEX VIRUS; CHAIN-REACTION ASSAY; REVERSE-TRANSCRIPTASE; ANGSTROM RESOLUTION; CRYSTAL-STRUCTURE; POLYMERASE; DNA; SEQUENCES; INVITRO; (-)-BETA-L-2',3'-DIDEOXY-3'-THIACYTIDINE AB Cirrhosis and hepatocellular carcinoma occur as longterm complications of chronic hepatitis B virus (HBV) infection. Antiviral therapy is potentially a successful approach for the treatment of patients with HBV infection, which includes the nucleoside analog, lamivudine [(-)2'-deoxy-3'-thiacytidine, 3TC], Although resistance to lamivudine therapy has been reported in several HBV-infected patients, the pattern of resistance-associated mutations in HBV has not been fully characterized. We report a DNA sequence database that includes a 500-base pair region of the HBV polymerase gene from 20 patients with clinical manifestations of lamivudine resistance. Analysis of the database reveals two patterns of amino acid substitutions in the tyrosine, methionine, aspartate, aspartate (YMDD) nucleotide-binding locus of the HBV polymerase. HBV DN4 from the sera of patients in Group I exhibits a substitution of valine for methionine at residue 552, accompanied by a substitution of methionine for leucine at residue 528. Patients in Group II had only an isoleucine-for-methionine substitution at position 552, Reconstruction of these mutations in an HBV replication-competent plasmid was performed in a transient transfection cell assay to determine the function/relevance of these mutations to lamivudine resistance. Both Group I and Group II mutations resulted in a substantial decrease in sensitivity to lamivudine treatment (>10,000-fold shift in IC50 over wild-type [wt] IC50), strongly indicating that these mutations were involved in resistance to lamivudine. A hypothetical model of the HBV reverse transcriptase has been generated for further study of the role of these mutations in lamivudine resistance. C1 Glaxo Wellcome Inc, Dept Virol, Res Triangle Pk, NC 27709 USA. Glaxo Wellcome Inc, Dept Struct Chem, Res Triangle Pk, NC 27709 USA. Glaxo Wellcome Inc, Dept Infect Dis & Rheumatol, Res Triangle Pk, NC 27709 USA. Univ Alberta, Dept Med Microbiol & Immunol, Edmonton, AB, Canada. Univ Alberta, Glaxo Wellcome Heritage Res Inst, Edmonton, AB, Canada. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Toronto Hosp, Toronto, ON M5T 2S8, Canada. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Greater Baltimore Med Ctr, Dept Med, Baltimore, MD USA. Alton Ochsner Med Fdn & Ochsner Clin, New Orleans, LA 70121 USA. Univ Pittsburgh, Med Ctr, Div Transplantat Med, Pittsburgh, PA USA. Hosp St Luc, Montreal, PQ, Canada. Queen Elizabeth Hosp, Birmingham B15 2TH, W Midlands, England. Med Hsch Hannover, Zentrum Innere Med & Dermatol, Abt Gastro & Hepatol, Hannover, Germany. Erasmus Univ, Hosp Dijkzigt, Dept Internal Med 2, Sect Hepatol, NL-3015 GD Rotterdam, Netherlands. Univ Alberta, Dept Med, Div Gastroenterol, Edmonton, AB, Canada. Osaka City Univ, Sch Med, Dept Internal Med 3, Osaka 545, Japan. RP Allen, MI (reprint author), Glaxo Wellcome Inc, Dept Virol, RC2 Room 712,POB 13398, Res Triangle Pk, NC 27709 USA. NR 28 TC 651 Z9 708 U1 1 U2 6 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JUN PY 1998 VL 27 IS 6 BP 1670 EP 1677 DI 10.1002/hep.510270628 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZQ460 UT WOS:000073864300028 PM 9620341 ER PT J AU George, MS Speer, AM Molloy, M Nahas, Z Teneback, CC Risch, SC Arana, GW Ballenger, JC Post, RM AF George, MS Speer, AM Molloy, M Nahas, Z Teneback, CC Risch, SC Arana, GW Ballenger, JC Post, RM TI Low frequency daily left prefrontal rTMS improves mood in bipolar depression: A placebo-controlled case report SO HUMAN PSYCHOPHARMACOLOGY-CLINICAL AND EXPERIMENTAL LA English DT Article DE depression; bipolar affective disorder; SPECT; imaging; transcranial magnetic stimulation ID TRANSCRANIAL MAGNETIC STIMULATION; LONG-TERM POTENTIATION; CORTEX AB Preliminary studies in unipolar depression indicate that daily left prefrontal repetitive transcranial magnetic stimulation (rTMS) reduces symptoms of depression. rTMS treatment of depression occurring in the setting of bipolar disorder has been less well studied. To assess the efficacy and toxicity of rTMS in the depressed phase of bipolar disorder, we treated a man with bipolar disorder who was known to develop hypomania and mania with conventional antidepressants. A 47 year old man with Bipolar Disorder type I, depressed phase, was entered into a double-blind parallel treatment trial of left prefrontal rTMS. He was randomized to receive left prefrontal rTMS at low frequency (5 Hz) for 2 weeks, which was then followed by an open phase. The patient's Hamilton Depression scores decreased 44 per cent across the first 2 weeks. In an open extension, his mood further improved over another 2 weeks and he was gradually tapered from rTMS treatments. He had no side effects. Importantly, he did not develop mania, as had occurred with all prior antidepressant trials. After several months he experienced a recurrence of depressive symptoms, was retreated, and re-responded. Further studies are warranted to investigate the optimum dose, duration, location and frequency of rTMS treatments for the depressed phase of bipolar disorder. (C) 1998 John Wiley & Sons, Ltd. C1 Med Univ S Carolina, Dept Radiol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Neurol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. NIMH, Biol Psychiat Branch, NIH, Bethesda, MD 20892 USA. RP George, MS (reprint author), Med Univ S Carolina, Dept Radiol, 171 Ashley Ave, Charleston, SC 29425 USA. NR 22 TC 21 Z9 21 U1 1 U2 2 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0885-6222 J9 HUM PSYCHOPHARM CLIN JI Hum. Psychopharmacol.-Clin. Exp. PD JUN PY 1998 VL 13 IS 4 BP 271 EP 275 PG 5 WC Clinical Neurology; Pharmacology & Pharmacy; Psychiatry; Psychology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry; Psychology GA ZV774 UT WOS:000074339800009 ER PT J AU Awwad, JT Sawaya, JT Leykin, L Isaacson, KB Sayegh, R Chen, Z Toth, TL AF Awwad, JT Sawaya, JT Leykin, L Isaacson, KB Sayegh, R Chen, Z Toth, TL TI The effects of pure follicle-stimulating hormone versus human menopausal gonadotrophins on steroidogenesis and folliculogenesis during controlled ovarian hyperstimulation for in-vitro fertilization and embryo transfer SO HUMAN REPRODUCTION LA English DT Meeting Abstract C1 Amer Univ Beirut, Med Ctr, Dept Obstet & Gynecol, Beirut, Lebanon. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD JUN PY 1998 VL 13 SI SI MA P136 BP 197 EP 197 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 110BL UT WOS:000075359300371 ER PT J AU Xavier, R Brennan, T Li, QQ McCormack, C Seed, B AF Xavier, R Brennan, T Li, QQ McCormack, C Seed, B TI Membrane compartmentation is required for efficient T cell activation SO IMMUNITY LA English DT Article ID PROTEIN-TYROSINE KINASES; GPI-ANCHORED PROTEINS; RECEPTOR ZETA-CHAIN; BASOPHILIC LEUKEMIA-CELLS; PHOSPHOLIPASE C-GAMMA-1; SIGNAL-TRANSDUCTION; PHOSPHATIDYLINOSITOL 3-KINASE; CAVEOLAE MEMBRANE; SELECTIVE MODULATION; ACTIN CYTOSKELETON AB The plasma membrane of mammalian cells contains detergent-resistant membrane rafts enriched in glycosphingolipids and cholesterol. Although several important signaling molecules have been found in such rafts, evidence documenting a functional role for their localization has been scarce. Using a fractionation scheme that preserves tyrosine phosphorylation, we show that T cell activation leads to a striking compartmentation in the rafts of activated T cell receptor and associated signal-transducing molecules. Conditions that reversibly disrupt raft structure either by dispersing their contents or by forcing their internalization reversibly disrupt the earliest steps of T cell activation. Thus, raft integrity is a prerequisite for efficient T cell receptor signal transduction. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Seed, B (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM seed@molbio.mgh.harvard.edu FU NIAID NIH HHS [AI01472, AI27849]; NIDDK NIH HHS [DK43031] NR 88 TC 776 Z9 785 U1 1 U2 7 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD JUN PY 1998 VL 8 IS 6 BP 723 EP 732 DI 10.1016/S1074-7613(00)80577-4 PG 10 WC Immunology SC Immunology GA ZW301 UT WOS:000074396300008 PM 9655486 ER PT J AU Wang, JH Springer, TA AF Wang, JH Springer, TA TI Structural specializations of immunoglobulin superfamily members for adhesion to integrins and viruses SO IMMUNOLOGICAL REVIEWS LA English DT Review ID FUNCTION-ASSOCIATED ANTIGEN-1; AMINO-ACID-RESIDUES; HUMAN-IMMUNODEFICIENCY-VIRUS; RECEPTOR ATTACHMENT SITE; T-CELL RECEPTOR; CRYSTAL-STRUCTURE; BINDING-SITE; A-DOMAIN; I-DOMAIN; ANGSTROM RESOLUTION AB The circulation and migration of leukocytes are critical for immune surveillance and immune response to infection or injury. The key step of leukocyte recruitment involves the adhesion between immunoglobulin superfamily (IgSF) proteins on endothelium and integrin molecules on leukocyte surfaces. Some of the IgSF members are subverted as virus receptors. Four crystal structures of N-terminal two-domain fragments of these IgSF proteins have been determined: intercellular adhesion molecule-1 (ICAM-1), ICAM-2, vascular adhesion molecule-1 (VCAM-1), and mucosal addressin cell adhesion molecule-1 (MAdCAM-1). An acidic residue near the bottom of domain 1 plays a key role in integrin binding. For ICAM-1 and ICAM-2, this glutamic add residue is located on a flat surface, complementary to the flat surface of the I domain of the integrin to which they bind, lymphocyte function-associated antigen-1 (LFA-1). For VCAM-1 and MAdCAM-1, the acidic residue is aspartic acid, and it resides on a protruded CD loop which may be complementary to a more pocket-like structure in the alpha 4 integrins to which they bind, which lack I domains. A number of unique structural features of this subclass of IgSF have been identified which are proposed to consolidate the domain structure to resist force during adhesion to integrins. Different mechanisms are proposed for the different CAMs to present the integrin binding surface toward the opposing cell for adhesion, and prevent cis interaction with integrins on the same cell. Finally, CD4 and ICAM-1 are compared in the context of ligand binding and virus binding, which shows how human immunodeficiency virus and rhinovirus fit well with the distinct structural feature of their cognate receptors. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Ctr Blood Res, Boston, MA 02115 USA. RP Wang, JH (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA31798]; NHLBI NIH HHS [HL48675]; NIAID NIH HHS [AI31921] NR 104 TC 127 Z9 130 U1 0 U2 3 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD JUN PY 1998 VL 163 BP 197 EP 215 DI 10.1111/j.1600-065X.1998.tb01198.x PG 19 WC Immunology SC Immunology GA 103TL UT WOS:000074973900016 PM 9700512 ER PT J AU Perera, PY Qureshi, N Christ, WJ Stutz, P Vogel, SN AF Perera, PY Qureshi, N Christ, WJ Stutz, P Vogel, SN TI Lipopolysaccharide and its analog antagonists display differential serum factor dependencies for induction of cytokine genes in murine macrophages SO INFECTION AND IMMUNITY LA English DT Article ID LPS-BINDING-PROTEIN; SOLUBLE CD14; (LPS)-BINDING PROTEIN; LIPID-A; BACTERIAL-ENDOTOXIN; BEARING PARTICLES; ESCHERICHIA-COLI; RECOGNITION; RECEPTOR; CELLS AB Monocytes/macrophages play a central role in mediating the effects of lipopolysaccharide (LPS) derived from gram-negative bacteria by the production of proinflammatory mediators. Recently, it was shown that the expression of cytokine genes for tumor necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and interferon-inducible protein-10 (IP-10) by murine macrophages in response to low concentrations of LPS is entirely CD14 dependent. In this report, we show that murine macrophages respond to low concentrations of LPS (less than or equal to 2 ng/ml) in the complete absence of serum, leading to the induction of TNF-alpha and IL-1 beta genes. In contrast to the TNF-or and IL-1 beta genes, the IP-10 gene is poorly induced in the absence of serum. The addition of recombinant human soluble CD14 (rsCD14) had very little effect on the levels of serum-free, LPS-induced TNF-alpha, IL-1 beta, and IP-10 genes. In contrast, the addition of recombinant human LPS-binding protein (rLBP) had opposing effects on the LPS-induced TNF-alpha or IL-1 beta and IP-10 genes, rLBP inhibited LPS-induced TNF-alpha and IL-1 beta genes, while it reconstituted IP-10 gene expression to levels induced in the presence of serum. These results provide further evidence that the induction of TNF-alpha or IL-1 beta genes occurs via a pathway that is distinct from one that leads to the induction of the IP-10 gene and that the pathways diverge at the level of the initial interaction between LPS and cellular CD14. Additionally, the results presented here indicate that LPS structural analog antagonists Rhodobacter sphaeroides diphosphoryl lipid A and SDZ 880.431 are able to inhibit LPS-induced TNF-alpha and IL-1 beta in the absence of serum, while a synthetic analog of Rhodobacter capsulatus lipid A (B 975) requires both rsCD14 and rLBP to function as an inhibitor. C1 Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA. William S Middleton Mem Vet Adm Med Ctr, Andover, MA 01810 USA. Novartis Forschungsinst, A-1235 Vienna, Austria. Eisai Res Inst, Andover, MA 01810 USA. RP Vogel, SN (reprint author), Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM vogel@usuhsb.usuhs.mil FU NIAID NIH HHS [R37 AI018797, AI 18797, R01 AI018797, R56 AI018797]; NIGMS NIH HHS [R01 GM050870, GM 50870] NR 46 TC 18 Z9 18 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUN PY 1998 VL 66 IS 6 BP 2562 EP 2569 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA ZP714 UT WOS:000073781100023 PM 9596717 ER PT J AU Rose, DJ Maresca, KP Nicholson, T Davison, A Jones, AG Babich, J Fischman, A Graham, W DeBord, JRD Zubieta, J AF Rose, DJ Maresca, KP Nicholson, T Davison, A Jones, AG Babich, J Fischman, A Graham, W DeBord, JRD Zubieta, J TI Synthesis and characterization of organohydrazino complexes of technetium, rhenium, and molybdenum with the {M(eta(1)-HxNNR)(eta(2)-HyNNR)} core and their relationship to radiolabeled organohydrazine-derivatized chemotactic peptides with diagnostic applications SO INORGANIC CHEMISTRY LA English DT Article ID POLYCLONAL IMMUNOGLOBULIN-G; IMAGING FOCAL SITES; STRUCTURAL CHARACTERIZATION; MOLECULAR-STRUCTURES; CRYSTAL-STRUCTURE; BACTERIAL-INFECTION; HYDRAZIDO-COMPLEXES; IN-VITRO; TC-99M; CHEMISTRY AB The reduction of perrhenate, molybdate and pertechnetate with 2-hydrazinopyridine dihydrochloride in methanol has led to the preparation of a class of complexes containing the {M(eta(1)-NNC5H4NHx)(eta(2)-HNNHyC5H4N)} core, represented by [TcCl3(NNC5H4NH)(HNNC5H4N)] (2), [ReCl3(NNC5H4NH)(HNNC5H4N)] (3), and [MoCl3(NNC5H4NH)(HNNHC5H4N)] (6). The reaction of 3 with NEt3 results in the formation of [HNEt3][[ReCl3(NNC5H4N)(HNNC5H4N)] . H2O (4) by deprotonation of the pyridine nitrogen site. Similarly, the reduction of perrhenate with 2-hydrazino-2-imidazoline hydrobromide has led to the preparation of the analogous [ReCl3(NNC3H4N2H)(HNNHC3H4N2H)] (5). Reaction of 3 with pyridine-2-thiol and pyrimidine-2-thiol yields two structurally characterized derivatives with a modified {Re(eta(1)-NNC5H4N)(eta(2)-HNNC5H4N)} core, [Re(C5H4NS)(2)(NNC5H4N)(HNNC5H4N)] (8) and [Re(C4H3N2S)(2)(NNC5H4N)(HNNC5H4N)] (9), respectively. Reaction of 6 with pyrimidine-2-thiol led to the isolation of the analogous [Mo(C4H3N2S)(2)(NNC5H4N)(HNNHC5H4N)] (11) and the seven-coordinate monohydrazine core complex [Mo(C4H3N2S)(3)(NNC5H4N)]. CH2Cl2(12). In similar fashion, the reaction of 2 with pyridine-2-thiol yielded a complex structurally analogous to 8, [Tc(C5H4NS)(2)(NNC5H4N)(HNNC5H4N)] (7). Crystal data for 3, C10H10Cl3N6Re: triclinic, P (1) over bar, a = 7.527(2) Angstrom, b = 7.599(2) Angstrom, c = 13.118(3) Angstrom, or 106.55(3)degrees, beta = 90.28(3)degrees, gamma = 93.83(3)degrees, V = 717.4(4) Angstrom(3), Z = 2. For 4, C16H27Cl3N7ORe: orthorhombic, P2(1)2(1)2(1), a = 7.503(2) Angstrom, b = 10.3643(2) Angstrom, c = 30.1540(5) Angstrom, V = 2345.20(6) Angstrom(3), Z = 2. For 5, C6H12Cl3N8Re: monoclinic, P2(1)/n, a = 9.093(2) Angstrom, b = 11.105(2) Angstrom, c = 14.295(3) Angstrom, beta = 94.71(3)degrees, V = 1438.6(7) Angstrom(3), Z = 4. For 6, C10H11Cl3N6Mo: monoclinic, P2(1)/c, a = 15.366(3) Angstrom, b = 7.804(2) Angstrom, c = 12.378(3) Angstrom, beta = 95.92(3)degrees, V = 1476.4(5) Angstrom(3), Z = 4. For 7, C20H17N8S2Tc: monoclinic, P2(1), a = 8.827(2) Angstrom, b = 9.278(2) Angstrom, c = 13.304(3) Angstrom, beta = 98.92(3)degrees, V = 1076.5(5) Angstrom(3) Z = 2, 2564 reflections. For 8, C20H17N8S2Re: monoclinic, P2(1), a = 8.848(2) Angstrom, b = 9.190(2) Angstrom, c = 13.293(3) Angstrom, beta = 98.89(3)degrees, V = 1067.9(5) Angstrom(3), Z = 2. For 9, C18H15N10S2Re: monoclinic, P2(1), a = 8.796(2) Angstrom, b = 9.008(2) Angstrom, c = 13.208(3) Angstrom, beta = 97.90(3)degrees, V = 1036.6(5) Angstrom(3), Z = 2. For 12, C18H15N9S3Cl2Mo: monoclinic, P2(1)/n, a = 10.52900(10) Angstrom, b = 15.1116(3) Angstrom, c = 15.8193(3) Angstrom, beta = 108.4790(10)degrees, V = 2387.23(7) Angstrom(3), Z = 4. Complexes 2 and 3 serve as models for the binding of Tc(V)-oxo and Re(V)-oxo species to hydrazinonicotinamide (HYNIC)-conjugated chemotactic peptides. Furthermore, since the use of the pyrimidinethiol coligand in the {Tc-99m-HYNIC-peptide} radiochemical species results in favorable pharmacokinetics, the thiolate derivatives 8 and 9 provide models for possible modes of interaction of metal-hydrazine cores with coligands in the radiopharmaceutical reagents. C1 Syracuse Univ, Dept Chem, Syracuse, NY 13244 USA. MIT, Dept Chem, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02214 USA. RP Rose, DJ (reprint author), Syracuse Univ, Dept Chem, Syracuse, NY 13244 USA. NR 69 TC 73 Z9 74 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0020-1669 J9 INORG CHEM JI Inorg. Chem. PD JUN 1 PY 1998 VL 37 IS 11 BP 2701 EP 2716 DI 10.1021/ic970352f PG 16 WC Chemistry, Inorganic & Nuclear SC Chemistry GA ZT351 UT WOS:000074076500015 ER PT J AU Maresca, KP Femia, FJ Babich, JW Zubieta, J AF Maresca, KP Femia, FJ Babich, JW Zubieta, J TI Expansion of the '3+1' concept of oxorhenium-thiolate chemistry to cationic and binuclear complexes SO INORGANIC CHEMISTRY COMMUNICATIONS LA English DT Article DE crystal structures; rhenium complexes; oxo complexes; thiolate complexes ID NUCLEAR-MEDICINE; MOLECULAR-STRUCTURE; COORDINATION; TECHNETIUM; RHENIUM AB The reactions of [(n-C4H9)(4)N] [ReOBr4(OPPh3)] with the appropriate tridentate and monodentate thiolate ligands yield the '3+1' oxorhenium(V) complexes [ReO(SCH2CH2OCH2CH2S)(SCH2C6H4-4-OMe)] (1), [ReO(SCH2CH2OCH2CH2S)(SC5H4NH)]Br (2) and [ Re2O2( SCH2CH2OCH2CH2S)(3)] (3). The versatility of this approach for the synthesis of oxorhenium(V) core complexes is manifest in the preparations of the cationic complex of 2 and of the thiolate bridged binuclear complex 3. (C) 1998 Elsevier Science S.A. All rights reserved. C1 Syracuse Univ, Dept Chem, Syracuse, NY 13244 USA. Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med, Boston, MA 02214 USA. RP Zubieta, J (reprint author), Syracuse Univ, Dept Chem, Syracuse, NY 13244 USA. NR 17 TC 19 Z9 19 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1387-7003 J9 INORG CHEM COMMUN JI Inorg. Chem. Commun. PD JUN PY 1998 VL 1 IS 6 BP 209 EP 212 DI 10.1016/S1387-7003(98)00056-2 PG 4 WC Chemistry, Inorganic & Nuclear SC Chemistry GA 109JW UT WOS:000075319800006 ER PT J AU Ghendler, Y Mizoguchi, E Bhan, AK Clayton, LK AF Ghendler, Y Mizoguchi, E Bhan, AK Clayton, LK TI Double-positive thymocytes resistant to antigen-MHC-induced negative selection lack active caspase SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE caspase; negative selection; TCRhigh; thymus; transgenic mouse ID T-CELL-RECEPTOR; TRANSGENIC MICE; INTERMEDIATE STEPS; CD4+8+ THYMOCYTES; INDUCED APOPTOSIS; EXPRESSION; DEATH; DELETION; PEPTIDE; LINEAGE AB Thymocytes bearing autoreactive TCR are eliminated from the organism by a process termed negative selection. The molecular basis of this deletion has been recently shown to be a consequence of TCR-triggered activation of a caspase by certain peptide-MHC ligands in the immature CD4(+)CD8(+) double-positive (DP) thymocyte subpopulation. Of note, the numerically minor TCRhigh DP thymocyte subpopulation, unlike the major TCRlow DP subset, is resistant to negative selection. Despite exposure to cognate peptide, TCRhigh DP thymocytes mature into single-positive thymocytes and are exported into the periphery. Here we investigated the mechanism by which these thymocytes escape negative selection. Using a cytochemical assay in conjunction with a caspase-specific affinity ligand, we demonstrate that the resistance of the TCRhigh Dp thymocytes to negative selection correlates with the disappearance of TdR-triggered caspase activity in these cells. Thus thymocytes which have presumably begun the positive selection process inactivate the thymic caspase pathway and are no longer susceptible to negative selection. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Immunobiol Lab, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Ghendler, Y (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Immunobiol Lab, 44 Binney St, Boston, MA 02115 USA. FU NIAID NIH HHS [AI9807]; NIDDK NIH HHS [DK47677, DK43551] NR 57 TC 5 Z9 5 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD JUN PY 1998 VL 10 IS 6 BP 767 EP 774 DI 10.1093/intimm/10.6.767 PG 8 WC Immunology SC Immunology GA ZW523 UT WOS:000074419500007 PM 9678757 ER PT J AU Bottaro, A Young, F Chen, JZ Serwe, M Sablitzky, F Alt, FW AF Bottaro, A Young, F Chen, JZ Serwe, M Sablitzky, F Alt, FW TI Deletion of the IgH intronic enhancer and associated matrix-attachment regions decreases, but does not abolish, class switching at the mu locus SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE class switching; gene targeting; IgH intronic enhancer; matrix attachment regions ID IMMUNOGLOBULIN HEAVY-CHAIN; BETA-GLOBIN LOCUS; B-CELL DIFFERENTIATION; DNA-BINDING PROTEIN; TARGETED DELETION; GENE-EXPRESSION; 3' ENHANCER; RECOMBINATION; TRANSCRIPTION; REARRANGEMENT AB The IgH locus intronic enhancer (E(mu)), located in the intron between the J(H) segments and the C(mu) gene, and flanked by two matrix attachment regions (MAR), has been shown to be a major regulator of IgH gene transcription and VDJ recombination, To define the potential role of E(mu) plus MAR in class switch recombination (CSR), we generated IgG-expressing hybridomas from B cells heterozygous for mutations that delete all of these elements or replace them with a neo(r) gene and analyzed the switch status of the mutated IgH loci. E(mu)/MAR-deleted IgH loci displayed a highly significant, although not complete, decrease in CSR when compared to unmutated loci in normal hybridomas. Surprisingly, mutant loci with a pgk promoter-driven neo(r) gene replacing the E(mu)/MAR showed relatively normal switch frequency, These findings indicate that the E(mu)/MAR region plays a significant, but not necessary role in facilitating class switching at the mu locus. Potential mechanisms for these findings are discussed. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. Univ Bonn, Inst Zool, Immunobiol Sect, D-53117 Bonn, Germany. UCL, Sch Med, Dept Med, London W1P 6DP, England. RP Alt, FW (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 200 Longwood Ave, Boston, MA 02115 USA. RI Sablitzky, Fred/A-2276-2011 OI Sablitzky, Fred/0000-0001-9718-1546 FU NIAID NIH HHS [AI31541]; Fondazione Telethon NR 71 TC 50 Z9 51 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD JUN PY 1998 VL 10 IS 6 BP 799 EP 806 DI 10.1093/intimm/10.6.799 PG 8 WC Immunology SC Immunology GA ZW523 UT WOS:000074419500011 PM 9678761 ER PT J AU Loewenstein, JI AF Loewenstein, JI TI Managed care - Preface SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Editorial Material C1 Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP Loewenstein, JI (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD SUM PY 1998 VL 38 IS 3 BP XI EP XII DI 10.1097/00004397-199803830-00002 PG 2 WC Ophthalmology SC Ophthalmology GA 111LV UT WOS:000075439600001 ER PT J AU Loewenstein, JI AF Loewenstein, JI TI Overview of quality measurement and improvement SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article ID HEALTH-CARE; CATARACT-SURGERY; PRACTICE GUIDELINES; MANAGED CARE; OUTCOMES C1 Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP Loewenstein, JI (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. NR 33 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD SUM PY 1998 VL 38 IS 3 BP 59 EP 68 DI 10.1097/00004397-199803830-00007 PG 10 WC Ophthalmology SC Ophthalmology GA 111LV UT WOS:000075439600006 PM 9742433 ER PT J AU Loewenstein, JI AF Loewenstein, JI TI Clinical practice guidelines SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article ID MEDICAL-PRACTICE GUIDELINES; HEALTH-CARE; PRACTICE POLICIES; QUALITY; REALITY C1 Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP Loewenstein, JI (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. NR 32 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD SUM PY 1998 VL 38 IS 3 BP 75 EP 85 DI 10.1097/00004397-199803830-00009 PG 11 WC Ophthalmology SC Ophthalmology GA 111LV UT WOS:000075439600008 PM 9742435 ER PT J AU Loewenstein, JI AF Loewenstein, JI TI Introduction to capitation SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Editorial Material ID FEE-FOR-SERVICE; CATARACT-SURGERY; CARE; QUALITY; RATES C1 Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP Loewenstein, JI (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. NR 12 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD SUM PY 1998 VL 38 IS 3 BP 101 EP 106 DI 10.1097/00004397-199803830-00012 PG 6 WC Ophthalmology SC Ophthalmology GA 111LV UT WOS:000075439600011 PM 9742438 ER PT J AU Lowry, MA AF Lowry, MA TI Non-capitation contract evaluation: A primer SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Lowry, MA (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD SUM PY 1998 VL 38 IS 3 BP 143 EP 161 DI 10.1097/00004397-199803830-00015 PG 19 WC Ophthalmology SC Ophthalmology GA 111LV UT WOS:000075439600014 PM 9742441 ER PT J AU Roemer, L Orsillo, SM Borkovec, TD Litz, BT AF Roemer, L Orsillo, SM Borkovec, TD Litz, BT TI Emotional response at the time of a potentially traumatizing event and PTSD symptomatology: A preliminary retrospective analysis of the DSM-IV criterion A-2 SO JOURNAL OF BEHAVIOR THERAPY AND EXPERIMENTAL PSYCHIATRY LA English DT Article DE post-traumatic stress disorder; emotional numbing; peritraumatic emotional response ID POSTTRAUMATIC-STRESS-DISORDER; VIETNAM THEATER VETERANS; PERITRAUMATIC DISSOCIATION AB DSM-IV added an emotional response component to the definition of Criterion A for PTSD. The present study investigated the relationship between retrospective reports of emotional responses (fear, helplessness, and horror) and disrupted emotional responses ("numbing") at the time of a potentially traumatizing event and reports of PTSD symptomatology among undergraduate participants. We found that, of the DSM-IV criteria, only helplessness was significantly correlated with post-traumatic symptomatology. Reports of peritraumatic emotional numbing uniquely predicted subsequent PTSD symptomatology beyond coincident emotional responses, suggesting that further research is needed to explore the various dimensions of peritraumatic emotional response relevant to the development of PTSD. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 Univ Massachusetts, Dept Psychol, Boston, MA 02125 USA. Oklahoma State Univ, Stillwater, OK 74078 USA. Penn State Univ, Stress & Anxiety Disorders Inst, University Pk, PA 16802 USA. Boston VA Med Ctr, Natl Ctr PTSD, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. RP Roemer, L (reprint author), Univ Massachusetts, Dept Psychol, 100 Morrissey Blvd, Boston, MA 02125 USA. OI Roemer, Lizabeth/0000-0002-2453-5435 FU NIMH NIH HHS [MH-39172] NR 19 TC 48 Z9 48 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0005-7916 J9 J BEHAV THER EXP PSY JI J. Behav. Ther. Exp. Psychiatry PD JUN PY 1998 VL 29 IS 2 BP 123 EP 130 DI 10.1016/S0005-7916(98)00007-X PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 117TJ UT WOS:000075797700003 PM 9762589 ER PT J AU Rosenthal, DI Hornicek, FJ Wolfe, MW Jennings, LC Gebhardt, C Mankin, HJ AF Rosenthal, DI Hornicek, FJ Wolfe, MW Jennings, LC Gebhardt, C Mankin, HJ TI Percutaneous radiofrequency coagulation of osteoid osteoma compared with operative treatment SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID PREOPERATIVE LOCALIZATION; DRILL RESECTION; CT GUIDANCE; EXCISION; ABLATION; REMOVAL; TALUS AB Osteoid osteoma, a benign bone tumor, has traditionally been treated with operative excision. A recently developed method for percutaneous ablation of the tumor has been proposed as an alternative to operative treatment. The relative outcomes of the two approaches to treatment have not previously been compared, to our knowledge. The rates of recurrence and of persistent symptoms were compared in a consecutive series of eighty-seven patients who were managed with operative excision and thirty-eight patients who were managed with percutaneous ablation with radiofrequency. Patients who had a spinal lesion were excluded, The minimum duration of follow-up was two years. There was a recurrence, defined as the need for subsequent intervention, after operative treatment in six (9 per cent) of sixty-eight patients who had been managed for a primary lesion and in two of nineteen who had been managed for a recurrent lesion. The average length of the hospital stay was 4.7 days for the patients who had a primary lesion and 5.1 days for those who had a recurrent lesion, There was a recurrence after percutaneous treatment in four (12 per cent) of thirty-three patients who had been managed for a primary lesion and in none of five who had been managed for a recurrent lesion. The average length of the hospital stay was 0.2 day for these thirty-eight patients. With the numbers available, we could detect no significant difference between the two treatments with regard to the rate of recurrence. The rate of persistent symptoms (that is, symptoms that did not necessitate additional treatment) was greater than the rate of recurrence, According to responses to a questionnaire, eight (30 per cent) of twenty-seven patients had persistent symptoms after operative treatment and six (23 per cent) of twenty-six patients had persistent symptoms after percutaneous treatment with radiofrequency, Two patients had complications after operative excision, necessitating a total of five additional operations. There were no complications associated with the percutaneous method. The results of the present study suggest that percutaneous ablation with radiofrequency is essentially equivalent to operative excision for the treatment of an osteoid osteoma in an extremity The percutaneous method is preferred for the treatment of extraspinal osteoid osteoma because it generally does not necessitate hospitalization, it has not been associated with complications, and it is associated with a rapid convalescence. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Orthopaed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Rosenthal, DI (reprint author), Massachusetts Gen Hosp, Dept Radiol, 32 Fruit St, Boston, MA 02114 USA. EM rosenthal.daniel@mgh.harvard.edu NR 45 TC 297 Z9 310 U1 2 U2 7 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD JUN PY 1998 VL 80A IS 6 BP 815 EP 821 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA ZW762 UT WOS:000074445800005 PM 9655099 ER PT J AU Mussolino, ME Looker, AC Madans, JH Langlois, JA Orwoll, ES AF Mussolino, ME Looker, AC Madans, JH Langlois, JA Orwoll, ES TI Risk factors for hip fracture in white men: The NHANES I Epidemiologic Follow-up Study SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID BONE-MINERAL DENSITY; RADIOGRAPHIC ABSORPTIOMETRY; DIETARY CALCIUM; SECULAR TRENDS; ELDERLY MEN; BLACK-WOMEN; WEIGHT; MASS; AGE; PREDICTION AB This prospective population-based study assessed predictors of hip fracture risk in white men, Participants were members of the Epidemiologic Follow-up Study cohort of the First National Health and Nutrition Examination Survey, a nationally representative sample of noninstitutionalized civilians who were followed for a maximum of 22 years, A cohort of 2879 white men (2249 in the nutrition and weight-loss subsample, 1437 in the bone density subsample) aged 45-74 years at baseline (1971-1975) were observed through 1992, Ninety-four percent of the original cohort were successfully traced. Hospital records and death certificates were used to identify a total of 71 hip fracture cases (61 in the nutrition and weight-loss subsample, 26 in the bone-density subsample), Among the factors evaluated were age at baseline, previous fractures other than hip, body mass index, smoking status, alcohol consumption, nonrecreational physical activity, weight loss from maximum, calcium intake, number of calories, protein consumption, chronic disease prevalence, and phalangeal bone density, The risk adjusted relative risk (RR) of hip fracture was significantly associated with presence of one or more chronic conditions (RR = 1.91, 95% confidence interval ICI] = 1.19-3.06), weight loss from maximum greater than or equal to 10% (RR = 2.27, 95% CI 1.13-4.59), and 1 SD change in phalangeal bone density (RR = 1.73, 95% CI 1.11-2.68), No other variables were significantly related to hip fracture risk Although based on a small number of cases, this is one of the first prospective studies to relate weight loss and bone density to hip fracture risk in men. C1 Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Div Epidemiol, Hyattsville, MD 20782 USA. NIA, Bethesda, MD 20892 USA. Oregon Hlth Sci Univ, Portland VA Med Ctr, Portland, OR 97201 USA. RP Mussolino, ME (reprint author), Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Div Epidemiol, 6525 Belcrest Rd,Room 730, Hyattsville, MD 20782 USA. OI Orwoll, Eric/0000-0002-8520-7355 NR 56 TC 123 Z9 124 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD JUN PY 1998 VL 13 IS 6 BP 918 EP 924 DI 10.1359/jbmr.1998.13.6.918 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZR283 UT WOS:000073958600002 PM 9626622 ER PT J AU Siris, ES Chines, AA Altman, RD Brown, JP Johnston, CC Lang, R Mcclung, MR Mallette, LE Miller, PD Ryan, WG Singer, FR Tucci, JR Eusebio, RA Bekker, PJ AF Siris, ES Chines, AA Altman, RD Brown, JP Johnston, CC Lang, R Mcclung, MR Mallette, LE Miller, PD Ryan, WG Singer, FR Tucci, JR Eusebio, RA Bekker, PJ TI Risedronate in the treatment of Paget's disease of bone: An open label, multicenter study SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID DISODIUM ETIDRONATE; DIPHOSPHONATE; ALENDRONATE; EHDP AB An open-label, multicenter study was conducted to determine the efficacy and safety of oral risedronate (a pyridinyl bisphosphonate) in 162 patients (102 men, 60 postmenopausal women; mean age, 68 years) with moderate to severe Paget's disease of bone (mean serum alkaline phosphatase [ALP] approximately seven times the upper limit of normal). Patients were treated with oral risedronate, 30 mg/day for 84 days, followed by 112 days without treatment. This 196-day cycle was repeated once if serum ALP did not normalize or increased from the nadir value by greater than or equal to 25%. At the end of the first and second cycles, the mean percentage decreases for serum ALP were 65.7% and 69.1%, and for urinary hydroxyproline/creatinine 50.4% and 66.9%, respectively. The decreases from baseline in ALP and urinary hydroxyproline/creatinine were significant (p < 0.001). Normalization of serum ALP was observed in 86 patients (53.8%): 53 during the first treatment cycle and 33 during the second. There was a significant proportion of patients reporting a decrease in the pagetic bone pain at days 84 and 196 (p < 0.001), Overall, risedronate was well tolerated. Five patients withdrew due to adverse events, none of which were considered to be drug related. In conclusion, 30 mg of oral risedronate administered daily for 84 days significantly reduced the biochemical indices of disease activity and was associated with pain reduction in patients with moderate to severe Paget's disease of bone. Normalization of ALP was observed in the majority of patients. Repeated administration of risedronate was shown to be beneficial. In general, risedronate was well tolerated and demonstrated a good safety profile. C1 Columbia Presbyterian Med Ctr, New York, NY 10032 USA. Procter & Gamble Co, Pharmaceut, Cincinnati, OH USA. Univ Miami, Miami, FL 33152 USA. VA Med Ctr, Miami, FL USA. CHU Laval, St Foy, PQ, Canada. Indiana Univ Hosp, Med Ctr, Indianapolis, IN 46202 USA. Oregon Osteoporosis Ctr, Portland, OR USA. Earle A Chiles Res Inst, Portland, OR USA. VA Med Ctr, Houston, TX USA. Colorado Ctr Bone Res, Lakewood, CO USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. John Wayne Canc Inst, Santa Monica, CA USA. Roger Williams Med Ctr, Providence, RI USA. RP Siris, ES (reprint author), Columbia Presbyterian Med Ctr, Harkness Pavil,Room 9-904,180 Washington Ave, New York, NY 10032 USA. NR 29 TC 88 Z9 90 U1 0 U2 2 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD JUN PY 1998 VL 13 IS 6 BP 1032 EP 1038 DI 10.1359/jbmr.1998.13.6.1032 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZR283 UT WOS:000073958600015 PM 9626635 ER PT J AU Li, N Oberley, TD Oberley, LW Zhong, WX AF Li, N Oberley, TD Oberley, LW Zhong, WX TI Inhibition of cell growth in NIH/3T3 fibroblasts by overexpression of manganese superoxide dismutase: Mechanistic studies SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID GLUTATHIONE-PEROXIDASE-ACTIVITY; ANTIOXIDANT ENZYME LEVELS; HYDROGEN-PEROXIDE; MALIGNANT PHENOTYPE; PARAQUAT RESISTANCE; HAMSTER-KIDNEY; RAT-LIVER; EXPRESSION; TOXICITY; DIFFERENTIATION AB NIH/3T3 mouse fibroblasts were transfected with the cDNA for manganese superoxide dismutase (MnSOD), and two clones overexpressing MnSOD activity were subsequently characterized by comparison with parental and control plasmid-transfected cells. One clone with a 1.8-fold increase in MnSOD activity had a 1.5-fold increase in glutathione peroxidase (GPX) activity (increased GPX-adapted clone), while a second clone with a 3-fold increase in MnSOD activity had a 2-fold decrease in copper, zinc superoxide dismutase (CuZnSOD] activity (decreased CuZnSOD-adapted clone). Increased reactive oxygen species (ROS) levels compared with parental or control plasmid-transfected cells were observed in nonsynchronous cells in the increased GPX-adapted clone, but not in the decreased CuZnSOD-adapted clone. The two MnSOD-overexpressing clones showed different sensitivities to agents that generate oxidative stress. Flow cytometry analysis of the cell cycle showed altered cell cycle progression in both MnSOD-overexpressing clones. During logarithmic growth, both MnSOD-overexpressing clones showed increased mitochondrial membrane potential compared with parental and control plasmid-transfected cells. Both MnSOD-overexpressing clones showed a decrease in mitochondrial mass at the postconfluent phase of growth, suggesting that mitochondrial mass may be regulated by MnSOD and/or ROS levels. Our results indicate that adaptation of fibroblasts to overexpression of MnSOD can involve more than one mechanism, with the resultant cell phenotype dependent on the adaptation mechanism utilized by the cell. (C) 1998 Wiley-iiss, Inc. C1 William S Middleton Mem Vet Hosp, Pathol & Lab Med Serv, Madison, WI 53706 USA. Univ Wisconsin, Sch Med, Dept Pathol & Lab Med, Madison, WI USA. Univ Iowa, Radiat Res Lab, Iowa City, IA 52242 USA. RP Oberley, TD (reprint author), William S Middleton Mem Vet Hosp, Pathol & Lab Med Serv, Room A35,2500 Overlook Terrace, Madison, WI 53706 USA. FU NCI NIH HHS [CA41267] NR 52 TC 63 Z9 66 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD JUN PY 1998 VL 175 IS 3 BP 359 EP 369 DI 10.1002/(SICI)1097-4652(199806)175:3<359::AID-JCP14>3.0.CO;2-0 PG 11 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 117MJ UT WOS:000075784900014 PM 9572481 ER PT J AU Kothare, SV Ebb, DH Rosenberger, PB Buonanno, F Schaefer, PW Krishnamoorthy, KS AF Kothare, SV Ebb, DH Rosenberger, PB Buonanno, F Schaefer, PW Krishnamoorthy, KS TI Acute confusion and mutism as a presentation of thalamic strokes secondary to deep cerebral venous thrombosis SO JOURNAL OF CHILD NEUROLOGY LA English DT Article ID ACTIVATED PROTEIN-C; CHILDREN; RESISTANCE; DEFICIENCY; MIGRAINE C1 Massachusetts Gen Hosp, Dept Pediat Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat Hematol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Stroke Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neuroradiol, Boston, MA 02114 USA. RP Kothare, SV (reprint author), Massachusetts Gen Hosp, Dept Pediat Neurol, Boston, MA 02114 USA. OI Kothare, Sanjeev/0000-0001-7849-6649 NR 25 TC 18 Z9 19 U1 0 U2 1 PU DECKER PERIODICALS INC PI HAMILTON PA 4 HUGHSON STREET SOUTH PO BOX 620, LCD 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 0883-0738 J9 J CHILD NEUROL JI J. Child Neurol. PD JUN PY 1998 VL 13 IS 6 BP 300 EP 303 PG 4 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA ZX355 UT WOS:000074507200015 PM 9660519 ER PT J AU Dershwitz, M Conant, JA Chang, YC Rosow, CE Connors, PM AF Dershwitz, M Conant, JA Chang, YC Rosow, CE Connors, PM TI A randomized, double-blind, dose-response study of ondansetron in the prevention of postoperative nausea and vomiting SO JOURNAL OF CLINICAL ANESTHESIA LA English DT Article DE emesis; dose-response study; nausea and vomiting, postoperative; ondansetron; 5-HT3 antagonists ID INTRAVENOUS ONDANSETRON; COMBINATION AB Study Objective: To determine the dose-response relationship of ondansetron in preventing postoperative nausea and vomiting (PONV) in women undergoing elective surgery. Design: prospective, randomized, double-blind study. Setting: University-affiliated hospital. Patients: 175 women aged 18 to 80 years scheduled for elective surgery. Interventions: One of six doses of ondansetron (0.5 mg, 1 mg, 2 mg, 4 mg, 8 mg, 16 mg) or placebo was given prior to the induction of general anesthesia with propofol. Maintenance was with nitrous oxide, isoflurane, opioid, and muscle relaxant. Measurements and Main Results: The study period began when the patient emerged from anesthesia. Nausea scores were recorded on a 0 to 10 scale at multiple time points during the 24-hour study period. Patient satisfaction via a visual analog scale (VAS) was determined at 1 and 24 hours after awakening. Rescue medication was given for severe nausea, three emetic episodes within 15 minutes, or if requested by the patient. The primary efficacy variable was the need for rescue antiemetic therapy. The dose-response curve (by logistic regression) of the percentage of patients not rescued versus dose indicated an ED50 of 0.54 mg (95% confidence interval 0.03-1.05 mg). Fewer patients required rescue in the 4 mg dose group compared with lower doses. However, the difference reached significance only in comparison with the 0.5 mg dose group. Survival analysis of the need for rescue, and nausea score versus lime curves, also both suggested the superiority of the 4 mg dose compared with lower doses. In addition, there was a highly significant correlation between the lack of need for rescue and satisfaction with anesthesia at 24 hours after emergence. Conclusion: The recommended dose of ondansetron for PONV prophylaxis in women remains 4 mg. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Dershwitz, M (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 32 Fruit St, Boston, MA 02114 USA. NR 5 TC 17 Z9 17 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0952-8180 J9 J CLIN ANESTH JI J. Clin. Anesth. PD JUN PY 1998 VL 10 IS 4 BP 314 EP 320 DI 10.1016/S0952-8180(98)00035-X PG 7 WC Anesthesiology SC Anesthesiology GA ZW512 UT WOS:000074418400010 PM 9667348 ER PT J AU Hayes, FJ Hall, JE Boepple, PA Crowley, WF AF Hayes, FJ Hall, JE Boepple, PA Crowley, WF TI Differential control of gonadotropin secretion in the human: endocrine role of inhibin SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Review ID FOLLICLE-STIMULATING-HORMONE; HUMAN MENSTRUAL-CYCLE; MONKEY MACACA-MULATTA; CLINICAL-RESEARCH CENTER; DIMERIC INHIBIN; SERUM INHIBIN; PRECURSOR PROTEINS; ALPHA-SUBUNIT; NORMAL MEN; POSTMENOPAUSAL WOMEN C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Natl Ctr Infertil Res, Boston, MA 02114 USA. RP Hayes, FJ (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, BHX 5,Fruit St, Boston, MA 02114 USA. FU NICHD NIH HHS [HD-18169, HD-15788, R01 HD015788, U54 HD029164, U54 HD028138, P30 HD028138, HD-15080] NR 44 TC 85 Z9 87 U1 0 U2 2 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 JUN PY 1998 VL 83 IS 6 BP 1835 EP 1841 DI 10.1210/jc.83.6.1835 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZT221 UT WOS:000074062200002 PM 9626105 ER PT J AU Margolis, ML Howlett, P Bubanj, R AF Margolis, ML Howlett, P Bubanj, R TI Pulmonary nodules in patients with esophageal carcinoma SO JOURNAL OF CLINICAL GASTROENTEROLOGY LA English DT Article; Proceedings Paper CT American-Thoracic-Society National Meeting CY MAY, 1996 CL NEW ORLEANS, LOUISIANA SP Amer Thorac Soc DE pulmonary nodules; esophageal cancer; pulmonary metastases ID SQUAMOUS-CELL CARCINOMA; METASTASES AB The clinical significance of lung nodules in patients with esophageal carcinoma has received little attention. Therefore, we carried out a retrospective detailed review of 116 consecutive cases of esophageal carcinoma, including 98 squamous cell cancers, seen at the Philadelphia Veterans Affairs Medical Center between 1984 and 1997. Seventy-four percent of our patients were black; it was not surprising therefore that 84% of our patients in this series had squamous cell cancers. Initially, chest radiographs, computed tomography (CT) scans, or thoracotomy showed solitary pulmonary nodules in 22 (19%) patients. A definitive diagnosis was established in 19 patients, including 15 (68%) benign nodules and 4 (18%) new primary lung carcinomas. Three (14%) nodules were indeterminate, but in no case could a solitary lung metastasis be identified. Radiographic evidence of multiple lung metastases was present, however, in 4 (3%) of 116 patients at diagnosis. Autopsies of six patients were later performed, and three showed multiple lung metastases; two of these patients had negative chest radiographs shortly before death. Our experience suggests that for a cohort of mostly squamous cell esophageal cancers, a solitary lung metastasis is rare at diagnosis; a solitary pulmonary nodule at this time likely represents a benign abnormality or primary lung cancer. Multiple pulmonary metastases are also very unusual at diagnosis, probably become increasingly common during the terminal phases of disease, and may be radiographically occult. C1 Vet Affairs Med Ctr, Div Pulm, Dept Internal Med, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Dept Pathol, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Dept Radiol, Philadelphia, PA 19104 USA. Allegheny Univ Hosp, Philadelphia, PA USA. RP Margolis, ML (reprint author), Vet Affairs Med Ctr, Div Pulm, Dept Internal Med, Philadelphia, PA 19104 USA. NR 13 TC 11 Z9 13 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0192-0790 J9 J CLIN GASTROENTEROL JI J. Clin. Gastroenterol. PD JUN PY 1998 VL 26 IS 4 BP 245 EP 248 DI 10.1097/00004836-199806000-00004 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZT854 UT WOS:000074134700004 PM 9649002 ER PT J AU Garvey, WT Maianu, L Zhu, JH Brechtel-Hook, G Wallace, P Baron, AD AF Garvey, WT Maianu, L Zhu, JH Brechtel-Hook, G Wallace, P Baron, AD TI Evidence for defects in the trafficking and translocation of GLUT4 glucose transporters in skeletal muscle as a cause of human insulin resistance SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE insulin resistance; type 2 diabetes mellitus; insulin-regulated aminopeptidase (vp165); vesicle trafficking; GLUT4 ID DEPENDENT DIABETES-MELLITUS; PLASMA-MEMBRANE; PROTEIN; NIDDM; OBESITY; HYPERINSULINEMIA; EXPRESSION; PHOSPHORYLATION; IDENTIFICATION; QUANTITATION AB Insulin resistance is instrumental in the pathogenesis of type 2 diabetes mellitus, and the Insulin Resistance Syndrome. While insulin resistance involves decreased glucose transport activity in skeletal muscle, its molecular basis is unknown. Since muscle GLUT4 glucose transporter levels are normal in type 2 diabetes, we have tested the hypothesis that insulin resistance is due to impaired translocation of intracellular GLUT4 to sarcolemma. Both insulin-sensitive and insulin-resistant nondiabetic subgroups were studied, in addition to type 2 diabetic patients. Biopsies were obtained from basal and insulin-stimulated muscle, and membranes were subfractionated on discontinuous sucrose density gradients to equilibrium or under nonequilibrium conditions after a shortened centrifugation time. In equilibrium fractions from basal muscle, GLUT4 was decreased by 25-29% in both 25 and 28% sucrose density fractions and increased twofold in both the 32% sucrose fraction and bottom pellet in diabetics compared with insulin-sensitive controls, without any differences in membrane markers (phospholemman, phosphalamban, dihydropyridine-binding complex alpha-1 subunit). Thus, insulin resistance was associated with redistribution of GLUT4 to denser membrane vesicles, Na effects of insulin stimulation on GLUT4 localization were observed. In non-equilibrium fractions, insulin led to small GLUT4 decrements in the 25 and 28% sucrose fractions and increased GLUT4 in the 32% sucrose fraction by 2.8-fold over basal in insulin-sensitive hut only by 1.5-fold in both insulin-resistant and diabetic subgroups. The GLUT4 increments in the 32% sucrose fraction were correlated with maximal in vivo glucose disposal rates (r = +0.51, P = 0.026), and, therefore, represented GLUT4 recruitment to sarcolemma or a quantitative marker for this process. Similar to GLUT4, the insulin-regulated aminopeptidase (vp165) was redistributed to a dense membrane compartment and did not translocate in response to insulin in insulin-resistant subgroups. In conclusion, insulin alters the subcellular localization of GLUT4 vesicles in human muscle, and this effect is impaired equally in insulin-resistant subjects with and without diabetes. This translocation defect is associated with abnormal accumulation of GLUT4 in a dense membrane compartment demonstrable in basal muscle, We have previously observed a similar pattern of defects causing insulin resistance in human adipocytes, Based on these data, we propose that human insulin resistance involves a defect in GLUT traffic and targeting leading to accumulation in a dense membrane compartment from which insulin is unable to recruit GLUT4 to the cell surface. C1 Med Univ S Carolina, Div Endocrinol Diabet & Med Genet, Dept Med, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29425 USA. Indiana Univ, Sch Med, Dept Med, Indianapolis, IN 46202 USA. Richard L Roudebush Vet Affairs Med Ctr, Indianapolis, IN 46202 USA. RP Garvey, WT (reprint author), Med Univ S Carolina, Div Endocrinol Diabet & Med Genet, Dept Med, 171 Ashley Ave, Charleston, SC 29425 USA. EM garveywt@musc.edu FU NIDDK NIH HHS [DK-42469, DK-38764, P60-DK-20542] NR 56 TC 209 Z9 211 U1 0 U2 15 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUN 1 PY 1998 VL 101 IS 11 BP 2377 EP 2386 DI 10.1172/JCI1557 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA ZU136 UT WOS:000074165900010 PM 9616209 ER PT J AU Steudel, W Scherrer-Crosbie, M Bloch, KD Weimann, J Huang, PL Jones, RC Picard, MH Zapol, WM AF Steudel, W Scherrer-Crosbie, M Bloch, KD Weimann, J Huang, PL Jones, RC Picard, MH Zapol, WM TI Sustained pulmonary hypertension and right ventricular hypertrophy after chronic hypoxia in mice with congenital deficiency of nitric oxide synthase 3 SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE nitric oxide synthase; hypertension, pulmonary; circulation, pulmonary; echocardiography, transesophageal; gene deletion ID SMOOTH-MUSCLE; RAT; RELAXATION; LUNGS; VASOCONSTRICTION; CIRCULATION; INHALATION; ARTERIES; LACKING; DISEASE AB Chronic hypoxia induces pulmonary hypertension and right ventricular (RV) hypertrophy. Nitric oxide (NO) has been proposed to modulate the pulmonary vascular response to hypoxia. We investigated the effects of congenital deficiency of endothelial NO synthase (NOS3) on the pulmonary vascular responses to breathing 11% oxygen for 36 wk, After 3 wk of hypoxia, RV systolic pressure was greater in NOS3-deficient than in wild-type mice (35+/-2 vs 28+/-1 mmHg, (x) over bar+/-SE < 0.001), Pulmonary artery pressure (P-PA) and incremental total pulmonary vascular resistance (R-PI) were greater in NOS3-deficient than in wild-type mice (PPA 22+/-1 vs 19+/-1 mmHg, P < 0.05 and R-PI 92+/-11 vs 55+/-5 mmHg.min.gram.ml(-1), P < 0.05), Morphometry revealed that the proportion of muscularized small pulmonary vessels was almost fourfold greater in NOS3-deficient mice than in wild-type mice. After 6 wk of hypoxia, the increase of RV free wall thickness, measured by transesophageal echocardiography, and of RV weight/body weight ratio mere more marked in NOS3-deficient mice than in wildtype mice (RV wall thickness 0.67+/-0.05 vs 0.48+/-0.02 mm, P < 0.01 and RV weight/body weight ratio 2.1+/-0.2 vs 1.6+/-0.1 mg.gram(-1), P < 0.05), RV hypertrophy produced by chronic hypoxia was prevented by breathing 20 parts per million NO in both genotypes of mice. These results suggest that congenital NOS3 deficiency enhances hypoxic pulmonary vascular remodeling and hypertension, and RV hypertrophy, and that NO production by NOS3 is vital to counterbalance pulmonary vasoconstriction caused by chronic hypoxic stress. C1 Harvard Univ, Sch Med, Dept Anesthesia & Crit Care, Massachusetts Gen Hosp,Dept Med, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Cardiac Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Cardiovasc Res Ctr, Boston, MA 02114 USA. RP Zapol, WM (reprint author), Harvard Univ, Sch Med, Dept Anesthesia & Crit Care, Massachusetts Gen Hosp,Dept Med, 32 Fruit St, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL-42397] NR 33 TC 170 Z9 177 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUN 1 PY 1998 VL 101 IS 11 BP 2468 EP 2477 DI 10.1172/JCI2356 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA ZU136 UT WOS:000074165900019 PM 9616218 ER PT J AU Seufert, J Weir, GC Habener, JF AF Seufert, J Weir, GC Habener, JF TI Differential expression of the insulin gene transcriptional repressor CCAAT/enhancer-binding protein beta and transactivator islet duodenum homeobox-1 in rat pancreatic beta cells during the development of diabetes mellitus SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE glucose toxicity; lipotoxicity; insulin gene; transcription factors; diabetes mellitus ID CHRONIC HYPERGLYCEMIA; GLUCOSE-CONCENTRATION; COMPLEMENTARY DNAS; MISSENSE MUTATION; CHRONIC EXPOSURE; HIT-T15 CELLS; FATTY-ACIDS; DYSFUNCTION; SECRETION; RECEPTOR AB Impairment of insulin secretion due to prolonged hyperglycemia is believed to contribute to the manifestation of diabetes mellitus, often referred to as glucose toxicity of pancreatic beta cells, In addition, impaired beta cell function has been associated with elevated islet triglyceride content (lipotoxicity), Impaired functions of the transactivating factors islet duodenum homeobox-l (IDX-1) and RIPE3b-binding proteins have been implicated in the pathological dawnregulation of insulin gene transcription by high glucose levels in pancreatic beta cell lines in vitro, and, similarly, the exposure of pancreatic islets to fatty acids decreases IDX-1, expression. Previously, we identified the basic leucine zipper transcription factor CCAAT/enhancer-binding protein beta (C/EBP beta) as an inhibitor of insulin gene transcription in pancreatic beta cells and showed that the expression of C/EBP beta is upregulated in insulinoma-derived beta cell lines by sustained high glucose concentrations. Here we describe the regulation of the expression of IDX-1, C/EBP beta, and insulin at the mRNA and protein levels in pancreatic islets in animal models of diabetes mellitus, Concomitant with a downregulation of IDX-1 and insulin expression, C/EBP beta is upregulated in association with the manifestation of hyperglycemia during the development of diabetes in the Zucker diabetic fatty (fa/fa) rat and in the 90% pancreatectomy rat model of diabetes. This regulation is demonstrated to influence both the amount of cellular protein and the level of steady state messenger RNA. Our findings indicate that the differential dysregulation of both IDX-1 and C/EBP beta, in response to sustained hyperglycemia or hyperlipidemia, may be involved in the impairment of insulin gene expression during the manifestation of diabetes mellitus. C1 Harvard Univ, Mol Endocrinol Lab, Massachusetts Gen Hosp, Sch Med,Howard Hughes Med Inst, Boston, MA 02114 USA. Joslin Diabet Ctr, Islet Transplantat & Cell Biol Sect, Boston, MA 02115 USA. RP Habener, JF (reprint author), Harvard Univ, Mol Endocrinol Lab, Massachusetts Gen Hosp, Sch Med,Howard Hughes Med Inst, Wellman Bldg 320,50 Blossom St, Boston, MA 02114 USA. EM habenerj@a1.mgh.harvard.edu FU NIDDK NIH HHS [DK35449, DK30457, DK30834] NR 68 TC 86 Z9 87 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUN 1 PY 1998 VL 101 IS 11 BP 2528 EP 2539 DI 10.1172/JCI2401 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA ZU136 UT WOS:000074165900025 PM 9616224 ER PT J AU Brander, C Hartman, KE Trocha, AK Jones, NG Johnson, RP Korber, B Wentworth, P Buchbinder, SP Wolinsky, S Walker, BD Kalams, SA AF Brander, C Hartman, KE Trocha, AK Jones, NG Johnson, RP Korber, B Wentworth, P Buchbinder, SP Wolinsky, S Walker, BD Kalams, SA TI Lack of strong immune selection pressure by the immunodominant, HLA-A(*)0201-restricted cytotoxic T lymphocyte response in chronic human immunodeficiency virus-1 infection SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE AIDS; immunodominance; escape; variant; antigen processing ID EPSTEIN-BARR-VIRUS; DYNAMICS IN-VIVO; FINE SPECIFICITY; REVERSE-TRANSCRIPTASE; GENETIC-VARIATION; HIV-1 INFECTION; PEPTIDE BINDING; CELL EPITOPES; TYPE-1; RECOGNITION AB Despite detailed analysis of the HIV-l-specific cytotoxic T lymphocyte response by various groups, its relation to viral load and viral sequence variation remains controversial. We analyzed HLA-A*0201 restricted cytotoxic T lymphocyte responses in 17 HIV-l-infected individuals with viral loads ranging from < 400 to 221,000 HIV RNA molecules per milliliter of plasma. In 13 out of 17 infected subjects, CTL responses against the SLYNTVATL epitope (p17 Gag; aa 77-85) were detectable, whereas two other HLA-A*0201 restricted epitopes (ILKEPVHGV, IV9; and VIYQYMDDL, VL9) were only recognized by six and five individuals out of 17 individuals tested, respectively. Naturally occurring variants of the SL9 epitope were tested for binding to HLA-A*0201 and for recognition by specific T cell clones generated from five individuals. Although these variants were widely recognized, they differed by up to 10,000-fold in terms of variant peptide concentrations required for lysis of target cells. A comparison of viral sequences derived from 10 HLA-A*0201-positive individuals to sequences obtained from 11 HLA-A*0201-negative individuals demonstrated only weak evidence for immune selective pressure and thus question the in vivo efficacy of inmunodominant CTL responses present during chronic HIV-1 infection. C1 Massachusetts Gen Hosp, AIDS Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, New England Reg Primate Ctr, Southborough, MA 01772 USA. Los Alamos Natl Labs, Div Theoret, Los Alamos, NM USA. Cytel Corp, San Diego, CA 92121 USA. Dept Publ Hlth, AIDS Off, San Francisco, CA 94102 USA. Northwestern Univ, Sch Med, Dept Med, Chicago, IL 60611 USA. RP Kalams, SA (reprint author), Massachusetts Gen Hosp East, Massachusetts Gen Hosp, AIDS Res Ctr, 149 13th St, Charlestown, MA 02129 USA. EM Kalams@helix.mgh.harvard.edu RI Wolinsky, Steven/B-2893-2012; OI Wolinsky, Steven/0000-0002-9625-6697; Korber, Bette/0000-0002-2026-5757 FU NIAID NIH HHS [R01 AI 33327, R01 AI30914, R37 AI28568] NR 67 TC 133 Z9 133 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUN 1 PY 1998 VL 101 IS 11 BP 2559 EP 2566 DI 10.1172/JCI2405 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA ZU136 UT WOS:000074165900028 PM 9616227 ER PT J AU Murohara, T Asahara, T Silver, M Bauters, C Masuda, H Kalka, C Kearney, M Chen, DH Chen, DF Symes, JF Fishman, MC Huang, PL Isner, JM AF Murohara, T Asahara, T Silver, M Bauters, C Masuda, H Kalka, C Kearney, M Chen, DH Chen, DF Symes, JF Fishman, MC Huang, PL Isner, JM TI Nitric oxide synthase modulates angiogenesis in response to tissue ischemia SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE angiogenesis; nitric oxide (NO); eNOS (NOS-3); vascular endothelial growth factor (VEGF); L-arginine ID ENDOTHELIAL GROWTH-FACTOR; L-ARGININE; DEPENDENT VASODILATION; IN-VIVO; MYOCARDIAL ANGIOGENESIS; CHRONIC INHIBITION; LIMB ISCHEMIA; GENE-TRANSFER; MICE LACKING; BLOOD-FLOW AB We tested the hypothesis that endothelial nitric oxide synthase (eNOS) modulates angiogenesis in two animal models in which therapeutic angiogenesis has been characterized as a compensatory response to tissue ischemia, We first administered L-arginine, previously shown to augment endogenous production of NO, to normal rabbits with operatively induced hindlimb ischemia, Angiogenesis in the ischemic hindlimb was significantly improved by dietary supplementation with L-arginine, compared to placebo-treated Controls; angiographically evident vascularity in the ischemic limb, hemodynamic indices of limb perfusion, capillary density, and vasomotor reactivity in the collateral vessel-dependent ischemic limb were all improved by oral L-arginine supplementation. A murine model of operatively induced hindlimb ischemia was used to investigate the impact of targeted disruption of the gene encoding for ENOS on angiogenesis. Angiogenesis in the ischemic hindlimb was significantly impaired in eNOS(-/-) mice versus wild-type controls evaluated by either laser Doppler flow analysis or capillary density measurement. Impaired angiogenesis in eNOS(-/-) mice was not improved by administration of vascular endothelial growth factor (VEGF), suggesting that eNOS acts downstream from VEGF, Thus, (a) eNOS is a downstream mediator for in vivo angiogenesis, and (b) promoting eNOS activity by L-arginine supplementation accelerates in vivo angiogenesis, These findings suggest that defective endothelial NO synthesis may limit angiogenesis in patients with endothelial dysfunction related to atherosclerosis, and that oral L-arginine supplementation constitutes a potential therapeutic strategy for accelerating angiogenesis in patients with advanced vascular obstruction. C1 Tufts Univ, Sch Med, St Elizabeths Med Ctr, Dept Med Cardiol, Boston, MA 02135 USA. Tufts Univ, St Elizabeths Med Ctr, Sch Med, Dept Cardiothorac Surg & Biomed Res, Boston, MA 02135 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02111 USA. Massachusetts Gen Hosp, Cardiac Unit, Charlestown, MA 02111 USA. RP Isner, JM (reprint author), Tufts Univ, Sch Med, St Elizabeths Med Ctr, Dept Med Cardiol, 736 Cambridge St, Boston, MA 02135 USA. EM jisner@opal.tufts.edu RI Murohara, Toyoaki/M-4958-2014 FU NHLBI NIH HHS [HL02824, HL40518, HL57516] NR 61 TC 885 Z9 917 U1 0 U2 20 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUN 1 PY 1998 VL 101 IS 11 BP 2567 EP 2578 DI 10.1172/JCI1560 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA ZU136 UT WOS:000074165900029 PM 9616228 ER PT J AU Hortobagyi, GN Theriault, RL Lipton, A Porter, L Blayney, D Sinoff, C Wheeler, H Simeone, JF Seaman, JJ Knight, RD Heffernan, M Mellars, K Reitsma, DJ AF Hortobagyi, GN Theriault, RL Lipton, A Porter, L Blayney, D Sinoff, C Wheeler, H Simeone, JF Seaman, JJ Knight, RD Heffernan, M Mellars, K Reitsma, DJ CA Protocol 19 Aredia Breast Canc Study Grp TI Long-term prevention of skeletal complications of metastatic breast cancer with pamidronate SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID LYTIC BONE METASTASES; DISODIUM; THERAPY; HYPERCALCEMIA; EFFICACY; ONCOLOGY; APD AB Purpose: Pamidronate, an aminabisphosphonate, has been shown to lower the risk of skeletal complications associated with lytic bone lesions for up to 1 year in women with stage IV breast cancer who received chemotherapy. We studied the long-term effectiveness and safety of continued treatment with intravenous pamidronate infusions for up to 2 years. Patients and Methods: Three hundred eighty-two women with metastatic breast cancer and lytic bone lesions who received chemotherapy were randomly assigned to receive either 90 mg of pamidronate or placebo intravenously every 3 to 4 weeks in this double-blind, multicenter, parallel-group trial. Patients were evaluated monthly for 2 years for skeletal complications, which included pathologic fractures, need for radiation or surgery to treat bone complications, spinal cord compression, and hypercalcemia. Bone pain, analgesic use, bone biochemical markers, performance status, quality of life, radiologic response in bone, and survival were also evaluated. Results: As in the first year of treatment, the proportion of patients with any skeletal complication was significantly less for the pamidronate than the placebo group at 15, 18, 21, and 24 months (P < .001). The proportions of patients with any pathologic fracture (ie, vertebral and nonvertebral fractures), need for radiation or surgery to treat bone complications, and hypercalcemia were also statistically less for the pamidronate than the placebo group, The median time to the first skeletal complication was 13.9 months in the pamidronate-treated women and 7.0 months in the placebo group (P < .001). Long term treatment did not result in any unexpected adverse events, Survival did not differ between the two groups. Conclusion: The risk for osteolytic bone lesion complications in metastatic breast cancer was significantly decreased with monthly infusions of 90 mg of pamidronate, and this effect wets maintained for at least 2 years, Pamidronate is a useful adjunct to standard chemotherapy in the palliative treatment of metastatic breast cancer. C1 Univ Texas, MD Anderson Cancer Ctr, Dept Breast Med Oncol, Houston, TX 77030 USA. Milton S Hershey Med Ctr, Hershey, PA USA. St Thomas Hosp, St Thomas Med Grp, Nashville, TN USA. Wilshire Oncol Med Grp, Glendora, CA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NE Ontario Reg Canc Ctr, Sudbury, ON, Canada. Royal N Shore Hosp, St Leonards, NSW 2065, Australia. RP Hortobagyi, GN (reprint author), Univ Texas, MD Anderson Cancer Ctr, Dept Breast Med Oncol, 1515 Holcombe Blvd, Houston, TX 77030 USA. NR 20 TC 402 Z9 412 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN PY 1998 VL 16 IS 6 BP 2038 EP 2044 PG 7 WC Oncology SC Oncology GA ZQ948 UT WOS:000073919200006 PM 9626201 ER PT J AU Chabner, E Nixon, A Gelman, R Hetelekidis, S Recht, A Bornstein, B Connolly, J Schnitt, S Silver, B Manola, J Harris, J Garber, J AF Chabner, E Nixon, A Gelman, R Hetelekidis, S Recht, A Bornstein, B Connolly, J Schnitt, S Silver, B Manola, J Harris, J Garber, J TI Family history and treatment outcome in young women after breast-conserving surgery and radiation therapy for early-stage breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID OVARIAN-CANCER; JEWISH WOMEN; BRCA1; MUTATIONS; RISKS; AGE AB Purpose: To evaluate the safety and efficacy of breast-conserving therapy for young women with a family history (FH) suggestive of inherited breast cancer susceptibility. Materials and Methods: A total of 201 patients aged 36 or younger at diagnosis treated with breast-conserving surgery and radiation therapy(greater than or equal to 60 Gy) for early-stage breast cancer were categorized by FH. FH was considered positive in 29 patients who, at the time of diagnosis, had a mother or sister previously diagnosed with breast cancer before age 50 or ovarian cancer at any age. Clinical, pathologic, and demographic variables; sites of first failure; disease-free survival; and overall survival (OS) were compared between FH-positive and -negative groups. Median follow-up time was 11 years. Results: Patient and tumor features were similar between those with and without an FH. Regression analysis of sites of first failure at 5 years demonstrated a risk ratio (RR) of 5.7 for opposite breast cancer for FH-positive patients. Rates of local, regional, and distant failure and disease-free survival or OS did not differ between FH-positive and -negative patients. Age at diagnosis and Ashkenazi heritage were not significant predictors of patterns of failure. Conclusion: Breast-conserving surgery combined with radiation therapy is not associated with a higher rate of local recurrence, distant failure, or second (nonbreast) cancers in young women with an FH suggestive of inherited breast cancer susceptibility compared with young women without an FH. However, their increased risk of opposite breast cancer should be taken into account when considering breast conservation as a treatment option. C1 Dana Farber Canc Inst, Joint Ctr Radiat Therapy, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Beth Israel Med Ctr, Boston, MA USA. RP Garber, J (reprint author), Dana Farber Canc Inst, Joint Ctr Radiat Therapy, 44 Binney St,Smith Bldg,2nd Floor, Boston, MA 02115 USA. EM garber@dfci.harvard.edu NR 39 TC 56 Z9 56 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN PY 1998 VL 16 IS 6 BP 2045 EP 2051 PG 7 WC Oncology SC Oncology GA ZQ948 UT WOS:000073919200007 PM 9626202 ER PT J AU Colombo, AP Eftimiadi, C Haffajee, AD Cugini, MA Socransky, SS AF Colombo, AP Eftimiadi, C Haffajee, AD Cugini, MA Socransky, SS TI Serum IgG2 level, Gm(23) allotype and Fc gamma RIIa and Fc gamma RIIIb receptors in refractory periodontal disease SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE periodontal diseases; periodontitis; refractory; serum; IgG2; Gm(23); allotype, Fc gamma R ID LOCALIZED JUVENILE PERIODONTITIS; G SUBCLASS CONCENTRATIONS; B POLYSACCHARIDE VACCINE; ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; IMMUNOGLOBULIN-G; CIGARETTE-SMOKING; HUMAN-MONOCYTES; ATTACHMENT LEVEL; TOOTH LOSS; LONG-TERM AB The purpose of this investigation was to compare the levels of serum IgG2, the frequency of detection of Gm(23)-negative allotype and frequency of detection of Fc gamma RIIa and Fc gamma RIIIb receptor haplotypes in 32 refractory, 54 successfully treated and 27 periodontally healthy individuals. Refractory subjects showed mean full mouth attachment loss and/or >3 sites with attachment loss >2.5 mm within 1 year after both scaling and root planing, and surgery plus systemically administered tetracycline. Successfully treated subjects showed mean attachment level gain and no sites with attachment loss >2.5 mm 1 year posttherapy. Periodontally healthy subjects exhibited no pocket depth or attachment level >3 mm, and no evidence of progressing disease during 1 year of monitoring. Blood was obtained from each subject at baseline. Serum IgG2 and Gm(23) allotype were determined using radial immunodiffusion. DNA was extracted from whole blood and the Fc gamma R genotypes determined using PCR and allele specific oligonucleotide probes. Significance of differences among clinical groups were sought using the Kruskal-Wallis or chi-square tests. Associations between 2 or more variables were tested using regression analysis. Refractory subjects exhibited higher mean attachment loss and pocket depth than successfully treated or periodontally healthy subjects. Smoking status did not differ significantly among groups. No significant differences in serum IgG2 levels and frequency of detection of Gm(23)-negative allotype were observed among the clinical groups. Serum IgG2 level was positively associated with the number of serum antibody responses to subgingival species (r = 0.51, p < 0.001). Subjects with the Gm(23)negative allotype exhibited lower mean levels of serum IgG2 (3.06 +/- 0.3 versus 3.9 +/- 0.2, p < 0.01) and mean number of serum antibodies to subgingival species (17.7 +/- 1.7 versus 23.3 +/- 1.4, p < 0.05) than allotype positive individuals. No significant differences in Fc gamma R haplotype distribution were observed among the 3 clinical groups. Associations of serum IgG2 level, Gm(23) allotype, Fc gamma RIIa and Fc gamma RIIIb receptor haplotypes and smoking status were weakly related or not related to clinical status. This lack of relationship may have been due to a reality of no relationship, or the inadvertent pooling of subjects where these factors were of primary importance with subjects in whom these factors played a less important role. C1 Forsyth Dent Ctr, Dept Periodontol, Boston, MA 02115 USA. RP Colombo, AP (reprint author), Forsyth Dent Ctr, Dept Periodontol, Boston, MA 02115 USA. RI Eftimiadi, Costantino/F-3491-2015 OI Eftimiadi, Costantino/0000-0003-1510-4614 FU NIDCR NIH HHS [DE-0488, DE-10977] NR 62 TC 37 Z9 41 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0303-6979 J9 J CLIN PERIODONTOL JI J. Clin. Periodontol. PD JUN PY 1998 VL 25 IS 6 BP 465 EP 474 DI 10.1111/j.1600-051X.1998.tb02475.x PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA ZU740 UT WOS:000074229700005 PM 9667480 ER PT J AU Saxon, AJ Sloan, KL Reoux, J Haver, VM AF Saxon, AJ Sloan, KL Reoux, J Haver, VM TI Disulfiram use in patients with abnormal liver function test results SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID ALCOHOLISM AB Background: Concern about the precipitation of severe hepatitis by disulfiram often causes clinicians to avoid using this effective treatment in patients who have elevated baseline transaminase levels, even though no empirical evidence has so far shown severe hepatotoxicity to be related to such laboratory abnormalities. This study examines the effects of disulfiram in alcohol-dependent patients with elevated liver function test results and/or serologic evidence of hepatitis C virus (HCV) infection. Method: Hepatitis serologies and baseline transaminase levels were obtained for 57 male alcoholics starting treatment with disulfiram. Sequential liver function test results were obtained for up to 12 weeks while subjects took disulfiram. Results: Although subjects with elevated baseline transaminase levels and serologic evidence of HCV infection were the most likely to evidence marked elevations in transaminase levels while taking disulfiram, most subjects took disulfiram without other adverse consequences. In only 1 subject did elevations appear directly related to disulfiram. Conclusion: Monitoring of liver function test results is warranted for patients taking disulfiram and permits most patients with moderately elevated transaminase levels to take it safely. C1 Univ Washington, Sch Med,VA Puget Sound Hlth Care Syst, Dept Psychiat & Behav Sci, Addict Treatment Ctr,Dept Lab Med, Seattle, WA 98195 USA. RP Saxon, AJ (reprint author), VA Med Ctr, 116 ATC,1660 S Columbian Way, Seattle, WA 98108 USA. NR 9 TC 17 Z9 17 U1 1 U2 1 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD JUN PY 1998 VL 59 IS 6 BP 313 EP 316 DI 10.4088/JCP.v59n0607 PG 4 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA ZX045 UT WOS:000074474700007 PM 9671344 ER PT J AU Smoller, JW McLean, RYS Otto, MW Pollack, MH AF Smoller, JW McLean, RYS Otto, MW Pollack, MH TI How do clinicians respond to patients who miss appointments? SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID OUTPATIENT AB Background: Although patients miss up to 60% of scheduled outpatient appointments, little is known about how clinicians respond to "no-shows." In an effort to determine how clinicians customarily handle missed appointments, we surveyed mental health clinicians and internists at 2 academic hospitals: a private psychiatric hospital and an urban general hospital. Method: An anonymous questionnaire survey was mailed to psychiatrists, psychologists, and social workers at both hospitals and to internists at the general hospital. Clinicians were surveyed about their usual response to psychotherapy, psychopharmacology, and internal medicine patients who miss appointments. Results: Among the 356 responses (39.5%) to 902 mailed questionnaires, there was substantial variability in clinicians' reported handling of "no-show" patients, although psychiatrists tended to be initially less active in pursuing patients than were nonphysician therapists and internists. A number of clinical variables were associated with clinicians' responses including the perceived risk of a bad outcome, hospital site, support staff availability, and billing practices. Conclusion: The results suggest that clinicians' responses to missed appointments are determined by a complex mixture of influences rather than adherence to a readily definable "standard of care." C1 Massachusetts Gen Hosp, Dept Psychiat, Psychopharmacol Unit, Boston, MA 02114 USA. RP Smoller, JW (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Psychopharmacol Unit, 15 Parkman St,WACC-815, Boston, MA 02114 USA. FU NIMH NIH HHS [2T32MH1711] NR 9 TC 9 Z9 11 U1 0 U2 1 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD JUN PY 1998 VL 59 IS 6 BP 330 EP 338 DI 10.4088/JCP.v59n0611 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA ZX045 UT WOS:000074474700015 PM 9671351 ER PT J AU Zajecka, J Fawcett, J Amsterdam, J Quitkin, F Reimherr, F Rosenbaum, J Michelson, D Beasley, C AF Zajecka, J Fawcett, J Amsterdam, J Quitkin, F Reimherr, F Rosenbaum, J Michelson, D Beasley, C TI Safety of abrupt discontinuation of fluoxetine: A randomized, placebo-controlled study SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID WITHDRAWAL; SYMPTOMS; PAROXETINE AB Selective serotonin reuptake inhibitors may be associated with new adverse events after abrupt discontinuation. Hypothesizing that the long half-life of fluoxetine would be protective, this study analyzed the effects of abrupt fluoxetine discontinuation during a randomized, double-blind, placebo-controlled study of depression maintenance treatment. After 12 weeks of fluoxetine treatment (20 mg/day), 395 responders were abruptly randomized to placebo (N = 96) or to continued fluoxetine (N = 299). Patients were seen at weeks 1, 2, 4, and 6 after randomization. Reports of new or worsened adverse events were similar for both groups at each visit after randomization. Patient discontinuations related to adverse events were also similar in both groups. Mild, self-limited lightheadedness or dizziness occurred in a small percentage of patients who discontinued fluoxetine treatment but was of little clinical significance. No cluster of symptoms suggestive of a discontinuation syndrome was observed. Abrupt discontinuation of fluoxetine treatment was well tolerated and did not seem to be associated with significant clinical risk. Fluoxetine may offer a potential safety advantage over shorter-acting agents with respect to treatment interruption and/or discontinuation and may be a better choice for those patients who are Likely to miss doses because of travel or forgetfulness. C1 Rush Presbyterian St Lukes Med Ctr, Dept Psychiat, Chicago, IL 60612 USA. Univ Penn, Philadelphia, PA 19104 USA. Columbia Univ, New York, NY USA. Univ Utah, Salt Lake City, UT USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA. RP Zajecka, J (reprint author), Rush Presbyterian St Lukes Med Ctr, Dept Psychiat, 1725 W Harrison, Chicago, IL 60612 USA. OI Beasley, Charles/0000-0001-8743-7691 NR 11 TC 40 Z9 40 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD JUN PY 1998 VL 18 IS 3 BP 193 EP 197 DI 10.1097/00004714-199806000-00003 PG 5 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA ZP285 UT WOS:000073737000003 PM 9617977 ER PT J AU Mueser, KT Goodman, LB Trumbetta, SL Rosenberg, SD Osher, FC Vidaver, R Auciello, P Foy, DW AF Mueser, KT Goodman, LB Trumbetta, SL Rosenberg, SD Osher, FC Vidaver, R Auciello, P Foy, DW TI Trauma and posttraumatic stress disorder in severe mental illness SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article ID CHILDHOOD ABUSE; SEXUAL ABUSE; PSYCHIATRIC-PATIENTS; SCHIZOPHRENIA; POPULATION; VICTIMS; HISTORY; FEMALE; WOMEN AB This research assessed the lifetime prevalence of traumatic events and current posttraumatic stress disorder (PTSD) in 275 patients with severe mental illness (e.g., schizophrenia and bipolar disorder) receiving public mental health services in Concord and Manchester, New Hampshire, and Baltimore, Maryland. Lifetime exposure to traumatic events was high, with 98% of the sample reporting exposure to at least 1 traumatic event. The rate of PTSD in our sample was 43%, but only 3 of 119 patients with PTSD (2%) had this diagnosis in their charts. PTSD was predicted most strongly by the number of different types of trauma, followed by childhood sexual abuse. The findings suggest that PTSD is a common comorbid disorder in severe mental illness that is frequently overlooked in mental health settings. C1 New Hampshire Dartmouth Psychiat Res Ctr, Dartmouth Med Sch, Dept Psychiat, Concord, NH 03301 USA. New Hampshire Hosp, Concord, NH USA. Univ Maryland, Dept Psychol, College Pk, MD 20742 USA. Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 USA. Mental Hlth Ctr Greater Manchester, Manchester, NH USA. W Los Angeles Vet Affairs Med Ctr, Malibu, CA USA. Pepperdine Univ, Dept Psychol, Malibu, CA 90265 USA. RP Mueser, KT (reprint author), New Hampshire Dartmouth Psychiat Res Ctr, Dartmouth Med Sch, Dept Psychiat, Main Bldg,105 Pleasant St, Concord, NH 03301 USA. FU NIMH NIH HHS [R24 MH56147] NR 30 TC 386 Z9 387 U1 3 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 JUN PY 1998 VL 66 IS 3 BP 493 EP 499 DI 10.1037//0022-006X.66.3.493 PG 7 WC Psychology, Clinical SC Psychology GA ZU589 UT WOS:000074213200005 PM 9642887 ER PT J AU Bradley, KA Bush, KR McDonell, MB Malone, T Fihn, SD AF Bradley, KA Bush, KR McDonell, MB Malone, T Fihn, SD CA Ambulatory Care Quality Improvement Project TI Screening for problem drinking - Comparison of CAGE and AUDIT SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE alcohol abuse; screening; CAGE; AUDIT; alcohol drinking ID ALCOHOL-USE DISORDERS; IDENTIFICATION TEST AUDIT; DSM-III-R; GENERAL-PRACTICE; COLLABORATIVE PROJECT; PROBLEM DRINKERS; EMERGENCY ROOM; CARE PATIENTS; CONSUMPTION; QUESTIONNAIRE AB OBJECTIVE: To compare self-administered versions of three questionnaires for detecting heavy and problem drinking: the CAGE, the Alcohol Use Disorders Identification Test (AUDIT), and an augmented version of the CAGE. DESIGN: Cross-sectional surveys. SETTING: Three Department of Veterans Affairs general medical clinics. PATIENTS: Random sample of consenting male outpatients who consumed at least 5 drinks over the past year ("drinkers"), Heavy drinkers were oversampled, MEASUREMENTS: An augmented version of the CAGE was included in a questionnaire mailed to all patients, The AUDIT was subsequently mailed to "drinkers," Comparison standards, based on the tri-level World Health Organization alcohol consumption interview and the Diagnostic Interview Schedule, included heavy drinking (>14 drinks per week typically or greater than or equal to 5 drinks per day at least monthly) and active DSM-IIIR alcohol abuse or dependence (positive diagnosis and at least one alcohol-related symptom in the past year). Areas under receiver operating characteristic curves (AUROCs) were used to compare screening questionnaires. MAIN RESULTS: Of 393 eligible patients, 261 (66%) returned the AUDIT and completed interviews. For detection of active alcohol abuse or dependence, the CAGE augmented with three more questions (AUROC 0.871) performed better than either the CAGE alone or AUDIT (AUROCs 0.820 and 0.777, respectively). For identification of heavy-drinking patients, however, the AUDIT performed best (AUROC 0.870). To identify both heavy drinking and active alcohol abuse or dependence, the augmented CAGE and AUDIT both performed well, but the AUDIT was superior (AUROC 0.861), CONCLUSIONS: For identification of patients with heavy drinking or active alcohol abuse or dependence, the self-administered AUDIT was superior to the CAGE in this population. C1 VA Puget Sound Hlth Care Syst, Seattle Div, Hlth Serv Res & Dev, Seattle, WA 98108 USA. RP Bradley, KA (reprint author), VA Puget Sound Hlth Care Syst, Seattle Div, Hlth Serv Res & Dev, Mailstop 152,1660 S Columbian Way, Seattle, WA 98108 USA. NR 46 TC 171 Z9 173 U1 5 U2 7 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 1998 VL 13 IS 6 BP 379 EP 388 DI 10.1046/j.1525-1497.1998.00118.x PG 10 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA ZW468 UT WOS:000074414000004 PM 9669567 ER PT J AU Tsuang, D Bird, TD AF Tsuang, D Bird, TD TI Genetics of dementia SO JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY LA English DT Editorial Material C1 Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, MIRECC 116,Dept Psychiat, Seattle, WA 98108 USA. Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, Dept Neurol, Seattle, WA 98108 USA. Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, Dept Med, Seattle, WA 98108 USA. RP Tsuang, D (reprint author), Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, MIRECC 116,Dept Psychiat, 1660 S Columbian Way, Seattle, WA 98108 USA. RI Tsuang, Debby/L-7234-2016 OI Tsuang, Debby/0000-0002-4716-1894 NR 0 TC 0 Z9 0 U1 0 U2 0 PU DECKER PERIODICALS INC PI HAMILTON PA 4 HUGHSON STREET SOUTH PO BOX 620, LCD 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 0891-9887 J9 J GERIATR PSYCH NEUR JI J. Geriatr. Psychiatry Neurol. PD SUM PY 1998 VL 11 IS 2 BP 41 EP 41 PG 1 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 151JE UT WOS:000077716300001 ER PT J AU Levy-Lahad, E Tsuang, D Bird, TD AF Levy-Lahad, E Tsuang, D Bird, TD TI Recent advances in the genetics of Alzheimer's disease SO JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY LA English DT Review ID AMYLOID PRECURSOR PROTEIN; APOLIPOPROTEIN-E GENOTYPE; RECEPTOR-RELATED PROTEIN; ELDERLY AFRICAN-AMERICANS; BETA-PEPTIDE DEPOSITION; E EPSILON-4 ASSOCIATION; AGE-OF-ONSET; DOWNS-SYNDROME; MISSENSE MUTATION; TRANSGENIC MICE AB Alzheimer's disease (AD) is a neurodegenerative disorder that is the most common cause of dementia in the elderly. It is a clinical-pathologic entity characterized by progressive dementia associated with the neuropathologic hallmarks of A beta amyloid plaques, neurofibrillary tangles (NFTs), neuronal loss, and amyloid angiopathy. Three "causative" AD genes (i.e., genes in which a mutation is sufficient to result in clinical AD) for early-onset familial Alzheimer's disease (FAD) and one "susceptibility" gene that affects risk and age of onset of AD in familial and sporadic late-onset AD have been identified. The three causative genes are the amyloid precursor protein (APP gene) on chromosome 21, the presenilin-1 gene on chromosome 14, and the presenilin-2 gene on chromosome 1, The susceptibility gene is the apolipoprotein E (APOE) gene on chromosome 19. Investigations of the normal and aberrant function of these genes will provide insights into the mechanisms underlying AD and will suggest new strategies for therapeutic intervention. C1 Shaare Zedek Med Ctr, Dept Med, IL-91000 Jerusalem, Israel. VA Puget Sound Hlth Care Syst, MIRECC 116, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, GRECC, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Neurol, Seattle, WA USA. Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Epidemiol, Seattle, WA 98195 USA. RP Levy-Lahad, E (reprint author), VA Puget Sound Hlth Care Syst, MIRECC 116, 1660 S Columbian Way, Seattle, WA 98108 USA. RI Tsuang, Debby/L-7234-2016 OI Tsuang, Debby/0000-0002-4716-1894 FU NIA NIH HHS [AG 0513C, R01-AG11762] NR 168 TC 29 Z9 30 U1 0 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0891-9887 J9 J GERIATR PSYCH NEUR JI J. Geriatr. Psychiatry Neurol. PD SUM PY 1998 VL 11 IS 2 BP 42 EP 54 PG 13 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 151JE UT WOS:000077716300002 PM 9877525 ER PT J AU Shen, DF Doukhan, L Kalam, S Delwart, E AF Shen, DF Doukhan, L Kalam, S Delwart, E TI High-resolution analysis of T-cell receptor beta-chain repertoires using DNA heteroduplex tracking: generally stable, clonal CD8+ expansions in all healthy young adults SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE DNA heteroduplex; T-cell receptor repertoire; immune response; nucleic acid population analysis ID JUNCTIONAL DIVERSITY; PREDOMINANCE; SEQUENCES; POPULATIONS; MISMATCHES; EXPRESSION; PHENOTYPE; EVOLUTION; ANTIGEN; COMPLEX AB The accurate measurement of T-cell receptor (TCR) repertoire changes requires the analysis of a representative sampling of complex T-cell populations. The number and frequency of clonally expanded TCR beta-chain transcripts bearing distinct CDR3 sequences were accurately determined using a simple DNA heteroduplex tracking assay. This method allowed major and minor clonal expansions(greater than or equal to 1% of a V beta subfamily's transcripts) to be rapidly and reproducibly quantified. Oligoclonal CD8 + cell expansions were detected in all young adults tested, while CD4 + cells generally expressed more polyclonal beta-chain repertoires. The same pattern of CD8 + cells oligoclonality and CD4 + cells polyclonality was observed in asymptomatic HIV-1 infected individuals with high CD4 + cell counts. CD8 + CD45RA + and CD8 + CD45RO + cell fractions both displayed oligoclonal, although distinct, TCR beta chain repertoires while CD8 + cells from umbilical cord blood were generally polyclonal. Oligoclonal CD8 + cell repertoires from young adults were generally stable over a period of weeks, although minor, transient, clonal expansions could also be detected in the absence of symptomatic infections. DNA heteroduplex tracking analysis provided a higher level of sensitivity for the detection of TCR beta chain transcript expansions than CDR3 length (spectrotyping/immunoscope) analysis. DNA heteroduplex tracking of TCR beta-chain transcripts is therefore a simple and sensitive method for assessing the level of clonality and for measuring changes in the TCR beta chain repertoire of different T-cell populations. (C) 1998 Published by Elsevier Science B.,V. All rights reserved. C1 Aaron Diamond AIDS Res Ctr, New York, NY 10016 USA. Rockefeller Univ, New York, NY 10016 USA. Massachusetts Gen Hosp, Ctr AIDS Res, Charlestown, MA 02129 USA. RP Delwart, E (reprint author), Aaron Diamond AIDS Res Ctr, 455 1st Ave, New York, NY 10016 USA. FU NIAID NIH HHS [AI27742, R29 AI40408] NR 32 TC 28 Z9 28 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD JUN 1 PY 1998 VL 215 IS 1-2 BP 113 EP 121 DI 10.1016/S0022-1759(98)00066-0 PG 9 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 116HB UT WOS:000075717500012 PM 9744753 ER PT J AU D'Aquila, RT Sutton, L Savara, A Hughes, MD Johnson, VA AF D'Aquila, RT Sutton, L Savara, A Hughes, MD Johnson, VA CA NIAID AIDS Clin Trials Grp Prot 241 Vi TI CCRS/triangle ccr5 heterozygosity: A selective pressure for the syncytium-inducing human immunodeficiency virus type 1 phenotype SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID HIV-1 INFECTION; LYMPHOCYTE CHEMOATTRACTANT; DISEASE PROGRESSION; RECEPTOR; ENTRY; SDF-1; MIP-1-ALPHA; LESTR/FUSIN; INDIVIDUALS; MIP-1-BETA AB Mechanisms underlying the delay in dominance of syncytium-inducing (SI) phenotype HIV-1 (human immunodeficiency virus type 1) in vivo are unknown. Both random mutational events and selective pressures operative only late in the disease process have been suggested to underlie the shift from CCR5 to alternative coreceptor usage, Among the moderately advanced patients who entered AIDS Clinical Trials Group protocol 241, SI viral phenotype was more common among CCR5/Delta ccr5 heterozygotes (7/7, 100%) than among CCR5/CCR5 homozygotes (29/88, 33%; P < .001, Fisher's exact test). Other characteristics did not differ at study entry by CCR5 genotype, including median CD4 cell counts, plasma RNA levels, and infectious HIV-I titers in circulating cells. These data indicate that CCR5/Delta ccr5 heterozygosity, which decreases cell-surface levels of CCR5 available to serve as an HIV-1 entry coreceptor, is a selective pressure for evolution of T cell line-tropic viruses that use an alternative coreceptor. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. London Sch Hyg & Trop Med, London WC1, England. Univ Alabama, Sch Med, Birmingham, AL USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP D'Aquila, RT (reprint author), Massachusetts Gen Hosp, Infect Dis Unit, 149 13th St, Charlestown, MA 02129 USA. EM daquila@helix.mgh.harvard.edu FU NIAID NIH HHS [AI-29193, AI-36611, AI-27659] NR 35 TC 28 Z9 28 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUN PY 1998 VL 177 IS 6 BP 1549 EP 1553 DI 10.1086/515307 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA ZP618 UT WOS:000073771500015 PM 9607832 ER PT J AU Takabayashi, T Vannier, E Burke, JF Tompkins, RG Gelfand, JA Clark, BD AF Takabayashi, T Vannier, E Burke, JF Tompkins, RG Gelfand, JA Clark, BD TI Both C3a and C3a(desArg) regulate interleukin-6 synthesis in human peripheral blood mononuclear cells SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID TUMOR-NECROSIS-FACTOR; PROTEIN-SYNTHESIS; MESSENGER-RNA; ANAPHYLATOXIN C3A; C5A ANAPHYLATOXIN; SEPSIS SYNDROME; PLASMA-LEVELS; MAST-CELLS; TNF-ALPHA; EXPRESSION AB Synthesis of complement components is part of the acute-phase response. Interleukin-6 (IL-6) is a critical mediator of the acute-phase response during infections and injuries. Plasma levels of C3a and IL-6 have been proposed as prognostic indicators in sepsis and trauma. The effects of C3a and C3a(desArg) on IL-6 gene expression and protein production in human peripheral blood mononuclear cells (PBMC) were investigated. Neither C3a nor C3a(desArg) alone induced detectable IL-6 protein or mRNA levels. However, C3a and C3a(desArg) affected endotoxin-induced IL-6 synthesis in a dose-dependent manner. In nonadherent PBMC, C3a or C3a(desArg) suppressed, while in adherent PBMC, C3a or C3a(desArg) enhanced IL-6 protein and mRNA levels. These results suggest that C3a and C3a(desArg) may provide a control mechanism of acute-phase responses by enhancing IL-6 synthesis in adherent monocytes at local inflammatory sites and by inhibiting IL-6 synthesis in circulating monocytes. C1 Tufts Univ, Sch Med, Dept Med, Tupper Res Inst, Boston, MA 02111 USA. Harvard Univ, New England Med Ctr, Sch Med, Dept Surg, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Shriners Burn Inst, Boston, MA 02114 USA. RP Clark, BD (reprint author), New England Med Ctr, Dept Med, 750 Washington St, Boston, MA 02111 USA. FU NIGMS NIH HHS [GM-50766, GM-21700] NR 40 TC 50 Z9 50 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUN PY 1998 VL 177 IS 6 BP 1622 EP 1628 DI 10.1086/515316 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA ZP618 UT WOS:000073771500025 PM 9607842 ER PT J AU Kaelin, WG Iliopoulos, O Lonergan, KM Ohh, M AF Kaelin, WG Iliopoulos, O Lonergan, KM Ohh, M TI Functions of the von Hippel-Lindau tumour suppressor protein SO JOURNAL OF INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 6th International Workshop on Multiple Endocrine Neoplasia and von Hippel-Lindau Disease CY JUN 25-28, 1997 CL NOORDWIJKERHOUT, NETHERLANDS DE elongins; tumour suppressor gene; tumour suppressor protein; von Hippel-Lindau disease ID ENDOTHELIAL GROWTH-FACTOR; RENAL-CELL CARCINOMA; GENE-PRODUCT; VHL GENE; EXPRESSION; IDENTIFICATION; BINDING; CYCLE; EMBRYOGENESIS; LOCALIZATION AB Von Hippel-Lindau disease (VHL) is caused by germline mutations in the VHL tumour suppressor gene. Tumour development in this setting is due to loss or inactivation of the remaining wild-type VHL allele, The VHL gene product (pVHL) resides primarily in the cytoplasm, A frequently mutated region of pVHL can bind to complexes containing elongin B, elongin C and Cul2. Loss of pVHL leads to an inappropriate accumulation of hypoxia-inducible mRNAs, such as the mRNA encoding vascular endothelial growth factor (VEGF), under normoxic conditions. This finding is most likely to account for the hypervascular nature of VHL-associated neoplasms, Current studies are focussed on understanding if and how binding to elongins and Cul2 is linked to the ability of pVHL to regulate hypoxia-inducible mRNAs, In this regard, it is perhaps noteworthy that elongin C and Cul2 are homologous to yeast proteins Skp1 and Cdc53, These latter proteins participate in the formation of complexes that target certain proteins for ubiquitination. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Kaelin, WG (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 46 TC 54 Z9 55 U1 0 U2 5 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0954-6820 J9 J INTERN MED JI J. Intern. Med. PD JUN PY 1998 VL 243 IS 6 BP 535 EP 539 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA ZZ238 UT WOS:000074709400020 PM 9681855 ER PT J AU Compton, CC Butler, CE Yannas, IV Warland, G Orgill, DP AF Compton, CC Butler, CE Yannas, IV Warland, G Orgill, DP TI Organized skin structure is regenerated in vivo from collagen-GAG matrices seeded with autologous keratinocytes SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE differentiation; pig; porcine; wound healing ID CULTURED EPITHELIAL AUTOGRAFTS; BURN WOUND CLOSURE; ARTIFICIAL SKIN; ATHYMIC MICE; LIVING SKIN; DERMIS; FIBROBLASTS; DIFFERENTIATION; REPLACEMENT; GROWTH AB A well-characterized collagen-glycosaminoglycan matrix (CGM) that has been shown to function as a dermal analog was seeded with freshly disaggregated autologous keratinocytes and applied to full-thickness wounds in a porcine model. CGM were impregnated with 50,000 keratinocytes per cm(2), a seeding density that produces a confluent epidermis within 19 d post-grafting and affords a 60-fold surface expansion of the donor epidermis, In this study, the temporal sequence of events in epidermal and neodermal formation was analyzed histopathologically and immunohistochemically from 4 to 35 d postgrafting. The epidermis was observed to form from clonal growth of individual keratinocytes into epithelial cords and islands that gradually enlarged, coalesced, differentiated to form large horn cysts, and finally reorganized at the graft surface to form a fully differentiated, normally oriented epidermis with rete ridges, Simultaneously, a neodermis formed from migration of endothelial cells, fibroblasts, and macrophages into the CGM from the underlying wound bed, resulting in formation of blood vessels, the production of abundant extracellular matrix, and the degradation of the CGM fibers, respectively. Gradually, the stromal cellularity of the CGM decreased and collagen deposition and remodeling increased to form a neodermal connective tissue matrix beneath the newly formed epidermis. Complete dissolution of the CGM occurred, partly as a result of degradation by an ongoing foreign-body giant cell reaction that peaked at 8-12 d post-grafting, but neither acute inflammation nor evidence of immune stimulation were observed. Within 1 mo, many structural components of normal skin were reconstituted. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Shriners Burns Hosp, Boston Unit, Boston, MA USA. Brigham & Womens Hosp, Div Plast Surg, Boston, MA 02115 USA. MIT, Fibers & Polymers Lab, Cambridge, MA 02139 USA. RP Compton, CC (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren 2,55 Fruit St, Boston, MA 02114 USA. NR 41 TC 78 Z9 81 U1 1 U2 4 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUN PY 1998 VL 110 IS 6 BP 908 EP 916 DI 10.1046/j.1523-1747.1998.00200.x PG 9 WC Dermatology SC Dermatology GA ZN928 UT WOS:000073697600011 PM 9620298 ER PT J AU de Sauvage, FJ Villeval, JL Shivdasani, RA AF de Sauvage, FJ Villeval, JL Shivdasani, RA TI Regulation of megakaryocytopoiesis and platelet production: Lessons from animal models SO JOURNAL OF LABORATORY AND CLINICAL MEDICINE LA English DT Review ID TRANSCRIPTION FACTOR NF-E2; THROMBOPOIETIN MPL LIGAND; LEUCINE ZIPPER PROTEIN; C-MPL; GLOBIN GENE; ERYTHROID PROGENITORS; DEFICIENT MICE; FACTOR GATA-1; EXPRESSION; GROWTH C1 Genentech Inc, Dept Mol Oncol, S San Francisco, CA 94080 USA. Harvard Univ, Sch Med, Boston, MA USA. Dana Farber Canc Inst, Dept Adult Oncol & Med, Boston, MA 02115 USA. RP de Sauvage, FJ (reprint author), Genentech Inc, Dept Mol Oncol, 460 Pt San Bruno Blvd, S San Francisco, CA 94080 USA. NR 47 TC 18 Z9 18 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0022-2143 J9 J LAB CLIN MED JI J. Lab. Clin. Med. PD JUN PY 1998 VL 131 IS 6 BP 496 EP 501 DI 10.1016/S0022-2143(98)90057-9 PG 6 WC Medical Laboratory Technology; Medicine, General & Internal; Medicine, Research & Experimental SC Medical Laboratory Technology; General & Internal Medicine; Research & Experimental Medicine GA ZT602 UT WOS:000074104300005 PM 9626984 ER PT J AU Potts, JT Herdman, RC Beauchamp, TL Robertson, JA AF Potts, JT Herdman, RC Beauchamp, TL Robertson, JA TI Commentary: Clear thinking and open discussion guide IOM's report on organ donation SO JOURNAL OF LAW MEDICINE & ETHICS LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Natl Acad Sci, Inst Med, Washington, DC 20418 USA. Georgetown Univ, Kennedy Inst Eth, Washington, DC 20057 USA. Univ Texas, Sch Law, Austin, TX 78712 USA. RP Potts, JT (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 4 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC LAW MEDICINE ETHICS PI BOSTON PA 765 COMMONWEALTH AVE, 16TH FL, BOSTON, MA 02215 USA SN 0277-8459 J9 J LAW MED ETHICS JI J. Law Med. Ethics PD SUM PY 1998 VL 26 IS 2 BP 166 EP 168 DI 10.1111/j.1748-720X.1998.tb01672.x PG 3 WC Ethics; Law; Medical Ethics; Medicine, Legal SC Social Sciences - Other Topics; Government & Law; Medical Ethics; Legal Medicine GA 122FA UT WOS:000076060200008 PM 11657353 ER PT J AU Donnet, C Caride, AJ Talgham, S Rossi, JPFC AF Donnet, C Caride, AJ Talgham, S Rossi, JPFC TI Chemical modification reveals involvement of different sites for nucleotide analogues in the phosphatase activity of the red cell calcium pump SO JOURNAL OF MEMBRANE BIOLOGY LA English DT Article DE PMCA; phosphatase activity; nucleotide analogues; Lys residues; chemical modification; partial reactions ID HUMAN-ERYTHROCYTE-MEMBRANES; (NA+ + K+)-ATPASE; CA2+ PUMP; SARCOPLASMIC-RETICULUM; CA-2+ PUMP; FLUORESCEIN ISOTHIOCYANATE; ADENOSINE-TRIPHOSPHATASE; ATP-BINDING; CALMODULIN; TRANSPORT AB The calcium pump of plasma membranes catalyzes the hydrolysis of ATP and phosphoric esters like p-nitrophenyl phosphate (pNPP). The latter activity requires the presence of ATP and/or calmodulin, and Ca2+ [22, 25], We have studied the effects of nucleotide-analogues and chemical modifications of nucleotide binding sites on Ca2+-pNPPase activity. Treatment with fluorescein isothiocyanate (FITC), abolished Ca2+-ATPase and ATP-dependent pNPPase, but affected only 45% of the calmodulin-dependent pNPPase activity. The nucleotide analogue eosin-Y had an inhibitory effect on calmodulin-dependent pNPPase (Ki(eosin-Y) = 2 mu M). FITC treatment increased Ki(eosin-Y) 15 times. Acetylation of lysine residues with N-hydroxysuccinimidyl acetate inactivates Ca2+-ATPase by modifying the catalytic site, and impairs stimulation by modulators by modifying residues outside this site [9]. Acetylation suppressed the ATP-dependent pNPPase with biphasic kinetics. ATP or pNPP during acetylation cancels the fast component of inactivation. Acetylation inhibited only partially the calmodulin-dependent pNPPase, but neither ATP nor pNPP prevented this inactivation. From these results we conclude: (i) ATP-dependent pNPPase depends on binding of ATP to the catalytic site; (ii) the catalytic site plays no role in calmodulin-dependent pNPPase. The decreased affinity for eosin-Y of the FITC-modified enzyme, suggests that the sites for these two molecules are closely related but not overlapped. Acetimidation of the pump inhibited totally the calmodulin-dependent pNPPase, but only partially the ATP-pNPPase. Since calmodulin binds to E-1, the E-1 conformation or the E-2 double left right arrow E-1 transition would be involved during calmodulin-dependent pNPPase activity. C1 Univ Buenos Aires, Fac Farm & Bioquim, Inst Quim & Fisicoquim Biol, CONICET,IQUIFIB, RA-1113 Buenos Aires, DF, Argentina. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Renal Unit, Charlestown, MA USA. Mayo Clin & Mayo Fdn, Dept Biochem & Mol Biol, Rochester, MN 55905 USA. RP Rossi, JPFC (reprint author), Univ Buenos Aires, Fac Farm & Bioquim, Inst Quim & Fisicoquim Biol, CONICET,IQUIFIB, Junin 956, RA-1113 Buenos Aires, DF, Argentina. OI Rossi, Juan Pablo/0000-0001-7087-844X NR 25 TC 6 Z9 6 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0022-2631 J9 J MEMBRANE BIOL JI J. Membr. Biol. PD JUN 1 PY 1998 VL 163 IS 3 BP 217 EP 224 DI 10.1007/s002329900385 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Physiology GA ZT023 UT WOS:000074039900006 PM 9625778 ER PT J AU Leszyk, J Tao, T Nuwaysir, LM Gergely, J AF Leszyk, J Tao, T Nuwaysir, LM Gergely, J TI Identification of the photocrosslinking sites in troponin-I with 4-maleimidobenzophenone labelled mutant troponin-Cs having single cysteines at positions 158 and 21 SO JOURNAL OF MUSCLE RESEARCH AND CELL MOTILITY LA English DT Article ID SKELETAL-MUSCLE TROPONIN; CROSS-LINKING; CONFORMATIONAL TRANSITION; BIOLOGICAL-ACTIVITY; INHIBITORY REGION; REGULATORY DOMAIN; THIOL MUTANTS; COMPLEX; RABBIT; CONTRACTION AB Our previous studies have shown that 3-maleimidobenzophenone (BP-Mal) attached to troponin-C (TnC) mutants with single cysteines at positions 12, 57, 89 and 98 forms crosslinks to troponin-I (TnI), and the identified crosslinking regions indicate an antiparallel course of the two interacting polypeptide chains, in agreement with other studies using fragments of TnC and TnI. In this work we extended the mapping of the TnC-TnI interface by analysing photocrosslinking between TnI and BP-Mal labelled TnC mutants with single Cys residues at positions 21 (TnC21) and 158 (TnC158). We determined the sites of these photocrosslinks in TnI by progressive proteolysis of the crosslinked product, followed by N-terminal sequencing and mass spectrophotometric analyses. The results show that whereas TnC158 forms a specific crosslink with Met-21, TnC21 forms multiple crosslinks in the range of residues 96 to 134 of TnI. The results are discussed in light of the antiparallel model of the TnI-TnC complex and a structural model derived from low-angle X-ray and neutron scattering studies. (C) Chapman & Hall Ltd. C1 Boston Biomed Res Inst, Muscle Res Grp, Boston, MA 02114 USA. Worcester Fdn Expt Biol Inc, Shrewsbury, MA 01545 USA. Perkin Elmer Corp, ABI Div, Foster City, CA 94404 USA. Massachusetts Gen Hosp, Serv Neurol, Boston, MA 02114 USA. Tufts Univ, Sch Med, Dept Biochem, Boston, MA 02111 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Gergely, J (reprint author), Boston Biomed Res Inst, Muscle Res Grp, 20 Staniford St, Boston, MA 02114 USA. FU NHLBI NIH HHS [R37-HL-5949]; NIAMS NIH HHS [R37-AR-21673] NR 41 TC 14 Z9 14 U1 1 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0142-4319 J9 J MUSCLE RES CELL M JI J. Muscle Res. Cell Motil. PD JUN PY 1998 VL 19 IS 5 BP 479 EP 490 DI 10.1023/A:1005352324741 PG 12 WC Cell Biology SC Cell Biology GA ZZ904 UT WOS:000074781100003 PM 9682135 ER PT J AU Lessell, S AF Lessell, S TI Nutritional amblyopia SO JOURNAL OF NEURO-OPHTHALMOLOGY LA English DT Article DE optic neuropathy; nutritional deficiency ID VISUAL EVOKED-POTENTIALS; OPTIC NEUROPATHY; DOPAMINERGIC DEFICIENCY; BRAIN NEUROTRANSMITTERS; SENSORY NEUROPATHY; FREE-RADICALS; CUBA; EPIDEMIC; VITAMIN-B12; DIET AB A review was conducted to examine the characteristics and pathogenesis of nutritional amblyopia. Published cases of amblyopia among malnourished allied prisoners of the Japanese during World War II and among Cubans malnourished during the recent economic embargo were analyzed. The picture of nutritional amblyopia derived from these publications is somewhat at variance with the conventional image of the disease. Surprising features include premonitory keratopathy, rapid onset of visual loss, a high incidence of hearing loss, and the presence of peripapillary retinopathy in some cases. No single causative factor can be identified. Genetic susceptibility rarely, if ever, plays a role. Vitamin deficiency may not be important. Protein deficiency, antioxidant deficiency, physical labor, and tobacco smoking are likely to contribute to the occurrence of amblyopia. C1 Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Lessell, S (reprint author), 243 Charles St, Lexington, MA 02173 USA. NR 64 TC 6 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1070-8022 J9 J NEURO-OPHTHALMOL JI J. Neuro-Ophthal. PD JUN PY 1998 VL 18 IS 2 BP 106 EP 111 PG 6 WC Clinical Neurology; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA 306YL UT WOS:000086626200006 PM 9621265 ER PT J AU Thomas, SA Marck, BT Palmiter, RD Matsumoto, AM AF Thomas, SA Marck, BT Palmiter, RD Matsumoto, AM TI Restoration of norepinephrine and reversal of phenotypes in mice lacking dopamine beta-hydroxylase SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE norepinephrine; epinephrine; dopamine; dihydroxyphenylserine; dopamine beta-hydroxylase; mice ID L-THREO-DOPS; NORADRENALINE; DEFICIENCY; PRECURSOR AB Mice with a targeted disruption of the dopamine beta-hydroxylase (DBH) gene are unable to synthesize norepinephrine (NE) and epinephrine. These mice have elevated levels of dopamine in most tissues, although the levels are only a fraction of those normally found for NE. It is noteworthy that NE can be restored to normal levels in many tissues after a single injection of the synthetic amino acid precursor of NE, L-threo-3,4-dihydroxyphenylserine (DOPS). In other tissues, NE can be restored to normal levels after multiple injections of DOPS, whereas in the midbrain and cerebellum, restoration of NE is limited to 25-30% of normal. NE levels typically peak similar to 5 h after DOPS administration and are undetectable by 48 h. Epinephrine levels are more difficult to restore. The elevated levels of dopamine fall modestly after injection of DOPS. S(-)-Carbidopa, which does not cross the blood-brain barrier, inhibits aromatic L-amino acid decarboxylase and effectively prevents restoration of NE by DOPS in the periphery, while allowing restoration in the CNS. Ptosis and reductions in male fertility, hindlimb extension, postdecapitation convulsions, and uncoupling protein expression in dopamine beta-hydroxylase-deficient mice are all reversed by DOPS injection. C1 Howard Hughes Med Inst, Seattle, WA USA. VA Puget Sound Hlth Care Syst, Dept Biochem, Seattle, WA USA. VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. Univ Washington, Dept Med, Seattle, WA USA. RP Thomas, SA (reprint author), Univ Penn, Dept Pharmacol, Philadelphia, PA 19104 USA. FU NICHD NIH HHS [HD 12629, HD 09172] NR 28 TC 135 Z9 135 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUN PY 1998 VL 70 IS 6 BP 2468 EP 2476 PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA ZN457 UT WOS:000073647800025 PM 9603211 ER PT J AU Viguera, A Rordorf, G Schouten, R Welch, C Drop, LJ AF Viguera, A Rordorf, G Schouten, R Welch, C Drop, LJ TI Intracranial haemodynamics during attenuated responses to electroconvulsive therapy in the presence of an intracerebral aneurysm SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Article DE electroconvulsive therapy; blood pressure; hypertension; blood vessels; aneurysm ID SACCULAR ANEURYSMS; RUPTURE AB Objectives-This report describes successful anaesthesia and electroconvulsive therapy (ECT) in a patient with an unruptured basilar artery aneurysm. ECT is associated with a hyperdynamic state characterised by arterial hypertension, tachycardia, and considerably increased cerebral blood flow rate and velocity. These responses pose an increased risk for subarachnoid haemorrhage when an intracranial aneurysm coexists. Methods-A 54 year old woman presented for ECT. She had a 20 year history of major depression which was unresponsive to three different antidepressant drugs. There was also an unruptured 5 mm saccular aneurysm at the basilar tip, which had been documented by cerebral angiography, but its size had remained unchanged for the previous four years. After she declined surgical intervention, she gave informed consent for ECT. During a series of seven ECT sessions middle cerebral artery flow velocity was recorded by a pulsed transcranial Doppler ultrasonography system. She was pretreated with 50 mg oral atenolol daily, continuing up to the day of the last ECT and immediately before each treatment, sodium nitroprusside was infused at a rate of 30 mu g/min, to reduce systolic arterial pressure to 90-95 mm Hg. Results-Systolic flow velocity during the awake state ranged from 62-75 cm/s, remaining initially unchanged with sodium nitroprusside infusion. After induction of anaesthesia (0.5 mg/kg methohexitone and 0.9 mg/kg succinylcholine), flow velocities decreased to 39-54 cm/s, reaching maximal values of 90 cm/s (only 20% above baseline) after ECT. These flow velocities recorded post-ECT were considerably below the more than twofold increase recorded when no attenuating drugs were used. Systolic arterial blood pressure reached maximal values of 110-140 mm Hg and heart rate did not exceed 66 bpm. Rapid awakening followed each treatment, no focal or global neurological signs were apparent, and the patient was discharged in remission. Conclusion-In a patient with major depression and a coexisting intracerebral saccular aneurysm who was treated with ECT, the combination of P blockade with atenolol and intravenous infusion of sodium nitroprusside prevented tachycardia and hypertension, and greatly attenuated the expected increase in flow velocity in the middle cerebral artery. C1 Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Anaesthesia, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02114 USA. RP Drop, LJ (reprint author), Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA. NR 17 TC 15 Z9 15 U1 0 U2 1 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-3050 J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD JUN PY 1998 VL 64 IS 6 BP 802 EP 805 DI 10.1136/jnnp.64.6.802 PG 4 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA ZU428 UT WOS:000074196100021 PM 9647316 ER PT J AU Trojanowski, JQ Growdon, JH AF Trojanowski, JQ Growdon, JH TI A new consensus report on biomarkers for the early antemortem diagnosis of Alzheimer disease: Current status, relevance to drug discovery, and recommendations for future research SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Editorial Material C1 Univ Penn, Sch Med, Dept Pathol & Lab Med, Ctr Neurodegenerat Dis Res, Philadelphia, PA 19104 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Trojanowski, JQ (reprint author), Univ Penn, Sch Med, Dept Pathol & Lab Med, Ctr Neurodegenerat Dis Res, HUP Maloney 3rd Floor,36th & Spruce St, Philadelphia, PA 19104 USA. NR 8 TC 12 Z9 12 U1 0 U2 2 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD JUN PY 1998 VL 57 IS 6 BP 643 EP 644 DI 10.1097/00005072-199806000-00010 PG 2 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 137DE UT WOS:000076898900010 PM 9630242 ER EF